To see the other types of publications on this topic, follow the link: Blood plasma exchange therapy.
Journal articles on the topic 'Blood plasma exchange therapy'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Blood plasma exchange therapy.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Sadler, J. Evan. "Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura." Blood 112, no. 1 (July 1, 2008): 11–18. http://dx.doi.org/10.1182/blood-2008-02-078170.
Full textAbstract:
Abstract Discoveries during the past decade have revolutionized our understanding of idiopathic thrombotic thrombocytopenic purpura (TTP). Most cases in adults are caused by acquired autoantibodies that inhibit ADAMTS13, a metalloprotease that cleaves von Willebrand factor within nascent platelet-rich thrombi to prevent hemolysis, thrombocytopenia, and tissue infarction. Although approximately 80% of patients respond to plasma exchange, which removes autoantibody and replenishes ADAMTS13, one third to one half of survivors develop refractory or relapsing disease. Intensive immunosuppressive therapy with rituximab appears to be effective as salvage therapy, and ongoing clinical trials should determine whether adjuvant rituximab with plasma exchange also is beneficial at first diagnosis. A major unanswered question is whether plasma exchange is effective for the subset of patients with idiopathic TTP who do not have severe ADAMTS13 deficiency.
2
Gertz, Morie A. "Acute hyperviscosity: syndromes and management." Blood 132, no. 13 (September 27, 2018): 1379–85. http://dx.doi.org/10.1182/blood-2018-06-846816.
Full textAbstract:
Plasma hyperviscosity is a rare complication of both monoclonal and polyclonal disorders associated with elevation of immunoglobulins. Asymptomatic patients with an elevation in the serum viscosity do not require plasma exchange, and the majority will have other indications for therapeutic intervention. For patients with hemorrhagic or central nervous system manifestations, plasma exchange is the therapy of choice and is relatively safe. Viscosity measurements are not required to initiate therapy if the index of suspicion is high and the clinical presentation is typical. However, patients should have a sample sent for confirmation of the diagnosis. Whole-blood hyperviscosity is seen in patients with extreme elevation of the red cell and white cell count. Phlebotomy of patients with primary and secondary elevation of the red cell count is a well-established therapy.
3
Farhat, M. H., B. de Souza, and A. Hanbali. "Cancer-related TTP: Role of plasma exchange." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e13527-e13527. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e13527.
Full textAbstract:
e13527 Background: Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disease classically described by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic manifestations and renal dysfunction. It is considered a hematologic emergency for which, the treatment of choice is plasma exchange therapy. However, its diagnosis and treatment can be particularly challenging in the setting of disseminated malignancy, as the misdiagnosis of TTP in a patient with cancer-associated thrombotic microangiopathy (TMA) will lead to ineffective use of plasma exchange and delay the timely delivery of chemotherapy. Moreover, patients with disseminated malignancy respond less often to plasma exchange and have a higher mortality rate. Methods: Three patients with disseminated malignancy who presented as TTP are discussed. Two of the three patients were given plasma exchange and had fatal outcomes, while the third patient received chemotherapy as the initial therapy and survived hospitalization. The three patients had prolonged PT with normal aPTT; LDH levels (>1,000 IU/L); and presence of schistocytes in the peripheral blood smear. Results: TMA associated with disseminated malignancy remains a challenging and underdiagnosed condition with very poor prognosis. Plasma exchange has no clinical use is potentially even life-threatening especially when it delays the administration of the appropriate chemotherapy which is the ultimate treatment for the underlying malignancy that resulted in TMA. We propose that the following criteria be used for diagnostic consideration of disseminated malignancy-associated TMA: evidence of hemolysis; leukoerythroblastic picture on the peripheral blood; coagulopathy consisting of elevated d-dimer, prolonged PT with normal aPTT; extreme elevations in the LDH levels (>1,000 IU/L); and presence of schistocytes in the peripheral blood smear. Such patients should be immediately considered for a bone marrow biopsy as chemotherapy should be initiated as soon as possible. Conclusions: See Table. [Table: see text] No significant financial relationships to disclose.
4
S., Aswin Kumar, Latha B., and Dhivya x. Dhivya K. "Therapeutic plasma exchange in neuro-immunological disorder." International Journal of Research in Medical Sciences 5, no. 4 (March 28, 2017): 1550. http://dx.doi.org/10.18203/2320-6012.ijrms20171263.
Full textAbstract:
Background: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique used to remove high molecular weight substances from the plasma. Examples of these substances include immune complexes, pathogenic autoantibodies, endotoxin, cryoglobulins and cholesterol-containing lipoproteins and myeloma light chains. Therapeutic Plasma exchange is a well-established therapeutic procedure most commonly used in many neuro-immunological disorders. The benefit of plasma exchange occurs by elimination of pathognomonic inflammatory mediators, including complement components, autoantibodies and cytokines. Various studied have demonstrated that TPE plays an important role in neuro-immunological disorder (eg. Guillain-Barré syndrome, myasthenia gravis and other forms of immune neuropathies).Methods: It is descriptive and prospective study on the effect of TPE in neuro-immunological disorders. TPE are studied prospectively for a period from September 2011 to August 2013. The amount of plasma to be exchanged during TPE was determined using the formula EPV = (0.065 x weight [kg]) x (1-hematocrit). TPE was performed using a Haemonetics MCS+ intermittent flow cell separator. An average of 1-1.5 plasma volume is removed on alternative days. Clinical outcome of TPE was assessed at the time of discharge.Results: A total of 138 Therapeutic plasma exchange procedure were performed on 30 patients. In which the improvement begins within days of commencing the treatments and progressed steadily so that 25 out of 30 patients who responded favourably to TPE with a manageable adverse reaction. And only 5 patients failed to respond this therapy. So the clinical outcome for therapeutic plasma exchange for Neuro-immunological cases were 83.3% and remaining 16.7% doesn’t show any improvement after five plasma exchanges.Conclusions: Therapeutic plasma exchange is a first line of management for most of the neuro-immunological disorder. In our study there was an improvement in motor performance after 3-5 plasma exchanges which are mainly due to removal of unbound antibodies from the plasma. Although the statistical power of our study was not sufficient to allow definitive conclusion, the result strongly suggest that 3-5 procedures on alternative days with 1-1.5 volume of plasma exchange gives a better result in patient with neuro-immunlogical diseases. The success of therapeutic plasma exchange also depends on composition of the replacement fluid. The risk and complication associated with procedure are also minimal and easily manageable.
5
Miletić, Marija, Miloš Stojanović, Biljana Nedeljković-Beleslin, Mirjana Stojković, Jasmina Ćirić, and Miloš Žarković. "Taking all the sideroads of hyperthyroidism therapy: Pitfalls and possibilities." Medicinski glasnik Specijalne bolnice za bolesti štitaste žlezde i bolesti metabolizma 26, no. 80 (2021): 108–25. http://dx.doi.org/10.5937/medgla2180108m.
Full textAbstract:
There are three basic modalities for the treatment of thyrotoxicosis: thyrosuppresive drug therapy, ablation with radioactive iodine and surgical treatment. Patients who do not achieve adequate thyrotoxicosis control, as was the case of described patient, have a high mortality rate due to the possibility of developing a thyroid storm. The use of drug therapy for hyperthyroidism, as the first line of treatment, is associated with the appearance of various side effects, as was the case in our patient. Side effects of Methimazole are dose-dependent, while in the case of Propylthiouracil, the occurrence of side effects is not clearly dose-dependent. In the case of the described patient, all alternative, lesser known modalities for the treatment of hyperthyroidism were applied, after the occurrence of adverse reactions to thyrosuppressive therapy. Sodium perchlorate, ie. Sodium with perchloric acid is rarely used in the treatment of hyperthyroidism, as in cases of severe idiosyncratic reactions to thionamides, agranulocytosis or hepatitis, if the eumetabolic state is not achieved and the application of a therapeutic dose of radioiodine is not possible. It is applied in the form of a solution, usually 8%; In more severe forms of the disease, when hyperthyroidism is very pronounced, 10 to 15 drops a day are given 4 to 6 times and the dose is sometimes reduced to the minimum maintenance dose. After the adverse reaction even to sodium perchlorate therapy we were left with one more, last option-Plasma Therapy exchange. Plasma Therapy Exchange (TPE) is an out-of-body blood purification technique designed to remove high-molecular-weight substances bound to plasma proteins (autoantibody pathogens, immunocomplexes, cryoglobulins, myeloma light chains, endotoxins, lipoprotein-containing cholesterol, and thyroid). The effectiveness of treatment depends on the volume of blood being processed, the volume of plasma exchanged in each process, the number of procedures performed, the frequency of exchange and the rate of mobilization, stabilization and re-synthesis of cells or plasma components. TPE is an effective alternative treatment that provides an opportunity to prepare patients for definitive treatment: ablative therapy such as RAI ablation or thyroidectomy. Therapeutic plasmapheresis, if performed in specialist centers, is a safe, fast and effective method.
6
Luo, Ming, Xian-jun Zhang, and Wu-kui Cao. "Blood Purification for Severe Hepatitis in Vivo and Vitro." Infection International 2, no. 1 (March 1, 2013): 43–46. http://dx.doi.org/10.1515/ii-2017-0039.
Full textAbstract:
Abstract Exterior and interior blood purification (EIBP) refers to the combined therapy of interior blood purification (IBP) and exterior blood purification (EBP) for severe hepatitis. For one thing, integrated traditional Chinese and Western medicine therapy should be applied in IBP to reduce and prevent the generation and absorption of harmful substances in vivo. For another, EBP such as the artificial liver support system (ALSS) can extract blood from the body and various kinds of existing harmful substances in the blood can be cleared in vitro, using the treatment of plasma exchange, plasma perfusion, plasma adsorption, hemofiltration, hemodialysis. Therefore, IBP should be cooperated with EBP for the treatment of severe hepatitis, and EIBP can prevent the deterioration of this disease and lower the mortality of patients.
7
Yamada, Yuji, Hiroyuki Ohbe, Hideo Yasunaga, and Yoshitaka Miyakawa. "Clinical Practice Pattern of Acquired Thrombotic Thrombocytopenic Purpura in Japan: A Nationwide Inpatient Database Analysis." Blood 134, Supplement_1 (November 13, 2019): 2374. http://dx.doi.org/10.1182/blood-2019-125170.
Full textAbstract:
Introduction: Acquired thrombotic thrombocytopenic purpura (TTP) is a medically emergent disorder that is almost always fatal without proper treatment. While daily plasma exchange is recommended by several guidelines, its optimal frequency is unclear, and until March 2018 plasma exchange up to only three times a week was reimbursed by Japanese health insurance. In addition, rituximab has not been approved for acquired TTP in Japan. While it is known that clinical practice guidelines for TTP treatment in Japan may differ from those in other countries, real-world practice patterns remain unknown. Thus, we evaluated patients' characteristics and clinical practice patterns using a large nationwide inpatient database. Methods: For this nationwide epidemiologic study, we used the Japanese Diagnosis Procedure Combination inpatient database, which includes discharge abstracts and administrative claims data from more than 1,200 acute-care hospitals and covers approximately 90% of all tertiary-care emergency hospitals in Japan. All hospitalized patients who were diagnosed with TTP (International Classification of Diseases-Tenth Revision, code M311) on admission and who received plasma exchange during hospitalization were included in the study. Patients younger than 18 years were excluded. When patients with the ICD code for TTP were admitted more than once during the study period, we used data only from the first admission. We then evaluated patients' characteristics and clinical practice patterns. Results: We identified 1,638 patients who were newly diagnosed with acquired TTP from July 2010 to March 2017. The median (interquartile range [IQR]) age was 64 (47-74) years, and 674 (41%) patients were male; 648 (40%) required ICU admission, 447 (34%) required catecholamine, and 497 (30%) required mechanical ventilation. Although relatively contraindicated, 658 (40%) patients received platelet transfusion. In-hospital mortality was 32% (n=529/1,638). Median (IQR) length of hospital stay was 45 (25-78) days, and median total cost was US$40,897 ($24,204-$64,012). Among survivors, 856 (77%) were discharged home and 235 (21%) required subacute rehabilitation or chronic care facility. The median (IQR) interval from admission to plasma exchange was 4 (2-10) days; 385 (24%) patients received plasma exchange on the day of admission. Median (IQR) frequency of plasma exchange within 7 days of initial exchange was 3 (2-5) days; median (IQR) duration of plasma exchange was 10 (4-21) days. Of the 1,519 (93%) patients who received steroids, 1,071 (71%) received steroid pulse therapy. Among the 529 (32%) patients administered immunosuppressants, 221 (13%) received cyclophosphamide, 152 (9.3%) rituximab, 140 (8.6%) cyclosporine, and 86 (5.3%) tacrolimus. Conclusions: We assessed real-world clinical practice for TTP patients in Japan for the first time using the nationwide inpatient database. Our analysis showed a disparity between guidelines and real-world clinical practice, especially regarding frequency of plasma exchange. Optimal treatment strategy, efficacy, and safety should be evaluated in future studies. Disclosures Miyakawa: Zenyaku Kogyo: Consultancy; Sanofi: Speakers Bureau; Ablynx: Speakers Bureau; Chugai: Speakers Bureau.
8
Laje, Pablo, Dezhi Shang, Wenjing Cao, Masami Niiya, Masayuki Endo, Antoneta Radu, Nicole DeRogatis, et al. "Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell–mediated gene therapy." Blood 113, no. 10 (March 5, 2009): 2172–80. http://dx.doi.org/10.1182/blood-2008-08-173021.
Full textAbstract:
Abstract ADAMTS13, a metalloprotease primarily synthesized in liver and endothelial cells, cleaves von Willebrand factor (VWF) at the central A2 domain, thereby reducing the sizes of circulating VWF multimers. Genetic or acquired deficiency of plasma ADAMTS13 activity leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). To date, plasma infusion or exchange is the only proven effective therapy for TTP. In search for a better therapy, an autologous transplantation of hematopoietic progenitor cells transduced ex vivo with a self-inactivating lentiviral vector encoding a full-length murine Adamts13 and an enhanced green fluorescent protein (GFP) reporter gene was performed in Adamts13−/− mice after irradiation. All recipient mice showed detectable ADAMTS13 antigen and proteolytic activity in plasma despite only low levels of bone marrow chimerism. The levels of plasma ADAMTS13 were sufficient to eliminate the ultralarge VWF multimers and offered systemic protection against ferric chloride–induced arterial thrombosis. The data suggest that hematopoietic progenitor cells can be genetically modified ex vivo and transplanted in an autologous model to provide adequate levels of functional ADAMTS13 metalloprotease. This success may provide the basis for development of a novel therapeutic strategy to cure hereditary TTP in humans.
9
Shah, Md Salahuddin, ATM Atikur Rahman, and Momena Begum. "Autoimmune haemolytic anaemia treated by therapeutic plasma exchange and retuximab: A case report." Bangladesh Medical Research Council Bulletin 45, no. 2 (August 7, 2019): 126–28. http://dx.doi.org/10.3329/bmrcb.v45i2.42546.
Full textAbstract:
Autoimmune haemolytic anaemia (AIHA) is an uncommon disorder characterized by shortened red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. It presents with anaemia, jaundice, and splenomegaly with reticulocytosis, unconjugated hyperbilirubinaemia, and direct antiglobulin test (DAT) positivity.' AIHA has an estimated incidence of 1—3 cases per 100,000 subjects per year, a prevalence of 17:100,000 and a mortality rate of 11%.' AIHA is classified as warm AIHA (75.0% of all AIHA cases), cold AIHA (about 15.0%), and mixed type AIHA (less than 5.0%), based on the thermal range of autoantibodies involved in the pathogenesis.6 It can be idiopathic (50.0%) or secondary to lymphoproliferative syndromes (20.0%), autoimmune diseases (20.0%), infections, tumors and drugs.’ The laboratory diagnosis of AIHA depends on the result of direct antiglobulin test (DAT) which shows positivity with anti-IgG (usually in warm AIHA) and/or anti-C3d (usually in cold AIHA) antisera, and also the presence of laboratory findings supporting hemolysis such as increase of serum lactate dehydrogenase (LDH), reticulocytosis and spherocytosis in peripheral blood smears.‘ The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA is corticosteroids, which are effective in 70.0-85.0% of patients and should be slowly tapered over a time period of 6-12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20.0%), rituximab (effective in approx. 80.0-90.0% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option.’ Most of the immunosuppressive drugs have many deleterious side-effects and the onset of action is slow. Splenectomy carries the risk of an overwhelming post splenectomy sepsis.‘ Rituximab (so called “medical splenectomy”) is an effective second-line therapy, can work quickly with lasting effects, providing high initial response rates up to 87.0% and prolonged disease free survivals of 56.0% up to 2 years with reduced adverse reactions.‘ ' For warm AIHA, rituximab therapy is considered as a second line option as monotherapy or combined therapy. It can also be used as a first line therapy in combination with steroids for newly diagnosed patients. ' Another option, with less supportive
evidence in the literature, is the use of therapeutic plasma exchange (TPE) to quickly reduce the pahologic antibody titer in patients with an overwhelming hemolysis. 2 TPE has been performed in a relatively small
number of severely affected warm AIHA patients in whom the anemia could not be stabilized with steroids
and transfusion therapy alone, as a temporizing measure which seemed to stabilize the disease and increase the efficiency of blood transfusions.4 Current indication categories endorsed by the American Association of Blood Banks (AABB) and the American Society for Apheresis, TPE for AIHA is considered as acategory III indication, i.e. an application representing “heroic or last-ditch efforts on behalf of a patient”." Decision to transfuse RBC in AIHA should be based on the clinical condition of the patient. No critical patient should be denied blood transfusion due to serological incompatibility and “the least incompatible” RBC should be transfused in this situation.4 ”' Severe AIHA cases sometimes misdiagnosed or lately diagnosed. Early diagnosis and appropriate emergency interventions can save the life of these patients. In this case, we demonstrate the concomitant use of TPE and rituximab in the treatment of life-threatening warm AIHA.
Bangladesh Med Res Counc Bull 2019; 45: 126-128
10
Dau, Peter C. "Increased antibody production in peripheral blood mononuclear cells after plasma exchange therapy in multiple sclerosis." Journal of Neuroimmunology 62, no. 2 (November 1995): 197–200. http://dx.doi.org/10.1016/0165-5728(95)00121-4.
Full text
11
Namikawa, Akio, Yuko Shibuya, Haruki Ouchi, Hiroko Takahashi, and Yoshitaka Furuto. "A case of ABO-incompatible blood transfusion treated by plasma exchange therapy and continuous hemodiafiltration." CEN Case Reports 7, no. 1 (January 31, 2018): 114–20. http://dx.doi.org/10.1007/s13730-018-0307-4.
Full text
12
Tenchov, Boris, Rumiana Koynova, Borislava Antonova, Stella Zaharinova, Silviya Abarova, Zlatan Tsonchev, Regina Komsa-Penkova, and Albena Momchilova. "Blood plasma thermal behavior and protein oxidation as indicators of multiple sclerosis clinical status and plasma exchange therapy progression." Thermochimica Acta 671 (January 2019): 193–99. http://dx.doi.org/10.1016/j.tca.2018.12.001.
Full text
13
Huang, Chengshuang, Pei Huang, Xueqin Jiang, Hongbo Xu, Jian Lu, Runmei Tian, Ping Zhu, and Yan Chen. "Control of Hypercytokinemia in Critically Ill Epstein-Barr Virus Related Hemophagocytic Lymphohistiocytosis with Plasma Exchange and Continuous Renal Replacement Therapy." Blood 134, Supplement_1 (November 13, 2019): 2335. http://dx.doi.org/10.1182/blood-2019-122529.
Full textAbstract:
Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a severe and potentially fatal disease associated with abnormal function of the immune system. Epstein-Barr virus (EBV) is one of the most common triggers of HLH, especially in Asian countries. The control of EBV-HLH is still a challenging issue, particularly the early mortality, which was mainly due to the multi-organ failure coursed by hypercytokinemia. Therefore, control the hypercytokinemia induced by EBV are very important in critical ill EBV-HLH patients. Extracorporeal blood purification techniques already have been successfully applied to control hypercytokinemia in sepsis and septic shock patients. But there are few studies by using plasma exchange (PE) and continuous renal replacement therapy (CRRT) to treat critically ill EBV-HLH. This study aimed to evaluate the effect of PE+CRRT in the control of hypercytokinemia in critical ill EBV-HLH patients. Material and methods: The diagnosis a series of critically ill EBV-HLH patients admitted to the pediatric intensive care unit (PICU) were confirmed by comparing to the clinical and laboratory criteria of the HLH-2004 consensus. Real time polymerase chain reaction was used to detect EBV-DNA copies in the patients' serum, all the patients showed a significantly increasing of EBV-DNA copies in the serum (>1×104 Copies/mL). With the approval of the Ethics Committee and informed consents from the guardians of the patients, PE and CRRT combined HLH-2004 chemo-immunotherapy was used to treat these cases at the initial treatment, all the PE and CRRT sessions were finished in 3-7 days according to the condition of the patients. In addition, other supportive treatments were applied accordingly. The levels of cytokines were measured by using the CBA Human Th1/Th2 Cytokine Kit II (BD Biosciences, San Jose, California). Death occurred in 30 days after the initiation of treatment was defined as early death. Results: Clinical symptoms of all patients were remarkably improved after the PE and CRRT sessions. The EBV-DNA copies in the patients' serum was significantly decreased to around the limits of detection. And the abnormal high levels of cytokines were rapidly recovered to normal values. More importantly, no serious side effects were observed during the treatment. In addition, all the patients except one patient who did not continue the therapy achieved complete remission after 4 weeks' treatment, and no early death occurred in 30 days after the initiation of the treatment. Furthermore, the EBV-DNA were undetectable in the serum of these patients after 6 months. The remissions of these patients were maintained for a median time of 17 months (13-22 months). Conclusions: PE+CRRT associated HLH-2004 chemo-immunotherapy is a safe and effective strategy to control hypercytokinemia in critically ill EBV-HLH patients, and may help in the reduction of early death. More data from randomized, large-scale and multicenter studies are needed to make this conclusion more reliable. Disclosures No relevant conflicts of interest to declare.
14
Ortel, Thomas L., Doruk Erkan, and Craig S. Kitchens. "How I treat catastrophic thrombotic syndromes." Blood 126, no. 11 (September 10, 2015): 1285–93. http://dx.doi.org/10.1182/blood-2014-09-551978.
Full textAbstract:
Abstract Catastrophic thrombotic syndromes are characterized by rapid onset of multiple thromboembolic occlusions affecting diverse vascular beds. Patients may have multiple events on presentation, or develop them rapidly over days to weeks. Several disorders can present with this extreme clinical phenotype, including catastrophic antiphospholipid syndrome (APS), atypical presentations of thrombotic thrombocytopenic purpura (TTP) or heparin-induced thrombocytopenia (HIT), and Trousseau syndrome, but some patients present with multiple thrombotic events in the absence of associated prothrombotic disorders. Diagnostic workup must rapidly determine which, if any, of these syndromes are present because therapeutic management is driven by the underlying disorder. With the exception of atypical presentations of TTP, which are treated with plasma exchange, anticoagulation is the most important therapeutic intervention in these patients. Effective anticoagulation may require laboratory confirmation with anti–factor Xa levels in patients treated with heparin, especially if the baseline (pretreatment) activated partial thromboplastin time is prolonged. Patients with catastrophic APS also benefit from immunosuppressive therapy and/or plasma exchange, whereas patients with HIT need an alternative anticoagulant to replace heparin. Progressive thrombotic events despite therapeutic anticoagulation may necessitate an alternative therapeutic strategy. If the thrombotic process can be controlled, these patients can recover, but indefinite anticoagulant therapy may be appropriate to prevent recurrent events.
15
Cataland, Spero R., and Haifeng M. Wu. "How I treat: the clinical differentiation and initial treatment of adult patients with atypical hemolytic uremic syndrome." Blood 123, no. 16 (April 17, 2014): 2478–84. http://dx.doi.org/10.1182/blood-2013-11-516237.
Full textAbstract:
Abstract Published data demonstrating the efficacy of complement inhibition therapy in patients with atypical hemolytic uremic syndrome (aHUS) are remarkable in contrast to the historically poor long-term prognosis for aHUS patients treated with plasma-based therapy. Although both aHUS and acquired thrombotic thrombocytopenic purpura (TTP) remain clinical diagnoses, an increased understanding of both conditions has improved our ability to differentiate aHUS from acquired TTP. These same data have also demonstrated the importance of a more rapid identification and diagnosis of aHUS as the recovery of end-organ injury present appears to be related to the time to initiate therapy with eculizumab. The diagnosis of acquired TTP can be confirmed by the finding of severely deficient ADAMTS13 activity (<10%) with evidence of an ADAMTS13 antibody inhibitor whereas merely deficient ADAMTS13 activity in the absence of an ADAMTS13 autoantibody is more consistent with congenital TTP. In the absence of an objective diagnostic test, clinicians must rely collectively on platelet count, serum creatinine, and ADAMTS13 activity in the context of the response to plasma exchange therapy to identify patients whose diagnosis is most consistent with aHUS, and thus be more likely to benefit from therapy with eculizumab.
16
Sharma, Sanjeev Kumar, Dharma Choudhary, Meet P. Kumar, Rasika Setia, Vipin Khandelwal, Anil Handoo, and Divya Doval. "Thrombotic Thrombocytopenic Purpura: A Case Series from a Tertiary Care Centre in Northern India." Blood 132, Supplement 1 (November 29, 2018): 5006. http://dx.doi.org/10.1182/blood-2018-99-110773.
Full textAbstract:
Abstract Abstract: Thrombotic thrombocytopenic purpura is a medical emergency with varied clinical manifestations. High index of suspicion with careful evaluation of thrombocytopenia and hemolytic anemia is of paramount importance. Laboratory parameters of microangiopathic hemolytic anemia i.e. schitocytosis and increased LDH and indirect hyperbilirubinemia support the diagnosis. Plasma exchange is the treatment of choice. Post stem cell transplant TTP carries a poorer prognosis. Introduction: Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia associated with fever, renal dysfunction and neurological manifestations. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange mortality decreases to about less than 10% (1). Recent reports indicate that rituximab can induce remission in the majority of patients with classic TTP (2). We report here 13 cases of TTP who were treated at our hospital in last 4 years. Six of these patients developed features of TTP post allogenic stem cell transplantation. Materials and Methods: The study included retrospective analysis of patients who presented with the features of TTP. Patients with characteristic features of TTP included two or more features among the pentad commonly considered diagnostic of TTP. Evidence of microangiopathic hemolytic anemia and thrombocytopenia were the minimal requirement for the diagnosis with or without fever, renal dysfunction and neurological manifestations. Coagulation profile included prothrombin time and APTT. Liver and kidney function analysis was done in all patients. Response was assessed by clinical and laboratory parameters with monitoring platelet counts, LDH, and schistocytes in the peripheral blood film. Patients with LDH in normal range and platelet counts more than 100,000/µl were considered to have achieved remission. Results: Patients with classic TTP recovered with plasma exchange and/or rituximab. Post-transplant TTP patients had a poorer prognosis as five out of six post-transplant TTP patients died. Discussion: TTP can have a varied clinical presentation and can be associated with many other diseases. Our case series highlight the varied manifestations and associations of TTP and their management and outcome. TTP is a medical emergency and needs high index of suspicion for the diagnosis. In our series, TTP was diagnosed by the findings of thrombocytopenia and hemolytic anemia evidenced by presence of schistocytes in the peripheral blood film and increased LDH, in the absence of coagulopathy. TTP should be suspected in the presence of microangiopathic hemolytic anemia and thrombocytopenia (1,3), and treatment should be started immediately, as delay in treatment can increase the mortality (1). Plasma exchange has changed the prognosis of this highly fatal disease to a highly curable disease. Rituximab has further improved the management of TTP (2). Patients with classic TTP were treated with plasma exchange but 3 patients also required rituximab. All patients with classic TTP are in remission. Transplant-associated microangiopathy (TAM) is a MAHA and thrombocytopenia that occurs after bone marrow transplantation. Patients with post-transplant TTP were diagnosed based on thrombocytopenia and features of microangiopathic hemolytic anemia with schistocytosis and raised LDH, in the absence of coagulopathy. They were treated with FFP and steroids, as plasma exchange is not beneficial for post-transplant TTP (1). Repeated plasma exchange with increased frequency and/or rituximab therapy are the agents of choice in relapsing disease (3). Rituximab is a safe and effective treatment for newly diagnosed TTP, and has been shown to decrease the number of plasma exchange required to achieve remission. We used rituximab in 3 patients and all improved. Post transplant MAHA carried poor prognosis. Conclusion: Diagnosis of TTP requires a high index of suspicion and prompt treatment with plasma exchange, which results in a high cure rate. Rituximab is useful in patients relapsing or showing partial recovery. Plasma exchange has not been reported to be effective in post-transplant TTP. Acknowledgment: We are thankful to Ms Bharti Sharma for compiling the data. Disclosures No relevant conflicts of interest to declare.
17
Reid, Justin H., Karin M. Durant, Sheh-Li Chen, Anthony J. Perissinotti, Richard King, Rami Khoriaty, and Bernard L. Marini. "Role of caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura." Journal of Oncology Pharmacy Practice 26, no. 7 (June 30, 2020): 1695–702. http://dx.doi.org/10.1177/1078155220934862.
Full textAbstract:
Acquired thrombotic thrombocytopenic purpura is a rare blood disorder with a high early mortality rate, if untreated. Standard of care plasma exchange and glucocorticoids have dramatically improved survival. However, additional advancements are necessary to further decrease mortality. Caplacizumab-yhdp (Cablivi®) is the first Food and Drug Administration-approved treatment indicated for adult patients with acquired thrombotic thrombocytopenic purpura, in combination with plasma exchange and immunosuppressive therapy. However, there are considerable risks associated with the use of caplacizumab and they must be weighed against the benefits of the medication.
18
Zheng, X. Long, Richard M. Kaufman, Lawrence T. Goodnough, and J. Evan Sadler. "Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura." Blood 103, no. 11 (June 1, 2004): 4043–49. http://dx.doi.org/10.1182/blood-2003-11-4035.
Full textAbstract:
Abstract Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of adisintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P < .00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% (≈ 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (> 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P < .02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment.
19
Lim, Ming Y., and Charles S. Greenberg. "Successful Management of Thrombotic Thrombocytopenic Purpura in a Jehovah’s Witness: An Individualized Approach With Joint Decision-Making." Journal of Patient Experience 7, no. 1 (February 14, 2019): 8–11. http://dx.doi.org/10.1177/2374373519829902.
Full textAbstract:
The management of thrombotic thrombocytopenic purpura (TTP) presents a unique challenge in individuals who are unable to accept plasma due to religious beliefs, given that therapeutic plasma exchange (TPE) is the standard of care. A 61-year-old Jehovah’s Witness woman presented to our hospital with neurological symptoms and laboratory findings suggestive of TTP. On admission, she refused transfusion of blood products, specifically red blood cells, platelets, and plasma but accepted albumin and intravenous immunoglobulin (IVIG); fractions of plasma. She was started on steroids, IVIG, and TPE with albumin as replacement therapy with minimal improvement. After a detailed discussion with the patient and family, they agreed to accept cryosupernatant. The patient started TPE with cryosupernatant for replacement therapy, which resulted in clinical improvement. This case highlights the importance of an individualized approach with joint decision-making given the significant heterogeneity that exists in Jehovah’s Witnesses’ attitude toward the receipt of blood products.
20
Abe, Yuriko, Mamoru Ayusawa, Kengo Kawamura, Ryuta Yonezawa, Masataka Kato, Akiko Komori, Ryutaro Kohira, and Ichiro Morioka. "A combination therapy for Kawasaki disease with severe complications: a case report." Open Medicine 15, no. 1 (December 26, 2019): 8–13. http://dx.doi.org/10.1515/med-2020-0002.
Full textAbstract:
AbstractKawasaki disease (KD) is a form of acute multisystem vasculitis that presents with various complications, including coronary artery aneurysm. Heart failure and brain damage are rare, but life-threatening complications are associated with KD. Here, we describe a 4-year-old girl who developed intravenous immunoglobulin-resistant KD with both left ventricular failure and acute encephalopathy. On day 8 of the illness, the low left ventricular ejection fraction, mitral regurgitation, and low blood pressure, which required continuous administration of dobutamine, were observed during the treatments for KD, including intravenous immunoglobulin. She also appeared unconscious, where the electroencephalogram showed slow waves of activity in all regions of the brain. The cardiac performance improved after she received plasma exchange for three days. However, her unconsciousness with slow waves of activity on electroencephalogram and fever continued after the plasma exchange. Therefore, she was treated with methylprednisolone pulse, followed by prednisolone, as well as intravenous immunoglobulin. Finally, she recovered without any cardiac or neurological sequelae not only at the time she was discharged, but also throughout the follow-up period. The combination therapy using plasma exchange and methylprednisolone pulse may be a treatment option for severe KD with left ventricular failure and acute encephalopathy complications.
21
Scully, Marie, Vickie McDonald, Jamie Cavenagh, Beverley J. Hunt, Ian Longair, Hannah Cohen, and Samuel J. Machin. "A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura." Blood 118, no. 7 (August 18, 2011): 1746–53. http://dx.doi.org/10.1182/blood-2011-03-341131.
Full textAbstract:
Abstract The safety and efficacy of weekly rituximab 375 mg/m2 (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 × 109/L and 38% > 150 × 109/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.
22
Deveci, Burak, Rabin Saba, Husnu Altunay, Tayfur Toptas, George Kublashvilli, and Ihsan Karadogan. "Severe Acute Hemolytic Transfusion Reaction Treated with Ruxolitinib and Plasma Exchange." Transfusion Medicine and Hemotherapy 48, no. 4 (2021): 250–53. http://dx.doi.org/10.1159/000513056.
Full textAbstract:
<b><i>Introduction:</i></b> Acute hemolytic transfusion reaction is a rare but extremely mortal condition. Even small quantities of ABO-incompatible erythrocytes, as much as 50 mL, can lead to fatality. Since there is no successful standard therapy, preventive measures are very important. In this case report, we presented a 29-year-old woman who was transfused with 2 units of AB Rh-positive instead of 0 Rh-positive red blood cells following a cesarean section. As far as we know, this is the first patient in the literature for whom ruxolitinib was used as a part of therapy. <b><i>Case Report:</i></b> The patient was referred to our center 22 h after the ABO-mismatched transfusion. On admission, she had severe hemolysis, acute renal failure, and disseminated intravascular coagulation. Massive plasma exchange, hemodialysis, and pulse steroid therapy were commenced. The patient was refractory to first-line therapies. She was intubated on day 2 due to hypoxia, respiratory failure and changes in consciousness. Ruxolitinib, 2 × 10 mg/day, was started on day 3. The patient’s clinical status improved on day 6. Ruxolitinib was withdrawn on day 15, and the patient was discharged without any complications or sequels on day 26. <b><i>Conclusion:</i></b> Ruxolitinib may be life-saving in patients with ABO-incompatible transfusion reaction which follows a severe and catastrophic course.
23
Kadikoylu, Gurhan, Irfan Yavasoglu, Adil Coskun, Ali Onder Karaoglu, and Zahit Bolaman. "Emergent Therapy with Therapeutic Plasma Exchange in acute pancreatitis due to Severe Hypertriglyceridemia." Blood 124, no. 21 (December 6, 2014): 5102. http://dx.doi.org/10.1182/blood.v124.21.5102.5102.
Full textAbstract:
Abstract Hypertriglyceridemia causes acute pancreatitis in 1.3-3.8% of the patients. It is generally believed that the risk of acute pancreatitis increases in patients with severe hypertriglyceridemia (a triglyceride level of more than 1000 mg/dL). Although the mechanism of hypertriglyceridemia-induced acute pancreatitis (HIAP) is not clear, hydrolysis of triglycerides in and around the pancreas by pancreatic lipase seeping out of the acinar cells leads to accumulation of free fatty acids (FFA) in high concentrations. FFA are toxic and destroy acinar cells and capillary endothelium. Moreover, an increased concentrations of chylomicrons causes capillary plugging, ischemia, and acidosis. FFA in acidosis activate trypsinogen and initiate acute edematous and necrotizing pancreatitis . Therapeutic plasma change (TPE) is effective in HIAP in a few case series. According to a committee of the American Society of Apheresis in 2013, TPE is recommended to treat patients with HIAP as Category III indication. In this study, we evaluated the effectiveness of TPE in patients with acute recurrent pancreatitis due to severe hypertriglyceridemia as emergent therapy. Ten patients (8 male and 2 female, mean age 39±9 years) were treated with 14 TPE procedures. All patients were admitted to intensive care unit and treated with serum saline (4-6 L/day) and antibiotics such as meropenem, imipenem, or piperacillin-tazobactam. There was recurrent pancreatitis in six patients’ medical history. According to Balthazar classification, while 4 patients were in stage-C, each 2 patients were in stages-A, D, and E. Mean Ranson’s scores (prognostic scoring system) were 1.3 and 1 in admission and after 48 hours, respectively. Central venous route in 64% of TPE and fresh frozen plasma in 71% of TPE were used. A Haemonetics MCS+ instrument with intermittent flow and acid citrate dextrose solution to whole blood ratio of 1:14 as anticoagulation solution were used. Mean 6280 ml. plasma was exchanged. Mean duration of TPE was 221±79 min. Mean 773 ml. ACD solution was used. In all patients, triglyceride levels lowered less than 1000 mg/dL after one day of TPE. Mean triglyceride levels of the patients significantly decreased from 2876±1701 mg/dL to 1015±1137 mg/dL (p<0.001). Moreover the levels of mean total cholesterol and VLDL-cholesterol were significantly lowered from 483±279 mg/dL to 222±74 mg/dL (p=0.043) and from 574±338 mg/dL to 202±228 mg/dL (p<0.001), respectively. After one hour PE, platelet counts significantly lowered (p=0.007), but the levels of amylase and hemoglobin levels, and white blood cell counts did not change (p>0.05). One patient with necrotizing pancreatitis was died from multi-organ failure after 7 days. Other nine patients were discharged from hospital without local and systemic complication. Two procedures could not be completed due to instrumental problems. Nausea/vomiting and hypotension were seen in each one patient. Hypertriglyceridemia should be considered as a cause of acute recurrent pancreatitis. In conclusion, although now there is no evidence about early application of TPE, this procedure can be of benefit by correcting the clinical course may be effective as adjunctive therapy along with medical treatment in the treatment of acute pancreatitis due to severe hypertriglyceridemia. Disclosures No relevant conflicts of interest to declare.
24
Zhu, Kanger, Jun-ping Li, and Tao Zhang. "Clinical Features and Risk Factors of Pure Red Cell Aplasia Following Major ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation." Blood 108, no. 11 (November 16, 2006): 5238. http://dx.doi.org/10.1182/blood.v108.11.5238.5238.
Full textAbstract:
Abstract Objective:To study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). Method:We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April, 1997 to December, 2005. Results:1. 11 out of the 42 patients developed PRCA (26.1%); 2. All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n=9) or blood group B donor (n=2). 3. The following factors were associated with an increased risk of PRCA:(1) blood group O recipient;(2) blood group A donor;(3) blood group O/A in recipient/donor pair;4. Only blood group O/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis (P=0.006); 5. 6 patients who received donor-type plasma exchange did not develop PRCA, and among them, 5 cases were the O blood group recipients. 8 patients obtained spontaneous remission and in the remaining 3 patients, 2 patients with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA. Conclusions:The incidence of PRCA in this series of patients was 26.1%. Only blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange is an effective approach for the treatment and prophylaxis of PRCA. Anti-CD20 monoclonal antibody is indicated for patients who are not response to conventional therapy.
25
Watanabe, S., I. Nakashima, T. Misu, I. Miyazawa, Y. Shiga, K. Füjihara, and Y. Itoyama. "Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica." Multiple Sclerosis Journal 13, no. 1 (January 2007): 128–32. http://dx.doi.org/10.1177/1352458506071174.
Full textAbstract:
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) with a poor prognosis in terms of the optic-spinal function. Recently, a serum autoantibody (NMO-IgG) binding to the blood–brain barrier region was detected exclusively in patients with NMO and its high risk group. We treated six NMO-IgG-positive patients (all female; age 21–67 years old, median 41; three with optic neuritis and three with myelitis) who were unresponsive to high-dose intravenous methylprednisolone (HIMP), with plasma exchange (PE) (three to five exchanges, 2–3 L each). Three of the patients(one with optic neuritis and two with myelitis) showed definite functional improvement following PE. The clinical improvement started to appear after one or two exchanges, while there was little or no improvement in the other three patients. Such quick clinical responses to PE suggest a pathogenetic role of humoral immune factors in NMO, although delayed responses to the corticosteroid therapy might have contributed to the therapeutic efficacy, in part. Further clinical and in vitro studies are needed to determine whether the removal of NMO-IgG is directly relevant to the therapeutic efficacy. PE may hasten the functional recovery from corticosteroid-resistant relapses in some NMO-IgG-positive patients with NMO.
26
Yükselmiş, Ufuk, Saniye Girit, Yakup Çağ, and Mustafa Özçetin. "A child with acute liver failure associated with influenza A and resolved with plasma exchange treatment." Hong Kong Journal of Emergency Medicine 25, no. 5 (February 7, 2018): 281–85. http://dx.doi.org/10.1177/1024907918754441.
Full textAbstract:
Introduction: Although liver support systems play a major role as a bridge to transplantation, they may sometimes serve as a lifesaving treatment eliminating this need. Case presentation: We report on a 4-year-old boy who developed acute liver failure due to an influenza A (H3N2) infection as confirmed by clinical and laboratory data (molecular typing, stage 3 encephalopathy, brain edema, increased levels of ammonia, bilirubin, and international normalized ratio 5.2). Testing for any possible underlying liver disease showed no congenital or acquired liver pathology. Oral oseltamivir treatment was initiated and liver support therapy with plasma exchange was performed as a bridge to transplantation. A total of three plasma exchange sessions every other day, with fresh frozen plasma 1.5 times the total blood volume for the first course and 1 times for the subsequent courses, were performed. After the first plasma exchange, encephalopathy improved to stage 2, accompanied by substantial decreases in the elevated liver function tests. At the end of three plasma exchange sessions, the patient’s clinical condition improved significantly. At 14 days after admission, deep tendon reflexes of the patient were normal and levels of alanine transaminase, aspartate transaminase, bilirubin, ammonia, and international normalized ratio returned to normal. Liver support treatment with plasma exchange resulted in complete recovery and the patient was discharged on the 17th day of admission. Conclusion: Acute supportive treatment with plasma exchange proved to be life-saving in our case.
27
Thews, O. "Simulation Analysis of the Influence of Hemodialysis Control Parameters on Exchange Processes during Therapy." International Journal of Artificial Organs 15, no. 4 (April 1992): 213–21. http://dx.doi.org/10.1177/039139889201500405.
Full textAbstract:
The effect of dialysis control parameters (dialysate composition, ultrafiltration rate, blood flow rate) on the patient's internal milieu were studied using a mathematical model for the description of the dynamic exchange processes during hemodialysis. This model simulates the electrolyte and water distribution, the acid-base and the oxygenation state as well as the ventilation. The dialysate sodium concentration affects mainly the intra-/ extracellular water and the potassium distribution. The dialysate bicarbonate and acetate concentrations control the acid-base state and the electrolyte distribution (sodium and potassium). In addition, the dialysate acetate concentration has a strong effect on arterial oxygenation and on ventilation. The ultrafiltration rate controls the water distribution between plasma and the interstitial space but also the sodium distribution and the arterial acid-base state. The blood flow rate through the dialyser influences the acid-base state and, by this, it affects the potassium and sodium distribution. The acid-base state is affected in opposite directions when acetate or bicarbonate is used as a buffer.
28
Sayani, Farzana A., and Charles S. Abrams. "How I treat refractory thrombotic thrombocytopenic purpura." Blood 125, no. 25 (June 18, 2015): 3860–67. http://dx.doi.org/10.1182/blood-2014-11-551580.
Full textAbstract:
Abstract Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy.
29
Vazquez Mellado, Alberto, Olga Graciela Cantu-Rodriguez, Myrna Pequeño-Luévano, Laura Villarreal-Martínez, José Carlos Jaime-Pérez, Andres Gomez-De-Leon, Oscar Gonzalez-Llano, Perla Colunga-Pedraza, Guillermo Sotomayor-Duque, and David Gomez-Almaguer. "Low Dose Rituximab and Plasma Exchange As Frontline Therapy for Patients with Thrombotic Thrombocytopenic Purpura." Blood 126, no. 23 (December 3, 2015): 2257. http://dx.doi.org/10.1182/blood.v126.23.2257.2257.
Full textAbstract:
Abstract Thrombotic thombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, caused mainly by autoimmunity. Plasmapheresis is the standard of care achieving complete remission (CR) in 77-83% of cases but figures are variable depending on clinical context and ADAMTS-13 activity. Relapse is frequent in patients with <10% ADAMTS-13, and has been reported in 34-41% of cases. In most of these patients, an inhibitor against ADAMS-13 is detected thus, an effective frontline immunosuppressive treatment is needed to prevent relapses. Originally rituximab was used as a 2nd line therapy in patients with relapsed and refractory TTP aiding to achieve CR and to reduce relapse rates. The assumption that B cell population may be smaller in patients with autoimmune diseases than in neoplasia supported low-dose rituximab use and therefore, we administered plasmapheresis and low-dose rituximab as frontline therapy in 11 patients with a first TTP episode. Newly diagnosed TTP Patients >15 years received plasmapheresis with 1-2 exchanges daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks, starting the 1st dose immediately after the 2nd or 3rd plasma exchange. Relapse was defined as readmission with thrombocytopenia (< 100 × 109/L), schistocytes in peripheral blood, and ADAMTS-13 <10% after discharge. Between March 2011-March 2015, eleven patients were included; three men (27%) and eight women (73%), median age was 34 years (15-46). The median follow-up is 22 months (range 4-49) and for patients evaluable for ADAMTS-13 activity (n=8) 18 months (range 4-34). Two patients had seizures and mucocutaneous bleeding, 7 numbness, confusion and petechiae and 2 severe headache. Only 2 patients had renal damage at diagnosis (creatinine>1.2). Five patients had additional comorbidities (two diabetes mellitus, two HIV positive and one hypothyroidism) Median laboratory parameters at diagnosis: platelets 11 X 10⁹/L (range 7-27.4 X 10⁹/L), LDH 1822 U/L (range 705-8220 U/L, normal 70-180 U/L), hemoglobin 6 g/dL (range 4.2-11.8 g/dL). ADAMTS-13 activity was determined in 8 patients at diagnosis and in all of them was <10% (normal 40-130%). ADAMTS-13 autoantibody titer was determined in 7 patients and in all of them was >18 units/ml (ref: negative <12, undetermined 12-15, positive > 15 units/ml), shigella toxin was negative in all patients. The median number of plasmapheresis exchanges until CR was 7 (range 4-12)andprednisone at 1 mg/kg was administered to 6 patients. The estimated two-year relapse-free survival was 90%. One HIV+ patient suffered a relapse at 8 months follow-up. A high antibody titer against ADAMTS-13 was detected at relapse with no ADAMTS-13 activity and the patient was retreated with plasmapheresis (3 exchanges) and low-dose rituximab as described and has been in CR for 4 months. There were no complications related to plasmapheresis or rituximab infusion. According to our results low-dose rituximab and plasma exchange are effective in achieving rapid and sustained response in TTP. Of note, the median of plasmapheresis needed to CR (7, range 4-12) was lower than that reported for patients with <10% ADAMTS-13 activity (19 procedures) (Kremer Hovinga JA et al Blood 2010). In our series, median follow-up for patients evaluable for severe ADAMTS-13 deficiency was 18 months, and only one HIV-positive patient relapsed at the 8th month. Our study suggest that frontline low-dose rituximab and plasmapheresis are effective as frontline treatment for TTP. This combination is associated with relatively rapid response and low relapse rate in previously untreated patients, however, a prospective clinical trial is needed to effectively demonstrate if rituximab 100 mg x 4 weekly dose is as effective as the conventional 375 mg/m2 X 4 weekly dose. Disclosures Off Label Use: Rituximab an anti CD monoclonal antibody is used in our work to deplete B cell population therefore stop the production of autoatibodies against ADAMTS-13.
30
Mintz, Paul D., A. Neff, M. MacKenzie, C. Hillyer, L. T. Goodnough, C. Kessler, K. McCrae, et al. "Therapeutic Plasma Exchange (TPE) for Thrombotic Thrombocytopenic Purpura (TTP) Using Plasma Prepared with Photochemical Treatment (INTERCEPT Plasma)." Blood 104, no. 11 (November 16, 2004): 838. http://dx.doi.org/10.1182/blood.v104.11.838.838.
Full textAbstract:
Abstract INTERCEPT Plasma (I-FFP) uses amotosalen (S-59, 150μM ) and UVA light (3 J/cm2 to inactivate pathogens in single plasma units. TPE is the mainstay therapy for TTP. Efficacy and safety of I-FFP for TPE of TTP were evaluated in a double-blinded, randomized, controlled trial. Eligible patients (pts) with TTP unrelated to cancer, cancer therapy, transplantation, AIDS, HUS, or SLE received daily TPE (1.0 to 1.5 blood volumes) with either I-FFP or conventional plasma (C-FFP) for up to 2 TPE cycles, each with a maximum of 35 days (d) of TPE. Treated pts were followed for 7 d after the last TPE to detect overall adverse events (AE) and for 60 d after achieving remission to detect relapse and serious adverse events (SAE). The primary endpoint was the proportion of pts in remission (platelet count ≥ 150,000/μL for 2 consecutive d without neurologic progression) within 30 d after the 1st TPE. Secondary endpoints were: time to 1st remission, volume of plasma used, number of TPEs, relapse rates after remission, vWF cleaving protease (vWF-CP) activity and inhibitor levels, antibodies to potential S-59 neoantigens, and safety. 35 pts (17 I-FFP, 18 C-FFP), mean age of 40 yr, 80% female were treated. TPE with I-FFP was comparable to C-FFP in remission rates (82% I-FFP, 89% C-FFP:p=0.66), median time to remission (6 d I-FFP, 6 d C-FFP:p=0.58), mean total volume of plasma exchanged (40.6 L I-FFP, 41.3 L C-FFP:p=0.86), mean number TPEs (11.3 I-FFP, 10.3 C-FFP:p=0.68), and relapse rates (36% I-FFP, 38% C-FFP:p=1.00). Baseline and post TPE vWF-CP activity and inhibitor levels were similar between groups. Overall AEs, serious AEs, deaths (1 I-FFP and 1 C-FFP: neither attributed to TPE), rates of discontinuation from study, laboratory abnormalities, and vital signs (VS) during TPE were comparable between groups. 1 C-FFP pt had TRALI. Five I-FFP pts had AEs coded to the cardiac system organ class compared to no C-FFP pts (p=0.02). In 4 of the I-FFP pts, these AEs were non-serious and did not interrupt TPE. One I-FFP pt with relapsing TTP had a serious AE after 12d of TPE, recovered without sequelae, was withdrawn from study, and continued on non-study FFP TPE with recurrent relapse. No antibodies to potential S-59 neoantigens were detected in any pts. In this trial, efficacy endpoints and safety profiles of TTP pts treated with I-FFP TPE were similar to those for TTP pts treated with C-FFP TPE.
31
Bambauer, Rolf. "Therapeutic Apheresis in Neurology." Journal of Clinical Research and Reports 5, no. 5 (November 21, 2020): 01–09. http://dx.doi.org/10.31579/2690-1919/118.
Full textAbstract:
Therapeutic plasma exchange (TPE) remove harmful plasma constituents from patient’s blood and replacing the extracted plasma with replacement solutions. The advantages of TPE with hollow fiber membranes are a complete separation of the corpuscular components from the plasma and due to increased blood flow rate higher efficacy. Therapeutic apheresis (TA) is used more and more throughout the world. The development of new, more sophisticated membranes and new adsorption technologies allow the most selective separation of plasma components. TA has been successfully introduced in a variety of autoantibody-mediated diseases. TA is the first- or second-line therapy in the treatment of neurological disorders. The updated information on immunology and molecular biology of different neurological diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different neurological diseases can be treated by various apheresis methods. Pathogenetical aspects are demonstrated in these diseases, in which they are clarified. TA has been shown to effectively remove the autoantibodies, immune complexes, inflammatory moderators, paraproteins, and other toxins from blood and lead to rapid clinical improvement. For the neurological diseases, which can be treated with TA, the guidelines of the Apheresis Application Committee (AAC) of the American Society for Apheresis (ASFA) are cited.
32
Diana, Jean-Sebastien, Sandra Manceau, Tioka Rabeony, Caroline Elie, anne-Marine Lenzotti, Valerie Jolaine, Mélodie Aubart, et al. "Therapeutic Plasma Exchange in Pediatrics for Immunologic Disorders; Tolerated and Safe Process for Pediatric Life-Threatening Conditions." Blood 134, Supplement_1 (November 13, 2019): 4986. http://dx.doi.org/10.1182/blood-2019-122106.
Full textAbstract:
Therapeutic plasma exchange (TPE) is advocated as a treatment to several conditions and applications: solid organs transplantation, kidney and pediatric immune disorder. Apheresis for children diseases has been poorly investigated in mostly small, uncontrolled studies.The purpose was to report our experience, and provide uniform and relatable data, in order to improve disease management. We included 94 patients, aged under 18 years old, who underwent TPE in the pediatric center of Necker-Enfants-Malades hospital from January 2005 to December 2014. Data were retrospectively collected in an electronic case report form via a web-based data collection system. 78 patients were selected, including 36 females and 42 males with a median age of 9.78 years [range 0.53; 17.93]. They achieved a total number of 731 procedures. Indications were antibody-mediated rejection (n= 33; 42%) or desensitization therapy (n= 5; 6%) for solid organ or hematopoietic transplantations; microangiopathy (n= 17; 22%); renal diseases (n= 6; 8%) and pediatric inflammatory diseases (n= 16; 21%); or hyperviscosity syndrome (n = 1; 1%). Each patient had an average of 6 procedures for the first session [range 1; 19] with a median volume of 1834 ml [range 500; 5000 ml] corresponding to a median total plasma volume (TPV) equivalent of 1.39 l/m2[range: 0.58; 2.1 l/m2].Within 15 days in the beginning of the sessions, 72 patients (92%) presented a total of 311 Advers Events(AEs) potentially related to TPE. 94 AEs were not related to TPE sessions.There was a median of 5 AEs/patients [range: 0; 24]. There was no significant increased risk of AEs due to diseases, intensity of care, venous access, plasma substitute and body weight. Few of AEs were potentially life-threatening and concerned pediatric critical care situations. Allergic reactions represented only 20 AEs for 14 patients (grade I n= 18; grade II n= 1; grade III n= 1). At the endpoint of M12, 15 (19%) patients had died, no death had been related to the TPE process. Nine patients performed a second or a third session of procedures and 10 (13%) patients had severe persistent clinical disease. We describe one of the largest retrospective pediatric cohort to date, to the last international recommendations. Our experience on children TPE feasibility concern specific life‐threatening conditions and otherwise potential refractory diseases. TPE were generally well tolerated and the majority of the adverse effects were anticipated and could therefore be avoided. Based on this work, and in order to progress in the understanding of the TPE field, it would be interesting to increase pediatric data with prospective and multicenter cohort. Disclosures Cavazzana: Smartimmune: Other: Founder of Smartimmune.
33
Bogdan, T. V., V. O. Onishchenko, V. V. Bogdan, and O. V. Savchenko. "The effect of L-arginine on the balance of essential amino acids in plasma of the patients with stable angina." Likarska sprava, no. 7-8 (December 30, 2020): 25–30. http://dx.doi.org/10.31640/jvd.7-8.2020(3).
Full textAbstract:
Background. Despite the significant achievements of clinical medicine in the prevention, diagnosis and treatment of coronary heart disease, the levels of morbidity, disability and mortality among the population of Ukraine from this pathology remain consistently high. The purpose. To improve the treatment of patients with stable angina by studying the effect of L-arginine on the balance of essential amino acids in blood plasma. Material and methods. It was examined 67 patients with stable angina. They were divided into two groups: group Ipatients received antianginal basic therapy, group II patients received basic antianginal therapy and L-arginine. The amino acid spectrum of patients' blood plasma was studied by ion-exchange liquid column chromatography, using an automatic amino acid analyzer T-339 Microtechna (Czech Republic, Prague). Results and discussion. In patients with stable angina who received basic therapy and L-arginine, in contrast to patients who received only basic therapy, plasma levels of arginine became normalized, which probably contributes to the synthesis of NO. The level of valine, leucine and isoleucine, which provide the synthesis of acyl-CoA and succinyl-CoA, became also normalized. Conclusion. Administration of L-arginine to patients with stable angina together with antianginal therapy helps to correct plasma amino acid imbalances, which is likely to effectively affect the course of the disease and prognosis.
34
Rossetti, Emanuele, Francesco Polisca, Francesca Tortora, Roberto Bianchi, and Sergio Picardo. "Early Hybrid Extracorporeal Therapies in Pediatric Acute Liver Failure of Unknown Etiology." Blood Purification 49, no. 3 (2020): 382–84. http://dx.doi.org/10.1159/000504559.
Full textAbstract:
We describe a 9-year-old boy with acute liver failure of unknown etiology, unresponsive to standard medical therapy, with increasing hyperammonemia blood level, lactate elevation, a pediatric end liver stage of 20, a hepatic encephalopathy (HE) score of 2, and scheduled for emergent liver transplantation on the waiting list. We admitted him in the pediatric intensive care unit and managed him in the early stages with continuous renal replacement therapy and therapeutic plasma exchange as soon as neurologic impairment started to worsen. He recovered from his HE after 3 days of blood purification and was removed from the transplantation waiting list due to progressive liver function improvement.
35
Goodnough, Lawrence Tim, David Strasburg, Dorothea Verbrugge, and Charles Fisher. "Morbidity and Mortality in Adults With “Idiopathic” Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome." Journal of Intensive Care Medicine 9, no. 4 (July 1994): 167–71. http://dx.doi.org/10.1177/088506669400900401.
Full textAbstract:
We attempt to define the morbidity and mortality of adult patients with idiopathic (i.e., absence of known co-existent factors) thrombotic thrombocytopenic purpura/hemolytic uremia syndrome (TTP/HUS) who underwent a standard program of aggressive plasma exchange therapy. We conducted a retrospective review of patients treated with a diagnosis of TTP/HUS at a single institution over 7 years. TTP/HUS diagnosis in 52 patients was based on presence of microangiopathic, hemolytic anemia, and thrombocytopenia (< 150,000/mm3), along with 1 or more of the following: neurological abnormalities, renal dysfunction, or fever (>38°. Thirteen patients with co-existent factors of systemic lupus erythematosis, pregnancy, HIV infection, and cyclosporin or mitomycin C therapy were excluded from analysis; therefore, 39 patients treated over 7 years were studied. Interventions involved therapeutic plasma exchange of 150% plasma volume, with daily plasma replacement, until remission or death. Steroid therapy, antiplatelet therapy, or splenectomy were added at the discretion of the participating physicians. We found an overall mortality of 13 (35%) in the 39 patients. Time from onset of symptoms until initiation of therapy for all patients was 17 ± 24 days (mean ± SD). Average hospital stay was 29 ± 32 days, of which 10 ± 29 days and 12 ± 26 days were spent on the ventilator and in the intensive care unit, respectively. No differences between patients who survived and those who died were found with respect to gender, age, or blood component support (i.e., platelet, red cell transfusions) required. Six (30%) of 20 patients relapsed after attaining initial remission with medical therapy. Nine (60%) of 13 patients refractory to medical management underwent splenectomy and survived. We conclude that despite aggressive medical and surgical management, idiopathic TTP/HUS remains a syndrome with significant morbidity and mortality in otherwise young and healthy adults. Our results suggest that these patients should not be considered stable and should not undergo trial therapy with steroid or plasma infusion therapy. Earlier diagnosis and treatment with daily plasma exchange, along with consideration of surgical splenectomy in patients refractory to medical management, may be necessary if outcomes are to be improved in the management of this syndrome.
36
Zhou, X.-J., M. Chen, S.-X. Wang, F.-D. Zhou, and M.-H. Zhao. "A 3-year follow-up of a patient with acute renal failure caused by thrombotic microangiopathy related to antiphospholipid syndrome: case report." Lupus 26, no. 7 (December 5, 2016): 777–82. http://dx.doi.org/10.1177/0961203316682098.
Full textAbstract:
Background Microvascular manifestations of antiphospholipid antibody syndrome in the kidneys include acute renal failure, thrombotic microangiopathy and hypertension. Therapy has been largely empiric. Case report A 49-year-old Chinese man presented with anuric acute renal failure without abundant proteinuria and heavy haematuria, but markedly low levels of urinary sodium, potassium and chlorine upon admission. On day 1 of hospitalization, his thrombocytopenia, anaemia and renal failure showed rapid progression. The presence of lupus anticoagulant and vascular ischaemia of the small vessels in renal arteriography were also observed. Anticoagulants, continuous renal replacement therapy, glucocorticoids and six sessions of plasma exchange were started. After the fourth plasma exchange (on day 20), his urine output increased and began to normalize. On day 25, haemodialysis was stopped and his general condition gradually improved. A renal biopsy was subsequently performed, and the histopathological diagnosis was thrombotic microangiopathy due to antiphospholipid antibody syndrome. A further 3-year follow-up showed that his haemoglobin level, platelet count and serum creatinine were within the normal range, with stable blood pressure. Conclusion Treatment modalities such as anticoagulation, immunosuppression and plasma exchange are likely to be necessary when severe acute renal failure combined with thrombotic microangiopathy present in nephropathy of antiphospholipid antibody syndrome.
37
Chen, Haifei, Ailin Fu, Jing Wang, Tianqin Wu, Zhengyang Li, Jieqing Tang, Hongshi Shen, et al. "Rituximab as first-line treatment for acquired thrombotic thrombocytopenic purpura." Journal of International Medical Research 45, no. 3 (March 21, 2017): 1253–60. http://dx.doi.org/10.1177/0300060517695646.
Full textAbstract:
Objective To investigate the efficacy and safety of rituximab (RTX) as first-line treatment of acquired thrombotic thrombocytopenic purpura (aTTP). Methods Twenty-five patients with acute aTTP and/or severe a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency were admitted to our centre from April 2009 to March 2015. Fourteen patients received RTX plus standard therapy (plasma exchange and corticosteroids) at acute episodes. Haemoglobin, platelet count, schistocytes, lactate dehydrogenase levels, ADAMTS13 activity and its inhibitors, and the ratio of B lymphocytes in the peripheral blood, were monitored. The number of plasma exchange (PEXs), total plasma volume, remission time, relapse ratio, and adverse effects were recorded. Results The median number of PEXs was 5 (2–17) sessions and median total plasma volume was 168.43 ml/kg (62.86–469.52 ml/kg). Patients achieved haematological remission at a median of 15 days (5–22 days), and the median time of immunological remission was 2 weeks (2–8 weeks) with a median follow-up of 13 months (3–61 months). ADAMTS13 activity significantly increased after 2 weeks. The B lymphocyte percentage in peripheral blood was reduced 1 week after the first dose of RTX infusion compared with before treatment (2.21% ± 5.23% vs 18.47% ± 7.34%, P = 0.000 [the result of statistical software]), and began to gradually increase 9 months later. Severe adverse effects and relapsing TTP were not observed during therapy and follow-up. However, one patient who had sustained immunological remission died of severe pneumonia 7 months later. Conclusion Although our study was limited by its small sample number and it was a non-controlled, clinical trial, it showed potential benefits of RTX therapy for acute aTTP. RTX may be administered as a first-line therapy for lowering patients’ relapse rate in the long term. Randomized, controlled trials of RTX for aTTP are required.
38
Ma, Yuanji, Fang Chen, Yan Xu, Ming Wang, Taoyou Zhou, Jiajie Lu, Ping Feng, Ying Wang, Lang Bai, and Hong Tang. "Safety and Efficacy of Regional Citrate Anticoagulation during Plasma Adsorption Plus Plasma Exchange Therapy for Patients with Acute-on-Chronic Liver Failure: A Pilot Study." Blood Purification 48, no. 3 (2019): 223–32. http://dx.doi.org/10.1159/000500408.
Full textAbstract:
Background: Patients with acute-on-chronic liver failure (ACLF) might be at risk for citrate accumulation during plasma adsorption plus plasma exchange (PE) therapy with regional citrate anticoagulation (RCA). Objectives: To assess the safety and efficacy of RCA during double plasma molecular adsorption system (DPMAS) plus PE therapy for patients with ACLF. Method: A prospective nonrandomized controlled pilot study was conducted at West China Hospital of Sichuan University. Patients with ACLF were enrolled to heparin anticoagulation (HA) group and RCA group. Serial blood samples were taken. Patients were followed up for 3 months. Results: Twenty-four patients with 94 sessions of HA and 28 patients with 106 sessions of RCA were enrolled. RCA method did not affect the therapeutic efficacy, the function of extracorporeal circulation, and the prognosis of these patients. The occurrences of citrate accumulation in RCA group were 0.0, 67.0, 100.0, 34.0, and 0.0% before DPMAS therapy, at the end of DPMAS therapy, immediately after PE therapy, 2 h after PE therapy, and the next morning, while that in HA group were 0.0, 0.0, 100.0, 7.4, and 0.0%, respectively. The occurrences of citrate accumulation at the end of DPMAS therapy and at 2 h after PE therapy in RCA group were much higher than that in HA group (67.0 vs. 0.0%, p = 0.000; 34.0 vs. 7.4%, p = 0.000, respectively). Although the trend of citrate accumulation in RCA group was much more obvious than that in HA group during and after DPMAS plus PE therapy (p = 0.000), the values on the next morning were similar between the 2 groups (p > 0.05). The main alteration of acid–base status was metabolic alkalosis with no difference between the 2 groups. Conclusions: RCA might be safe and effective in patients with ACLF receiving plasma adsorption plus PE therapy. RCA method might offer an alternative anticoagulation method for them.
39
Hobbs, William E., Emily E. Moore, and Jill M. Johnsen. "Von Willebrand Factor Activity Increases Following Automated But Not Simple Red Blood Cell Exchange Transfusion In Sickle Cell Disease Patients." Blood 122, no. 21 (November 15, 2013): 986. http://dx.doi.org/10.1182/blood.v122.21.986.986.
Full textAbstract:
Abstract Background Red blood cell (RBC) exchange transfusion is a commonly used therapy for acute and chronic complications of sickle cell disease (SCD). However, the therapeutic benefit of RBC exchange in many clinical situations is not well established. RBC exchange can be performed in two ways: 1) manually, involving repeated cycles of whole blood phlebotomy followed by simple transfusion of donor RBC, or 2) automated exchange utilizing apheresis to rapidly remove patient RBC while returning patient plasma, platelets, and leukocytes along with donor RBC to the patient. Unlike manual exchange transfusion, automated RBC exchange exposes patient blood to high shear stress as blood transits the apheresis machine, reaching wall shear stresses of 30-50 dyne/cm2 (within the range of arterial shear) with regional peak wall shear stresses of over 500 dyne/cm2 (supraphysiologic shear). Increased wall shear stress increases the reactivity of plasma von Willebrand Factor (VWF), in part by enhancing exposure of the VWF A1 domain which is directs binding to the platelet glycoprotein (GP) Ib-IX-V. Increased VWF reactivity has been implicated in SCD pathogenesis, likely by promotion of adhesive interactions between VWF and sickle erythrocytes, platelets, leukocytes, and the vessel wall. Hypothesis We hypothesized that automated RBC exchange would increase the reactivity of VWF as compared to manual RBC exchange in SCD patients. Methods We assessed VWF parameters in the plasma of SCD patients before and after manual exchange transfusion and/or automated RBC exchange transfusion performed for non-acute clinical indications. The VWF parameters assessed were VWF antigen level (VWF:Ag), VWF activity (VWF:Act) as assessed by ELISA (DiaPharma) detecting the spontaneous Gp Ib-IX-V binding conformation in the VWF A1 domain, total active VWF (VWF:TA) calculated by VWF:TA = (VWF:Ag) x (VWF:Act), VWF ristocetin cofactor activity (VWF:RCo), and VWF multimer composition. Results Six SCD patients on chronic, monthly exchange transfusion support were enrolled in the study. Blood samples were obtained prior to and immediately following multiple separate exchange transfusion episodes for each patient. Three patients underwent only automated RBC exchange transfusion, one underwent only manual RBC exchange transfusion, and two patients underwent both manual and automated RBC exchange transfusion. Compared to normal pooled plasma (NPP), SCD patients prior to RBC exchange transfusion had increased VWF:Ag (1.3-2.1 fold), VWF:Act (mean 124% of normal), and VWF:TA (0.6-2.2, mean 1.52; VWF:TA of NPP= 1.02). There was no statistically significant change in VWF:Ag following manual or automated exchange. There was a statistically significant increase in VWF:Act in patients following automated RBC exchange (mean 25% increase, p<0.05 with range 12%- 53%) but not manual exchange (mean 3.4% increase, range 1.4%-6.3%). In addition, we found an increased VWF:TA following automated (mean 31% increase, p<0.05) but not manual exchange transfusion. Patients exhibiting the highest VWF:TA post-exchange transfusion also had increased VWF:Rco in response to low dose and high dose ristocetin. The patient plasma with the highest VWF:TA post-RBC exchange (3.59) was noted to initiate spontaneous platelet agglutination in the absence of ristocetin. The observed increases in VWF:TA or VWF:RCo did not correlate with differences in VWF multimer composition on non- reducing agarose gels. Conclusions VWF activity is increased after automated RBC exchange but not manual RBC exchange in adult sickle cell patients on chronic exchange transfusion. These increases are likely a result of shear induced activation of VWF in the apharesis machine circuit. We speculate that the increased VWF reactivity observed following automated RBC exchange transfusion could contribute to VWF-mediated adhesive interactions and aggravate SCD vascular complications, potentially conferring a microangiopathic effect, in certain clinical situations. Maneuvers to decrease automated RBC exchange transfusion-induced VWF activation may lead to improved outcomes for SCD patients requiring exchange transfusion. Disclosures: No relevant conflicts of interest to declare.
40
T. S., Akingbola, Shonde-Adebola K. B., Anyanwu-Yeiya C. C., Ezekekwu C. A., Adeoye O. A., Odebiyi H. A., Akinyemi R., and Kotila T. R. "Therapeutic Plasma Exchange in the Management of Myasthenia Crisis in a Resource Poor Setting." International Journal of Healthcare and Medical Sciences, no. 55 (May 20, 2019): 22–25. http://dx.doi.org/10.32861/ijhms.55.22.25.
Full textAbstract:
BACKGROUND: Therapeutic Plasma Exchange (TPE) is an apheresis treatment in which the plasma component of blood is removed and replaced with supplemental fluids. It is an immunomodulatory treatment that has been reported to be a successful therapeutic procedure for the treatment of severely compromised patients with myasthenia gravis when given at short intervals. TPE is known to have a comparable efficacy to intravenous immunoglobulin (IVIG) in the treatments of patients with moderate to severe myasthenia crisis. METHODOLOGY: We report a case of a 47year old male patient with severe myasthenia crisis. He was managed using cobe spectra version 6.1 to carry out an automated TPE, with a suboptimal response and subsequent use of IVIG resulting in full recovery. This report highlights the possible factors that may hinder optimal response of a patient with Myasthenia crisis to TPE procedure in a poor resource setting. CONCLUSION: TPE is an essential immunomodulatory therapy in the management of acute myasthenia crisis whether given alone or in combination with immunosuppressive drugs. There can be a rebound overproduction of the offending autoantibodies in MG following TPE which can be cleared from circulation using immunosuppressive therapy.
41
Sinanović, Osman, Sanela Zukić, Adnan Burina, Nermina Pirić, Renata Hodžić, Mirza Atić, Mirna Alečković-Halilović, and Enisa Mešić. "Plasmapheresis in neurological disorders: six years experience from University Clinical center Tuzla." F1000Research 6 (July 26, 2017): 1234. http://dx.doi.org/10.12688/f1000research.11841.1.
Full textAbstract:
Background: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique that is designed to remove substances with a large molecular weight. The TPE procedure includes removal of antibodies, alloantibodies, immune complexes, monoclonal protein, toxins or cytokines, and involves the replenishment of a specific plasma factor. The aim of the study was to describe the clinical response to TPE in various neurological patients, and to assess the clinical response to this therapy. Methods: The study was retrospective. We analyzed the medical records of 77 patients who were treated at the Department of Neurology, University Clinical Center (UCC) Tuzla from 2011 to 2016. Results: 83 therapeutic plasma exchanges were performed in the 77 patients. There was a slight predominance of male patients (54.5%), with an average age of 51±15.9 years. The most common underlying neurological diseases were Guillain–Barré syndrome (GBS) (37.7%), then chronic inflammatory demyelinating polyneuropathy (CIDP) (23.4%), multiple sclerosis (MS) (11.7%) and myasthenia gravis (10.4%). Less frequent neurological diseases that were encountered were paraneoplastic polyneuropathies (5.2%), neuromyelitis optica (also known as Devic’s disease) (3.9%), motor neuron disease (3.9%), polymyositis (2.6%) and multifocal motor neuropathy (1.2%). Conclusions: Six years experience of therapeutic plasma exchange in neurological patients in our department have shown that, following evidence-based guidelines for plasmapheresis, the procedure was most effective in patients with GBS, CIDP and myasthenia gravis.
42
Ignjatovic, Ljiljana, Zoran Kovacevic, Dragan Jovanovic, Neven Vavic, Zoran Paunic, Milorad Radojevic, Violeta Rabrenovic, et al. "Our first experiences in applying an original method for removal of ABO-isoagglutinins in ABO-incompatible kidney recipients." Vojnosanitetski pregled 66, no. 2 (2009): 117–22. http://dx.doi.org/10.2298/vsp0902117i.
Full textAbstract:
Background/Aim. Due to improved methods for removal of ABO isoagglutinins and novel immunosuppressive protocols, short and long term outcome in blood group incompatible is similar to blood group compatible kidney transplantation. The aim of this study was to determine the efficacy of our original method for removal of ABO isoagglutinins from the blood in ABO-incompatible kidney allograft recipients. Method. Between 2006 and 2008 twelve patients were transplanted from ABO incompatible living donors. Titers of ABO isoagglutinins were 4-128 (IgG). Immunosuppressive therapy started 14 days before kidney transplantation with rituximab, followed by a triple therapy (prednisone + tacrolimus + mycophenolate mofetil) and the first plasma exchange (PE) procedure, in which one plasma volume was substituted with albumin and saline on day 7 before transplantation. For selective extracorporeal immunoadsorption, the removed plasma was mixed with donor blood type filtered red blood cells, centrifuged and the supernatant separated and preserved. In the next PE procedure, the removed plasma was replaced with immunoadsorbed plasma, and so on. Titers of ABO agglutinins, renal allograft function and survival were followed-up. Results. The pre-transplant treatment consisting of 1-5 PE procedures and immunosuppressive therapy resulted in target ABO agglutinins titers below 4. During a 10-24 month follow-up three patients had an early acute rejection, one patient acute rejection and hemolytic anemia, two patients surgical complications and one of them lost his graft. In the post-transplant period, the titers of ABO antibodies remained below 4. All the patients had stable kidney allograft function with mean serum creatinine ?SD of 129 ? 45 ?mol/l at the end of the study. Conclusion. Our method for removal of ABO antibodies was effective in a limited series of patients and short-term follow-up.
43
Haraya, Kenta, Zenjiro Sampei, Tatsuhiko Tachibana, Taku Fukuzawa, Siok Wan Gan, Meiri Shida-Kawazoe, Yuichiro Shimizu, et al. "SKY59: A Long-Lasting Engineered Anti-C5 Antibody for Subcutaneously Injectable Anti-Complement Therapy." Blood 132, Supplement 1 (November 29, 2018): 3611. http://dx.doi.org/10.1182/blood-2018-99-110145.
Full textAbstract:
Abstract Modulating the complement system is a promising approach in drug discovery for overcoming uncontrolled complement activation, which is known to cause various disorders. While these disorders can be effectively treated by inhibiting complement C5 with a therapeutic antibody, the high concentration of C5 in plasma requires a huge dosage and frequent intravenous administration of the antibody. We have generated SKY59, an engineered humanized anti-C5 monoclonal antibody that shows long-lasting neutralization of C5 in cynomolgus monkeys, which enables subcutaneous delivery or less frequent administration. We found that, although the effective duration of the antibody was prolonged by engineering a pH-dependent C5 binding, it was not sufficient to achieve subcutaneous delivery with less frequent administration. Here, we further improved the effectiveness of the pH-dependent anti-C5 antibody by applying a novel approach: surface charge engineering. Intravenous injection of 40 mg/kg CFA0322, a high affinity anti-C5 monoclonal antibody that is not pH-dependent, caused about 3-fold increase of total C5 concentration in the plasma of cynomolgus monkeys. This is because the C5-antibody immune complexes (ICs) have slower clearance than C5 alone. The increase in total C5 concentration then requires an even higher dosage of the antibody to neutralize the increased amount of C5. To reduce the required dosage of anti-C5 antibody, pH-dependent antibodies were identified from rabbit immunization. A humanized lead antibody, 305LO1, showed a pH-dependent binding property and reduced the plasma total C5 concentration compared to CFA0322. However, we still observed an increase in total C5 plasma concentration over the baseline. We assumed that this was due to a slow uptake rate of the C5-antibody ICs into the cell. We hypothesized that the surface charges of the ICs partially contributed to the slow uptake rate. Surface-charge engineered antibodies were generated by engineering both the variable and the constant regions. Both approaches successfully reduced the increase of plasma C5 in cynomolgus monkey and the combination of the two completely suppressed the accumulation. Interestingly, surface-charge engineering did not affect the pharmacokinetics of the antibody. The effect of surface-charge engineering on C5 reduction correlated clearly with the retention time of the C5-antibody ICs in cation exchange chromatography, indicating the contribution of positive surface charges of the ICs. After further engineering to optimize various properties such as immunogenicity and physicochemical properties, SKY59 was successfully generated. Our surface-charge engineered pH-dependent antibody suppressed the increase of total C5 concentration in vivo by accelerating the rate of IC uptake into cells, C5 release from the antibody in endosomes, and salvage of the antigen-free antibody. Thus, SKY59 can be expected to provide significant benefits for patients with complement-mediated disorders. Disclosures Kitazawa: Chugai Pharmaceutical Co., Ltd: Employment, Equity Ownership, Patents & Royalties: Patents related to emicizumab.
44
Muharremi, Shkelqim, Aleksandar Poposki, Vangelka Kovaceska, Liljana Tozija, Gordana Petrusevska, Biljana Gerasimovska, Blerim Bexheti, et al. "A Case of Seronegative Pulmonary-renal Syndrome: Diagnostic and Therapeutic Challenge." Open Access Macedonian Journal of Medical Sciences 9, no. C (January 4, 2021): 25–30. http://dx.doi.org/10.3889/oamjms.2021.5617.
Full textAbstract:
BACKGROUND: Pulmonary renal syndrome (PRS) is not a single entity but is caused by varied etiologies, including anti-neutrophil cytoplasmic antibody (ANCA), associated small vessel vasculitis (such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss vasculitis), Goodpasture’s syndrome, systemic lupus erythematosus, Henoch-Schonlein purpura, cryoglobulinemia, and rare causes such as druginduced vasculitis and subacute endocarditis.
CASE REPORT: We report a case of a 51-year-old man who was referred to our hospital with a 2-month history of breathing difficulties, mild hemoptysis, and deteriorated renal function with a serum creatinine of 269 μmol/L. Serological testing was negative for anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody, and also all cultures, including blood and urine, remained negative. In the renal biopsy, not linear deposition of IgG along the GBM and crescents at varying stages with extracapillary glomerulonephritis emphasizes the possibility of a double-seronegative pulmonary renal syndrome. Regarding therapeutic dilemmas, on the 3rd day of hospitalization, we initiated immunosuppression with cyclophosphamide and corticosteroids as well as plasma exchange (5 treatments). Under immunosuppressive therapy and plasma exchange, the patient’s status continually improved; there was no pulmonary bleeding, but the serum creatinine remained high and renal function remained in stage 4 chronic kidney disease. Four weeks later, he was hospitalized again, and we faced a new therapeutic dilemma because of the rapid relapse during immunosuppressive therapy and renal function deterioration that required hemodialysis treatment. Despite repeatedly negative results for anti-GBM and ANCA, initial immunosuppressive therapy with plasma exchange (9 treatments) was included again. The patient was discharged 30 days after admission in a stable general condition, with the maintenance immunosuppressive therapy with mycophenolate mofetil and hemodialysis 3 times/week. After 24 months, we have received information from the hemodialysis center that he is on regular hemodialysis and that he is in good condition.
CONCLUSION: We think that in this atypical case, intensive plasma exchange and immunosuppressive therapy are crucial in the early stage and maintenance therapy is necessary for vasculitis in remission. This reported case has important clinical implications because pulmonary-renal syndrome with negative ANCAs and anti-GBM antibodies is extremely rare and no treatment recommendations have been established yet.
45
Zhang, Zhimin, Yamei Shen, Xiangwu Shu, Bijuan Li, and Ning Li. "Successful whole-blood exchange transfusion in a patient with paroxysmal nocturnal hemoglobinuria: A case report and literature review." Journal of International Medical Research 47, no. 9 (August 21, 2019): 4562–67. http://dx.doi.org/10.1177/0300060519861165.
Full textAbstract:
Objective Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disorder of the hematopoietic stem cells that involves all blood cells. The primary aim of this study was to assess the role of whole-blood exchange (WBE) in treating patients with PNH. Methods A 32-year-old male patient was admitted our hospital because of severe anemia. His clinical test results indicated serious hemolysis, with positive anti-I on pretransfusion antibody screening tests. Because immunosuppressive therapy was ineffective and red blood cell (RBC) transfusion may aggravate hemolytic symptoms, the COBE Spectra blood cell separator was used for WBE. Results We performed WBE, where 1789 mL of the patient’s blood was removed and replaced with 12 U of packed RBCs, along with 150 mL of frozen plasma and 200 mL of normal saline (total volume, 1883 mL), representing an exchange of 42.5% of the patient’s total blood volume (approximately 4209 mL). The WBE treatment was considered successful. Rapid improvement in clinical signs and symptoms were observed after the WBE transfusion. The patient was discharged from the hospital on the third day after treatment. Conclusion Whole-blood exchange may be an applicable emergency treatment for rescuing PNH patients with severe or life-threatening hemolysis.
46
Cuker, Adam, Spero R. Cataland, Paul Coppo, Javier de la Rubia, Kenneth D. Friedman, James N. George, Paul N. Knoebl, et al. "Redefining outcomes in immune TTP: an international working group consensus report." Blood 137, no. 14 (April 8, 2021): 1855–61. http://dx.doi.org/10.1182/blood.2020009150.
Full textAbstract:
Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti–von Willebrand factor (VWF) nanobody. In light of these limitations, the IWG aimed to develop revised consensus outcome definitions that incorporate ADAMTS13 activity and the effects of anti-VWF therapy, by using an estimate-talk-estimate approach. The updated definitions distinguish clinical remission and clinical relapse (defined primarily by platelet count) from ADAMTS13 remission and ADAMTS13 relapse (defined by ADAMTS13 activity). The revised definitions of exacerbation and remission are benchmarked against not only the timing of discontinuation of TPE but also that of anti-VWF therapy. Retrospective validation of the revised definitions is described, although they have yet to be prospectively validated. Clinical implications of the updated outcome definitions are also discussed and an example of their application to clinical practice is provided to highlight their clinical relevance.
47
Sharma, A., P. Bumerts, J. Gomez-Navarro, D. Pavlov, and A. Ribas. "Clearance of monoclonal antibody (mAb) CP-675,206 by therapeutic plasma exchange (TPE) or plasmapheresis." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 13515. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.13515.
Full textAbstract:
13515 Background: CP-675,206 is a fully human, cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blocking mAb with immune stimulating properties under development for the treatment of metastatic melanoma. The pharmacokinetics of CP-675,206 is similar to endogenous IgG, with a long plasma half-life (22 days). We explored the use of TPE in two patients (pts) receiving CP-675,206, postulating that TPE could be used to remove mAb in cases where toxicities are thought to result from persistence of mAb in circulation. Methods: For both pts, five TPEs were performed over 7 days using a Cobe Spectra blood cell separator (TPE daily x 3, 2 days rest, and TPE daily x 2). One plasma volume was processed per TPE and replaced with a 60%/40% albumin/saline solution. Plasma CP-675,206 concentration was measured at baseline and after the 3rd and 5th TPE. Results: Patient 1 was a 62 year-old with metastatic melanoma who received 8 monthly doses of CP-675,206 (10 mg/kg). Six days after the last dose, the pt was found to have elevated ALT and bilirubin and detectable anti- smooth muscle and anti-microsomal antibodies. Based on a suspicion of therapy-related autoimmune hepatitis, the pt underwent TPE. Plasma CP-675,206 concentration declined by 96% following the 5th TPE, and ALT and bilirubin normalized over the 4 weeks following TPE with no other evidence of clinical hepatitis. Patient 2 was a 78 year-old with in-transit melanoma who received 3 monthly doses of CP-675,206 (10 mg/kg) and was responding to therapy. Two weeks after the last dose the pt developed diffuse bilateral arthralgias. The pt was diagnosed with rheumatoid factor-negative rheumatoid arthritis, presumably related to therapy with CP-675,206, and underwent TPE. Pre- and post-TPE plasma CP-675,206 concentrations are pending. The arthralgias persisted, and the pt subsequently received oral methotrexate with slow improvement in symptoms over the next 6 months. Conclusions: TPE is highly effective for reducing the plasma concentration of CP-675,206 and may be useful to avert the progression of drug-related adverse events. Clinical benefit from TPE may vary depending on the interval from dosing and may be limited by slow reversibility of T-cell immunostimulation. [Table: see text]
48
Sadler, J. Evan, Joshua Muia, Leili Dolatshahi, Lisa A. Westfield, Patricia Nieters, Anita Rodrigues, Ana G. Antun, Ara Metjian, and Jeffrey I. Zwicker. "Efficacy of Adjuvant Low Dose Rituximab and Plasma Exchange for Acquired TTP with Severe ADAMTS13 Deficiency — Results of the ART Study." Blood 132, Supplement 1 (November 29, 2018): 374. http://dx.doi.org/10.1182/blood-2018-99-113677.
Full textAbstract:
Abstract Introduction:Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13 that prevent the cleavage of von Willebrand factor and allow the growth of microvascular thrombi, causing microangiopathic hemolysis and severe thrombocytopenia. Untreated TTP is almost always fatal but plasma exchange enables ~80% of patients to survive. Those who respond often have exacerbations or relapses that require more therapy. Exacerbations and refractory TTP usually can be treated effectively by combining plasma exchange, corticosteroids, and rituximab. A typical regimen for TTP is 4 weekly doses of rituximab 375 mg/m2, which is borrowed from protocols for B cell lymphomas. However, the pathogenic B cell mass in TTP is much less than in lymphoma and lower doses of rituximab may be enough. For example, case reports in TTP and studies in immune thrombocytopenia suggest that fixed doses of 100 mg and conventional doses of 375 mg/m2 have similar efficacy. Methods:The ART study (Adjuvant Rituximab in TTP, NCT01554514) was designed as a pilot safety/efficacy study of low dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for TTP. The study enrolled at Washington University, Beth-Israel Deaconess Medical Center, Emory University, and Duke University. Eligibility criteria include age ≥18 years with acute TTP and ADAMTS13 <10%. Exclusions include treatment for TTP within 2 months, severe infection, cancer, organ or stem cell transplant, pregnancy, hepatitis B, and use of calcineurin inhibitors within 6 months or rituximab within the past year. Treatment included daily 1.5 volume plasma exchanges, prednisone 1 mg/kg, and rituximab 100 mg weekly for 4 doses starting before the 5thplasma exchange. Treatment Response is defined as 2 consecutive days with a platelet count ≥150,000/µl. A Durable Treatment Response persists ≥30 days after stopping plasma exchange. The primary endpoint is a composite of Exacerbation or Refractory TTP, where Exacerbation is recurrence of TTP ≤30 days after a treatment response and Refractory TTP is failure to achieve a Treatment Response by day 28 or failure to achieve a Durable Treatment Response by day 60.Secondary endpoints include the relapse rate at 2 years. Results:19 patients were enrolled. Two patients were subsequently excluded: 1 proved to have congenital TTP and was ineligible, 1 was withdrawn for protocol violations during the first week. The 17 evaluable patients have a median age of 48 years (range 30-71), 14 (82%) are African-American and 11 (65%) are female. All had a treatment response in a median of 5 days (range 3-16 days). 13 patients achieved normal ADAMTS13 levels after treatment, 2 had persistent severe ADAMTS13 deficiency, and 2 patients have yet to be assessed for ADAMTS13 responses. No patients had refractory disease and 2 had exacerbations; both achieved Durable Treatment Responses after 29 and 35 days. No patient died of TTP; 1 patient died of metastatic cancer. To date, 13 patients have completed 2 years of follow up and 3 (23%)have relapsed at 11, 19, and 22 months. For comparison, among 54 episodes of TTP at Washington University treated without rituximab, the primary endpoint occurred in 26 (48%). These included exacerbation in 23 (43%), refractory disease in 9 (17%), and both in 6 (11%). 6 patients died, and the incidence of relapse within 2 years was 51%. Treatment with low dose rituximab (100 mg) was associated with a significant decrease in the primary endpoint from 48% to 12% (P= 0.01, Fisher's exact test) and an encouraging decrease in 2-year relapse rate from 51% to 23% (P= 0.06). Conclusions:These results with low dose rituximab (100 mg x 4 doses) are consistent with reports that immediate treatment of TTP with standard dose rituximab (375 mg/m2x 4 doses) reduces the incidence of exacerbation and refractory disease, and prevents or delays relapses. A direct comparison of these regimens would be useful to establish whether low dose rituximab has similar efficacy with greater ease of administration, less cost, and less risk of infusion reactions and late complications. Disclosures Sadler: Ablynx: Consultancy. Zwicker:Quercegen: Research Funding; Daiichi: Honoraria; Parexel: Consultancy; Incyte: Research Funding.
49
Kaur, Harjot, Appalanaidu Sasapu, Michele H. Fox, and Pooja Motwani. "Successful Eculizumab Therapy in Thrombotic Thrombocytopenic Purpura (TTP) Refractory to Plasma Exchange, Steroids and Rituximab." Blood 124, no. 21 (December 6, 2014): 2794. http://dx.doi.org/10.1182/blood.v124.21.2794.2794.
Full textAbstract:
Abstract Introduction We present a case of TTP refractory to usual therapies treated successfully with eculizumab. Case presentation A 64 year-old African American female with history of diabetes and hypertension presented with left sided weakness and seizure-like activity preceded by 2 days of headaches and 2 weeks of easy bruising. On admission her vital signs and physical exam were unremarkable. Her basic metabolic panel, ANA panel, hepatitis panel, HIV, and anti-phospholipid panel was negative. Her hemoglobin was 9.0 g/dL, platelets were 13K/uL, LDH was 954IU/L, haptoglobin <30 mg/dL, eGFR was 50, and blood smear showed 4-5 schistocytes/high power field. ADAMTS13 activity was <5% and there was an inhibitor level of 1.1BU. C3 level was 75.3 (normal range 90-180mg/dL), C4 was <10 mg/dL (normal range 15-45 mg/dL). On day 1, she was started on oral prednisone (1mg/kg/day) and daily plasma exchange (TPE). changes. After 6 days of TPE without signs of improvement, the first dose of rituximab 375 mg/msq/dose was given on day 7. During the second week of hospitalization, patient also developed delirium and mental status changes. Vincristine 2 mg was given on day 13 for refractory TTP. Due to clinical worsening of microangiopathy and mental status, a decision was made to administer eculizumab 900 mg on day 17. Within a few hours of eculizumab administration, her platelets improved from 8k/uL to 21k/uL and to 47k/uL 12 hours later. After the second dose of eculizumab on day 24, platelets improved to 117k/uL and continued to rise. Eculizumab 900 mg was given weekly for 4 weeks, at which time ADAMTS13 activity was 75% and ADAMTS13 inhibitor was undetectable. Eculizumab 1200 mg was then given every two weeks, for a total of 3 more doses, during which the CBC, LDH, and haptoglobin remained in the normal range. Eculizumab was stopped, and after four months of close follow up, platelets, LDH, renal function and mental status were still normal range. C3 level was 203 (normal range 90-180 mg/dl), C4 was 35 mg/dl (normal range 15-45 mg/dl), ADAMTS 13 activity assay is >100% and there is no inhibitor. Discussion TTP and aHUS are both thrombotic microangiopathies (TMA). TTP is caused by acquired or inherited deficiency of the ADAMTS 13 protein or due the formation of an inhibitor to the ADAMTS13 protein. aHUS results, in most cases, from a genetic mutation in complement factor H in the alternative pathway of the complement cascade. Recent studies have described the importance of the complement system in all forms of TMA (Update on the role of the complement system in the pathogenesis of thrombotic microangiopathies. Prilozi. 2014;35(1):115-22). While plasma exchange is the cornerstone of TTP treatment, complement inhibition with drugs such as eculizumab is the treatment of choice for aHUS. The use of complement inhibiting drugs has not yet been studied in TTP. We report an unusual case of TTP, with confirmed ADAMTS 13 inhibitor and low activity, which did not respond to conventional treatment for TTP. Theorizing that this patient either had concurrent aHUS or had TTP with a dysregulated alternate complement pathway, we used eculizumab, to which the patient had a remarkable and persistent response. There are other reports in literature of patients with aHUS having reduced levels of ADAMTS13 protein; however, these patients did not have an inhibitor as was seen in our patient (Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome. Blood. 2013 Aug 22;122(8):1487-93). There is one other case in the literature where TTP was treated successfully with eculizumab. In that case, discontinuation of eculizumab was associated with a relapse of TTP and so had to be continued (Eculizumab in the treatment of refractory idiopathic thrombocytopenic purpura. Br J Haematology. 2012 June;157 (6):772-4). To our knowledge, we report the first case of a confirmed diagnosis of TTP treated successfully with eculizumab with remission continuing 3 months after discontinuation of the drug. The use of eculizumab and the role of the complement pathway in TTP deserves further study. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.
50
Hsia, Carleton JC, and Li Ma. "SOD3-Mimetic As a Complement for Genetic Therapy in Sickle Cell Disease." Blood 132, Supplement 1 (November 29, 2018): 2355. http://dx.doi.org/10.1182/blood-2018-99-120287.
Full textAbstract:
Abstract Background and Objectives: Genetic therapy relieves transfusion-dependence in patients 12 years and older with ß-Thalassemia (1) There is an urgent need to develop a complementary approach to genetic therapy for children younger than 12 years of age. The objective of this report is to describe the potential development of an extracellular superoxide dismutase-mimetic (SOD3-mimetic) to relieve sickle cell disease (SCD) children susceptible to stroke from being transfusion-dependent in order to avoid stroke. SanFlow [aka polynitroxylated pegylated hemoglobin (PNPH)], a SOD3-mimetic has been evaluated and approved by the FDA for further development as drug for the treatment of traumatic brain injury (TBI) complicated by hemorrhagic shock (HS), stroke, and SCD. PK&PD studies demonstrated that SanFlow works as a macromolecular SOD3-mimetic by protecting the endogenous vascular nitric oxide (NO) leading to enhanced blood flow. SanFlow has been shown to protect against superoxide induced hypoxia and inflammation in transgenic SCD and rat model of ischemic stroke as well as a mouse model of TBI+HS. In a rat middle cerebral artery occlusion (MCAO) model of stroke the spreading of the hypoxic core of the ischemic brain as measured by Pial arterial diameter is maintained over 2 hours post onset of stroke with associated reduction in inflammatory markers and brain infraction (3). In a mouse TBI+SH model, SanFlow was shown to be superior to fresh shed whole blood. The safety and efficacy of SanFlow was tested over a 50 fold dose range (i.e. from 0.1 to 5 times the shed blood volume). SanFlow was shown to work at extremely low volume in conjunction with volume replacement crystalloid to substitute whole blood resuscitation (3). Experimental Results: Using Berkeley model of sickle mice (Hba0/0 Hbb0/0Tg (HuminiLCRα1GγAγδβS) we have measures the PK&PD of SanFlow as a complementary or a substitute for genetic therapy. We have non-invasively measured the blood flow and vasoconstriction using transgenic SS mice (N=7) against WT littermates (N=4) as control. A single bolus dose of SanFlow (20ml/kg at hemoglobin of 4g/dl) significantly corrected the aortic stiffness and pulmonary flow of the SS mice to that of WT littermates (P<0.05). This is also correlated with the decrease of superoxide level in the lung as measure by Luminol activity assays (which fluoresces in the presence of superoxide) (P<0.05). Plasma cGMP (downstream effector of NO and natriuretic peptide activity) and NOx (breakdown product of NO and a measure of NOS activity) concentrations were measured in plasma of mice after infusion of SanFlow. SanFlow infusion was shown to significantly increased plasma cGMP concentrations in plasma. SanFlow infusion also resulted in a significant increase in NOx in plasma after infusion (P<0.05). SanFlow resulted in an increase in plasma cGMP and NOx in SS mice. Thus, the pathophysiological defects or difference of SS mice and WT littermates are corrected by SanFlow infusion. Conclusions:The present results support development of SanFlow, delivered through continuous infusion, for anemic SCD children to prevent the development of blood transfusion dependency in order to avoid stroke and painful vaso-occlusive crisis (VOC). These results also demonstrated that SanFlow can be used safely and effectively in the elimination of serious painful vaso-occlusive crisis and protect silent and major strokes. Clinical trials of SanFlow in SCD children, prior to their transfusion dependence, as well as in transfusion-dependent teenagers and adults with SCD patients are warranted. By extension, ß-Thalassemia patients can also be treated like SCD patients using SanFlow to relieve them from dependence on life-long blood exchange transfusion. However, these patients would be treated with SOD3-mimetic while waiting for genetic therapy. References: Thompson AA., et.al. Eng. J. Med 2018; 398: 1479-1493 Brockman EC., et. al. 2017 Neurotrauma, 34(7):1337-50 Cao S., et. al. 2017 J. Am Heart Assoc., 6(9):e006505. Disclosures Hsia: AntiRadical Therapeutics LLC: Employment.