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1

Roehr, Bob. "Scott Hitt". BMJ 335, n. 7630 (29 novembre 2007): 1160. http://dx.doi.org/10.1136/bmj.39408.718958.be.

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2

Jy, Wenche, Wei Wei Mao, Lawrence Horstman, Peter Valant e Yeon Ahn. "A Flow Cytometric Assay of Platelet Activation Marker P-Selectin (CD62P) Distinguishes Heparin-induced Thrombocytopenia (HIT) from HIT with Thrombosis (HITT)". Thrombosis and Haemostasis 82, n. 10 (1999): 1255–59. http://dx.doi.org/10.1055/s-0037-1614371.

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Abstract (sommario):
SummaryHeparin induced thrombocytopenia (HIT) is a well-known complication of heparin administration but usually resolves upon discontinuation without sequelae. However, a small proportion of HIT patients develop thrombosis associated with HIT, designated as HITT, which is often life-threatening and may lead to gangrene and amputations. Existing laboratory methods of confirming HIT/HITT do not distinguish between HIT and HITT. We report a flow cytometric assay of platelet activation marker CD62P to distinguish the effects of addition of HIT vs. HITT plasma to normal blood. Briefly, normal whole blood was incubated with platelet-poor plasma from 12 patients with HITT, 30 with HIT, and 65 controls, in presence and absence of heparin, and expression of CD62P was assayed by flow cytometry. When the ratios of fluorescent intensity of CD62P with heparin divided by that without heparin were compared, HITT plasma induced significantly higher ratios than HIT plasma (HITT ratios ~2.5 vs. HIT ratios ~1.2; p <0.001). Eleven of 12 HITT patients were positive by this test but only 5 of 30 HIT patients were positive (p < 0.0005). In a case of HIT with silent thrombosis, this assay gave a positive results prior to clinically evident thrombosis. In conclusion, this method distinguishes HITT from HIT and may be clinically useful in the detection of HITT, allowing early intervention for preventing catastrophic thrombosis.
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3

Kondo, Kimi, D. Johnson e Eric Wannamaker. "Heparin-Induced Thrombocytopenia and Thrombosis: Preventing your Thrombolysis Practice from Taking a HITT". Seminars in Interventional Radiology 34, n. 04 (dicembre 2017): 409–14. http://dx.doi.org/10.1055/s-0037-1608864.

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AbstractHeparin-induced thrombocytopenia and thrombosis (HITT) is an under-recognized cause of deep venous thrombosis treatment failure and of complications during catheter-directed thrombolysis. After a review of HITT pathophysiology, diagnosis, and management, three different cases are presented in this article. Each case highlights subtleties and challenges of HITT diagnosis and management. An example of a practical approach to the diagnosis of HITT is presented.
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4

Donie, Donie, Yanuar Kiram, Hermanzoni Hermanzoni e Eval Edmizal. "The Effectiveness of Footwork Exercises with the HIIT Method in Developing VO2max and Anaerobic Capacity". AL-ISHLAH: Jurnal Pendidikan 13, n. 2 (14 agosto 2021): 998–1005. http://dx.doi.org/10.35445/alishlah.v13i2.803.

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The purpose of this study was to determine the development of physiological aspects of increasing aerobic and anaerobic performance in students who become badminton athletes through optimizing footwork exercises using the high-intensity interval method (HITT). This research will provide a solution for trainers in combining and optimizing footwork exercises as a technique in badminton combined with the principles of interval training to increase badminton athletes' aerobic and anaerobic capacity. This study used an experimental approach by giving footwork training treatment (HITT) to 30 Padang State University students who became badminton athletes. Researchers saw the effect of the exercise given on aerobic capacity (VO2max) and anaerobic capacity. The statistical analysis results showed that footwork exercise with The HIIT (High High-Intensity Interval Training) method positively affects badminton athletes' maximal aerobic capacity (VO2max) anaerobic capacity. In this concept, footwork training using the HIIT method effectively develops aerobic and anaerobic metabolism in response to energy requirements during total energy production in training maximum.
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5

Sabnani, Indu, Ajaz Khan e Patricia Tsang. "Pattern of Platelet Recovery in Predicting Outcome in Heparin-Induced Thrombocytopenia and Thrombosis." Blood 108, n. 11 (16 novembre 2006): 4085. http://dx.doi.org/10.1182/blood.v108.11.4085.4085.

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Abstract (sommario):
Abstract Heparin-induced thrombocytopenia and thrombosis (HITT), a severe immune-mediated drug reaction, is often underdiagnosed. Early management of HITT with alternative anticoagulants can result in a favorable outcome. However, the morbidity and mortality associated with HITT remain high, posing challenges for patient management. We describe the clinical profile and pattern of platelet count recovery in a cohort of 34 patients diagnosed with HITT. This retrospective study consists of 164 patients screened for HITT over 18 months at our institution based on positive platelet factor 4 (PF4) IgG antibodies in the proper clinical setting. Patients who tested positive were divided on the basis of recovery of platelet count (increase to &gt;100 × 109/L or by 1.5-fold by day 5 of diagnosis) into two groups: delayed and normal recovery. Of the 164 patients screened, 107 were admitted with cardiac diseases while 57 non-cardiac conditions. A total of 34 patients (21%) were tested positive for PF4 antibodies. Patients with underlying cardiac conditions were more likely to be diagnosed with HITT than non-cardiac patients (28% versus 7%, p=0.0012). The male to female ratio was 1:1.1, and the median age was 65 years. Nineteen of 34 patients (56%) had delayed platelet recovery, while the remaining 15 patients (44%) had normal platelet recovery by day 5. The mortality rate was 68% (13 of 19) in the delayed recovery group, compared to only 7% (1 of 15) in the normal recovery group (p=0.0004). Twelve of the 34 patients with liver dysfunction had delayed platelet recovery and died (figure 1). There were 6 venous and 5 arterial thrombotic episodes. A total of 13 patients (38%) were treated with Argatroban, a direct thrombin inhibitor (DTI) indicated for the treatment of HITT, but it did not seem to improve platelet recovery (Table 1). Eight of the 13 treated patients (62%) and 11 of the 21 untreated patients (52%) showed no platelet recovery by day 5. In conclusion, early diagnosis of HITT is critically important for patient management, and yet, diagnosis is often elusive due to a general lack of awareness of this condition. Underlying cardiac diseases appear to predispose patients to HITT, probably due to previous exposure and sensitization to heparin. Despite the availability of new anticoagulants, HITT remains an undertreated and highly fatal condition with overall mortality of 38% in our series. Underlying liver dysfunction appears to be associated with delayed platelet recovery and poor survival. Affect of DTI on platelet recovery needs to be further investigated. Optimal response to therapy requires early diagnosis and intervention. Further studies are necessary to enhance our understanding of this devastating condition to facilitate early diagnosis and proper treatment. Treatment and Survival of HITT Patients Outcome Treated with DTI Not treated Total Dead 6 7 13 Alive 7 14 21 Total 13 21 34 Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery &gt; 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery &gt; 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery &lt; 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery &lt; 5 days
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6

Arepally, Gowthami M., e Irene M. Mayer. "Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8". Blood 98, n. 4 (15 agosto 2001): 1252–54. http://dx.doi.org/10.1182/blood.v98.4.1252.

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Thrombosis is a life-threatening complication that occurs in a subset of patients with heparin-induced thrombocytopenia (HITT). The pathogenic mechanisms underlying the variable occurrence of thrombosis in HITT is poorly understood. It was hypothesized that monocyte activation leading to tissue factor expression may play a role in promoting a thrombogenic state in HITT. This study demonstrates that a human platelet factor 4 (PF4)/heparin-specific murine monoclonal antibody (KKO) binds to peripheral blood-derived human monocytes in a PF4-dependent manner. KKO and antibodies from patients with HITT induce monocytes to synthesize and secrete interleukin-8 and induce cell-surface procoagulant activity, which is abrogated following treatment with antihuman tissue factor antibody. The findings suggest a novel mechanism by which PF4/heparin antibodies may promote a hypercoagulable state in patients with HITT.
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7

Gade, Kristine, Jack Melson, Alex Jepsen, Surabhi Palkimas, Bethany Horton e Hillary S. Maitland. "A Single Institution's Adherence to Heparin-Induced Thrombocytopenia and Thrombosis Testing Guidelines". Blood 132, Supplement 1 (29 novembre 2018): 4720. http://dx.doi.org/10.1182/blood-2018-99-117132.

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Abstract Introduction: What was once an under-recognized clinical entity, heparin induced thrombocytopenia and thrombosis (HITT) has become a well-recognized and frequently tested disease. HITT is a serious and potentially fatal antibody mediated drug reaction to platelet factor 4 and early identification and treatment is essential. The 4T score is well-validated to guide appropriate testing of HITT where a low-probability score of 0-3 equates to a 99.8% negative predictive value for HITT2,3. In an effort to promote cost-conscious care and efficient use of healthcare resources, the American Society of Hematology (ASH) recommends against testing for HITT if the 4T score is 3 or less4. HITT laboratory testing at our institution is not restricted based on 4T score. We hypothesize that many providers are not following cost-conscious guidelines regarding HITT testing at our institution. Methods: We performed a single-institution retrospective analysis of patients who had a heparin-induced platelet antibody assay with reflexive serotonin release assay ordered between July 1, 2016 to July 1, 2017 at the University of Virginia Medical Center (UVA). We primarily assessed how our institution's ordering of heparin-induced platelet antibody for HITT compared to ASH's Choosing Wisely recommendation of forgoing laboratory testing on patients with a 4T score of 0-3 by retrospectively calculating 4T scores on all patients who had laboratory testing4. Patients were also assessed for episodes of bleeding and clotting and were scored on severity via the CTCAE and ISTH grading systems. Data on anticoagulant used after HITT testing was collected. We also checked to see if the blood specimen for assay was collected 2 hours after last heparin product as recommended by lab. Patients were excluded if they were not inpatient when their heparin-induced platelet antibody assay was drawn or if they were transferred or discharged immediately after assay was collected. Ultimately, of the initial 196 patients who had heparin-induced platelet antibody assay collected during this time frame, 184 patients were included for analysis. Results: Of the 184 patients who had a heparin-induced platelet antibody assay sent and were included in analysis, 55.4% of the patients (n=102) had a low pre-test probability of HITT with a 4T score of less than or equal to 3. Of the patients who had HITT testing sent, only 44% (n=81) received treatment with a non-heparin anticoagulant. Of the 102 patients who had a low pre-test probability of HITT with a 4T score of ≤3, 37.3% (n=38) were placed on an alternative anticoagulant. Of this low pre-test probability of HITT cohort, 7.8% (n=8) experienced bleeding as a complication. Interestingly, 15.5% (n=29) of all patients who had HITT testing continued to receive heparin products while awaiting results. Additionally, 19.3% (n=36) of samples were drawn within 2 hours of receiving heparin products. Conclusion: The guidelines for HITT testing and treatment have been well-validated and widely disseminated. Despite providers' familiarity with this clinical entity, the results depict that ordering practices at our institution do not follow guidelines in cost-conscious ordering nor in standard of treatment. Applying ASH's Choosing Wisely recommendation of not ordering laboratory testing on patients with a 4T low-probability score of 0-3, we see that 55.6% of the HITT assays ordered in this time period were inappropriate and at a cost of $455 to the institution per assay resulted in $46,865 of unnecessary health care costs to our institution in one year's time. This does not include the cost of alternative anticoagulation. Heparin costs just $0.04 per mL while argatroban costs $3.81 per mL and bivalirudin $12 per mL resulting in a 100 to 300 fold cost increase respectively. Standard work regarding HITT assay collection and treatment does not exist at our institution. Of concern, 15.5% of patients continued to receive heparin products after HITT testing was sent. The results of this study prompted implementation of a quality improvement project to decrease inappropriate HITT testing and standardize treatment of suspected HITT via an electronic medical record order set that uses the 4T score to suggest appropriate ordering of assays. We plan to collect data on changes in our ordering practices after this intervention. Disclosures No relevant conflicts of interest to declare.
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8

Madhavan, Sangeetha, James W. Stinear e Neeta Kanekar. "Effects of a Single Session of High Intensity Interval Treadmill Training on Corticomotor Excitability following Stroke: Implications for Therapy". Neural Plasticity 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/1686414.

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Abstract (sommario):
Objective. High intensity interval treadmill training (HIITT) has been gaining popularity for gait rehabilitation after stroke. In this study, we examined the changes in excitability of the lower limb motor cortical representation (M1) in chronic stroke survivors following a single session of HIITT. We also determined whether exercise-induced changes in excitability could be modulated by transcranial direct current stimulation (tDCS) enhanced with a paretic ankle skill acquisition task.Methods. Eleven individuals with chronic stroke participated in two 40-minute treadmill-training sessions: HIITT alone and HITT preceded by anodal tDCS enhanced with a skill acquisition task (e-tDCS+HIITT). Transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability of paretic and nonparetic tibialis anterior (TA) muscles.Results. HIIT alone reduced paretic TA M1 excitability in 7 of 11 participants by ≥ 10%. e-tDCS+HIITT increased paretic TA M1 excitability and decreased nonparetic TA M1 excitability.Conclusions. HIITT suppresses corticomotor excitability in some people with chronic stroke. When HIITT is preceded by tDCS in combination with a skill acquisition task, the asymmetry of between-hemisphere corticomotor excitability is reduced.Significance. This study provides preliminary data indicating that the cardiovascular benefits of HIITT may be achieved without suppressing motor excitability in some stroke survivors.
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9

Shatskov, A. "Hitt. ninink- and Lat. nītor". Indo-European Linguistics and Classical Philology XXIII (giugno 2019): 1131–40. http://dx.doi.org/10.30842/ielcp230690152385.

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10

Lee, S. K., R. Willinsky e K. terBrugge. "Dural Sinus Thrombosis Complicated with Heparin Induced Thrombocytopenia and Thrombosis (HITT)". Interventional Neuroradiology 8, n. 1 (marzo 2002): 77–80. http://dx.doi.org/10.1177/159101990200800114.

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Abstract (sommario):
A case of dural sinus thrombosis complicated with heparin induced thrombocytopenia and thrombosis (HITT) is presented. Interventional neuroradiologic procedures have potential risks of this devastating complication that is related with heparin. Clinical features and pathophysiologic mechanisms of HITT are discussed.
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11

McGowan, Kelly E., Joy Makari, Artemis Diamantouros, Claudia Bucci, Peter Rempel, Rita Selby e William Geerts. "Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program". Blood 127, n. 16 (21 aprile 2016): 1954–59. http://dx.doi.org/10.1182/blood-2015-07-660001.

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Abstract (sommario):
Key Points Use of LMWH is associated with a lower risk of HIT and HITT compared with use of UFH. The Avoid-Heparin Initiative resulted in a dramatic reduction in the burden of suspected HIT, adjudicated HIT, HITT, and associated costs.
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12

Arepally, G. M., S. Kamei, K. S. Park, K. Kamei, Z. Q. Li, W. Liu, D. L. Siegel, W. Kisiel, D. B. Cines e M. Poncz. "Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies". Blood 95, n. 5 (1 marzo 2000): 1533–40. http://dx.doi.org/10.1182/blood.v95.5.1533.005k01_1533_1540.

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Abstract (sommario):
Antibodies to PF4/heparin can be demonstrated in almost all patients with heparin-induced thrombocytopenia/thrombosis (HIT/HITT) and in some persons exposed to heparin who do not have clinical manifestations. The role of anti-PF4/heparin antibodies in the pathogenesis of HIT/HITT has been difficult to establish because the antibodies found in serum are generally polyclonal and polyspecific. To circumvent this problem, we developed a murine monoclonal antibody (mAb) to human (h) PF4/heparin complexes. A monoclonal IgG2bκ antibody (designated KKO) was identified that bound specifically to hPF4/heparin complexes. Maximal binding of KKO to hPF4/heparin complexes occurred at similar molar ratios of PF4:heparin observed for HIT/HITT antibodies. KKO also bound to hPF4 in association with other glycosaminoglycans. Platelet activation by KKO required heparin and was abrogated by blockade of FcγRIIA. In the presence of PF4, KKO bound to endothelial cells, but not to CHO cells lacking heparan sulfate proteoglycans. Variants of PF4 complexed to heparin were recognized equally well by KKO and HIT/HITT sera. KKO competes for binding with a subset of HIT/HITT antibodies that are relatively spared by mutations in the 3rd domain of PF4. The nucleotide and predicted amino acid sequences of KKO and RTO, a murine anti-hPF4 mAb that does not require heparin for binding, revealed no obvious relationship in either the heavy- or the light-chain immunoglobulin variable regions. These studies suggest that KKO recapitulates the antigenic and functional specificity of a subset of HIT/HITT antibodies and may, therefore, provide insight into the pathogenesis of thrombocytopenia and thrombosis in affected persons.
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13

Arepally, Gowthami, Steven E. McKenzie, Xiao-Ming Jiang, Mortimer Poncz e Douglas B. Cines. "FcγRIIA H/R131 Polymorphism, Subclass-Specific IgG Anti-Heparin/Platelet Factor 4 Antibodies and Clinical Course in Patients With Heparin-Induced Thrombocytopenia and Thrombosis". Blood 89, n. 2 (15 gennaio 1997): 370–75. http://dx.doi.org/10.1182/blood.v89.2.370.

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Abstract (sommario):
Abstract The explanation why only a subset of patients with heparin-induced thrombocytopenia (HIT) develop clinically apparent thromboses (HITT) remains uncertain. It has been proposed that platelet activation induced by cross-linking of FcγRIIA by anti-heparin/platelet factor 4 (PF4) antibodies is central to the pathogenesis of thrombosis. The observation that a common functional polymorphism of FcγRIIA, involving either an arginine (R) or histidine (H) at amino acid 131, may underlie disease susceptibility prompted us to investigate the prevalence of receptor isoforms in patients with HIT and HITT. Furthermore, because these isoforms reportedly differ in their avidity for immune complexes containing human IgG2 , we also analyzed sera from patients with HIT and HITT for the prevalence of various subclass-specific IgG anti-heparin/PF4 antibodies. No difference in the allele frequency of FcγRIIA-H131 or R131 was identified among 13 patients with HIT or 23 with HITT compared with 102 controls (χ2 = 1.21, P = .8). Furthermore, although most patients had IgG2 antibodies (62%), IgG1 was the predominant subclass in 30 of the 34 patients with IgG anti-heparin/PF4 antibodies and in 12 was the exclusive subclass found. Also, there was no association between the concordance of IgG2 anti-heparin/PF4 antibodies and the expression of FcγRIIA-H131 in patients with HITT compared with patients with thrombocytopenia alone. These results make it unlikely that the FcγRIIA-H131 isoform or IgG2 anti-heparin/PF4 antibodies are required to develop HITT, suggesting that factors in addition to cross-linking of FcγRIIA receptors contribute to the pathogenesis of thrombosis in patients with heparin-dependent antiplatelet antibodies.
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14

Parney, Ian F., e David E. Steinke. "Heparin-induced thrombocytopenia and thrombosis following subarachnoid hemorrhage". Journal of Neurosurgery 93, n. 1 (luglio 2000): 136–39. http://dx.doi.org/10.3171/jns.2000.93.1.0136.

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Abstract (sommario):
U The authors present a case of heparin-induced thrombocytopenia and thrombosis (HITT) that occurred after aneurysmal subarachnoid hemorrhage (SAH), and they review the relevant literature. An immune-mediated syndrome, HITT is characterized by moderate thrombocytopenia and paradoxical vascular thromboses. Although it has been estimated in prospective studies that HITT occurs in between 1 and 3% of patients receiving heparin, it is underrecognized in the neurosurgical literature. In the present case, a 49-year-old woman underwent clipping of a right posterior communicating artery aneurysm after suffering a Hunt and Hess Grade III SAH. She had an uncomplicated postoperative course with good clip positioning and no vasospasm observed on a cerebral angiogram obtained on Day 7.On Day 23, the patient developed a right hemiparesis and experienced a grand mal seizure. A head computerized tomography scan revealed a hemorrhagic infarct in the left middle cerebral artery distribution. Repeated cerebral angiograms did not show vasospasm. She was thrombocytopenic (platelet count as low as 46 × 109/L on Day 28 compared with 213 × 109/L on Day 1) and had been receiving heparin flushes to maintain intravenous catheter patency. An assay for HITT-associated antibodies was positive. The heparin flushes were discontinued and the platelet count recovered (121 × 109/L). She improved neurologically, but was left with a significant right hemiparesis at discharge. This patient had assay-proven heparin-induced thrombocytopenia despite minimal exposure to heparin. Because there was no evidence of vasospasm or other factors to account for her delayed hemorrhagic infarction, an HITT-related disorder seemed most likely. Despite a large body of literature describing HITT in nonneurosurgical patients, only three previous neurosurgical cases have been published. This case report may serve to heighten awareness of this disorder.
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Bacsi, S., R. De Palma, G. P. Visentin, J. Gorski e R. H. Aster. "Complexes of Heparin and Platelet Factor 4 Specifically Stimulate T Cells From Patients With Heparin-Induced Thrombocytopenia/Thrombosis". Blood 94, n. 1 (1 luglio 1999): 208–15. http://dx.doi.org/10.1182/blood.v94.1.208.413a06_208_215.

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Abstract (sommario):
Heparin-induced thrombocytopenia with thrombosis (HITT) is associated with antibodies specific for complexes consisting of heparin and platelet factor 4 (PF4). Studies in individual patients with HITT have demonstrated immunoglobulin (Ig) class switching from IgM to the IgG or IgA isotypes. This transition is thought to require helper T cells, but no studies of the cellular or molecular basis of this process have yet been reported. To characterize T-cell involvement in HITT, peripheral blood mononuclear cells (PBMC) from two patients with classical HITT obtained shortly after the acute episode were restimulated with heparin:PF4 complexes, PF4 alone, heparin alone, and medium alone in the presence of autologous antigen-presenting cells (APC). Responding T cells were then examined using the technique of “spectratyping,” in which sequences encoding CDR3 domains of individual V beta (BV) families are amplified and separated by gel electrophoresis. After 14 days in culture with antigen (heparin:PF4 complexes), but not after culture with PF4, heparin, or medium alone, patient cells, but not cells from normal subjects, preferentially expressed T-cell receptor (TCR)-containing β chains of the BV 5.1 family. Nucleotide sequencing of BV 5.1 TCR CDR3 showed that each patient had a personal repertoire, but also shared a tetrapeptide motif (PGTG). These findings provide evidence that the humoral immune response associated with HITT is driven by helper T cells that presumably recognize peptides derived from PF4. Identification of a common β-chain CDR3 motif in responding T cells from each of two patients suggests that a limited number of helper TCRs may be used to mount an antibody response to heparin:PF4 complexes. TCR spectratyping appears to offer a new way to examine the molecular basis of pathologic immune responses and may be useful in further studies of HITT and other immune-mediated hematologic disorders.
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16

Tessler, Oren, Joshua Vorstenbosch, Sebastien Lalonde, Jonathan Kanevsky e Teanoosh Zadeh. "“Donʼt Let Your Flap Get HITT”". Plastic and Reconstructive Surgery 130 (novembre 2012): 110. http://dx.doi.org/10.1097/01.prs.0000421829.90421.b6.

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17

Roche, Kristina, Brian Harnett, Leona Browne, Stephanie Young e Rufaro S. Chitsike. "The Incidence of Heparin Induced Thrombocytopenia before and after the Implementation of the Venous Thromboembolism Thromboprophylaxis Protocols within Eastern Health". Blood 134, Supplement_1 (13 novembre 2019): 2447. http://dx.doi.org/10.1182/blood-2019-129340.

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Abstract (sommario):
Background: A recognized complication of exposure to heparin is the development of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT). The frequency of HIT in patients exposed to unfractionated heparin (UFH) is higher than those exposed to low-molecular-weight heparin (LMWH). Where the use of unfractionated heparin is not necessary, HIT may be largely preventable by using LMWH rather than UFH on an institution-wide scale. At our institution, UFH was largely substituted by the LMWH for thromboprophylaxis gradually throughout 2014 with the implementation of the venous thromboembolism (VTE) thromboprophylaxis protocols. The VTE thromboprophylaxis protocols had their final implementation at the beginning of 2015. Objectives: - To determine the incidence of HIT and HITT before and after the implementation of the VTE thromboprophylaxis protocols within Eastern Health. - ACP Learning Objective: Educate learners about the risk of using UFH as well as alternative treatment for DVT prophylaxis (LMWH). Methods: Charts of all patients who had HIT screening assays requested between January 1, 2012 and December 31, 2017 were examined to determine which patients went on to have positive screening assays as well as positive confirmatory testing. The type of heparin which the patient was exposed was recorded, the sequelae of HITT within 30 days of medication exposure, as well as the correlation of these findings with the implementation of the VTE thromboprophylaxis protocols. Preliminary Results: In surgical patients the average number of confirmed cases of HIT per year decreased by 51%, and the average number of confirmed cases of HITT per year decreased by 83% after implementation of thromboprophylaxis protocols. In medical patients the average number of confirmed cases of HIT per year decreased by 15%, and the average number of confirmed cases of HITT per year decreased by 47% after implementation of thromboprophylaxis protocols. Between 2012 and 2017 a total of 24 patients experienced HITT, resulting in 33 poor outcomes, including: pulmonary embolism, cerebrovascular accident, DVT, ischemic bowel, arterial thrombosis, venous thrombosis, cardiac thrombus, splenic infarct, and death. The majority of patients experiencing HITT had a history of UFH usage, be it alone or in combination with LMWH, equaling 19 out of 24 patients. Preliminary Conclusion: The incidence of HIT and HITT was reduced after the implementation of the VTE prophylaxis protocols. Further Direction: The next step in the project involves assessing the statistical significance of the above results and assessing the data from 2018 in the same manner as above. Disclosures Young: Sanofi-Aventis: Honoraria, Research Funding. Chitsike:Sanofi-Aventis: Honoraria, Research Funding; Bayer: Research Funding; Bristol Myers Squib: Honoraria; Pfizer: Honoraria; Servier: Honoraria.
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18

Sachais, Bruce S., Ann H. Rux, Jillian L. Hinds e John J. Rux. "Rational Design and Characterization of Platelet Factor 4 Antagonists". Blood 116, n. 21 (19 novembre 2010): 724. http://dx.doi.org/10.1182/blood.v116.21.724.724.

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Abstract Abstract 724 Background: Heparin-induced thrombocytopenia and thrombosis (HITT) is a serious complication of heparin therapy, placing patients at increased risk for thrombosis and death. The chemokine platelet factor 4 (PF4) is central to the pathogenesis of HITT. Tetrameric PF4 forms ultralarge complexes (ULC) with heparin, which, when bound to specific antibodies, lead to thrombocytopenia and thrombosis. We have previously shown that the tetrameric form of PF4 is required for ULC formation. Since a large number of hospitalized patients are exposed to heparin, HITT is a major iatrogenic cause of morbidity and mortality in this patient population. There are currently no specific therapies for the treatment of HITT. Objectives: Identify small molecule antagonists of PF4 tetramerization to serve as reagents for the mechanistic study of HITT as well as lead compounds for development of novel HITT therapies. Approach: Using the crystal structure of PF4, we identified a potential antagonist binding site near residues glutamic acid 28 (E28) and lysine 50 (K50). These residues form salt bridges between two PF4 dimers which are required for tetramer formation. We then performed an in silico screen of 1.1×10^6 lead-like small molecules using the program DOCK to identify compounds likely to bind to this site. A subset of these compounds were obtained and tested for their ability to inhibit PF4 tetramerization and PF4:heparin ULC formation in vitro. Results: In silico screening identified 109 compounds with DOCK scores (lower scores predict higher binding affinity) which were greater than 10 standard deviations below the mean (see Figure). We have obtained 12 of these compounds for in vitro testing. The ability of antagonists to inhibit PF4 tetramerization was measured as previously described by quantitation of silver stained SDS-PAGE gels of cross-linked PF4 in the absence and presence of putative antagonists. 5 of the compounds showed inhibition of tetramerization in a dose dependent manner, with 2 of these compounds (PA31 and PA35) demonstrating micromolar potency (IC50 of tetramerization = 500uM and 600uM respectively). The ability of these antagonists to inhibit ULC formation between PF4 and heparin was measured by both gel filtration and ELISA as previously described. PA31 and PA35 both inhibited ULC formation with potencies similar to that for inhibition of tetramerization. Conclusions: We have identified two small molecule PF4 antagonists. These compounds will be useful in future mechanistic studies of HITT. They also may serve as lead drug discovery compounds for chemical modification to create PF4 antagonists with increased affinity and potency. Such compounds may be tested as novel therapeutics for the treatment and/or prevention of HITT. Disclosures: Rux: In sillico Molecular, LLC: Employment, Owner.
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Segna, E., A. R. Bolzoni, C. Baserga e A. Baj. "Free flap loss caused by heparin-induced thrombocytopenia and thrombosis (HITT): a case report and literature review". Acta Otorhinolaryngologica Italica 36, n. 6 (dicembre 2016): 527–33. http://dx.doi.org/10.14639/0392-100x-1188.

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La trombocitopenia eparino-indotta con trombosi rappresenta una complicanza che può portare a esiti drammatici nella chirurgia ricostruttiva microvascolare, tanto più che il suo riconoscimento non è sempre semplice. In ogni caso di trombosi microvascolare, in corso di terapia eparinica, il sospetto di HITT deve subito insorgere, così da poter intercettare e trattare la catena di eventi che porterebbe alla necrosi del lembo ricostruttivo. Presentiamo un caso che dimostra quanto possa essere difficile la diagnosi di HITT, così come appare negli altri reports reperibili in letteratura internazionale. I lembi microvascolari sono il gold standard nella chirurgia ricostruttiva cervico-facciale: purtroppo però il successo della metodica può essere inficiato da eventi trombo-embolici imprevedibili. Crediamo che una maggior divulgazione e la formulazione di domande anamnestiche specifiche possano essere utili nel limitare le conseguenze devastanti della HITT.
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20

Piovella, Franco, Marisa Barone, Chiara Beltrametti, Chiara Piovella, Andrea M. D’Armini, Federico Capra Marzani, Vittorio Arici et al. "Efficacy of Fondaparinux in the Treatment of Heparin-Induced Thrombocytopenia with Venous Thromboembolism: Reduction of Thromboembolic Burden, Normalization of Platelet Count and Disappearance of Anti-Platelet Factor 4/Heparin Antibodies." Blood 108, n. 11 (16 novembre 2006): 575. http://dx.doi.org/10.1182/blood.v108.11.575.575.

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Abstract Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) may develop during anticoagulant treatment in patients submitted to various regimens of unfractionated or low-molecular weight heparins. Several molecules have been studied as alternative anticoagulants in patients with HIT or HITT, including danaparoid, argatroban, lepirudin. Lepirudin requires dosage adjustments in patients with renal insufficiency and has potential for antibody formation. Argatroban requires dosage adjustments in patients with hepatic insufficiency. Argatroban increases the International Normalized Ratio (INR) when co-administered with warfarin, leading to dosage difficulties when transitioning to warfarin therapy. Anticoagulation of patients with HIT or HITT may be limited by antibodies cross-reactivity with danaparoid and by new generation of antibodies with lepirudin. Fondaparinux is the first of a new class of synthetic antithrombotics: the selective inhibitors of coagulation factor Xa. It is the most advanced competitor of low molecular weight heparins, which are the reference drugs in prophylaxis and treatment of venous thromboembolism. Fondaparinux does not bind to platelet factor 4 (PF4) and does not react with anti-PF4/heparin antibodies in in vitro testing. We treated 20 patients who develop HIT (3 patients) or HITT (17 patients, of whom 4 had both DVT and PE). Nine patients were previously submitted to extracorporeal circulation with unfractionated heparin (UFH) followed by low-molecular weight heparin (LMWH) for major cardiac surgery. The remaining patients had been previously treated with either UHF or LMWH at therapeutic or prophylactic dosage in internal medicine or surgery wards. In the 17 patients who developed HITT, we applied therapeutic dosages of fondaparinux, i.e. 7.5 mg QD or lower, accordingly with their bleeding risk. To the remaining patients with HIT we gave prophylactic dosages of fondaparinux, i.e. 2.5 mg QD. Patients with HITT were treated for 4 to 25 days before starting warfarin. Fondaparinux was stopped when INR of 2.0 or more was reached. All patients showed a significant reduction of their thromboembolic burden. One episode of major bleeding was recorded in a post-surgical patient. All patients but one showed sustained normalization of the platelet number. In the remaining patient platelet count remained unchanged. Treatment was switched from fondaparinux to lepirudin and after few days her platelets reverted to close-to-normal levels. In seven patients, submitted to therapeutic dosages of fondaparinux, anti-PF4/heparin antibody titers were determined using a PF4/heparin enzyme-linked immunosorbent assay (ELISA): in all cases antibody levels progressively decreased close to disappearance by 30–45 days. This series of cases provides further evidence for the safety and efficacy of fondaparinux in the treatment of both HIT or HITT.
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21

Vucelic, Dragica, Nebojsa Antonijevic, Danijel Galun, Predrag Bulajic, Dragan Basaric e Miroslav Milicevic. "Heparin-induced thrombocytopenia with iliacofemoropopliteal thrombosis in a patient operated for colorectal carcinoma liver metastases". Acta chirurgica Iugoslavica 58, n. 4 (2011): 93–96. http://dx.doi.org/10.2298/aci1104093v.

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Abstract (sommario):
We report a case of heparin-induced thrombocytopenia thrombosis (HITT) syndrome in a patient prophylactically treated with low molecular weight heparin. A 66-year-old men underwent radiofrequency-assisted partial liver resection for colorectal carcinoma liver metastases a year-and-ahalf after he had been operated for rectal cancer. In the postoperative period, patient was prophilactically treated with reviparin sodium. On the 8th postoperative day, the platelet count decreased by more than 50% without clinical signs of thrombosis. HITT syndrome was suspected on the 19th postoperative day, after iliacofemoropopliteal thrombosis had developed, and related diagnosis was supported by the strongly positive particle gel agglutination technique immunoassay. Heparin was withdrawn and alternative anticoagulant, danaparoid sodium, was introduced in therapeutic doses. Despite delayed recognition, favorable clinical outcome was achieved. HITT syndrome should be considered with priority among the possible causes of thrombocytopenia in a surgical patient on heparin.
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22

Pravinkumar, E., e N. R. Webster. "HIT/HITT and alternative anticoagulation: current concepts". British Journal of Anaesthesia 90, n. 5 (maggio 2003): 676–85. http://dx.doi.org/10.1093/bja/aeg063.

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23

Knight, David J. W., D. Selwyn e K. Girling. "HIT/HITT and alternative anticoagulation: current concepts". British Journal of Anaesthesia 91, n. 3 (settembre 2003): 445–46. http://dx.doi.org/10.1093/bja/aeg606.

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24

Saad, R. A. "HIT/HITT and alternative anticoagulation: current concepts". British Journal of Anaesthesia 91, n. 4 (ottobre 2003): 606–7. http://dx.doi.org/10.1093/bja/aeg619.

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25

Sabnani, Indu, Marc Cohen, David A. Baran, Patricia Tsang, Luis H. Arroyo, Margarita Camacho e Mark J. Zucker. "The Role of Serial Testing for Heparin/PF4 Antibodies in Evolving HITT: A Unique Phenomenon of Delayed Seroconversion with Thrombosis." Blood 110, n. 11 (16 novembre 2007): 1309. http://dx.doi.org/10.1182/blood.v110.11.1309.1309.

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Abstract (sommario):
Abstract In the appropriate clinical setting, a negative ELISA test for Hep/PF4 antibodies (Ab) has traditionally been considered sufficient to rule out HIT/HITT. We describe a series of 20 cases of HIT/HITT in which the ELISA at the onset of thrombocytopenia was negative despite high (6/8) “4T’s” scores (Thrombocytopenia, Timing of thrombocytopenia in relation to heparin exposure, Thrombosis, and no oTher explanation of thrombocytopenia) but showed strong seroconversion subsequently. This suggests that the negative predictive value of the ELISA test may be too low to definitively exclude HITT. We retrospectively reviewed 494 consecutive Hep/PF4 ELISA assays (sensitivity >90%) performed on 395 patients (pts). Of the 292 pts who tested negative, 73 pts underwent repeat ELISA testing due to the development of a new thrombotic event or the persistence of strong clinical suspicion of HIT/HITT. Twenty of the 73 pts (27%) were observed to have initial negative Hep/PF4 titers (mean = 0.13) at the time of thrombocytopenia but a positive assay (mean = 1.5) on follow-up testing (figure 1 right panel). All 20 pts presented with high “4T’s” scores (6 of 8) at the time of the negative ELISA and had a history of recent heparin exposure. The M:F ratio was 11:9. Eleven pts had prior cardiopulmonary bypass while six had left ventricular assist devices. Fifteen pts (75%) had >50% drop in platelet count (figure 1 left panel). Mean platelet count at the time of negative ELISA was 71x109/l (vs. baseline mean platelet count of 171x109/l) (figure 2). Fourteen of 15 pts (for which data was available) had thrombotic events (9 arterial, 5 venous). Strong seroconversion was seen in all pts (mean = 8 days after initial test) and surprisingly, it accompanied platelet recovery in 15 of 20 pts (figure 1 left panel), with mean platelet count of 136x109/l at the time of the positive ELISA (figure 2). Argatroban was used as a direct thrombin inhibitor (DTI) in 16/20 pts. The prognosis was poor: 10 pts (50%) succumbed with multi-system organ failure. Conclusion: We have described 20 cases of HIT/HITT with initial negative Hep/PF4 Ab titers at the time of thrombocytopenia, followed by delayed seroconversion. This observation suggests that in the proper clinical setting one isolated negative ELISA result cannot exclude evolving HIT/HITT. Follow-up testing may be informative even as the platelet count begins to recover. As HIT/HITT may have potentially fatal outcome, clinicians should maintain a high degree of suspicion despite a negative serology by ELISA, especially in pts with “4T’s” scores ≥ six. Empiric treatment with DTI’s may be warranted until two consecutive ELISA tests are negative. Figure Figure Figure Figure
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26

Piovella, Chiara, John Fanikos, Matthew Labreche, Jay Lin, Samuel Z. Goldhaber e Steven Baroletti. "Heparin-induced thrombocytopenia (HIT): Clinical and economic outcomes". Thrombosis and Haemostasis 100, n. 12 (2008): 1130–35. http://dx.doi.org/10.1160/th08-05-0312.

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Abstract (sommario):
SummaryHeparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction that occurs following exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH).HIT with thrombosis (HITT) can cause devastating venous thromboembolism or arterial clots, prolonged hospitalization, and increased costs. To explore the economic and clinical implications of HIT and HITT, we initiated a single-center patient registry. In this report, we describe patient characteristics, comorbidities, management strategies, clinical outcomes, and costs. We enrolled 349 hospitalized patients with an enzyme immunoassay-confirmed diagnosis of HIT over a 40-month period. Patients were assessed for the primary outcome of 30-day mortality, as well as baseline characteristics, development of thrombosis, and the economic impact of HIT. The primary outcome measure was 30-day mortality and occurred in 58 (16.6%) patients, 40 (15.3%) in the HIT group versus 18 (20.7%) in the HITT group (p=0.25).The frequency of HIT was greater in patients exposed to UFH than in patients exposed to LMWH (0.8% vs. 0.2%, respectively, p<0.001). Both HIT and HITT patients who were exposed to UFH had higher hospital costs than those exposed to LMWH ($113,100 vs. $56,352, respectively, p<0.001). HIT remains an important clinical problem with a high mortality rate and significant cost, regardless of development of thrombosis. Prospective controlled trials need to be conducted to determine the optimal strategy to reduce the frequency of HIT.
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27

Kellermanns, Franz W., e Tim Barnett. "Commentary: What Were They Thinking? The Role of Family Firm Mental Models on Threat Recognition". Entrepreneurship Theory and Practice 32, n. 6 (novembre 2008): 999–1006. http://dx.doi.org/10.1111/j.1540-6520.2008.00268.x.

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In this commentary, we extend Sirmon, Arregle, Hitt, and Webb's work in this issue by introducing shared mental models as antecedents of threat of imitability recognition and as moderators of the relationship between threat recognition and strategic action. Specifically, while Sirmon, Arregle, Hitt, and Webb focus on responses to threat recognition, we develop propositions on how shared mental models related to business issues affect the threat recognition process and on how shared mental models related to family issues influence strategic responses to recognized threats. Implications and areas for future research are discussed.
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28

Suh, Jang-Soo, Richard H. Aster e Gian P. Visentin. "Antibodies From Patients With Heparin-Induced Thrombocytopenia/Thrombosis Recognize Different Epitopes on Heparin: Platelet Factor 4". Blood 91, n. 3 (1 febbraio 1998): 916–22. http://dx.doi.org/10.1182/blood.v91.3.916.

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Abstract (sommario):
Abstract Antibodies associated with heparin-induced thrombocytopenia/thrombosis (HITT) are now thought to be specific for complexes formed between heparin and platelet factor 4 (PF4), a basic protein found normally in platelet alpha granules. How these antibodies cause thrombocytopenia and, in some patients, thrombosis, is not fully understood, in part because purified antibodies that could be labeled and used as probes to characterize target epitopes have not been available. We developed a novel method for antibody purification involving binding to and elution from PF4 complexed to heparin immobilized by end-linkage (EL) to a solid phase. Isolated antibodies were functional and after biotinylation, reacted with heparin: PF4 complexes in the same manner as unlabeled antibodies. Using these probes, we found that antibodies from 11 patients with HITT recognized two, and probably three, distinct sites on heparin: PF4 complexes. The antibodies did not bind to PF4 complexed with heparin immobilized by multiple chemical cross-linkages, suggesting that the heparin molecule must be in a flexible, relatively unconstrained state to react with PF4 in such a way as to create sites for HITT antibody binding.
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29

Suh, Jang-Soo, Richard H. Aster e Gian P. Visentin. "Antibodies From Patients With Heparin-Induced Thrombocytopenia/Thrombosis Recognize Different Epitopes on Heparin: Platelet Factor 4". Blood 91, n. 3 (1 febbraio 1998): 916–22. http://dx.doi.org/10.1182/blood.v91.3.916.916_916_922.

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Abstract (sommario):
Antibodies associated with heparin-induced thrombocytopenia/thrombosis (HITT) are now thought to be specific for complexes formed between heparin and platelet factor 4 (PF4), a basic protein found normally in platelet alpha granules. How these antibodies cause thrombocytopenia and, in some patients, thrombosis, is not fully understood, in part because purified antibodies that could be labeled and used as probes to characterize target epitopes have not been available. We developed a novel method for antibody purification involving binding to and elution from PF4 complexed to heparin immobilized by end-linkage (EL) to a solid phase. Isolated antibodies were functional and after biotinylation, reacted with heparin: PF4 complexes in the same manner as unlabeled antibodies. Using these probes, we found that antibodies from 11 patients with HITT recognized two, and probably three, distinct sites on heparin: PF4 complexes. The antibodies did not bind to PF4 complexed with heparin immobilized by multiple chemical cross-linkages, suggesting that the heparin molecule must be in a flexible, relatively unconstrained state to react with PF4 in such a way as to create sites for HITT antibody binding.
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30

Henry Edmunds, L. "Hit, hitt, and desulfatohirudin: Look before you leap". Journal of Thoracic and Cardiovascular Surgery 110, n. 1 (luglio 1995): 1–3. http://dx.doi.org/10.1016/s0022-5223(05)80002-9.

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31

Demenge, Jonathan, e Bibek Shrestha. "High Impact Tourism Training (HITT) Programme in Nepal". Journal of International and Comparative Education 7, n. 2 (2018): 97–109. http://dx.doi.org/10.14425/jice.2018.7.2.97.

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32

Elliott, Michelle A., Sandra Schulte, Elizabeth A. Plumhoff, Rajiv K. Pruthi, William L. Nichols, Mark R. Litzow, Dennis A. Gastineau e John A. Heit. "Frequency of Heparin-Induced Thrombocytopenia and Heparin-Dependent IgG Antibodies in Hematopoietic Stem Cell Transplant Recipients." Blood 108, n. 11 (16 novembre 2006): 4059. http://dx.doi.org/10.1182/blood.v108.11.4059.4059.

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Abstract (sommario):
Abstract Background Heparin-induced thrombocytopenia (HIT) is an immune-mediated drug reaction in which heparin-dependant IgG antibodies (HIT-IgG) to heparin-platelet factor 4 complexes form with the potential for platelet activation with resultant thrombocytopenia (HIT) and thrombosis (HITT). The frequency of HIT-IgG formation and clinically apparent HIT or HITT varies considerably, according to the patient population (surgical versus medical) and type of heparin (unfractionated [UFH] vs low molecular weight [LMWH]). One large prospective study showed a frequency of HIT-IgG formation of 7.5% with clinical HITT in 34.5% of these orthopedic patients receiving prophylactic LMWH and corresponding figures in cardiac surgery patients receiving UFH were 50% and 2%, respectively [Warkentin et al. Blood2000;96: 1703]. Due to daily exposure to heparin flushes (UFH) and prophylactic LMWH (to prevent venoocclusive disease) hematopoietic stem cell transplant (HSCT) recipients may be at risk for HIT/HITT. However, due to anticipated post-transplant thrombocytopenia, clinical cases of HIT/HITT may be overlooked. We retrospectively determined the incidence of HIT-IgG formation and its clinical significance in this population. Methods: HIT-IgG was measured retrospectively using a commercially available ELISA kit in samples collected from patients prior to conditioning therapy and on day 14 post-HSCT. Medical records were reviewed to in order to determine the clinical significance (development of clinical HIT/HITT) in those with detectable HIT-IgG. Patients Samples from a total of 103 HSCT recipients with hematologic malignancy (including 25 myeloma, 17 lymphoma, 16 AML, 14 amyloid, 10 MDS, 10 ALL, 8 CML and 3 CLL) were tested, of which 52 and 49 underwent allogeneic and autologous HSCT, respectively. All patients were exposed to UFH flushes during line care. In addition, all allogeneic recipients received prophylactic subcutaneous dalteparin 5000U daily beginning with conditioning until engraftment. Conditioning regimens included high dose melphalan (n=34), cyclophosphamide/TBI (n=30), carmustine, etoposide, cytarabine, melphalan (n=15), busulfan/cyclophosphamide (n=9), fludarabine/melphalan (n=10) and fludarabine/TBI (n=4). The median age was 51.5 years (20–72) and 68 were male. Results: The median platelet count prior to initiation of conditioning therapy and at day 14 was 157 × 109/L (range: 10–672) and 40 × 109/L (range: 9–289), respectively. Prior to conditioning, two of 103 (1.9%) patients had a positive HIT-IgG assay, that became negative in one and equivocal in the other by day 14 post-HSCT, and one patient had an equivocal HIT assay that became negative by day 14. All 3 were autologous recipients. None of the previously negative patients had a positive HIT-IgG assay at day 14, although 3 patients (2 autologous and one allogeneic) had an equivocal result of uncertain significance. No patients developed clinical or symptomatic thrombosis (HITT). Conclusion: In spite of frequent exposure to heparin, the frequency of seroconversion is low, and in those patients with preexisting HIT-IgG, no patient developed symptomatic thrombosis, including the 2 patients with positive HIT IgG assays prior to conditioning. The low frequency of HIT-IgG formation may reflect the profound immunosuppression of the conditioning regimens employed. Nevertheless, in this population, a high index of clinical suspicion must be maintained.
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33

Rauova, Lubica, Mortimer Poncz, Steven E. McKenzie, Michael P. Reilly, Gowthami Arepally, John W. Weisel, Chandrasekaran Nagaswami, Douglas B. Cines e Bruce S. Sachais. "Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia". Blood 105, n. 1 (1 gennaio 2005): 131–38. http://dx.doi.org/10.1182/blood-2004-04-1544.

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Abstract (sommario):
Abstract Heparin-induced thrombocytopenia and thrombosis (HITT) is a severe complication of heparin therapy caused by antibodies to complexes between unfractionated heparin (UFH) and platelet factor 4 (PF4) that form over a narrow molar range of reactants and initiate antibody-induced platelet activation. We observed that UFH and tetrameric PF4 formed ultralarge (&gt; 670 kDa) complexes (ULCs) only over a narrow molar range with an optimal ratio of PF4 to heparin of approximately 1:1. These ULCs were stable and visible by electron microscopy, but they could be dissociated into smaller complexes upon addition of heparin. ULCs formed inefficiently when PF4 was incubated with low-molecular-weight heparin, and none formed with the pentasaccharide fondaparinux sodium. In addition, mutation studies showed that formation of ULCs depended on the presence of PF4 tetramers. The ULCs were more reactive as determined by their capacity to bind to a HITT-like monoclonal antibody and showed greater capacity to promote platelet activation in an antibody- and FcγRIIA-dependent manner than were the smaller complexes. The capacity of PF4 to form ULCs composed of multiple PF4 tetramers arrayed in a lattice with several molecules of UFH may play a fundamental role in autoantibody formation, antibody-dependent platelet activation, and the propensity for thrombosis in patients with HITT.
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34

Ketelhut, Sascha, Eva Kircher, Sebastian R. Ketelhut, Emanuel Wehlan e Kerstin Ketelhut. "Effectiveness of Multi-activity, High-intensity Interval Training in School-aged Children". International Journal of Sports Medicine 41, n. 04 (14 gennaio 2020): 227–32. http://dx.doi.org/10.1055/a-1068-9331.

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Abstract (sommario):
AbstractThe present study aimed to evaluate the effectiveness of a school-based multi-activity HIIT on aerobic fitness (AF) and hemodynamic parameters in children. 46 students were randomized into an intervention group (INT) (N=22) and a control group (CON) (N=24). Throughout a 3-month intervention period, both INT and CON participated in the regular physical education classes (PE) twice a week. Only INT received an instructed HIIT during the first 20 min of the PE. In addition to an AF-test, peripheral (pBP) and central (cBP) blood pressure, augmentation pressure (AP), and aortic pulse wave velocity (aPWV) were assessed. Significant differences in intervention effects in favor of INT were detected for AF (7.73, P=0.007), peripheral systolic BP (−6.13 mmHg, P=0.038), central systolic BP (−5.19 mmHg, P = 0.041), AP (−2.02 mmHg, P=0.013), and aPWV (−0.19 m/sec, P=0.031). The regular HITT intervention showed beneficial effects on AF, BP, and parameters of vascular stiffness already in children.
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35

Gould, Nadia N., Christine L. Haley, Lu Song, Mervyn A. Sahud e Jeffrey Dlott. "In Vitro Characteristics of Fondaparinux On HIT/HITT Samples." Blood 114, n. 22 (20 novembre 2009): 1319. http://dx.doi.org/10.1182/blood.v114.22.1319.1319.

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Abstract (sommario):
Abstract Abstract 1319 Poster Board I-335 Heparin-induced thrombocytopenia (HIT) and HIT-associated thrombosis (HITT) are secondary to immune-mediated IgG antibodies that develop against the molecular complex of platelet factor 4 (PF4)–heparin, occurring with exposure to unfractionated heparin (UFH) and low molecular weight heparins (LMWH). Fondaparinux, a synthetic pentasaccharide that binds antithrombin and selectively inhibits Factor Xa, is indicated for prophylaxis and treatment of thrombosis. Fondaparinux has occasionally been reported to induce production of PF4–heparin antibodies; whether these antibodies activate platelets, in vitro or in vivo, remains unclear. Thus, fondaparinux has not been approved for patients with HIT/HITT. This study examined the in vitro cross-reactivity of fondaparinux in 2 HIT assays: a serotonin release assay (SRA) and an anti-PF4 enzyme-linked immunosorbent assay (ELISA) with neutralization. Serum samples (n=10) from patients with confirmed HIT/HITT were tested by SRA with UFH, LMWH (enoxaparin), and fondaparinux; and for anti-PF4 using a polyspecific ELISA (GTI, Waukesha, WI). In addition, 20 previously characterized samples strongly positive on the anti-PF4 ELISA (>1.000 OD) were used for confirmatory quenching studies with UFH, LMWH, and fondaparinux. LMWH-SRA and UFH-SRA results were concordant (positive) in all but one sample, which was positive with UFH but indeterminate with LMWH (Table). The fondaparinux-SRA was negative in 6 of 10 cases and indeterminate in 4. The indeterminate fondaparinux-SRA results were reproducible with a second platelet donor and when diluted 1:4 with negative anti-PF4 serum. Of note, platelet activation was observed in the buffer well (ie, without UFH, LMWH, or fondaparinux) in 3 of the 4 indeterminate cases but not in the 6 negative fondaparinux-SRA samples. All 10 samples showed positive results in the anti-PF4 ELISA (range=0.423-3.408 OD; median OD=2.588). In the second group of samples tested by anti-PF4 ELISA (range=1.395-3.204 OD; median=2.417 OD), quenching studies with excess UFH or LMWH yielded ≥50% inhibition, confirming anti-PF4 positivity, in 17 of 20 samples. Quenching with fondaparinux was not confirmatory, yielding only equivocal inhibition (range=0 to 46.7%; median=9.1%). In conclusion, fondaparinux appears to be generally not cross-reactive in SRAs performed on HIT/HITT-positive samples. The four fondaparinux-SRA cases were indeterminate despite heat inactivation of complement and the addition of hirudin to neutralize any thrombin contamination; this suggests that there may be heterogeneous pathogenic subpopulations that bind PF4 even in the absence of heparin or heparin-like molecules. The considerable variability in anti-PF4 confirmation studies with fondaparinux, relative to UFH and LMWH, warrants further study. Table. SRA* and Anti-PF4 ELISA** Results from Patients with Clinical HIT/HITT UFH-SRA LMWH-SRA Fondaparinux-SRA Anti-PF4 ELISA Sample (% release) (% release) (% release) (OD units) 1 100 96 indeterminate 0.798 2 98 100 <20 2.573 3 34 indeterminate indeterminate 0.423 4 72 90 <20 3.012 5 100 107 indeterminate 3.275 6 95 92 <20 2.903 7 80 99 <20 2.602 8 74 70 <20 2.349 9 55 86 indeterminate 1.756 10 100 108 <20 3.408 * Positive result defined as ≥20% serotonin release with standard drug concentration and ≥50% inhibition with excess drug. Negative result defined as <20% serotonin release. Indeterminate result defined as ≥20% serotonin release with standard drug concentration and <50% inhibition with excess drug. ** Positive result defined as OD ≥0.400. Disclosures No relevant conflicts of interest to declare.
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36

Kong, Jian Pei, Linda Jok, Azlee Bin Ayub e Rawa Ak Bau. "Worksite weight management program". Nutrition & Food Science 47, n. 4 (10 luglio 2017): 490–510. http://dx.doi.org/10.1108/nfs-08-2016-0132.

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Purpose This study aims to pilot test a new multi-component worksite intervention for weight loss in a primary healthcare setting. Design/methodology/approach This randomized trial involved 88 participants (43, 45; intervention, control group). The intervention group enrolled in a 12-week lifestyle program that involved modification of dietary intake by community Registered Dietitian (RDs) and increasing high-intensity interval training (HITT) with motivational interviewing (MI) to support changes. The control group received traditional counselling and weekly aerobic exercise from Medical Officer and physiotherapist. The primary outcome measure was the changes in body weight. Secondary measures were changes in blood pressure, fasting blood glucose, fasting blood lipid and dietary changes. Assessments were repeated at a three-month interval. Findings There was a significant reduction in body weight and waist circumference within groups. Intervention group demonstrated a significant improvement in all cardiometabolic risk factors. This study showed that primary healthcare setting can be successful locations in promoting short-term health benefits. RDs were more successful and HITT appeared to be a favorable workout with MI in achieving drastic weight loss. Research limitations/implications The short-term worksite intervention and not recording of body composition were the major drawbacks in this study. Originality/value The efficacy of multi-component worksite intervention (Diet–HITT–MI) in primary healthcare setting has not been clearly defined.
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37

Höfler, Stefan. "Dark Matter". Indo-European Linguistics 3, n. 1 (2015): 24–41. http://dx.doi.org/10.1163/22125892-00301004.

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The assumption of a root *√k̑u̯el ‘dark, black’ offers new possible etymologies for Arm. šaɫax, Gk. πηλός, Toch. B kwele, Hitt. kuu̯aliu-, Gk. κύλα, Lat. culex, and Lat. color, whose derivational background will be dealt with in the course of this paper.
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38

Smoot, Betsy Rohaly. "An Accidental Cryptologist: The Brief Career of Genevieve Young Hitt". Cryptologia 35, n. 2 (31 marzo 2011): 164–75. http://dx.doi.org/10.1080/01611194.2011.558982.

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39

PATEL, CHIRAG, SALIM SURANI, CHINTHAKA BULATHSINGHALA, BRYAN ANDERSON, AFTAB MAHMOOD, DEANNA YAMAMURA, AHMED HASSAN e PALLA DE SILVA. "A CASE OF SPONTANEOUS HEPARIN-INDUCED THROMBOCYTOPENIA AND THROMBOSIS (HITT)". Chest 154, n. 4 (ottobre 2018): 308A—309A. http://dx.doi.org/10.1016/j.chest.2018.08.283.

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40

Souza, Rafael Luiz Mesquita, Felipe José Aidar, Sílvia Schütz, Jymmys Lopes Dos Santos, Nara Michelle Moura Soares, Silvan Silva De Araújo e Anderson Carlos Marçal. "Effects of high-intensity interval training on health-related physical fitness in children and adolescents: a systematic review". Revista Brasileira de Fisiologia do Exercício 19, n. 6 (24 dicembre 2020): 519. http://dx.doi.org/10.33233/rbfex.v19i6.4376.

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Introduction: High-intensity interval training (HIIT) can promote improvement in health and physical conditioning and contribute to the increase in cardiorespiratory capacity (VO2max), local muscular endurance, and improved body composition. However, its effects on health-related physical fitness in children and adolescents are still unclear. Objective: The objective of the study was to analyze the effectiveness of HIIT in the health-related physical fitness of children and adolescents. Methods: The present study analyzed articles from databases (SPORTDiscus, Web of Science, Medline via Pubmed, Scopus, Scielo, and Bireme). The PICO strategy was applied to select articles and CONSORT to assess the quality of randomized controlled trials. 511 studies were found. Of this total, 101 articles were eligible for analysis of the abstract. Results: At the end of the selection process, 10 articles resulted in the inclusion criteria. The results suggest that among the variables analyzed by the articles referring to health-related physical fitness, HIIT demonstrated effectiveness in VO2max, body mass index (BMI), and percentage of fat (%F) in this population. Conclusion: However, it was not possible to state that HITT promoted adjustments in flexibility, strength and local muscular endurance, and further studies are needed to assess its effects on health-related physical fitness.Keywords: physical exercise, adolescent, primary health care.
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Souza, Rafael Luiz Mesquita, Felipe José Aidar, Sílvia Schütz, Jymmys Lopes Dos Santos, Nara Michelle Moura Soares, Silvan Silva De Araújo e Anderson Carlos Marçal. "Effects of high-intensity interval training on health-related physical fitness in children and adolescents: a systematic review". Revista Brasileira de Fisiologia do Exercício 19, n. 6 (24 dicembre 2020): 519. http://dx.doi.org/10.33233/rbfex.v19i6.4376.

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Abstract (sommario):
Introduction: High-intensity interval training (HIIT) can promote improvement in health and physical conditioning and contribute to the increase in cardiorespiratory capacity (VO2max), local muscular endurance, and improved body composition. However, its effects on health-related physical fitness in children and adolescents are still unclear. Objective: The objective of the study was to analyze the effectiveness of HIIT in the health-related physical fitness of children and adolescents. Methods: The present study analyzed articles from databases (SPORTDiscus, Web of Science, Medline via Pubmed, Scopus, Scielo, and Bireme). The PICO strategy was applied to select articles and CONSORT to assess the quality of randomized controlled trials. 511 studies were found. Of this total, 101 articles were eligible for analysis of the abstract. Results: At the end of the selection process, 10 articles resulted in the inclusion criteria. The results suggest that among the variables analyzed by the articles referring to health-related physical fitness, HIIT demonstrated effectiveness in VO2max, body mass index (BMI), and percentage of fat (%F) in this population. Conclusion: However, it was not possible to state that HITT promoted adjustments in flexibility, strength and local muscular endurance, and further studies are needed to assess its effects on health-related physical fitness.Keywords: physical exercise, adolescent, primary health care.
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42

Kawakami, K., B. K. Shafer, D. J. Garfinkel, J. N. Strathern e Y. Nakamura. "Ty element-induced temperature-sensitive mutations of Saccharomyces cerevisiae." Genetics 131, n. 4 (1 agosto 1992): 821–32. http://dx.doi.org/10.1093/genetics/131.4.821.

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Abstract Temperature-sensitive mutants of Saccharomyces cerevisiae were isolated by insertional mutagenesis using the HIS3 marked retrotransposon TyH3HIS3. In such mutants, the TyHIS3 insertions are expected to identify loci which encode genes essential for cell growth at high temperatures but dispensable at low temperatures. Five mutations were isolated and named hit for high temperature growth. The hit1-1 mutation was located on chromosome X and conferred the pet phenotype. Two hit2 mutations, hit2-1 and hit2-2, were located on chromosome III and caused the deletion of the PET18 locus which has been shown to encode a gene required for growth at high temperatures. The hit3-1 mutation was located on chromosome VI and affected the CDC26 gene. The hit4-1 mutation was located on chromosome XIII. These hit mutations were analyzed in an attempt to identify novel genes involved in the heat shock response. The hit1-1 mutation caused a defect in synthesis of a 74-kD heat shock protein. Western blot analysis revealed that the heat shock protein corresponded to the SSC1 protein, a member of the yeast hsp70 family. In the hit1-1 mutant, the TyHIS3 insertion caused a deletion of a 3-kb DNA segment between the delta 1 and delta 4 sequences near the SUP4 locus. The 1031-bp wild-type HIT1 DNA which contained an open reading frame encoding a protein of 164 amino acids and the AGG arginine tRNA gene complemented all hit1-1 mutant phenotypes, indicating that the mutant phenotypes were caused by the deletion of these genes. The pleiotropy of the HIT1 locus was analyzed by constructing a disruption mutation of each gene in vitro and transplacing it to the chromosome. This analysis revealed that the HIT1 gene essential for growth at high temperatures encodes the 164-amino acid protein. The arginine tRNA gene, named HSX1, is essential for growth on a nonfermentable carbon source at high temperatures and for synthesis of the SSC1 heat shock protein.
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43

Adika, Rohfik, e Subandrio Subandrio. "The Effect Of Electronic Commerce And Brand Awareness On Purchasing Decisions At Shopee Online Shopping". BIMA Journal (Business, Management, & Accounting Journal) 2, n. 1 (31 maggio 2021): 53–66. http://dx.doi.org/10.37638/bima.2.1.53-66.

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The impact of the dynamics of business competition in the development of the world of information technology is getting more advanced and rapid from time to time so that purchases via virtual are increasing. The purposee off thiss study was to know the effect off electronic commercee and brand awareness on purchasing decision non Online shopee shopping (Case study on online shopping consumers of muhammadiyah university of bengkulu students).This research uses survey research method with quantitative data analysis. The population in this study were students of the University of Muhammadiyah Bengkulu who shop online at shopee with a total of 140 people, anddtheesample was taken usinggpurposiveesamplinggmethod. based on the resultssoffmultipleelinearr regression, it issobtained theeregressionnequationnY = 2.621 + 0.060 (X1) + 0.540 (X2).The resultssoffthe research and hypotheses show that electronic commerce (X1) is t-hitt-table (3.328 1.9774) and (sig α = 0.001 0.050), brand awareness (X2) is t-hitt-table (7,418 1.9774) and (sig α = 0.000 0.050) simultaneously haveea significantteffectton purchasing decisions. Partially the two variables of electronic commerce and brand awareness have a significant effect on purchasing decisions.
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44

Hussain, Farrukh, Roger Philipp e Shelley Zieroth. "HITT and stent thrombosis: A “CLINICAL” diagnosis not to be missed". International Journal of Cardiology 133, n. 1 (marzo 2009): e11-e13. http://dx.doi.org/10.1016/j.ijcard.2007.08.078.

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45

Kalyan Kunchapudi, S., Greeshma Issac, Saravana Pandian e Indira Jayakumar. "A case of HITT in a child on extracorporeal Membrane Oxygenation". Egyptian Journal of Critical Care Medicine 6, n. 3 (dicembre 2018): 111–12. http://dx.doi.org/10.1016/j.ejccm.2018.12.009.

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46

Pathak, Ranjan, Smith Giri, Madan Raj Aryal, Paras Karmacharya, Anthony Donato e Vijaya R. Bhatt. "Medical and Economic Burden of Heparin-Induced Thrombocytopenia: Data from the National Inpatient Sample 2009-2011". Blood 126, n. 23 (3 dicembre 2015): 3272. http://dx.doi.org/10.1182/blood.v126.23.3272.3272.

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Abstract Background Although generally safe, heparin use can trigger an immune response in which platelet factor 4-heparin complexes set off an antibody-mediated cascade that can result in heparin-induced thrombocytopenia (HIT). Although older studies report incidences as high as 5% in high-risk subgroups of surgical patients, recent studies report a much lower incidence (0.02% of hospital admissions and <0.1-0.4% among patients exposed to heparin). As hospitals transition to the less immunogenic low molecular weight heparins, reassessment of the overall national burden of HIT would help inform needs for monitoring strategies for this potentially fatal complication of anticoagulation. Methods We used the 2009-2011 National Inpatient Sample database to identify patients aged ≥18 years with primary and secondary diagnoses of HIT (International Classification of Diseases, 9th Revision, Clinical-Modification [ICD-9-CM] code 289.84). We derived the prevalence rate of HIT overall as well as among subgroup of patients undergoing 3 types of surgeries (cardiac, vascular and orthopedic surgeries). We compared characteristics of patients diagnosed with versus without HIT, and HIT with thrombosis (HITT) versus those without thrombosis. Statistical analysis was performed using Stata 13.1, which accounted for the complex survey design and clustering. We used a 2-sided p- value of <0.05 to determine statistical significance. Results We identified 72,515 cases of HIT among a total of 98,636,364 hospitalizations (0.07%). Arterial and venous thromboses were identified in 24,880 (34.3%) of cases with HIT. Males were slightly more likely to be diagnosed with HIT (50.12% vs. 49.88%, odds ratio, OR 1.48, 95% CI: 1.46-1.51), but females had higher rates of post-cardiac and vascular surgery-associated HIT (OR: 1.41, 95% confidence interval, CI: 1.26-1.58, p<0.001 and OR 1.42, 95% CI: 1.29-1.57, p<0.001 respectively). Prevalence rates of HIT among cardiac, vascular and orthopedic surgeries were 0.53% (95% CI: 0.51-0.54%), 0.28% (95% CI: 0.28-0.29%) and 0.05% (95% CI: 0.05-0.06%) respectively. Patients with HIT and HITT were significantly more likely to be fatal than cases without diagnosed HIT (9.63% and 12.28% versus 2.19% respectively, p<0.001), and have significantly higher costs ($137401 and $179735 versus $35905) and length of stay (14.07 and 16.51 days versus 4.76 days). Conclusion Although rates of HIT appear lower in the modern era of widespread low molecular weight heparin use, patients undergoing cardiac and vascular surgeries remain at significant risk. Even in recent years, one-third of patients with HIT develop thrombosis, which significantly increases mortality, cost and length of stay. Strategies to monitor and mitigate that risk in high-risk patients appear to be warranted. Table 1. In-hospital mortality, mean LOS and Mean hospital charges for patients with heparin induced thrombocytopenia (HIT) and HIT with thrombosis (HITT) No HIT HIT P HIT without thrombosis HITT P In-hospital mortality 2.19% 9.63% (OR 4.75, 95% CI 4.45-5.08) <0.001 8.24% 12.28% (OR 1.56, 95% CI 1.40-1.74) <0.001 Mean LOS (days) 4.76 (95% CI 4.71-4.82) 14.07 (95% CI 13.67-14.48) <0.001 12.80 (95% CI 12.38-13.23) 16.51 (95% CI 15.96-17.06) <0.001 Mean total hospital charge (USD) 35905 (95% CI 34626- 37185) 137401 (95% CI 129369-145433) <0.001 115456 (95% CI 108251-122661) 179735 (95% CI 168582-190889) <0.001 HIT= Heparin induced thrombocytopenia; HITT= Heparin induced thrombocytopenia with thrombosis; LOS=Length of stay; USD=US Dollars. Disclosures No relevant conflicts of interest to declare.
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47

Nanwa, Natasha, Nicole Mittmann, Sandra Knowles, Rita Selby, Neil Shear, Scott Walker e William Geerts. "The Direct Medical Costs Associated with Suspected and Confirmed Cases of Heparin-Induced Thrombocytopenia." Blood 110, n. 11 (16 novembre 2007): 972. http://dx.doi.org/10.1182/blood.v110.11.972.972.

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Abstract (sommario):
Abstract Introduction: Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction associated with heparin exposure. Few studies have assessed the economic burden associated with HIT and none have assessed the costs of suspected HIT. The objective of our study was to identify and quantify the direct medical costs associated with suspected and confirmed cases of HIT from the Canadian hospital perspective. Methods: Over the last 7 years SHSC, a tertiary care adult academic hospital, experienced on average 125 cases of suspected HIT per year. A retrospective burden of illness analysis was conducted to examine the costs associated with suspected and confirmed cases of HIT at SHSC in 2005. Suspected HIT was defined by the performance of a HIT enzyme linked immunosorbent assay (ELISA) from January 1, 2005 to December 31, 2005. Confirmed HIT cases were defined as those who had a positive serotonin release assay (SRA) or a positive HIT ELISA plus a high clinical probability for HIT. In addition, HIT-related resource utilization variables were assessed by chart review and included: inpatient medication use; laboratory and imaging tests; and duration of hospital stay. Physician visits and post-discharge costs were not included in the cost analysis. The average cost per case of confirmed HIT, confirmed HIT with thrombosis (HITT), and negative HIT was calculated in 2007 Canadian dollars. Cost information was obtained from multiple sources, including the pharmacy database (WORx©) and Ontario Health Insurance Program (OHIP) Schedule of Benefits. For this analysis, we did not assume that length of stay (LOS) was prolonged by HIT unless the patient was readmitted with a HIT-related complication. The costs attributable to prolongation of LOS due to HIT or its treatment are being determined, although it is difficult to allocate some costs to the presence of HIT alone. The cost for a negative HIT case only includes the cost of inpatient medication use, laboratory and imaging tests. Results: There were 110 suspected HIT cases in 2005. We excluded 2 patients because their HIT status could not be determined after careful review. There were 88 HIT negative cases, 8 cases with confirmed HIT and 12 with HITT (Table). In this conservative analysis, patients with HITT incurred substantially greater costs than those with HIT. The average attributable cost of managing a HIT negative case was $116. Cardiovascular surgery (CVS) patients accounted for 48% of the suspected HIT cases and 65% of the confirmed cases. This represents 5% and 1% of the 960 CVS patients seen over the year. Conclusions: This is the first study to identify and quantify the direct medical costs associated both with confirmed HIT and HITT and also negative HIT cases. Clearly, if LOS is prolonged by HIT, as has been shown by others, the costs per case will escalate. Cardiovascular surgery cases are being analyzed separately. Table. Demographics and Incremental Costs for Suspected HIT Cases (n=108) Negative HIT Confirmed HIT Confirmed HITT n 88 8 12 CVS patients (%) 44% 75% 58% Other Surgical patients (%) 16% 13% 8% Medical patients (%) 40% 12% 34% Mean Age ± SD (range) 69 ± 13 (19–94) 64 ± 12 (47–83) 73 ± 7 (59–83) LOS ± SD (range) 37 ± 44 (3–244) 29 ± 21 (5–62) 37 ± 35 (12–128) Average HIT-attributable Cost per Case $116 $966 $6,762
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48

Stirrup, Tracey, Diane Williams, Samantha Sharman, Joan Williamson e Mark Aldersley. "Micro-elimination in prisons: a high-intensity test and treat (HITT) programme". Journal of Hepatology 73 (agosto 2020): S329. http://dx.doi.org/10.1016/s0168-8278(20)31160-0.

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49

Goti, F., D. Gianom, W. Korte, D. Sege e M. Decurtins. "Postoperative Heparin- induzierte Thrombopenie mit Thromboembolie (HITT) - Eine seltene Komplikation der Heparintherapie?" Swiss Surgery 7, n. 2 (2001): 0051–56. http://dx.doi.org/10.1024/1023-9332.7.2.51.

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50

Stannard, Alicja, Jonathan Hudak, Kayla Kowalczyk, Bianca DeLucia, Victoria Lynch e Jessica Wade. "Validity Of Activity Monitors For Energy Expenditure During Walking, Running, And Hitt". Medicine & Science in Sports & Exercise 53, n. 8S (agosto 2021): 272. http://dx.doi.org/10.1249/01.mss.0000762252.46129.02.

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