Letteratura scientifica selezionata sul tema "White clot syndrome"

In a minority of patients, heparin administration is associated with thrombocytopenia and this thrombocytopenia may be associated with thromboembolic events. Heparin-associated thromboembolism is described as heparin-associated thrombocytopenia and thrombosis or white clot syndrome. White clot syndrome is caused by antibodies to a heparin-platelet membrane complex. The diagnosis carries a high mortality and morbidity from limb thromboembolism. Treatment includes discontinuation of heparin, use of alternate anticoagulants, and aggressive treatment of thromboses. A case in which acute renal failure occurred in the setting of heparin treatment and thrombocytopenia is described, and evidence that renal failure was a result of white clot syndrome is provided.

Immune heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin therapy and is associated with antibodies directed against a complex of platelet factor 4 (PF4) and heparin. Early diagnosis of HIT is important to reduce morbidity and mortality. I developed an enzyme immunoassay that detects the binding of HIT IgG to PF4-heparin in the fluid phase. This required techniques to purify and biotinylate PF4. The fluid phase assay produces consistently low background and can detect low levels of anti-PF4-heparin. It is suited to testing alternative anticoagulants because, unlike in an ELISA, a clearly defined amount of antigen is available for antibody binding. I was able to detect anti-PF4-heparin IgG in 93% of HIT patients. I also investigated cross-reactivity of anti-PF4-heparin antibodies with PF4 complexed to alternative heparin-like anticoagulants. Low molecular weight heparins cross-reacted with 88% of the sera from HIT patients while half of the HIT sera weakly cross-reacted with PF4-danaparoid (Orgaran). The thrombocytopenia and thrombosis of most of these patients resolved during danaparoid therapy, indicating that detection of low affinity antibodies to PF4-danaparoid by immunoassay may not be an absolute contraindication for danaparoid administration. While HIT patients possess antibodies to PF4-heparin, I observed that HIT antibodies will also bind to PF4 alone adsorbed on polystyrene ELISA wells but not to soluble PF4 in the absence of heparin. Having developed a technique to affinity-purify anti-PF4-heparin HIT IgG, I provide the first estimates of the avidity of HIT IgG. HIT IgG displayed relatively high functional affinity for both PF4-heparin (Kd=7-30nM) and polystyrene adsorbed PF4 alone (Kd=20-70nM). Furthermore, agarose beads coated with PF4 alone were almost as effective as beads coated with PF4 plus heparin in depleting HIT plasmas of anti-PF4-heparin antibodies. I conclude that the HIT antibodies which bind to polystyrene adsorbed PF4 without heparin are largely the same IgG molecules that bind PF4-heparin and thus most HIT antibodies bind epitope(s) on PF4 and not epitope(s) formed by part of a PF4 molecule and part of a heparin molecule. Binding of PF4 to heparin (optimal) or polystyrene/agarose (sub-optimal) promotes recognition of this epitope. Under conditions that are more physiological and sensitive than previous studies, I observed that affinity-purified HIT IgG will cause platelet aggregation upon the addition of heparin. Platelets activated with HIT IgG increased their release and surface expression of PF4. I quantitated the binding of affinity-purified HIT 125I-IgG to platelets as they activate in a plasma milieu. Binding of the HIT IgG was dependent upon heparin and some degree of platelet activation. Blocking the platelet Fc??? receptor-II with the monoclonal antibody IV.3 did not prevent HIT IgG binding to activated platelets. I conclude that anti-PF4-heparin IgG is the only component specific to HIT plasma that is required to induce platelet aggregation. The Fab region of HIT IgG binds to PF4-heparin that is on the surface of activated platelets. I propose that only then does the Fc portion of the bound IgG activate other platelets via the Fc receptor. My data support a dynamic model of platelet activation where released PF4 enhances further antibody binding and more release.

Given the life-threatening nature of cancer, one might expect that children with cancer and their parents would be especially vigilant about following prescribed medical treatments. As illustrated in this chapter, this is not always the case (Partridge, Avorn, Wang, & Winer, 2002). Nonadherence can potentially lead to outright treatment failure, relapse, compromised outcomes, bone marrow transplant failures, or resistance to drugs such as antibiotics (Rapoff, 1999). The purpose of this chapter is to (a) review treatment demands on children with acute leukemia (the most common childhood cancer) and their families to understand better the complex behavioral requirements associated with medical treatments; (b) review studies that have investigated the extent of nonadherence to treatments for pediatric cancer, primarily leukemia; (c) examine factors predictive of adherence; (d) describe strategies for assessing adherence; (e) provide suggestions for improving adherence; and (f) suggest future directions to advance the field of adherence research in pediatric oncology. Strategies for improving adherence were gleaned from the pediatric medical adherence literature on other chronic diseases because we could not find a single adherence intervention study involving children with cancer. Acute leukemia is the most common malignancy in children (Ries et al., 1999). The specific etiology of childhood leukemia is unknown, but the causes appear to be multifactorial. Some of the factors involved in the pathogenesis of acute leukemia include exposure to ionizing radiation or certain drugs (e.g., benzene), certain chromosome abnormalities (e.g., Down syndrome), and congenital or acquired immune deficiencies (e.g., human immunodeficiency virus infection) (Golub & Arceci, 2002; Margolin, Steuber, & Poplack, 2002). The incidence of acute leukemia is 3–4 per 100,000 white children, and approximately 3,000 children will develop acute leukemia in the United States within a given year (Ries et al., 1999). The hallmark of leukemia is bone marrow failure. The bone marrow makes red blood cells, which carry oxygen; white cells, which fight infections; and platelets, which help blood clot. Children with acute leukemia commonly present with pallor and fatigue (secondary to anemia), fever and infections (caused by reduced normal white cells), and excess bruising and bleeding (secondary to low platelets).

Antiphospholipid syndrome which is also known as APS is an autoimmune disease which represents an acquired form of thrombophilia. The etiology of APS remains unknown. This disorder occurs when the immune system mistakenly attacks some of the normal human proteins and manifests itself as recurrent arterial or venous thrombosis and it could emerge after abortions or in recurrent pregnancy loss. In APS, the body produces the wrong antibodies against phospholipid-binding proteins, that is present in the blood and plays an important role in coagulation. Antibodies are specific proteins that usually target and neutralize the body’s invaders, such as viruses and bacteria. When antibodies attack phospholipid-binding proteins, blood clots abnormally. Specifically, it could cause blood clots in veins or arteries leading to stroke and various pregnancy complications such as: endometrial death, miscarriage, preeclampsia, intrauterine growth restriction and prematurity. APS is divided into primary and secondary, which is associated with autoimmune diseases and more often with systemic lupus erythematosus (SLE), while antibodies against cardiolipin are detected in many other conditions (infections, malignancies, drugs, etc.). The symptoms of APS, in addition to arterial and/or venous thrombosis and pregnancy complications, are multisystemic and the differential diagnosis of the primary APS from the secondary, in the context of SLE, is of particular clinical interest and is subject of this literature review.

Examination of the skin can provide information about cutaneous or systemic diseases. As always, examination of the skin is best performed in correlation with the available medical history. Even if the examination is conducted in a different order, you should have a systematic method of presenting the findings. Examination comprises inspection and palpation of skin and skin appendages (hair, nails, teeth, and mucous membranes) and is performed in one of two scenarios. 1. The skin may be sequentially examined alongside the examination of other systems (e.g. neurocutaneous syndromes, which are disorders with neurological features, characteristics lesions on the skin, and tumours in different parts of the body) (table 14.1). 2. A dedicated examination of the skin may need to be carried out when it is the suspected primary involved organ and includes evaluation of the hair, nails, teeth, and mucous membranes of the mouth and genitalia. Key competence skills required in examination of the skin are given in table 14.2. Some of the clinical features of common paediatric dermatoses are given in table 14.3. These steps are repeated in every system to reiterate their importance and to help you recollect the initial approach of any clinical exam. Also refer to chapter 4. • On entering the examination room, demonstrate strict adherence to infection control measures by washing your hands or by using alcohol rub. • Introduce yourself both to the parents and the child. • Talk slowly and clearly with a smile on your face. • Establish rapport with the child and parents. • Expose adequately while ensuring their privacy. • Positioning: the patient must be undressed adequately to carry out a complete examination. Inadequate skin exposure with the cloth pushed to one side or lifted momentarily often casts shadows on the skin and is not conducive for proper examination. Infants and very young children should be undressed completely. The younger child is examined preferably on the parent’s lap. Older children can lie down except for the examination of back, which can be examined in the sitting position.