Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin-induced thrombocytopenia is an uncommon but potentially dangerous adverse effect of heparin therapy. Late onset thrombocytopenia is usually observed several days after initiating treatment and can be distinguished from early-onset benign thrombocytopenia which is more moderate and transitory and which results from a direct interaction between heparin and platelet membrane proteins which potentialize ADP-induced aggregation. Severe late-onset thrombocytopenia clearly results from an immunological mechanism due to the development of heparin-independent antiplatelet antibodies, often IgGs. These antibodies do not cause cell lysis but have a platelet-activating effect with release of the contents of the dense alpha granulations. This cell activation requires the formation of a heparin-dependent antibody-platelet complex. In most cases, platelet factor 4, an alpha granule protein, would be implicated. The antibody-platelet interaction has an activating effect following binding of the IgG Fc fragment to the Fc gamma RII receptor. The antibodies could also bind, favoring the development of thrombosis. The diagnosis of heparin-induced thrombocytopenia is evidenced by a platelet count under 100 Giga/l, usually from the 5th to 20th week of heparin therapy. Occasionally, the only sign is the low platelet count (drop of over 40% from pretreatment levels). Coagulation activation can lead to diffuse consumption coagulopathy in about 25% of the cases. Clinically, thrombosis is observed in about one half of the cases. Arterial thrombosis is the most characteristic and concerns the aorta and its branches as well as cerebral, coronary, mesenteric, renal and upper limb arteries. Venous thrombosis may be underestimated as they often occur as paradoxical recurrence after heparin therapy. Hemorrhage is much less frequent (less than 20% of cases) and often benign. To diagnose heparin-induced thrombocytopenia, one must eliminate other potential causes (infection, drug...), observe complete normalization of platelet count after heparin withdrawal, and demonstrate heparin-dependent antibodies in the plasma or serum. Different laboratory tests are quite helpful but have variable sensitivity. The incriminated heparin must be discontinued immediately. Use of low-molecular-weight heparins, even when cross-reactivity is not demonstrated in vitro, is not recommended. Other compound however, such as Orgaran 10,172 (or Lomoparan, appear to be the best choice. The action of antivitamin K agents is delayed and, due to the early dissociated drop in protein C at the beginning of treatment further raise the major risk of thrombosis. Classic antiplatelet agents such as aspirin are ineffective if used alone. More powerful compounds such as Ilomedine, are not available for this indication and are difficult to titrate. Part of the therapeutic problem with heparin-induced thrombocytopenia may be resolved with the advent of molecules with a direct antithrombin effect such as hirudine or its analogues. As suggested by a recent study, widespread use of low-molecular-weight heparin will undoubtedly have a highly significant effect on reducing the number of cases of severe thrombocytopenia.
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PMID:[Thrombopenia induced by heparin. From physiopathology to treatment]. 923 38

Danaparoid sodium (danaparoid) is a low molecular weight heparinoid with anticoagulation properties, which mainly consists of heparan sulfate. Compared with heparin sodium (heparin), danaparoid has a much higher anti-Xa/anti-thrombin ratio. We compared the effect of danaparoid on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats with heparin. A bolus injection of endotoxin (10 mg/kg) induced gradual decreases in the platelet count, and the plasma fibrinogen, antithrombin III (AT-III) and heparin cofactor II levels, as well as an increase in the fibrinogen/fibrin degradation products level from 1 to 6 hours after the injection, indicating that both coagulation and fibrinolysis were activated. The intravenous administration of danaparoid or heparin 3 hours after the endotoxin injection inhibited the endotoxin-induced decreases in the platelet count and plasma fibrinogen level and also inhibited the endotoxin-induced increase in glomerular fibrin deposition in the kidney. Differences between danaparoid and heparin were observed in their effects on the plasma AT-III level and clotting time. Danaparoid significantly inhibited both the decrease in the plasma AT-III level and the prolongation of the prothrombin time induced by endotoxin, where as heparin showed no effect on those responses. Moreover, danaparoid enhanced the prolongation of the activated partial thromboplast in time induced by endotoxin to a lesser degree than heparin. These findings suggest that the effects of danaparoid on the endotoxin-induced decrease of the plasma AT-III level and the prolongation of the clotting time are more advantageous than those of heparin. The results may have been due to a higher anti-Xa/anti-thrombin ratio of danaparoid than that of heparin, indicating that danaparoid may be useful in the treatment of DIC.
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PMID:The effect of danaparoid sodium (danaparoid) on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. 975 34