CURRENT DRUG-TREATMENT STRATEGIES FOR DISSEMINATED INTRAVASCULAR COAGULATION

Disseminated intravascular coagulation (DIC) can be caused by a variet y of diseases. Experimental models of DIC have provided substantial in sight into the pathogenesis of this disorder, which may ultimately res ult in improved treatment. Disseminated coagulation is the result of a complex imbalance of coagulation and fibrinolysis. Simultaneously occ urring tissue factor-dependent activation of coagulation, depression o f natural anticoagulant pathways and shutdown of endogenous fibrinolys is all contribute to the clinical picture of widespread thrombotic dep osition in the microvasculature and subsequent multiple organ failure. Cornerstone for the treatment of DIC is the optimal management of the underlying disorder. At present, specific treatment of the coagulatio n disorders themselves is not based on firm evidence from controlled c linical trials. Plasma and platelet transfusion are used in patients w ith bleeding or at risk for bleeding and low levels of coagulation fac tors or thrombocytopenia. The role of heparin and low molecular weight heparin is controversial, but their use may be justified in patients with active DIC and clinical signs of extensive fibrin deposition such as those with meningococcal sepsis. There is some evidence to indicat e that low molecular weight heparin is as effective as unfractionated heparin but may be associated with a decreased bleeding risk. Antithro mbin III (AT III) replacement appears to bt effective in decreasing th e signs of DIC if high doses are administered, but effects on survival or other clinically significant parameters are at best uncertain. If AT III supplementation is used, the dosage should be selected to achie ve normal or supranormal plasma levels of 100% or higher. Results of s tudies on protein C concentrate, thrombomodulin or inhibitors of tissu e factor are promising, but the efficacy and safety of these novel str ategies remains to be established in appropriate clinical trials.