Anticoagulant proteins in childhood venous and arterial thrombosis: A review

Thrombotic disease is less frequent in children than in adults, but may res ult in severe morbidity and mortality. The coagulation system is balanced t o provide rapid activation to stop bleeding and appropriate inhibition to p revent unwanted clot extension. It is regulated by fibrinolysis and by thre e major anticoagulant pathways: the protein C, antithrombin, and tissue fac tor pathway inhibitor systems. Acquired or inherited abnormalities of coagu lation proteins or hemostatic regulatory mechanisms, particularly when comb ined with dehydration or the presence of indwelling catheters, may pose a h igh risk for thrombosis. Thrombosis in a child warrants investigation of po tential underlying prothrombotic conditions. These include acquired antipho spholipid antibodies or the lupus anticoagulant as well as abnormalities of the inherited anticoagulant factors including protein C, protein S, antith rombin, and Factor V Leiden. Other abnormalities may result in heightened l evels of otherwise normal coagulation proteins such as hyperprothrombinemia due to the prothrombin 20210 mutation. A large survey of children with thr ombosis indicated that Factor V Leiden, protein C deficiency, and increased lipoprotein(a) were found most commonly. The most severe predisposition oc curs with homozygous protein S or protein C deficiency with resultant purpu ra fulminans in the newborn. The risk of thrombosis in children with hetero zygous deficiencies of anticoagulant proteins is not well defined, although it is clear that combined heterozygotes or a combination of an inherited a nd an acquired defect heightens the risk for thrombosis. Treatment of throm bosis primarily involves a rapidly acting anticoagulant such as heparin or low-molecular-weight heparin to prevent extension, and long-term anticoagul ation with warfarin may be instituted to prevent recurrence. Fibrinolytic t herapy is infrequently used because of the risk of serious bleeding complic ations and is reserved for selected cases of arterial thrombosis to initiat e rapid reperfusion of ischemic tissue or used in those patients with a lar ge venous thrombosis and pulmonary emboli causing hemodynamic compromise, ( C) 2000 Academic Press.