Prothrombotic mechanisms and anticoagulant therapy in dogs with immune-mediated hemolytic anemia

Abstract

Objective: To review the pathophysiology of thrombosis in hemolytic disease, and the efficacy of thromboprophylaxis in dogs with immune-mediated hemolytic anemia (IMHA).

Data sources: Computerized searches of Pubmed, INDEX VETERINARIUS, and the journal database of the Veterinary Information Network, and a manual search of bibliographies of published manuscripts.

Human data synthesis: Experimental data suggest that hemolysis leads to the induction of the potent procoagulant tissue factor on monocytes and endothelial cells and subsequent activation of coagulation. In addition, damaged red cells, activated platelets, and small cell-derived membrane vesicles called microparticles may contribute to coagulation by providing membrane surfaces containing exposed anionic phospholipids that serve as docking sites for prothrombinase (factor Va-factor Xa) and tenase (factor VIIIa-factor IXa) complexes of the coagulation cascade. Some microparticles also contain tissue factor, further fueling coagulation. Thromboprophylaxis for hemolytic disease in people primarily targets the coagulation cascade rather than platelets, as most thromboemboli are of venous rather than arterial origin. The use of unfractionated heparin is closely monitored to ensure therapeutic levels are reached.

Veterinary data synthesis: Thromboembolic disease is a major factor affecting survival in dogs with IMHA. It is likely that hemolysis contributes to the prothrombotic state. Thrombosis occurs in both veins and arteries, with pulmonary thromboembolism (a venous thrombus) occurring very commonly. Evidence suggests that tissue factor mediates the development of the prothrombotic state. Heparin, and the anti-platelet agents aspirin, and clopidogrel have been used for thromboprophylaxis in dogs with IMHA. However, a lack of validated therapeutic endpoints and controlled studies make it difficult to determine if survival is affected or if 1 drug is more effective than another.

Conclusions: Prospective clinical trials comparing individually adjusted heparin or other anti-coagulant drugs to anti-platelet drugs are needed to make evidence-based recommendations for thromboprophylaxis in dogs with IMHA.