Hemolysis may lead to activation of coagulation via induction of procoagulant tissue factor on monocytes and endothelial cells, subsequently activating coagulation. Abnormal RBCs, activated platelets, and microparticles (small cell-derived membrane vesicles) may provide membrane surfaces containing exposed anionic phospholipids; these serve as sites for attachment of factors Va-Xa and VIIIa-IXa, which promote venous stasis and coagulation and directly cause vascular occlusion. Some microparticles may also contain procoagulant tissue factor, further fueling coagulation; platelet activation contributes to this process as well. In addition, therapeutic measures (eg, splenectomy), glucocorticoids, cyclosporine, and IV catheters may contribute to coagulation with immune-mediated hemolytic anemia (IMHA).
Thromboembolic disease often affects dogs with IMHA. In humans, such drugs as heparin are used to inhibit factor Xa to prevent venous thrombosis (eg, pulmonary thromboembolism [PTE]). Platelet inhibitors (eg, aspirin, clopidogrel) are used to prevent arterial thrombosis. Arterial thrombosis is mediated by platelet activation in areas of high blood flow, whereas coagulation may contribute to the risk for venous thrombosis in the lower flow, fibrin-rich venous environment. In dogs, PTE is a common sequela of IMHA, and thrombosis occurs in veins and arteries. Validated therapeutic endpoints and monitoring standards are needed for evidence-based recommendations for thromboprophylaxis in canine IMHA. Future areas of promise include the development of direct inhibitors of factor Xa.
IMHA continues to frustrate, as many patients succumb to thrombosis, and commonly used anticoagulants (eg, heparin, aspirin, clopidogrel [alone or in combination]), have not consistently affected canine IMHA outcome; standard doses of heparin do not reliably reach therapeutic blood concentrations in dogs. This study emphasized the importance of evidence-based medicine when examining standards of care; common treatments may not always be supported by clinical-based studies.—Elke Rudloff, DVM, DACVECC
Prothrombotic mechanisms and anticoagulant therapy in dogs with immune-mediated hemolytic anemia. Kidd L, Mackman N. JVECC 23:3-13, 2013.
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