Hypercoagulable States in Cardiovascular Disease

Abstract

Certain individuals may have an abnormal propensity to develop venous or arterial thrombosis and either experience thromboembolic events relatively early in life or suffer recurring events.1 This well-described clinical phenomenon, paralleled by familial clustering of thrombotic phenotypes, has led to a comprehensive search for inherited and acquired forms of hypercoagulability as part of the condition known as thrombophilia. Although clearly defined associations have been described for hypercoagulable states and thrombosis within the venous system, the establishment of causative or contributing roles for these same thrombophilic conditions and the occurrence of arterial thrombosis has been considerably more elusive.2 The World Health Organization/International Society of Thrombosis and Hemostasis in 1995 defined thrombophilia as an unusual tendency toward thrombosis.1 Frequently cited features traditionally include (1) early age of onset; (2) recurrent episodes; (3) strong family history; (4) unusual, migratory, or widespread locations; and (5) severity out of proportion to any recognized stimulus. Here, we provide an updated review of hypercoagulable states in cardiovascular disease in 3 sections: (1) inherited hypercoagulable states; (2) acquired hypercoagulable states; and (3) diagnosis and management. Establishment of the role of pathways that lead to heritable hypercoagulable phenotypes in multifactorial disorders such as cardiovascular diseases is complicated by the inability to adequately discern the necessity and sufficiency of proposed mediators of hypercoagulability (Figure 1).2 Hyperhomocysteinemia is a good example of the challenges faced.3 Elevated homocysteine levels exert numerous vasotoxic effects on the endothelium, which lead to endothelial cell dysfunction, platelet activation, and thrombus formation and an increased risk of thrombotic events.4 A C677T point mutation within the coding region of the methylenetetrahydrofolate reductase ( MTHFR ) gene is the most common genetic cause of hyperhomocysteinemia, with homozygotes for the 677T allele exhibiting mild to moderate elevations of serum homocysteine and a varying propensity for …