Familial Thrombophilia

Familial thrombophilia is an encompassing term used to describe multiple inherited disorders that increase the risk of developing venous thromboembolism (VTE). There are several types of familial thrombophilia, each caused by unique genetic mutations. The most common types are factor V Leiden and prothrombin gene mutation which together account for 50–60% of cases. The relative thrombosis risk for patients who harbor heterogeneous or homozygous Factor V Leiden mutations is 3–7 times or 50–100 times than those without, respectively. Other types of familial thrombophilia include protein C deficiency, protein S deficiency, and antithrombin (AT) deficiency. The probability of developing thrombosis compared with those with no defect was 8.5 times higher for carriers of protein S deficiency, 8.1 for AT deficiency, 7.3 for protein C deficiency, and 2.2 for factor V Leiden. Despite some case reports indicating a possible link with an increased risk of arterial thrombosis, this has not been validated nor substantiated in larger studies. The book chapter will focus on the common familial thrombophilia and summarize the standard clinicopathologic features, underlying mechanisms, and prophylactic and treatment strategy. Rarely thrombophilia syndromes, such as hereditary hyperhomocysteinemia, elevated FVIII level, hereditary dysfibrinogenemia, Factor XII deficiency, and plasminogen activator inhibitor, can lead to thrombosis.