Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ INTRODUCTION ++ Risk factors for thromboembolism may be genetic and acquired (Table 89–1). Hereditary thrombophilia is a genetically determined increased risk of thrombosis. Up to 50 percent of patients presenting with a first deep venous thrombosis will have an abnormal laboratory test suggesting a thrombophilic defect, and patients with recurrent thromboses or with a strong family history are even more likely to have laboratory evidence of a thrombophilic state (Table 89–2). Up to 16 percent of patients with thrombophilia have inherited more than one abnormality. These inherited defects also interact frequently with acquired risk factors, such as inactivity, trauma, malignancy, or oral contraceptive use, to lead to clinical thrombosis. ++Table Graphic Jump LocationTABLE 89–1THROMBOPHILIAS AND PREDISPOSING RISK FACTORS FOR VENOUS THROMBOEMBOLISMView Table||Download (.pdf) TABLE 89–1 THROMBOPHILIAS AND PREDISPOSING RISK FACTORS FOR VENOUS THROMBOEMBOLISM Thrombophilias Acquired Predisposing Risk Factors for Venous Thrombosis Common Increasing age Factor V Leiden Surgery or trauma Prothrombin G20210A Prolonged immobilization Increased factor VIII level* Obesity Homozygous C677T polymorphism in methylenetetrahydrofolate reductase† Smoking Malignant neoplasms Rare Myeloproliferative diseases Protein C deficiency Superficial vein thrombosis Protein S deficiency Previous venous thrombosis/Varicose veins Antithrombin deficiency Pregnancy and puerperium Very rare Use of female hormones Dysfibrinogenemia Antiphospholipid antibodies/Lupus anticoagulants Homozygous homocystinuria Hyperhomocysteinemia Activated protein C resistance unrelated to factor V Leiden *Heritability is inferred. No gene alteration has been discerned.†A questionable thrombophilia that can be associated with hyperhomocysteinemia in patients with deficiencies of folic acid or vitamin B12.Source: William Hematology, 8th ed, Chap. 131, Table 131–1, p. 2122. ++Table Graphic Jump LocationTABLE 89–2FREQUENCY OF THROMBOPHILIAS IN HEALTHY SUBJECTS AND UNSELECTED AND SELECTED PATIENTS WITH VENOUS THROMBOSISView Table||Download (.pdf) TABLE 89–2 FREQUENCY OF THROMBOPHILIAS IN HEALTHY SUBJECTS AND UNSELECTED AND SELECTED PATIENTS WITH VENOUS THROMBOSIS Healthy Subjects Unselected Patients Selected Patients Thrombophilia No. Percent Affected No. Percent Affected No. Percent Affected Factor V Leiden 16,150* 4.8 1142 18.8 162 40 2192† 0.05 Prothrombin G20210A 11,932* 2.7 2884 7.1 551 16 1811† 0.06 Protein C deficiency 15,070 0.2–0.4 2008 3.7 767 4.8 Protein S deficiency 3788 0.16–0.21 2008 2.3 649 4.3 Antithrombin deficiency 9669 0.02 2008 1.9 649 4.3 *Whites.†Africans and Orientals.Adapted with permission from Seligsohn U, Lubetsky A: Genetic susceptibility to venous thrombosis. N Engl J Med Apr 19;344(16):1222-1231, 2001.Source: William Hematology, 8th ed, Chap.131, Table 131–2, p. 2123. +++ HEREDITARY RESISTANCE TO ACTIVATED PROTEIN C (APC) +++ Etiology and Pathogenesis ++ APC resistance is an abnormally reduced anticoagulant response of a patient's plasma that, in more than 90 percent of cases, is caused by a genetic abnormality of factor V (substitution of glutamine for arginine at position 506), which significantly retards inactivation of factor Va by APC. The abnormal factor V is generally referred to as "factor V Leiden." +... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Download the Access App: iOS | Android Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.