Chapter 111. Venous Thrombosis (Part 2) Figure 111-1 Models of thrombosis risk. In each panel, the figure shows the thrombosis (black) potential of each risk f actor present during an individual's life and the resultant thrombosis potential (red). (From FR Rosendaal: Venous thrombosis: A multicausal disease. Lancet 353:1167, 1999; with permission.) Several acquired risk factors are very strong, causing thrombosis in several percent of those afflicted, which implies a relative risk of ≥50. These are orthopedic, neurosurgical, and major abdominal interventions; major trauma with multiple fractures; central venous catheters; and metastasized cancer, particularly adenocarcinomas. Moderate risk factors are antiphospholipid antibody syndrome, puerperium, prolonged bedrest, and nonmetastasized cancers; pregnancy, oral contraceptive use, hormone replacement therapy, obesity, and long-distance travel are mild risk factors, with a two- to fivefold increased risk. Homozygous protein C or protein S deficiency leads to potentially fatal purpura fulminans directly after birth, while homozygous antithrombin deficiency is not compatible with life. These are exceedingly rare, except in communities with a high frequency of consanguinity. Heterozygous antithrombin deficiency and homozygous factor V Leiden are the strongest genetic risk factors, increasing the risk of thrombosis 20- to 50-fold. Heterozygous protein C and protein S deficiencies are moderate contributors to risk, with a relative risk of 10. Other genetic factors that are associated with venous thrombosis are either mild and increase the risk two- to fivefold (as is the case for factor V Leiden, prothrombin 20210A, and non-O blood groups) or have negligible effects on risk that are only of academic interest (MTHFR 677T, factor V HR2, FXIII val34leu, PAI-1 4G/5G). Mildly increased risks are also present for abnormalities in the coagulation system of which the origin is unclear, such as elevated levels of procoagulant factors (fibrinogen, II, von Willebrand factor, VIII, IX, X, and XI) and antifibrinolytic factors (TAFI), and low levels of anticoagulant factors (TFPI) (Table 111-1). Prognosis Patients who have had a venous thrombosis have a high risk (3–10% per year) of another. Up to half of the recurrences after a first thrombosis in one leg occur in the other, indicating that systemic changes rather than residual local damage are associated with rethrombosis. Nevertheless, few of the established risk factors associated with a hypercoagulable state (such as factor V Leiden, prothrombin 20210A, and elevated levels of clotting factors VIII, IX, and XI) are associated with recurrence risk. Even the strongest prothrombotic abnormalities— antithrombin, protein C, and protein S deficiencies—increase the risk of recurrent thrombosis by 50% at most. The only two clear risk factors for recurrence are male sex (increasing risk three- to fourfold) and the absence of a clear precipitating factor at the first event (doubling recurrence risk); in other words, a first thrombosis following surgery or plaster cast is unlikely to recur. Acquired risk factors, such as surgery, immobilization, and cancer, increase the risk of recurrent thrombosis—as they increase the risk of a first event. Prevention The presence of prothrombotic defects or a history of thrombosis does not usually lead to different preventative strategies, with the exception of the postpartum period, where anticoagulation seems indicated, particularly for antithrombin deficiency. Similarly, the decision for long-term or lifelong anticoagulation, i.e., beyond the period of increased risk, depends on the clinical presentation rather than on the presence of prothrombotic abnormalities. Before prescribing long-term anticoagulation, clinicians should be aware of the cumulative annual risk of major hemorrhage of 1–2%. Patients with a history of thrombosis should not use estrogen-containing drugs, i.e., hormone replacement therapy is contraindicated and for contraception, mechanical methods are preferred. . Chapter 111. Venous Thrombosis (Part 2) Figure 111- 1 Models of thrombosis risk. In each panel, the figure shows the thrombosis (black) potential of each risk f actor. f actor present during an individual's life and the resultant thrombosis potential (red). (From FR Rosendaal: Venous thrombosis: A multicausal disease. Lancet 353:1167, 1999; with permission.). factors (TFPI) (Table 111- 1). Prognosis Patients who have had a venous thrombosis have a high risk (3–10% per year) of another. Up to half of the recurrences after a first thrombosis in one leg