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Cancer is associated with an increased risk of both venous and arterial thrombosis In some cases, low-grade DIC appears to be responsible In unusual cases, a unique cancer procoagulant stimulates the clotting system Myeloproliferative disorders such as polycythemia vera, essential thrombocytosis, and paroxysmal nocturnal hemoglobinuria are associated with a high incidence of thrombosis, caused by qualitative platelet abnormalities Venous thrombosis may occur in unusual locations such as the mesenteric, hepatic, or splenic venous beds Arterial thrombosis occurs as well and may be manifested as large vessel occlusion (stroke, myocardial infarction) or as microvascular events with burning in the hands and feet A number of congenital biochemical defects have also been associated with hypercoagulability (Table 13 24) A family history is usually present The thromboses are almost always venous and may occur in the large veins of the abdomen Thromboses often occur during early adulthood rather than in childhood and are often precipitated by factors such as trauma or pregnancy The most common of these disorders is an abnormal factor V (factor V Leiden), which is resistant to degradation by activated protein C Dysfibrinogenemia is diagnosed by a prolonged reptilase time The syndrome of warfarin-induced skin necrosis may occur in patients with undiagnosed protein C deficiency Protein C is vitamin K dependent and has a shorter half-life than the coagulation proteins Warfarin, by creating a vitamin K-dependent state, will transiently deplete protein C before it leads to anticoagulation During the period of hypercoagulability due to unopposed protein C depletion, thrombosis of skin vessels may lead to infarction and necrosis The syndrome can be prevented by the use of heparin for 5 7 days until warfarin induces anticoagulation

Bockenstedt PL Management of hereditary hypercoagulable disorders Hematology Am Soc Hematol Educ Program 2006: 444 9 [PMID: 17124097] Prandoni P How I treat venous thromboembolism in patients with cancer Blood 2005 Dec 15;106(13):4027 33 [PMID: 16076870] Rieder MJ et al Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose N Engl J Med 2005 Jun 2;352(22): 2285 93 [PMID: 15930419]

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The lupus anticoagulant is an IgM or IgG immunoglobulin that produces a prolonged PTT by binding to the phospholipid used in the in vitro PTT assay As such, it is a laboratory artifact and does not cause a clinical bleeding disorder The lupus anticoagulant is seen in 5 10% of patients with systemic lupus erythematosus More commonly, it is seen without an underlying disorder or in patients taking phenothiazines There is no bleeding defect unless a second disorder such as thrombocytopenia, hypoprothrombinemia, or a prolonged bleeding time is present In fact, the lupus anticoagulant has been associated with an increased risk of thrombosis and of recurrent spontaneous abortions The PTT is prolonged and fails to correct when the patient s plasma is mixed in a 1:1 dilution with normal plasma The PT is either normal or slightly prolonged The fibrinogen level and thrombin time are normal The Russell viper venom (RVV) time is a more sensitive assay and is specifically designed to demonstrate the presence of a lupus anticoagulant An antiphospholipid, the lupus anticoagulant will cause a false-positive VDRL test for syphilis A related autoantibody, anticardiolipin, can be detected by separate assays Lupus anticoagulant should be suspected in cases of a markedly prolonged PTT without clinical bleeding (other causes are factor XII or contact factor deficiency) The plasma mixing test will demonstrate the presence of an inhibitor by the failure of normal plasma to correct the PTT When acquired factor VIII inhibitors are being considered, a factor VIII:C level may be measured; this will be normal in patients with lupus anticoagulant No specific treatment is necessary Prednisone will usually rapidly eliminate the lupus anticoagulant, and it has been suggested that prednisone therapy reduces spontaneous abortions in this syndrome It is not clear whether prednisone has any effect on the thrombotic tendency associated with lupus anticoagulant Patients with thromboses should be treated with anticoagulation in standard doses Because of the artificially prolonged PTT, heparin therapy is difficult to monitor properly, and low-molecular-weight heparin may be preferred The dose of warfarin administered may also be inadequate if the baseline PT is prolonged.

Brouwer JL et al The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus Blood 2004 Jul 1;104(1):143 8 [PMID: 15026314]

If a patient is recognized to be at increased risk of thrombosis, effective prophylactic therapy is usually available (Table 9 19) Low-molecular-weight heparin has largely replaced unfractionated heparin because of improved efficacy and ease of monitoring Warfarin has long been the standard outpatient therapy for prevention of thrombosis, except in cancer-associated thrombosis when low-grade DIC is a pathogenic mechanism The investigational agent ximelagatran, a direct thrombin inhibitor, may come to replace current anticoagulants based on its ease of use (oral administration, fixed dose, no monitoring) as well as its efficacy and safety (see 9) In patients with myeloproliferative disease who have had symptoms of thrombosis, antiplatelet therapy may be helpful However, such therapy should not be used indiscriminately, because these patients are also at increased risk of bleeding For patients with erythromelalgia (painful redness and burning of the hands), aspirin, 325 mg daily, is effective In congenital biochemical defects such as deficiency of antithrombin III or the vitamin K-dependent proteins C and S, warfarin is effective and is given indefinitely Family members are screened for the presence of the defect

Patients scheduled for elective surgery may donate blood for autologous transfusion These units may be stored for up to 35 days

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Proven A et al Clinical importance of positive test results for lupus anticoagulant and anticardiolipin antibodies Mayo Clin Proc 2004 Apr;79(4):467 75 [PMID: 15065611]

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