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Key Clinical Questions

  • image Which hospitalized patients are at risk for venous thromboembolism (VTE)?

  • image Who is at increased risk for complications from thromboprophylaxis?

  • image How do we make sure that thromboprophylaxis is prescribed to all patients who should get it?

The main question in most patient groups detailed below is whether they can expect a net benefit from pharmacological thromboprophylaxis, mainly low-molecular-weight heparins (LMWH). One has to balance the risk of venous thromboembolism (VTE) and the consequences of VTE with the risk of bleeding and other complications. Ideally, this balance is sought in every individual patient, also taking the values and preferences of that patient into consideration.

To facilitate this balancing process, institutions and national and international organizations have developed guidelines for the use of thromboprophylaxis. The use of these guidelines and local protocols has greatly improved patient outcomes, mainly by increasing the use of pharmacological thromboprophylaxis in patients at risk for VTE. We strongly advise the development and use of a local protocol.



Less than 1% of the general population has a congenital deficiency of one of the natural inhibitors of coagulation, antithrombin, protein C, and protein S. These deficiencies are associated with a high lifetime risk of VTE (60%-70% in a recent study) and with a high risk of recurrence after a first event (50% after 10 years). A limitation to these data is that they are derived from highly selected families, which might have led to an overestimation of risk. No population-based data are available.

Acquired deficiencies are seen with disseminated intravascular coagulation (DIC), extensive deep vein thrombosis (DVT), severe liver disease, infection, malignancy, adult respiratory distress syndrome (ARDS), the hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), and following L-asparaginase therapy. The result of consumption or decreased synthesis of both pro- and anticoagulant factors, they may predispose the individual to bleeding or to thrombosis. This is often difficult to judge. In the case of liver disease, a convincing case has been made that the resultant is a new hemostatic balance, with no clearly increased risk of bleeding or thrombosis.

Total and free protein S decrease steadily during pregnancy, with the lowest levels at term. They are also somewhat decreased in patients who take the combined oral contraceptive pill. Protein C levels are lower before puberty, which should be born in mind when testing children in affected families. Antithrombin levels are increased with cholestasis.

Patients with a known congenital deficiency, primarily of antithrombin, but to some extent also protein C and protein S, have a strong indication for pharmacological thromboprophylaxis in any situation that increases the risk of thrombosis, including lower-limb immobilization, pregnancy, and bed rest as a medical patient. Given the high risk of recurrence, long-term anticoagulation should be considered in these patients ...

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