From the Guidelines
A hypercoagulability panel should not be routinely ordered for primary prevention of ischemic stroke, as the association between hypercoagulable states and cerebrovascular arterial thrombosis has not been clearly proven 1. When considering a hypercoagulability panel, it is essential to evaluate the patient's overall risk profile and medical history. The panel typically includes tests for:
- Factor V Leiden mutation
- Prothrombin gene mutation (G20210A)
- Protein C and S deficiencies
- Antithrombin III deficiency
- Lupus anticoagulant
- Anticardiolipin antibodies
- Homocysteine levels However, the presence of antiphospholipid antibodies (aPL) has been shown to be associated with ischemic stroke, but the definition of a significant positive result on testing for aPL has not been uniformly delineated 1. The decision to order a hypercoagulability panel should be based on individual patient risk factors, such as unexplained venous thromboembolism (VTE), thrombosis at unusual sites, recurrent thrombosis, thrombosis at a young age (under 50), or a strong family history of thrombotic events. It is crucial to note that acute thrombosis and anticoagulants can affect test results, and the panel should be ordered at least 2-3 months after an acute thrombotic event and ideally when the patient is not on anticoagulation therapy 1. Positive findings may guide treatment decisions, including the duration of anticoagulation therapy, with some conditions requiring lifelong treatment, and genetic counseling may be appropriate for patients with hereditary thrombophilias 1.
From the Research
Hypercoagulable States
The hypercoagulable states that predispose patients to venous and arterial thrombosis include:
- Activated protein C resistance/factor V Leiden
- Prothrombin G20210A
- Deficiencies of protein C, protein S, or antithrombin
- Antiphospholipid antibodies 2
Protein C and Protein S Deficiency
Protein C and protein S are vitamin K-dependent coagulation factors that act as anticoagulants, and their deficiencies have been associated with venous thromboembolism (VTE) and arterial thrombosis 3, 4
- Protein C deficiency is found in 6% of families with inherited thrombophilia and 0.2-0.3% of healthy individuals
- Protein S deficiency is detected more commonly than protein C deficiency, with a prevalence of less than 0.5% in the general European population and 2% to 12% of selected groups of thrombophilic patients 4
Diagnosis and Risk Assessment
The diagnosis of protein C and protein S deficiencies is challenging due to preanalytical and analytical factors that may affect their levels 4
- Molecular analysis of the protein C and protein S genes (PROC and PROS1) involves direct gene sequencing and multiplex ligation-dependent probe amplification (MLPA) method
- Patients with low protein C and protein S levels and known mutations within PROC or PROS1 genes, combined with other genetic or environmental thrombosis factors, are at increased risk of recurrent thromboembolic events and require lifelong oral anticoagulation 4, 5
Inherited Thrombophilias
Inherited thrombophilias, including factor V Leiden and prothrombin gene mutation, are passed down in an autosomal dominant fashion 6
- Factor V Leiden is the most common inherited thrombophilia, followed by prothrombin gene mutation
- Patients harboring antiphospholipid antibodies have an increased risk for thrombosis 6