What is the significance of an elevated Dilute Russell's Viper Venom Time (DRVVT) screen with an intermediate Activated Protein C (APC) resistance due to Factor V Leiden mutation?

From the Guidelines

The combination of an elevated dilute Russell's viper venom time (dRVVT) screen with intermediate activated protein C (APC) resistance suggesting Factor V Leiden requires comprehensive thrombophilia evaluation and potential anticoagulation therapy, with a strong consideration for genetic testing to confirm Factor V Leiden mutation and additional testing for antiphospholipid antibodies. Given the potential for increased risk of recurrent venous thromboembolism, especially in patients with persistent risk factors or idiopathic venous thromboembolism, as noted in the American College of Medical Genetics consensus statement on factor V Leiden mutation testing 1, a thorough evaluation is crucial.

Key Considerations

• The presence of Factor V Leiden, even in heterozygotes, may influence patient management, particularly in cases of recurrent venous thromboembolism or in individuals with additional thrombophilic conditions like the prothrombin 20210A mutation 1.
• The decision for anticoagulation therapy should take into account the risk of major bleeding with chronic warfarin therapy, which may reach 8% per year, as well as the potential benefits of reducing venous thromboembolism recurrence 1.
• For patients with confirmed thrombophilia and a history of thrombosis, anticoagulation with direct oral anticoagulants (DOACs) like rivaroxaban or apixaban, or warfarin with a target INR of 2-3, is typically indicated, with the duration of therapy depending on the specific clinical scenario and risk factors.
• Counseling on modifiable risk factors such as smoking cessation, avoiding estrogen-containing contraceptives, and maintaining a healthy weight is also essential for managing thrombosis risk.

Testing and Management

• Genetic testing for Factor V Leiden mutation, along with testing for antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-beta2 glycoprotein I, should be considered to guide management decisions.
• The identification of Factor V Leiden status can also inform the management of asymptomatic family members, particularly in guiding antithrombotic prophylaxis during periods of risk and in making informed decisions about the use of oral contraceptives.
• The association of Factor V Leiden with increased risk of severe preeclampsia, placental abruption, unexplained intrauterine fetal growth retardation, and stillbirth highlights the importance of considering this condition in the management of pregnant women with a history of thrombosis or recurrent pregnancy loss 1.

From the Research

Elevated Drvvt Screen with Intermediate APC Resistant Factor V Leiden

• An elevated Drvvt screen with intermediate APC resistant factor V Leiden indicates a potential hypercoagulable state, which may increase the risk of venous thrombosis 2.
• The Drvvt test is used to diagnose factor V Leiden mutation, and an intermediate result may suggest the presence of this mutation or other acquired causes of thrombophilia, such as the use of direct oral anticoagulants (DOACs) 3.
• Factor V Leiden mutation is a common cause of inherited thrombophilia, and patients with this mutation are at increased risk of recurrent venous thromboembolism (VTE) 4, 5.
• The use of DOACs in patients with inherited thrombophilia, including factor V Leiden mutation, has been studied, and results suggest that these agents may be effective in preventing VTE 6.
• However, the effect of DOACs on Drvvt assays can be variable, and some reagents may be more affected than others, leading to false-positive results 3.
• The management of patients with elevated Drvvt screen and intermediate APC resistant factor V Leiden should be individualized, taking into account the patient's risk factors, medical history, and the results of other diagnostic tests 4, 2, 5, 6.

Diagnostic Considerations

• The sensitivity of Drvvt-based APCR assays for detecting factor V Leiden mutation is high, but may be affected by the use of DOACs or other acquired causes of thrombophilia 2, 3.
• The use of modified Drvvt assays with predilution in factor V-deficient plasma may improve the sensitivity and specificity of the test for detecting factor V Leiden mutation 2.
• Other diagnostic tests, such as PCR, may be necessary to confirm the presence of factor V Leiden mutation or other inherited thrombophilic conditions 2, 5.

Treatment Considerations

• Patients with elevated Drvvt screen and intermediate APC resistant factor V Leiden may require anticoagulant therapy to prevent recurrent VTE 4, 6.
• The choice of anticoagulant agent should be individualized, taking into account the patient's risk factors, medical history, and the results of other diagnostic tests 4, 6.
• Long-term, low-dose warfarin may be effective in preventing recurrent VTE in patients with factor V Leiden mutation, but the use of DOACs may also be considered 4, 6.