What is the significance of a positive Factor VIII activity in a patient with a history of Deep Vein Thrombosis (DVT)?

From the Guidelines

Patients with elevated Factor VIII activity and a history of deep vein thrombosis (DVT) should be considered for long-term anticoagulation therapy. The decision to extend anticoagulation is guided by the risk of recurrence, which is significantly higher in patients with unprovoked DVT, as suggested by the study published in the Journal of Thrombosis and Haemostasis 1. Given that the annual risk of recurrence exceeds 5% in such cases, and considering the risk of VKA-related bleeding, long-term anticoagulation is often recommended.

Key considerations in managing these patients include:

• The initial treatment duration, which should be at least 3-6 months, as per general guidelines for DVT management.
• The choice of anticoagulant, which could be direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, or edoxaban, or warfarin with a target INR of 2-3, depending on patient-specific factors and bleeding risk.
• Regular follow-up to monitor for signs of recurrent thrombosis, assess bleeding risk, and ensure medication adherence.
• Lifestyle modifications to reduce the risk of further thrombotic events, including maintaining a healthy weight, regular physical activity, and avoiding prolonged periods of immobility.
• The use of compression stockings to prevent post-thrombotic syndrome, a potential complication of DVT.

It's crucial to weigh the benefits of extended anticoagulation against the risks of anticoagulant-related bleeding in each patient, considering factors such as the presence of provoking factors for the initial DVT, the location of the DVT (proximal vs. distal), and the patient's overall health status, as discussed in the study 1. Elevated Factor VIII levels are a significant and persistent risk factor for venous thromboembolism recurrence, supporting the consideration for long-term anticoagulant therapy in these patients.

From the FDA Drug Label

For patients with a first episode of DVT or PE who have documented deficiency of antithrombin, deficiency of Protein C or Protein S, or the Factor V Leiden or prothrombin 20210 gene mutation, homocystinemia, or high Factor VIII levels (>90th percentile of normal), treatment for 6 to 12 months is recommended and indefinite therapy is suggested for idiopathic thrombosis

• Factor VIII activity positive with a history of DVT suggests that the patient may have high Factor VIII levels, which is a thrombophilic condition.
• The recommended treatment duration for patients with DVT and high Factor VIII levels is 6 to 12 months, with indefinite therapy suggested for idiopathic thrombosis 2.

From the Research

Factor VIII Activity and Deep Vein Thrombosis (DVT)

• Factor VIII activity is a significant risk factor for venous thromboembolism, including DVT 3.
• Elevated plasma factor VIII levels (>150 IU/dL) increase the risk of venous thrombosis, with levels above 200 IU/dL associated with a higher risk of DVT recurrence 4.
• Patients with a history of DVT and elevated factor VIII levels may require extended anticoagulation therapy to prevent recurrent VTE 3, 5.

Anticoagulation Therapy for DVT

• Apixaban, an oral factor Xa inhibitor, is a promising alternative to traditional anticoagulation therapy for VTE, offering a fixed-dose regimen and reduced risk of major bleeding 6.
• Rivaroxaban, another oral direct factor Xa inhibitor, is approved for the initial treatment of DVT and pulmonary embolism, as well as the prevention of recurrent VTE 5.
• Assays such as the diluted prothrombin time (dPT) and diluted Fiix-PT (dFiix-PT) can be used to measure the anticoagulant effects of various drugs, including warfarin, dabigatran, rivaroxaban, apixaban, and heparins 7.

Clinical Implications

• Elevated factor VIII levels should be considered a risk factor for DVT recurrence, and patients with a history of DVT and elevated factor VIII levels may require closer monitoring and extended anticoagulation therapy 3, 4.
• The choice of anticoagulation therapy should be individualized based on patient-specific factors, including the presence of elevated factor VIII levels and the risk of recurrent VTE 6, 5.