How is elevated Factor VIII (F8) activity managed to prevent thrombotic events?

From the Guidelines

Elevated Factor VIII activity is managed by reducing thrombotic risk through anticoagulation therapy, with long-term anticoagulation with warfarin or direct oral anticoagulants (DOACs) recommended for patients with persistently high Factor VIII levels and a history of thrombosis. The goal of treatment is to prevent thrombotic events, which are a major concern in patients with elevated Factor VIII activity. According to the study by 1, substantially elevated plasma FVIII levels are often observed in patients following inhibitor eradication, and constitute an independent thrombotic risk factor.

Treatment Options

• Long-term anticoagulation with warfarin (target INR 2-3) or DOACs like rivaroxaban (20 mg daily), apixaban (5 mg twice daily), or dabigatran (150 mg twice daily) is recommended for patients with persistently high Factor VIII levels and a history of thrombosis.
• For acute thrombotic events, initial treatment with low molecular weight heparin (LMWH) such as enoxaparin (1 mg/kg twice daily) followed by transition to oral anticoagulants is standard practice.
• The duration of therapy depends on the patient's risk factors, with indefinite anticoagulation often considered for unprovoked thrombosis with persistently elevated Factor VIII levels (>150%).

Risk Factor Modification

• Risk factor modification is also essential, including weight management, smoking cessation, and avoiding estrogen-containing contraceptives.
• Regular monitoring of Factor VIII levels every 3-6 months helps guide treatment decisions.
• Anticoagulation is effective because elevated Factor VIII increases thrombin generation and promotes clot formation by accelerating the conversion of Factor X to its active form, thereby enhancing the coagulation cascade, as noted in the study by 1.

Thromboprophylaxis

• Thromboprophylaxis according to American College of Chest Physicians (ACCP) guidelines is recommended following inhibitor eradication and sustained response in former AHA patients, especially those with very elevated FVIII:C levels, as suggested by 1.

From the Research

Elevated Factor VIII Activity Management

Elevated Factor VIII (F8) activity is a risk factor for thrombotic events, and managing it is crucial to prevent these events. The following points highlight the management of elevated F8 activity:

• Elevated F8 levels have been associated with an increased risk of death in patients with venous thrombosis and in individuals from the general population 2.
• High F8 levels are also an independent risk factor for venous thromboembolism (VTE) 3.
• The management of elevated F8 activity may involve the use of anticoagulants, such as rivaroxaban, which is a direct factor Xa inhibitor 4.
• Rivaroxaban has been shown to be effective in preventing VTE in patients undergoing elective hip or knee replacement surgery, treating deep-vein thrombosis, and preventing recurrent VTE 4.
• Other anticoagulants, such as apixaban and dabigatran, may also be used to manage elevated F8 activity 5.
• The choice of anticoagulant and the duration of treatment should be individualized based on the patient's risk factors and medical history.
• In some cases, prolonged anticoagulation therapy may be necessary to prevent recurrent VTE in patients with elevated F8 levels 3.

Risk Factors and Screening

The following points highlight the risk factors and screening for elevated F8 activity:

• Elevated F8 levels can be caused by a combination of genetic and acquired variables 6.
• Physicians should screen for elevated F8 levels in patients with a history of VTE or other thrombotic events 6.
• Screening for elevated F8 levels may involve measuring F8 activity using one-stage clotting or chromogenic assays 3.
• Patients with elevated F8 levels should be monitored regularly for signs of thrombotic events and adjusted anticoagulation therapy as needed 2, 3.