What is the treatment for protein S deficiency?

From the Guidelines

Treatment for protein S deficiency primarily involves anticoagulation therapy to prevent blood clots, with low molecular weight heparin being preferred in pregnant women due to the teratogenicity of warfarin. For patients who have already experienced a clot (thrombosis), warfarin (Coumadin) is typically prescribed with a target INR of 2.0-3.0, often preceded by a 5-7 day course of heparin or low molecular weight heparin (such as enoxaparin 1mg/kg twice daily) to prevent warfarin-induced skin necrosis 1.

Key Considerations

• The risk of recurrent thromboembolism when anticoagulant therapy is discontinued depends on whether thrombosis is unprovoked (idiopathic) or is secondary to a reversible cause; a longer course of therapy is warranted when thrombosis is idiopathic or associated with a continuing risk factor 1.
• For pregnant women with protein S deficiency, the American Society of Hematology suggests postpartum clinical surveillance if there is no family history and postpartum prophylaxis with prophylactic- or intermediate-dose LMWH for 6 weeks if there is a family history of VTE rather than routine care 1.
• Direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, or dabigatran may be alternatives, though evidence specifically for protein S deficiency is limited.
• Prophylactic anticoagulation may be considered during high-risk situations like surgery, prolonged immobility, or pregnancy for those without previous clots but with protein S deficiency.

Management Approach

• Antepartum management: For pregnant women with protein S deficiency, antepartum clinical surveillance is suggested, regardless of family history of VTE 1.
• Postpartum management: Postpartum prophylaxis with prophylactic- or intermediate-dose LMWH for 6 weeks is suggested if there is a family history of VTE 1.
• Long-term management: Warfarin is usually continued indefinitely, especially for those with recurrent clots, with a target INR of 2.0-3.0 1.

From the Research

Treatment Options for Protein S Deficiency

• The treatment for protein S deficiency typically involves anticoagulant therapy to prevent venous thromboembolism (VTE) and other thrombotic complications 2, 3, 4.
• Oral anticoagulation with vitamin K antagonists, such as warfarin, is commonly used, but may not be effective in all cases, particularly in patients with severe protein S deficiency 2, 3.
• Direct oral anticoagulants (DOACs), such as rivaroxaban, apixaban, and edoxaban, may be considered as alternative treatment options for patients with protein S deficiency, especially those who experience recurrent VTE or have contraindications to vitamin K antagonists 2, 4.
• The choice of anticoagulant therapy should be individualized based on the patient's specific needs and risk factors, as well as the severity of their protein S deficiency 2, 3, 4.

Special Considerations

• Patients with protein S deficiency may require lifelong anticoagulation therapy to prevent recurrent thromboembolic events 3, 5.
• Pregnant women with protein S deficiency may be at increased risk of VTE and may require anticoagulant therapy during pregnancy 6.
• Hypoxia, such as that caused by COVID-19, may decrease plasma protein S levels and increase the risk of thrombosis in patients with protein S deficiency 6.

Diagnostic Considerations

• The diagnosis of protein S deficiency can be challenging and may involve measurement of protein S levels, as well as molecular analysis of the PROS1 gene 5.
• Patients with low protein S levels and a known mutation within the PROS1 gene may be at increased risk of recurrent thromboembolic events and require lifelong oral anticoagulation 5.