What is the treatment for Protein S deficiency?

From the Guidelines

Treatment for protein S deficiency typically involves anticoagulation therapy to prevent blood clots, with antepartum clinical surveillance and postpartum prophylaxis with prophylactic- or intermediate-dose low-molecular-weight heparin (LMWH) for 6 weeks if there is a family history of venous thromboembolism (VTE) 1. For acute thrombotic events, initial treatment includes heparin (either unfractionated or low-molecular-weight heparin like enoxaparin 1mg/kg twice daily) followed by long-term oral anticoagulation with warfarin (target INR 2.0-3.0) 1. Some key points to consider in the management of protein S deficiency include:

• The use of direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, or dabigatran may be considered in some cases, though warfarin remains the standard for hereditary thrombophilias 1.
• The duration of anticoagulation depends on whether the deficiency is inherited or acquired and if there are additional risk factors 1.
• For patients with recurrent thrombosis, lifelong anticoagulation is usually recommended 1.
• During pregnancy, when warfarin is contraindicated, low-molecular-weight heparin is the preferred treatment 1.
• Regular monitoring of anticoagulation levels is essential, particularly with warfarin therapy 1.
• Protein S concentrate replacement is not typically used as standard therapy 1.
• Patients should also be advised to minimize additional thrombotic risk factors such as smoking cessation, maintaining healthy weight, and avoiding prolonged immobility 1. The American Society of Hematology 2018 guidelines for management of venous thromboembolism suggest antepartum clinical surveillance for pregnant women with protein S deficiency, regardless of family history of VTE, and postpartum prophylaxis with prophylactic- or intermediate-dose LMWH for 6 weeks if there is a family history of VTE 1.

From the FDA Drug Label

Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. 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

The treatment for Protein S deficiency involves anticoagulation therapy.

• Warfarin is recommended for patients with a first episode of DVT or PE who have documented deficiency of Protein S.
• The recommended treatment duration is 6 to 12 months, and indefinite therapy is suggested for idiopathic thrombosis.
• The dose of warfarin should be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations 2.

From the Research

Treatment Options for Protein S Deficiency

• Anticoagulant therapy is a common treatment approach for protein S deficiency, with the goal of preventing thromboembolic events 3, 4, 5.
• Vitamin K antagonists, such as warfarin, are often used for long-term anticoagulant therapy, but may not be effective in patients with severe protein S deficiency and may even cause skin necrosis 3, 5.
• Direct oral anticoagulants (DOACs), such as rivaroxaban, may be a valid alternative to vitamin K antagonists in patients with severe protein S deficiency and warfarin-induced skin necrosis 3, 4.
• Antiplatelet therapy may be considered as a treatment option for patients with protein S deficiency who experience arterial thrombotic events 6, 7.

Specific Treatment Considerations

• Patients with severe protein S deficiency may require higher international normalized ratio (INR) targets to prevent recurrent thromboembolic events 3.
• The use of DOACs, such as rivaroxaban, may be safe and effective in patients with protein S deficiency, including those with recurrent ischemic stroke 4.
• Early implementation of long-term preventive therapy is crucial in patients with protein S deficiency to prevent recurrent thrombosis 5.