From the Guidelines
Protein S deficiency should be managed with anticoagulation therapy, and the choice of anticoagulant and duration of treatment depend on the individual's risk factors and the presence of thrombotic events. The management of protein S deficiency involves anticoagulation therapy to prevent thrombotic events.
- The treatment typically involves medications like warfarin (Coumadin) at doses adjusted to maintain an INR (International Normalized Ratio) of 2.0-3.0, or direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, or dabigatran 1.
- For acute thrombotic events, initial treatment with heparin or low-molecular-weight heparin (like enoxaparin 1mg/kg twice daily) is recommended before transitioning to long-term anticoagulation 1.
- The duration of treatment depends on whether the deficiency is hereditary (often lifelong therapy) or acquired (treating the underlying cause) 1.
- Patients should avoid additional risk factors for clotting such as smoking, oral contraceptives containing estrogen, and prolonged immobility 1.
- Regular monitoring of anticoagulation levels is essential, particularly with warfarin 1. Protein S deficiency increases thrombosis risk because protein S normally works with activated protein C to inactivate clotting factors Va and VIIIa, and when deficient, this regulatory mechanism fails, leading to excessive clot formation, particularly in deep veins of the legs, lungs, and sometimes unusual sites like abdominal veins 1. In pregnant women with protein S deficiency, antepartum clinical surveillance is suggested, regardless of family history of VTE, and postpartum prophylaxis with prophylactic- or intermediate-dose LMWH for 6 weeks is recommended 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.
Protein S deficiency is a condition that may increase the risk of tissue necrosis when taking warfarin.
- The FDA drug label recommends caution when using warfarin in patients with known or suspected deficiency in protein C mediated anticoagulant response, including protein S deficiency.
- It is recommended to consider concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of therapy with warfarin to minimize the incidence of tissue necrosis 2.
From the Research
Protein S Deficiency Overview
- Protein S deficiency is a condition that increases the risk of venous thromboembolism (VTE) due to an imbalance in coagulation factors 3, 4, 5, 6, 7
- It can be inherited or acquired, and patients with this condition may require anticoagulant therapy to prevent recurrent thrombotic events
Anticoagulant Therapy for Protein S Deficiency
- Vitamin K antagonists, such as warfarin, have been traditionally used to treat VTE in patients with protein S deficiency, but they can be ineffective or cause detrimental effects in some cases 3, 4, 6
- Direct oral anticoagulants (DOACs), such as rivaroxaban, have been shown to be effective in treating warfarin-refractory VTE in patients with protein S deficiency 3, 4
- However, the efficacy of DOACs in patients with thrombophilia, including protein S deficiency, is still unknown and requires further investigation 5
Treatment Duration and Considerations
- The optimal treatment duration for patients with protein S deficiency and VTE varies depending on the type of initial event, age, and time passed since the initial thromboembolic episode 7
- Life-long duration of prophylaxis may not be warranted in all patients, and the decision to continue or discontinue anticoagulant therapy should be made on a case-by-case basis 7
- Unbalanced protein S deficiency due to warfarin treatment can be a possible cause for thrombosis, and discontinuation of warfarin may be necessary in some cases 6