What are the implications of Protein S deficiency?

From the Guidelines

Protein S deficiency should be managed with postpartum antithrombotic prophylaxis to prevent a first venous thromboembolic event, especially in women with a family history of VTE, as suggested by the American Society of Hematology 2018 guidelines 1.

Key Considerations

• Protein S deficiency is an inherited or acquired condition that increases the risk of developing abnormal blood clots, particularly deep vein thrombosis and pulmonary embolism.
• The risk of antepartum VTE in thrombophilic women, including those with protein S deficiency, is low (less than 1%) in those with no family history of VTE, but may be higher in those with a family history of VTE 1.
• Treatment typically involves anticoagulation therapy with medications like warfarin, heparin, or direct oral anticoagulants (DOACs) such as rivaroxaban or apixaban.
• For pregnant women with protein S deficiency, low molecular weight heparin is preferred over warfarin due to safety concerns.

Management Strategies

• Postpartum antithrombotic prophylaxis is recommended to prevent a first venous thromboembolic event in women with protein S deficiency and a family history of VTE 1.
• Regular blood tests are necessary to ensure proper anticoagulation levels, especially when using warfarin.
• Lifestyle modifications, including maintaining a healthy weight, staying physically active, avoiding prolonged immobility during travel, and not smoking, are also important.

Important Notes

• The certainty of the benefits of antepartum thrombosis prophylaxis in women with protein S deficiency is low due to the lack of randomized studies and imprecision of risk estimates 1.
• The American Society of Hematology 2018 guidelines suggest that the risk reduction with prophylaxis would be approximately 75%, as reported in other settings 1.

From the Research

Protein S Deficiency Overview

• Protein S (PS) is an essential natural anticoagulant that plays a crucial role in preventing thrombotic disorders 2
• PS deficiency is a major contributor to acquired hypercoagulability, which can lead to conditions such as myocardial infarction, stroke, and deep vein thrombosis 2
• The prevalence of PS deficiency is estimated to be less than 0.5% in the general European population and 2% to 12% in selected groups of thrombophilic patients 3

Clinical Implications of Protein S Deficiency

• PS deficiency is associated with an increased risk of recurrent venous thromboembolism (VTE) and fetal loss 4
• The diagnosis of PS deficiency is challenging due to various preanalytical and analytical factors that can affect PS levels 3
• Patients with low PS levels and known mutations within the PROS1 gene, combined with other genetic or environmental thrombosis factors, are at increased risk of recurrent thromboembolic events and require lifelong oral anticoagulation 3

Treatment Options for Protein S Deficiency

• Historically, warfarin was the mainstay anticoagulant agent used to manage patients with thrombotic disorders caused by PS deficiency 5
• Direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban have shown promise in preventing recurrent thrombotic events in patients with PS deficiency 5, 6
• Rivaroxaban may be considered a valid anticoagulant alternative in patients with severe inherited PS deficiency and warfarin-induced skin necrosis 6

Research and Future Directions

• Further large-scale studies are needed to investigate the safety and efficacy of DOACs in patients with PS deficiency 5
• Recent discoveries, such as the direct inhibition of Factor IXa by PS, have shed new light on the anticoagulant function of PS and may lead to the development of new treatments for PS deficiency 2