What are the implications of low Protein S (Protein S deficiency) levels?

From the Guidelines

Low protein S levels can indicate an increased risk of blood clots, and individuals with this condition should consult a hematologist for proper evaluation and management to reduce the risk of morbidity and mortality. The implications of low Protein S (Protein S deficiency) levels are significant, as they can lead to an increased risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) 1. According to the European Heart Journal, protein S deficiency is a primary risk factor for VTE, along with other conditions such as antithrombin deficiency, protein C deficiency, and factor V Leiden 1.

Risk Factors and Considerations

Some key points to consider for individuals with low protein S levels include:

• The risk of VTE is increased in certain situations, such as surgery, pregnancy, and the use of hormonal contraceptives 1
• Lifestyle modifications, such as maintaining a healthy weight, staying active, and avoiding prolonged immobility, can help reduce the risk of blood clots
• Women with protein S deficiency should discuss the use of hormonal contraceptives with their doctor, as these may further increase the risk of clotting
• Regular follow-up with a healthcare provider is essential to monitor the condition and adjust treatment as needed

Treatment and Management

Treatment for low protein S levels depends on whether the individual has a temporary decrease or an inherited deficiency, and whether they have already experienced blood clots. For patients with previous clots, anticoagulation therapy is typically recommended, often with medications like warfarin, rivaroxaban, apixaban, or dabigatran. The duration of treatment varies based on the individual's specific situation and risk factors. For those without previous clots but with low protein S, preventive anticoagulation might be considered during high-risk situations like surgery or pregnancy 1.

In terms of specific management, a study published in the journal Stroke found that protein C deficiency was a significant risk factor for cerebral venous thrombosis, with a combined odds ratio of 11.1 1. While this study did not specifically examine protein S deficiency, it highlights the importance of natural anticoagulant proteins in preventing excessive blood clotting. Overall, the management of low protein S levels requires a comprehensive approach that takes into account the individual's medical history, risk factors, and lifestyle.

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. The implications of low Protein S (Protein S deficiency) levels include an increased risk of tissue necrosis following warfarin administration, as it is a cofactor in the protein C mediated anticoagulant response 2.

• Key points:
  • Protein S deficiency is associated with an increased risk of tissue necrosis
  • Warfarin administration may exacerbate this risk
  • Tissue necrosis can occur in patients with protein S deficiency, but not all patients with this condition develop necrosis 2

From the Research

Implications of Low Protein S Levels

• Low Protein S levels, also known as Protein S deficiency, can lead to an increased propensity to experience thromboembolic events 3, 4.
• These events can be precipitated by factors such as trauma, pregnancy, or surgery, and can result in deep venous thrombosis, pulmonary emboli, or cerebrovascular occlusion 3, 4, 5.
• Protein S deficiency has been found to be associated with arterial thrombosis, such as arterial ischemic stroke, although the effect of Protein S deficiency in this area is uncertain 6.
• Patients with Protein S deficiency may require long-term anticoagulation therapy to prevent recurrent thrombotic events 4, 7.
• The use of direct oral anticoagulants (DOACs) such as apixaban may be effective in preventing recurrent thrombotic events in patients with Protein S deficiency, although further studies are needed to investigate the safety and efficacy of these agents in this population 7.
• Protein S deficiency can also be a predisposing factor for venous thromboembolism (VTE), and hypoxia can downregulate plasma Protein S levels, increasing the risk of thrombotic events 6.
• Inherited thrombophilias, including Protein S deficiency, can be an important etiology for recurrent pregnancy loss, and anticoagulation therapy may be beneficial for women with recurrent pregnancy loss who have documented Protein S deficiency 6.

Clinical Management

• Anticoagulation therapy, such as warfarin or DOACs, may be instituted in patients with Protein S deficiency to prevent recurrent thrombotic events 3, 7, 5.
• Measurement of total and free Protein S levels should be part of the evaluation for any young adult who has had a stroke or other thrombotic event 4.
• Serial measurement of Protein C, factor II, and factor X at various International Normalization Ratio (INR) levels can help diagnose Protein C deficiency in warfarinized patients, although this method may not be effective for diagnosing Protein S deficiency 5.

Risk Factors

• Pregnancy can decrease plasma Protein S concentration, increasing the risk of thrombotic events 6.
• Hypoxia, such as that caused by COVID-19, can downregulate plasma Protein S levels, increasing the risk of thrombotic events 6.
• Inherited thrombophilias, including Protein S deficiency, can be an important etiology for recurrent pregnancy loss and thrombotic events 6.