What are the implications of Protein S deficiency?

From the Guidelines

Protein S deficiency should be managed with anticoagulation therapy, and the choice of treatment depends on the clinical context, such as pregnancy or acute thrombotic events, with a preference for low-molecular-weight heparin during pregnancy and consideration of direct oral anticoagulants or warfarin in other cases. The management of protein S deficiency involves anticoagulation to prevent thrombotic events, and the approach can vary based on the specific circumstances of the patient, including whether the deficiency is inherited or acquired, and any concurrent conditions such as pregnancy 1. Key considerations include:

• The use of low-molecular-weight heparin as a preferred treatment during pregnancy due to the contraindication of warfarin in this context 1.
• The consideration of direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, or dabigatran as alternatives to warfarin for long-term anticoagulation in appropriate patients.
• The importance of regular monitoring of coagulation parameters, particularly when using warfarin, to ensure the international normalized ratio (INR) remains within the therapeutic range of 2.0-3.0.
• The role of protein S as a cofactor for activated protein C in regulating the coagulation cascade, and how its deficiency leads to a hypercoagulable state. In terms of specific guidelines for pregnant women with protein S deficiency, the American Society of Hematology suggests antepartum clinical surveillance regardless of family history of venous thromboembolism (VTE), and postpartum prophylaxis with low-molecular-weight heparin for 6 weeks if there is a family history of VTE 1. For non-pregnant patients, the decision to use anticoagulation therapy and the choice of agent should be individualized based on the patient's risk of thrombosis and bleeding, as well as other clinical factors. Given the potential for protein S deficiency to increase the risk of thrombotic events, anticoagulation therapy is a critical component of management, with the goal of preventing venous thromboembolism and reducing the risk of morbidity and mortality associated with these events.

From the Research

Protein S Deficiency Overview

• Protein S deficiency is a rare condition that can lead to deep vein thrombosis, pulmonary embolism, or stroke 2.
• It is often treated with long-term anticoagulant therapy.
• Protein S deficiency may be hereditary or acquired, with the latter usually due to hepatic diseases or a vitamin K deficiency 2.

Diagnosis and Treatment

• The diagnosis of protein S deficiency is challenging, with many preanalytical and analytical factors affecting protein S levels 3.
• Molecular analysis of the protein S gene (PROS1) involves direct gene sequencing and, if negative, multiplex ligation-dependent probe amplification (MLPA) method 3.
• Treatment with vitamin K antagonists, such as warfarin, is common, but may not be sufficient in some cases, particularly if the international normalized ratio is <4.0 4.
• Direct oral anticoagulants (DOACs), such as rivaroxaban, may be considered as a valid anticoagulant alternative in patients with severe inherited protein S deficiency and warfarin-induced skin necrosis 4, 5.

Recurrent Venous Thrombosis

• Patients with protein S deficiency have an increased risk of recurrent venous thromboembolism compared to patients without such a deficiency 6.
• The optimal treatment duration for protein S deficiency will vary, depending on the type of the initial event, age, and time passed since the initial thromboembolic episode 6.
• Recurrent venous thrombosis during DOAC therapy has been reported in patients with protein S deficiency, highlighting the need for careful monitoring and adjustment of treatment 5.