What is the recommended treatment for S (serine) protein deficiency?

Management of Protein S Deficiency

For patients with Protein S deficiency, long-term anticoagulation with vitamin K antagonists (VKAs) targeting an INR of 2.0-3.0 is recommended for those with a history of thrombosis. 1

Treatment Recommendations Based on Clinical Presentation

For Patients with Previous Thrombotic Events:

• Long-term anticoagulation therapy with vitamin K antagonists (VKAs) is recommended with a target INR of 2.0-3.0 1
• Indefinite anticoagulation should be considered for patients with severe thrombophilia, including Protein S deficiency, who have experienced thromboembolic events 1
• High-intensity anticoagulation (INR > 3.0) should be avoided as it significantly increases bleeding risk without providing additional protection 1

For Asymptomatic Individuals with Protein S Deficiency:

• Prophylactic anticoagulation should be considered during high-risk situations such as surgery, prolonged immobilization, or pregnancy 1
• Clinical surveillance is appropriate for most asymptomatic patients without additional risk factors 2

Special Considerations for Pregnant Women with Protein S Deficiency

Antepartum Management:

• For women without a family history of VTE who have protein S deficiency, antepartum clinical surveillance is suggested rather than prophylactic anticoagulation 2
• The ASH guideline panel suggests against using antepartum antithrombotic prophylaxis to prevent a first venous thromboembolic event in these patients (conditional recommendation, very low certainty in evidence) 2

Postpartum Management:

• For women without a family history of VTE who have protein S deficiency, postpartum clinical surveillance is suggested rather than routine prophylactic anticoagulation 2
• For women with a family history of VTE who have protein S deficiency, postpartum antithrombotic prophylaxis is suggested to prevent a first venous thromboembolic event (conditional recommendation, very low certainty in evidence) 2
• When prophylaxis is indicated, it should be given for 6 weeks postpartum 2

Medication Options

Traditional Anticoagulants:

• Vitamin K antagonists (e.g., warfarin) with target INR 2.0-3.0 remain the standard treatment for long-term management 1
• Low molecular weight heparin (LMWH) is the preferred agent during pregnancy and immediate postpartum period 2

Direct Oral Anticoagulants (DOACs):

• Emerging evidence suggests DOACs like apixaban may be effective in preventing recurrent thrombotic events in patients with inherited thrombophilia, including Protein S deficiency 3
• However, cases of recurrent venous thrombosis during DOAC therapy have been reported, suggesting that some patients may require traditional anticoagulation with VKAs 4
• Current guidelines do not specifically recommend DOACs for Protein S deficiency, as large studies investigating their safety and efficacy in this specific population are lacking 1, 3

Monitoring and Follow-up

• Regular INR monitoring is essential for patients on VKA therapy: initially twice or three times weekly until therapeutic range is achieved, then weekly, and eventually every 4 weeks once stable 1
• Patients should be educated about potential drug interactions that may affect anticoagulation status 1
• Monitoring for complications of anticoagulation, particularly bleeding, is necessary 1

Special Clinical Scenarios

Neonates with Homozygous Protein S Deficiency:

• For neonates with clinical presentations of homozygous protein deficiency, administration of either 10-20 mL/kg of FFP every 12h or protein concentrate (when available) is recommended until clinical lesions resolve 2
• After initial stabilization, long-term treatment options include VKA, LMWH, protein replacement, or liver transplantation 2

Patients with Renal Disease:

• Anticoagulation should be considered for patients with Protein S deficiency undergoing renal transplantation due to increased risk of graft thrombosis 1
• In patients with nephrotic syndrome and Protein S deficiency, antithrombotic prophylaxis with heparin should be considered due to the compounded risk from urinary loss of anticoagulant proteins 5

Pitfalls to Avoid

• Abrupt discontinuation of anticoagulation therapy should be avoided as it may result in a temporary hypercoagulable state 1
• Failure to recognize the increased thrombotic risk during high-risk situations (surgery, pregnancy, immobilization) 1, 5
• Inadequate duration of anticoagulation therapy, especially in patients with recurrent thrombotic events 6, 4
• Overlooking the potential for arterial thrombotic events in patients with Protein S deficiency, which may require consideration of antiplatelet therapy in addition to anticoagulation in some cases 7