What are the implications of Protein C deficiency?

From the Guidelines

For pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency, anticoagulation plus protein C replacement is recommended over anticoagulation alone. This approach is supported by the American Society of Hematology 2018 guidelines for management of venous thromboembolism, which suggest that combination therapy is preferable to anticoagulation alone in situations where complete protein C replacement is not possible due to cost or pragmatic reasons 1. The use of protein C replacement in addition to anticoagulation reduces the cost of replacement therapy and reduces the intensity of anticoagulation required, hence reducing the bleeding risk 1.

Key Considerations

• Protein C deficiency is an inherited blood clotting disorder that increases the risk of developing abnormal blood clots, and treatment typically involves anticoagulation therapy 1.
• For acute thrombotic events, heparin therapy is initiated first, followed by warfarin overlap for 5-7 days, and some patients may require protein C concentrate (Ceprotin) at 60-80 IU/kg initially, followed by 45-60 IU/kg every 6-12 hours as needed 1.
• Long-term management depends on whether the deficiency is mild (heterozygous) or severe (homozygous), with patients with severe deficiency or recurrent clots typically needing lifelong anticoagulation 1.
• Direct oral anticoagulants (DOACs) like rivaroxaban or apixaban are sometimes used as alternatives to warfarin, and protein C deficiency occurs due to mutations in the PROC gene, which reduces the body's ability to regulate clotting, leading to increased thrombosis risk 1.

Treatment Approach

• The treatment approach should be individualized based on the patient's specific needs and circumstances, taking into account the severity of the deficiency, the presence of recurrent clots, and other factors such as cost and accessibility of protein C replacement therapy 1.
• Regular monitoring of anticoagulation levels is essential, and patients should be educated about bleeding risks, medication interactions, and the importance of medical alert identification 1.
• Liver transplantation is a curative option for homozygous protein C deficiency, but it has the upfront risk of morbidity and mortality and confers a separate set of long-term risks, including long-term immunosuppression 1.

From the Research

Protein C Deficiency Overview

• Protein C deficiency is a hereditary disorder that increases the risk of thrombotic events, such as deep vein thrombosis and pulmonary embolism 2.
• The deficiency can be classified into two types: type I (quantitative decrease in protein C) and type II (qualitative decrease in protein C) 2.
• Patients with protein C deficiency often develop venous thrombotic complications between the ages of 15 and 40 years, with a high incidence of deep vein thrombosis and pulmonary embolism 2.

Treatment Options

• Historically, warfarin was the mainstay anticoagulant agent to manage patients presenting with thrombotic disorders caused by protein C or S deficiency 3.
• Direct oral anticoagulants (DOACs) such as apixaban have shown superiority over warfarin in patients with venous thromboembolism in many landmark trials 3.
• Protein C concentrate has been shown to be effective in treating purpura fulminans and thromboembolic events in patients with severe congenital protein C deficiency 4.
• Subcutaneous protein C concentrate has been used as maintenance treatment for severe protein C deficiency, with a low incidence of thrombotic events and few side effects 5.

Efficacy and Safety

• The use of apixaban in patients with protein C or S deficiency has been shown to be effective in preventing recurrent thrombotic events without safety concerns 3.
• Protein C concentrate has been shown to be safe and effective in treating thromboembolic events in patients with severe congenital protein C deficiency, with no treatment-related adverse events or serious adverse events 4.
• The combined use of prothrombin complex concentrates and warfarin has been shown to be beneficial in a patient with severe protein C deficiency, with improved global anticoagulation and no thrombotic events 6.

Clinical Implications

• Patients with protein C deficiency require long-term anticoagulant management to prevent recurrent thrombotic events 2.
• The choice of anticoagulant therapy should be individualized based on the patient's specific needs and medical history 3, 2, 4, 6, 5.
• Further studies are needed to investigate the safety and efficacy of different anticoagulant therapies in patients with protein C deficiency 3, 4.