From the FDA Drug Label
Known or suspected deficiency in protein C mediated anticoagulant response Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration.
The patient's protein C activity of 59% is generally considered normal or mildly decreased, as the normal range is typically between 60-150%. However, the exact cutoff for deficiency can vary depending on the laboratory and testing method.
- Based on the information provided, it is unclear if the patient's protein C activity level would qualify as a deficiency.
- The decision to anticoagulate should be based on individual clinical judgment, weighing the risks and benefits of anticoagulant therapy.
- If the patient is suspected to have a protein C deficiency, caution should be exercised when administering warfarin, and consideration should be given to concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of warfarin therapy to minimize the incidence of tissue necrosis 1.
From the Research
A protein C activity level of 59% in a 35-year-old male is considered mildly deficient, and anticoagulation therapy should be considered based on the patient's clinical presentation, personal history of thrombosis, and family history of thrombotic events. The normal range for protein C activity is typically considered to be between 70-140% [ 2 ]. According to a study published in 2017, patients with protein C deficiency are at increased risk for thrombotic diseases, and non-vitamin K antagonist anticoagulant options should be considered in patients with warfarin-induced skin necrosis in the setting of protein C deficiency [ 3 ].
Key Considerations
- Anticoagulation should be based on the patient's clinical presentation, personal history of thrombosis, and family history of thrombotic events.
- If the patient has experienced unprovoked venous thromboembolism or has a strong family history of thrombosis with protein C deficiency, anticoagulation might be considered.
- For patients with mild protein C deficiency without prior thrombotic events, clinical observation and risk factor modification (avoiding oral contraceptives, smoking cessation, maintaining healthy weight) are generally recommended rather than prophylactic anticoagulation.
- If anticoagulation is deemed necessary based on clinical factors, standard options include direct oral anticoagulants (DOACs) like apixaban or rivaroxaban, or warfarin with a target INR of 2-3.
Additional Recommendations
- Protein C deficiency can be hereditary or acquired, so further evaluation including family screening might be appropriate.
- Repeat testing during a non-acute phase is recommended to confirm the deficiency, as levels can be temporarily decreased during acute illness or inflammation.
- A study published in 2008 found that protein C concentrate supplementation can be effective in preventing thromboembolic complications in patients with congenital protein C deficiency while initiating oral anticoagulants [ 4 ].
Clinical Decision Making
The decision to initiate anticoagulation therapy should be made on a case-by-case basis, taking into account the patient's individual risk factors and clinical presentation. The most recent and highest quality study [ 3 ] suggests that non-vitamin K antagonist anticoagulant options should be considered in patients with warfarin-induced skin necrosis in the setting of protein C deficiency.