From the Guidelines
Protein C deficiency is the protein deficit most strongly associated with an increased risk of deep vein thrombosis (DVT), with affected individuals having a 7-10 fold increased risk of developing venous thromboembolism compared to the general population. This is because protein C is a natural anticoagulant that inactivates factors Va and VIIIa in the coagulation cascade, thereby regulating thrombin generation 1. When protein C is deficient, this regulatory mechanism is impaired, creating a prothrombotic state. Protein C deficiency can be inherited in autosomal dominant fashion or acquired due to conditions like liver disease, vitamin K deficiency, or warfarin therapy.
Some key points to consider in the management of protein C deficiency include:
- Patients with protein C deficiency often experience their first thrombotic event before age 45, with DVT of the lower extremities being the most common presentation 1.
- These patients may require long-term anticoagulation therapy, typically with direct oral anticoagulants (DOACs) or warfarin, especially after an unprovoked thrombotic event 1.
- Testing for protein C deficiency should be considered in patients with unprovoked DVT, family history of thrombosis, or thrombosis at unusual sites 1.
- The risk factors for venous thrombosis in general are linked classically to the Virchow triad of stasis of the blood, changes in the vessel wall, and changes in the composition of the blood 1.
Overall, protein C deficiency is a significant risk factor for DVT, and patients with this deficiency require careful management to prevent recurrent thrombotic events 1.
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 protein deficits associated with a higher risk of DVT are:
- Protein C deficiency
- Protein S deficiency These deficiencies have been associated with tissue necrosis following warfarin administration and may increase the risk of DVT 2, 2.
From the Research
Protein Deficit and Risk of DVT
- Antithrombin deficiency is a significant risk factor for deep vein thrombosis (DVT) 3, 4, 5, 6, 7
- Studies have shown that patients with antithrombin deficiency have a higher risk of venous thromboembolism (VTE) compared to those without the deficiency 3, 5, 6, 7
- The risk of VTE is increased in patients with antithrombin deficiency due to enhanced thrombin generation and a prothrombotic plasma fibrin clot phenotype 6
- Antithrombin activity is crucial for the effectiveness of enoxaparin prophylaxis, and low antithrombin activity is associated with reduced responsiveness to enoxaparin and increased risk of VTE 7
Mechanisms of Antithrombin Deficiency
- Antithrombin deficiency can be inherited or acquired, with acquired deficiency occurring in various medical conditions such as sepsis, liver dysfunction, and major surgery 3, 5
- Microvascular leakage and endothelial loss are potential mechanisms of antithrombin depletion, leading to increased thrombotic risk 5
- Antithrombin deficiency is associated with reduced fibrin clot permeability and prolonged clot lysis time, contributing to the prothrombotic state 6
Clinical Implications
- Patients with antithrombin deficiency require careful management, including long-term anticoagulation and/or thromboprophylaxis, especially in high-risk situations such as surgery and pregnancy 3, 4
- Antithrombin concentrates can be used for treatment and prevention of acute venous thrombosis in patients with antithrombin deficiency 3, 4
- Ex vivo antithrombin supplementation may improve responsiveness to enoxaparin prophylaxis and reduce the risk of VTE 7