- Protein C deficiency is an inherited or acquired thrombophilic disorder characterized by decreased levels or impaired function of protein C, a natural anticoagulant that plays a crucial role in regulating blood clotting. This condition leads to an increased risk of developing blood clots, particularly in the deep veins of the legs (deep vein thrombosis) and lungs (pulmonary embolism).
- The inheritance pattern of protein C deficiency is typically autosomal dominant, meaning an individual needs only one defective copy of the PROC gene to develop the condition. There are two main types of inherited protein C deficiency: Type I, characterized by reduced levels of protein C, and Type II, where protein C levels are normal but the protein doesn’t function properly. Acquired protein C deficiency can occur due to various conditions including liver disease, vitamin K deficiency, or during acute thrombotic events.
- Protein C normally functions as part of the body’s natural anticoagulation system. When activated by thrombin bound to thrombomodulin, protein C (along with its cofactor protein S) inactivates factors Va and VIIIa, thereby reducing thrombin generation and preventing excessive blood clotting. It also has anti-inflammatory properties and helps maintain the integrity of blood vessel walls.
- Clinical manifestations of protein C deficiency vary significantly among affected individuals. Some people may remain asymptomatic throughout their lives, while others experience recurrent thrombotic events starting at a young age. The first thrombotic event often occurs in early adulthood and may be triggered by risk factors such as surgery, pregnancy, immobilization, or oral contraceptive use.
- Severe hereditary protein C deficiency, when present in homozygous or compound heterozygous forms, can cause purpura fulminans in newborns, a life-threatening condition characterized by widespread blood clots in small blood vessels, leading to skin necrosis and organ dysfunction. This severe form requires immediate treatment after birth to prevent fatal complications.
- Diagnosis involves both clinical assessment and laboratory testing. Initial testing includes measurement of protein C activity and antigen levels. If levels are low, genetic testing may be performed to identify specific mutations in the PROC gene. It’s important to note that protein C levels can be temporarily decreased during acute thrombosis or while on vitamin K antagonists, so timing of testing is crucial for accurate diagnosis.
- Treatment approaches depend on the severity of the deficiency and the clinical situation. For acute thrombotic events, anticoagulation is required, typically starting with heparin or low molecular weight heparin and transitioning to oral anticoagulants. The duration of anticoagulation depends on various factors, including whether the thrombosis was provoked or unprovoked, and the presence of other risk factors.
- Prophylactic anticoagulation may be necessary in high-risk situations such as surgery, pregnancy, or prolonged immobilization. In severe cases, particularly in newborns with purpura fulminans, protein C concentrate replacement therapy is essential. Some patients may require long-term anticoagulation if they have experienced multiple thrombotic events or have additional risk factors.
- Special consideration is needed during pregnancy, as women with protein C deficiency have an increased risk of pregnancy-related complications including recurrent miscarriage, preeclampsia, and venous thromboembolism. Prophylactic anticoagulation is often recommended throughout pregnancy and the postpartum period.
- Prevention strategies focus on avoiding or minimizing additional risk factors for thrombosis. This includes maintaining a healthy weight, staying physically active, avoiding prolonged immobility during travel, and careful consideration of hormonal contraceptive use. Patients should also be educated about the signs and symptoms of thrombosis to ensure prompt medical attention when needed.
- The prognosis for individuals with protein C deficiency varies depending on the severity of the deficiency and the effectiveness of preventive measures. With appropriate management and careful attention to risk factors, many people with protein C deficiency can lead normal lives. However, they require ongoing medical supervision and may need to adjust their lifestyle and medication regimens based on changing risk factors.
- Family screening is important when protein C deficiency is diagnosed, as early identification of affected family members allows for appropriate preventive measures and risk management. Genetic counseling may be beneficial, particularly for individuals planning pregnancy or considering family planning
