Activated protein C resistance

Activated Protein C Resistance (APCR) is a hemostatic disorder characterized by a reduced response to the anticoagulant actions of activated protein C (APC), leading to an increased risk of venous thromboembolism (VTE). This condition is significant in the field of hematology and thrombosis, as it underlines a crucial aspect of the coagulation cascade and its regulation.

Etiology

The most common cause of activated protein C resistance is a point mutation in the factor V gene, known as Factor V Leiden. This mutation results in a variant of factor V that cannot be efficiently inactivated by APC. Other less common causes include acquired conditions such as antiphospholipid syndrome, certain medications, and some malignancies.

Pathophysiology

Under normal circumstances, activated protein C functions as a natural anticoagulant by inactivating factors Va and VIIIa, thus downregulating the coagulation cascade. In individuals with APCR, the efficiency of APC in inactivating factor Va is significantly reduced, leading to a prothrombotic state. This imbalance increases the risk of developing venous thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

Clinical Presentation

Patients with activated protein C resistance may present with recurrent venous thromboembolism at a young age, often without traditional risk factors. Family history of VTE may also be present, indicating a hereditary predisposition.

Diagnosis

The diagnosis of APCR involves a combination of clinical assessment and laboratory testing. The APC resistance assay, typically performed using a coagulometer, is the standard diagnostic test. Genetic testing for the Factor V Leiden mutation may also be conducted, especially in individuals with a family history of APCR or unexplained VTE.

Management

Management of APCR focuses on the prevention and treatment of venous thromboembolism. Anticoagulant therapy, such as warfarin or direct oral anticoagulants (DOACs), is the cornerstone of treatment. In individuals with a history of VTE, long-term anticoagulation may be recommended. Lifestyle modifications and avoidance of risk factors for thrombosis are also important aspects of management.

Prognosis

With appropriate management, individuals with activated protein C resistance can have a good prognosis. However, the risk of recurrent VTE remains, necessitating ongoing vigilance and possibly long-term anticoagulation therapy.

Epidemiology

Activated protein C resistance is the most common hereditary thrombophilia in Caucasians, with the Factor V Leiden mutation present in 3-8% of the population. The prevalence varies widely among different ethnic groups.

See Also

• Factor V Leiden
• Venous thromboembolism
• Deep vein thrombosis
• Pulmonary embolism
• Anticoagulant
• Hematology