Activated protein C resistance
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Activated protein C resistance is a hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). This results in an increased risk of venous thrombosis.
Activated protein C (with protein S as a cofactor) degrades Factor Va and Factor VIIIa. Activated protein C resistance is the inability of protein C to cleave Factor Va and/or Factor VIIIa, which allows for longer duration of thrombin generation and may lead to a hypercoagulable state. This may be hereditary or acquired. The best known and most common hereditary form is Factor V Leiden. Acquired forms occur in the presence of elevated Factor VIII concentrations.
It has been estimated that up to 64% of patients with venous thromboembolism might have activated protein C resistance.
Figure: The Protein C Anticoagulant Pathway: Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. Activated protein C (APC) functions as a circulating anticoagulant, which specifically degrades and inactivates the phospholipid-bound factors Va and VIIIa. This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating [Disease] from Other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
References
- Nicolaes GA, Dahlback B (2003). "Congenital and acquired activated protein C resistance". Semin Vasc Med. 3 (1): 33–46. PMID 15199491
- Dahlback B (2003). "The discovery of activated protein C resistance". J Thromb Haemost. 1 (1): 3–9. PMID 12871530
- Sheppard DR (2000). "Activated protein C resistance: the most common risk factor for venous thromboembolism". J Am Board Fam Pract. 13 (2): 111–5. PMID 10764192