Activated protein C resistance

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.

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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

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