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Activated protein C resistance
Classification and external resources
ICD-9 289.81
OMIM 188055
MeSH D020016

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, which can cause heart attacks, strokes, and other problems with circulation.[1]

The disorder can be acquired or inherited, the hereditary form having an autosomal dominant inheritance pattern.[2]

Pathophysiology

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

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.[3] The best known and most common hereditary form is Factor V Leiden. Acquired forms occur in the presence of elevated Factor VIII concentrations.

Associated conditions

Up to 64% of patients with venous thromboembolism might have activated protein C resistance.[4]

References

  1. ^ Dahlbäck B (2003). "The discovery of activated protein C resistance". J. Thromb. Haemost. 1 (1): 3–9. doi:10.1046/j.1538-7836.2003.00016.x. PMID 12871530.  
  2. ^ Koster T, Rosendaal FR, De Ronde H, Briët E, Vandenbroucke JP, Bertina RM (December 1993). "Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study". Lancet 342 (8886-8887): 1503–6. doi:10.1016/S0140-6736(05)80081-9. ISSN 0140-6736. PMID 7902898.  
  3. ^ Nicolaes GA, Dahlbäck B (2003). "Congenital and acquired activated protein C resistance". Semin Vasc Med 3 (1): 33–46. doi:10.1055/s-2003-38331. PMID 15199491.  
  4. ^ 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.  
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