Activated Protein C Resistance

An inherited (autosomal dominant) or acquired defect in the anticoagulant response to activated protein C, resulting in an increased risk of thrombosis.
Clinical findings Increased risk of deep vein thrombosis (DVT), venous thrombosis; it is responsible for 20% to 50% of DVT.
Pathogenesis Protein C, a key regulator of coagulation, circulates in an inactivated form and is activated by the binding of thrombin to thrombomodulin receptors on vascular endothelial cells; once activated, protein C lyses coagulation factors Va and VIIIa. Activated protein C resistance is caused by a failure of protein C to cleave Factor Va and/or Factor VIIIa.

activated protein C resistance

APC resistance Hematology A condition caused by an inherited defect in the anticoagulant response to APC and clinically characterized by ↑ venous thrombosis; it is responsible for 20-50% of DVT Pathogenesis Protein C, a key regulator of coagulation, circulates in an inactivated form and is activated by the binding of thrombin to thrombomodulin receptors on vascular endothelial cells; once activated, protein C lyses coagulation factors Va and VIIIa; APCR may be due to a selective defect in factor V coagulant function

activated protein C resistance

An abnormality in the regulation of blood clotting often found in patients with an unexplained THROMBOSIS. It is associated with a mutation in the gene for the clotting factor, Factor V, and may provide an explanation of the common genetic predisposition to thrombosis (thrombophilia).

Collins Dictionary of Medicine © Robert M. Youngson 2004, 2005

References in periodicals archive

Activated Protein C Resistance (APCR) Results With and Without Rivaroxaban in Patients With and Without Heterozygous Factor V Leiden Heterozygous/ Heterozygous/ Wild Type/ Rivaroxaban No Rivaroxaban Rivaroxaban APCR, mean 1.75 (0.12) 1.64 (0.09) 2.63 (0.23) (SD), N = 60 Rivaroxaban 143 (95;45-349) Not applicable 147 (79;68-311) concentration, ng/mL, mean (SD; range) Normal APCR/No Rivaroxaban APCR, mean 2.49 (0.18) (SD), N = 60 Rivaroxaban Not applicable concentration, ng/mL, mean (SD; range) Table 2.

Rivaroxaban Causes Missed Diagnosis of Protein S Deficiency but Not of Activated Protein C Resistance (Factor V Leiden)

Association of primary antiphospholipid syndrome with inherited activated protein C resistance. J Rheumatol 1998;25:1232-4.

Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

Acquired activated protein C resistance is associated with the co-existence of anti-prothrombin antibodies and lupus antico agulant activity in patients with systemic lupus erythematosus.

Activated protein C resistance caused by Arg506G1n mutation in factor Va.

[5] Nonstandard abbreviations: aPL, anti-phospholipid; anti-CL/[beta]2-GPI, anti-cardiolipin/[beta]2-glycoprotein I; anti-PS/PT, anti-phosphatidylserine/prothrombin; LA, lupus anficoagulant; SLE, systemic lupus erythematosus; PE, pulmonary embolism; VTE, venous thromboembolism; APC, acfivated protein C; APC-R, activated protein C resistance; DVT, deep vein thrombosis; TBS, Tris-buffered saline; BSA, bovine serum albumin; APTT, activated partial thromboplastin time; OR, odds rafio; CI, confidence interval; and mAU, milliabsorbance unit(s).

Acquired activated protein C resistance associated with IgG antibodies against [[beta].sub.2]-glycoprotein I and prothrombin as a strong risk factor for venous thromboembolism

Although factor V Leiden mutation is the cause of activated protein C resistance in most cases, we recommend that activated protein C resistance testing be done first, as it is a less expensive and more widely available test than the DNA-based factor V Leiden mutation test.

If testing for activated protein C resistance is possible and the result is positive, confirmatory testing for factor V Leiden is indicated.

Evaluating idiopathic venous thromboembolism: what is necessary, what is not

CLINICAL TESTING FOR ACTIVATED PROTEIN C RESISTANCE AND FACTOR V LEIDEN

The Clot-Based Tests for Activated Protein C Resistance

The original test for activated protein C resistance that was offered for use in clinical laboratories was a partial thromboplastin time (PTT) performed in the presence and absence of exogenously supplied activated protein C.

The limitations in the originally devised assay for activated protein C resistance led to the development of a modified assay.

Activated protein C resistance, the factor V Leiden mutation, and a laboratory testing algorithm. (Original Articles)