Activated Protein C Resistance

Optimal result: 2.2 – 3.5 Ratio

Labcorp

By Healthmatters Editorial Team

Peer-reviewed sources

More than 95% of cases of aPC resistance are caused by a specific polymorphism in the factor V gene that is referred to as factor V Leiden. This single point mutation results in a substitution of glutamine for arginine at amino acid number 506 of factor V. Arginine number 506 is an aPC cleavage site of normal factor V, making factor V Leiden resistant to inactivation by aPC. Heterozygous factor V Leiden mutation occurs in 3% to 7% of persons of Northern European descent. However, this mutation is essentially absent in Asian, African, and Mediterranean populations.

Individuals with heterozygous factor V Leiden have a three- to tenfold increased risk of thrombosis. The risk of thrombosis is approximately 80-fold increased in individuals who are homozygous for factor V Leiden.

The incidence of factor V Leiden in unselected individuals experiencing their first venous thrombosis or pulmonary embolism is approximately 20%. In patients with a family history of thrombophilia, the likelihood of factor V Leiden being the cause reaches as high as 50%.

Risk of thrombosis is further increased if the factor V Leiden mutation is accompanied by other prothrombotic conditions (ie, antithrombin, protein C or protein S deficiency, prothrombin G20210, pregnancy, oral contraceptive usage, prolonged immobilization, or surgery).

While factor V Leiden is, by far, the most common genetic cause of aPC resistance, other polymorphisms can produce this condition. aPC resistance can occur due to an elevated factor VIII level, in itself a risk factor for thrombosis.

Factor V Cambridge, a very rare mutation at another arginine residue of factor V, can produce aPC resistance.

The HR2 haplotype, also referred to as A4070G mutation, is another rarely observed genetic cause of aPC resistance.

Screening test for the factor V Leiden gene mutation and other causes of activated protein C resistance

Activated Protein C Resistance detects thrombotic risk factors other than factor V Leiden.

In some cases, this test will fail to distinguish individuals who are heterozygous for the factor V Leiden mutation from normals.

Genetic testing may be required to distinguish between heterozygous and homozygous factor V Leiden mutation.

Elevated factor VIII levels, as can be seen in acute phase reaction, can normalize the aPTT and effectively reduce the anticoagulant effect of aPC.

Abnormal results can also be seen in pregnancy, especially during the third trimester, due to decreased levels of protein S and increased levels of factors V and VIII.

Activated protein C (aPC), in a complex with protein S, inactivates procoagulant factors Va and VIIIa by proteolytic cleavage at specific arginine residues. This serves to control coagulation and limit the extent of thrombus formation. The functionality of the aPC inhibitory system in a given individual can be assessed through an in vitro clotting assay. Addition of aPC to a patient's plasma serves to extend the activated partial thromboplastin time (aPTT) for individuals who are sensitive to aPC. Individuals are considered to be aPC resistant when addition of aPC fails to extend the time to clot formation in this assay.

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Written by Healthmatters Editorial Team

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