Additional indirect evidence that substantiates this possibility is the infrequency of factor V Leiden among non-Europeans. A dilution of the patient and control is made with factor V-deficient plasma. This dilution enables testing on patients who are on oral anti-coagulant and heparin therapy. If APC resistance is not present, the addition of APC will prolong the aPTT by at least twofold. Likewise, if the mutated factor V molecule is present, the aPTT is prolonged, but not as much as in normal plasma.
Heterozygous carriers have an increased risk of thrombosis of up to sevenfold.
It is, however, becoming increasingly apparent that additional genetic or non-genetic risk factors are important in precipitating thrombotic events. Many patients with recurrent episodes of thrombosis have more than one genetic risk factor, such as concomitant protein C deficiency or homocystinemia. In addition, women suffering second trimester pregnancy loss, as well as pregnant females with thrombosis, should be investigated for inherited disorders, particularly APC resistance and antiphospholipid antibodies. Most patients with APC resistance will have the factor V Leiden mutation identified by DNA testing. Ratios less than 0.75 suggest APC resistance.