We wanted to investigate whether APC resistance in the absence of factor V Leiden, determined with global coagulation test such as the thrombin generation assay, could be used as a marker for increased risk of recurrent VTE among women 18-65 years old after a first event of VTE.
Myocardial infarction (MI) can be due to inherited thrombophilia caused by resistance to activated protein C resulting from factor V Leiden (FVL) mutation.
Secondly, resistance to activated protein C as a result of factor V Leiden is associated with thromboembolic disease at an early age (Price DT, Ridker PM.Ann Intern Med.1997;127:895-903).
Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, Protein C and Protein S, and genetic polymorphisms such as prothrombin G20210A and cleavage-resistant forms of factor V (in particular factor V Leiden), that lead to a condition commonly known as activated protein C resistance.
One of the most frequent hereditary causes of thrombophilia is, without a doubt, resistance to Activated Protein C (APC-resistance), which is a consequence of point mutation in gene coding for coagulation Factor V (Factor V Leiden) in 90-95% of cases.
However, contrary to common expectations, factor V Leiden was observed much less frequently in patients showing activated protein C resistance (10 out of 23; 43.4%) than is commonly observed in the Caucasian population (almost 90%).
In addition, abnormal activated protein C resistance (or Factor V Leiden), Factor II G20219A variant, and the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR C677T) need to be considered.
Thrombophilia was suspected and the relative investigation revealed high levels of factor VIII procoagulant, which is frequent in hemodialysis patients, and resistance to activated protein C. Polymerase chain reaction detected that the patient was heterozygous for factor V Leiden, which is quite common in general population.
There is a possibility that Factor V HR2 Haplotype might also be associated with activated protein C resistance even in the absence of Factor V Leiden.
Clinical evaluation of a new functional test for detection of activated protein C resistance (Pefakit APC-R Factor V Leiden) at two centers in Europe and the USA.
Acquired activated protein C resistance (aAPCR), not associated with factor V Leiden, has been described in cancer patients with an increased risk of venous thromboembolism (VTE).
However, the frequencies of these thrombophilic defects and of APC resistance associated with factor V Leiden was lower than the corresponding frequencies previously reported for Caucasian populations.
APC resistance with factor V Leiden was seen in 27% of patients compared to 11.5% of controls, while APC resistance without factor V Leiden was seen in 12.5% of patients compared to 9.5% of controls.
Laboratories using the RVVT APCR generally performed better in detection of factor V Leiden-associated APCR, with the aPTT method group yielding higher false-negative and/or false-positive findings (approximately 5% of occasions).
Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, protein C and protein S, and genetic polymorphisms such as prothrombin G20210A and the cleavage-resistant factor mutation, factor V Leiden, which leads to a condition known as activated protein C resistance.
Sensitivity of the APC resistance test in the absence of factor V-deficient plasma was shown to be improved through normalization of results, and errors in the genetic diagnosis of factor V Leiden and the P20210A prothrombin gene mutation are described.
In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively).
Crucially, oral but not transdermal hormone-replacement therapy increases activated protein C resistance independently of the presence of factor V Leiden.