Usefulness of factor V Leiden mutation testing in clinical practice

Abstract

We have investigated the clinical usefulness of the activated protein C resistance (APCR)/factor V Leiden mutation (FVL) test by sending out questionnaires to all Norwegian physicians who ordered these tests from our publicly funded service laboratory during a 3-month period, and of whom 70% (267/383) responded. Indications for testing, patient follow-up, the use of APCR versus FVL tests and differences in practice between hospital doctors and GPs were examined. We found that 46% of the tests were predictive, ordered for risk assessment in healthy individuals with no previous history of venous thromboembolism (VTE). Among these, 42% of the tests were taken on the initiative of the patient and 24% were screening tests before prescription of oral contraceptives. In total, 54% of the tests were classified as diagnostic, among which 42% were ordered owing to a previous history of VTE and 22% to a history of brain stroke or myocardial infarction. The prevalence of FVL heterozygotes was not significantly different between the predictive and diagnostic test groups, that is, 26 and 20%, respectively. Only the predictive tests influenced patient follow-up. Here, the physician's advice to patients depended on the test result. In general, the clinical usefulness of APCR/FVL testing was low. Many tests were performed on unsubstantiated or vague indications. Furthermore, normal test results led to unwarranted refrain from giving advice about antithrombotic measures, leading to potential harm to the patient. INTRODUCTIONThe clinical utility of tests for common genetic variants associated with slightly increased risk for multi-factorial disorders such as type II diabetes 1 and atherosclerosis 2 has been questioned. 3 Among such tests, the currently most commonly used test is the activated protein C resistance (APCR) test or factor V Leiden mutation DNA (FVL) test. Clinical utility refers to the likelihood that a test will lead to improved outcome for the patient tested. 3 As the presence of APCR (measured by the second generation APCR assay) is almost always because of the FVL, these tests are equivalent in a population with high FVL mutation prevalence, regardless of the test being performed on the biochemical or DNA level. 4 Both tests identify heterozygotes and homozygotes for the FVL mutation. About 3-8% of subjects in Caucasian populations are heterozygous for the FVL mutation and B0.2% are FVL homozygous. 4 In our laboratory, FVL heterozygosity was found in 8.5% of anonymous blood samples from 200 healthy blood donors (unpublished data). The heterozygotes have a fivefold and the homozygotes an 18-fold increased relative risk for venous thromboembolism (VTE). 5,6 The risk for VTE is determined by several known genetic factors (for example, the FVL and factor II prothrombin 20210G4A mutations, protein C, protein S and antithrombin deficiency), as well as by age, obesity, immobility, anti-phospholipid antibodies, infections, malignancies and smoking.The annual incidence of VTE is about 1 per 1000 individuals, 7,8 which cor...

Genetics of stroke

“…For example, genotype-guided warfarin therapy for anticoagulation in elderly patients with AF was reported to be potentially cost-effective, and its benefits were closely related to efficacy in preventing bleeding events [120] . However, in general, the clinical usefulness of genetics testing was low, such as the activated protein C resistance/factor V Leiden mutation test [121] . Many tests were performed based on unsubstantiated or vague indications.…”

How do laboratory specialists advise clinicians concerning the use and interpretation of renal tests?

“…The case histories and questionnaires were carefully designed after exploring the literature of specialists in primary health care and clinical chemistry with long-term experience in designing questionnaires used among primary health-care physicians (126)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136). For Articles I, II and IV, real patients were used as models for the case histories, whilst for Article III the questionnaire obtained data of one of the patients enlisted with a GP.…”

Activated Protein C Resistance Does Not Increase Risk for Recurrent Stroke or Death in Stroke Patients

“…Indications, benefits and drawbacks of testing for inherited thrombophilias within the diagnostic work-up of ischemic stroke patients are therefore controversially discussed [ 37 – 41 ]. Nevertheless, current clinical practice frequently includes testing for FV Leiden in patients with a history of stroke [ 42 ], particularly in young patients who have suffered from a cryptogenic stroke.…”