Abstract

Background: The identification of prothrombin G20210A polymorphism (PT20210) is normally included in the thrombophilia laboratory panel and evaluated by DNA-based molecular analysis. To date, a routine coagulation test that helps to identify PT20210 carriers has not been set, in contrast to the FV Leiden mutation, for which a functional coagulation test, the Activated Protein C Resistance test (APCR), is available as a screening tool. Moreover the molecular tests are expensive and are used inappropriately. The aim of the study is to characterize the effects of the prothrombin G20210A mutation on routine clotting assays in order to identify, if any, coagulation tests that can be used as a first-line cost-effective assay for prothrombin G20210A polymorphism.
Methods: Our cohort consisted of 80 PT20210 polymorphism carriers and 82 age and gender matched controls. All subjects were investigated for PT-INR, aPTT, dRVVT, FII (%), and Endogenous Thrombin Potential (EPT) parameters.
Results: In heterozygotes and wild-type, PT, aPTT, and dRVVT values were not significantly different. The plasma activity of Factor II (%), AUC TG (%), and C max (%) of EPT were significantly higher in heterozygotes than in controls (p < 0.0001, Mann-Whitney test). In the absence of oral anticoagulant therapy and/or heparin, lupus anticoagulants, and liver disease, the discriminating abilities of the FII , AUC TG, and C max (%) to separate properly the study population into carriers and controls were equal to 0.99 (95% CI 0.98 to 1.00); 0.97 (95% CI 0.94 to 0.99), and 0.84 (95% CI 0.77 to 0.90), respectively.
Conclusions: All routine clotting assays performed in the present work are not useful as a screening tool for the G20210A prothrombin gene allele in a general population. Definitely, to date, the exclusive possible approach to identify the PT20210 mutation is molecular genetic testing, but unfortunately it is used inappropriately, contributing significantly to an uncontrolled waste of resources. It is mandatory to restrict the genetic thrombophilia test ordering to when it is actually recommended by the guidelines and to educate clinicians on the waste and danger of over-testing, particularly genetic tests, taking into account the fact that the PT20210 polymorphism is extremely variable (0.7 to 8% in Europe; 1.3 - 5% in the USA).

DOI: 10.7754/Clin.Lab.2014.140215