Abstract
Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk.
Highlights
The G20210A variant in the 3' UTR of prothrombin gene (FII G20201A) is associated with higher plasma prothrombin activity and has a prevalence of 1.2–4.6% in the general Caucasian population, and higher in patients affected by venous thromboembolism (VTE, [1,2])
Several studies described the early onset of venous thromboembolism in subjects bearing inherited thrombophilia [17] and the trigger action of oral contraceptives in particular in subjects with already known thrombophilia [19]
The patient suffered of two episodes of early recurrent pregnancy losses and one episode of late pregnancy loss that are more frequently associated to inherited thrombophilia [18]
Summary
The G20210A variant in the 3' UTR of prothrombin gene (FII G20201A) is associated with higher plasma prothrombin activity and has a prevalence of 1.2–4.6% in the general Caucasian population, and higher in patients affected by venous thromboembolism (VTE, [1,2]). She was homozygote for FII G20210A, without other laboratory alterations (i.e. PC, PS or ATIII deficiencies, FVL or MTHFR variants, anticardiolipin antibodies and lupus anticoagulant) This patient did not show further thrombotic risk factor as personal history of venous thromboembolism as recent surgery as recent immobility as first degree relative affected by venous thromboembolism as malignancy nor risk factor for arterial thrombosis as smoking as hypertension, diabetes, dyslipidemia. All other laboratory data (i.e., AT III, PC, PS, FVL and MTHFR C677T variant) were normal His father died at 40 years from AMI; his mother (heterozygote for FII G20210A) had never suffered from vascular diseases. The patient is a non-smoker, without hypertension, diabetes and\or dyslipidaemia; thrombotic risk factors for venous thromboembolism were absent as recent surgery as recent immobility as malignancy and its therapies as previous personal history of venous thrombosis. No episode of vascular disease occurred during the last 4 years and none antithrombotic treatment was suggested for him
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
