Prothrombin and the prothrombin 20210 G to A polymorphism: their relationship with hypercoagulability and thrombosis

Polymorphisms of several clotting factors have been associated during the past few years with an increased risk of both venous or arterial thrombosis. However, final proof for the existence of a pathogenetic relationship between a given polymorphism and an increased risk for thrombosis is still lacking. Particular emphasis has been placed recently on a 20210 G to A prothrombin polymorphism. A critical review of available data indicates that such an abnormality may be associated with an increased risk of venous thrombosis but not arterial thrombosis (with a possible exception for myocardial infarction). However, this conclusion is based only on retrospective cohort studies which compared the prevalence of the abnormality in a group of patients with past venous or arterial thrombosis with a normal group (with no thrombosis). No prospective study has yet to show that patients with the abnormality, given similar additional acquired risk factors, have a higher incidence of thrombotic complications as compared with controls. The mechanism whereby the abnormality might cause thrombosis has been assumed to be an increase in prothrombin levels. Since an association between two phenomena does not necessarily mean that a causal relationship exists between the same events, it is important to be cautious before claiming that such abnormality is responsible for thrombosis. Therefore, although included commonly in the investigation profile, the search for the 20210 G to A prothrombin abnormality should not be considered yet to be an essential component in the routine study of hypercoagulable and/or thrombotic conditions.