The HR2 haplotype of coagulation factor V: Biochemistry, epidemiology, and clinical relevance = Der HR2-haplotyp des gerinnungsfaktors V: Biochemie, epidemiologie und klinische bedeutung

The HR2 haplotype of factor V represents an apparently very ancient group of tightly linked mutations throughout the factor V gene. It has been associated with increased activated protein C resistance, reduced factor V levels, and an increased risk of venous thromboembolism. However, reports are not consistent. Recent studies about the functional activity of factor V HR2 demonstrated that factor V HR2 is inactivated by activated protein C at the same rate as normal factor V and that in the prothrombinase complex it acts as well as factor V. On the other hand, it is more prothrombotic because of an increased ratio of factor V1 to factor V2, with factor V1 being the more procoagulant isoform of circulating factor V, with reduced affinity to negatively charged phospholipids. It is possible that discrepancies in the results of epidemiological studies linking factor V HR2 to thrombosis are due to several factors, e.g. differences in end-points, characteristics of patients and controls, and methods of measurement of resistance to activated protein C. Then again, factor V HR2 might be a mild risk factor on its own, while it might increase thrombotic risk if in combination with other risk factors (such as factor V Leiden) as preliminary studies suggest. Another intriguing possibility is that the association of reduced factor V levels and factor V HR2 might also be prothrombotic, since the combination would presumably lead to a globally reduced cofactor activity of factor V to factor VIII inactivation by activated protein C. Finally, several aspects of the relationship of HR2 and venous thromboembolism have not been explored until now, such as the association of this haplotype with thrombosis in unusual sites or in combination with acquired risk factors.