[Molecular biology and haemostasis]

Abstract

Molecular biological methods have become increasingly important not only in the diagnostics of inherited monogenetic diseases such as hemophilia A or B but also in the diagnostics of polygenetic diseases e.g. venous and arterial thrombosis. In haemophilia A, sequencing of the factor VIII gene has been established in addition to the analysis of the two most frequent genetic abnormalities, the inversions in intron 22 and intron 1, in several centers. Molecular testing has proved helpful to identify haemophilia patients at high risk to develop inhibitors as well as in carrier analysis. In patients with familial protein C or protein S deficiency mutation analysis contributes to the verification of the diagnosis. The frequently performed tests for the factor V Leiden mutation and the prothrombin 20210G>A variation can potentially support the estimation of the thrombotic risk as well as the risk of recurrence. However, any uncritical application of these genetic tests does not improve diagnostics nor does it support therapeutic decision making or counselling of the patient. Therefore, one should only do genetic tests with medical or therapeutic consequences. The applicability of mutation analysis in the daily routine is still limited in spite of the importance of molecular diagnostics in the understanding of pathomechanisms of haemostatic disorders. As has been demonstrated in large studies, the phenotypic effects of mutations can vary significantly between individuals. Endogenous and exogenous modulators that are still largely unknown, play a role. Currently, the understanding of these modulators is limited, and large multicenter studies and meta-analyses are needed for a better understanding of gene-gene and gene-environment interactions.