Inserm U734, Faculté de médecine de l’Université Henri Poincaré-Nancy 1, Boîte Postale 184, 54505 Vandoeuvre-lès-Nancy Cedex, France, CHRU de Nancy, Service d’hématologie biologique, Nancy, France, CHRU de Nancy, médecine interne et vasculaire, Nancy, France
The aim of this review is to explain why the monitoring of the whole thrombin activity that arises in vitro under well-defined and realistic experimental conditions – thrombography – can be a reliable and useful laboratory intermediary phenotype: a relevant link between molecular and cellular mechanisms with their numerous and intricate interplays on the one hand, and clinical manifestations on the other. For the last 10 years main advances regarding the apparatus and the reagents have made it more user-friendly, convenient, reliable and efficient. Continuous standardization is ongoing and thorough clinical evaluation according to current high standards of clinical research is timely. Our main interest regards acquired thrombophilia such as the so-called antiphospholipid antibodies. We showed that such a phenotyping of the clotting system in the presence of platelets displayed the still surprising coexistence of a true anticoagulant phenomenon with an interference with activated protein C (APC). The latter can be so conspicuous that hypercoagulability is in all likelihood the net result of these complicated effects on the membrane surface. Up to now in this setting the currently used laboratory approaches have failed to give a clear and reliable insight of what was going on. Moreover there are several pieces of evidence that this experimental approach is truly integrative. We identified one set of quantitative parameters: basal (endogenous) thrombin potential and the APC concentration able to halve the potential, or IC
50-APC. Thus such a laboratory phenotyping of one main part of the haemostatic system might well have an important clinical impact but could also allow us to raise new mechanistic hypotheses and to design new antithrombotic approaches.