Thrombinography shows acquired resistance to activated protein C in patients with lupus anticoagulants

In patients with lupus anticoagulants (LA), acquired resistance to activated protein C (APC) is difficult to demonstrate with clot-based assays due to the presence of the anticoagulant. Via the conversion of a fluorogenic substrate (thrombinography), we. monitored the complete process of thrombin formation and decay and its delimitation by the protein C system in eight consecutive LA-patients without anticoagulant therapy and non-carriers of the V Leiden polymorph ism. Thrombin generation was triggered in platelet-poor and platelet-rich plasma by recalcification in the presence of a low concentration of tissue factor.In 7 out of 8 patients we observed a long lag-time before the thrombin burst, (LA effect) together with a marked inability of APC to diminish the thrombin activity-The lag-phase was however prolonged to some degree by APC. The effects were more outspoken in the presence. of phospholipids from patients' platelets than-with added phospholipids.Thrombinography thus demonstrates APC resistance in LA-patients despite the occurrence of long lag-times (clotting times). The amount of thrombin activity generated, in the presence of APC could be a better indicator of the thrombotic risk than the moment at which the thrombin burst starts.