Influence of direct thrombin inhibitor argatroban on coagulation assays in healthy individuals, patients under oral anticoagulation therapy and patients with liver dysfunction.

Abstract

We assumed that argatroban, a direct thrombin inhibitor, has a strong influence on different coagulation tests which is even more pronounced in patients with an established reduced factor activity like those under oral anticoagulation therapy or with liver dysfunction. To validate this influence we spiked plasma samples from healthy individuals, patients under oral anticoagulation therapy or with liver dysfunction with increasing argatroban concentrations (0-2000 ng/ml) and performed routine laboratory coagulation tests. Consequently, prothrombin time, activated partial thromboplastin time, thrombin time, batroxobin time, coagulation factor activity (FII-FXIII), protein S (activity), protein C (chromogen) and fibrinogen (derived and Clauss fibrinogen method) were measured. Furthermore, the influence of argatroban on the induced platelet aggregation was evaluated. Argatroban interference on standard coagulation assays differed markedly depending on the different subgroups of patients investigated. Prolongation of prothrombin time by argatroban (at 2000 ng/ml 2.7-fold in healthy persons) was significantly higher in oral anticoagulation therapy (3.9-fold) and even more pronounced in liver dysfunction (6.0-fold). The fibrinogen concentration was determined falsely even at low-argatroban concentrations using functional methods in healthy persons and all patient subgroups. The influence of argatroban on standard laboratory coagulation tests is significantly increased by a preexisting factor deficiency. Functional fibrinogen measurement may be helpful to assess in-vivo fibrinogen function but should be avoided to evaluate fibrinogen concentration in argatroban treated patients. Argatroban had no influence on chromogenic protein C measurement, batroxobin time and induced platelet aggregation. Knowledge of argatroban interference is a prerequisite for the reliable interpretation of coagulation assays.