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

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.

Comparison of the ecarin chromogenic assay and different aPTT assays for the measurement of argatroban concentrations in plasma from healthy individuals and from coagulation factor deficient patients.

INTRODUCTION: The aim of this study was to assess the usefulness of different aPTT assays and the ecarin chromogenic assay reaction time (ECA) for measurement of argatroban concentration in plasma from healthy persons as well as in different patient subgroups. METHODS: We spiked plasma samples from healthy individuals, patients under oral anticoagulation (OAT) or with liver dysfunction (LD) with increasing argatroban concentrations (0-2000 ng/ml) and performed 4 different aPTTs assays and the ECA. RESULTS: Depending on argatroban concentrations aPTTs increased in a curvilinear fashion; in plasma from healthy individuals means of calculated argatroban concentration at 2-fold aPTT differed extensively depending on the aPTT reagent used (725 ng/ml to 1136 ng/ml) and were even more pronounced in plasma from coagulation factor deficient patients (460 ng/ml in patients with LD vs. 1172 ng/ml in patients with OAT), whereas ECA showed linear argatroban influence and reliable results in all subgroups. CONCLUSIONS: Because of wide differences in aPTT measurements depending on the aPTT reagent used, interindividual variations and different clinical conditions the aPTT is not the method of choice for monitoring argatroban and the ECA should be preferred.