[Potential Application of Fibrinogen Measurement Based on the Clauss Assay to Monitoring of Dabigatran]

A direct thrombin inhibitor (DTI), dabigatran was expected to be available for therapeutic use without mon- itoring. However, a number of severe bleedings occurring in patients on medication with dabigatran have been reported. The impact of dabigatran concentrations on major bleeding risk has also been revealed. Therefore, the significance of monitoring of dabigatran is of considerable interest. Hemoclot thrombin inhib- itor assay enables quantification of dabigatran concentrations but is not yet routinely available for clinical la- boratories in Japan. Based on spiking experiments with another DTI, argatroban, we previously demon- strated that the discrepancy in resulting quantification of fibrinogen concentrations between two different thrombin concentrations used in the Clauss assay may enable monitoring of DTIs. In the present study, analogous experiments using dabigatran were carried out, providing similar findings. The measured values of fibrinogen in the presence of dabigatran were similar to those in the absence of dabigatran when assayed using the high thrombin concentration (high-thrombin). The measured values of fibrinogen decreased in parallel with the increase in dabigatran concentrations when assayed using the low thrombin concentration (low-thrombin). Fibrinogen ratio, which is calculated by dividing the fibrinogen value measured with high- thrombin by that measured with low-thrombin, increased more sensitively at the high range of dabigatran concentrations than at the low range. Our observations suggest that the fibrinogen measurement based on the Clauss assay is practically applicable to monitoring of dabigatran especially for prediction of the bleeding risk. [Original].