PB1187 - High plasma dabigatran levels causing falsely low fibrinogen results: a report of two cases

Background: Direct oral auto-coagulants (DOACs) have been in regular use for over a decade. These drugs can interfere with several routinely performed coagulation assays to variable degrees, dependent on assay type, DOAC type and concentration, and test principle.

Aims: We describe two cases where excessively high levels of plasma dabigatran caused falsely low fibrinogen results in the Clauss assay. These cases draw attention to the need for added vigilance in monitoring fibrinogen levels by standard methods in the presence of supra-therapeutic plasma levels of dabigatran.

Methods: Routine assays included prothrombin time, activated partial thromboplastin time, Clauss fibrinogen and dabigatran levels using reagents of Recombiplastin 2G, Synthasil, Q.F.A. Thrombin and Direct Thrombin Inhibitor assay, respectively, on the ACLTOP analyser. Clauss fibrinogen was also measured on a STA-R analysers with Liquid Fibrinogen, including multiple sample dilutions in Case 1. In Case 2, routine assays were repeated after treatment of plasma with activated charcoal (DOAC Stop).

Results: Case 1 had a dabigatran level of 1212ng/mL on presentation which rose to 2161ng/mL within 24 hours. Fibrinogen fell from from 2.3g/L to 1.0g/L on the ACLTOP at standard 1/10 dilution. STA-R Fibrinogen fell from 2.7g/L to 2.0g/L at standard 1/20 dilution. The latter sample read 0.4g/L at 1/10 dilution, and plateaued at 3.6/3.7g/L at 1/40 and 1/60 dilutions. Case 2 had a dabigatran level of 4422ng/mL at presentation, with fibrinogen of 0.4g/L (ACLTOP) and 1.2g/L (STA-R). After 24 hours, including Praxbind treatment, the dabigatran level was 1286ng/mL and ACLTOP fibrinogen 4.1g/L. Several previously tested samples were retested after treatment with DOAC Stop, showing levels from 4.4g/L to 5.0g/L, confirming previously measured levels to be large underestimates.

Conclusion(s): These cases demonstrate that very high dabigatran levels may cause falsely reduced Clauss fibrinogen levels, and laboratories need strategies of serial plasma dilutions and/or DOAC Stop treatment to obtain more accurate levels.