From laboratory to clinical practice: Dabigatran effects on thrombin generation and coagulation in patient samples.

Abstract

INTRODUCTION:

Dabigatran (Dabi) is not routinely monitored. However, in emergency cases quantitative assessment is required and laboratories must provide suitable tests at all hours. Little is known about Dabi effects on thrombin generation.

MATERIALS AND METHODS:

Patient samples (n=241) were analyzed for functional Dabi concentrations (Dabi-TT) using a combination of the Hemoclot Thrombin Inhibitors assay (HTI®) and, for samples with low levels, undiluted thrombin time (TT). Results were compared to prothrombin time (PT) and activated partial thromboplastin time (APTT). In 49 samples Dabi effects were further investigated with Calibrated Automated Thrombogram (CAT®) for thrombin generation and with Russell's viper venom time (RVVT), prothrombinase-induced clotting time (PiCT®), chromogenic Anti-IIa® and ecarin clotting assay (ECA®). Fibrinogen and D dimer were assessed to reflect the coagulation status of the patient. A subset of these samples (n=21) were also analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

RESULTS:

Dabi-TT correlated with RVVT (R(2)=0.49), PiCT® (R(2)=0.73), ECA® (R(2)=0.89), Anti-IIa® (R(2)=0.90) and LC-MS/MS (R(2)=0.81). APTT correlated curvi-linearly with Dabi-TT (R(2)=0.71), but was normal in many cases (18/70) despite Dabi-TT>40ng/mL. There was no association between Dabi-TT and fibrinogen or D dimer levels. Increasing Dabi concentrations prolonged lag time (R(2)=0.54) and, surprisingly, elevated the ETP and Peak of CAT® (p<0.001).

CONCLUSIONS:

Thrombin-specific tests measure Dabi accurately, whereas coagulation time based assays depend more on other factors. The enhanced thrombin generation in Dabi-treated patients may predict clinically relevant hypercoagulability and warrants further investigation.

• Authors: Tuukka A Helin, Marja Lemponen, Paul Hjemdahl, Yuko Rönquist-Nii, Riitta Lassila, Lotta Joutsi-Korhonen
• Journal: Thrombosis research (Thromb Res) Vol. 136 Issue 1 Pg. 154-60 (Jul 2015) ISSN: 1879-2472 [Electronic] United States
• PMID: 25981140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antithrombins
• Thrombin
• Dabigatran

Topics

• Antithrombins (pharmacology)
• Blood Coagulation (drug effects)
• Blood Coagulation Tests
• Dabigatran (pharmacology)
• Drug Monitoring
• Female
• Humans
• Partial Thromboplastin Time
• Prothrombin Time
• Tandem Mass Spectrometry
• Thrombin (antagonists & inhibitors, metabolism)
• Thrombin Time