Detection of elevated INR by thromboelastometry and thromboelastography in warfarin treated patients and healthy controls.
BACKGROUND
The diagnostic potential of whole blood viscoelastic tests thromboelastography (TEG®) and thromboelastometry (ROTEM®) to detect warfarin-induced INR elevation remains elusive.


METHODS
Viscoelastic tests were performed in 107 patients on warfarin and 89 healthy controls. Tests were activated by kaolin for TEG, and ellagic acid (INTEM) or tissue factor (EXTEM) for ROTEM.


RESULTS
Viscoelastic tests revealed significant differences in clotting profiles between controls and warfarin-treated patients. Compared with healthy controls, patients treated with warfarin had prolonged EXTEM clotting and TEG reaction time (p<0.001), both of which were also increased beyond the reference range. Increased INR values correlated with EXTEM CT (Spearman rho=0.87) and TEG R-time (rho=0.73). EXTEM CT had a sensitivity and specificity of 0.89 and 1.00, respectively, to detect elevated INR above 1.2 units, with a positive and negative predictive values (PPV and NPV) of 1.00 and 0.88, respectively. Similarly, TEG R-time had a sensitivity and specificity of 0.86 and 0.87, respectively, with a PPV of 0.89 and a NPV of 0.83. The corresponding receiver operator characteristic area under the curve was 0.99 (95% confidence interval [CI], 0.99 - 1.00) for EXTEM CT and 0.94 (95% CI, 0.91 - 0.97) for TEG R-time.


CONCLUSIONS
Tissue factor-activated viscoelastic testing (EXTEM) revealed individuals with warfarin-induced INR elevation accurately, while TEG - activated through the intrinsic pathway - still was of acceptable diagnostic value. Further studies are required to evaluate the diagnostic potential of viscoelastic tests in relation to standard laboratory tests in other mixed patient populations, where the PPV and NPV may be inferior.
Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Utrecht University Medical Center, Utrecht, The Netherlands.
David E
DE
Schmidt
Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Margareta
M
Holmström
Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ammar
A
Majeed
Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Doris
D
Näslin
Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Håkan
H
Wallén
Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Electronic address: anna.agren@karolinska.se.
Anna
A
Ågren
D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use; D016022:Case-Control Studies; D004610:Ellagic Acid; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods* / Q000706:statistics & numerical data; D007616:Kaolin; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012016:Reference Values; D013916:Thrombelastography / Q000379:methods* / Q000706:statistics & numerical data; D013925:Thromboplastin; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D004610:Ellagic Acid; D007616:Kaolin; D014859:Warfarin; D013925:Thromboplastin