Does the Russell Viper Venom time test provide a rapid estimation of the intensity of oral anticoagulation? A cohort study.
BACKGROUND
Dilute Russell Viper Venom Time (DRVV-T) might be useful in urgent settings for screening patients on Non-VKA Oral Anticoagulants (NOACs).


OBJECTIVE
To compare the accuracy of DRVV-T with gold standard assays for the assessment of pharmacodynamics of dabigatran, rivaroxaban and vitamin K antagonist (VKA) in plasma samples from patients.


METHODS
Sixty rivaroxaban, 48 dabigatran and 50 VKA samples from patients were included. DRVV-T was performed in all groups using STA®-Staclot®DRVV-Screen and -Confirm. For NOACs, PT and aPTT were performed using different reagents while plasma drug concentrations were measured by liquid mass-spectrometry (LC-MS/MS). For VKA, INR was performed using RecombiPlasTin 2G®.


RESULTS
For NOACs, correlations between calibrated STA®-Staclot®DRVV-Confirm and LC-MS/MS (rs=0.88 and 0.97 for rivaroxaban and dabigatran, respectively) were higher than the ones obtained with STA®-Staclot®DRVV-Screen (rs=0.87 and 0.91), PT (rs=0.83 to 0.86) or aPTT (rs=0.84 to 0.89). Bland Altman analyses showed that calibrated DRVV-T methods tend to overestimate plasma concentrations of NOACs. ROC curves revealed that cut-off to exclude supra-therapeutic levels at Ctrough (i.e. 200ng/mL) are different for dabigatran and rivaroxaban. Neither STA®-Staclot®DRVV-Screen nor -Confirm correlated sufficiently with the intensity of VKA therapy (rs=0.35 and 0.52).


CONCLUSIONS
STA®-Staclot®DRVV-Confirm provides a rapid estimation of the intensity of anticoagulation with rivaroxaban or dabigatran without specific calibrators. At Ctrough, thresholds for rivaroxaban and dabigatran can be used to identify supra-therapeutic plasma level. However, this test cannot differentiate the nature of the NOACs. The development of a point-of-care device optimising this method would be of particular interest in emergency situations.
Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium. Electronic address: jonathan.douxfils@unamur.be.
Jonathan
J
Douxfils
Haematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium.
Bernard
B
Chatelain
Department of Clinical Pharmacology, Karolinska University Hospital and Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Paul
P
Hjemdahl
Haematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium.
Bérangère
B
Devalet
Haematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium.
Anne-Laure
AL
Sennesael
Laboratory of Clinical Chemistry, Saint-Luc University Hospital, Université catholique de Louvain, Brussels, Belgium.
Pierre
P
Wallemacq
Department of Clinical Pharmacology, Karolinska University Hospital and Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Yuko
Y
Rönquist-Nii
Department of Clinical Pharmacology, Karolinska University Hospital and Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Anton
A
Pohanka
Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium.
Jean-Michel
JM
Dogné
Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium; Haematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium.
François
F
Mullier
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069604:Dabigatran / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D019934:International Normalized Ratio; D013058:Mass Spectrometry; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D012372:ROC Curve; D012189:Retrospective Studies; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013923:Thromboembolism / Q000453:epidemiology / Q000517:prevention & control; D013997:Time Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D014812:Vitamin K; D000069552:Rivaroxaban; D000069604:Dabigatran