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

Helin, Tuukka; Lemponen, Marja; Hjemdahl, Paul; Rönquist-Nii, Yuko; Lassila, Riitta; Joutsi‐Korhonen, Lotta

doi:10.1016/j.thromres.2015.04.032

Cited by 21 publications

(24 citation statements)

References 36 publications

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“…The RVVT is sensitive to low concentrations of dabigatran. Dabigatran concentrations below 40 ng/mL prolong the RVVT in 72% of plasma samples [58]. Rivaroxaban prolongs much more the RV-VT using reagents with small phospholipid content compared with apixaban, while there is no difference in the RVVT if reagents with high phospholipid content are used.…”

Section: Effect Of Doacs On Results Of Thrombophilia Testing Lupus Anmentioning

confidence: 94%

“…Both APTTand RVVT-based assay are affected by DOACs. It was shown that dabigatran prolongs the RVVT in an almost linear manner, although the correlation was not potent [58]. The RVVT is sensitive to low concentrations of dabigatran.…”

Section: Effect Of Doacs On Results Of Thrombophilia Testing Lupus Anmentioning

confidence: 97%

“…Linear dose response is followed by flattening at about 300 ng/mL [62]. The percentage of normal APTT samples with dabigatran concentrations of 40-160 ng/mL may reach 26% [58]. The APTT was always prolonged when dabigatran concentrations exceeded 160 ng/mL [58].…”

Section: Effect Of Doacs On Routine Coagulation Testsmentioning

confidence: 97%

“…The percentage of normal APTT samples with dabigatran concentrations of 40-160 ng/mL may reach 26% [58]. The APTT was always prolonged when dabigatran concentrations exceeded 160 ng/mL [58]. Dabigatran may induce hypercoagulable effects by inhibiting thrombomodulin-mediated activation of protein C, which may be the cause of normal APTT in individuals with high dabigatran concentrations [58].…”

Section: Effect Of Doacs On Routine Coagulation Testsmentioning

confidence: 99%

“…The Owren-type PT may be normal in up to about ¾ samples with dabigatran of 40 ng/ml or above [58]. The PT is not recommended to quantify or even detect dabigatran [59].…”

Section: Effect Of Doacs On Routine Coagulation Testsmentioning

confidence: 99%

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Direct Oral Anticoagulants in Patients with Thrombophilia: Challenges in Diagnostic Evaluation and Treatment

Undas

Góralczyk

2016

Adv Clin Exp Med

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Section: Effect Of Doacs On Results Of Thrombophilia Testing Lupus Anmentioning

confidence: 94%

Section: Effect Of Doacs On Results Of Thrombophilia Testing Lupus Anmentioning

confidence: 97%

Section: Effect Of Doacs On Routine Coagulation Testsmentioning

confidence: 97%

Section: Effect Of Doacs On Routine Coagulation Testsmentioning

confidence: 99%

“…The Owren-type PT may be normal in up to about ¾ samples with dabigatran of 40 ng/ml or above [58]. The PT is not recommended to quantify or even detect dabigatran [59].…”

Section: Effect Of Doacs On Routine Coagulation Testsmentioning

confidence: 99%

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Direct Oral Anticoagulants in Patients with Thrombophilia: Challenges in Diagnostic Evaluation and Treatment

Undas

Góralczyk

2016

Adv Clin Exp Med

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Assessment of the effect of direct oral anticoagulants dabigatran, rivaroxaban, and apixaban in healthy male volunteers using a thrombin generation assay

Artang

Anderson

Riley

et al. 2017

Research and Practice in Thrombosis and Haemostasis

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Essentials The value of thrombin generation assay (TGA) in monitoring direct oral anticoagulants (DOAC) is not well defined.TGA parameters were measured and correlated to DOAC levels in 10 healthy volunteers after oral intake of DOACs.Lag time is the only sensitive TGA parameter across different DOACs, dabigatran, rivaroxaban and apixaban.Endogenous thrombin potential had weak correlation with DOAC levels and not suitable as stand‐alone parameter. BackgroundThere are clinical situations where monitoring direct oral anticoagulants (DOACs) may be useful. The clinical application of thrombin generation assay (TGA) in monitoring the effect of DOACs has not been well established. An ex vivo study was performed to systematically evaluate the anticoagulant effect of dabigatran, rivaroxaban and apixaban on each individual TGA parameter through serial measurements over time to assess suitability of these parameters for monitoring the anticoagulant effect of DOACs.MethodsTen healthy volunteers were given oral dabigatran 150 mg, rivaroxaban 20 mg, or apixaban 10 mg once. TGA parameters lag time, endogenous Thrombin potential (ETP), and thrombin peak height, time to peak, and velocity index were measured at times 0, 2, 4, and 24 hours after intake of DOAC. TGA parameters and DOAC concentrations were correlated.ResultsThe lag time was significantly correlated with all DOAC concentrations (r ≥ .81, P < .0001 for all). Thrombin peak height best correlated with direct Factor Xa inhibitor (FXa) concentrations in nonlinear fashion (R² ≥ .87). ETP was weakly correlated with DOAC levels (r ≤ .68). Besides lag time, the other TGA parameters were not significantly altered over time by dabigatran.ConclusionLag time was the only sensitive TGA parameter across the different classes of DOACs evaluated. Thrombin peak height was strongly correlated to FXa inhibitor concentrations and potentially a useful parameter to monitor FXa inhibitors at low concentrations. ETP had a weak correlation with achieved DOAC concentrations and is likely less suitable for assessment of DOAC effect as a stand‐alone parameter.

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Anticoagulated patients exhibit intact endogenous thrombin potential using ST Genesia unlike the Calibrated Automated Thrombogram

Helin

Lemponen

Lassila

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Background The thrombin generation (TG) assay is a feasible but labor‐intensive method for detecting global coagulation. It enables comprehensive assessment of anticoagulation, while drug‐specific assays assess only exposure. Traditionally, the Calibrated Automated Thrombogram (CAT) has been used, however the ST Genesia (Diagnostica Stago) allows automated evaluation. Objective We aimed to observe coagulation using the ST Genesia and compare the data with those of CAT in anticoagulated patients. Patients and methods In total, 43 frozen‐thawed samples were studied using DrugScreen to assess direct oral anticoagulants (DOACs), warfarin, and low‐molecular‐weight heparin. Twenty samples (nine rivaroxaban, five apixaban, three warfarin, and three heparin) were also compared using CAT (5 pM tissue factor). Results TG reduction in DrugScreen depended on the specific drug and modestly correlated with DOAC levels (lag time R2 = 0.36; peak R2 = 0.50). The best correlation was observed with peak thrombin and rivaroxaban‐specified anti–activated factor X (anti‐Xa) activity (R2 = 0.60). When comparing ST Genesia with CAT, only the results for apixaban concorded (R2 = 0.97). Unlike CAT, ST Genesia yielded a normal endogenous thrombin potential (ETP) in 77% (24/31) activated factor X inhibitor cases, and it failed to give readouts at international normalized ratio (INR) ≥4.5 and at anti‐Xa ≥1.0 IU/mL. Conclusion The ST Genesia data did not correlate with CAT, but it was independently associated with INR, anti‐Xa, and DOAC concentrations. The lag time and peak responses were similar; the major differences were that ST Genesia showed no ETP effect of DOACs and failed to give readout at high INR or anti‐Xa activity.

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

Cited by 21 publications

References 36 publications

Direct Oral Anticoagulants in Patients with Thrombophilia: Challenges in Diagnostic Evaluation and Treatment

Direct Oral Anticoagulants in Patients with Thrombophilia: Challenges in Diagnostic Evaluation and Treatment

Assessment of the effect of direct oral anticoagulants dabigatran, rivaroxaban, and apixaban in healthy male volunteers using a thrombin generation assay

Anticoagulated patients exhibit intact endogenous thrombin potential using ST Genesia unlike the Calibrated Automated Thrombogram

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