What question did this study set out to answer?

To evaluate whether six coagulation factor concentrates can reverse dabigatran-induced bleeding in a rat model and assess whether standard coagulation assays reflect bleeding reduction.

April 8, 2014AnesthesiologyOpen Access

Reversal of Dabigatran-induced Bleeding by Coagulation Factor Concentrates in a Rat-tail Bleeding Model and Lack of Effect on Assays of Coagulation

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Why the study?

Do coagulation factor concentrates reduce bleeding induced by dabigatran in a rat-tail bleeding model?

Population

Rat-tail bleeding model treated with oral dabigatran etexilate and human plasma spiked with dabigatran

Comparison

Coagulation factor concentrates vs Dabigatran alone (baseline prolonged bleeding)

Design

Preclinical

Follow-up

30 min

Authors

JRJoanne van RynCross-Cutting Cardiology JSJohanna SchurerBoehringer Ingelheim (Germany)MKMonika Kink‐EibandBoehringer Ingelheim (Germany)

Discussion

Member takes

Implication

May reduce dabigatran bleeding in rat models; leaves open clinical translation and requires human trials.

Key Points

To evaluate whether six coagulation factor concentrates can reverse dabigatran-induced bleeding in a rat model and assess whether standard coagulation assays reflect bleeding reduction.
Administered oral dabigatran etexilate (30 mg/kg) to rats (n = 5 to 8 per group) and tested bleeding time reduction following infusion of 3-factor PCCs, 4-factor PCCs, aPCC, and rFVIIa.
Evaluated in vitro thrombin generation in human plasma (n = 5) spiked with therapeutic (200 ng/ml) and supratherapeutic (600 and 1,000 ng/ml) dabigatran concentrations alongside routine coagulation assays.
Dabigatran prolonged bleeding time approximately three-fold, which was significantly reduced over 30 minutes by Beriplex, Octaplex, Profilnine, Bebulin, FEIBA, and NovoSeven (P < 0.001).
Coagulation assays were prolonged three- to eight-fold over baseline (P = 0.01), but none of the concentrates produced consistent assay changes that predicted bleeding reduction.
Thrombin generation reversal depended on drug and concentrate concentrations, normalizing at 200 ng/ml dabigatran for most concentrates but failing at 600 and 1,000 ng/ml.

Structured PICO

Do coagulation factor concentrates reduce bleeding induced by dabigatran in a rat-tail bleeding model?

Population

Rat-tail bleeding model (n=5 to 8 per group) treated with oral dabigatran etexilate (30 mg/kg) and human plasma (n=5) spiked with dabigatran

Intervention

Coagulation factor concentrates (three-factor PCCs [Profilnine, Bebulin], four-factor PCCs [Beriplex, Octaplex], activated PCC [Factor Eight Inhibitor Bypassing Activity], and recombinant factor VIIa [NovoSeven])

Comparator

Dabigatran alone (baseline prolonged bleeding)

Outcome

Reduction in bleeding time over 30 minsurrogate

Coagulation factor concentrates can reduce bleeding induced by high doses of dabigatran in an animal model, but routine coagulation assays do not reliably predict this reversal effect.

Cite This Study

Ryn et al. (2014) studied this question.

synapsesocial.com/papers/6a70e76e660549caf2c58bb3 https://doi.org/10.1097/aln.0000000000000255

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Reversal of Dabigatran-induced Bleeding by Coagulation Factor Concentrates in a Rat-tail Bleeding Model and Lack of Effect on Assays of Coagulation

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Reversal of Dabigatran-induced Bleeding by Coagulation Factor Concentrates in a Rat-tail Bleeding Model and Lack of Effect on Assays of Coagulation

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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