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Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants01:18

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Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
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Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood
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Optimizing warfarin reversal--an ex vivo study.

A Gatt1, A Riddell, J J van Veen

  • 1The Royal Free Hospital Haemophilia Centre & Thrombosis Unit, Hampstead, London, UK. alexander.gatt@royalfree.nhs.uk

Journal of Thrombosis and Haemostasis : JTH
|July 7, 2009
PubMed
Summary
This summary is machine-generated.

Prothrombin complex concentrates (PCCs) effectively reverse warfarin, with specific doses normalizing International Normalized Ratios (INRs) and thrombin generation. This simplifies warfarin reversal, potentially reducing costs and thrombotic risk.

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Area of Science:

  • Hematology
  • Pharmacology
  • Clinical Medicine

Background:

  • Warfarin reversal is a frequent clinical necessity.
  • Current reversal agents include vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), and activated factor VII.
  • The optimal dosing strategy for PCCs remains undefined.

Purpose of the Study:

  • To compare warfarin reversal efficacy of FFP, recombinant FVIIa (rFVIIa), and PCC.
  • To investigate the correlation between supratherapeutic International Normalized Ratios (INRs) and thrombin generation (TG).
  • To determine ideal PCC concentrations for reversing various INR thresholds.

Main Methods:

  • Ex vivo analysis of warfarinized plasma using calibrated automated thrombography.
  • Assessment of FFP, rFVIIa, and Beriplex P/N (a PCC) effects on INR and TG.
  • In vitro spiking of plasma with varying Beriplex P/N concentrations.

Main Results:

  • Beriplex P/N was the sole agent to fully normalize TG and INR.
  • Endogenous thrombin potential (ETP) and peak thrombin correlated negatively with INR.
  • A PCC dose of 30 IU/kg normalized ETP and INR for INRs ≥ 4.0; 20 IU/kg sufficed for INRs 2.0-3.9.
  • Higher PCC doses induced hypercoagulable TG patterns.

Conclusions:

  • A simplified warfarin reversal strategy using two PCC doses based on INR is proposed.
  • This approach may lead to cost savings and decreased thrombotic risk.
  • Further investigation into standardized PCC dosing for warfarin reversal is warranted.