Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions

Stroke. 2017 Sep;48(9):2457-2463. doi: 10.1161/STROKEAHA.117.017981. Epub 2017 Aug 3.

Abstract

Background and purpose: In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation.

Methods: Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values.

Results: Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established.

Conclusions: Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070.

Keywords: anticoagulants; blood coagulation tests; dabigatran; emergency medicine; emergency treatment; rivaroxaban; stroke.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antithrombins / therapeutic use
  • Blood Coagulation Disorders / chemically induced
  • Blood Coagulation Disorders / diagnosis*
  • Blood Coagulation Tests*
  • Dabigatran / therapeutic use*
  • Emergencies
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Point-of-Care Testing
  • Prothrombin Time
  • Pyrazoles / therapeutic use*
  • Pyridones / therapeutic use*
  • Rivaroxaban / therapeutic use*
  • Sensitivity and Specificity
  • Stroke / drug therapy*
  • Thrombin Time
  • Thrombolytic Therapy

Substances

  • Antithrombins
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
  • Dabigatran

Associated data

  • ClinicalTrials.gov/NCT02371044
  • ClinicalTrials.gov/NCT02371070