title: Pathology consultation on monitoring direct thrombin inhibitors and overcoming their effects in bleeding patients.
abstract: OBJECTIVE
  Direct thrombin inhibitors (DTIs), a relatively new class of anticoagulants, present several challenges regarding monitoring of their anticoagulant effects and overcoming bleeding associated with their use. The aim of this article is to (1) briefly present the pharmacologic properties of currently available DTIs, (2) discuss approaches to laboratory assessment of these drugs, and (3) review management of bleeding associated with their use.
  
  
  METHODS
  Published literature on DTIs, including clinical trials, case reports, and experimental animal models, was reviewed. The primary authors also reviewed their first-hand experiences with DTI anticoagulation.
  
  
  RESULTS
  Based on the literature review and the practical experiences of the authors, suggestions for the monitoring of DTIs and algorithmic approaches for the management of DTI-associated bleeding were developed.
  
  
  CONCLUSIONS
  Routine coagulation assays (eg, the prothrombin time) show a relatively poor correlation with the degree of anticoagulation and DTI drug concentrations. Newer assays, such as the ecarin clotting time and dilute thrombin time, may be more useful in assessing DTI anticoagulation, but these assays are not yet widely available. Low-grade DTI-associated bleeds are best managed with cessation of the drug and supportive care, while higher-grade and/or life-threatening bleeds may best be reversed by active drug removal (eg, via the administration of activated charcoal or hemodialysis). At present there is little evidence to suggest that transfusion products such as factor concentrates or thawed plasma are of any particular benefit in DTI reversal; however, these products may play a supportive role in the management of bleeding.
authors.affiliation: 333 Cedar St, PO Box 208035, New Haven, CT 06520; christopher.tormey@yale.edu.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Winkler
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Tormey
mesh_terms: D000368:Aged; D000465:Algorithms; D000818:Animals; D000991:Antithrombins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D062787:Drug Overdose; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000628:therapy*; D006489:Hemostatic Techniques; D006801:Humans; D010336:Pathology; D012017:Referral and Consultation
chemical_list: D000991:Antithrombins
keywords: Direct thrombin inhibitors; Laboratory monitoring; Pathology consultation; Transfusion therapy