Bivalirudin resistance in a patient on veno-venous extracorporeal membrane oxygenation with a therapeutic response to argatroban

BMJ Case Rep. 2020 Jan 7;13(1):e232262. doi: 10.1136/bcr-2019-232262.

Abstract

A 48-year-old male patient requiring extracorporeal membrane oxygenation (ECMO) support for hypoxaemic respiratory failure failed to achieve therapeutic anticoagulation with bivalirudin after continuous dose escalations, and continued to have recurrent fibrin stranding in the circuit over a 6-day course of treatment. Suspecting bivalirudin resistance, the patient was transitioned to argatroban and achieved a therapeutic response in less than 24 hours. The case describes the challenges of anticoagulation in ECMO supported patients. The interplay between bivalirudin metabolism, renal replacement therapy, and immunological effects leading to a heparin-like-effect, inflammatory mediators, and thrombotic burdens may all impact the clinical effect during bivalirudin therapy. The structural biochemistry of thrombin and bivalirudin likely plays a role in the presented patient's successful response to argatroban. Bivalirudin may fail at achieving therapeutic anticoagulation in patients with genetic thrombin mutations or structural defects that alter the binding pockets at the thrombin exosites.

Keywords: adult intensive care; mechanical ventilation; pharmacology and therapeutics; therapeutic indications; venous thromboembolism.

Publication types

  • Case Reports

MeSH terms

  • Anticoagulants / therapeutic use*
  • Arginine / analogs & derivatives
  • Combined Modality Therapy
  • Drug Resistance*
  • Extracorporeal Membrane Oxygenation*
  • Hirudins
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / therapeutic use*
  • Pipecolic Acids / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Respiratory Insufficiency / therapy*
  • Sulfonamides

Substances

  • Anticoagulants
  • Hirudins
  • Peptide Fragments
  • Pipecolic Acids
  • Recombinant Proteins
  • Sulfonamides
  • Arginine
  • argatroban
  • bivalirudin