Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis

Jerrold H Levy; Roman M Sniecinski; Bianca Rocca; Kamrouz Ghadimi; James Douketis; Corinne Frere; Julie Helms; Toshiaki Iba; Andreas Koster; Tara K Lech; Cheryl L Maier; Mathew D Neal; Ecatarina Scarlestscu; Alex Spyropoulos; Marie E Steiner; Alfonso J Tafur; Kenichi A Tanaka; Jean M Connors

doi:10.1016/j.jtha.2023.08.013

Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis

J Thromb Haemost. 2023 Dec;21(12):3649-3657. doi: 10.1016/j.jtha.2023.08.013. Epub 2023 Aug 22.

Authors

Jerrold H Levy¹, Roman M Sniecinski², Bianca Rocca³, Kamrouz Ghadimi⁴, James Douketis⁵, Corinne Frere⁶, Julie Helms⁷, Toshiaki Iba⁸, Andreas Koster⁹, Tara K Lech¹⁰, Cheryl L Maier¹¹, Mathew D Neal¹², Ecatarina Scarlestscu¹³, Alex Spyropoulos¹⁴, Marie E Steiner¹⁵, Alfonso J Tafur¹⁶, Kenichi A Tanaka¹⁷, Jean M Connors¹⁸

Affiliations

¹ Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address: jerrold.levy@duke.edu.
² Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.
³ Department of Safety and Bioethics-Section of Pharmacology, Catholic University School of Medicine, Rome, Italy.
⁴ Department of Anesthesiology, Divisions of Cardiothoracic Anesthesiology and Critical Care Medicine, Clinical Research Unit, Duke University School of Medicine, Durham, North Carolina, USA.
⁵ Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
⁶ UMRS 1166, Sorbonne Université, Pitié-Salpêtrière Hospital, Paris, France.
⁷ University Hospital, Medical Intensive Care Unit, Nouvel Hôpital Civil, Strasbourg, France; French National Institute of Health and Medical Research, UMR 1260, Regenerative Nanomedicine, FMTS, Strasbourg, France.
⁸ Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁹ Institute of Anesthesiology and Pain Therapy, Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
¹⁰ Division of Pharmacy, Beth Israel Lahey Health, Westwood, Massachusetts, USA.
¹¹ Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
¹² Department of Surgery, Trauma and Transfusion Medicine Research Center, University of Pittsburgh, Pittsburgh, USA.
¹³ Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, University of Medicine and Pharmacy "Carol Davila," Bucharest, Bucharest, Romania.
¹⁴ Department of Medicine, Anticoagulation and Clinical Thrombosis Service, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA; Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA.
¹⁵ Department of Pediatrics, Divisions of Hematology/Oncology and Critical Care, University of Minnesota, Minneapolis, Minnesota, USA.
¹⁶ Department of Medicine, Vascular Medicine, NorthShore University Health System, Evanston, Illinois, USA; Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
¹⁷ Department of Anesthesiology, University of Oklahoma School of Medicine, Oklahoma City, Oklahoma, USA.
¹⁸ Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 37619694
DOI: 10.1016/j.jtha.2023.08.013

Abstract

The term heparin resistance (HR) is used by clinicians without specific criteria. We performed a literature search and surveyed our SSC membership to better define the term when applied to medical and intensive care unit patients. The most common heparin dosing strategy reported in the literature (53%) and by survey respondents (80.4%) was the use of weight-based dosing. Heparin monitoring results were similar based on the proportion of publications and respondents that reported the use of anti-Xa and activated partial thromboplastin time. The most common literature definition of HR was >35 000 U/d, but no consensus was reported among survey respondents regarding weight-based and the total dose of heparin when determining resistance. Respondent consensus on treating HR included antithrombin supplementation, direct thrombin inhibitors, or administering more heparin as the strategies available for treating HR. A range of definitions for HR exist. Given the common use of heparin weight-based dosing, future publications employing the term HR should include weight-based definitions, monitoring assay, and target level used. Further work is needed to develop a consensus for defining HR.

Keywords: COVID-19; ECMO; anticoagulation; heparin; resistance; sensitivity.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anticoagulants / adverse effects
Antithrombins / therapeutic use
Communication
Critical Care
Hemostasis
Heparin* / adverse effects
Humans
Partial Thromboplastin Time
Thrombosis* / drug therapy

Substances

Heparin
Anticoagulants
Antithrombins