Résumé
Background: In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotoninrelease assay-positive (SRA 1) status. A trend to a lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (fi ve vs 12 patients, P = .14), which was statistically signifi cant (three vs 12 patients, P = .046) in a prespecifi ed per-protocol analysis that excluded patients with DVT at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis may reduce HIT frequency in patients in the ICU. Methods: In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to the study drug and other open-label heparin, to determine whether the study drug plausibly explained seroconversion to SRA 1 status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT. Results: HIT-associated thrombosis occurred in 10 of 17 patients (58.8%) (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events (P = .020), including less seroconversion (P = .058) and less breakthrough of thrombocytopenia/thrombosis (P = .032). Antiplatelet factor 4/heparin IgG antibodies by enzyme-linked immunosorbent assay were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%, P < .001). One patient with HIT-associated DVT died after UFH bolus (anaphylactoid reaction), whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeuticdose UFH. Conclusions: The lower risk of HIT in patients in the ICU receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.
| Langue d'origine | English |
|---|---|
| Pages (de-à) | 848-858 |
| Nombre de pages | 11 |
| Journal | Chest |
| Volume | 144 |
| Numéro de publication | 3 |
| DOI | |
| Statut de publication | Published - sept. 2013 |
Note bibliographique
Funding Information:Funding/Support: PROTECT was funded by the Canadian Institutes of Health Research and the Australian and New Zealand College of Anesthetists Research Foundation. We also acknowledge the support of the Heart and Stroke Foundation of Ontario to Dr Warkentin [ Grant T6950 ].
Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Warkentin has served as consultant and/or has received honoraria for speaking on behalf of companies that manufacture LMWH (Pfizer Canada, Inc; Sanofi), heparin-coated grafts (W. L. Gore & Associates Inc), heparin-like molecules (Paringenix Inc), and non-heparin anticoagulants for management of HIT (Canyon Pharmaceuticals, GlaxoSmithKline). His institution has received funding from GlaxoSmithKline and Instrumentation Laboratories, as well as from the Heart and Stroke Foundation of Ontario for research related to HIT. Dr Warkentin has also received royalties from Informa for the book, Heparin-Induced Thrombocytopenia. He receives compensation for medicolegal consultation and testimony regarding thrombocytopenic disorders including HIT. Ms Sheppard is employed through grants received from the Heart and Stroke Foundation of Ontario for research pertaining to HIT. Dr Ernest has served as a consultant to and received grant monies from Hospira, Inc, a company that manufactures heparin. Dr Vlahakis is employed by Genentech, a company that manufactures thrombolytic agents (alteplase, tenecteplase). Dr Crowther has sat on advisory boards for Leo Pharma Inc; Pfizer Inc; Bayer; Boehringer-Ingelheim GmbH; Alexion Pharmaceuticals, Inc; CSL Behring; and Artisan Pharma, Inc. Dr Crowther has prepared educational materials for Pfizer Inc; Octapharma Plasma, Inc; and CSL Behring. Dr Crowther has provided expert testimony for Bayer and for Merck & Co. Dr Crowther holds a Career Investigator award from the Heart and Stroke Foundation of Ontario, and is the Leo Pharma Chair in Thromboembolism Research at McMaster University. His institution has received funding for research projects from Boehringer-Ingelheim, Octapharma Plasma, Inc; Pfizer Inc; and Leo Pharma Inc. Dr Crowther has received funding for presentations from Leo Pharma Inc and CSL Behring. Ms Heels-Ansdell and Drs Marshall, McIntyre, Rocha, Mehta, Davies, Bersten, Crozier, Hall, Wood, Poirier, and Cook have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
ASJC Scopus Subject Areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine