On-Treatment Change in d-Dimer Is Associated With Differential Outcomes Among Therapeutic Dose Heparin-Treated Noncritically Ill Patients Hospitalized for COVID-19

Lana Wahid^{1

2}, Joshua D Froess³, Thomas L Ortel^{4

5

6}, Ryan Zarychanski⁷, Jeffrey S Berger⁸, Mary Cushman^{9

10}, Derek C Angus¹¹, Valerie Renard¹², Parisa Farahani¹, Steven Webb¹³, Anna Heath^{14

15}, Lucas C Godoy^{16

17}, Michael E Farkouh¹⁸, Judith S Hochman⁸, Matthew D Neal^#¹⁹, Patrick R Lawler^#^{20

21

22}

Affiliations

¹ Department of Medicine, Carilion Clinic, Roanoke, VA (L.W., P.F.).
² Department Internal of Medicine, Virginia Tech Carilion School of Medicine, Roanoke (L.W.).
³ Department of Epidemiology, School of Public Health (J.D.F.), University of Pittsburgh, PA.
⁴ Division of Hematology (T.L.O.), Duke University, Durham, NC.
⁵ Department of Medicine (T.L.O.), Duke University, Durham, NC.
⁶ Department of Pathology (T.L.O.), Duke University, Durham, NC.
⁷ University of Manitoba and CancerCare Manitoba, Canada (R.Z.).
⁸ Department of Medicine, New York University Grossman School of Medicine (J.S.B., J.S.H.).
⁹ Departments of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
¹⁰ Pathology and Laboratory Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
¹¹ Division of Critical Care Medicine (D.C.A.), University of Pittsburgh, PA.
¹² Hospital Medicine, Department of Medicine, Duke University Health, Durham, NC (V.R.).
¹³ Australian and New Zealand Intensive Care Research Centre, Monash University, Clayton, VIC, Australia (S.W.).
¹⁴ Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada (A.H.).
¹⁵ Division of Biostatistics, Dalla Lana School of Public Health (A.H.), University of Toronto, ON, Canada.
¹⁶ Peter Munk Cardiac Centre (L.C.G.), University of Toronto, ON, Canada.
¹⁷ Institute of Health Policy Management and Evaluation (L.C.G.), University of Toronto, ON, Canada.
¹⁸ Division of Cardiology, Cedars-Sinai Health System, Los Angeles, CA (M.E.F.).
¹⁹ Department of Surgery (M.D.N.), University of Pittsburgh, PA.
²⁰ Division of Cardiology (P.R.L.), University of Toronto, ON, Canada.
²¹ Division of Critical Care Medicine (P.R.L.), University of Toronto, ON, Canada.
²² Division of Cardiology, McGill University Health Centre, Montreal, QC, Canada (P.R.L.).

^# Contributed equally.

PMID: 39633573
PMCID: PMC11694890
DOI: 10.1161/ATVBAHA.124.321108

On-Treatment Change in d-Dimer Is Associated With Differential Outcomes Among Therapeutic Dose Heparin-Treated Noncritically Ill Patients Hospitalized for COVID-19

Lana Wahid et al. Arterioscler Thromb Vasc Biol. 2025 Jan.

. 2025 Jan;45(1):162-164.

doi: 10.1161/ATVBAHA.124.321108. Epub 2024 Dec 5.

Authors

Affiliations

¹ Department of Medicine, Carilion Clinic, Roanoke, VA (L.W., P.F.).
² Department Internal of Medicine, Virginia Tech Carilion School of Medicine, Roanoke (L.W.).
³ Department of Epidemiology, School of Public Health (J.D.F.), University of Pittsburgh, PA.
⁴ Division of Hematology (T.L.O.), Duke University, Durham, NC.
⁵ Department of Medicine (T.L.O.), Duke University, Durham, NC.
⁶ Department of Pathology (T.L.O.), Duke University, Durham, NC.
⁷ University of Manitoba and CancerCare Manitoba, Canada (R.Z.).
⁸ Department of Medicine, New York University Grossman School of Medicine (J.S.B., J.S.H.).
⁹ Departments of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
¹⁰ Pathology and Laboratory Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
¹¹ Division of Critical Care Medicine (D.C.A.), University of Pittsburgh, PA.
¹² Hospital Medicine, Department of Medicine, Duke University Health, Durham, NC (V.R.).
¹³ Australian and New Zealand Intensive Care Research Centre, Monash University, Clayton, VIC, Australia (S.W.).
¹⁴ Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada (A.H.).
¹⁵ Division of Biostatistics, Dalla Lana School of Public Health (A.H.), University of Toronto, ON, Canada.
¹⁶ Peter Munk Cardiac Centre (L.C.G.), University of Toronto, ON, Canada.
¹⁷ Institute of Health Policy Management and Evaluation (L.C.G.), University of Toronto, ON, Canada.
¹⁸ Division of Cardiology, Cedars-Sinai Health System, Los Angeles, CA (M.E.F.).
¹⁹ Department of Surgery (M.D.N.), University of Pittsburgh, PA.
²⁰ Division of Cardiology (P.R.L.), University of Toronto, ON, Canada.
²¹ Division of Critical Care Medicine (P.R.L.), University of Toronto, ON, Canada.
²² Division of Cardiology, McGill University Health Centre, Montreal, QC, Canada (P.R.L.).

^# Contributed equally.

PMID: 39633573
PMCID: PMC11694890
DOI: 10.1161/ATVBAHA.124.321108

Abstract

Trial registration: ClinicalTrials.gov NCT04372589.

Keywords: COVID-19; critical care; heparin; precision medicine; thromboinflammation.

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Conflict of interest statement

L. Wahid reports unrelated consulting fees from Dompe’. T.L. Ortel is supported by grants from the National Institutes of Health (NIH) and a contract with the CDC (Centers for Disease Control). He receives research support from Instrumentation Laboratory, Stago, and Siemens. He has received consulting fees from Sanofi and royalties from UpToDate. A. Heath is supported by a Canada Research Chair in Statistical Trial Design and the Natural Sciences and Engineering Research Council of Canada (award No. RGPIN-2021-03366). M.E. Farkouh receives grants from Novartis and AstraZeneca and is a consultant at Otitopic. J.S. Hochman serves as the study chair for ACTIV-4a (Accelerating COVID-19 Therapeutic Interventions and Vaccines-4a) under a National Heart, Lung, and Blood Institute–University of Pittsburgh grant subaward. M.D. Neal is supported by grants from the NIH, DoD (Department of Defense), and DARPA. He is the chief medical officer of Haima Therapeutics. He has received honoraria for consulting or advisory board participation at Octapharma, Haemonetics, and Instrumentation Laboratories. P.R. Lawler reports unrelated consulting fees from Novartis, CorEvitas, and Brigham and Women’s Hospital and unrelated royalties from McGraw-Hill Publishing. The other authors report no conflicts.

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References

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1. Goligher EC, Lawler PR, Jensen TP, et al. ; REMAP-CAP, ATTACC, and ACTIV-4a Investigators. Heterogeneous Treatment Effects of Therapeutic-Dose Heparin in Patients Hospitalized for COVID-19. JAMA. 2023. Apr 4;329(13):1066–1077. doi: 10.1001/jama.2023.3651. - DOI - PMC - PubMed
1. Lawler PR, Goligher EC, Berger JS, et al. ; ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators. Therapeutic anticoagulation with heparin in noncritically ill patients with COVID-19. N Engl J Med. 2021;385(9):790–802. - PMC - PubMed
1. Lawler PR, Hochman JS, Zarychanski R. What Are Adaptive Platform Clinical Trials and What Role May They Have in Cardiovascular Medicine? Circulation. 2022. Mar;145(9):629–632. doi: 10.1161/CIRCULATIONAHA.121.058113. Epub 2022 Feb 28. - DOI - PubMed

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On-Treatment Change in d-Dimer Is Associated With Differential Outcomes Among Therapeutic Dose Heparin-Treated Noncritically Ill Patients Hospitalized for COVID-19

Affiliations

On-Treatment Change in d-Dimer Is Associated With Differential Outcomes Among Therapeutic Dose Heparin-Treated Noncritically Ill Patients Hospitalized for COVID-19

Authors

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Abstract

Conflict of interest statement

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Publication types

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Grants and funding

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Medical