A pair of studies recently published in the New England Journal of Medicine (NEJM) report that therapeutic-dose anticoagulation with heparin appears to improve outcomes for non-critically ill patients hospitalized with COVID-19, but not for critically ill patients hospitalized with the disease.

The studies are the result of an international, multiplatform, randomized clinical trial that combined data from three individual trials: ACTIV-4a, REMAP-CAP and ATTACC.

John Sheehan, MD, professor, Hematology, Medical Oncology and Palliative Care; Kraig Kumfer, MD, PhD, clinical associate professor, Hospital Medicine; and faculty in the Division of Hospital Medicine were among the investigators in one of those trials, ACTIV-4a, and led participation here.

Left: Dr. John Sheehan and Dr. Kraig Kumfer

It’s the first clinical trial in which the Division of Hospital Medicine has participated, and one of the first published inpatient COVID-related clinical trials in which UW Health has participated.

Are Higher Doses of Heparin More Effective?

Patients who are hospitalized with COVID-19 are at high risk for venous thromboembolism, or blood clots in the veins. Early studies have shown an association between plasma d-dimer levels (the protein that’s formed when a blood clot dissolves) and survival.

However, because venous thromboembolism often occurred in patients who were already receiving preventive doses of anticoagulation medication, the international group of investigators wanted to determine whether higher doses would be more effective and still be safe.

They identified two groups of patients hospitalized with COVID-19: 1) those who were not critically ill (defined as an absence of critical care–level organ support at enrollment) and 2) those who were critically ill with severe COVID-19. Patients in each group were randomly assigned to receive regimens of either therapeutic-dose anticoagulation with heparin or usual care preventive anticoagulation.

For the moderately ill patients, therapeutic-dose heparin appeared to increase the probability of survival until hospital discharge with a reduced need for organ support (probability 98.6%). However, more major bleeding occurred with heparin than with usual care (1.9% vs. 0.9%).

For the critically ill patients, therapeutic-dose heparin did not improve the outcome of days without organ support and was associated with more major bleeding complications than usual care (3.8% vs. 2.3%).

Read the complete studies:

• Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19
• Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

“At UW, our work on this study was a multidisciplinary effort between the Division of Hospital Medicine, Dr. Sheehan, and Rafael Veintimilla, MD, the senior director of clinical trials integration at the UW School of Medicine and Public Health,” Dr. Kumfer noted.

“I want to thank Dr. Kumfer for leading our division efforts in identifying potential participants, keeping us up to speed on logistics and changes in the trial, and meeting with all of us to keep us on track,” said Ann Sheehy, MD, MS, associate professor and chief, Hospital Medicine.

“This collaboration represents a significant step forward in establishing a framework for inpatient trials at UW, in which the Division of Hospital Medicine will play a critical role,” said Dr. Sheehan.

Banner: Division of Hospital Medicine faculty in a 2019 file photo. Credit: Clint Thayer/Department of Medicine.