Patients with COVID-19 in the intensive care unit (ICU) prescribed full-dose blood thinners are significantly more likely to experience heavy bleeding than patients prescribed a smaller yet equally effective dose, according to a University at Buffalo-led study.
The research, which compared the safety and effectiveness of blood clot treatment strategies for more than 150 critically ill COVID-19 patients at two hospitals, found that almost all those who experienced significant bleeding were mechanically ventilated and receiving full-dose anticoagulants.
The results, published in Hospital Pharmacy, may inform treatment guidelines for blood clots in hospitalised COVID-19 patients, who are at an increased risk for both blood clots and severe bleeding. Previous reports have found that 17% of hospitalised COVID-19 patients experience blood clots, says first author Dr Maya Chilbert, clinical assistant professor in the UB School of Pharmacy and Pharmaceutical Sciences.
"A wide variety of practice exists when it comes to approaching blood clots in hospitalised patients with COVID-19, and there is little data to suggest improved outcomes using one strategy versus another,” says Chilbert. “Caution should be used in mechanically ventilated patients with COVID-19 when selecting a regimen to treat blood clots, and the decision to use full-dose blood thinners should be based on a compelling indication rather than lab markers alone.”
Additional investigators in the UB School of Pharmacy and Pharmaceutical Sciences include Collin Clark, PharmD, clinical assistant professor, and Ashley Woodruff, PharmD, clinical associate professor. The research was also conducted by investigators at the Buffalo General Medical Center, Millard Fillmore Suburban Hospital and Erie County Medical Center.
The study analysed the outcome of blood clot treatments and the rate of bleeding events for more than 150 patients with COVID-19 who received either of two blood thinner regimens: a full-dose based on patient levels of D-dimer (a protein present in the blood after a blood clot dissolves), and the other a smaller but higher-than-standard dosage.
The average patient age was 58, and all experienced elevated levels of D-dimer, fibrinogen (a protein that helps the body form blood clots), and prothrombin time (a test that measures the time it takes for blood plasma to clot).
Nearly 14% of patients who received full-dose blood thinners experienced a significant bleeding event, compared to only 3% of patients who received a higher-than-standard dosage. All patients who experienced bleeding events were mechanically ventilated. No difference was reported in the regimens' effectiveness at treating blood clots.
Further investigation is needed to determine the optimal strategy for treating blood clots and bleeding in hospitalised COVID-19 patients, says Chilbert.
Study details
Comparison of Higher-Than-Standard to D-Dimer Driven Thromboprophylaxis in Hospitalized Patients With COVID-19.
Maya R. Chilbert, Collin M. Clark, Ashley E. Woodruff, Kimberly Zammit, Cynthia Lackie, Kristen Kusmierski, Patrick McGrath, Gregory Fuhrer, Anna Augostini, Olivia Denny, Nicole Ross, Marissa Saber, Natalie DelGuidice.
Published in Hospital Pharmacy on 27 December 2021
Abstract
Introduction
Coronavirus disease 2019 is a global health threat often accompanied with coagulopathy. Despite use of thromboprophylaxis in this population, thrombotic event rates are high. Materials and methods: This was a multicenter, retrospective cohort study comparing the safety and effectiveness of thromboprophylaxis strategies at 2 institutions in hospitalized patients with coronavirus disease 2019. Regimen A utilized a higher-than-standard thromboprophylaxis dosage and Regimen B received full-dose anticoagulation for any D-dimer 3 mcg/mL or greater and prophylactic for less than 3 mcg/mL. The primary outcome compared the rate of thrombotic events between treatment groups. Secondary endpoints compared rates of major or clinically relevant non-major bleeding as well as the proportion of patients in each group experiencing thrombotic events within 30 days of discharge.
Results
One-hundred fifty-three patients were included in the analysis, 64 receiving Regimen A and 89 receiving Regimen B. Seven (4.6%) thrombotic events occurred, 3 (4.7%) in patients receiving Regimen A, and 4 (4.5%) in Regimen B (P = 1.0). Twelve patients (13.5%) receiving Regimen B had a bleeding event versus 2 (3.1%) in Regimen A (P = .04), half of which were major in each group. All patients who bled in either treatment group were receiving mechanical ventilation, and 12 of 14 were receiving full-dose anticoagulation. One patient receiving Regimen A was readmitted with a pulmonary embolism.
Conclusions
In this study, the thromboprophylactic regimen impacted bleeding, but no significant difference was seen with thrombotic outcomes. Almost all patients who experienced a bleed were mechanically ventilated and receiving full-dose anticoagulation. The use of full-dose anticoagulation should be cautioned in this population without an additional indication.
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