Anticoagulation for Sickest COVID-19 Patients: Tread Carefully

COVID-19 patients without overt venous thromboembolism (VTE) should receive anticoagulation in the hospital but only at relatively low doses, according to American Society of Hematology (ASH) draft guidance.

ASH endorsed prophylactic-intensity anticoagulation — not intermediate- or therapeutic-intensity — to prevent clotting in COVID-19 patients who are acutely or critically ill.

This conditional recommendation was based on very low certainty in the evidence about the effects of anticoagulation in affected patients, the guideline panel acknowledged.

But that may change in the near future, as there are currently 20 or so global randomized trials studying the question of anticoagulation dosing for primary thromboprophylaxis in sick, hospitalized COVID-19 patients, according to Alex Spyropoulos, MD, of Northwell Health at Lenox Hill Hospital in New York City, who was not involved with the group.

A pilot randomized trial, HESACOVID, recently suggested that therapeutic-level dosing of enoxaparin (Lovenox) improved respiratory outcomes in severe COVID-19.

Spyropoulos said he agreed with the proposed ASH guideline recommendations, and he noted that VTE rates from large U.S. health systems have been much lower than those reported from earlier, smaller studies from China and Europe.

Reasons for the difference may include reporting bias, bias from the use of systematic screening for VTE, or simple overestimations of VTE risk due to small samples in those older studies, he said.

Abnormal clotting was observed in COVID patients almost from the pandemic’s outset, and discussions of whether, when, and how to prevent it followed almost immediately.

“COVID-19 is the most important public health problem of our lifetime, with more than one million deaths worldwide. Data suggest that abnormal blood clotting plays an important role in why patients die or get very sick from this disease. Thus, it is important that these patients be given anticoagulants to try to prevent clots, and data available right now suggest that standard dosing provides the best balance of benefits and risks,” said ASH President Stephanie Lee, MD, in a press release.

For patients at high clotting risk and low bleeding risk, however, higher doses may be appropriate.

An intermediate dose of unfractionated or low molecular weight heparin may be considered in people with morbid obesity or those in the ICU, for example, Spyropoulos suggested.

Guideline authors cautioned that available clotting and bleeding risk assessment tools have not been validated in people with SARS-CoV-2.

In addition, no single anticoagulant was endorsed for COVID-19 patients given the lack of high-quality evidence.

“The selection of a specific agent (e.g., low molecular weight heparin, unfractionated heparin, etc.) may be based on availability, resources required, familiarity, and the aim of minimizing PPE use or staff exposure to COVID-19 infected patients as well as patient-specific factors (e.g., renal function, history of heparin-induced thrombocytopenia, concerns about gastrointestinal tract absorption),” the authors offered.

ASH will finalize the guideline before December. Public comments are being accepted until October 16.

As they are, the proposed recommendations are “very reasonable,” according to Stephan Moll, MD, of the University of North Carolina in Chapel Hill.

“Overall, I agree with these recommendations. Higher intensities of anticoagulation should be used only with prospective data collection. That way, our practice recommendations will be informed by high-quality data,” commented Behnood Bikdeli, MD, MS, of Brigham and Women’s Hospital and Harvard Medical School.

Bikdeli said he is working with the INSPIRATION group that is midway through enrollment for a trial randomizing critically ill COVID patients to intermediate-dose vs standard dose anticoagulation.

Ongoing studies that answer similar questions include ACTIV-4, COVID-PACT, DAWN-ANTICO, and IMPROVE-COVID.

“They will help clarify the benefit and risk of various intensities of anticoagulation and will help guide who should be considered for anticoagulation therapy, at what dose, and for what length,” Moll commented.

The ASH recommendations do not apply to VTE patients or those requiring anticoagulation to prevent thrombosis of extracorporeal circuits (e.g., extracorporeal membrane oxygenation or continuous renal replacement therapy).

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    Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

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