A small, preliminary case series led by physicians at the Icahn School of Medicine at Mount Sinai found that five severely ill patients with the SARS-CoV-2 virus responded to the blood-clot-busting drug tPA when it was introduced as a life-saving measure. This response, and the large number of critically ill COVID-19 patients who have blood clots in their lungs, have raised new questions concerning the course of the disease and may present new possibilities for treating it.
“This case series pushes us to consider avenues of clinical investigation that are different from what they are now,” says the paper’s first author, Hooman D. Poor, MD, Assistant Professor of Medicine (Pulmonology, Critical Care and Sleep Medicine, and Cardiology). “Perhaps we should be looking at the disease from the standpoint of clots that form in the blood vessels and travel to the lungs.”
Dr. Poor says that more testing will be needed to determine whether the clots are the “inciting events in a subset of patients,” and not a complication that develops after these patients develop acute respiratory distress syndrome (ARDS). “ARDS looks the same, but it’s not,” he says. It requires “dramatically different treatments.”
According to the paper, the critically ill COVID-19 patients had relatively well-preserved lung mechanics, and did not develop stiffness of the lungs, despite severe gas exchange abnormalities. This feature is more consistent with pulmonary vascular disease and not with classic ARDS. The COVID-19 patients also demonstrated markedly abnormal coagulation with elevated D-dimers—small protein fragments present in the blood after a blood clot—and higher rates of venous thromboembolism, a condition where blood clots that form in the deep veins of the legs or groin travel and become lodged in the lungs.
Mount Sinai’s paper cited autopsy studies from the SARS outbreak in the early 2000s, which revealed that patients had “pulmonary thrombi, pulmonary infarcts, and microthrombi in other organs.” SARS-CoV-1, the virus that caused SARS, and SARS-CoV-2, which causes COVID-19, belong to the same family of coronaviruses.
With mounting evidence that a consistent pattern of COVID-19 patients are presenting with blood clots, front-line clinicians at the Mount Sinai Health System and throughout the United States are reassessing and modifying existing guidelines that incorporate anticoagulation therapies.
Mount Sinai has provided treatment guidelines for its eight hospitals that address the significant role microthrombi—tiny clots composed of platelets—may play in patients with severe cases of COVID-19. The new guidelines help to inform clinical decision-making on administering anti-coagulation therapy for critically ill patients throughout the Health System. They call for patients who require hospitalization to be assessed for blood clots in their lungs by measuring their oxygen levels, testing for markers of clotting in their blood, and assessing their difficulty breathing or shortness of breath. Patients in intensive care units may also be eligible for a clinical trial at Mount Sinai that will examine the use of thrombolysis in respiratory failure due to COVID-19.
The recommendation was made by a panel of expert clinicians within Mount Sinai, and was based on published and rapidly emerging data, international and local experience, and autopsy reports.
Recently, the International Society on Thrombosis and Haemostatis recommended that all hospitalized COVID-19 patients, even those not in intensive care units, should receive prophylactic-dose low molecular weight heparin—a blood thinner—unless they have contraindications, such as active bleeding.
“If patients with COVID-19 show a small problem with their lungs, perhaps we should start them on blood thinners to prevent the clots from reaching the point where we have to administer tPA,” says Dr. Poor. “However, this treatment paradigm with early anticoagulation will need to be evaluated with well-designed clinical trials.”
Hooman D. Poor, MD, Assistant Professor of Medicine (Pulmonology, Critical Care and Sleep Medicine, and Cardiology is a ConduITS LEAD Program graduate. The Leadership Emerging in Academic Departments (LEAD) Program is aimed at supporting Junior Faculty to develop personal and professional leadership skills. The curriculum includes modules in self-discovery, communication, influence, negotiation, strategic vision, inspiring trust and embracing diversity.
The LEAD program is supported by The ConduITS Institutes for Translational Sciences at Mount Sinai, which is funded by The Clinical and Translational Science Awards (CTSA) grant UL1TR001433 from the National Center for Advancing Translational Sciences.