Blood Clotting Causes Significant Mortality in COVID-19 Patients

Although the underlying pulmonary pathophysiology remains incompletely understood, severe COVID-19 infection is associated with a marked alveolar inflammatory cell infiltrate, together with a systemic cytokine storm response.

Consistent with the hypothesis that coagulation activation may play a role in COVID-19 pathogenesis, post-mortem studies have highlighted marked pathological changes specifically involving the lung microvasculature, including disseminated micro-thrombi and significant hemorrhagic necrosis.

Clinical scientists collaborating with those at the Royal College of Surgeons University of Medicine and Health Sciences (Dublin, Ireland) recruited consecutive adult patients with COVID-19 from March 13^th to April 10^th 2020. Hemostasis assays were performed including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and D-dimer levels. The PT, APTT and Fibrinogen assays were measured on the ACL Top 550 analyzer (Werfen, Barcelona, Spain).

Coagulation testing performed on admission in the total cohort demonstrated normal PT and APTT. In contrast, plasma D-dimer levels were significantly increased (median 732; range 200 to 10,000 ng/mL). D-dimer levels were above the normal range in 67% of the total cohort on admission. Fibrinogen levels were significantly increased (median 4.7; range 3.0 to 9.9 g/L) on admission, with levels remaining persistently elevated throughout hospitalization. The team noted that that they had found that abnormal blood clotting occurring in Irish patients with severe COVID-19 infection, causing micro-clots within the lungs. They also found that Irish patients with higher levels of blood clotting activity had a significantly worse prognosis and were more likely to require ICU admission.

James S. O'Donnell, a Professor and Consultant Hematologist and senior author of the study, said, “Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focused within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19. In addition to pneumonia affecting the small air sacs within the lungs, we are also finding hundreds of small blood clots throughout the lungs. This scenario is not seen with other types of lung infection, and explains why blood oxygen levels fall dramatically in severe COVID-19 infection. Understanding how these micro-clots are being formed within the lung is critical so that we can develop more effective treatments for our patients, particularly those in high risk groups.” The study was published on April 24, 2020 in the British Journal of Haematology.

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