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High rate of thromboembolic events seen in autopsies of deceased COVID-19 patients

Stephen Padilla
11 May 2020

The incidence of thromboembolic events in patients with the novel coronavirus disease (COVID-19) is surprisingly high, which suggests a significant role of COVID-19–induced coagulopathy, according to the results of a prospective cohort study in Germany.

“When haemodynamic deterioration occurs in a patient with COVID-19, pulmonary embolism should always be suspected,” the researchers said.

Clinical findings from the first 12 consecutive COVID-19–positive deaths were validated and confirmed using data from medical autopsy, virtual autopsy and virologic tests at a single academic medical centre, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19.

The median age of patients was 73 years (range, 52–87 years), and majority were male (n=9; 75 percent). Ten of them died in the hospital and two in the outpatient sector. Their most common comorbid conditions were coronary heart disease (50 percent) and asthma or chronic obstructive pulmonary disease (25 percent). [Ann Intern Med 2020;doi:10.7326/M20-2003]

Autopsy findings revealed deep venous thrombosis in more than half of the patients (n=7; 58 percent), in whom venous thromboembolism was not suspected prior to their death. In the remaining four patients, the direct cause of death was pulmonary embolism.

Reticular infiltration of the lungs with severe bilateral, dense consolidation was seen in postmortem computed tomography, while histomorphologically diffuse alveolar damage was observed in eight patients. Notably, high concentrations of SARS-CoV-2 RNA were detected in the lung in all patients. Six patients had viraemia, five of whom showed high viral RNA titres in the liver, kidney or heart.

Mechanisms

Different viruses, such as HIV, dengue and Ebola, may activate the coagulation system. As such, coronavirus infections could be a trigger for venous thromboembolism. [Blood 2014;123:2605-2613; Radiology 2020:201629]

“[S]everal mechanisms are involved, including endothelial dysfunction, characterized by increased levels of von Willebrand factor; systemic inflammation, by Toll-like receptor activation; and a procoagulatory state, by tissue factor pathway activation,” according to the researchers. [J Clin Virol 2020;127:104362]

A subgroup of patients with severe COVID-19 demonstrated high plasma levels of proinflammatory cytokines. Some patients also developed severe hypoxaemia. [Lancet 2020;doi:10.1016/S0140-6736(20)30920-X; Med Klin Intensivmed Notfmed 2020;doi:10.1007/s00063-020-00689-w]

“The vascular response to hypoxia is controlled primarily by the hypoxia-inducible transcription factors, whose target genes include several factors that regulate thrombus formation,” the researchers explained. [Thromb Res 2019;181:77-83]

Indirect causes, such as immune-mediated damage by antiphospholipid antibodies, could also contribute to this phenomenon. [Ann Intern Med 2020;doi:10.7326/M20-0533]

“That patients with COVID-19 who have increased D-dimer levels, a sign of coagulopathy, may benefit from anticoagulant treatment seems plausible,” the researchers said. “As demonstrated in our cohort, this might be important for hospitalized patients and outpatients.” [J Thromb Haemost 2020;18:1094-1099]

Recommendations have been made by some professional societies for antithrombotic therapy for COVID-19 patients, according to the researchers. However, further research is warranted to confirm and validate these findings.

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Most Read Articles
15 Nov 2018
In adult cardiac arrest (CA) patients treated with targeted temperature management (TTM), male sex, bystander cardiopulmonary resuscitation (CPR) and the presence of initial shockable rhythm all correlate with greater chances of favourable neurological outcomes, a recent meta-analysis has shown.
Elaine Soliven, 12 Apr 2019
The use of catheter ablation as first-line treatment reduces the number of premature ventricular complexes (PVCs) in a paediatric population, according to a study presented at EHRA 2019.