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Heparin dose capable of preventing deaths from COVID-19 is higher than recommended by the WHO

Publicado em 17 outubro 2021

Por Karina Toledo | Agência FAPESP

The finding was made in a clinical trial with 465 patients treated in 28 hospitals in six countries, including Brazil

The anticoagulant heparin reduces the risk of dying from complications of COVID-19 by 78% if administered in a therapeutic dose as soon as the patient arrives at the hospital with signs of respiratory failure, he indicates. study published this Thursday (10/14) in British Medical Journal.

Currently, the World Health Organization (WHO) recommends for these cases only a prophylactic dose of the drug (indicated to prevent thrombosis), which is four times lower than the therapeutic dose and did not show benefits in the randomized clinical trial. The research involved 465 patients treated at 28 hospitals in six countries, including Brazil.

“We believe that these results should change clinical practice,” he tells FAPESP Agency the doctor Elnara Negri, co-author of the article and member of the teams at Hospital das Clínicas, Faculty of Medicine, University of São Paulo (FM-USP) and at Hospital Sírio-Libanês.

The researcher emphasizes, however, that the recommendation is not valid for everyone who is diagnosed with COVID-19. “The treatment is indicated only for those who are hospitalized and only under medical supervision. If a person takes anticoagulants without need or guidance, they can bleed to death.”

Patients of both sexes, with a mean age of 60 years, who were admitted to the hospital with oxygen saturation equal to or less than 93% participated in the clinical trial. The objective was to evaluate the effect of heparin on several possible outcomes of SARS-CoV-2 infection. In addition to reducing mortality, therefore, we sought to observe whether the treatment would reduce the need for non-invasive ventilation (with a high-flow catheter or oxygen mask), intubation and admission to the Intensive Care Unit (ICU).

The volunteers were divided into two groups, one treated with the therapeutic dose and the other that received only the prophylactic dose (control group). The effect on outcomes was assessed 28 days after drug administration.

“We did not see a significant difference in terms of the need for ICU admission, non-invasive ventilation or intubation. But the number of deaths was significantly lower in the group that received the therapeutic dose. And the occurrence of major bleeding, which was the main adverse effect observed in the study, was very low. In other words, the therapy is safe”, says the doctor.

The results also show that, to bring benefits, heparin must be administered between the seventh and the 14thO day after the onset of symptoms. Previous studies had already shown that anticoagulation does not bring important results when it is performed after admission to the ICU.

The doctor emphasizes that the benefits at this stage of the disease were observed only with the use of injectable heparin. Anticoagulants given orally had no effect. “This is possibly due to the fact that this drug also has antiviral and anti-inflammatory effects already confirmed in the context of COVID-19. The good news is that it is a cheap drug available in the SUS [Sistema Único de Saúde].”

first evidence

In partnership with colleagues from the FM-USP Department of Pathology Marisa Dolhnikoff and Paulo Saldiva, Negri was one of the first people in the world to hypothesize that blood clotting disorders were at the base of COVID-19’s most severe symptoms – including respiratory failure and pulmonary fibrosis. The group published the first article from the scientific literature that described “pathological evidence of pulmonary thrombotic phenomena in severe COVID-19” (Read more at: agency.fapesp.br/33175).

“The virus enters through the respiratory system and some organisms manage to contain it before it reaches the pulmonary alveoli. But when it invades the capillaries that supply the lung, it starts to make holes in the endothelium [camada de células que reveste a parte interna dos vasos] and that makes the blood start to clump. Microthrombi form that prevent the passage of blood to the pulmonary structures where gas exchange takes place”, he explains.

Heparin helps to prevent this from happening by two mechanisms: the drug breaks down the microthrombi that prevent oxygen from passing from the alveoli to the small pulmonary arteries and, in addition, it helps in the recovery of the vascular endothelium.

Studies published in the last year indicate that approximately 15% of those infected with the new coronavirus develop changes in blood coagulation. “This is the population that can benefit from treatment with heparin, but the timing it’s fundamental,” says Negri.

The article Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomized clinical trial can be read in: www.bmj.com/content/375/bmj.n2400.

This text was originally published by Agência FAPESP under the Creative Commons CC-BY-NC-ND license. Read the original here.

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