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Heparin dose in covid cases is 4 times higher than that suggested by the WHO - 10/15/2021

Publicado em 16 outubro 2021

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, indicates a study published this Thursday (14/10) in British Medical Journal.

Currently, the WHO (World Health Organization) 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,” says Dr. Elnara Negri, a co-author of the article and a member of the teams at the Hospital das Clínicas at FM-USP (Faculty of Medicine of the University of São Paulo) and at the FAPESP Agency. Syrian-Lebanese Hospital.

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 ICU (Intensive Care Unit).

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 didn’t 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 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 14th 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 that have already been 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 Department of Pathology at FM-USP, Marisa Dolhnikoff and Paulo Saldiva, Negri was one of the first people in the world to raise the hypothesis that blood clotting disorders were at the base of the most serious symptoms of COVID-19 – between they respiratory failure and pulmonary fibrosis. The group published the first article in the scientific literature that described “pathological evidence of pulmonary thrombotic phenomena in severe COVID-19” (read more at: agencia.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 timing is critical,” 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 at: www.bmj.com/content/375/bmj.n2400.

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