Therapeutic heparin to prevent deaths from COVID-19 is four times higher than the prophylactic dose


Anticoagulant heparin reduces the likelihood of death from COVID-19 by 78% when given in therapeutic doses to patients with signs of respiratory failure on hospital admission, according to a study published on the 14th October in the British medical journal.

The World Health Organization (WHO) currently recommends only the prophylactic use of heparin for these patients. The prophylactic dose of the drug, prescribed primarily to prevent blood clots, is only a quarter of the therapeutic dose. Prophylactic administration was not found to be beneficial in the randomized clinical trial described in the article. The study involved 465 patients treated in 28 hospitals in six countries, including Brazil.

“We believe these results should change clinical practice,” Elnara Negri, co-author of the article, told Agência FAPESP. Negri is a professor and doctor at the Syrian-Lebanese Hospital of São Paulo and at the Hospital das Clínicas (HC), the hospital complex managed by the Faculty of Medicine of the University of São Paulo (FM-USP).

Treatment is not recommended for everyone diagnosed with COVID-19. “It is only indicated for patients admitted to hospital and only under medical supervision,” said Negri. “Anyone who takes a blood thinner without needing or without proper monitoring can bleed to death.”

The clinical trial involved men and women with an average age of 60 admitted to hospital with an oxygen saturation of 93% or less. It was designed to observe the effect of heparin on the outcome of SARS-CoV-2 infection. In addition to reducing mortality, the goal was to find out whether treatment reduced the need for non-invasive ventilation (with high-flow catheter or oxygen mask), intubation and admission to the intensive care unit (ICU). .

The volunteers were divided into two groups. One group received the therapeutic dose. The other served as a control group and received only the prophylactic dose. The effect on the results was evaluated 28 days after administration of the drug.

“We found no significant difference in terms of the need for ICU admission, non-invasive ventilation or intubation, but the mortality rate was significantly lower for the therapeutic dose group, and heavy bleeding. , the main adverse effect observed in the study, was very small. In other words, the therapy is safe, ”said Negri.

The results also showed that for heparin to be of benefit, it must be administered between seven and 14 days after the onset of symptoms. Previous research had already shown that treatment with the anticoagulant did not produce significant benefits when given after admission to intensive care.

Benefits were only seen at this stage of the disease with the heparin injection. Oral heparin had no effect. “This may be because the drug also has antiviral and anti-inflammatory effects which have been confirmed in the context of COVID-19. The good news is that the drug is cheap and available through SUS. [Brazil’s national health service]”said Negri.

First proof

Working in partnership with colleagues in the pathology department of FM-USP, Marisa Dolhnikoff and Paulo Saldiva, Negri was one of the first people in the world to hypothesize that blood clotting disorders could be responsible for some of the more serious symptoms of COVID-19, such as respiratory failure and pulmonary fibrosis. The group published the first article in the scientific literature to describe “pathological evidence of pulmonary thrombotic phenomena in severe COVID-19” (more on: agencia.fapesp.br/33233).

“The virus enters the body 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 lungs, it begins to poke holes in it. endothelium [the layer of cells that line the interior of blood vessels], and this leads to blood clotting. Microthrombi are formed and prevent the passage of blood to the lung structures in which gas exchange takes place, ”explained Negri.

Heparin helps prevent this process through two mechanisms. It dissolves the microthrombi which prevent oxygen from flowing from the alveoli to the small blood vessels in the lungs, and it helps in the regeneration of the vascular endothelium.

Studies published last year show that about 15% of people infected with the novel coronavirus develop blood clotting disorders. “It’s the population that can benefit from heparin treatment, but timing is vitally important,” Negri said.

Source:

São Paulo Research Foundation (FAPESP)

Journal reference:

Sholzberg, M., et al. (2021) Efficacy of Therapeutic Heparin Compared to Prophylactic Heparin on Death, Mechanical Ventilation, or Intensive Care Unit Admission in Moderately Ill patients with covid-19 admitted to hospital: clinical trial randomized RAPID. BMJ. doi.org/10.1136/bmj.n2400.

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