A close friend fell ill with Covid and had a thrombosis. But is it true that this disease is related to Covid?

Thrombosis is a severe complication in 50% of those who get Covid-19. One of the most recent scientific articles published in the Thrombosis Research Journal tries to shed some light on how Covid-19 may be responsible for the state of hypercoagulability. Is the pulmonary response to Sars-Cov2 responsible for many complications of patients in intensive care, or of survivors but with permanent outcomes, or are they outcomes of venous thrombosis both pulmonary and elsewhere?

The numerous recent scientific data, contrary to what was thought at the beginning of the pandemic, suggest that this virus manifests itself with systemic effects and with both arterial and venous thrombotic risk of small or large vessels: it is therefore not just a disease respiratory.

The data comes to us from New York City, where cardiologist B. Bidkeli compares the effects to "a storm of blood clots", while in other European studies it seems that it is not only the presence of thrombi that puzzles scientists, but also "The way they manifest themselves," says J. O'Donnell of Dublin.

In fact, in Covid-19 patients, the response to anticoagulants is not always optimal, and young people may begin with cerebral ischemia, an event theoretically unrelated to Covid-19.

Why this variability of manifestations? One possibility is that SARS-Cov-2 directly attacks endothelial cells - with the function of lining blood vessels - favoring some organs over others: researchers from Zurich and Boston found SARS-Cov-2 in endothelial cells within the kidney tissue.
Endothelial cells then house the same receptor that the virus uses to enter lung cells. The endothelium physiologically prevents the formation of clots, but, quoting Peter Liu, scientific director of the University of Ottawa, "the viral infection can damage these cells, causing them to produce proteins that trigger the thrombotic process".

The effects of the virus on the immune system, which activates the mechanisms promoting the coagulation cascade, could also influence coagulation. "All the systems that underlie inflammation and clotting are interrelated," citing a University of Vancouver study. "In some patients with Covid-19, it is as if all of these systems have suddenly accelerated." P. Liu then adds “that there may be other factors at play that are not specific to Covid-19. They may be elderly or overweight and have high blood pressure or diabetes. They present with a high fever and, because they are seriously ill, they are likely to have been immobilized. They could have a genetic predisposition to clotting or take drugs that increase the risk.

An Italian study by the University of Milan-Bicocca also consensually discovered and confirmed that an alteration in endothelial cells caused by the virus is responsible in many cases for thrombotic events.

What therapy or prevention for thrombosis?

Anticoagulant drugs are the standard for thrombosis prevention for all ICU patients, and those with Covid-19 are no exception. Some researchers from the Mount Sinai School of Medicine, but also in many Italian centers, reported that patients admitted with Covid-19 undergoing mechanical ventilation who had received anticoagulants had a lower mortality than those who did not clot. The dilemma, however, lies in the dosages: it seems that high doses of anticoagulant are more effective than prophylaxis, at a lower dosage.

Scientists at Beth Israel Medical Center have also started a trial to evaluate an even more potent drug for preventing blood clots, but one that carries a greater risk of bleeding, called tissue plasminogen activator, or tPA.

Other interesting conclusions have been reached through studies on fat cells: overweight people run the risk of having a higher viral load than normal weight people. Therefore, having a higher "inflammatory" state is connected to a greater risk of forming clots: in fact, "during infection, the fat cells release substances into the blood that increase the inflammatory reaction, making the storm more fearful of cytokines, increasing the thrombotic risk up to 5 times ”, as appears from a study by the University of Sao Paulo.

The excess of cytokines in the circulation could explain both thrombosis and multi-organ failure, says Alberto Mantovani, immunologist at Humanitas in Milan.

A new drug that could counter these dire consequences has been developed by a team of researchers from the University of Malaga: 4-phenylbutyric acid (4-P

A new drug that could counter these terrible consequences has been developed by a team of researchers from the University of Malaga: 4-phenylbutyric acid (4-PBA) which can modulate the inflammatory response when Covid-19 infection occurs.

When to start anticoagulant treatment?

According to the recommendations of the American Society of Hematology, "it is advisable to start anticoagulant therapy as soon as possible in patients with Covid-19 and continue it even after discharge from the hospital", as well as "it is important to further follow these patients even after complete recovery. and maintain clinical monitoring and venous Doppler ultrasound over time to exclude possible recurrences ».

"These results will require confirmation through prospective studies - concludes Carlo Gambacorti Passerini of the University of Milan-Bicocca - but their rapid spread will allow for a more rational and effective treatment of this complex disease".

Hypotheses are growing that see the vascular and coagulative system increasingly involved and probably responsible for the clinical manifestations: according to a thesis by cardiologist Maurizio Viecca of the Sacco hospital in Milan, Covid-19 would first cause venous thrombosis, causing pulmonary microembolias that would be been observed up to this time. If the theory were confirmed, it would perhaps be possible to avoid intensive therapy to stop the evolution of the disease.

A clinical trial on volunteers began at the Sacco hospital, testing the so-called "Viecca Protocol". This involves the use of antiplatelet, anti-inflammatory and anticoagulants at the first symptoms of the disease. To corroborate the theses set out so far, it should be noted that the Start-Covid-19 register was born in Italy, which aims to know and counter the effects of Covid-19 on blood coagulation, using data from the medical records of hospitalized patients . This will allow, among other things, to correlate the use and doses of anticoagulant drugs with the clinical conditions of patients and above all with the evolution of their disease.

An initiative of the Arianna Anticoagulation Foundation chaired by Gualtiero Palareti, which brings together the most important Italian specialists involved in the treatment and prevention of coagulation disorders, states: "In addition to the aforementioned register, we are preparing a project for local medicine and to support general practitioners ".

(from the Gazzetta di Parma of 9/12/2020)