Coagulation disorders – “That makes you think”

After Denmark decided last week to suspend AstraZeneca’s vaccine for a period, several other countries followed suit, first Norway and Romania, and now Sweden, France, Ireland, Italy, Spain and Germany. The European Medicines Agency (EMA) remains convinced of the benefits of the vaccine, and a decision on how to proceed is expected on Thursday.

After vaccinations with AstraZeneca, various coagulation disorders had occurred: In Austria, a 49-year-old nurse from the Zwettl State Hospital died presumably of a thrombosis and two other nurses suffered a pulmonary embolism. Cases of cerebral vein thrombosis occurred in Germany, cases of blood clots and skin bleeding were reported from Norway.

Unknown for vaccinations

“Thromboses or blood clots are not known in connection with vaccinations. In no existing study has such a connection occurred. Not even in the approval studies for AstraZeneca”, explains Bernd Salzberger, infectiologist at the University Hospital Regensburg. Vaccinations are not yet on the list for the cause of thrombosis or bleeding.

The most common cause of thrombosis – one assumes around one case per thousand inhabitants annually – is lack of exercise and immobility, according to Albert Wölfler, hematologist at the Medical University of Graz. “When lying down, the venous blood flow is slowed down and so is the coagulation process. This is why the blood is thinned with low-molecular heparin. Because you know that this immobility is a trigger for the thrombosis.”

Sitting for long periods of time can also cause thrombosis. In a thrombosis, a blood clot forms in a blood vessel, dissolves and travels to the lungs. A thrombosis can cause an embolism.

There are also genetic causes for thrombosis, such as the “Factor V Leiden mutation”. This is a change in one of the clotting factors. Around five percent of the Austrian population have this gene mutation and thus an increased risk of thrombosis. “Especially when there is a trigger factor”, as Wölferl explains.

“The coagulation system, in particular the blood platelet system, is a system that is regulated in many ways and can be unbalanced by a wide variety of mechanisms,” says the doctor.

The multitude of factors that influence the system makes it difficult in this case to investigate the cause and refers you to the analysis of data and statistics: “The problem with thromboses is that they are something like background noise and keep coming back in among the population without always being able to find a clear cause. That is why it is difficult to identify an association. This would only be recognizable through an increased frequency. Whether this exists is still open at the moment, “says Salzberger.

Mysterious decrease in platelets

Not only at AstraZeneca, but also with the vaccines from BionTech Pfizer and Moderna, bleeding disorders had also occurred or a reduction in the number of platelets was observed. Platelets are essential for clotting. When infected with a pathogen, many of these platelets are produced in the bone marrow. Typically, there are 150,000 to 400,000 of these nucleated cells in every microliter of blood. A decrease in the number of blood platelets can be a factor in an increased tendency to bleed. It becomes critical from a value below 30,000. “Punctiform skin bleeding and mucosal bleeding are typical, but there is also the risk of cerebral haemorrhage,” said Wölfler. The decrease in the number of platelets indicates the risk, but it does not mean that you will actually bleed.

The causes are also diverse: it may be that no platelets can be formed from the outset, for example due to an acute disease of the bone marrow, or, one of the most common causes, that they are broken down too quickly because the immune system has antibodies against them this developed. This is what is known as an immune-mediated platelet decrease. The platelets are marked as foreign by the immune system and removed from the blood by the spleen.

This immune reaction sometimes takes place as a result of infections when “clearing up” after a cold or a cold and the body’s own cells are also taken along. “When we go through an infection, not only a specific antibody against a pathogen is formed, but a whole series of antibodies,” says Wölfler.

Bernd Salzberger believes the temporary suspension of the vaccine is right. At the same time, the reaction of the Paul Ehrlich Institute does not indicate to him that the vaccine is related to the coagulation disorders. Because of the comparatively small group of vaccinated people in the studies compared to reality, it is possible “to miss a very rare side effect. But there was no signal in this direction. In this respect, it is thought-provoking and one has to look at it carefully and examine it whether it is a batch problem or a quality problem, for example. You have to give yourself time to assess it properly. “

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