University Medicine Greifswald Reports Breakthrough in SARS-CoV-2 Vaccination-Related Thrombotic Complications

Prof. Dr. Andreas Greinacher ©Manuela-Jahnke, UMG, 2018
Prof. Dr. Andreas Greinacher ©Manuela-Jahnke, University Medicine Greifswald, 2018

Led by Prof. Dr. Andreas Greinacher's research group, Transfusion Medicine, at University Medicine Greifswald, researchers from the Medical University of Vienna in Austria, the McMaster University in Canada, the German Paul-Ehrlich-Institut (Federal Institute for Vaccines and Biomedicines), and University Medicine Greifswald investigated the clinical and laboratory features of patients in Germany and Austria who developed cerebral vein thrombosis and thrombocytopenia following the AZD1222 vaccination. The Transfusion Medicine research group has also developed a new specific confirmatory assay that allows the detection of these antibodies.

Patients tested strongly positive for anti-platelet antibodies by immunoassay and strongly positive in the newly developed functional test (platelet activation assay) in the presence of a newly identified cofactor (still under embargo). The test allows for clear differentiation between the new syndrome and the long-known adverse drug effect of heparin-induced thrombocytopenia (HIT). Platelet activation by the AZD1222 vaccination associated with antibodies was inhibited by intravenous immunoglobulin, a widely available and approved medication.

Greifswald's research group highlights the unique collaboration of international scientists, physicians, and the Paul-Ehrlich-Institut (German regulatory agency), treating physicians who referred blood samples and patients who agreed to donate their blood for research. Within a short period of time, from receiving the first samples on Tuesday, 16 March 2021, at noon until Friday, 19 March 2021, the group was able to:

-  identify the mechanism of SARS-CoV-2 vaccination induced severe thrombotic complications,
- identify a widely available screening test (this has already been confirmed by researchers in the UK),
- develop a confirmatory test which seems to be highly sensitive and specific (cautionary note: the number of samples investigated is still limited),
- and to identify a treatment that can rapidly deescalate the catastrophic prothrombotic mechanism. As the research group's work has demonstrated in the past, intravenous immunoglobulin (IVIG) is highly effective in treating catastrophic HIT; and as the clinical and laboratory characteristics of HIT closely resemble those of vaccine-associated complications, it is very likely that IVIG will also be an important therapeutic option (in addition to anticoagulant treatment) for patients. IVIG is approved and available in most hospitals.

University Medicine Greifswald proposes to call this syndrome VIPIT Virus/Vaccine Induced Prothrombotic Immune Thrombocytopenia.

Recording of the international press conference (20/03/2021) 
Recording of the German press conference [de] (19/03/2021) 

Updated statement on vaccination with the AstraZeneca COVID-19 vaccine from the Gesellschaft für Thrombose- und Hämostaseforschung (GTH) (German Society for Thrombosis and Hemostasis (GTH)) (22/03/2021)


FAQs about the treatment

General Information:

Who developed the treatment?
Researchers and physicians from Germany and Austria have developed the treatment in close collaboration with the German Paul-Ehrlich-Institut (Federal Institute for Vaccines and Biomedicines).

Which research data has been used?
Blood samples from four patients have been studied intensively. Blood samples from three additional patients have been studied to confirm the most important findings. New samples, which are being studied, are arriving every day. The samples studied are improving our findings; and, so far, they are also confirming them.

How large was the group of negative controls?
The group of negative controls at University Medicine Greifswald comprised approximately 300 vaccinated people

Do these results contradict the findings of the European Medicines Agency (EMA)?
No, they do not contradict the findings of the EMA. The EMA is right in stating that there is no accumulation of typical thromboses, such as leg vein thromboses or pulmonary embolisms. On the whole, cerebral vein thromboses (sinus thromboses) among vaccinated persons still occur in very rare cases; however, they are occurring more frequently than expected, given the size of the vaccinated cohort. The research group is studying the links between thromboses and vaccinations, even though thromboses merely occur in very rare cases.

To what should vaccinated persons pay attention? 
Many vaccinated people are experiencing unpleasant symptoms for 1-2 days after receiving their vaccination (amongst other things, aching joints and limbs and headaches). Because vaccines work by triggering the body’s immune system to produce a reaction, vaccinated people can have side effects, however, they do not mean that those who are experiencing them will automatically experience severe complications. Complications usually only occur from the fourth/fifth day after receiving the vaccination onwards. After 16 days, severe complications are less likely to occur. If side effects persist for longer than three days, or if they reoccur (especially in the case of dizziness, headaches, visual impairment, nausea/vomiting, shortness of breath, acute chest pain, acute abdominal pain, or acute pain in the arms or legs), the persons affected should contact a physician.

For more information, please take a look at the updated statement from the Gesellschaft für Thrombose- und Hämostaseforschung (GTH) (German Society for Thrombosis and Hemostatis (GTH))



What kind of mechanism causes thromboses after vaccinations?
Thromboses are caused by the activation of thrombocytes (platelets). Usually, platelets seal vascular lesions (e.g. wounds). In this way, bleedings are stopped. After vaccination, the vaccinated persons develop antibodies. These antibodies then bind to the platelets and activate them. This leads to clots forming in the blood; and, these clots could eventually obstruct the vessel (thrombosis). At the same time, the number of free platelets in the blood decreases (so-called thrombocytopaenia).

What causes the development of these antibodies?
At the present moment, this cannot be clearly established. We could be dealing with a component of the vaccine or with an excessive reaction of the body, or the development of these antibodies could be caused by a combination of these two aspects; at the moment, further research is being done on this.

How do you identify this mechanism?
The research group developed a screening assay that can identify if patients suffering from thromboses and thrombocytopaenias have these antibodies.
CAUTIONARY NOTE! The screening assay can also indicate a positive result for other causes. If the screening is negative, vaccine reactions are unlikely. Positive results have to be confirmed by another test (confirmatory test), which has also been developed by the group.

Is it possible to perform such a test in advance?
No, it is not possible to perform a prophylactic test.

Does the screening assay need to be confirmed?
Yes, if the screening is positive, a confirmatory test will be performed.

Who is being tested?
Patients who are experiencing clinical symptoms in the second week after receiving their vaccination are being tested.


Is the treatment available in every hospital?
It should be possible to apply this treatment in every medium-sized hospital.

How does the treatment work?
The antibodies consist of two components. One of them identifies the antigen, the other component, the so-called effector activates immune cells. The immune cells then bind to the thrombocytes (platelets). The receptor can be blocked by using intravenous immunoglobulin (IVIg). To suppress the mechanism, one gram of intravenous immunoglobulin per kilogram of body weight per day for two consecutive days is needed.

Further Information

Can intravenous immunoglobulin be used prophylactically?

Are women at a higher risk?
When it comes to immune reactions, women are affected slightly more often than men. Whether oestrogens play a role in this risk is still being studied.

Which tests should physicians perform?
For more information, please take a look at the updated statement from the Gesellschaft für Thrombose- und Hämostaseforschung (GTH) (German Society for Thrombosis and Hemostatis (GTH))

Is this treatment only suitable for sinus vein thromboses?
No, if a thrombosis, regardless of where its location and thrombocytopaenia occur after receiving the vaccination, we are probably dealing with this mechanism. The treatment should work regardless of the location of the thrombosis.

Are there any pre-existing conditions in which cases vaccination is not advisable based on findings? (Such as Faktor V Leiden mutation, autoimmune diseases, allergies, antiphospholipid syndrome, von Willebrand disease, etc.)?
So far, there is no evidence of certain pre-existing conditions being associated with an increased risk of thrombosis after receiving the vaccination. Thromboses can also occur in patients with severe COVID-19. This means that the benefits and risks of the vaccination have to be weighed.

 If you have any queries, feel free to contact University Medicine Greifswald, preferably via email at kommunikationmed.uni-greifswaldde


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