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                                                        3. NEJM 2021

                                                        BTK inhibitors against vaccine-related thrombotic complications

                                                        NEJM 2021

                                                        ➤ IPEK scientists propose treatment for rare, life-threatening complication from Astra-Zeneca vaccine.

                                                        LMU Klinikum

                                                        In rare cases, platelet activation and thrombosis (blood clots) have occurred in unusual locations, such as veins in the brain, after vaccination with the Astra-Zeneca vaccine.

                                                        Certain drugs used in cancer therapy, known as BTK inhibitors, are able to normalize the pathological activation of platelets with associated blood clot formation which occurs in rare cases after vaccination with the Astra-Zeneca COVID-19 vaccine. This is reported by IPEK director Christian Weber and colleagues in the latest issue of the New England Journal of Medicine. Weber calls the development “an urgently needed way of treating this worrying vaccine complication.” Germany has seen well over twelve and a half million doses of Astra-Zeneca’s Vaxrevia vaccine administered so far, and over 67 million doses have been given EU-wide. The severe side effect known as VITT (vaccine-induced immune thrombotic thrombocytopenia) that has been the subject of much attention occurs in about one to one and a half out of 100,000 vaccinations, “so it is a rare but life-threatening side effect with high mortality,” says Weber. Moreover, many more doses of the Astra-Zeneca vaccine have been and are being donated to countries in need around the world, making VITT a global problem.
                                                        In a laboratory model, the medical experts had blood serum from VITT patients available. When they added the serum to blood from healthy subjects, they observed the activation of platelets and the subsequent formation of blood clots. However, when a BTK inhibitor had been added to the subjects’ blood samples, “the formation of blood clots did not occur,” says Priv.-Doz. Dr. Philipp von Hundelshausen, a visiting lecturer who was involved in the study. The drug blocks an enzyme that is essential for blood clot formation.One BTK blocker has already been approved for cancer treatment, while others are currently in the clinical trial stage.
                                                        In order for the drugs to be used against VITT, “they would need to be tested in clinical trials as well,” explains Weber. The BTK inhibitors might also help in the treatment of two other diseases that arise through the same mechanisms as VITT. One is when some people who suffer from an autoimmune disease suddenly experience blood clots when heparin is administered as part of the treatment. And then in rare cases, some patients develop blood clots even without the administration of heparin.

                                                        Sources

                                                        • LMU Klinikum News
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                                                        • LMU Press Release
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                                                        • DZHK Press Release
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