Covid-19 Vaccines: Is there genetic predisposition for thrombosis?

March 28, 2021 – Recent reports from the United Kingdom (UK) and from throughout the European Union (EU) have suggested that the SARS-CoV-2 (Covid-19) vaccine made by AstraZeneca was at the origin of the development of a very rare type of thrombosis (blood clots) that is associated with thrombocytopenia (low blood platelets) in individuals vaccinated.

These reports have led to the halt by governments of a number of countries of the EU of the general vaccination campaigns for their respective populations with the vaccine from AstraZeneca (i.e., Covid-19 Vaccine (ChAdOx1-S [recombinant]), the temporary slowing down of approval processes by other authorities such as the FDA or Swissmedic, and a delay of the beginning of vaccination campaigns in some countries worldwide, such as Thailand.

Covid-19 Vaccine (ChAdOx1-S [recombinant] was approved by the European Medicines Agency (EMA) end of January 2021. In the following weeks, some reports emerged to the fact that the vaccine may cause in some vaccinated individuals thrombosis associated with thrombocytopenia, resulting in cases of blood clots in the brain, more precisely referred to as cerebral venous sinus thrombosis (CVST). Thrombosis Canada, an organzation dedicated to education and awareness of thrombotic disease resumed that based on the reports received through pharmacovigilance (PhV), these blood clots were found to occur in about 1 in 250,000 to 1 in 500,000 individuals who received the vaccine.

In contrast, we need here to understand that by comparison patients who have full blown Covid-19 disease are at much higher risk of developing blood clots, which occur in about 1 in 20 people who are in the hospital because of a severe form of the Covid-19 disease and in about 1 in 100 people who have a more benign form of  Covid-19 disease but are not hospitalized. Closer analyses in the general population also indicate that the frequency of spontaneous thrombosis occurring is in in the range of the frequency found here with individuals vaccinated with Covid-19 Vaccine (ChAdOx1-S [recombinant].

Taken all this evidence together in a risk/benefit analysis would at this point in time suggest, that there is an absolute minimal if any risk of individuals to develop thrombosis under Covid-19 Vaccine (ChAdOx1-S [recombinant] vaccination at a higher rate than those occurring spontaneously in the general population. In the light of these considerations, it is not surprising that the EMA on March 19, 2021 has decided, that the Covid-19 Vaccine (ChAdOx1-S [recombinant] still can be considered safe in its application to the population and that its benefits by far outweigh its risk.

Factor V Leiden

In this context, it might also be of particular interest, not only to clinical researchers and physicians, but also to the public at large, that in the general population there exists inherited genetic variation in blood clotting (i.e., hypercoagulability) based on the Factor V Leiden (rs6025 or F5 p.R506Q) variant. Factor V Leiden (rs6025 or F5 p.R506Q) is a variant (mutated form) of human factor V (one of several proteins involved in the formation of blood clots). Due to this mutation, protein C, an anticoagulant protein which normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots. Factor V Leiden is the most common hereditary hypercoagulability  disorder amongst ethnic Europeans.

However, Factor V Leiden is not the only predisposing factor for inherited clotting tendency, collectively called inherited thrombophilia. At least the mutation G20210A in the prothrombin gene (affecting about 3 -7% of the population) and mutations in the genes for protein C, protein S, and antithrombin (each affecting less than 1% of the population).