Sanquin Diagnostic Services monitors the side effect of the SARS CoV 2 vaccinesNews
Thrombocytopenia and thrombosis after vaccination with the AstraZeneca COVID-19 vaccine have caused quite a stir. The Dutch Society of Clinical Science (NVKC), the Dutch society of clinical haematology (VHL) and several (academic) hospitals have written a diagnostic guideline for vaccine induced prothrombotic immune thrombocytopenia (VIPIT). This guideline advises specific diagnostics to be executed at Sanquin in case of VIPIT.
VIPIT is a rare complication that has been observed in very few cases after vaccination with the AstraZeneca – and the Janssen COVID-19 vaccine. Although much is still unclear, a similarity was seen with heparin induced thrombocytopenia (HIT).
Heparin and HIT
Heparin potentiates the action of anti-thrombin and thereby inhibits the action of various coagulation factors, such as factor V and factor X. The relevant side effect of heparin is caused by the fact that it forms complexes with platelet factor 4 (PF4). This alters the shape of PF4, which may lead to antibody formation against the altered structure.
Because this occurs on or around the platelet membrane, the Fc-tails of the antibodies can bind to the Fc-gamma receptor IIa (FcγRIIa, CD32, low affinity IgG receptor) located on platelets. This causes platelet degranulation and aggregation and the release of more PF4.
Also, activation of platelets and formation of micro particles from platelets activates the coagulation cascade and thrombin formation. In addition, by increasing the amount of PF4, other cells expressing heparinoid-like structures (so-called glycosaminoglycans), such as monocytes, granulocytes and endothelial cells, may be activated. The activation of these cells leads to the formation of thrombin, but also to vascular wall damage and the release of tissue factor (TF).
All these processes lead to the breakdown of thrombocytes and the release of pro-coagulant material, which in combination with vessel wall damage can result in thrombosis. A nice review article by Matteo.Marchetti et al. on HIT was published recently. The AstraZeneca COVID-19 vaccine does not contain heparin. VIPIT does, however, show a 'HIT-like' picture, hence Professor Andreas Greinacher (Greifswald, Germany) and Scully at al. applied diagnostics used for HIT. This research showed that in patients with VIPIT, antibodies formed after vaccination recognise (activated) PF4 and thus activate the coagulation cascade, just as in HIT. An important finding, because this has consequences for the therapeutic policy: administration of heparin is in those cases an absolute contraindication! Treatment with direct oral anticoagulants and intravenous IgG (IVIg) is indicated.
Two tests to lead clinical decisions
Also because of the therapeutic policy, it is important to quickly know whether there is a case of VIPIT. Two different tests are required to determine VIPIT, a PF4 antibody detection method and a platelet function assay. Sanquin's Platelet/Leukocyte Serology Laboratory execute both the PF4 IgG ELISA and the heparin induced platelet activation (HIPA) assay on a regular basis.
If you want more information, please do contact us. More detailed information can be found in the guideline: 'Diagnosis and treatment of patients with thrombocytopenia with or without thrombosis after COVID-19 vaccination'.
Attention: Blood samples must be taken prior to IVIg treatment!