Changes in anti-PF 4 antibodies in patients with VITT including changes of the antibodies after vaccination against COVID-19
- Conditions
- Y59.9Vaccine or biological substance, unspecified
- Registration Number
- DRKS00025738
- Lead Sponsor
- Abteilung TransfusionsmedizinUniversitätsmedizin Greifswald
- Brief Summary
Background: Rapid diagnosis and treatment improved outcome of patients with Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT). However, after the acute episode many questions on long term management of VITT remained. This prompted the European Medicines Agency to initiate a prospective patient registry to be performed by the Institute for Transfusion Medicine of the Universitätsmedizin Greifswald. Methods: 71 patients with serologically confirmed VITT in Germany were enrolled into this prospective registry and followed by median 18 months. The course of anti-PF4 antibodies was analyzed by consecutive anti-PF4/heparin IgG enzyme immunoassay (EIA) and PF4-enhanced platelet activation assay. Patients and their treating physicians were regularly contacted by letter, email and telephone to obtain information on new events and changes in health. Informed consent was obtained to perform genome wide analysis to identify potential genetic risk factors to develop VITT. Findings: Platelet activating anti-PF4-antibodies were transient in 87.3% of patients. In six patients platelet activating anti-PF4-antibodies persisted >18 months. Five of 71 patients (7.0%) showed recurrent episodes of thrombocytopenia and/or thrombosis. In four of them alternative explanations beside VITT were present. After further COVID-19 vaccination with an mRNA vaccine no reactivation of platelet activating anti-PF4-antibodies or new thrombosis was observed. No adverse events occurred in patients with a history of VITT vaccinated against influenza, tick-borne encephalitis, varicella, tetanus, diphtheria, pertussis, and polio. No new thrombosis occurred in 24 patients with a history of VITT developing COVID-19. We further identified the characteristics of anti-PF4 antibodies in VITT patients. There was a strong correlation between antibody reactivity in the PF4/heparin EIA and the probability that these antibodies also activate platelets. Most important, a subset of these antibodies only activates platelets in the confirmatory functional assay, if the serum is further diluted. The explanation for this is that these antibodies form aggregates of PF4 only if the molar ratio between antibodies and PF4 are in an optimal range. Because antibody titers are very high in VITT patients, sensitivity of the confirmatory assay increases if antibodies are diluted. The genetic studies are still ongoing. Analyses up to now did not reveal any candidate gene polymorphism. As the numbers are limited, we plan to combine the genetic data with the data of similar studies performed in other countries. Interpretation: Once the acute episode of VITT is over, patients seem to have a low risk for recurrent thrombosis. VITT Patients tolerate further vaccination. The immune response against PF4 is not boosted by a new SARS-CoV2 infection in VITT patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 71
VITT with confirmed platelet activating anti-PF4 antibodies
none
Study & Design
- Study Type
- observational
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Changes in antibody titers; endpoint = date of the last, received blood sample of the patient. Antibody titers will be detected with PF4/heparin immuno assay
- Secondary Outcome Measures
Name Time Method Occurrence of new thrombosis and/or thrombocytopenia