Vaccine-induced immune thrombotic thrombocytopenia and thrombosis syndrome (VITT/TTS) after vaccination against SARS-CoV-2 (COVID-19)

Study type

• Study topic:
  Disease /health condition
• Study type:
  Not applicable
• Scope of the study:
  Other
• If ‘Not applicable’, further details on the study type:
  Patient registry
• If ‘other’, further details on the scope of the study:
  Patient registry
• Data collection methods:
  Primary data collection

Study drug and medical condition

• Medical condition to be studied:
  Vaccination complication
• Additional medical condition(s):
  Vaccine-induced immune thrombotic thrombocytopenia

Population studied

• Short description of the study population:
  The study involved two cohorts: subjects with clinical diagnosis of vaccine-induced immune thrombotic thrombocytopenia and thrombosis syndrome (VITT/TTS) with platelet activating PF4-dependent antibodies identified by Greifswald reference laboratory, and those with clinically suspected VITT/TTS after vaccination with an adenoviral vector-based COVID-19 vaccine, confirmed by positive anti-PF4/heparin IgG ELISA and positive PF4-enhanced platelet activation.; Inclusion Criteria:; Prospective patient registry (Cohort 1): ; 1. Signed written informed consent by the subject who is able to assess the nature, significance and scope of the patient registry. If the subject is temporarily incapable of consent, the consent of a legal representative or authorized representative will be accepted if permitted under applicable local regulations/ethics committee recommendations. ; 2. Males or females ; 3. Subjects with clinically suspected VITT/TTS between day 4 and 30 after vaccination with an adenoviral vector-based COVID-19-vaccine in whom VITT is confirmed by a positive anti-PF4/heparin IgG ELISA and a positive PF4-enhanced platelet activation assay; Genome wide analysis (Cohort 2): All subjects with clinically suspected VITT/TTS after vaccination with an adenoviral vector-based COVID-19-vaccine in whom VITT is confirmed by a positive anti-PF4/heparin IgG ELISA and a positive PF4-enhanced platelet activation.; ; Exclusion Criteria:; There are no exclusion criteria.
• Age groups:
  • Paediatric Population (< 18 years)

    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Renal impaired

  Hepatic impaired

  Immunocompromised

  Pregnant women

  Other
• Special population of interest, other:
  Patients with vaccine-induced immune thrombotic thrombocytopenia and thrombosis syndrome
• Estimated number of subjects:
  69

Study design details

• Main study objective:
  What are the characteristics of the immune response against PF4 induced by SARS-CoV-2 vaccine? Evaluation of the Brighton Collaboration interim case definition of TTS Genome wide analysis of patients with VITT/TTS Characterization of the anti-PF4 antibodies in VITT/TTS
• Outcomes:
  First day of clinical symptoms of VITT/TTS - Last day of positive anti-PF4 antibody test by EIA - Last date of a positive functional test for PF4 dependent platelet activating antibodies - Boostability of PF4-antibodies: to assess anti-PF4 antibody response to second or third dose of Covid-19 vaccine, vaccination with any other vaccine, or surgical interventions or heparin application. - Reevaluation of TTS patients according to the Brighton collaboration case definition with special emphasis on occurrence of VITT/TTS in the absence of thrombosis. - Sequencing the genome of VITT/TTS patients and comparison with the genomes of the matched probands of the normal population obtained by the Study of Health in Pomerania (SHIP) - Assessment of the IgG subclasses of the anti-PF4 abs
• Data analysis plan:
  Following laboratory methods are used: - Anti-PF4/heparin IgG ELISA - Platelet activation assay with washed platelets (PIPA) - Glycosylation analysis of the affinity purified anti-PF4 IgG will be performed by mass spectrometry - Sequencing will be performed in the Competence Center for Genomic Analysis of the subcontractor University Kiel using standard methods (30x coverage by paired end Illumina sequencing on a NovaSeq instrument). The whole genome sequencing will be performed by the Illumina DNA Prep protocol Statistical analysis - performed in R - Assembled genome sequences of the VITT patients will be compared to age and sex matched probands of the population-based Study of Health in Pomerania. Chi-squared / likelihood ratio tests will be used to perform univariate tests of association between variants and cases/controls.