key: cord-1019569-sn1k45nt authors: Uaprasert, Noppacharn; Watanaboonyongcharoen, Phandee; Vichitratchaneekorn, Rattaporn; Trithiphen, Sasinipa; Akkawat, Benjaporn; Sukperm, Autcharaporn; Tongbai, Thanisa; Jantarabenjakul, Watsamon; Paitoonpong, Leilani; Rojnuckarin, Ponlapat title: Prevalence of thrombocytopenia, anti–platelet factor 4 antibodies and D‐dimer elevation in Thai people After ChAdOx1 nCoV‐19 vaccination date: 2021-09-18 journal: Res Pract Thromb Haemost DOI: 10.1002/rth2.12580 sha: 5e3e862f1de9d9c6bea88b6534c2725b3330f418 doc_id: 1019569 cord_uid: sn1k45nt BACKGROUND: Vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a rare distinctive syndrome characterized by unusual site thrombosis accompanied by thrombocytopenia after ChAdOx1 nCoV‐19 vaccination. Platelet‐activating anti–platelet factor 4–dependent antibodies (anti‐PF4 Abs) were detected in most cases of VITT. To date, data from Asian countries are lacking. OBJECTIVES: To determine the prevalence of thrombocytopenia, anti‐PF4 Abs, and D‐dimer elevation in Thai people administered the ChAdOx1 vaccine. PATIENTS/METHODS: A total of 521 vaccinated and 146 nonvaccinated subjects were enrolled. Blood samples were collected to determine platelet counts, anti‐PF4 Abs using ELISA and D‐dimer levels 5 to 30 days after the first vaccination. RESULTS: None of the participants developed thrombocytopenia or had significantly decreased platelet counts from baseline after ChAdOx1 vaccination. The frequencies of anti‐PF4 Abs between vaccinated (16/521; 3.1%; 95% confidence interval [CI], 1.8‐4.9) and nonvaccinated Thai people (6/146; 4.1%; 95% CI, 1.5‐8.7) were similar. None of the detectable anti‐PF4 Abs activated platelets in vitro. The average D‐dimer levels between vaccinated and control groups were similar (282.2 ± 286.3 vs 267.8 ± 219.3 ng/mL; P = 0.58). Four vaccinated and one nonvaccinated participants had markedly elevated D‐dimer levels >2000 ng/mL without detectable anti‐PF4 Abs. Imaging studies of these asymptomatic subjects revealed incidental pulmonary embolism in a vaccinated elderly woman. CONCLUSIONS: This study demonstrated a low prevalence of thrombocytopenia and pathogenic anti‐PF4 Abs after ChAdOx1 vaccination. D‐dimer testing revealed no significant coagulation activation. Routine tests for platelet counts, anti‐PF4 Abs, and D‐dimer levels are not recommended for VITT screening without clinical suspicion. • Low platelet counts were not observed in 521 Thai people after ChAdOx1 vaccination. • The frequency of platelet-activating antibodies was low after ChAdOx1 vaccination. • No significant activation of blood clotting was observed after ChAdOx1 vaccination. • Blood tests are not recommended in asymptomatic people administered the ChAdOx1 vaccine. A meta-analysis has estimated the pooled incidence of VITT across 10 countries (8 from Europe, Canada, and Australia) after ChAdOx1 vaccination of 0.73 per 100 000 persons. 10 Despite its rarity, many European countries have restricted or even terminated the ChAdOx1 vaccine from their national COVID-19 vaccine campaigns. There have been no reports of confirmed VITT from Asian countries. In Thailand, the ChAdOx1 vaccine is the cornerstone vaccine against SARS-CoV-2 and will be administered to at least 30 million Thai people in the second half of 2021. To date, the prevalence of anti-PF4 Abs after ChAdOx1 vaccination have never been evaluated in Asian cohorts. This study aimed to estimate the prevalence of thrombocytopenia, anti-PF4 Abs, and evaluated D-dimer levels within the first 30 days after ChAdOx1 vaccination among Thai people. Unvaccinated health care workers and faculty members were recruited for comparison. Participants with documented thrombocytopenia within 12 months, receiving high-dose immunosuppressive drugs (such as prednisolone ≥30 mg/day) and/or heparin within 3 months before enrollment were excluded. Informed consent 1.8-4.9) and nonvaccinated Thai people (6/146; 4.1%; 95% CI, 1.5-8.7) were similar. None of the detectable anti-PF4 Abs activated platelets in vitro. The average Ddimer levels between vaccinated and control groups were similar (282.2 ± 286.3 vs 267.8 ± 219.3 ng/mL; P = 0.58). Four vaccinated and one nonvaccinated participants had markedly elevated D-dimer levels >2000 ng/mL without detectable anti-PF4 Abs. Imaging studies of these asymptomatic subjects revealed incidental pulmonary embolism in a vaccinated elderly woman. This study demonstrated a low prevalence of thrombocytopenia and pathogenic anti-PF4 Abs after ChAdOx1 vaccination. D-dimer testing revealed no significant coagulation activation. Routine tests for platelet counts, anti-PF4 Abs, and D-dimer levels are not recommended for VITT screening without clinical suspicion. Participants with detectable anti-PF4 Abs and/or markedly elevated D-dimer levels (>1000 ng/mL) were evaluated for symptoms and signs related to thrombosis, and relevant laboratory and imaging studies were performed. Demographic data and medical history, including data on underlying diseases, current medications, previous vaccination, and solicited and unsolicited adverse reactions developed after ChAdOx1 vaccination were recorded in the questionnaire. Any symptoms and signs suggestive of thromboembolic or hemorrhagic events were assessed and investigated according to standard practice. Blood samples were collected in EDTA and citrated tubes, as appropriate. Specimens were processed within 60 minutes of collection. Complete blood count (CBC) was assessed using a Sysmex XN-9000 hematology analyzer (Sysmex, Kobe, Japan). Platelet-poor plasma was stored at 80℃ until it was tested. The normality of the data was tested using the Shapiro-Wilk test. Continuous data were presented as mean (± standard deviation) or median (interquartile range [IQR]), as appropriate. Comparisons between continuous and categorical data were analyzed using Student's t-test and the chi-square test, respectively, as appropriate. Statistical significance was considered when P values were <0.05. All statistical parameters were analyzed using SPSS version 22.0, for Windows (SPSS Inc., Chicago, IL, USA). ing for VITT screening. 17, 18 The British guidance has suggested that VITT is very unlikely when D-dimer levels are <2000 ng/ mL. 18 In this study, the average D-dimer levels between the vaccinated and nonvaccinated cohorts were similar (282.2 ± 286.3 vs. 267.8 ± 219.3 ng/mL; P = 0.58) ( Figure 2) . Additionally, there were no significant differences in the proportions of elevated D-dimer levels using different cutoff values between both groups (Table 2) . These findings suggested no significant coagulation activation after This study has some limitations. Although the prevalence of an- be as sensitive as modified heparin-induced platelet activation or serotonin release assays. However, all participants with detectable anti-PF4 Abs were periodically evaluated for signs and symptoms related to thrombosis, CBC and D-dimer levels up to 12 weeks to ascertain their nonfunctionality. In conclusion, this is the first Asian cohort study that demonstrated a low prevalence of thrombocytopenia and pathogenic anti-PF4 Abs after ChAdOx1 vaccination. The evidence did not suggest significant activation of platelets and the coagulation system after The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. NU, PW, LP, and PR designed the study. RV, ST, and WJ collected data. BA, and AS performed laboratory tests. TT performed interpretation of imaging studies. NU analyzed data and wrote the first draft of manuscript. All authors discuss data, revised the manuscript, and approved the final version for publication. 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