SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP

Abstract

Cases of de novo immune thrombocytopenia (ITP) - including a fatality - following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in pre-existing ITP. In this study, four data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a ten-center retrospective study of adults with pre-existing ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA, United States) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] x109/L approximately 1-week post-vaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 109 patients with pre-existing ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30x109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK ITP patients, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in pre-existing ITP or be identified de novo post-SARS-CoV2-vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those post-splenectomy and with more refractory disease, is indicated.

Platelet trends after Covid‐19 vaccination in patients with chronic or persistent immune thrombocytopenia

“… 4 A subset of 13 patients in this cohort were included in a multicenter retrospective observational study evaluating platelet trends following Covid‐19 immunization among those with a history of ITP. 5 Here, we corroborate findings that approximately half had a drop in platelet count following vaccination, but that intervention was required in a minority of cases. Further, with additional follow‐up data, our study demonstrates that adverse events were rare and platelet decreases were mostly transient.…”

“…One subject was described in a previously published case report. 4 We also contributed data from this subject and 12 others to a multicenter retrospective observational study 5 ; outcomes in these subjects are described in additional detail and with further follow‐up data here.…”

Consensus on COVID-19 vaccination in pediatric oncohematological patients, on behalf of infectious working group of Italian Association of Pediatric Hematology Oncology

“…Unlike adenoviral vector vaccines (AstraZeneca/VaxZevria and Janssen/COVID-19), no serious complication of vaccine-induced thrombosis/thrombocytopenia (VIIT) was reported in mRNA vaccines [48]. On the other hand, cases of immune thrombocytopenia appearing in the first 2 weeks after vaccination (usually the first dose) have been reported: 17 cases in the United States in the period January-February 2021 in which 20 million people were vaccinated [49]. Thrombocytopenia immune is also reported for other vaccinations, for example 1:40,000 children vaccinated for measles-rubella-mumps, but the rarity of the recorded events does not allow the distinction between the event induced by vaccination (causal relationship) and event coinciding with vaccination (random relationship), as immune thrombocytopenia occurs in the pediatric or adult population even beyond any temporal correlation with vaccinations.…”

Detection of anti-GPIbα autoantibodies in a case of immune thrombocytopenia following COVID-19 vaccination

“…Autoimmune responses following other vaccines, including those against Measles, Mumps and Rubella (MMR), Influenza, Polio, and Human Papillomavirus have been previously reported, and molecular mimicry has been implicated as a mechanism of undesired immune responses. Interestingly, the recent COVID-19 vaccination follow-up study of the patients with pre-existing ITP showed higher exacerbation risk in those post-splenectomy and those with more refractory disease [8] . Previous studies reported that resistance to IVIG treatment was more frequent when ITP was caused by anti-GPIb/IX compared to anti-GPIIb-IIIa [9] [10] .…”

“…In addition, our previous study using mouse models demonstrated that platelet hepatic sequestration and TPO upregulation occurs when platelets are acutely depleted by high-dose anti-GPIbα [5] . Higher exacerbation risk of thrombocytopenia in patients with prior splenectomy [8] may indicate hepatic platelet clearance mediated by anti-GPIbα. Further investigation is warranted to determine the mechanism by which the administration of mRNA vaccine and the expression of spike proteins not only trigger T cell responses against spike proteins but also potentiate the production of anti-GPIbα antibodies.…”