Sars-Cov-2 Vaccination in Pre-Existing and De Novo ITP: A Single Center Experience with Long-Term Follow-up

Abstract

Introduction: SARS-CoV-2 vaccines can induce de novo immune thrombocytopenia (ITP) and worsen pre-existing ITP. Almost all cases of vaccine-induced or -exacerbated ITP respond to ITP therapies. We investigated longer-term outcomes of patients with ITP de novo or relapsed post-SARS-CoV-2 vaccination requiring treatment. We included outcomes following SARS-CoV-2 booster vaccines and considered that some post-vaccination relapses may NOT be related to vaccination. Methods: This is a single-center retrospective study of patients ≥18 years old with pre-existing ITP or de novo ITP following SARS-CoV-2 vaccination seen at The Center for Blood Disorders at New York-Presbyterian/Weill Cornell Medicine from January 2021 to May 2022. We included consecutive ITP patients with at least one platelet count following initial SARS-CoV-2 vaccinations or boosters. The study was approved by the NYP-WCM Institutional Review Board. An "ITP exacerbation” was defined as: a) ≥50% decline in platelet count from pre-vaccination baseline; b) >20% decline from pre-vaccination baseline to a platelet nadir <30x109/L; and/or c) receiving rescue therapy for ITP. Results: Among 95 patients with pre-existing ITP, sixteen (17%) experienced at least one ITP exacerbation after one (or several) SARS-CoV-2 vaccinations. Ten of 84 (12%) had an ITP exacerbation after dose#1. Among these, 7 experienced another exacerbation: 6 after dose#2 (with 3 receiving boosters, all without exacerbation) and 1 only after a booster. Of the remaining 3 who had had an ITP exacerbation after dose#1, 2 tolerated dose#2, and 1 was not re-challenged. Seventy-four received dose#2 of a SARS-CoV-2 vaccine. Nine (12%) experienced ITP exacerbations, including 6 who also had exacerbations following dose#1. Three tolerated dose#1 and an ITP exacerbation following dose#2. Two of these patients received booster vaccines, with 1 experiencing another ITP exacerbation. Of 24 patients who received at least one booster, 5 (21%) had ITP exacerbations after their boosters. While 3 of the 5 patients had tolerated previous vaccinations well, 1 had had an exacerbation following dose#1 and 1 following dose#2. Eleven of 16 patients experiencing ITP exacerbation(s) following SARS-CoV-2 vaccine(s) received rescue treatment, of whom seven (64%) had difficult-to-control ITP on chronic treatment, including intravenous immune globulin (IVIG) every 2 to 8 weeks. All responded to rescue treatment; the frequency of intermittent IVIG infusions did not increase following SARS-CoV-2 vaccination. Excluding these 7 whose ITP exacerbations were possibly not related to vaccination, 5/77 (6.5%) patients had exacerbations after dose #1, 4/68 (5.9%) after dose #2, and 4/20 (20%) after a booster. Four patients had exacerbations after more than 1 vaccination. Six patients had presumed de novo ITP post-SARS-CoV-2 vaccine: 2 females, 4 males, median age 35 years (range 30-72), and median follow-up 11 months (range 3-15) post ITP diagnosis. All presented with mucocutaneous bleeding and a median platelet count of 4 x109/L (1-29x109/L) at a median of 12 days post-vaccination (range 1-21). De novo ITP developed following dose#1 in 4 patients (mRNA-1273 = 2, BNT162b2 mRNA COVID-19 = 1, Ad26COV2 =1) and a first booster vaccine in 2 (BNT162b2 mRNA COVID-19). All 6 responded to IVIG and corticosteroids; 3 did not require further treatment remaining in complete response (CR) at 7-15 months post-vaccination. One completed a steroid taper and remains in CR 1 month off steroids; the other 2 patients remain on TPO-RA in on-treatment CR - at 3 and 12 months, 1 being tapered. Two received additional doses of the same vaccine and did well, both in CR off treatment up to 15 months since the initial diagnosis of ITP. Conclusions: ITP exacerbations and de novo ITP can occur with subsequent vaccination doses (including boosters) of the SARS-CoV-2 vaccine despite tolerance to previous doses. Conversely, many tolerate subsequent doses well, implying that the mechanism is unlikely to involve the generation of anti-platelet antibodies. Furthermore, in certain patients, ITP "exacerbations” may not be due to the vaccination but part of the course of their ITP. ITP exacerbation post-SARS-CoV-2 vaccination does not seem to cause lasting change in the state of the ITP on follow-up. Cases of de novo ITP generally responded well to standard treatments for ITP and, in our small cohort, had favorable longer-term outcomes.