Sars-cov-2 vaccination in patients with pre-existing immune thrombocytopenia

ABSTRACT

Introduction: Cases of de novo immune thrombocytopenia (ITP), including a fatality following SARS-CoV-2 vaccination in a previously healthy recipient, led to studying its impact in pre-existing ITP. Published reports are limited but suggest that most patients with ITP tolerate the COVID-19 vaccines well without frequent ITP exacerbations (Kuter, BJH, 2021). Data regarding risk factors for exacerbation and relationship of response to first dose to that of second dose are limited. Methods: Data for patients with pre-existing ITP were obtained via 3 sources. First, via a ten-center retrospective study of adults with ITP who received a SARS-CoV-2 vaccine between December 2020 and March 2021 and had a post-vaccination platelet count (n=117);9 centers were in the United States. Eighty-nine percent of patients received mRNA-based vaccines. The second and third sources of data were surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom ITP Support Association. A 'stable platelet count' was defined as a post-vaccination platelet count within 20% of the pre-vaccination level. ITP exacerbation was defined as any one or more of platelet decrease ≥ 50% compared to pre-vaccination baseline, platelet decrease by >20% compared to prevaccination baseline with platelet nadir < 30x10 9/L, receipt of rescue therapy for ITP. Continuous variables were described as mean ±SD or median [interquartile range];categorical variables were described as n (%). Relative risks and 95% confidence interval were calculated to estimate strength of association. Results: Among 117 patients with pre-existing ITP from 10 centers who received a SARS-CoV-2 vaccine, mean age was 63±17 years, 62% were female, with median 12 [4-23] years since diagnosis of ITP;patients had received a median of 3 [2-4] prior medical treatments. Sixtynine patients were on ITP treatment at the time of vaccination (Table 1). There was an almost even distribution of platelet count response following each vaccine dose. In 109 patients with data for dose 1, platelet counts increased in 32 (29%), were stable in 43 (39%), and decreased in 34 (31%);in 70 patients following dose 2, platelet counts increased in 24 (34%), were stable in 25 (36%), and decreased in 21 (30%) (Figure 1). Nineteen (17%) patients experienced an ITP exacerbation following the first dose and 14 (20%) of 70 after a second dose. In total, fifteen patients received and responded to rescue treatments (n = 6 after dose 1, n = 8 after dose 2, n = 1 after both doses). Of 7 patients who received rescue treatment after dose 1, 5 received dose 2 and only 1/5 received rescue treatment again. Rescue consisted of increased dose of ongoing medication, steroids, IVIG, and rituximab. Splenectomized persons and those who received 5 or more prior lines of medical therapy were at highest risk of ITP exacerbation. Only 1 of 47 patients who had neither undergone splenectomy nor received 5 or more lines of therapy developed ITP exacerbation after dose 1. There were 14 patients offtreatment at the time of dose 1 and 7 patients at time of dose 2;1 patient in each group developed ITP exacerbation with both these having had normal counts prior to vaccination and having undergone splenectomy. In 43 patients whose platelet counts were stable or increased after dose 1 and received dose 2, only 6 (14%) had platelet decreases to <50 x10 9/L after dose 2. Age, gender, vaccine type, and concurrent autoimmune disease did not impact post-vaccine platelet counts. In surveys of 57 PDSA and 43 U.K. ITP patients, similar rates of platelet change were seen (33% of participants reported decreased platelet count in both surveys) and prior splenectomy was significantly associated with worsened thrombocytopenia in each. Conclusions: Thrombocytopenia may worsen in pre-existing ITP post-SARS-CoV2-vaccination but when ITP exacerbation occurred, it responded well to rescue treatment. No serious bleeding events were noted. Rescue treatment was needed in 13% of patients. Proactive vaccination surveillance of patien s with known ITP, especially those post-splenectomy and with more refractory disease, is indicated. These findings should encourage patients with ITP to not only be vaccinated, but to receive the second dose when applicable to ensure optimal immunization. Rituximab interferes with vaccination response and ideally would be held until a minimum of 2 weeks after completion of vaccination.