Effects of COVID‐19 vaccination on platelet counts and bleeding in children, adolescents, and young adults with immune thrombocytopenia

Abstract

Coronavirus disease 2019 (COVID‐19) vaccines rarely cause de novo immune thrombocytopenia (ITP) but may worsen preexisting ITP in adults. Whether severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines impact platelet counts and bleeding in children, adolescents, and young adults (C‐AYA) with preexisting ITP is unknown. We report here the very limited effect of COVID‐19 vaccination on platelet counts and bleeding in a single‐center series of 2 C‐AYA with ITP. No patient experienced worsening bleeding and only one child had a significant decrease in platelet count which improved spontaneously to her baseline without intervention. SARS‐CoV2 vaccination was safe in C‐AYA with ITP in this small cohort.

Abbreviations

C‐AYA

children and adolescents/young adults

COVID‐19

coronavirus disease 2019

ITP

immune thrombocytopenia

SARS‐CoV‐2

severe acute respiratory syndrome coronavirus 2

1. INTRODUCTION

Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been implemented globally for adults, teens, and now children and has effectively reduced the burden of severe disease. However, despite vaccines being generally safe, ¹ , ² there are reports of vaccine‐associated immune thrombocytopenia (ITP) ³ , ⁴ , ⁵ , ⁶ and of a new entity: “vaccine induced thrombotic thrombocytopenia (VITT). ⁷ , ⁸ ” These very rare but sometimes very serious events have received substantial media attention creating widespread apprehension about vaccine safety. ⁹ No published data to date have described the effects of vaccination for SARS‐CoV‐2 in children and AYA with preexisting ITP. With emerging reports of worsening ITP following COVID vaccination in adults, families of children with preexisting ITP have been concerned about vaccinating their children. Responses to patient queries are currently dependent on data in adults. Since serious COVID‐19 infections can occur in children, ¹⁰ our policy has been to advise families of patients with ITP, or a history of ITP, to pursue vaccination in their children unless there is a specific contraindication. As a precaution, we have suggested obtaining a baseline platelet count and then rechecking platelet counts approximately a week after each vaccine dose whether in clinic or at a local laboratory. Since the best time to check a platelet count after vaccination for SARS‐CoV‐2 has not been determined in adults, our recommendation to check counts at baseline and a week after undergoing vaccination is based on adult experience. ³ Emerging data suggest that monitoring of platelet counts perhaps even twice a week might be required to accurately assess vaccine effect on platelet numbers. We report here the effects of the COVID‐19 vaccine on bleeding and platelet counts on children, adolescents, and young adults (C‐AYA) with ITP.

2. METHODS

This was a retrospective, deidentified study approved by the Weill Cornell IRB without requirement of patient consent. We included data for all C‐AYA who were being followed in our pediatric hematology clinic with a diagnosis of ITP and who sought counseling regarding SARS‐CoV‐2 vaccination. Our data were collected by review of electronic medical records from patients who were counseled over a period of ten months between May 2021 and March 2022. We recommended vaccination for all patients in this cohort, and platelet count checks at baseline and a week after each dose of vaccination. Families were encouraged to call and self‐report any new bleeding symptoms that were above their individual baseline. No formal bleeding questionnaires were administered. Standard definitions were used with newly diagnosed ITP (disease lasting 0–3 months), persistent ITP (3–12 months), and chronic ITP (>12 months) respectively from initial diagnosis. ¹¹ History of ITP was defined as patients who had previously received a diagnosis of ITP but had no current evidence of disease, were not on treatment and had normal platelet counts. Only patients with chronic ITP or a history of ITP sought vaccination counseling at the time of this report; thus, no patients with newly diagnosed or persistent ITP were included. New bleeding symptoms after vaccination were self‐reported by the patient as worsening from their own baseline. Data for bleeding symptoms were obtained by reviewing clinic notes and telephone encounters in the post vaccination period up to 1 month after the second dose. A “stable platelet count” was defined as a postvaccination platelet count within 20% of the prevaccination level. An “exacerbation of ITP” was defined as previously described by development of any one or more of the following: (1) ≥50% decline in platelet count from pre‐vaccination baseline; (2) >20% decline from prevaccination baseline and platelet nadir <30 × 10⁹/L; and/or (3) receipt of rescue therapy for ITP. ³

3. RESULTS

The effects of COVID‐19 vaccination were reported on platelet counts, disease exacerbation, and bleeding in 20 C‐AYA patients with ITP. Patients had chronic ITP (16) or ITP in remission (four); none had newly diagnosed or persistent ITP. Eighteen of the 20 patients were 12 years of age or older with two children aged 5 years and 6 years old. The age distribution was a result of sequential vaccine approval by the United States Food and Drug Administration first for 12–15 year olds (in May 2021) and then for 5–11 year olds (in October 2021). Our patient cohort was heterogenous with regards to disease phenotype, duration, and type of ITP‐directed treatments received (Table 1). There were 14 females and six males with an age range of 5–21 years (median: 15 years). There were four children with ITP in full remission. Only two of these four children with remote ITP in off‐treatment remission followed our advice and checked platelets counts pre‐ and post‐vaccination, although none reported bleeding. Sixteen patients had chronic ITP: six were on Eltrombopag, three on Romiplostim, one on Sirolimus, one on mycophenolate mofetil, and one on hydroxychloroquine and intermittent steroids because of concomitant lupus; four were being actively observed and monitored but not on any ITP‐directed treatment. The duration of chronic ITP ranged from 1 to 13 years. Several patients had received multiple treatments in the past (Table 1); however, all but one were currently stable on a single agent or were being observed. No patient had undergone splenectomy. Except for the one child with SLE, there were no other comorbidities or other autoimmune disease. No child had Evans syndrome. Two patients had never received treatment for ITP. All children received the Pfizer‐BioNTech mRNA vaccine except for one (patient 18; Table 1) who opted for the single dose Janssen (J&J) vaccine andsubsequently received a Pfizer booster. There was considerable variability in the timing to check platelet counts post vaccination. Eighteen of 20 children had baseline platelet counts checked prior to vaccination. The two children with remote ITP who were counseled but did not obtain any platelet counts are not included in Table 1. Post vaccine dose# 1: 15 patients had platelet counts checked on day 7 (±1 day), one patient on day 20, one on day 30, and not checked at afor one child. More variability was observed in the interval between vaccination and platelet count check after vaccine dose# 2: nine patients checked their counts on day 7, three on day 11, one on day 12, two on day 14, one on day 26, and one patient had counts done on both days 2 and 14 (patient 6; Table 1) and not checked for one patient. No child reported new bleeding symptoms after vaccination. Only one patient (patient 6; Table 1), with refractory chronic disease and wide variability in her platelet counts, dropped her count to 9 × 10⁹/L, 2 days after receiving vaccine dose# 2. Her count increased to her baseline, 40 × 10⁹ /L, 2 weeks later without administration of rescue therapy. Most patients in this cohort maintained stable counts after vaccination with several showing a slight upward trend in their platelet counts post vaccination with a gradual return to their baseline.

TABLE 1.

Patient characteristics and platelet counts at baseline and after first and second dose of COVID‐19 vaccine

	Demographic	Diagnosis	Current treatment	Disease duration (years)	Previous treatment history	Baseline platelets ×103/μl	Platelet ×103/μl (After Pfizer Dose# 1)	Platelet ×103/μl (After Pfizer Dose# 2)
1	14 Y, White, F	H/O ITP in remission	None	Single episode (at the age of 5 years)	IVIG x 1	214	213	ND
2	14 Y, White, F	H/O ITP in remission	None	5 years (disease free 7 years)	IVIG, steroids, anti‐D	233	262	265
3	15 Y, Asian, F	Chronic	Romiplostim	10 years	IVIG, steroids, azathioprine, Danazol, MMF, rituximab, eltrombopag	55	95	91
4	15 Y, Hispanic, F	Chronic	None	4.5 years	Observation only	89	ND	136
5	17 Y, Asian, F	Chronic	Eltrombopag	13 years	IVIG, steroids, rituximab, cyclosporine	399	393	399
6	12 Y, White, F	Chronic	Romiplostim	10 years	IVIG, steroids, anti‐D, eltrombopag, dapsone	38	32	9 (Day 2) 40 (Day 14)
7	17 Y, Asian, M	Chronic	Eltrombopag	1.5 years (+COVID exposure)	IVIG, steroids	75	91	137
8	14 Y, White, M	Chronic	None	11 years	IVIG, steroids, anti‐D, eltrombopag	42	63	50
9	21 Y, African American, F	Chronic, SLE	Hydroxychloroquine, Steroid pulses (intermittent)	3 years	Steroid pulses	17	43	ND
10	14 Y, African American, F	Chronic	Sirolimus (on wean)	7.5 years	IVIG, steroids, mycophenolate, eltrombopag, Rituximab	396	402	382
11	16 Y, White, F	Chronic	Eltrombopag	2 years	none	112	152	111
12	16 Y, Hispanic, M	Chronic	Romiplostim	1.5 years	IVIG, steroids, eltrombopag	43	75	136
13	12 Y, Asian, M	Chronic	Eltrombopag	6 years	IVIG, anti‐D, steroids	110	108	70
14	15 Y, Caribbean, F	Chronic	Mycophenolate	9 years	IVIG, steroids, Rituximab, dapsone, eltrombopag, sirolimus	26	41	116
15	5 Y, White, M	Chronic	None	3 years	IVIG intermittently, steroids x 1	69	96	110
16	6 Y, Asian, M	Chronic	Eltrombopag	1.5 Y	Steroids	300	180	229
17	12 Y, Hispanic, F	Chronic	Eltrombopag	4 years	IVIG	113	108	114
18	19 years; Asian; F	Chronic (mild)	None	1 year (disease free 2 years)	Observation only	181	155 (After J+J vaccine)	178 (After booster with Pfizer vaccine)

ND, not done; H/O, “history of.”

Two of four patients with past H/O ITP were counseled but did not get platelet counts checked after vaccination and reported no bleeding. They are excluded from this table.

Patient# 6 had counts checked twice after vaccine dose 2 (day 2 and day 14); patient# 18 had her first vaccine with J+J and then received a Pfizer vaccine booster.

4. DISCUSSION

Recent data from adults who had preexisting ITP and received COVID‐19 vaccine showed that ITP exacerbations can occur in up to 20% percent of patients. ³ , ⁴ , ⁵ , ⁶ Almost half of these patients had severe enough ITP exacerbations after COVID‐19 vaccination to receive rescue therapy. The effect of COVID‐19 vaccination on ITP exacerbation in children with preexisting ITP, despite its importance, has not been reported to date as highlighted by Hillier et al. ¹² In our single center retrospective review of 20 children with chronic ITP ranging from 5 to 21 years of age who received the Pfizer‐BioNTech mRNA vaccine with one patient receiving the J+J vaccine, no clinically significant ITP exacerbations nor any hemorrhagic manifestations or need for rescue medication was seen. The data with one exception (one patient received J&J vaccine) are restricted to the Pfizer‐BioNTech mRNA COVID‐19 vaccine; this vaccine was approved for children above the age of 5 years in the United States at the time of data collection for this report and is now approved for children >6 months of age.

Our study has several limitations including small sample size and being limited to a single center analysis. All but two children in this cohort were 12 years of age or older. Since this is a retrospective data collection, platelet counts were not always measured a week after vaccination in spite of our recommendations during prevaccination counseling. Despite these limitations, data from this small study point to the fact that COVID vaccination in children with preexisting ITP appears to be generally safe. A strength of our study is that our patient cohort was quite heterogenous and included patients with varying length of disease duration, types of treatments given, and variable treatment responses. Many children had a transient small increase in their platelet counts post vaccination with a subsequent return to their baseline. While a larger multi‐center registry study is underway through ICON (Pediatric ITP Consortium of North America) and will provide considerable data on the effects of COVID vaccination in children with preexisting ITP, our single center study supports ongoing SARS‐CoV‐2 vaccination for C‐AYA with preexisting ITP.

CONFLICT OF INTEREST

The authors declare no conflict of interest relevant to this work.

Kaicker S, Martinko K, Bussel JB. Effects of COVID‐19 vaccination on platelet counts and bleeding in children, adolescents, and young adults with immune thrombocytopenia. Pediatr Blood Cancer. 2023;70:e30051. 10.1002/pbc.30051