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.
ABSTRACT
[Formula presented] BACKGROUND AND AIMS Fear of receiving protective vaccinations against the COVID-19 virus is high among patients with immune thrombocytopenia (ITP), an autoimmune bleeding disorder, due to uncertainty around effects on platelet count (PC) reactivity. Decreases in PC have been previously reported, including decreases of >100,000/µL including a need for rescue treatment in a small fraction of patients. For ITP patients, a further reduction in PC could trigger bleeding symptoms that require hospitalization and additional treatments. Here, we report on differences in PC changes between not-splenectomized (NS) and (Spl) splenectomized adult ITP patients to explore if Spl ITP patients have a greater risk for PC decreases following COVID-19 vaccination. Methods Data were collected using the ITP COVID-19 web-based survey that is part of the Platelet Disorder Support Association's ITP Natural History Study Patient Registry. As of June 2021, 241 adults with ITP had received at least one vaccine dose, a post vaccine PC, and had disclosed their splenectomy status. Comparisons were made between Spl and NS groups focusing on quantitative differences in reported PC changes post-vaccination. Data was analyzed using descriptive statistics, chi-square analysis, and Fisher exact tests. Results Following Dose#1 (D1): For the Spl group (n=59), 2 (4%) experienced a PC increase from baseline, 38 (64%) reported their count remained unchanged, and 19 (32%) experienced a decrease. Within the NS group (n=182), 35 (19%) experienced an increased PC, for 89 (49%) the count remained unchanged, and 58 (32%) had a decrease. PC differences between the Spl and NS groups following D1 were significant (p =.018) using a Fisher exact test. Regarding large decreases in PC, 13 Spl patients (22%) experienced a decrease >50,000/µL and 6 (10%) a decrease >100,000/µL. Within the NS group, 15 (8%) experienced a PC decrease >50,000/µL and 5 (3%) a decrease >100,000/µL. Differences in large PC changes following D1 between both groups were significant (X 2 = 8.254;p =.004). Following Dose#2 (D2): For the Spl group (n=34), comparing their post-vaccination count to their typical baseline count, 1 (3%) experienced an increased PC, 26 (76%) reported their PC remained unchanged, and 7 (21%) experienced a decreased PC. Within the NS group (n=103) comparing their post-vaccination count to their typical baseline count, 17 (17%) experienced an increased PC, 56 (54%) reported their PC remained unchanged, and 30 (29%) experienced a decreased PC. These differences were not statistically significant. Within the Spl group, 3 out of 34 (9%) experienced a large PC decrease > 50,000/µL, all 3 >100,000/µL. Within the NS group, only 5 out of 103 (5%) experienced a PC decrease >50,000/µL with only 1 >100,000/µL. The Spl group experienced more PC decreases >100,000/µL compared to the NS group following D2;this difference was statistically significant (p =.047) using a Fisher exact test. Comparison of D1 and D2 Although more PC decreases were reported in both the Spl and NS group after receipt of D1 compared to D2, this difference was not statistically significant. Comparison between Spl and NS participants with the same PC result (increase, decrease, or no change) following both D1 and D2 (n=133) did not reveal a statistically significant difference;within the NS group (n=101), 73 (73%) reported the same result while for the Spl group (n=32) 25(78%) experienced the same result. Regardless of splenectomy status (n=133), 62 (72%) participants experienced the same PC result for D1 and D2. Conclusion Fear of a post-vaccination PC decrease, especially a large decrease, may influence an ITP patient's decision to accept or refuse vaccination. Spl participants were more likely than those NS to experience larger (>50,000/µL) albeit transient decreases in their PC following vaccination. However, the overall risk for large PC decreases is minimal among individuals with ITP, even among those who have had a splenectomy. Our results should provide reassurance to mo t ITP patients and reduce vaccine hesitancy, especially for those who have not undergone splenectomy;those who have can readily be vaccinated with close monitoring and planning with a hematologist familiar with ITP. Additional studies could focus on identifying more specific factors affecting PC changes post vaccination which in turn would lead to better understanding of platelet variability in ITP patients. Disclosures: MacWhirter - DiRaimo: JD has not personally received any payment personally, but PDSA has received grants and consultancy fees from Novartis, grant and honorarium from Amgen, grant and consultancy fees from Pfizer and UCB, and grants from Argenx, Principia, Rigel, and CSL Behr: Consultancy, Honoraria, Other. Kruse: CK has not personally received payment but reports that PDSA received grants and consultancy fees from Novartis, grant and honorarium from Amgen, grant and consultancy fees from Pfizer and UCB, and grants from Argenx, Principia, Rigel, and CSL Behring: Consultancy, Honoraria, Other. Bussel: CSL: Other: DSMB;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;UptoDate: Honoraria;Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees;UCB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB;Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees;Dova/Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees;Principia/Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees;Momenta/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees;RallyBio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kruse: Alex has not personally received any payment but reports that PDSA received grants and consultancy fees from Novartis, grant and honorarium from Amgen, grant and consultancy fees from Pfizer and UCB, and grants from Argenx, Principia, Rigel, and CSL Behri: Consultancy, Honoraria, Other.
ABSTRACT
[Formula presented] BACKGROUND AND AIMS Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder causing low platelet counts (PC) and increased bleeding. COVID-19 vaccines are a major concern for ITP patients who fear vaccination might exacerbate their thrombocytopenia. To assess these concerns, PDSA developed a survey to explore how COVID-19 vaccinations impact individuals with ITP. Methods Data was collected using the ITP-COVID-19 web-based survey part of the Platelet Disorder Support Association's ITP Natural History Study. As of June 2021, 338 adult ITP patients had completed the survey. Data was analyzed with descriptive statistics and chi-squared tests. Results The majority of the 338 participants were female (78%) between 18-64 years of age (83%);118 (35%) participants reported they were in remission, and 79 (24%) reported they had undergone splenectomy. Viral Disease: Forty participants (12%) were diagnosed with COVID-19: 7 (18%) reported their PC increased from baseline, 20 (50%) reported their PC was unaffected, and 13 (32%) reported their PC decreased. Of the 20 participants who reported a PC change (increase or decrease) following a positive COVID-19 test, 13 (65%) reported their PC returned to baseline within four weeks following vaccination. Four patients (10%), all between the ages of 41-50 years, were hospitalized: 2 received dexamethasone, 1 received IVIG, and 1 required oxygen. Two of the 4 had been treated for ITP with corticosteroids within the last 6 months. Three out of 4 were female, and no additional autoimmune conditions were reported however, and 2 out of 4 reported co-morbid conditions including increased blood pressure, under-active thyroid, and allergies. No deaths occurred. Vaccination impacts: 267 (79%) participants reported receiving at least one vaccine dose at survey completion, and 137 (41%) of participants reported they were fully vaccinated: Pfizer (45%), Moderna (38%), other (17%). Following at least one vaccine dose, platelet increases were reported by 37 (15%), 127 (53%) reported no change, and decreases were reported by 77 (32%);26 did not answer. Of the 114 participants who reported a PC change following dose 1 (D1), 82 addressed the time for their PC to return to baseline;69 (84%) reported their PC returned to baseline within four weeks. Following dose two (D2), PC increases were reported by 18 (13%), 82 (60%) were unchanged, and 37 (27%) saw a decrease. Of 55 participants who reported a PC change following D2, 44 addressed the time for their PC to return to baseline with 31(71%) indicating their PC returned to their normal within four weeks. Changes in PC following receipt of D1 vs D2 were not statistically significantly (X 2=1.01, p=.31). Following at least D1, three participants reported bleeding symptoms including epistaxis, wet purpura, petechiae, bruising, and a gastrointestinal internal bleed in an asplenic 64-year-old female with alpha-gal allergy. Twenty-four (9%) participants of 262 who answered the question, reported adverse effects other than bleeding including chills and fever. Two women, aged 35 and 47, developed a blood clot after receiving the Pfizer vaccine, despite reporting no past personal or family history of hypercoagulability. Fourteen participants (13 females;1 male) reported platelet decreases >100,000/µL following vaccination, but only one received rescue treatment. Two had a pre-existing autoimmune disorder and eight a previous splenectomy. Eight received the Pfizer vaccine, five Moderna, and one AstraZeneca. Thirty (21%) participants reported a past change in platelets following a non-COVID vaccine;23/30 shared their experience following receipt of D1 of a COVID-19 vaccine including 11 (48%) who experienced a platelet decrease, 4(17%) an increase, and 8 (35%) reporting no change. Conclusion The results are very reassuring for ITP patients that the risks of aggravated thrombocytopenia due specifically to getting COVID-19 infection or vaccine are small. There were only three cases of bleeding and two of clotting;all were well-treate . Decreases in PC following viral infection and vaccine receipt did occur, but they were rarely substantial and most resolved within four weeks. These very positive findings should reduce vaccine hesitancy among ITP patients and encourage them to be vaccinated. Disclosures: MacWhirter - DiRaimo: JD has not personally received any payment personally, but PDSA has received grants and consultancy fees from Novartis, grant and honorarium from Amgen, grant and consultancy fees from Pfizer and UCB, and grants from Argenx, Principia, Rigel, and CSL Behr: Consultancy, Honoraria, Other. Kruse: CK has not personally received payment but reports that PDSA received grants and consultancy fees from Novartis, grant and honorarium from Amgen, grant and consultancy fees from Pfizer and UCB, and grants from Argenx, Principia, Rigel, and CSL Behring: Consultancy, Honoraria, Other. Bussel: UCB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB;CSL: Other: DSMB;Momenta/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees;UptoDate: Honoraria;Principia/Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees;Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees;Dova/Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees;RallyBio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kruse: Alex has not personally received any payment but reports that PDSA received grants and consultancy fees from Novartis, grant and honorarium from Amgen, grant and consultancy fees from Pfizer and UCB, and grants from Argenx, Principia, Rigel, and CSL Behri: Consultancy, Honoraria, Other.