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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 preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) 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] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count 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 patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting 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 postsplenectomy and with more refractory disease, is indicated.

Introduction: Emicizumab-a subcutaneously administered, bispecific, humanized, monoclonal antibody-promotes effective hemostasis in people with hemophilia A (PwHA). The primary efficacy and safety of emicizumab were reported previously, but long-term data are limited. Here, data from a wide age-range of PwHA with/without factor (F)VIII inhibitors enrolled in the Phase III HAVEN 1 (NCT02622321), HAVEN 2 (NCT02795767), HAVEN 3 (NCT02847637), and HAVEN 4 (NCT03020160) studies are pooled to establish the durable efficacy and safety of emicizumab. Methods: The studies enrolled pediatric and adult PwHA with/without FVIII inhibitors. Participants received emicizumab prophylaxis 1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. All participants assigned to receive emicizumab (including those assigned to control arms who later switched) are included in this analysis. Participants and/or caregivers recorded outcomes of bleeding events via the Bleed and Medication Questionnaire (BMQ). Data from HAVEN 1-4 were pooled for an aggregate analysis of emicizumab efficacy and safety. Efficacy endpoints include calculated mean annualized bleed rates (ABRs; discrete, consecutive 24-week treatment intervals), model-based ABRs (calculated via negative binomial regression for full study period), percentage of participants with zero and 1-3 treated bleeds, and annualized cumulative dose of coagulation factor (ACD). Safety endpoints include incidence of adverse events (AEs) and AEs of special interest. Results: Overall, 400 PwHA in HAVEN 1, 2, 3 and 4 (n=113, 88, 151, and 48, respectively) are included in the efficacy analysis for a total of 970.3 patient years (cutoff: 15 May 2020). The safety population comprises 399 PwHA who received ≥1 dose of emicizumab (1 PwHA was randomized to receive emicizumab but did not start treatment). The median age at baseline was 28.5 (range 1-77) years. The majority of participants were White (66.8%) or Asian (18.8%); 52.3% had FVIII inhibitors. In the 24 weeks prior to study entry, 60.9% of participants had target joints. The median duration of efficacy period was 120.4 (interquartile range 89.0-164.4) weeks; 85.0% of participants had an efficacy period of ≥74 weeks; 11 participants (2.8%) discontinued study treatment. Across all 4 studies, 90.9-94.8% of the observation period was covered by completed BMQs. Across all studies, the model-based treated bleed ABR was 1.4 (95% confidence interval 1.1-1.7); treated bleed ABRs remained low throughout, and were seen to decrease with successive 24-week treatment intervals (Table 1). During Weeks 121-144 (n=170), 82.4% of participants had zero treated bleeds, and 15.3% of participants had 1-3 treated bleeds. During the same period, 91.8% and 90.0% had zero treated spontaneous/joint bleeds respectively (Figure 1). The proportion of participants with target joints reduced from 60.9% prior to study entry to 4.6% at Weeks 1-24, then ACD of FVIII (Table 2), activated prothrombin complex concentrate (aPCC) and activated recombinant FVII (rFVIIa, Table 3) generally decreased across each 24-week treatment interval. Emicizumab was well tolerated (Table 4), and no participants discontinued due to AEs beyond the five previously described (Oldenburg et al. N Engl J Med 2017; Young et al. Blood 2019; Mahlangu et al. N Engl J Med 2018; Pipe et al. Lancet Haem 2019). At data cut, 1 fatality, 3 thrombotic microangiopathies (TMAs), and 4 thromboembolic events (TEs) have been reported; all but 1 occurred in HAVEN 1. All TMAs and 2 of 4 TEs were associated with concomitant aPCC use. The percentage of participants with ≥1 drug-related AE in Weeks 1-24, 25-48 and 49-72 were 28.8%, 6.8%, and 3.0% respectively; over the same intervals, injection site reactions were observed in 23.3%, 4.8%, and 2.5% of participants. Conclusions: With nearly 3 years of follow-up, emicizumab maintained low bleed rates in PwHA of all ages, with/without FVIII inhibitors. ABRs continued to decrease and the proportion of participants with zero treated bleeds increased with each consecutive 24-week period; the trend was the same for the proportion of participants with zero joint bleeds and almost all target joints resolved. The ACDs of FVIII, aPCC, and rFVIIa decreased with successive treatment intervals. Emicizumab remains well tolerated over long-term follow-up, and no new safety concerns have been identified to date. Disclosures Callaghan: Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Research Funding; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Hema Biologics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alnylum: Current equity holder in publicly-traded company; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Roche/Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; NovoNordisk: Other, Speakers Bureau; Sancillio: Other. Négrier:CSL Behring, Octapharma, Shire/Takeda, Sobi: Research Funding; CSL, F. Hoffmann-La Roche Ltd, Sobi: Other: Travel support; Bayer, Biomarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Shire/Takeda, Sobi, Spark: Consultancy. Paz-Priel:Genentech, Inc: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Other: All authors received editorial support for this abstract, provided by Scott Battle, PhD, of Health Interactions and funded by F. Hoffmann-La Roche.. Chang:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Chebon:F. Hoffmann-La Roche Ltd: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Lehle:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in private company. Mahlangu:CSL Behring, Catalyst Biosciences, Freeline Therapeutics, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda: Consultancy; South Africa Medical Research Council, Wits Health Consortium, Colleges of Medicine of South Africa: Membership on an entity's Board of Directors or advisory committees; CSL Behring, Catalyst Biosciences, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda: Speakers Bureau; BioMarin, CSL Behring, Freeline Therapeutics, Novo Nordisk, Novartis, Pfizer, Sanofi, F. Hoffmann-La Roche Ltd, uniQure: Research Funding. Young:Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding; BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria. Kruse-Jarres:Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Consultancy; CSL Behring, Genentech, Inc., Spark: Research Funding; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Honoraria; F. Hoffmann-La Roche Ltd: Speakers Bureau. Mancuso:Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Sobi, PedNet Foundation: Consultancy; Bayer, CSL Behring, Novo Nordisk, F. Hoffmann-La Roche Ltd, Octapharma, Grifols, Sobi: Speakers Bureau; Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Catalyst, Kedrion, Sobi: Membership on an entity's Board of Directors or advisory committees; Center for Thrombosis and Hemorrhagic Diseases, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy: Current Employment. Niggli:F Hoffmann-La Roche Ltd: Current Employment. Kuebler:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Selak Bienz:F. Hoffmann-La Roche Ltd: Current Employment. Shima:Chugai Pharmaceutical Co., F. Hoffmann-La Roche Ltd, BioMarin, Bayer, Sanofi: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co. , Sanofi, Bayer, Sysmex: Speakers Bureau; Patents related to anti-FIXa/FX bispecific antibodies: Patents & Royalties; Chugai Pharmaceutical Co.: Honoraria; Chugai Pharmaceutical Co. , F. Hoffmann-La Roche Ltd, Sanofi, CSL Behring, KM Biologics, Novo Nordisk, Shire/Takeda: Research Funding; Chugai Pharmaceutical Co.: Consultancy. Jimenez-Yuste:F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer, Grifols, Octapharma, CSL Behring, Bayer: Honoraria; F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer: Consultancy; Grifols, Novo Nordisk, Takeda, Sobi, Pfizer: Research Funding. Schmitt:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Asikanius:Fimea: Current Employment; F Hoffman-La Roche Ltd: Ended employment in the past 24 months; F Hoffmann-La Roche Ltd: Divested equity in a private or publicly-traded company in the past 24 months. Levy:F Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Ended employment in the past 24 months; Spark Therapeutics: Current Employment; Baxalta US: Patents & Royalties: Royalties from ADAMTS13 patent . Pipe:Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees; Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding. Oldenburg:Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Speakers Bureau; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche. Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Other; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Membership on an entity's Board of Directors or advisory committees; University Clinic Bonn: Current Employment; Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer and Takeda: Research Funding; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Honoraria.

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 most 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.

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-treated. 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.

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 pre-vaccination 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. Sixty-nine 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 off-treatment 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 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 patients 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. Figure 1 Figure 1. Disclosures Lee: Principia Biopharma: Consultancy. Beltrami Moreira: Kadmon: Other: Spouse current employer; Jounce Therapeutics: Other: Spouse employment ended in the past 24 months. Al-Samkari: Amgen: Research Funding; Argenx: Consultancy; Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding; Rigel: Consultancy; Sobi: Consultancy; Novartis: Consultancy. Cuker: Novo Nordisk: Research Funding; Pfizer: Research Funding; Bayer: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; Novartis: Research Funding; UpToDate: Patents & Royalties; Alexion: Research Funding; Spark Therapeutics: Research Funding; Synergy: Consultancy. 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. Gernsheimer: Cellphire: Consultancy; Rigel: Research Funding; Principia: Research Funding; Novartis: Honoraria; Amgen: Honoraria; Dova: Consultancy; Sanofi: Consultancy. 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. Kessler: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees. 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. Leavitt: Pfizer: Research Funding; Merck: Consultancy; CSL DOVA: Consultancy; Catalys: Consultancy; Behring: Consultancy; BPL: Consultancy; HEMA Biologics: Consultancy; Rigel: Consultancy; Syntimmune: Research Funding; Sangamo Therapeutics: Research Funding; BioMarin: Consultancy, Research Funding. Liebman: Sanofi/Genzyme: Research Funding; Novartis: Consultancy, Research Funding; Argenx: Research Funding; Amgen: Consultancy; Dova: Consultancy, Honoraria; Pfizer: Consultancy. Newland: Novartis: Consultancy, Research Funding, Speakers Bureau; UCB Biosciences: Consultancy; Roche: Speakers Bureau; Octapharma: Research Funding; GSK: Consultancy, Research Funding, Speakers Bureau; BMS: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Argenx: Consultancy, Speakers Bureau; Angle: Consultancy; Grifols: Consultancy, Speakers Bureau. Tarantino: Pfizer: Research Funding; Novo Nordisk: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; UCB: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Grifols: Research Funding, Speakers Bureau; Principia: Membership on an entity's Board of Directors or advisory committees, Research Funding; Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioMarin: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Thachil: Amgen: Speakers Bureau; Novartis: Speakers Bureau. Kuter: Up-to-Date: Patents & Royalties: Up-To-Date; Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Pfizer, Principia, Protalex, Protalix, Rigel: Consultancy, Other: grant support and consulting fees; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), UCB: Research Funding; Rubius: Current equity holder in publicly-traded company. Cines: Dova: Consultancy; Rigel: Consultancy; Treeline: Consultancy; Arch Oncol: Consultancy; Jannsen: Consultancy; Taventa: Consultancy; Principia: Other: Data Safety Monitoring Board. Bussel: CSL: Other: DSMB; Dova/Sobi: 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; 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; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; UptoDate: Honoraria; RallyBio: 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; Rigel: 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.

Background:Immune thrombocytopenia purpura (ITP) is an autoimmune bleeding disorder that is heterogeneous in presentation, disease course, treatment response, and impact on quality of life. Treatments often cause unpleasant side effects, and prolonged use can lead to tolerability issues and toxicity. Both disease symptoms and treatments available impact the health-related quality of life (HRQoL) among patients living with this rare condition. Here, we compare self-reported fatigue and its impact among adult ITP patients and determine whether these fatigue levels differ depending on treatment status. Methods: For this study, we used three of the five surveys from the PDSA Natural History Study Registry including; treatment history and two adult QoL surveys. As of June 2020, 357 adult patients completed the survey assessing treatment history. A total of 310 adult patients completed the adult QoL (part one) survey, and 301 adults completed the adult QoL (part two) survey. Patients were stratified by 1) no treatment received 2) treated in the past 3) on therapy within the last six months; patients currently on therapy were further stratified by first and second-line therapy. Results: Among the 357 completed surveys on treatment history, 11% (n=40) reported they have never received treatment for their ITP, while 46% (n=166) have in the past, and 43% (n=158) currently receive therapy (within the last six months). Among those currently on treatment, 82% receive monotherapy; 47 (26%) use a first-line therapy (corticosteroid, IVIG, or Anti-D), and 78 (43%) are using a second-line therapy (TPO-RA, rituximab, and other second-line options). Therapies reported include TPO-RA's (41%), corticosteroids (24%), IVIG (7%), rituximab (3%), SYK inhibitor (1%), antibiotics (4%), anti-D (1%), other second-line treatments (such as MMF, dapsone etc.), and "other" therapies including complementary treatments (14%). Overall, 93 (23%) reported having had a splenectomy at some point to manage their active ITP. When asked to reflect on general tiredness, 98% of patients (n=310) reported being tired overall, with 55% reporting feeling tired 'almost always/often' regardless of treatment group or type. Those who have never been treated reported they felt tired 94% of the time, and 55% reported feeling tired 'almost always/often'. Among those who are not currently on treatment (but have received therapy in past), 99% reported feeling tired overall, and 50% reported feeling tired 'almost always/often'. Respondents using a first line therapy reported feeling tired overall 100% of the time, and reported feeling tired 53% 'almost always/often'. Respondents using a second line therapy reported feeling tired 99% of the time, and indicated they were tired 59% 'almost always/often'. There were no significant differences between these treatment types and groups identified. When asked to reflect on fatigue levels over the last seven days, collectively, 86% reported fatigue, and 30% reported experiencing it 'very much/quite a bit'. Among those who had never been treated, 85% reported fatigue, and indicated they felt fatigue 27% of the time 'very much/quite a bit'. Respondents who were not receiving treatment reported feeling fatigue 84% of the time, of which 26% was experienced 'very much/quite a bit'. Among those receiving a first line therapy, 90% reported fatigue in the last seven days, and 34% reported they experienced this 'very much/quite a bit'. Those using a second line therapy reported feeling fatigue 91% of the time, and 29% reported this was 'very much/quite a bit'. There were no significant difference among these treatment types and groups. Conclusion: Reported fatigue and overall tiredness are high among those currently on treatment, not on treatment, and those who have never been treated for their ITP. We did not find that fatigue levels were related to treatment type or group, indicating that the underlying causes may not be platelet count, or disease severity, but rather a combination of factors associated with having an unpredictable chronic disease. The multi-faceted effects of ITP often take a significant toll on patients' quality of life. The registry continues to collect data with the intent of understanding the longitudinal impact of ITP and in future with more of a sample size we can learn if these trends continue. Disclosures Kruse: CSL Behring: Other: Grant paid to PDSA; UCB: Other: Grant and consultancy fee, all paid to PDSA; Rigel: Other: Grant paid to PDSA; Principia: Other: Grant paid to PDSA; Pfizer: Other: Grant and consultancy fee, all paid to PDSA; Argenx: Other: Grant paid to PDSA; Amgen: Other: Grant and honorarium, all paid to PDSA; Novartis: Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work. Lambert:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Consultancy; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; Octapharma: Consultancy, Research Funding; Bayer: Consultancy; Argenix: Consultancy; ClinGen: Honoraria; Platelet Disorder Support Association (PDSA): Consultancy; 22qSociety: Consultancy; ITP Australia: Consultancy; CdLS Foundation: Consultancy; RDMD ITP study: Consultancy; Sysmex: Research Funding; AstraZeneca: Research Funding.

Background:Immune thrombocytopenia purpura (ITP) is an autoimmune bleeding disorder that is heterogeneous in presentation, disease course, treatment response, and impact on quality of life. Treatments often cause unpleasant side effects, and prolonged use can lead to tolerability issues and toxicity. Disease symptoms and treatments available impact the health-related quality of life (HRQoL) among patients living with ITP. Here, we compare anxiety and its impact among adult ITP patients and determine whether anxiety levels differ dependent on treatment. Methods: For this study, we used three of the five surveys from the PDSA Natural History Study Registry including; treatment history and two adult QoL surveys. As of June 2020, 357 adult patients completed the survey assessing treatment history. A total of 310 adult patients completed the adult QoL (part one) survey, and 301 adults completed the adult QoL (part two) survey. Patients were stratified by 1) no treatment received 2) treated in the past 3) on therapy within the last six months; patients currently on therapy were further stratified by first and second-line therapy. Results: Among the 357 completed surveys on treatment history, 11% (n=40) have never received treatment for ITP, 46% (n=166) have in past, and 43% (n=158) currently receive therapy (within the last six months). Among those currently on treatment, 82% receive monotherapy; 26% use a first-line therapy (corticosteroid, IVIG, or Anti-D), and 43% are using a second-line therapy (TPO-RA, rituximab, and other second-line options). Therapies reported include TPO-RA's (41%), corticosteroids (24%), IVIG (7%), rituximab (3%), SYK inhibitor (1%), antibiotics (4%), anti-D (1%) and other second-line treatments (such as MMF), and "other" treatments including complementary therapies (14%). Overall, 23% had a splenectomy at some point to manage their active ITP. When asked to reflect on the last seven days, patients completing the QoL survey (n=310), 66% felt anxious; 17% reported this was experienced 'almost always/often'. Among those who have never been treated, feeling anxious was reported 67% of the time; 18% reported feeling this way 'almost always/often'. A similar trend was observed in patients not currently on treatment. Among those receiving a first line therapy, anxiousness was reported 74% overall; 19% 'almost always/often'. Among those receiving a second line therapy, 72% reported feeling anxious; 9% reported feeling this way 'almost always/often'. Differences in high levels of anxiousness reported among the different treatment groups was not significant (X2= 3.4, p=.48). Difficulties focusing were reported (51%, 9% reporting this occurred 'almost always/often'). Among those who have never been treated, difficulties were reported (48%, 12%, 'almost always/often'). Those not currently receiving treatment had difficulties focusing due to anxiety (50%, 4% reporting this 'almost always/often'). Those on first line treatment indicated focus was impacted by anxiety overall (60%, 36% 'almost always/often') and those receiving second-line therapy reported (58%, 8% 'almost always/often'). Differences in high levels of anxiety affecting concentration reported among the treatment groups was significant (X2= 20.87, p=.00033), revealing a higher anxiety profile among those using corticosteroids. When difficulty with focus due to anxiety was compared between those receiving corticosteroids and those receiving a TPO-RA specifically, anxiety was significantly higher in the steroid group (X2=9.15, P=.0024); this trend was not found to be statistically significant among other second line therapies. Conclusion: The physical symptoms of ITP often guide treatment selection for patients however, providers should also focus on mitigating stress and other indicators of mental health in order to provide the best outcome and quality of life in disease course. Differences in interpretation behind the terms feeling 'anxious' vs ' anxiety affecting focus' may explain our conflicting results. Higher anxiety levels (in contrast to higher anxiousness) appeared related to treatment type in those currently receiving therapy; corticosteroid users were more impacted by their anxiety than those receiving TPO-RAs; steroids are known to interfere with mood and concentration, and this is confirmed by patients in this survey. Disclosures Kruse: CSL Behring: Other: Grant paid to PDSA; UCB: Other: Grant and consultancy fee, all paid to PDSA; Rigel: Other: Grant paid to PDSA; Principia: Other: Grant paid to PDSA; Pfizer: Other: Grant and consultancy fee, all paid to PDSA; Argenx: Other: Grant paid to PDSA; Amgen: Other: Grant and honorarium, all paid to PDSA; Novartis: Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work. Lambert:AstraZeneca: Research Funding; Principia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shionogi: Consultancy; Sysmex: Research Funding; RDMD ITP study: Consultancy; ITP Australia: Consultancy; CdLS Foundation: Consultancy; 22qSociety: Consultancy; Platelet Disorder Support Association (PDSA): Consultancy; ClinGen: Honoraria; Bayer: Consultancy; Argenix: Consultancy; Octapharma: Consultancy, Research Funding; Educational Concepts in Medicine: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Epigenetic control of gene expression occurs within discrete spatial chromosomal units called topologically associating domains (TADs), but the exact spatial requirements of most genes are unknown; this is of particular interest for genes involved in cancer. We therefore applied high-resolution chromosomal conformation capture sequencing to map the three-dimensional (3D) organization of the human locus encoding the key myeloid transcription factor PU.1 in healthy monocytes and acute myeloid leukemia (AML) cells. We identified a dynamic ∼75-kb unit (SubTAD) as the genomic region in which spatial interactions between PU.1 gene regulatory elements occur during myeloid differentiation and are interrupted in AML. Within this SubTAD, proper initiation of the spatial chromosomal interactions requires PU.1 autoregulation and recruitment of the chromatin-adaptor protein LDB1 (LIM domain–binding protein 1). However, once these spatial interactions have occurred, LDB1 stabilizes them independently of PU.1 autoregulation. Thus, our data support that PU.1 autoregulates its expression in a “hit-and-run” manner by initiating stable chromosomal loops that result in a transcriptionally active chromatin architecture.

Introduction Acquired hemophilia A (AHA) is a severe bleeding disorder due to autoantibodies against factor VIII (FVIII) with high morbidity/mortality from bleeding and complications from immunosuppression. Outcomes could improve with adequate hemostatic prophylaxis in the outpatient setting and reduced immunosuppression. Emicizumab, a FVIII-mimetic bispecific antibody, has revolutionized prophylaxis for congenital hemophilia A, but the role in AHA is unknown with limited data. Methods 87 hematologists at different US hemophilia treatment centers (HTCs) were queried on the use of emicizumab for AHA. Pediatric hematologists were excluded given the negligible incidence of pediatric AHA. 10 respondents had experience with off label emicizumab for AHA and were prompted for de-identified data on AHA cases treated with emicizumab at their HTC. These responses were compiled into a central database at the University of Washington under IRB exemption. Results Of the 87 US HTCs queried, 32 reported experience treating AHA; combined, 358 patients with AHA were treated at the 32 HTCs within the last 5 years. 10 respondents (31%) used off label emicizumab for a total of 40 patients with AHA. HTCs that had not used emicizumab for AHA had seen fewer cases of AHA in the last 5 years (average 8 vs 17 patients). Most HTCs (86%) would consider emicizumab if safety data in AHA was available. Of the 10 respondents who used emicizumab for AHA, 7 submitted deidentified data for a total of 24 cases of AHA treated with emicizumab. The median age of subjects was 73 years (range 34-87), 10 were female. The majority (17) were Caucasian. 15 had conditions often associated with AHA: autoimmune disease (7, with 4 on immunosuppression), cancer (6), and peripartum (2). Additionally, one patient had mild congenital hemophilia A and developed an autoantibody to FVIII. Other comorbidities included metabolic syndrome (11), vascular disease (10), prior venous thrombosis (3, none on anticoagulation), alcoholic pancreatitis (1) and Alzheimer's dementia (1). 3 had no comorbidities. At time of diagnosis, 4 were on antiplatelet therapy and 2 on therapeutic anticoagulation, which were discontinued in all cases. The majority presented with bleeding (92%): 63% was spontaneous with most in soft tissue (67%), followed by hematuria (17%), hemarthrosis (8%), retroperitoneal (8%), gastrointestinal (8%), subdural hematoma (4%). At diagnosis, the median FVIII was Emicizumab was mostly started to improve bleeding prophylaxis and/or facilitate outpatient management (Table A). Dosing varied with most receiving the standard loading regimen used for congenital hemophilia A (Table A). Bleeding resolved in most after starting emicizumab (Table B). One patient had new ecchymoses after the first loading dose, which resolved after further doses. 3 patients had breakthrough bleeding on maintenance emicizumab: two had hematuria that resolved with hemostatic agents and in one case a procedure; another had severe gastrointestinal bleeding 4 months after starting emicizumab that required an endoscopy and hemostatic agents (Table B). The majority (95%) tolerated emicizumab without complications. One patient developed a lower extremity deep vein thrombosis (DVT) while on maintenance emicizumab 3 mg/kg every other week. This patient had no history of DVT, but was on apixaban for atrial fibrillation until AHA diagnosis. Anticoagulation was resumed after the DVT. Emicizumab was held for 4 weeks and restarted at 1.5 mg/Kg every other week with no additional adverse events. At the time of the survey, 4 patients had died, of whom 2 were on emicizumab. No deaths were attributed to emicizumab. Of the living patients, 8 remain on emicizumab with persistent inhibitors, with 6 off immunosuppression (Figure One). Conclusion Emicizumab could improve AHA outcomes by providing outpatient hemostatic prophylaxis with lower intensity immunosuppression. Additional safety and dosing data are needed to clarify the role of emicizumab in AHA. Figure 1 Figure 1. Disclosures Poston: TeraImmune: Consultancy. von Drygalski: Hematherix, Inc: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Super FVa; uniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Parnes: Shire/Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Genentech/Hoffman LaRoche: Research Funding; Sigilon: Membership on an entity's Board of Directors or advisory committees; Sunovion: Consultancy; I-mAb: Consultancy; Aspa: Consultancy; UniQure: Membership on an entity's Board of Directors or advisory committees. Walsh: Tremeau: Consultancy; Takeda: Consultancy; Biomarin: Consultancy; Genentech: Consultancy; Novo Nordisk: Consultancy. Kessler: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding. Janbain: Bayer: Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee member; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Malec: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy, Research Funding; Takeda: Consultancy. Kruse-Jarres: Biomarin: Consultancy; Genentech: Consultancy, Research Funding; Genentech/Roche: Speakers Bureau; CSL Behring: Consultancy; CRISPR: Consultancy; Pfizer: Consultancy. OffLabel Disclosure: Emicizumab is FDA approved for congential hemophilia A and is a bispecific monoclonal antibody that binds coagulation factors IXa and X. We will discuss off label use for acquired hemophilia A.

Introduction: Sickle cell disease (SCD) causes devastating complications that can affect any organ in the body. Particularly, SCD can present with neurological complications of overt strokes, silent infarcts and cognitive impairment. As patients are living longer with SCD, cognitive functioning is an important aspect of their disease as deficits can impact education, employment, or adherence to medications. Most of the studies assessing cognitive impairment in this population have been in children with limited data on adults. This study explored the results of cognitive testing in adult patients with SCD when compared to normative data. This study also sought to determine any association between psychological factors (baseline anxiety and depression) as well as biological factors (i.e. hemoglobin levels). Methods: This was a cross-sectional study conducted at the Sickle Cell Center of Southern Louisiana in New Orleans.The study included adults with a diagnosis of sickle cell disease regardless of subtype who were over the age of 18. Patients were excluded if they were not able to physically complete the tasks. Executive function, memory, psychomotor speed, and memory were assessed using the following tasks from standardized pencil-and-paper cognitive tasks from the Cambridge Neuropsychological Automated Battery (CANTAB) test: Stocking of Cambridge (SOC),Delayed Matching to Sample (DMS), Paired Associates Learning (PAL), Motor Screening Task (MOT), Intra-Extra Dimensional Set Shift (IED), Spatial Working Memory (SWM). The Hospital Anxiety and Depression Subscale (HADS) clinical assessment tool was used to screen for anxiety and depression at the time of testing. A HADS score >8 denotes significant anxiety or depression. Results: A total of 22 patients (59% females, mean age 29.6±2.1 years) were included in this study. Attention and psychomotor speed were relatively preserved cognitive domains with 59.1% of patients scoring greater than 75 thpercentile relative to normative mean. Conversely, executive functioning often appeared impaired with 72.7% and 77.3% of patients scoring below 25 thpercentile in outcome measures of IED and SWM, respectively. Similarly, a significant percentage of patients scored below 25 thpercentile in outcome measures of visual memory, PAL and DMS, 63.6% and 45.4%, respectively. Fifteen participants (68%) screened positive for anxiety while two screened positive for depression. Patients with anxiety tended to perform worse on most cognitive tasks, although the differences in scores did not reach statistical significance. Additional analyses of association of biologic factors and neurocognitive functioning are currently underway. Discussion and Conclusion: Our results support that adults with sickle cell disease often suffer from cognitive deficits, which was expected based on pediatric studies demonstrating cognitive impairment in children with SCD. Interestingly, we observed a predominance of poor executive function over changes in attention and psychomotor speed in this study. This is in contrast with what providers familiar with "mini mental assessment" for dementia may expect. Typical dementia patients develop attention and memory changes before executive function is affected. Therefore, it is possible that cognitive impairment in SCD may go by unnoticed without proper testing. Additionally, in this cohort, anxiety was frequent and tended to associate with worse performance. Since this is a cross-sectional study, it is unclear whether cognition is progressively impaired over the years. Prospective studies are required to help determine whether and how fast progression occurs and what risk factors are implicated in the development and progression of cognitive impairment. Such deficits have been demonstrated to be associated with difficulties around employment and adherence to medication, which ultimately jeopardizes long term outcomes. Overall, we recommend neurocognitive and psychological evaluations as part of the routine care for adult SCD patients since abnormal findings seem common and may not be obvious without adequate testing for different domains. Treatment of anxiety disorder and cognitive rehabilitation may prove helpful to improve cognition in SCD patients. Disclosures Fertrin: Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kruse-Jarres: Genentech/Roche: Speakers Bureau; Pfizer: Consultancy; CSL Behring: Consultancy; CRISPR: Consultancy; Biomarin: Consultancy; Genentech: Consultancy, Research Funding.