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Introduction Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, but severe side effect after vaccination with adenovirus vector-based vaccines (ChAdOx1 nCoV-19, AstraZeneca and Ad26.COV2.S, Johnson & Johnson/ Janssen) in which platelet activating anti-platelet factor 4 (PF4) antibodies cause thrombocytopenia and thrombosis at unusual sites. Patients and treating physicians are concerned about whether other vaccinations can also trigger thrombosis in patients with a history of VITT. We showed that VITT patients can safely receive their second and third vaccination against Covid-19 with an mRNA-based vaccine. [1] However, there is limited information on whether other vaccines than against Covid-19 could booster platelet activating anti-PF4 antibodies. Uncertainty increased after a report of VITT caused by human papilloma vaccination. [2] Method In our follow-up study of patients with laboratory confirmed VITT (EUPAS45098), an anti-PF4/heparin IgG enzyme immune assay (EIA) and a PF4-dependent platelet activation assay (PIPA) were performed at regular intervals and after each vaccination reported to us. Results Seventy-one VITT patients (43 female, median age at VITT diagnosis 48, range 18-80) were followed for a median of 56 weeks (range: 13-77 weeks). During the follow-up period, eight vaccinations other than against Covid-19 were reported: Six vaccinations against influenza (three Influvac, two Vaxigrip Tetra, one Influsplit Tetra) and two consecutive vaccinations against tick-borne encephalitis (TBE) in one patient. In six patients who received vaccination against influenza, all patients showed decreasing or stable EIA optical density (OD) levels. None of them showed a reactivation of platelet-activating anti- PF4-antibodies in the PIPA. The patient who was vaccinated against TBE twice showed stable EIA OD levels and remained negative in the PIPA throughout. No new thrombosis or recurrent thrombocytopenia were observed after any vac- cination. Five out of six patients still received therapeutic anticoagulation, one patient did not receive any anticoagulative drug (Fig. 1). Conclusion Similar to observations after consecutive mRNA-vaccinations against Covid-19 in VITT patients, vaccinations against influenza and TBE very unlikely reactivate platelet-activating anti-PF4-antibodies. Further follow up of the VITT patient cohort is performed to detect any new safety signal related to recurrence of VITT. (Table Presented).
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Background: Prevalence of antiplatelet-factor 4 (PF4)/polyanionic antibodies occurring after vaccination with ChAdOx1 nCoV-19 was low. Most of these antibodies are weak and not associated with vaccine-induced thrombotic thrombocytopenia. It remains unknown whether these antibodies are preexisting or occur after the vaccination. Aim(s): In this study, we demonstrated the incidence of anti-PF4/ polyanionic antibodies, thrombocytopenia, and thrombosis after vaccination with ChAdOx1 nCoV-19 in Thais. Method(s): We conducted a prospective study in health care workers and the general population who received COVID-19 vaccination with ChAdOx1 nCoV-19. Blood collection for complete blood count, D-dimer, and anti-PF4/ polyanionic antibodies was performed before vaccination (day 0), day 10, and day 28 after vaccination. Anti-PF4/ polyanionic antibodies were detected using enzyme-link immunosorbent assay (ELISA). Functional assay with platelet aggregation was performed for all positive anti-PF4/ polyanionic antibody ELISA tests. Result(s): A total of 720 participants receiving the first, second, or third booster dose of ChAdOx1 nCoV-19 were included in the study. Baseline characteristics are presented in Table 1. Three participants developed seroconversion. Therefore, the incidence of anti-PF4/ polyanionic antibodies was 0.42% (95% confidence interval 0.08, 1.23). However, these antibodies were low titer. Fourteen (1.9%) participants had preexisting anti-PF4/ polyanionic antibodies before the vaccination but the optical density of anti-PF4/ polyanionic antibodies did not significantly increase over time (Figure 1). None of the anti-PF4/ polyanionic positive sera induced platelet aggregation. Abnormal D-dimer levels following the vaccination were not different among the positive and negative anti-PF4/ polyanionic groups (11.8% vs. 13.2%, p = 0.86). Thrombocytopenia occurred in one person with negative anti-PF4/ polyanionic antibodies. No clinical thrombosis occurred. Conclusion(s): We found a low incidence of seroconversion of anti-PF4/ polyanionic antibodies after vaccination with ChAdOx1 nCoV-19 in Thais. Most of the anti-PF4/ polyanionic antibodies are preexisting and did not significantly increase after vaccination with ChAdOx1 nCoV-19. Some participants with anti-PF4/ polyanionic antibodies had elevated D-dimer levels. However, no thrombocytopenia and thrombosis were observed. (Table Presented).
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SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Ever since the global introduction of adenovirus-vector COVID-19 vaccines, cases of cerebral venous sinus thrombosis and thrombocytopenia after immunization has been reported, posing a challenge to global effects on vaccine implementation. CASE PRESENTATION: A previously healthy 33 year old male presented to emergency room with altered mental status after a left sided seizure episode at home. Patient had a 1week history of occipital headache after receiving Ad26.COV2·S Johnson and Johnson vaccine 2 weeks prior. MRI showed superior sagittal sinus thrombosis and right high frontal hemorrhage 8.6x4.7x4.9 cm. CT angiography confirmed nearly occlusive thrombosis of superior sagittal sinus with extension to right transverse sinus. Noted to have a hemoglobin of 15, platelet count of 74000, PT/INR 16/1.2 and PTT of 28. Started on intravenous heparin and intubated for GCS of 4. Heparin was stopped due to supra therapeutic PTT of 200 overnight, drop in platelet count to 55 and hemoglobin to 13. Repeat ct head done for change in neurological exam of dilated right pupil, showed frontoparietal hemorrhage 9.3 cmx4.1 cm and 7 mm midline shift. Heparin was reversed with protamine and transfused 1 unit platelets prior to emergent decompressive craniectomy and thrombectomy. Heparin induced platelet antibody and SRA came back positive confirming vaccine induced thrombocytopenia and thrombosis. Treatment was initiated with argatroban and IVIG. Platelet count improved with no further propagation of thrombus. Patient underwent feeding tube and tracheostomy placement after 10 days due to prolonged ventilator weaning period and poor mental status. Patient's neurological status continued to improve significantly over subsequent months in acute rehabilitation facility with only residual left sided hemiparesis. Patient was successfully decannulated and anticoagulation switched to apixaban DISCUSSION: Possible pathophysiology is thought to be due to a trigger in spike protein production after biodistribution of adenovirus vaccine and a subsequent autoimmune response resulting in thrombosis. Similar to HIT, platelet consumption leads to thrombocytopenia and the continued platelet and monocyte activation increases thrombin generation, resulting in thrombosis. CDC advices to maintain a high suspicion of cases with symptoms that may indicate an underlying thrombotic event along with simultaneous thrombocytopenia. Heparin use is discouraged, unless HIT testing is negative. The International Society on Thrombosis and Hemostasis (ISTH), recommend considering non-heparin anticoagulants and high-dose intravenous immunoglobulin (IVIG). While platelet transfusions are avoided, rapid progression with rising ICP may necessitate transfusion to enable neurosurgical intervention CONCLUSIONS: Management of complications including seizures and elevated intracranial pressure (ICP) is essential to reduce morbidity and mortality risk. Reference #1: Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021;384:2092–101. Reference #2: Muir KL, Kallam A, Koepsell SA, Gundabolu K. Thrombotic thrombocytopenia after Ad26.COV2.S vaccination. N Engl J Med 2021;384:1964–5 Reference #3: Pavord S, Scully M, Hunt BJ, et al. Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. N Engl J Med 2021;385:1680–9 DISCLOSURES: No relevant relationships by Axel Duval No relevant relationships by Nadish Garg No relevant relationships by ARCHANA SREEKANTAN NAIR
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A 73-year-old man presented with left shin ulceration two weeks after receiving his first dose of the Oxford-AstraZeneca vaccine. Within 24 h of vaccination, the patient became generally unwell with fever and headache. On the third day after vaccination, he developed left shin erythema and blistering, which rapidly ulcerated. This formed two superficial ulcers with a necrotic base and a violaceous edge on the lateral aspect of his left shin, measuring approximately 2 cm × 3 cm. He had a background of atrial fibrillation and ischemic cardiomyopathy, and had been on several longstanding medications including apixaban. Blood tests revealed normal clotting, full blood count, liver and renal function. The differential diagnosis included pyoderma gangrenosum, vasculitic ulceration, and a cutaneous adverse drug reaction to vaccination. A punch biopsy was obtained from the edge of an ulcer, which revealed microthrombi within blood vessels, an ischemic epidermis, and fat necrosis of subcutaneous tissue. The patient experienced slow healing of ulceration with topical clobetasol propionate 0.05%, neomycin sulphate and nystatin ointment, and compression bandaging treatment. To our knowledge, this is the first reported case of cutaneous thrombosis associated with skin necrosis following Oxford/AstraZeneca vaccination. Recently there have been concerns related to reports of thrombotic events at atypical sites (including cerebral and splanchnic vascular beds) associated with thrombocytopenia following Oxford/ AstraZeneca vaccination (Greinacher A, Thiele T, Warkentin TE et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021;384: 2092-101). These findings extend the range of atypically located thromboses associated with COVID-19 vaccination and reinforce the necessity for physicians to be vigilant for signs and symptoms related to thromboses at atypical sites in recently vaccinated patients.
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Background and aims: Since initiation of COVID-19 vaccination, cases of cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) have been reported. Reported in-hospital mortality varies between 20-50%, but data on longterm outcome of surviving patients with CVT-VITT are not available. Methods: We report follow-up data of CVT-VITT cases after COVID- 19 vaccination from an international registry. VITT was classified according to the Pavord criteria. Outcomes were mortality, functional dependency, relapse of VITT, new thrombosis, and new bleeding events. Results: Of 62 patients with CVT-VITT who survived initial hospital admission, follow-up data were available for 48/62 (77%) cases (32 (67%) definite VITT, 7 (15%) probable VITT, 9 (19%) possible VITT). Median time from diagnosis to last follow-up was 110 days (IQR 86-174). There were no new venous or arterial thrombotic events reported in any case. Among 35/44 (80%) cases that achieved clinical remission, 0/29 cases had a relapse of VITT. Major bleeding was reported in 1/45 (2%) cases (intracranial bleed). Mortality at follow-up was 1/48 (2%, 95%CI 0-11%). 44/48 (92%) cases had a modified Rankin Scale score of 0-2 at follow-up, compared to 32/46 (70%) at hospital discharge. 16/34 (47%) of cases had returned to work or school. Conclusions: In patients who survive the acute phase of CVT-VITT, long-term mortality is low and thrombotic and bleeding events are rare. Approximately half of the CVT-VITT patients at follow-up could resume all daily activities.
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Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder against platelets characterized by a low platelet count and increased bleeding risk. ITP is likely to rise from defective immune tolerance in addition to a triggering event, such as vaccination. COVID-19 vaccination is associated with a small increased risk of development of de novo ITP. In patients historically diagnosed with ITP, relapse of thrombocytopenia after COVID-19 vaccination has been described. However, the precise platelet dynamics in previously diagnosed ITP patients after COVID-19 vaccination is unknown Aims: To investigate the effect of the COVID-19 vaccine on platelet count, the occurrence of severe bleeding complications and necessity of rescue medication in patients historically diagnosed with ITP. Methods: Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after the first and second vaccination. Linear mixed effects modelling was applied to analyse platelet count dynamics over time. Results: We included 218 ITP patients (50.9% women) with a mean (SD) age of 58 (17) years and 200 healthy controls (60.0% women) with a mean (SD) age of 58 (13) years. Healthy controls and ITP patients had similar baseline characteristics (Table 1). 201/218 (92.2%)ITP patients received the mRNA-1273 vaccine, 16/218 (7.3%) the BNT162b vaccine and 1/218 (0.46%) the Vaxzevria vaccine. All healthy controls received the mRNA-1273 vaccine. Fifteen (6.8%) patients needed rescue medication (Table 1). Significantly more ITP patients who needed rescue medication were on ITP treatment prior COVID-19 vaccination compared to patients without exacerbation (56.2% (7/16) vs 27.4% (55/202), p=0.016). We found a significant effect of vaccination on platelet count over time in both ITP patients and healthy controls (Figure 1A). Platelet counts of ITP patients decreased 7.9% between baseline and 4 weeks after second vaccination (p=0.045). Rescue medication and prior treatment significantly increased platelet count over time (p=0.042 and p=0.044). Healthy controls decreased 4.5% in platelet count (p<0.001) between baseline and 4 weeks after second vaccination. There was no significant difference in platelet count between ITP patients and healthy controls (p=0.78) (Figure 2). IPT patients with a baseline platelet count of >150x10 9/L had a significant decrease of platelet count 4 weeks after second vaccination compared to baseline (median platelet count (IQR) 205 (94) vs 203 x10 9/L (109) p=0.001). No significant decrease was seen in ITP patients with a baseline platelet count <150 x10 9/L. Median (IQR) platelet counts were similar between patients with and without exacerbation, except for 4 weeks after second vaccination (112 (105) vs 45 x 10 9/L (70), p=0.025) (Figure 1B). No significant effect was observed over time in ITP patients with rescue medication (p=0.478) (Figure 1C). In ITP patients without rescue medication, COVID-19 vaccination had a significant effect over time (p=0.001), especially 1 week after second vaccination (Figure1B). Of the 15 patients who needed rescue medication, 8/15 patients (53.3%) received rescue medication within 4 weeks after first vaccination and 4/15 (26.67%) needed rescue medication after the first as well as after the second vaccination. 3/15 (20.0%) patients needed rescue medication after the second vaccination. In the total ITP population, 5/218 (2.2%) experienced a WHO grade 2-4 bleeding complication and 3/218 (1.4%) needed platelet transfusion. 4/5 (80%) bleedings occurred before the second vaccination. One of these patients had fatal varices bleeding, although platelet count was normal. Conclusion: COVID-19 vaccination has a significant effect on platelet count in ITP patients and healthy controls. In 6.8% of ITP patients rescue medication was needed and in 2.2% of ITP patients a WHO grade 2-4 bleeding occurred. The majority of rescue medication was given and the majority bleeding complications occurred in the 4 weeks after the first vaccination. Our results demonstrate th t close monitoring of platelet count after COVID-19 vaccination is important in patients historically diagnosed with ITP.
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Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia]. Methods: The study population included adults >18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes. Results: Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR. Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT);and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to >44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment. Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67;D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients. Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. [Formula presented] Disclosures: Carrier: Sanofi: Honoraria;Pfizer: Honoraria, Research Funding;Servier: Honoraria;Bayer: Honoraria;Leo Pharma: Honoraria, Research Funding;BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria;Aspen: Honoraria;Bayer: Honoraria;LEO Pharma: Honoraria;Pfizer: Honoraria;Sanofi: Honoraria. Castellucci: BMS: Honoraria;Pfizer: Honoraria;Amag Pharmaceuticals: Honoraria;The Academy: Honoraria.