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Introduction: Due to the COVID-19 outbreak, many chronic patients and elective surgical procedures have been postponed to create spaces for the hospitalization of COVID-19 patients, raising issues related to this change. The objective of this study is to assess the effect of the COVID-19 pandemic on the demand for blood products transfusion. Materials ant methods: The study presents the results of a retrospective study of blood transfusions in COVID-19 patients admitted to the Constanta County Emergency Clinical Hospital. The period of study was January-December 2021. We compared the transfusion requirement for each type of blood component in COVID 19 patients versus patients with non-COVID pathology. Results and discussions: During 2021, we transfused 282 COVID-19 patients;150 patients had only Covid pneumonia (of which 19 patients with severe forms needed intensive care in ICU-Covid), and 132 patients had various co-morbidities. The maximum blood requests was registered in the period February - April 2021, with a peak of 63 patients in April 2021. The main co-morbidities in patients with Covid 19 were: severe anemia in patients with malignant hemopathies. Anemia at admission in patients with Covid pneumonia is reported in more than 40% of patients. Moderate anemia (Hb <11 g/dL) is considered as an independent risk factor for the severe course of COVID-19 infection and mortality in these patients. The transfusion requirement in these patients was greater than 1.43 RBC (units/patient), 0.81 Plasma units/patient, 0.40 Platelets concentrate units + single donor platelet concentrate units/patient, in accordance with the associated pathology. Conclusion(s): The most requested product was packed red blood cells, the correction of anaemia being an important factor in preventing the severe course of the disease. The platelet requirement was 0.15 units/patient, thrombocytopenia being present in patients with severe evolution of the infection (hospitalized in ICU-COVID). The most requested blood groups were O+ and A+. COVID-19 transfusion data will help plan and prepare for the use of blood resources during the pandemic.Copyright © 2022 Sevigean Ali et al., published by Sciendo.
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With increasing evidence of the success of hematopoietic progenitor cell (HPC) transplantation in the cure of many benign and malignant diseases, such interventions have been performed at increasing rates for the past several years. Due to myelosuppression caused by the conditioning and graft-versus-host disease (GVHD) prophylaxis regimens, blood component transfusions are almost inevitably needed. During transplantation, patient's hematopoietic lineages reconstitute to the HPC donor's progenitor cell types. Therefore, specific immunoserologic and hemotherapeutic aspects need to be considered for the selection of blood components during different phases of transplantation for successful outcomes. Those considerations include but are not limited to ABO and human leucocyte antigen (HLA) compatibility of the transfused blood components with either or both the patient and the HPC donor according to the particular phase of transplantation, and the special blood component processing to reduce the risk of transfusion associated graft-versus-host disease (TA-GVHD), cytomegalovirus (CMV) transmission in CMV seronegative patients and immune mediated platelets refractoriness. Complications may still arise, particularly in major, minor, or bidirectional ABO mismatched transplantations and/or due to the HLA mismatch and alloimmunization. Here we discuss the indications, immunoserologic considerations and the special component processing of red blood cells (RBCs), platelets, granulocytes, and plasma transfusions, based upon the current evidence and describe the prevention and management of salient, pertinent complications.Copyright © 2022 The authors.
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Background/Purpose: Concomitant systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection cases are rare worldwide. It is established that SLE patients have an increased risk of opportunistic infection due to immune dysregulation, as well as in HIV. Method(s): A case of a 25-year- old Filipino man with systemic lupus erythematosus admitted due to a 1-week intermittent fever associated with headache, loss of appetite, and generalized body weakness was reviewed in a tertiary hospital in the Philippines. Result(s): An initial diagnosis was made from the clinical presentation of Raynaud's phenomenon, an elevated antinuclear antibody (1:320;nuclear, speckled), 2+ proteinuria, thrombocytopenia, and nail fold capillaroscopy findings consistent with mixed connective tissue disease. Patient was started on hydroxychloroquine and prednisone. He was admitted as a case of Streptococcus bacteremia with COVID-19 pneumonia after initial diagnosis, presenting as fever, and thrombocytopenia as low as 23.000/mul. Patient presented with a scaly erythematous annular lesion at his left wrist since December 2021 where a skin punch biopsy showed findings consistent with dermatophytosis. Direct immunofluorescence staining showed deposition of granular IgM (+3), C3 (+1), Fibrinogen (+3), and C1q (+1) in the basement membrane zone consistent with Lupus Erythematosus. Additional findings were oral thrush, dermatophytosis, and Pneumocystis pneumonia. Patient was started on antibiotics, remdesivir, and antifungal medications. Being severely immunocompromised, work up for HIV was initiated. Rapid HIV screening was positive, CD4 count revealed 7 (3.14%), and subsequent confirmatory western blot was positive. Additional treatment included hydroxychloroquine, methylprednisolone pulse therapy, and platelet concentrate transfusion. He was referred for CD4 monitoring, and ARV treatment enrollment, however, the patient expired a month after his discharge. Conclusion(s): This case is thereby reported to document a rare case of systemic lupus erythematosus (SLE) male patient with concomitant HIV, SARS-CoV- 2, and opportunistic infections secondary to AIDS. Diagnosis becomes challenging in patients with autoimmune diseases and multiple infectious diseases as clinical presentations tend to overlap and may show similar manifestations. In this setting, skin biopsy utilizing direct immunofluorescence can help establish an accurate diagnosis especially when clinical features and histopathology are overlapping.
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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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SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: We present a case of diffuse alveolar hemorrhage (DAH) secondary to Immune Thrombocytopenia (ITP) temporally related to SARS-CoV-2 (CoV) vaccine. CASE PRESENTATION: An 80-year-old female presented with dyspnea, hemoptysis, diffuse petechiae, and ecchymosis;no focal neurological deficits or hepatosplenomegaly. She had no history of bleeding or autoimmune disorders;no recent respiratory or gastrointestinal infections;but received Moderna CoV vaccine 4 weeks prior to presentation. Chest X-ray (CXR) and CTA of chest demonstrated multifocal bilateral patchy airspace opacities. Initial platelet was 1 x 109/L with normal morphology of platelet and WBC, and no schistocytes. Coagulation panel, LDH, haptoglobin, and bilirubin were all normal. CoV NAAT was negative. Dexamethasone and IVIG for high suspicion of ITP was initiated. Supportive care including platelet transfusion and oxygen via nasal cannula was maintained. Platelets were severely consumed in spite of treatment with platelets undetectable at nadir and rapid decrease of hemoglobin, approximately 6 g/dL, within 24 hours of admission. IgM and IgG plasma platelet autoantibodies returned positive, confirming ITP diagnosis. Additional workup was unremarkable for infections, rheumatologic disorders, and malignancy. Respiratory state rapidly declined with worsening hemoptysis and significant increase of bilateral airspace opacities on repeat CXR, indicative of DAH. Lung protective mechanical ventilation protocol was initiated on day 2 with medically induced deep sedation and paralysis to minimize hemorrhage exacerbation. Rituximab, romiplostim, and nebulized tranexamic acid were added for severe and refractory ITP, which eventually slowed platelet consumption, reduced pulmonary hemorrhage, and stabilized hemoglobin. Platelets recovered above 30 x 109/L on day 9, and subsequent bronchoscopy showed persistent blood on bronchoalveolar lavage. She was successfully extubated after prolonged 14-day intubation. Platelet normalized before discharge. DISCUSSION: Incidence of ITP related to CoV vaccine is approximately 0.8-0.9 case per million vaccinated. Most cases present with superficial bleeding and respond to first-line agents with rapid recovery. GI bleeding and intracranial hemorrhage, but not DAH, have been reported in several cases, requiring third-line agents to promote platelets recovery and achieve hemostasis. We report a case of DAH secondary to ITP following CoV vaccine. Temporal relationship and severe presentation are consistent with other reports of ITP with life-threatening internal bleeding probably secondary to CoV vaccine. CONCLUSIONS: When DAH is suspected, rapid escalation of treatment to include third-line agents is desired. If intubated, lung protective ventilation with paralysis is preferred to minimize further lung injury due to DAH. Reference #1: Lee EJ, Cines DB, Gernsheimer T, et al. Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination. Am J Hematol. 2021;96(5):534-537. doi:10.1002/ajh.26132 doi:10.1016/J.VACCINE.2021.04.054 Reference #2: Welsh KJ, Baumblatt J, Chege W, Goud R, Nair N. Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2021;39(25):3329-3332. Reference #3: Tarawneh O, Tarawneh H. Immune thrombocytopenia in a 22-year-old post Covid-19 vaccine. Am J Hematol. 2021;96(5):E133-E134. doi:10.1002/ajh.26106 DISCLOSURES: No relevant relationships by Timothy Barreiro No relevant relationships by Tiewei Cheng No relevant relationships by Zeina El Amil No relevant relationships by Jin Huang No relevant relationships by Sanaullah Khalid
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Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. Approximately 2% of patients with CLL develop immune thrombocytopenic purpura (ITP) during the course of the disease. When resistant to steroids, this constitutes as indication for treatment of the CLL. Here we report a patient with refractory ITP secondary to CLL successfully treated with venetoclax. Aims: To present an interesting case with CLL related refractory ITP treated successfully with novel agent venetoclax. Methods: Patient data was taken from the patient herself and Hospital records. Informed consent to publish the case is obtained from patient. Permission for off-label venetoclax and eltrombopag was obtained from Ministry of Health of Turkey. Results: 46-year-old female patient presented with lumps on her neck that were present for the last 9 months in November 2020. She has a history of frequent pneumonia and otitis but no constitutional symptoms. Her physical examination reveals multiple 2cm lymphadenopathies on her neck and no organomegaly or other pathological features. Blood work shows mild lymphocytosis (6800/mm3) with no serious cytopenias. Peripheral blood smear, flow cytometry and bone marrow biopsy were all compatible with CLL. She was classified as Binet A CLL and was followed up with no treatment after appropriate vaccinations against capsulated pathogens. In July and August 2021 she received two doses of mRNA vaccination against COVID-19. On 1st November 2021 she experienced excessive menstrual bleeding and blood work showed platelet count of 23000/mm3, she was started on steroids (1 mg/kg/day) and after 4 days platelet count has risen to 55000/mm3, she discontinued steroids on her own against medical advice. On 13th of November she presented with extensive petechiae and purpura and was again started on steroids and was given the courses of intravenous immunoglobulins (IVIG) without any sustained response. She was refractory to platelet transfusions too. She was transferred to our clinic. She was found to have del11q and del13q. She refused bone marrow examination. She was treated with rituximab, steroids, vincristine, IVIG and eltrombopag for ITP without success (Fig. 1). She had a minimal response to IVIG only. She received two courses of bendamustine (90 mg/kg for two days) also without success. Three courses of plasmapheresis yielded no response either. After mild success with immunadsorbtion apharesis she was started on venetoclax plus rituximab with ramp-up. Sustained response was achieved within the first week of venetoclax therapy. (Figure Presented ) Summary/Conclusion: Gordon et al. reported 2 CLL cases one with ITP and other with Evans syndrome successfully treated with venetoclax. We think, this treatment should be considered in patients with refractory immune cytopenias secondary to CLL and assessed with prospective clinical trials.
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Background & Aim: During the COVID pandemic the National Marrow Donor Program® (NMDP)/Be The Match® required cryopreservation of unrelated hematopoietic stem cell (HPSC) products prior to initiation of recipient conditioning to minimize risks associated with logistical complications. Transplant centers are still evaluating cryopreservation associated risk factors due to reported concerns on poor postthaw graft quality compared to fresh products. We evaluated the effect of cryopreservation on engraftment outcomes. Methods, Results & Conclusion: Data from patients receiving either unrelated HPSC fresh or cryopreserved products obtained through the NMDP were included in this study. There were 43 fresh infusions during (Table Presented) during 2019 and 54 cryopreserved infusions between January 2020 and January 2022. Neutrophil and platelet engraftments were our primary endpoints. Absolute neutrophil count (ANC) recovery was defined as an ANC of ≥ 0.5×109/L for three consecutive laboratory values obtained on different days. While platelet engraftment was determined as the first day of three consecutive measurements, obtained on different days, where the platelet count is ≥ 20×109/L without a platelet transfusion in the previous seven days. Medians for two unpaired groups were compared by using Mann-Whitney U test. Two-sided p-values < 0.05 were considered statistically significant. Of the total of fresh transplants, 62.8% of patients underwent reduced intensity conditioning (RIC) while 37.2% underwent myeloablative conditioning (MAC). Regardless of the diagnosis category and in accordance with the American Society of Blood and Marrow Transplantation (ASBMT) Standardized Request for Information (RFI), 11.6% of recipients were classified as a high risk, 20.9% as an intermediated risk, 41.9% as a low risk and 25.6% unclassified. Whereas 52.8% of patients who received cryopreserved products underwent RIC and 47.2% underwent MAC;according to ASBMT-RFI classification, 18.9% were considered as a high risk, 24.5% as an intermediated risk, 41.5% as a low risk and 15.1% unclassified. Engraftment characteristics for both groups of patients is summarized in Table I. No statistically significant differences in engraftment were observed. Our analysis suggests that compared to outcomes of fresh product transplantation, cryopreservation does not negatively effect allograft quality in terms of neutrophil and platelet engraftment.
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Background & Aim: Background: Traditionally, ‘fresh’ Hematopoietic progenitors cell (HPC) infusions have been preferred over cryopreserved HPC in Allo-HCT because cryopreservation and thawing leads to cell loss, besides DMSO-related adverse reactions in patients. Emergence of COVID-19 pandemic has severely affected fresh HPC infusions and most professional bodies recommend cryopreservation of HPC products before initiating conditioning chemotherapy. Although some western studies suggest no significant impact of graft manipulation on patient outcome, there is no available data from the developing world.Aim: We compare neutrophil and platelet engraftment in patients undergoing Allo-HCT with fresh and cryopreserved HPC products. Methods, Results & Conclusion: Material and Method: Allo-HCT data from October 2018 to October 2021 were analyzed. Cryopreservation was performed by controlled-rate freezing using 10% DMSO, plasmalyte- A and human albumin ( 1:2:1) as cryoprotectant. Cryopreserved products were stored in vapour-phase of Liquid nitrogen tank. CD34+ enumeration and viablity( by 7-AAD) was done on Flow-cytometry on fresh and post-thaw HPC samples. Neutrophil engraftment was defined as absolute neutrophil count >0.5 ×109/L for 3 days. Platelet engraftment was defined as independence from platelet transfusion for at least 7 days with a platelet count >20 × 109/L. Statistical analysis using Wilcoxon Rank Sum test. Results: Ninety-six patients underwent allo-HCT (46 received fresh and 50 received cryopreserved HPC products) (Table 1). There was no significant difference in neutrophil engraftment with fresh and cryopreserved grafts (p>0.05) in different types of transplants( Matched related/unrelated and haploidentical). 22% (11/50) of cryopreserved graft infusions were associated with Grade-1 DMSO-related adverse reactions, which were managed with symptomatic treatment. Cryopreservation increased the cost of related allogeneic transplants by USD1100. No cryopreserved HPC product was culture positive on microbiological assessment. Conclusion: In our experience, the engraftment kinetics were similar with fresh and cryopreserved HPC products as CD34+cell dose administered was almost the same. Cryopreserved grafts had a median 7% CD34+cell loss, associated with mild DMSO-related adverse reactions and cost increment. Even though, graft cryopreservation is a feasible alternative during the pandemic, it is crucial to ensure graft quality and promptly manage DMSO-related adverse reactions.(Table Presented) Table 1 Comparison of Fresh and cryopreserved HPC products in Allo-HCT
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CASE: A 25-year-old female with no medical history presented with progressive petechial rash at the chest, trunk, bilateral forearms, and thighs. Patient had the COVID-19 vaccine three weeks prior. However, denied recent travel or tick bites. No home medications nor recent hospitalizations, other than a tooth extraction a month earlier. On physical exam, the patient's vitals were unremarkable and had non-blanching petechial rash noted on her torso and bilateral extremities. Labs were significant of platelet count 1,000/mcL, hemoglobin 12.9 mg/dL, WBC 7.52 x103 /mcL, absolute lymphocytes 3.33x103 /mcL. Patient was administered two units of platelets followed by intravenous immunoglobulin (IVIG) and dexamethasone. No bleeding or hemodynamic instability was identified. Platelet count improved to 100,000/mcL over the next 24 hours. Further work-up revealed a positive HIV-1 antibody, absolute CD4 256 cells/mcL, viral load 27,300 copies/mcL. Once starting antiretroviral therapy (ART);bictegravir, emtricitabine, and tenofovir alafenamide, platelet count increased within a month to more than 200,000/mcL. IMPACT/DISCUSSION: Thrombocytopenia is defined as platelet count below 150,000/mcL. HIV-induced cytopenias are common, mainly neutropenia. However, sentinel events of thrombocytopenia are very rare in otherwise healthy individuals. A review of 5,290 HIV patients at the University of British Columbia from 1996 to 2012 revealed only 0.6% incidence of severe thrombocytopenia which they defined as platelet count <20,000/mcL. The exact pathophysiology is not clearly understood, but it is possible that antibodies against HIV cross-react with platelets or possible immune alteration. This is suggested by the prompt resolution of thrombocytopenia once ART is initiated. Immune thrombocytopenia (ITP) is a diagnosis of exclusion typically presenting with thrombocytopenia while other cell lines are normal. The greatest concern is when platelet counts drop less than 20,000/mcL due to fears of intracranial bleeding. Literature is not decisive in a correlation between platelet counts and risk of bleeding, yet it is suggested that circulating platelets are younger and more effective to maintain hematopoiesis in ITP when compared to other causes of thrombocytopenia. Treatment approach for ITP depends on the bleeding risk. In the presence of bleeding, urgent platelet transfusion, glucocorticoids, and IVIG are the mainstay of treatment. In absence of bleeding, individualized assessment of the condition is recommended to either monitor or treat. Platelet counts below 20,000-30,000/mcL require steroids or IVIG. In our case, she surprisingly presented only with minor petechial bleeding. Prompt initiation of ART, close monitoring of platelet response and CD4 count, as well as identifying resistant thrombocytopenia is indicated once patient is medically stable. CONCLUSION: Sole presentation of ITP due to HIV infection is rare. Risks of critical bleeding and further management are crucial to prevent fatal outcomes.
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CASE: 54-year-old female presented with 1 week of generalized weakness, headache, congestion, cough with dark- colored phlegm, and several days of decreased smell and taste. She was unvaccinated and had positive sick contacts. Patient tested positive for Covid and found to have severe thrombocytopenia with platelets of 5K/uL, very rare schistocytes on smear, and no other notable abnormalities. She received platelet transfusion and was treated for presumed immune thrombocytopenia with IVIG and dexamethasone. The patient had no petechiae, bleeding, or other symptoms concerning for secondary TMA, notably TTP. The platelet count was 93 K/uL by day 5 and she was discharged home. Later that day her ADAMTS13 test resulted at <2% and the ADAMTS13 antibody was elevated. The patient was asked to return to the hospital for monitoring of TTP symptoms. She reported improvement in her weakness. Her thrombocytopenia and oxygen saturation remained normal. Bilateral lower extremity ultrasound showed no lower extremity VTE. On the day of discharge, 10 days after her original thrombocytopenia identified, she had a platelet count of 373 K/uL and repeated ADAMTS13 of 14.8%. IMPACT/DISCUSSION: ADAMTS13 is known as von Willebrand factor (VWF) protease as it cleaves prothrombotic and highly adhesive to platelets ultra-large multimers of VWF into smaller multimers, thus modulating VWF activity and regulating the adhesive function. A severe deficiency of ADAMTS13 characterizes TTP, a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. There are literature reports of TTP and TTP-like syndromes in Covid-19. It is speculated that in COVID-19, the excess of VWF released in response to endothelial activation likely exhausts the available reserves of ADAMTS13, which may then propagate formation of microthrombi in different organs. We report an extreme thrombocytopenia, marked decrease of ADAMTS 13 and elevated ADAMTS13 antibodies, which would be confirmative evidence of TTP should our patient have clinical features of it. Our patient did not have fever, neurologic abnormalities, renal dysfunction, or active hemolysis. She was followed in outpatient clinic after the discharge. The platelet count recovered and ADAMTS 13 trended up without need for plasmapheresis. Our case is a good example of a fortunate outcome without any complications despite threatening presenting criteria. CONCLUSION: Covid-19 associated endothelial stimulation and damage could mimic a life-threatening disorder without expected fatal complications. On the other hand, it can ultimately lead to the most severe form of thrombotic microangiopathy, TTP, for which the mortality rate is close to 90%. It is hard to know which outcome to expect in different circumstances. Therefore, it is crucial for physicians to promptly recognize clinical picture of TTP as treatment is lifesaving.
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Background and aims: Cerebral venous sinus thrombosis with thrombocytopenia syndrome (CVST-TTS) is a rare adverse effect of adenovirus- based SARS-CoV-2 vaccines. After the autoimmune pathogenesis of TTS was discovered, treatment recommendations were issued. The aim of this study was to evaluate if adherence to treatment recommendations was associated with lower mortality. Methods: TTS was defined according to the Brighton criteria. Cases from a prospective international CVT registry with symptom onset within 28 days of adenovirus-based SARS-CoV-2 vaccination were analysed. Treatment recommendations, following the International Society of Thrombosis and Haemostasis, included use of immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusions, unless needed for surgery. Results: Out of 178 CVT cases from 117 centres in 19 countries reported between March 29 and September 3, 2021, 95 patients fulfilled inclusion criteria. Five of 37 (14%), 13/25 (52%), and 29/33 (88%) of patients diagnosed in March, April, and from May onwards, respectively, were treated according to recommendations. Proportion of patients diagnosed in March, April, and from May onwards who received immunomodulation increased from 19/37 (51%) over 15/25 (60%) to 30/33 (90%), and the percentage of patients who were treated with heparins [26/37 (70%), 4/25 (16%), 1/33 (3%)] and platelet transfusion [15/37 (41%), 4/25 (16%), 7/33 (21%), respectively] decreased accordingly. Mortality of patients treated according to recommendations was 14/47 (30%, 95%CI 19-44%) compared to 28/48 (58%, 95%CI 44-71%) in patients not treated according to recommendations (OR 3.30, 95%CI 1.41-7.71). Conclusions: Over time, adherence to treatment recommendations improved, and mortality rate of patients with CVST-TTS decreased.
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Background: The Radom Regional Blood Transfusion Center supports hospitals in the Radom Region and southern Masovian voivodeship. During the COVID-19 pandemic, pathogen reduction (PR) was introduced for the treatment of COVID-19 convalescent plasma (CCP) to reduce the risk of window-period viral transmission. Subsequently PR was expanded to the treatment of apheresis platelets to reduce the risk of transfusion-transmitted infections. From May 26th, 2021, PRplatelets were issued in addition to conventional platelets to assess the acceptance and tolerability of PR-platelets. Aims: To assess transfusion practice after the introduction of PRplatelets and identification of the most exposed patient groups benefitting most from PR-platelets. Methods: Apheresis platelets collected with a Trima device (Terumo BCT) or an Amicus device (Fresenius Kabi) in 65% T-PAS+ (Terumo BCT) and 35% plasma or in 100% plasma and pooled buffy coat platelets in 65% T-PAS+ and 35% plasma or 100% plasma were issued in the Radom Region and southern Masovian voivodeship on demand with a minimum dose of 3 ± 1011 platelets/unit (platelet dose was assessed regularly for quality control). 18.9% of the platelet units (apheresis platelets in 100% plasma or 65% T-PAS+ and 35% plasma) were pathogen reduced (INTERCEPT Blood System, Cerus). Platelet transfusion reports from 16 hospitals in the Radom City and southern Masovian voivodeship between May 1st, 2021 and January 31st, 2022 were collected and analysed for transfusion frequency (platelet concentrates per patient) in four patient groups (haematology, oncology, COVID-19, other). Since COVID 19 appeared as a new indication, that patient group was analysed separately from the 'other' group to assess the transfusion practice. Statistical analysis was performed with the two-sample t-test. Results: The median age of all transfused patients was 65 years (14- 91), it was elevated in the haematology (70 years [24-91]) and COVID-19 (70 years [62-79]) patient groups. 28.2% of transfused platelets in the haematology patient group were PR, 13.7% in the other, 13% in the oncology and 0% in the COVID-19 patient group. The median number of transfusions received per patient (n = 164) was 2 (1-26). For haematology patients (n = 31) it was 9 (1-26), oncology (n = 24) 2 (1-8), COVID-19 (n = 6) 2 (2-11) and other (n = 103) 2 (1-12). The average platelet dose per unit was 3.4 ± 1011 ± 0.4 for all platelet units, 3.4 ± 1011 ± 0.4 for conventional platelets (n = 525) and 3.3 ± 1011 ± 0.3 for PR-platelets (n = 99), p > 0.05. There was also so significant difference in average platelet dose/unit between the different indication groups (p > 0.05). No unexpected adverse events were reported during the analysis time. Summary/Conclusions: The newly emerging COVID-19 patient group had a comparable platelet transfusion rate to the non-haematology/ oncology patient group. The patients belonging to the haematology group had the highest exposure to platelet transfusion with an increased risk for transfusion-transmitted infections and a high median age. 48% of patients in that group received 10 or more platelet transfusions. An increase of PR-platelet production to 50% would be needed to have sufficient PR-platelets support that vulnerable group. There was no significant difference in platelet dose between PR-platelets and conventional platelets.
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Blood transfusions are an essential part of supportive care for certain patient cohorts, particularly those on palliative care. Most transfusions occur in the hospital setting, including community hospitals. Transfusion in the patient's home supports individualised care, reduces demand on acute services and inconvenience for patient travel to hospital. Decision to undertake home transfusions requires assessment of risks and benefits, with regular review. Risk of acute transfusion reaction in any setting is rare but can result in major morbidity or death. This review looks at adverse events and reactions reported to Serious Hazards of Transfusion (SHOT), the UK haemovigilance scheme, where the transfusion was performed in the patient's home. SHOT cases submitted 2010-2020 were identified using the terms 'home', 'home transfusion' and 'patient's home'. Data were manipulated in MS Excel identifying reactions (febrile, allergic and hypotensive [FAHR], transfusion-associated circulatory overload [TACO]) and events (right blood right patient (RBRP), avoidable, delayed and over/under-transfusion [ADU], incorrect blood component transfused-specific requirements not met [IBCT-SRNM]). 20 cases of home transfusion were identified. FAHR accounted for 10/20 cases, IBCT-SRNM (3/20), HSE (3/20), RBRP (2/20), TACO (1/20) and ADU (1/20). Where patient sex was recorded, 12/19 were male. Age range 3-90 years (median 66, SD 24.9). Red cell components were implicated in 12/20 cases, platelet concentrates in 7/20 cases and one fresh frozen plasma. Patient underlying condition was haematological in 12/20 cases, others included pancytopaenia, angiodysplasia, metastatic cancer and anaemia. Chronic anaemia was the indication in 8/12 red cell transfusion cases and prophylaxis for 4/7 of platelet transfusions. Reactions ( n -11) were febrile (5/11), allergic reactions (3/11), TACO (1/11), 1 anaphylaxis and 1 unclassified. 7/11 patients (6 FAHR and 1 TACO) required hospital admission as a result of the reaction. Four patients were identified as not suitable for home transfusion after the event, SHOT expert review noted one patient should have been ineligible in the first place due to risk of TACO. Adverse events ( n = 9) included cold chain failures (2/9), one failure to inform the laboratory of home transfusion, failure to provide irradiated red cells (2/9), errors in labelling (2/9), incorrect administration rate, failure to provide antigen-negative blood and delay due to an incorrect Hb result. There are no data regarding the number of home transfusions in the UK, therefore it remains unclear whether reactions and errors are over-represented in these cases. Careful consideration should be given to the eligibility of patients to receive home transfusion, particularly the risk of TACO and previous transfusion reactions, before this regime is implemented. No data were available regarding staff performing the transfusions, nurses administering home transfusions must be transfusion trained and competent in identification and management of reactions. There must be robust processes for urgent transfer to hospital. There are no national guidelines for safe practice for home transfusions, including informed consent. Home transfusion is an increasingly important component of patient care, particularly during the COVID-19 pandemic to minimise risk for vulnerable patients, the infrastructure supporting this must have patient safety at its core.
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Restrictive transfusion thresholds are accepted as optimal blood management for patients receiving transfusions. 1 Unnecessary blood transfusions result in increased blood product shortages (exacerbated by the COVID-19 pandemic), 2 adverse patient outcomes and significant costs to health systems. 3 To improve transfusion practice, we aimed to minimise inappropriate transfusions through exploring and targeting areas of noncompliance with locally agreed red blood cell (RBC) and platelet transfusion thresholds of 80 g/l and 10∗109/l respectively. We conducted a retrospective multicycle audit over 4 months (Aug 2020, Feb 2021, May 2021 and Jun 2021) for all patients on the Haematology-Oncology ward. Standards were set at 100% compliance with local hospital guidelines. We analysed the number of RBC and platelet transfusions, pre-and post-transfusion haemoglobin and platelet counts, and clinical indications for transfusion. Actions implemented following each cycle composed of departmental meetings, teaching for foundation doctors and trainees, trust guideline updates and creation of a RBC transfusion checklist on our electronic 'EPIC' prescribing system. 4 Percentage compliance for RBC transfusions improved from 89% to 95% following actions implemented per audit cycle. Inappropriate RBC transfusions associated with discharge decreased from 10% to 1% and transfusion of two RBC units without appropriate increment decreased from 10% to 3%. Although percentage compliance of platelet transfusions did not improve from Aug 2020 to Jun 2021, they were consistently higher (97%) compared to RBC transfusions. This may be secondary to differing causes for inappropriate platelet transfusions detected each cycle. Despite inappropriate HLA-platelet use detected in the latest cycle, there are improvements in documentation to justify platelet transfusions outside normal threshold (100% in latest cycle), total number of platelets transfused and transfusion associated with discharge. Our audit has been successful in improving overall transfusion practice on the Haematology-Oncology ward. Ongoing education and re-audit will ensure this is maintained. (Table Presented).
ABSTRACT
Background: The combination of an anti-CD38 monoclonal antibody, Dara, to the main induction protocols (VRd, VTd,VCd) significantly improved the response rate of TE NDMM before transplantation. However, there is a concern regardingthe possible interference in the SC collection and bone marrow engraftment, since SC, to some degree, express CD38on their surface. In the MAX Dara study, Dara-CTd protocol was used sequentially close to the pre- and post-autologousstem cell transplantation-(ASCT) (D-30 and D + 30), in order to take advantage of the molecule's action as an in vivopurge. Aims: In this analysis, we examine the impact of the number of Dara doses administered pre-mobilization on CD34 cellcount, SC apheresis yield, and post-ASCT engraftment. Methods: This is a phase II, open-label single-center clinical trial. The original protocol was Dara-CTd for up to four 28-day induction cycles and Dara-Td for up to four 28 days consolidation cycles. C-1500 mg oral (PO) per cycle, duringcycles 1 to 4, T at 100-200 mg PO on days 1 to 28, during cycles 1-8, (d) at 160 mg PO per cycle, during cycles 1 - 8 andDara at 16 mg/kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 8. Because of the Covid pandemic we had to adapted the protocol and moving 5-6 consolidation cycles to be used asinduction, increasing the total dose of Dara from 12 to 16 and the number of cycles from 4 to 6 before ASCT. Granulocytecolony-stimulating factor (G-CSF) was administered alone for SC mobilization and plerixafor added based on day 4 preharvestperipheral blood CD34 counts. The target of SC collection was to enable the performance of one ASCT (>2,5 x 106/kg). PMN and platelet engraftment post-ASCT was defined as the first day with sustained PMN count >1000 x 106/L andindependence from platelet transfusion in the preceding 7 days with a count >20 x 109/L, respectively Results: From a total of 21 pts that were included, 19 pts completed mobilization. 12 pts received 12and 7 pts received 16 induction Dara doses, respectively. The median number (range) of daysbetween the last dose of Dara infusion and SC harvest was 23 (16-63) days. A total of five (26%) ptsreceived plerixafor during mobilization. More pts from Dara 16 doses needed plerixafor comparingwith Dara 12 doses (42% vs 16%), but without difference between the groups. Pts underwent amedian (range) of 1 (1-2) days of apheresis. The median number of CD34+ cells collected in the totalgroup was 3.94×106/kg, and no difference was found between Dara 12 vs 16 doses (3.61×106/kg vs4.01x106/kg), p = 0.27. There was no difference in the number of SC collected considering theresponse rate after induction > or < VGPR, and the last day of Dara use > or < 30 days, before SCharvesting. Hematopoietic reconstitution rates were similar for Dara 12 vs 16 doses, a median(range) of 11.0 (9-13) vs 11.0 (11-14) days was required to achieve sustained ANC > 1000 cells/mm3, and a median (range) of 12.0 (9-14) vs 11.0 (8-16) days was required to achieve sustained platelets> 20,000 cells/mm3 without transfusion, respectively. Summary/Conclusion: SC mobilization was feasible with Dara-CTd induction. Despite the more doses of Dara usebefore mobilization increases the need of plerixafor use, the SC number difference was not significant comparing Dara 12vs 16 doses (p = 0.3). The infusion of Dara close to harvest did not interfere with SC collection. Adding DARA to CTdallowed successful transplantation in pts with TE NDMM.
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Background: Pulmonary Mucormycosis is uncommon but serious opportunistic fungal infection caused by fungi of Mucor genus through spores inhalation. Risk factors are diabetes mellitus, hematologic malignancy, transplant and moderate to severe COVID. Here we present a case of 18- year female, with new onset diabetes mellitus with dengue, finally diagnosed as a case of pulmonary mucormycosis. Case Study: 18-year female with high grade fever, dry cough, presented in diabetic ketoacidosis (new onset diabetes). Blood investigations revealed metabolic ketoacidosis, leucocytosis, thrombocytopenia, HbA1C of 14.4, ketone and glucose in urine examination, dengue serology positive. She was admitted in ICU under broad spectrum antibiotics, insulin infusion and platelet transfusion. Chest X-ray suggested bilateral inhomogeneous nodular opacities. Chest computed tomography showed multiple groundglass nodules and focal consolidation. Bronchoscopy done for nonresolving pneumonia suggested crusting at opening of right lowe lobe apical segment. Biopsy taken which resulted in diagnosis of pulmonary mucormycosis. Patient started on oral Posaconazole (300mg) along with insulin to manage diabetes and currently under follow-up. Discussion: In our case hyperglycemia, ketoacidosis, dengue all act to suppress innate immune response and provide facultative environment for fungal proliferation. Diagnosis based on both histopathology and cultures. Our patient is young age and clinically/vitally stable, so we started Posaconazole (300mg) while majority of published studies recommended liposomal amphotericin-B. Conclusion: Pulmonary mucormycosis can even occur in young age with new-onset type 1 diabetes mellitus.
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Introduction: hip fractures in elderly patients have been associated with high morbidity and mortality rate and are dependent on the presence of associated comorbidities. SARS-CoV-2 disease (Covid-19) is nowadays considered to be an independent risk factor increasing mortality rates. The aim of our report was to analyse the management of a vaccinated versus a non-vaccinated elderly patient that were both diagnosed positive to SARS-CoV-2 after having sustained an intracapsular neck of femur fracture. Methods: Two patients (Patient A 91 and Patient B 88 years old, both female) were referred to our hospital after sustaining an intracapsular neck of femur hip fracture as a result of low energy trauma. Both patients tested positive for Covid-19 during their preoperative screening tests. Patient A had not been vaccinated against Covid-19 in contrast to patient B who had completed the 2 dose regimen of the Pfizer-BioNTech COVID-19 vaccine. Patient A presented on arrival Leukopenia (WBC: 1.2 μc/l, Neutrophils 0.4 mcL) and Thrombocytopenia (PLT 70.000). The Procalcitonin, C-Reactive Protein and Ferritin levels long as Arterial blood Gases were measured in both patients on arrival. Patient A required administration of Granulocyte colony stimulating factor and platelet transfusion prior to surgery. Results: Both patients underwent uncemented hip hemiarthroplasty. Patient A was operated 5 days after hospital admission as optimization of the patient's Covid-19 related Leukopenia and Thrombocytopenia was required and Patient B was operated within 24 hours after hospital admission. Patient A required transfusion of 4 blood Units (bleeding related to Thrombocytopenia) compared to 2 blood units that were administered in Patient B. Patient A developed Covid 19 related Pneumonia and Lung disease on the 6th post-operative day (PO2 SO2) and required high flow nasal cannula therapy for 7 days followed by oxygen therapy for 8 days delaying her mobilization and hospital discharge. Patient A was discharged on the 29th post-operative day and Patient B was discharged on the 6th post-operative day. Conclusion: Covid 19 related complications in elderly hip fracture patients are challenging and require multidisciplinary approach and hospital resources. However, Vaccination against covid-19 seems to prevent Covid related complications and can improve the outcome. Large series studies and further research is required to support our thesis.
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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.
ABSTRACT
Introduction: Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT), with over 12,000 transplants per year in Europe. Due to low toxicity, an entirely outpatient procedure or an early discharge after ASCT can be considered as alternatives to inpatient transplantation. Thus, we launched an Early Discharge Program (EDP) for patients qualified for ASCT due to MM who were under 60 years of age, without significant comorbidities, who had a caregiver available 24/7, and who lived within a 60-minute drive of our hospital. Material and methods: Patients spent 72 hours in the hospital being administered melphalan 200 mg/m2 intravenous followed by an infusion of hematopoietic stem cells. They were eventually discharged and remained under outpatient care. The program was launched in September 2019 and was temporarily halted due to the coronavirus disease 19 (COVID-19) pandemic in early 2020. Five patients were enrolled to the EDP. Results: Non-hematological toxicity was mild and manageable in an outpatient setting. Only one patient was readmitted due to exacerbation of ulcerative colitis that was probably not related to ASCT. We observed neither infections nor bleeding. Due to hematological toxicity, three of the five patients received platelet transfusion on the 6th day after ASCT as outpatients. No packed erythrocytes were transfused. The EDP demonstrated lower costs compared to an inpatient approach. Conclusions: We believe that early discharge, which is an intermediate step to full at-home transplantation due to patients' wellbeing, reduction of infections caused by resistant microorganisms, and costs, will eventually replace a full inpatient procedure for a significant population of patients suffering from multiple myeloma and indeed other diseases.
ABSTRACT
Background: Atypical Hemolytic Uremic Syndrome (aHUS) is a complement-mediated thrombotic microangiopathy. Pathophysiological mechanism involves uncontrolled complement activation due to a genetic or acquired anomaly coupled with a triggering event. We report a case of aHUS recurrence following COVID-19 vaccination. Material and methods: Whole blood (EDTA) was collected and processed with CD46-PE, CD45-PerCP, isotype control-PE markers. Staining was measured through median fluorescence intensity and expressed as CD46/isotype ratio. Sanger sequencing was used for identification of variants in CD46 gene. All the participants provided informed written consent. Results: Proband (P) is a 39-year-old woman admitted for nausea, vomiting, epigastric pain and haematuria, three days after first dose of ChAdOx1 nCov-19 vaccine. Laboratory testing showed MAHA (Hb:8.8g/dL, Ht:26%), thrombocytopenia (80x109/mm3) and acute kidney injury (Cr:2.15mg/dL, Ur:92mg/dL). P and three of her siblings have experienced recurrent TMA episodes since childhood. In 2019, genetic study from P's sister (S) identified two heterozygous variants in CD46, one pathogenic (Glu179Gln) and one of uncertain significance (Cys94Tyr). We demonstrated that P carries the same variants and observed a 50% decrease of CD46 expression in both P and S (fig.1). Platelet transfusion, corticosteroids and 9 sessions of plasmapheresis contributed to rapid recovery of P. Discussion: Glu179Gln was reported to increase CD46 expression on granulocytes in aHUS patient and to reduce C4b cofactor activity1. We observed that combination of Glu179Gln and Cys94Tyr was associated with low levels of CD46 on cell surface. Conclusion: This case report supports the evidence of COVID-19 vaccine as a precipitating event for aHUS recurrence.