Managing severe warm autoimmune haemolytic anaemia after the SARS-Cov- 2 vaccine with emergency splenectomy and eculizumab

Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.

Hematological Profile in COVID-19 Infection Among Patients in a Tertiary Care Hospital in Tamil Nadu, South India.

Introduction A wide range of hematological abnormalities has been observed in SARS-CoV-2 infection which is directly related to the disease progression, clinical severity, and mortality among affected individuals. The objective of this study was to evaluate the abnormalities in hematological parameters among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients in a tertiary care hospital in south India. Methods This was a cross-sectional study carried out in the pathology department of Karpaga Vinayaga Institute of Medical Sciences and Research Centre, Chengalpattu, Tamil Nadu, India from 1st May 2021 to 30th June 2021. The hematological reports including complete blood count (CBC), neutrophil-lymphocyte ratio (NLR), serum ferritin, serum C-reactive protein (CRP), serum lactate dehydrogenase (LDH), and D-dimer levels of all the blood samples from COVID-19 positive patients were retrieved from the laboratory records. The Leishman-stained peripheral smear findings were also tabulated and analyzed. Results Out of 65 patients, 38 (58.5 %) were males and 27 (41.5%) were females with a majority (78.4%) of them being more than 40 years of age. The salient hematological abnormalities were leukopenia (21.5%), elevated NLR (43%), and thrombocytopenia (6.2%). Peripheral smear showed schistocytes (15.4%), neutrophils with ring nuclei (84.6%), and toxic granules (81.5%). A statistically significant association between elevated NLR and serum CRP was seen among male patients. The association between the presence of schistocytes with serum LDH and D-dimer levels was statistically insignificant. Conclusions The significant hematological abnormalities in patients with COVID-19 infection were elevated NLR, lymphopenia, thrombocytopenia, and elevated D-dimer levels. Careful evaluation of the hematological parameters will help in categorizing the high-risk cases and thereby initiating early intervention and appropriate intensive care management. This will bring down the morbidity and mortality among COVID-19 patients.

Morphological Changes in Blood Cells as Indicators for Disease Progression in COVID-19

BACKGROUND: COVID-19 as a pandemic has caused an alarming increase in mortality and morbidity. Viral-induced morphologic changes in the peripheral blood cells are well characterized in certain infections and can direct diagnostic workup to ensure timely therapeutic intervention. This study describes the morphological changes of blood cells in various stages of COVID disease. MATERIALS AND METHODS: A total of thousand COVID-positive patients admitted in the tertiary care center were taken for the study. They were classified as mild, moderate, and severe based on the clinical criteria suggested by World Health Organization. Peripheral smears of the patients were analyzed, and the morphological changes in various blood cells were correlated with the disease stage and coagulation parameters. RESULT(S): The study demonstrated significant morphological changes in the blood cells of COVID patients during the course of disease progression and during the onset of COVID-associated coagulopathy. Leukocytosis, neutrophilia, and toxic changes in neutrophils were seen in the severe stage of the disease and in COVID coagulopathy suggesting these are important indicators of disease severity. Activated lymphocyte was found to be the most common morphological presentation seen in all patients irrespective of the disease stage, whereas plasmacytoid lymphocytes were an important finding in severe-stage disease. Schistocytes an important finding in any other coagulopathy was present only in 1% of cases of COVID coagulopathy. CONCLUSION(S): The study demonstrated significant morphological changes in the blood cells of COVID-positive patients during the course of disease progression. Comprehensive daily complete blood count and peripheral smear examination should be undertaken in patients hospitalized with COVID-19 to predict potential clinical deterioration and signs of disease progression. These morphological changes in peripheral smear can be used as one of the factors indicating disease progression which can formulate for further evaluation. Since follow-up and post-COVID morphological examination were not done, additional research in this aspect can shed light on the clinical categorization of COVID patients based on the morphological findings.Copyright © 2023 Journal of Applied Hematology Published by Wolters Kluwer - Medknow.

Kidney Limited Complement-Mediated Thrombotic Microangiopathy- a Challenging Case

Introduction: Complement-mediated thrombotic microangiopathy (CM-TMA) is a rare disease characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and organ injury. The absence of hemolysis and thrombocytopenia is rare. We present a case of kidney limited CM-TMA successfully treated with eculizumab. Method(s): A 36 year-old man with poorly controlled hypertension, obesity, CKD (baseline creatinine (sCr) 2,6mg/dL, albuminuria 150mg/g), hyperlipidemia, obstructive sleep apnea, hyperuricemia, SARS-CoV-2 infection 3 months earlier, and family history of CKD of unknown etiology (father started kidney replacement therapy (KRT) at young age) presented to the ER with high blood pressure and right hemiplegy. Head CT scan showed left thalamo-capsular hemorrhage. Oftalmologic exam was normal. Laboratory findings were: hemoglobin (Hb) 12.5g/dL, elevated white cell count (17.900/uL), platelet count 214.000/uL, sCr 4.3mg/dL, lactate dehydrogenase (LDH) 303U/L. Urine dipstick revealed protein+ and Hb++. Chest X-ray showed signs of pneumonia. The patient was admitted in ICU and mechanically ventilated. After 3 weeks, renal function recovered to its baseline (sCr 1.5mg/dL, no proteinuria) without KRT, and the patient was transferred to the medical ward. Several infectious complications prolonged hospital stay. After 3 months, a new mild SARS-CoV-2 infection was detected. At this time: Hb 9.9g/dL, platelets 220.000/uL, sCr 2.2mg/dL. Six days later the patient showed Hb 9.5 g/dL, without reticulocytosis, platelets 195.000/uL, sCr 6.3mg/dL, LDH 348U/L, normal haptoglobin, no schizocytes on blood smear. After 3 days, the patient was anuric and sCr increased to 10mg/dL, prompting KRT. Kidney ultrasound showed no abnormalities. Autoimmunity study was negative, normal C3/C4, no monoclonal gammopathy, and negative viral serologies. Kidney biopsy (KB) was performed as the etiology of AKI remained unclear. Light microscopy revealed thickned glomerular capillary walls with subendothelial expansion forming double contouring, arteriolar intimal expansion and fibrin thrombi occluding the vascular lumina. Scarse C3 deposition was observed in capillary walls. Since the morphological features were consistent with TMA, secondary causes were excluded and primary causes also investigated: ADAMTS13 activity, complement factor B and I were within normal range, slight decrease of factor H with normal anti factor H antibody. The molecular studies of complement genes were performed by NGS-based gene panel revealing a rare heterozygous missense mutation on gene CFB, c.1189G>A (p.Asp397Asn), described as a genetic risk factor of CM-TMA in the presence of a trigger. Result(s): Treatment with eculizumab was started and the patient showed signs of kidney recovery allowing KRT suspension 1 month later (sCr 5.53mg/dL). Of note, the patient never presented MAHA or thrombocytopenia. After 5 months, renal function improved to sCr 3.9mg/dL. Conclusion(s): We report a case of CM-TMA with isolated kidney injury without laboratory hallmarks of TMA. Patients usually require a secondary trigger for the disease to manifest, and in this case SARS-CoV-2 infection may have been the causative agent. A mutation in gene CFB may have predisposed the patient to the outcome. KB was crucial for diagnosis and prompted the treatment with eculizumab with partial recovery without the need for chronic KRT. No conflict of interestCopyright © 2023

Thrombotic Thrombocytopenic Purpura (TTP) secondary to Covid-19 infection in a patient with Systemic Lupus Erythematosus (SLE)

Background: Covid-19 infection has caused a global pandemic in the recent years and although initially it was considered mainly a respiratory ailment it has proven over time to cause a constellation of complications across various systems such as hematological, immune, cardiovascular, gastrointestinal, and neurological. Method(s): We report a case of a lupus patient with Covid-19 infection who presented initially with fever and gum bleeding with a negative dengue serology and negative HIV serology. Result(s): A 45-year- old lady with a 30-year history of SLE was admitted to our hospital with Covid 19 infection. She had relatively stable disease over the past few years but was admitted to the hospital with complaints of fever, gum bleeding and shortness of breath with no chest x-ray changes. Her oxygen saturations were 95% under room air and her vital signs were stable. Laboratory examinations revealed raised white cell count (11.63) with neutrophilia and elevated C-reactive protein (2.84mg/dl). Her platelet count was low at 113 when compared to her baseline of 549. An urgent peripheral blood film showed an incidental finding of Stomato-ovalocytosis with mild anaemia however there was no features of haemolysis. She was initially treated as acquired Immune thrombocytopenia provoked by Covid-19 infection and was started on IV hydrocortisone. She had a lack of response as evident of a further decline in her platelet counts and the following day, she developed rapid decline in her renal function wherein her creatinine increased from 83 to 207. An urgent ultrasound doppler of the kidneys to rule out acute renal vein thrombosis was organised however it showed normal patent renal vessels. Peripheral blood films were repeated which showed minimal schistocytes and the diagnosis was clinched with the Adamst13 activity levels being less than 0.2%. She was started on 20g IVIG per day with plasma exchange however succumbed to the illness. Conclusion(s): The diagnosis of TTP classically involves the recognition of the pentad of fever, microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure, and neurological abnormalities however 60% of patients do not fulfil the pentad. It is essential to recognize that Covid-19 is an acquired cause of TTP, and a high index of suspicion must be maintained for early treatment institution.

Complete response to eculizumab in atypical hemolytic uremic syndrome with homozygous C3 mutation

Case Report: Atypical Hemolytic Uremic Syndrome (atypical HUS) is a rare and severe form of thrombotic microangiopathy (TMA) characterized by thrombocytopenia, intravascular hemolysis, and acute kidney injury with an incidence of 1 per million.1 Dysregulation and overactivation of the complement alternative pathway due to genetic mutations have been detected in 40-60% of patients with sporadic or familial atypical HUS.2,4 Triggers include viral illness, pregnancy, malignancy, sepsis, or sporadically with no known inciting event.1 Atypical HUS is a severe disease with a 2-10% risk of mortality, 33% risk of end-stage renal failure, and 50% chance of relapse.5 A 24-year-old female with prior history of atypical HUS at the age of 16 (with response to plasmapheresis) presented to the ER with a 5-day history of fever, chills, sore throat, nausea, vomiting, and dark urine. She tested positive for COVID-19. The exam revealed scleral icterus and scattered petechiae. Labs demonstrated nadir hemoglobin (Hgb) of 9.2 g/dL, platelet count of 52 000k/uL, haptoglobin < 30 mg/dL, peak LDH 1128U/L and creatinine 4.62 mg/dL. Urinalysis is consistent with hemoglobinuria. Schistocytes were noted on the peripheral smear. Rapid streptococcal antigen test and C3, C4, and IgA levels were unremarkable. Chest X-Ray, X-ray KUB, and ultrasound abdomen were unremarkable. The pregnancy test was negative. ADAMTS13 was >100%. Genetic analysis after the initial episode at age 16 revealed autosomal recessive inheritance c.193A > c gene mutations in C3. The patient received IV fluids, ceftriaxone for cystitis, and two units of Fresh Frozen Plasma. She initiated treatment with eculizumab. She also received the MENVEO and meningitis B vaccine per protocol due to the risk of meningitis from terminal complement deficiencies. After 4 infusions of eculizumab, patient's labs improved to platelet count of 307 000 k/uL, Hgb 12.2 g/ dL (nadir 9.2 g/dL), haptoglobin 78 mg/dL normalization of LDH and improved creatinine. Atypical HUS is a rare form of TMAwith mutations in C3 noted in 5% of cases. Complement cascade dysfunction leads to endothelial deposits and microvasculature damage. The resulting prothrombotic state causes obstructive microvascular thrombi predominantly affecting the kidneys but can cause multiorgan dysfunction. The SARS-CoV-2 virus may precipitate atypical HUS relapse due to endothelial damage and complement activation further intensified in patients with existing complement aberrations. Plasma exchange remains a standard of care for atypical HUS, as it effectively removes the antibodies and other proteins. Eculizumab a humanized monoclonal IgG antibody binds to complement proteins, preventing cleavage into C5a and C5b blocking C5b-9(MAC) activation. In patients with CFH, CFI, C3, and CFB mutations, eculizumab is the preferred intervention. Copyright © 2023 Southern Society for Clinical Investigation.

LATE-ONSET IMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) AFTER ASYMPTOMATIC COVID-19 INFECTION

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: SARS-CoV-2 related autoimmune and thrombotic complications due to vigorous immune system stimulation and induction of hypercoagulable state are not uncommon. Two hypotheses have been proposed for thrombotic microangiopathy associated with low ADAMTS13 levels in patients with COVID-19 disease. First underscores a significant increase in von Willebrand factor (vWF), likely due to endothelial activation, that overwhelms ADAMTS13. It is observed in the absence of thrombocytopenia or ADAMTS13 inhibitor. The second highlights the formation of autoantibodies against ADAMTS13 because of an immunological trigger (SARS-CoV-2), resulting in the diagnosis of TTP. CASE PRESENTATION: This is a case of a 72-year-old Caucasian man with a history of hypertension, diabetes, chronic obstructive lung disease, and asymptomatic SARS-CoV-2 infection three weeks ago who was transferred to our institution to initiate plasmapheresis for suspected TTP due to new-onset confusion, anemia and worsening renal function. Patient had presented with confusion a day before transfer. Vital signs were remarkable for tachycardia (heart rate of 105 beats/min). Labs were significant for anemia (hemoglobin:6.7 g/dL), thrombocytopenia (platelet count:13 K/µL), acute kidney injury (creatinine:1.8 mg/dL), elevated lactate dehydrogenase (1983 IU/L), high bilirubin (2.3 mg/dL), low haptoglobin (<4 mg/dL), and demonstration of schistocytes on peripheral smear. The coagulation profile was normal. On arrival, he required emergent intubation due to multiple seizures. Computed tomography scan of the head was normal. SARS-CoV-2 molecular testing was negative. Given a PLASMIC score of six, urgent plasmapheresis and high-dose methylprednisolone were started. Screening for human immunodeficiency virus, hepatitis viruses, Epstein-Barr virus, and Cytomegalovirus were negative. Subsequently, his ADAMTS13 activity resulted as being ≤5% with an elevated inhibitor Bethesda titer of 0.9 (normal < 0.4). The patient completed six sessions of plasmapheresis. He was discharged on steroid taper and weekly rituximab. DISCUSSION: COVID-19 associated de-novo TTP has been mostly reported with typical COVID-19 symptoms within a few days of a positive test. One report described presentation with only neurological symptoms 19 days after a positive test with low autoantibody titers, favoring the hypothesis of consumption of ADAMTS13. To the best of our knowledge, this is the first case of new, late-onset immune TTP developing three weeks after asymptomatic COVID-19 infection with a robust positive inhibitor screen and infinitesimal ADATMS13 levels. The temporal sequence of events and lack of other plausible causes aided in the diagnosis of COVID-19 induced TTP. CONCLUSIONS: Our report aims to make clinicians aware of ruling out TTP as a cause of thrombocytopenia and/or altered mental status in patients with past COVID-19 infection, aiding in early management. Reference #1: 1. Mancini I, Baronciani L, Artoni A, Colpani P, Biganzoli M, Cozzi G, Novembrino C, Boscolo Anzoletti M, De Zan V, Pagliari MT, Gualtierotti R, Aliberti S, Panigada M, Grasselli G, Blasi F, Peyvandi F. The ADAMTS13-von Willebrand factor axis in COVID-19 patients. J Thromb Haemost. 2021 Feb;19(2):513-521. doi: 10.1111/jth.15191. Epub 2020 Dec 18. PMID: 33230904;PMCID: PMC7753796. Reference #2: 2. Tehrani HA, Darnahal M, Vaezi M, Haghighi S. COVID-19 associated thrombotic thrombocytopenic purpura (TTP);A case series and mini-review. Int Immunopharmacol. 2021;93:107397. doi:10.1016/j.intimp.2021.107397 Reference #3: 3. Beaulieu, M.-C., Mettelus, D.S., Rioux-Massé, B. and Mahone, M. (2021), Thrombotic thrombocytopenic purpura as the initial presentation of COVID-19. J. Thromb. Haemost., 19: 1132-1134. https://doi-org.libproxy.uams.edu/10.1111/jth.15231 DISCLOSURES: No relevant relationships by Harmeen Goraya No relevant relationships by PRACHI SALUJA

DIFFUSE ALVEOLAR HEMORRHAGE SECONDARY TO IMMUNE THROMBOCYTOPENIA FOLLOWING SARS-COV-2 VACCINATION: A CASE REPORT

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

COVID-19-ASSOCIATED THROMBOTIC THROMBOCYTOPENIA PURPURA (TTP)

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a rare medical emergency with mortality rates reported to be as high as 90% if untreated. We report a case of severe TTP in an immunocompetent patient diagnosed with COVID 19 infection. CASE PRESENTATION: A 34-year-old morbidly obese female not vaccinated for COVID presented to PCP 2 weeks prior with complaints of fatigue. CBC showed Hb 12.2, platelet count 108 (baseline > 200), and covid resulted positive. The patient was reluctant for further workup at the time. After 2 weeks she felt short of breath prompting ICU admission for high flow oxygen with blood work showing hemoglobin of 8.8, platelet count of 11, Reticulocyte count 3.9%, LDH 763, fibrinogen 639, schistocytes on peripheral smear, MCV < 90, INR<1.5, Creatinine 1 giving her a PLASMIC Score of 7. For concerns of TTP, she was urgently started on plasmapheresis, prednisone 1 mg/kg, and remdesivir for COVID. ADAMTS13 was sent prior to the initiation of plasmapheresis resulted at 5% indicating severe deficiency and a high risk of relapse. She underwent 3 cycles of plasma exchange and was also started on Caplacizumab. Rituximab was not started in the setting of active COVID infection and negative COVID IgG. Repeat ADAMTS13 level at 2-week interval increased to 43%. The patient was discharged on steroids and completed 1 month of Caplacizumab. On outpatient follow up the patient was asymptomatic but repeat ADAMTS13 declined to 16%. COVID IgG now resulted positive, and she was started on Rituximab. Ultimately patient was treated with 4 months of steroids and 4 doses of weekly Rituximab with the final two ADAMTS 13 levels normalized above 100. DISCUSSION: TTP is caused by decreased activity of the plasma metalloproteinase ADAMTS 13, the key enzyme involved in the cleavage of ultra-large von Willebrand Factor (vWF) multimers into smaller less procoagulant multimers. It is reported that COVID-19 infection is associated with almost a five-fold increase in vWF levels which the body's ADAMTS-13 enzyme activity cannot adequately regulate, resulting in an excess of unchecked ultra-large vWF, diffuse microthrombi, and systemic ischemia. The presentation of this disease is often characterized by the pentad of fever, thrombocytopenia, hemolytic anemia, renal dysfunction, and neurologic dysfunction. However, the full pentad is often not present in many patients Plasma exchange and immunosuppression are the mainstays of treatment for TTP. A high index of suspicion is required for a timely diagnosis. Early diagnosis is crucial as without treatment TTP is associated with a high mortality rate. CONCLUSIONS: Health care providers should be aware of this life-threatening complication of COVID-19 so that prompt and appropriate interventions can be undertaken if it is suspected or confirmed. Rituximab should be delayed until the acute COVID-19 infection has cleared, and neutralizing antibodies have been produced. Reference #1: Hindilerden F, Yonal-Hindilerden I, Akar E, Kart-Yasar K. Covid-19 associated autoimmune thrombotic thrombocytopenic purpura: Report of a case. Thromb Res. 2020;195:136-138. doi:10.1016/j.thromres.2020.07.005 DISCLOSURES: No relevant relationships by Hanish Jain No relevant relationships by Dragos Manta No relevant relationships by Parth Sampat No relevant relationships by Garima Singh No relevant relationships by Simant Thapa

AN UNUSUAL ASSOCIATION between THROMBOTIC THROMBOCYTOPENIC PURPURA and PRIMARY ANTIPHOSPHOLIPID SYNDROME

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangio-pathic haemolytic anemia, consumption thrombocytopenia and organ injury, particularly kidney failure and neurological manifestation1. Two forms are distinguished: the hereditary one, caused by a deficit of the metallopro-tease ADAMTS13, and the idiopathic one characterized by the presence of antibodies directed against ADAMTS13. The second one is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, disseminated malignancies and drugs. Antiphospholipid syndrome (APS) is a clinical immunological condition characterized by thromboembolic events, repe-tead miscarriages or stillbirth and thrombocytopenia;it can be a primary disorder or due to connective tissue disease, in particular systemic lupus erythematosus2. Objectives: We describe a case of TTP associated with a primary APS. The real clinical challenge lies in the differential diagnosis between TTP and anti-phos-pholipid antibody syndrome. Methods: A 37-year-old man presented to the emergency department for short-term episodes of anesthesia of the right upper limb and face with spontaneous resolution. In his past medical history, he suffered of antiphospholipid syndrome treated with warfarin. Upon admission, blood tests revealed severe thrombocytopenia, haemolytic anemia with schistocytes on peripheral blood smear, low thrombin time and prolongation in the prothrombin time. Neurological symptoms were assessed by electroencephalogram and CT brain, resulted negative, while a brain MRI revealed acute-subacute ischemic stroke. Based on these fndings we suspected a diagnosis of TTP, subsequently confrmed by reduced activity of ADAMTS-13 with borderline ADAMTS-13 inhibitory antibodies. Immunological testing confrmed positivity of antiphospholipid antibodies and antinuclear antibodies. Results: According to the last guidelines3 about management of acute episode of TTP, immediate therapy with high-dose corticosteroids (prednisone 1 mg/kg) and plasmapheresis was started and then we added infusion of ritux-imab (375 mg/m2/week for 4 times). Efficacy of treatment was evaluated by weekly dosage of ADAMTS13 activity, with a gradual rise in values (3 → 78%) and improvement in symptoms and laboratory examination. After persistent remission, we gradually reduced steroid therapy. Few months later, in February 2021, patient developed a bilateral comunitary pneumonia, that required hospitalization, oxygen-therapy (also with C-PAP) and endovenous antibiotics. After two weeks patient was discharged from hospital in good clinical health and he was subjected to periodic outpatients visits. Disease activity was in remission, so steroid therapy was reduced and recently we added hydroxychloroquine for APS. Some days ago patient developed covid-19 infection, despite vaccination, and he was treated with monoclonal antibodies, with good clinical response. Conclusion: We have described a rare clinical case of TTP, despite concomitant warfarin treatment for primary anti-phospholipid syndrome. A careful follow-up of these medical conditions is recommended for patient's fragility and for the risk of related serious clinical complications.

Scleroderma Renal Crisis and COVID—Is There an Association?

Scleroderma renal crisis (SRC) is a rare but potentially devastating complication of systemic sclerosis as it is associated with significant morbidity and mortality. We present an interesting case of a patient who developed SRC following infection with COVID-19. A 37-year-old female presented with new-onset hypertension, AKI, anemia and thrombocytopenia. She had a history of diffuse cutaneous systemic sclerosis diagnosed 8 years ago, that had been well controlled with immunosuppression. The patient had contracted COVID-19 infection about 2 weeks ago but had remained largely asymptomatic except for a sore throat. Urinalysis revealed sub-nephrotic proteinuria but was otherwise bland. Peripheral blood smear was notable for 12-15 schistocytes per HPF. ADAMTS13 and complement levels were normal. Serologies for ANA, ANCA, anti-Scl70, anti-Jo1, anti-Sm, lupus anticoagulant, anti-beta2-glycoprotein I, anti-RNA polymerase III, RF, cryoglobulin, RPR, hepatitis and HIV, all returned negative. Renal biopsy revealed an arterial predominant thrombotic microangiopathy (TMA) (Figure) consistent with a diagnosis of SRC. The patient was treated with anti-hypertensives including an ACE-inhibitor, but her AKI continued to worsen, ultimately leading to dialysis dependence. SRC classically develops in patients with early or progressive diffuse cutaneous disease or positivity for anti-RNA polymerase III antibodies. Our patient did not have any such risk factors and rather developed SRC following infection with COVID-19. COVID-19 has been reported to cause TMA by inducing immune dysregulation via an overactive complement system. It is plausible that infection with COVID-19 triggered an exaggerated immune response, in turn leading to the development of SRC in our patient. COVID-19 may trigger SRC in patients with systemic sclerosis in the absence of other risk factors. (Figure Presented)

Atypical Presentation of Cocaine-Induced Thrombotic Microangiopathy

Cocaine is one of the most used illicit drugs. Cocaine induced toxicity can result in hepatotoxicity, pulmonary toxicity, and renal dysfunction. Acute kidney injury (AKI) is an emergent complication in cocaine abusers. Rhabdomyolysis and vasoconstrictions mechanism are well known cause of AKI, cocaine induce thrombotic microangiopathy (TMA) is rarely reported. Cocaine is widely used in the United States, we report a case of Cocaine induced TMA in a cocaine abuser. We chronicle a case of a 42-Year-old male cocaine abuser, who presented to ED with complaints of Dyspnea, cough, anorexia and chest tightness for two days. He attributed to inhaling ammonia from cat urine along with cocaine abuse. No prior history of kidney disease or any other chronic illness. On examination, the patient appeared malnourished and cachectic. He was normotensive, lethargic and oriented. There were crackles at the lung bases. Blood tests revealed serum creatinine 18.0 mg/dL, blood urea nitrogen 150 mg/dL, hemoglobin 8.2 g/dL, platelets 173000/mm3, Retics count 8 %, LDH 1120 (84–246 IU/L) and haptoglobin < 8 (30–200mg/dL). A blood film revealed occasional schistocytes. Urinalysis showed proteinuria and microscopic hematuria. Urine toxicology revealed cocaine. Routine blood and urine cultures showed no growth. Serologic tests showed reduced complement C3 level of 40 (82-185 mg/dL) and normal C4 level of 32 (10–53mg/dL). There were no antibodies against HIV 1/2 and Covid 19. His ADAMTS-13 results showed 0.61 and 0.63 (0.68 to 1.63). Renal Ultrasound was unremarkable. Patient was intubated and ventilated in ICU;he was initiated on hemodialysis. He was provided four sessions of plasma exchanges till his ADAMTS-13 result came back near normal that was indicative of Cocaine induce TMA. Cocaine abuse is a global issue with increasing number of cases in the USA. It can cause AKI due to well-known etiologies like Rhabdomyolysis, Vasculitis, Acute interstitial Nephritis and Renal Infarction. However, Clinicians and nephrologists should also consider rare causes like TMA as a possible differential cause of AKI in the setting of cocaine abuse.

FORTUNATELY, NOT A TTP (THROMBOTIC THROMBOCYTOPENIC PURPURA). A CASE OF COVID INFECTION WITH EXTREME THROMBOCYTOPENIA (PLATELETS 5K/UL) AND SEVERE DEFICIENCY OF ADAMTS 13 (<2 %) WITHOUT TTP SYMPTOMS AND WITHOUT NEED FOR PLASMAPHERESIS

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.

ATYPICAL HAEMOLYTIC UREMIC SYNDROME ASSOCIATED WITH COVID-19: CASE REPORT

BACKGROUND AND AIMS: Renal manifestations are common in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report here the case of a patient with confirmed SARS-CoV-2 infection with the clinical picture of atypical haemolytic uremic syndrome (aHUS). METHOD: Case report RESULTS: Our case is a 31-year-old man with a nasopharyngeal swab with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 positive, who was hospitalized in the Clinic of Infectious Diseases. His medical history had a respiratory illness of 7-day evolution characterized by cough, fever, dyspnoea, muscle pain, nausea, vomiting and non-bloody diarrhoea, and decreased urine output with dark colour urine. The chest computed tomography (CT) scan showed few rounded ground-glass opacities. Laboratory tests at admission revealed the following: (i) acute kidney injury stage 3 with a serum creatinine of 3.85 mg/dL (basal value 0.9 mg/dL);serum urea 221 mg/dL. His urinary volume in the first 24 h of hospitalization was 800 mL. (ii) Severe haemolytic anaemia with haemoglobin (Hgb) level of 3.7 g/dL, and peripheral smear showing large number of schistocytes, haptoglobin <10 mg/dL and indirect bilirubin 9.7 mg/dL, direct coombs testing was negative;reticulocyte count 8.9%. (iii) Severe thrombocytopaenia with platelet count of 25 000/μL, prothrombin time 45%, international normalized ratio 1.7, D-dimer 1082 ng/dL and fibrinogen 880 mg/dL. Increased blood levels of enzymes and inflammatory markers were present: lactate dehydrogenase 1867 U/L and protein C reactive 9.1 mg/dL. Electrolyte disturbances characterized by hyperkalaemia, hyperphosphatemia, hypocalcaemia and severe metabolic acidosis. Dynamic changes of laboratory data are presented in Table 1. The usual liver panel tests, alkaline phosphatase, γ -glutamyl transferase and albuminemia were normal. Toxic hepatitis was excluded. Hepatobiliary and spleen imaging (ultrasonography) was normal. ELISA serologic tests for HIV, hepatitis B, hepatitis C virus and cytomegalovirus were negative. Serological and virological tests for hepatitis A, B, C, HIV and CMV were negative. Stool was negative for Shiga toxin-producing Escherichia coli (STEC). The results of antinuclear antibodies and anti-smooth-muscle antibodies were negative, C3 serum level was mildly depressed (82 mg/dL;normal range 88- 201 mg/dL) and C4 serum level was normal (20 mg/dL;normal range 10-44 mg/dL). ADAMTS13 activity was 90% on day 10. He was treated with broad spectrum antibiotics, intravenous dexamethasone and supportive therapy. One week from admission, renal function recovered, and 1 week after intravascular haemolysis and thrombocytopaenia recovered. The patient was hospitalized for 21 days. CONCLUSION: Close monitoring and early intervention can help for a better outcome of SARS-CoV-2 patients complicated with aHUS.

TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY SUCCESSFULLY TREATED WITH RAVULIZUMAB

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic stem cell therapy (HSCT) with incidence rates ranging from 10-35%. The predominant mechanism leading to TA-TMA is endothelial cell damage leading to complement dysregulation and microvascular hemolysis. Complement dysregulation is particularly important in the pathophysiology of TA-TMA as initial trials have shown response to complement blockade using eculizumab, a humanized monoclonal antibody targeting the terminal complement pathway. Ravulizumab is a longer acting monoclonal antibody with the same target as eculizumab that is increasingly used for treatment of atypical hemolytic uremic syndrome. Herein, we describe the case of an African American female with relapsed/refractory infantile B-cell acute lymphoblastic leukemia (B-ALL) who underwent 10/10 HLA-matched sibling donor allogeneic transplant (conditioning: busulfan/fludarabine/thiotepa;GVHD prophylaxis: tacrolimus/methotrexate) who developed TA-TMA marked by pericardial effusion, elevated LDH, proteinuria, hypertension, thrombocytopenia, anemia, and evidence of microangiopathy. Upon diagnosis, as ravulizumab was on formulary and readily available unlike eculizumab, she was treated with ravulizumab instead of eculizumab. Objectives: To describe the therapeutic response to ravulizumab in one patient diagnosed with TA-TMA. Design/Method: A retrospective chart review was performed regarding this patient's ravulizumab treatment course, and direct discussions were had with the patient's care team. Results: Ravulizumab (loading dose of 600 mg followed 2 weeks later by maintenance dosing of 600 mg every 4 weeks) was administered. Pre-treatment CH50 was >75 U/mL (range: 30-75 U/mL) with sC5b9 and C3 complement levels at the upper limit of normal at 220 ng/mL (range: ≤244 ng/mL) and 143 mg/dL (range: 72-164 mg/dL), respectively. Clinical normalization of the patient's TA-TMA was achieved two weeks after loading dose administration with normalization of LDH and blood pressure values, improved proteinuria, decreased transfusion requirements, absence of schistocytes on peripheral smear, and complete resolution of pericardial effusion. A total of 5 maintenance doses of ravulizumab were administered approximately every 4 weeks with CH50 ranging <3-33 U/mL during this time period. Five maintenance doses were administered as the optimal duration was unknown and the patient's TA-TMA treatment course was complicated by COVID-19 infection, for which there was concern could lead to TA-TMA reactivation (which did not occur). The ravulizumab was well tolerated throughout with amoxicillin used for meningococcal prophylaxis. Conclusion: While studies evaluating ravulizumab for treatment of TA-TMA are ongoing, ravulizumab successfully led to complement blockade and clinical improvement in this patient with TA-TMA.

Vaccine-Induced Immune Thrombocytopenia and Thrombosis Syndrome post second dose of ChAdOx1 nCov -19 vaccine: Case Presentation

We present the case of a 39-year-old female who presented to University Hospitals of Leicester 14 days after the second dose of ChAdOx1 nCov-19 vaccine. Her presenting symptoms included skin rash, nausea, intermittent abdominal pain and occasional episodes of dizziness. Her past medical history included Type 2 Diabetes Mellitus and hidradenitis suppurativa. The first dose of ChAdOx1 nCov-19 vaccine had been administered on 27th February 2021, following which the patient reported flu like symptoms that resolved after four days and did not require further medical input. Following this, a preplanned surgical procedure to incise and drain a vulval abscess was performed on 17th May 2021. Preoperative testing performed on 13th May 2021 showed a normal platelet count of 219 × 10 9 /l. The second dose of ChAdOx1 nCov-19 vaccine was subsequently administered on 23rd May 2021. On presentation, examination revealed mild epigastric tenderness and features of classical thrombocytopenic rash affecting all limbs with no other associated bleeding. Initial blood results confirmed thrombocytopenia of 11 × 10 9 /l, with D-Dimer 14.26 μg/ml and fibrinogen 2.1 g/l. Blood film microscopy revealed an occasional schistocyte and microangiopathic haemolysis was considered. Treatment with plasmapheresis of 1.5 x plasma volume using Octaplas was administered. Subsequent abdominal computed topography imaging identified extensive thrombotic events. This included bilateral pulmonary embolism, superior mesenteric vein non-occlusive thrombus and multiple soft atheromas lining the abdominal aorta causing moderate infrarenal stenosis. In view of the recent history, vaccine associated thrombosis and thrombocytopenia (VITT) was considered. Subsequent testing showed a normal ADAMTS13 level. Treatment for VITT with intravenous immunoglobulin along with oral steroids and anticoagulation using Argatroban was commenced in line with national guidance. Anti-PF4 antibody, tested using the Asserachrom HPIA ELISA assay, was positive at a level of 1.298 OD units confirming the diagnosis of VITT;the first case we are aware of in the UK following second dose administration. Given high-risk presentation, Rituximab therapy was given as an inpatient with good clinical response. Prior to discharge, anticoagulation was switched to oral apixaban with a platelet count on discharge of 170 × 10 9 /l. Subsequent follow-up has shown ongoing clinical remission with consistently negative Anti-PF4 antibody titres. This report outlines the first known definite case of VITT identified following administration of the second dose of ChAdOx1 nCov-19 vaccine in the United Kingdom. The subsequent clinical course was similar to those of patients presenting after their first dose but the atypical presentation mimicking that of Thrombotic Thrombocytopenia is noted..

Bortezomib As Frontline Therapy in the Management of TTP

Introduction The current International Society on Thrombosis and Hemostasis (ISTH) guideline of Thrombotic Thrombocytopenic Purpura (TTP) recommends Therapeutic Plasma exchange (TPE) and corticosteroid in the management of TTP, with Rituximab and Caplasizumab as additional potential therapies [X Long Zheng et al, J Thromb Haemost. 2020;18:2496-2502]. This potentially fatal condition requires prompt diagnosis and treatment but large volume plasma treatment is not without risk and in settings with limited access with sufficient compatible plasma for apheretic exchange, this can delay this emergency therapy. We have been running the first therapeutic apheresis services with an Optia instrument in Uganda at the Joint Clinical Research Centre in Kampala city and TTP is the main indication for TPE. We present 2 recent sequential cases of TTP that were successfully managed when Bortezomib was combined with plasma therapy. Case1. A 25yr woman referred to our service on 29/09/2020, with recent onset of bruising, icterus, severe anemia Hgb5.7g/dL, Severe thrombocytopenia 8 x 10 3/uL, a high LDH 3909U with schistocytes on the peripheral blood film severe thrombocytopenia and a negative Direct Antiglobulin test. She was Blood Group B+. She was managed with 3 sessions of TPE of 2.1, 1.1 and 2.0 plasma volume exchanges with 6727mL, 3026mL and 5459mL of replacement plasma respectively and oral prednisone 60mg daily without remission. Subsequent quantities of plasma were insufficient for apheresis and were instead transfused. She also received weekly Rituximab 500mg (IV) but without significant recovery in the platelet count until she received Bortezomib 2mg (SC) when there was corresponding recovery of the platelet count and with each dose to a total of 4 doses (Figure 1). Case2. A 55yr man was previously well and shopping in a mall when he had an index episode of seizures on 19.Jun.2021 and was hospitalized that day with altered consciousness and focal motor signs. He required intubation for 3 days and at the time of hospitalization, he had Hgb 9gm/dL, PLT 17 x 10 3/uL, LDH2177U, with numerous schistocytes on the peripheral blood film and a negative Direct Antiglobulin Test. The baseline blood sample functional ADAMTS13 was 3% and had Blood Group AB+. He had received the 1 st dose of the Astra-Zeneca Covid19 vaccine on 06.May.2021. It was not possible to get any AB plasma and we considered it risky to perform large volume TPE with non-AB plasma and he was instead treated with daily transfusion with Group A+ Plasma concurrent with daily Prednisone 60mg. Because of our previous experience of poor response to Rituximab, we opted to treat him upfront with 4 doses of 2mg bortezomib (SC) given 3 days apart. He made brisk recovery to complete remission and was discharged for weekly outpatient CBC and LDH monitoring. His platelet count subsequently dropped without a corresponding drop in the Hgb and no rise in the Hgb. We initially re-hospitalized him for 4 more days of plasma transfusion but without a brisk response and since the LDH was not increasing, the isolated Thrombocytopenia was considered a side effect of Bortezomib that was expected to resolve and he receive no further treatment but continued to recover to complete remission as an out-patient (figure 2). Discussion: Our findings suggest a possible role for Bortezomib in frontline therapy for TTP with potential to reduce the plasma requirement in TPE and this approach warrants a randomized clinical trial. [Formula presented] Disclosures: No relevant conflicts of interest to declare. OffLabel Disclosure: Bortezomib Indicated in the management of Multiple Myeloma and Plasma Cell Dyscrasia

Pseudothrombotic microangiopathy and pancytopenia as a rare presentation of vitamin B12 deficiency

Case Report A 62-year-old male presented to our hospital with a few days of worsening dyspnea, associated with numbness in the left lower extremity, dizziness and transient brief chest pain that was described as a sharp intermittent pain. He denied any fever, chills, nausea, vomiting, diarrhea, headache, or recent ill contacts. The patient also denied any family history of blood or bone morrow disease. He had been released from incarceration 2 days prior to the presentation. Complete blood count revealed pancytopenia with hemoglobin of 6.8 g/dL, MCV of 112 fL, white blood cell count of 1.2 K/uL, and platelet count of 78 K/uL. The patient was transfused with packed red blood cells and then admitted to the inpatient medicine ward for further treatment and evaluation. Blood smear confirmed the pancytopenia with severe neutropenia, macrocytosis, and moderate thrombocytopenia. In addition, it showed erythrocytes with marked poikilocytosis including occasional schistocytes and teardrop cells. His lab investigations were notable for B12 level below 150 pg/mL (Normal range 211-911), fibrinogen of 144 mg/dL , haptoglobin less than 10 mg/dL, LDH of 1013 U/L. Other lab studies including troponin, ferritin, TIBC, serum iron, vitamin B1, PT/INR, PTT, SPEP, COVID-19, EBV, CMV, HIV, Hepatitis A, B, and C were all unrevealing. Abdominal ultrasound was significant for splenomegaly. CT head and chest xray were unremarkable. After starting treatment with cobalamin therapy, the patient has shown improvement in terms of cell counts, resolution of hemolysis. He also reported significant improvement in tingling and dizziness. All this confirms the diagnosis. Vitamin B12 deficiency manifestations can vary between asymptomatic, mild, and severe. In our case, the patient presented with pseudothrombotic microangiopathy and pancytopenia. Both are rare and serious manifestations of vitamin B12 deficiency. Physicians should be aware of cobalamin deficiency as one of the etiologies for pancytopenia and pseudothrombotic microangiopathy. Therefore, an early recognition and treatment is crucial. (Figure Presented).

Clinicopathological Parameters of Haemolytic Anaemia in COVID-19 Infection: A Series of Three Cases

Coronavirus Disease 2019 (COVID-19) patients show various haematological abnormalities like cytopenia and coagulation disorders. Corona virus can induce an inflammatory state, leading to extensive coagulation manifestations. Association between COVID-19, Autoimmune Haemolytic Anaemia (AIHA) and thrombotic state is still the subject of extensive research. In this study, three cases of haemolytic anaemia are discussed. First case was a 28-year-old female with a history of abruptio placentae who presented with complaints of generalised weakness and oliguria for five days. She was diagnosed as thrombotic microangiopathy based on peripheral smear finding of schistocytes and spherocytes and few polychromatophils and normal prothrombin time (International Normalized Ratio (INR)) with very high D-dimer levels on coagulation profile. Second case was of a 25-year-old female who presented with complaints of fatigue, rashes, dark urine, nausea and abdominal pain. She was diagnosed as a case of AIHA based on peripheral smear finding of Red Blood Cells (RBC) clumping and positive direct coomb test. Third case was of a two-month-old child who presented with respiratory distress and pallor. He was diagnosed as a case of haemolytic anaemia either due to direct effect of COVID-19 infection or Cytomegalovirus (CMV) and mycoplasma infection. Thus, COVID-19 infection can directly or indirectly lead of a wide spectrum of haemolytic manifestations and every patient with anaemia should be thoroughly investigated for early detection and treatment.