Case Of Autoimmune Hemolytic Anemia Research Articles

Autoimmune Hemolytic Anemia during Pregnancy or Post-Partum: An International Multi-Center Experience

Autoimmune hemolytic anemia (AIHA) developing or relapsing during pregnancy or postpartum is a rare finding, and few is known about maternal and fetal outcomes. Furthermore, AIHA management during pregnancy and lactation is not standardized and drug use is often limited by safety concerns. Here, we report the results of a multi-center retrospective cohort study evaluating AIHA impact on pregnancy focusing on disease severity, treatment need and maternal and fetal outcome. Forty-one pregnancies occurring in 31 women were registered from 1997 to 2022 at 11 European centers in Italy, Denmark, France, the Netherlands, USA, and Spain. AIHA was classified according to the direct antiglobulin test as warm, cold, mixed or atypical. Outcomes were compared with a control group of 56 healthy women matched for age at pregnancy and decade of pregnancy. Overall, we observed 21 warm AIHA (13 IgG; 8 IgG+C3d), 2 cold agglutinin diseases, 3 mixed and 5 atypical forms (Table 1). Evans syndrome (i.e., association of AIHA and immune thrombocytopenia or neutropenia) was present in 5 women. Mean age at AIHA diagnosis was 27 (3-39) years and at pregnancy 32 (21-41) years. AIHA diagnosis predated pregnancy in 16 women and had required at least 1 therapy line in all of them, and ≥2 lines in 13 (rituximab, N=8; cytotoxic immunosuppressants, N=6; splenectomy, N=5). Among these 16 patients, 7 had a relapse during pregnancy, 3 during postpartum and 9 were on active treatment at the time of pregnancy (steroids, N=7; cyclosporine, N=1; steroids plus azathioprine, N=1; the latter stopped after positive pregnancy test). A patient with a previous AIHA, relapsed as immune thrombocytopenia during pregnancy. Further 9 patients developed AIHA during gestation and 2 in the postpartum. A patient had AIHA onset during the postpartum of the 1st pregnancy and relapsed during the 2nd one. In total, we observed 22 hemolytic events in 21 women during pregnancy/postpartum. Median Hb and LDH levels were 6.4 g/dL (3.1 - 8.7) and 599 IU/L (269-1631), respectively. Management consisted in blood transfusions (N=11, 50%) and prompt establishment of steroid therapy +/- intravenous immunoglobulins (N=22, 100%), all with response (complete N=15, partial N=7). After delivery, rituximab was necessary in 4 patients and cyclosporine was added in one. Anti-thrombotic prophylaxis was given in 7 patients. Overall, we registered 10 maternal complications (10/41, 24%), including 4 early miscarriages, a premature rupture of membranes, a placental detachment, 2 preeclampsia, a postpartum infection and a biliary colic. Notably, 8/10 complications occurred during active hemolysis and treatment for AIHA. Ten fetal adverse events (10/41, 24%) were reported: a transitory respiratory distress of the newborn in a mother with active AIHA; 4 cases of fetal growth restriction; a preterm birth; an infant reporting neurologic sequelae; a case of AIHA of the new-born requiring intravenous immunoglobulins, blood transfusions and plasma exchange; and 2 perinatal deaths. The latter two occurred in women on active AIHA therapy and were secondary to a massive placental detachment and a symptomatic SARS-CoV-2 infection. Finally, the comparison between AIHA women and the control group showed a similar prevalence of maternal complications (24% in AIHA versus 18% in controls). At variance, AIHA was marked by a significant increase of fetal adverse events versus control group (24% versus 5%, p=0.008), with more severe complications in the former. In conclusion, AIHA developing/reactivating during pregnancy or postpartum is rare but mainly severe, requiring red cell transfusions in half of cases and steroid therapy in all patients. Notably, severe maternal and fetal complications may occur in up to a quarter of cases mostly associated with active hemolysis. Finally, AIHA was significantly associated with severe fetal complications compared with healthy population, further pinpointing the importance of maintaining a high level of awareness. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Development and exacerbation of autoimmune hemolytic anemia following COVID-19 vaccination: A systematic review.

Autoimmune hemolytic anemia (AIHA) is caused by the production of autoantibodies against RBCs. COVID-19 vaccines can reduce the risk of severe disease, however, various adverse effects such as AIHA were observed following vaccination. This review aimed to assess the relationship of AIHA and COVID-19 vaccination using the PRISMA guidelines. Among 18 cases included in this review, new post-vaccination AIHA development was reported in 11 patients (7 women and 4 men) with a median age of 67.0 years. In 7 of 11 and 3 of 11 cases, the onset of symptoms occurred after first and second vaccine dose with median times of 7 and 14 days, respectively. In 1 of 11 cases, the AIHA occurred on Day 17 after booster vaccination. Ten of 11 and 1 of 11 AIHA patients received mRNA- and vector-based vaccine, respectively. After vaccination, 9 of 11, 1 of 11, and 1 of 11 AIHA patients developed warm IgG, cold IgM, and mixed autoantibodies against RBCs, respectively. Significant AIHA exacerbation was reported in seven patients (four women and three men) with a median age of 73.0 years. In 4 of 7 and 2 of 7 exacerbated AIHA cases, the onset of symptoms occurred after first and second vaccine dose with median times of 7 and 3 days, respectively. In 1 of 7 exacerbated AIHA cases, the onset of symptoms was observed on Day 2 after booster vaccination. All exacerbated AIHA cases received mRNA-based vaccines; 3 of 7 and 4 of 7 exacerbated AIHA cases developed IgG and IgM against RBCs, respectively. This review provides a comprehensive explanation regarding the AIHA development and exacerbation after COVID-19 vaccination.

A Case of Autoimmune Haemolytic Anaemia After Allogeneic Stem Cell Transplantation in Adult Patient: A Refractory and High Mortality Outcome

A Case of Autoimmune Haemolytic Anaemia After Allogeneic Stem Cell Transplantation in Adult Patient: A Refractory and High Mortality Outcome

Autoimmune Hemolytic Anemia After Inactivated Virus COVID-19 Vaccination: A Report of 2 Cases

Very few cases of autoimmune hemolytic anemia (AIHA) have been reported after mRNA COVID-19 vaccinations. But herein we found 2 cases of AIHA after inactivated virus COVID-19 vaccination. Case 1: a 47-year-old Thai woman suffered from malaise, fatigue, and feverish feeling since the evening of the day of the first dose of inactivated virus COVID-19 vaccination (Sinopharm). She did not have any serious health problem prior this illness. Physical examination revealed marked pallor and body temperature was 38.1°C. Blood tests showed hemoglobin (Hb) 55 g/L, white blood cell (WBC) 12.2 × 109/L, platelet 310 × 109/L, nucleated red blood cell (RBC) 8/100 WBC, reticulocyte count 25.0%, direct antiglobulin test-4+ positive, indirect antiglobulin test-2+ positive. She was diagnosed with severe AIHA and well responsive to steroid therapy. Case 2: a 78-year-old Thai woman felt fatigue without fever 3 days after the second dose of inactivated virus COVID-19 vaccine (Sinopharm). Her underlying disease was anemia of the elderly with alpha thalassemia-1 heterozygosity. Her averaged Hb concentration before transfusion was 85 ± 3 g/L and she always needed transfusion every 2 months. Physical examination revealed only pallor. Blood test showed Hb 79 g/L, WBC 3.7 ×109/L, platelet 104 × 109/L, direct antiglobulin test-4+ positive, indirect antiglobulin test-4+ positive. She was diagnosed with AIHA and treated with cyclophosphamide and blood transfusion. Although the association between the inactivated virus COVID-19 vaccination and AIHA could not be simply concluded and the mix-and-match combination of different COVID-19 vaccines is promoted by Thai government, both of our patients chose to postpone the next dose of any kind of COVID-19 vaccine.

P1525: MANAGEMENT OF AUTOIMMUNE HAEMOLYTIC ANAEMIA DURING PREGNANCY OR POST-PARTUM: AN INTERNATIONAL MULTI-CENTRE EXPERIENCE.

Background: Autoimmune haemolytic anaemia (AIHA) during pregnancy is a rare finding, and few is known about maternal and foetal outcomes. AIHA may either develop or relapse during gestation and postpartum or be an issue in a patient on active therapy who becomes pregnant. AIHA management during pregnancy and lactation is not standardized and drug use is often limited by safety concerns. Aims: We studied AIHA impact on pregnancy focusing on disease severity, treatment need and maternal/foetal outcome. Methods: Through a multicentric retrospective cohort study, we identified 38 pregnancies occurred in 28 women from 1997 to 2021 in 10 European centres in Italy, Denmark, France, the Netherlands, USA, and Spain. All included patients had a previous AIHA history or developed/exacerbated AIHA during gestation or postpartum. AIHA was classified according to the direct antiglobulin test. Results: We registered 18 warm AIHA (10 IgG; 8 IgG+C3d), 2 cold agglutinin disease, 3 mixed and 5 atypical forms (Table 1). Evans syndrome (i.e., association of AIHA and immune thrombocytopenia or neutropenia) was present in 4. Mean age at AIHA diagnosis was 27 (3-39) and at pregnancy 32 (21-41) years. AIHA diagnosis predated pregnancy in 15 women and had required at least 1 therapy line in all of them, and ≥2 lines in 12 (rituximab, N=7; cytotoxic immunosuppressants, N=6; splenectomy, N=5). Among these 15 patients, 6 had a relapse during pregnancy, 3 during postpartum and 9 were on active treatment at the time of pregnancy (steroids, N=8; cyclosporine, N=1; azathioprine, N=1; the latter stopped after positive pregnancy test). A patient with a previous AIHA, relapsed as immune thrombocytopenic purpura during pregnancy. Further 8 patients had an AIHA onset during gestation and 2 postpartum. A patient had AIHA onset during the postpartum of the 1st pregnancy and relapsed during the 2nd one. In the 20 women experiencing AIHA during pregnancy/postpartum, median Hb and LDH levels were 6,4 g/dL (3,1 – 8,7) and 588 UI/L (269-1631), respectively. Management consisted in blood transfusions (N=10) and prompt establishment of steroid therapy+/-IVIG (N=20), all with response (complete N=13, partial N=7). After delivery, rituximab was necessary in 4 patients and cyclosporine was added in one. Anti-thrombotic prophylaxis was given in 7 patients. Overall, we registered 10 obstetric complications (10/38, 26%), including 4 early miscarriages, a premature rupture of membranes, a placental detachment, 2 preeclampsia, a postpartum infection and a biliary colic. Apart from the case of biliary colic and one of the two cases of preeclampsia, 8/10 complications occurred during active haemolysis and treatment for AIHA. Nine foetal adverse events (9/38, 24%) were reported: a transitory respiratory distress of the new-born in a mother with active AIHA, 3 cases of foetal growth restriction, a preterm birth, an infant reporting neurologic sequelae, a case of AIHA of the new-born requiring intravenous immunoglobulins, blood transfusions and plasma exchange, and 2 perinatal deaths. The latter both occurred in women on active AIHA therapy and were secondary to a massive placental detachment and a symptomatic SARS-CoV-2 infection. Image:Summary/Conclusion: AIHA developing/reactivating during pregnancy or postpartum is rare (about 5%) but mainly severe requiring steroid therapy and transfusions. Importantly, severe maternal and foetal complications may occur in up to 26% of cases mostly associated with active disease, pinpointing the importance of maintaining a high level of awareness. Passive maternal autoantibodies transfer to the foetus seems a rare event.

P1552: A PHASE 2, OPEN-LABEL STUDY TO ASSESS SAFETY, TOLERABILITY, AND CLINICAL EFFECT OF ANX005 IN PATIENTS WITH WARM AUTOIMMUNE HEMOLYTIC ANEMIA AND EVIDENCE OF COMPLEMENT ACTIVATION

Background: Autoimmune hemolytic anemia (AIHA) is caused by autoantibody destruction of red blood cells (RBCs) and is divided into warm autoimmune hemolytic anemia (wAIHA) and cold agglutinin disease. In wAIHA, which accounts for 60-70% of AIHA cases, polyclonal immunoglobulin G (IgG) antibodies cause hemolysis of RBCs at core body temperatures. However, approximately 50% of wAIHA cases are not caused by pathogenic IgG alone. The correlation between autoimmune hemolysis and presence of complement on RBCs in wAIHA patients suggests a role for the complement system in the pathogenesis of wAIHA, which can be triggered by C1q binding to autoantibodies bound to RBCs. ANX005 is a humanized IgG4 monoclonal antibody that selectively binds and inhibits C1q, blocking activation of the classical complement pathway, with the potential to inhibit complement-mediated hemolysis in wAIHA. Aims: The goal of this clinical study is to evaluate two once-weekly IV infusions of ANX005 in patients with wAIHA having evidence of complement pathway activation to understand the effect of C1q inhibition on pathway markers and objective disease parameters. Methods: This is an open-label, repeat-dose, Phase 2 study (NCT04691570) of ANX005 in patients with wAIHA and evidence of classical complement pathway activation. Up to 12 patients will be enrolled in this study and undergo a screening period of up to six weeks prior to Day 1. Patients will receive two doses of ANX005 on Days 1 and 8. Safety and pharmacokinetic (PK)/pharmacodynamic (PD) evaluations will be completed on Days 4, 15, 22, 29, 36, 43, 50, 57, and 71. Individual study duration will be up to 16 weeks, and patients will complete study participation on Day 71. The primary objective is to evaluate the safety and tolerability of ANX005. Secondary objectives include evaluating the PK and PD profile of ANX005, examining markers of classical pathway activation, and determining the impact of classical complement inhibition on hemoglobin levels and biomarkers of hemolysis through Day 71 in this subset of patients. Results: Results from the Phase 2 trial are expected by the end of 2022. Image:Summary/Conclusion: In this Phase 2 study of ANX005 in patients with wAIHA and evidence of classical complement pathway activation, patients will receive two IV doses of ANX005 one week apart with the goal of evaluating its safety, tolerability, PK/PD, and clinical effect to further understand the role of classical complement in this heterogeneous disease as a target for effective therapy.

Evan’s Syndrome: Case Series with Review of Literature

Evans syndrome is a rare autoimmune disease in which an individual’s antibodies attack the body’s own red blood cells and platelets. It is characterised by simultaneous or sequential development of Immune Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA) with positive Direct Antiglobulin test (DAT). AIHA can be cold, warm or mixed type depending on the type of antibody. 80% of total AIHA cases are warm AIHA. Warm AIHA is mostly caused by IgG antibody which reacts at 370 C. Warm AIHA is associated with classical case of Evan’s syndrome. Some variants of Evan’s syndrome are associated with leucocytosis. The current article discusses 3 cases of Evan’s syndrome, all presenting differently - Classical Evan’s syndrome, Evan’s syndrome associated with leucocytosis and Evan’s syndrome associated with neuropathic pain. In this case series, pathophysiology, workup done at blood centre and blood component transfusion support in patients with Evan’s syndrome has been discussed. Keywords: Evan’s syndrome, Anemia, Autoimmune

Report of a rare case of autoimmune haemolytic anaemia in a patient with hodgkin's disease in whom routine serology was negative

Autoimmune haemolytic anaemia can be negative for direct antiglobulin test. Hence the DAT negative patients cannot be ruled out from having AIHA when there is clinical suspicion of AIHA. We hereby report our case of AIHA with Hodgkin’s lymphoma who is DAT- negative.

A Case of Overlapping Autoimmune Sclerosing Cholangitis and Autoimmune Hemolytic Anemia

This case study revolves around a 14-year old female patient, who was otherwise healthy and normal, but brought to the hospital for her condition. The patient presented with complaints of fever, sore throat, severe abdominal pain, and generalized body aches for the last two days.
 She appeared to be lethargic and weak. Her condition had made her fatigued and a yellowish tinge of the face and sclera was obvious, pointing towards a likely case of jaundice. Upon abdominal examination, the patient also had hepatomegaly and splenomegaly present, and the muscles appeared to be tender as well.
 The child was admitted to the hospital, where her lab investigations revealed that she was anemic. Other investigations revealed that her liver enzymes and bilirubin levels were significantly elevated. Her DAT was positive and there was a presence of high eosinophilia.
 However, her Hepatitis A, B, and C screening came out to be negative. She was kept as a suspected case of Autoimmune Hemolytic Anemia as it appeared to be the most probable diagnosis, given her condition, but following a biopsy she was also confirmed as a case of Autoimmune Sclerosing Cholangitis.
 Once the diagnosis was confirmed, the child was treated accordingly. This was a unique case because it involved a significant overlap in the presence of two diseases. Both of the diseases, although similar in appearance, could have caused great havoc if they were not separately diagnosed and treated accordingly.
 This case study deals with such an overlapping case that was brought to the hospital. With a myriad of confusing symptoms, it was obvious that the diagnosis could have been misdiagnosed or incorrectly diagnosed. However, the lab reports and examinations that were carried out smartly helped in excluding the other diagnoses which would have obviously lead to confusions and also in starting the wrong treatment.
 This case study deals with the examination, laboratory protocols, along with the association of symptoms, all of which help in reaching towards the final diagnosis in a timely manner and thus, helped treat the patient effectively.
 The case study also highlights how both of these diseases present in a patient of the younger population, and how they need to be managed effectively and efficiently to ensure that there are no complications that might alter the already deteriorating state of the patient.

COVID-19 DILEMMA: EARLY SEVERE HEMOLYTIC JAUNDICE IN NEWBORN BORN TO MOTHER WITH SARS-COV-2 INFECTION IN PREGNANCY

COVID-19 has been associated with hemolytic anemia in pediatric as well as adult age group. However, very little is known about the clinical course and immune responses in newborn born to a mother who contracted SARS-CoV-2 infection during pregnancy. Previously, few cases of autoimmune hemolytic anemia with SARS-CoV-2 infection due to the cytokine storm or through molecular mimicry has been found. Through this report, we would discuss about the SARS-COV-2 reactive antibodies as a potential etiology of severe early hemolysis leading to severe neonatal hyperbilirubinemia in a neonate born to a mother with SARS-CoV-2 infection.

Blood Transfusion Therapy in Patients with Autoimmune Hemolytic Anemia

Management therapy of autoimmune hemolytic anemia (AIHA) with severe clinical symptoms requires supportive therapy such as blood components transfusion to improve hemodynamic conditions. This literature study aims to explain the role of blood transfusion therapy in AIHA cases. The method used is through searching articles in national and international journals published in the last 10 years that discuss transfusion in AIHA cases using the Google Scholar application. From the search results, it can be concluded that blood transfusion is a supportive therapy in cases of AIHA with symptoms of severe hypoxemia that interfere with hemodynamics and work function of body organ systems and findings of Hb levels < 7 mg/dL with the selection of blood components in the form of packed red cells (PRC), washed packed red cells (WPRC) and Leucoreduction (LR).

Red Blood Cell Transfusion for Pediatric Autoimmune Hemolytic Anemia in an Emergency Situation

Autoimmune hemolytic anemia (AIHA) is often presented with severe anemia. Currently, several centers in Indonesia use washed red blood cells (RBCs) to transfuse AIHA patients. However, washed RBCs are not widely available, causing a delay in therapy. We herein report two cases of pediatric AIHA who presented with severe anemia with hemoglobin level of 4.1 g/dL and 5.3 g/dL. Both patients were delayed for two and five days to be given blood transfusion because of the unavailability of washed RBC in Sorong General Hospital and Fatmawati Hospital and must wait to be referred to RSCM to receive washed RBCs. We conducted literature searches to review several articles that focus on AIHA transfusion management. AIHA is characterized by the production of autoantibodies directed against antigens on the surface of RBCs. RBC washing is not currently required in AIHA patients. It is also not widely available, takes a long time to process, and can cause a delay in emergency cases. Although RBC transfusion is not contraindicated in AIHA, its use should be limited to life-threatening cases of anemia with signs of cardiac and neurological compromises. In emergency cases, ABOmatched and Rhesus-matched RBCs can be safely administered if alloantibodies are reasonably excluded based on the previous transfusion and pregnancy history. ABO-matched and Rh-matched RBC transfusion is safe as AIHA’s transfusion management for patients with severe anemia with clinical symptoms.

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.

Pregnancy-Associated Autoimmune Hemolytic Anemia: Meta-Analysis of Clinical Characteristics, Maternal and Neonatal Outcomes

▪Introduction: Autoimmune hemolytic anemia (AIHA) is a rare condition that can cause potentially serious complications in pregnant women and newborns. With the lack of prospective trials, physicians often have to make treatment decisions for this vulnerable population based on scarce literature with poor evidence. We sought to summarize existing literature and analyze maternal and neonatal outcomes in pregnancy-associated AIHA (p-AIHA).Methods: Cases of AIHA in pregnancy were collected using MEDLINE/PubMed and Google Scholar literature search using terms “autoimmune hemolytic anemia” and “pregnancy”. Bibliography of each article was hand-searched for additional reports. Only publications in English were included. Cases of preexisting AIHA, autoimmune disease associated AIHA, non-immune hemolysis, and cases where direct antiglobulin testing (DAT) was not performed, were excluded. Laboratory, obstetric, neonatal and treatment data were collected. Data were analyzed using descriptive statistics. We used Wilcoxon rank sum test for continuous variables and Fisher's exact test for categorical variables. When missing data were encountered, we reported a valid number of analyzed patients in parentheses.Results: We identified 87 cases of p-AIHA from case reports, case series, abstracts and posters. Final analysis included 51 individual women. Median age at p-AIHA presentation was 28 years. Presentation was less common in the first pregnancy (34%); most cases presented in the second or third trimester (83.3%).Median nadir hemoglobin (Hb), lactate dehydrogenase, total bilirubin and peak reticulocyte count were 5.8 g/dL, 457 U/L, 2.2, and 13.6%, respectively. DAT negative hemolysis was reported in 41% of cases (Table 1). DAT positivity was not associated with pregnancy trimester, hemolysis severity, response to steroids, AIHA recurrence, adverse pregnancy outcomes, or hemolysis in newborn. There was a trend for longer duration of hemolysis postpartum in women with positive DAT compared to negative DAT (10 vs 2 weeks, p = 0.08). Median duration of hemolysis postpartum was 6 weeks (n=27, range 0-96 weeks). Two thirds of women were treated with steroids with hemoglobin response of 88.9% (n=27). There was no association between steroid use and duration of hemolysis postpartum. Blood transfusion was administered in 27 out of 33 women, with a median number of units transfused 5. Recurrent p-AIHA was seen in 40% (12/30) of women; there was no difference in nadir Hb levels for those with recurrent p-AIHA vs. not recurrent (6.8 vs 5.2 g/dL, p=0.11).Pregnancy resulted in term delivery in 61.9%, preterm delivery in 23.8%, and stillbirth in 9.5% (n=42). Adverse pregnancy outcomes, which included preterm labor and stillbirth, were reported in 50% of women who presented in the first or second trimester compared to 16% who presented in the third trimester (p=0.049, Table 2).Women with adverse pregnancy outcomes had significantly lower median nadir hemoglobin compared to women without adverse pregnancy outcomes (4.3 and 6.2 p = 0.0078) and were more likely to receive transfusion (73% and 56%, p= 0.071). Hemolysis at birth was reported in 59% (n=22) of newborns with available data with 13 neonates (38%) requiring transfusion support . Use of steroids had no effect on presence of hemolysis in the newborn.Conclusions: We present the largest cohort of p-AIHA described in the literature. Our study reports that p-AIHA is uncommon in primigravidas and typically presents later in pregnancy. Presentation in first or second trimester in pregnancy and lower Hb nadir were significantly associated with adverse pregnancy outcomes. Steroids and blood transfusions were needed in most patients, and hemolysis persisted on average for 6 weeks postpartum. There was a high frequency of Coombs negativity which was associated with shorter duration of postpartum hemolysis. Preterm labor and stillbirth were observed in 33.3% of pregnancies. The incidence of hemolysis in newborns from p-AIHA mothers is very high and is often clinically significant. Recurrence in subsequent pregnancy is common but has similar Hb nadir as non-recurrent cases. This study provides insights into the clinical course of pregnancy and neonatal outcomes in p-AIHA. Our findings may help guide management of this rare condition. A prospective study of patients with p-AIHA is needed to determine optimal therapy to reduce antepartum and neonatal complications. [Display omitted] DisclosuresMurakhovskaya: Alexion, Rigel, Bioverativ/Sanofi, Momenta, Annexion, Incyte: Research Funding; Bioverativ/Sanofi, Momenta, Apellis, Novartis: Consultancy; Cardiff Oncology, Trillium Therapeutics: Current holder of individual stocks in a privately-held company.

Diagnostic algorithm for classification and characterization of direct antiglobulin test-negative autoimmune hemolytic anemia with 1-year clinical follow-up.

Approximately 5%-10% of autoimmune hemolytic anemia (AIHA) cases are negative for direct antiglobulin test (DAT). We previously reported a classification system for untreated patients with DAT-negative AIHA by quantifying levels of red blood cell (RBC)-bound IgG. This study investigated the clinical utility of a novel diagnostic algorithm with a comprehensive classification system and characterized each subgroup in DAT-negative AIHA. We assessed 637 patients with undiagnosed hemolytic anemia using our diagnostic algorithm and classification system, which was based on RBC-bound IgG levels and results of column method-DAT before and after washing RBCs. Patients were diagnosed with DAT-negative AIHA with 97% sensitivity and 84% specificity when the laboratory tests were performed before treatment and classified into the following six categories: tube DAT-negative, low-affinity IgG, double DAT-negative, IgA- or IgM-positive, low-affinity IgM, and s/o non-AIHA. The first three types were major conditions and accounted for 76% of DAT-negative AIHA cases. Based on multivariate analyses of idiopathic DAT-negative AIHA (n=71), platelet count and albumin concentration were significant factors for survival at 1-year follow-up. The low-affinity IgG group showed the highest platelet count and albumin levels, better response to steroids, and higher 1-year survival rate than those in other groups. Our classification included DAT-negative, IgA-driven, and warm-IgM AIHA categories, which were atypical forms of AIHA with the severe onset and increased risk of relapse. When treating a patient with DAT-negative hemolysis, atypical AIHA should be considered and tested in reference laboratories, especially before treatment.

GUILLAIN-BARRÉ SYNDROME AND HEMOLYSIS IN COVID-19

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: The spectrum of autoimmune phenomena associated with Coronavirus disease 2019 (COVID-19) continues to expand. Guillain-Barre Syndrome (GBS) manifesting as a post-infectious sequela of COVID-19 has been increasingly reported [1]. Rare cases of autoimmune hemolytic anemia (AIHA) associated with COVID-19 are also emerging [2]. Our case describes a novel presentation of GBS and hemolysis in a patient with COVID-19. CASE PRESENTATION: A 62-year-old male with a past medical history of hypertension initially presented with 5 days of low-grade fever and cough. He denied dyspnea and was not hypoxic. Nasopharyngeal PCR confirmed COVID-19. He received bamlanivimab and etesevimab infusion and was discharged from the emergency room. He returned 6 days later with new-onset unsteady gait and weakness of the lower extremities. He had 1+ reflexes in the patellar and ankle bilaterally and 3+ in both triceps and biceps. This worsened into flaccid paralysis of bilateral lower extremities by admission day 2. Labs showed a drop in hemoglobin (Hgb) from 14.7 mg/dL to 10.9 mg/dL, haptoglobin 2) at time of discharge [1, 3]. AIHA has also been associated with COVID-19, with mixed warm and cold agglutin formation [2]. A negative CSF PCR panel with high protein suggests that novel antibodies may mediate myelin damage, which may also target other components such as fibrinogen in α/β chains. Immunoglobulin fragment alteration resulting in molecular mimicry may also occur following antigen-antibody complex formation directed against the virus [1]. CONCLUSIONS: GBS and AIHA are rare but important complications in patients with COVID-19. The spectrum of autoimmune phenomena associated with COVID-19 continues to expand. This case highlights the need for the differential to include autoimmune disease in patients with extrapulmonary manifestations of COVID-19. Further studies are needed to determine if causal relationships are present. REFERENCE #1: Sheikh AB, Chourasia PK, Javed N, et al. Association of Guillain-Barre syndrome with COVID-19 infection: An updated systematic review. 2021 Apr 18. J Neuroimmunol. 2021;355:577577. doi:10.1016/j.jneuroim.2021.577577 REFERENCE #2: Lazarian G, Quinquenel A, Bellal M, et al. Autoimmune haemolytic anaemia associated with COVID-19 infection. Br J Haematol. 2020;190(1):29-31. doi:10.1111/bjh.16794 REFERENCE #3: Hasan I, Saif-Ur-Rahman KM, Hayat S, et al. Guillain-Barre syndrome associated with SARS-CoV-2 infection: A systematic review and individual participant data meta-analysis. J Peripher Nerv Syst. 2020 Dec;25(4):335-343. doi: 10.1111/jns.12419. DISCLOSURES: No relevant relationships by Mateus Fernandes, source=Web Response No relevant relationships by Ifediba Nwachukwu, source=Web Response

Primary Autoimmune Hemolytic Anemia Due To Warm Reactive Autoantibodies: A Rare Case Report

Autoimmune hemolytic anemia (AIHA) is an acquired form of hemolytic anemia in which autoantibodies target red blood cell (RBC) membrane antigens, inducing cell rupture (lysis). It affects both pediatric and adult populations, although its presentation in childhood is relatively rare, with the annual incidence estimated to be approximately 0.8 per 100,000 individuals under 18 years old [3]. Here we report one such a rare case of autoimmune hemolytic anemia due to primary warm reactive autoantibodies in a 3 year old female child. As there was presence of hemolysis in peripheral blood smear & other investigations also, Direct coomb’s test was done & it came out to be positive which was suggestive of autoimmune hemolytic anemia, as following lab reports are suggestive of continuous destruction of RBC & after introduction of steroids parameters of hemolysis came out to be normal suggestive of warm reactive autoantibodies type of AIHA. Clinically also patient improved & her urine colour also became normal after when prednisolone started. Patient also did not have any features of secondary causes of warm autoantibody like Systemic lupus erythematous, immunodeficiency disorders, ulcerative colitis & lymphoproliferative disorders so it was considered primary or idiopathic. W-AIHA tends to have a chronic course and is not expected to subside without treatment. It can be a fatal disease, with a mortality rate of up to 4% in children, either because of the acuity of the presentation or because of being refractory to treatment and requiring multiple lines of therapy with frequently associated toxicity [14]. Fortunately our patient responded to steroid therapy.

SARS‐CoV‐2 vaccination in patients with autoimmune cytopenias: The experience of a reference center

<scp>SARS‐CoV</scp>‐2 vaccination in patients with autoimmune cytopenias: The experience of a reference center

Проблема диагностики приобретенных гемолитических анемий в детском возрасте

Аутоиммунная гемолитическая анемия (АИГА) — это группа заболеваний, в основе которых лежит декомпенсированный приобретенный гемолиз. АИГА у детей чаще всего наблюдается после вирусного заболевания. Это достаточно редкое состояние с частотой менее 0,2 случая на 100 000 педиатрического населения. Целью статьи было представить клинический случай больного АИГА. Представлен случай гемолитической анемии у ребенка 4 лет на фоне острой вирусной инфекции с пневмонией и диспептическим синдромом. Во время пребывания в больнице состояние мальчика резко ухудшилось за счет быстрого нарастания слабости и бледности кожных покровов. Общий анализ крови выявил прогрессирующую гемолитическую анемию (Hb 57 г/л, эритроциты 2,58 × 1012/л, Ht 0,16, лейкоциты 13,88 × 109/л, СОЭ 69 мм/ч, тромбоциты 400 × 109/л). Наблюдалось умеренное повышение билирубина за счет неконъюгированной фракции (31,3 и 21,2 мкмоль/л соответственно). В связи с критическим нарастанием анемического синдрома встал вопрос о необходимости гемотрансфузии, но в результате теста на индивидуальную совместимость 20 пакетов крови одной группы было отклонено из-за несовместимости. Интенсивная иммуносупрессивная терапия (комплексное введение высоких доз кортикостероидов в сочетании с внутривенными иммуноглобулинами в дозе 2 г/кг/день) позволила остановить гемолиз и улучшить состояние пациента, вопрос о переливании крови был отклонен. Особенностью представленного случая было критическое нарастание анемии при отсутствии классических признаков гемолиза, невозможность проведения гемотрансфузии и положительная динамика при назначении высоких доз кортикостероидов и иммуноглобулина. Осведомленность об АИГА должна присутствовать у педиатров, и важно расширить их знания о правильном алгоритме диагностики в таких случаях. Препаратами выбора для лечения АИГА являются внутривенные иммуноглобулины в иммуносупрессивных дозах и глюкокортикоиды коротким курсом. В случаях резистентности к такому лечению показано переливание перфторана.

Autoimmune Hemolytic Anemia as a Complication of Congenital Anemias. A Case Series and Review of the Literature.

Congenital anemias may be complicated by immune-mediated hemolytic crisis. Alloantibodies are usually seen in chronically transfused patients, and autoantibodies have also been described, although they are rarely associated with overt autoimmune hemolytic anemia (AIHA), a serious and potentially life-threatening complication. Given the lack of data on the AIHA diagnosis and management in congenital anemias, we retrospectively evaluated all clinically relevant AIHA cases occurring at a referral center for AIHA, hemoglobinopathies, and chronic hemolytic anemias, focusing on clinical management and outcome. In our cohort, AIHA had a prevalence of 1% (14/1410 patients). The majority were warm AIHA. Possible triggers were recent transfusion, infection, pregnancy, and surgery. All the patients received steroid therapy as the first line, and about 25% required further treatment, including rituximab, azathioprine, intravenous immunoglobulins, and cyclophosphamide. Transfusion support was required in 57% of the patients with non-transfusion-dependent anemia, and recombinant human erythropoietin was safely administered in one third of the patients. AIHA in congenital anemias may be challenging both from a diagnostic and a therapeutic point of view. A proper evaluation of hemolytic markers, bone marrow compensation, and assessment of the direct antiglobulin test is mandatory.