Case Of Autoimmune Hemolytic Anemia Research Articles

A case of autoimmune haemolytic anaemia associated with mediastinal teratoma

A case of autoimmune haemolytic anaemia associated with mediastinal teratoma

Autoimmune Hemolytic Anemia Associated with Mature Ovarian Cystic Teratoma Containing Monoclonal Immunoglobulin G: A Case Report and Review of Literature

Background. Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated case of secondary AIHA in a mature cystic teratoma containing antibodies against red blood cells. Case description. A 22-year-old woman was referred to our hospital with progressive anemia. Laboratory findings revealed hemolysis with a positive direct and indirect antiglobulin test. Imaging studies identified a left ovarian mass, suspected to be a mature cystic teratoma, which was later confirmed by histopathology after laparoscopic oophorocystectomy. The patient was treated with prednisolone, resulting in improved anemia. To examine the relationship between the tumor and AIHA, an indirect antiglobulin test was performed on the tumor contents. Stronger aggregations were observed at any concentration diluted by 10 times from 10 to 10,000 times of the tumor contents compared to the patient’s serum. Additionally, immunofixation electrophoresis of the tumor contents revealed the presence of monoclonal immunoglobulin G-κ. Conclusion. The presence of monoclonal IgG-κ in the tumor suggests intratumoral antibody production as a possible mechanism. Further research is necessary to elucidate the pathogenic relationship between such tumors and AIHA. The report also highlights the importance of considering secondary AIHA in patients with unexplained anemia and solid tumors.

Challenges in the diagnosis and management of autoimmune hemolytic anemia: A case-based approach. Experience from a tertiary care hospital in the Haryana region.

Autoimmune hemolytic anemia (AIHA) is a rare immune disorder which occurs when antibodies are directed against self red blood cells (RBCs) leading to hemolysis. AIHA is widely classified as warm autoimmune hemolytic anemia, cold agglutinin syndrome, mixed AIHA, paroxysmal cold hemoglobinuria and rarely drug induced AIHA. The pathogenesis of AIHA is complex interplay between genetic predisposition, immune dysregulation and enviornmental triggers. A direct antiglobulin test can be used to assess the immunological origin of the hemolysis in order to diagnose AIHA after identifying laboratory and clinical symptoms of hemolysis. The objective is to understand underlying mechanism in AIHAs, and usage of targeted therapies to modulate specific components of the immune response. We are hereby presenting a case series of 11 clinically suspected cases of AIHA in collaboration with their clinical features, immuno-hematological and other laboratory parameters, Flow cytometric analysis of lymphocyte subset in relevant cases, underlying etiology as well as serological subtype are also included. Majority of the patients were categorized as secondary AIHA (7/11, 63.63%). Out of 11 cases 7 were serologically subtyped as warm AIHA (7/11, 63.63%) ,2 cases were DaaT negative AIHA (2/11;18.18%), 2 cases were characterized as mixed AIHA subtype (2/11, 18.18%). Accurate subtyping of AIHA requires a systematic immunohematological approach coupled with comprehensive evaluations of clinical, hematological, and biochemical parameters.

Laparoscopic excision of accessory spleen for recurrent autoimmune hemolytic anemia after splenectomy: a case report

BackgroundSplenectomy is indicated in cases of autoimmune hemolytic anemia (AIHA), which are refractory to medical management. In post-splenectomy, there exists a theoretical risk of AIHA recurrence, especially if an accessory spleen undergoes compensatory hypertrophy. In this context, we present a unique case of recurrent AIHA managed through laparoscopic excision of the accessory spleen (LEAS).Case presentationA 60-year-old male underwent laparoscopic splenectomy (LS) for AIHA refractory to standard medical therapies. Following the surgery, there was a marked improvement in hemolytic anemia symptoms, and oral steroid therapy was terminated 7 months post-LS. Nonetheless, a year after the LS, the patient exhibited a marked decline in hemoglobin levels, dropping to a concerning 5.8 g/dl, necessitating the reintroduction of oral steroids. A subsequent contrast-enhanced computed tomography (CT) scan unveiled an enlarged accessory spleen. The patient then underwent LEAS, during which the accessory spleen, obscured within adipose tissue, proved challenging to visualize laparoscopically. This obstacle was surmounted utilizing intraoperative ultrasonography (US), enabling successful excision of the accessory spleen. The post-surgical period progressed without complications, and the steroid dosage was reduced to one-twelfth of its initial preoperative quantity.ConclusionsRecurrent AIHA can be instigated by post-splenectomy compensatory hypertrophy of the accessory spleen. Ensuring comprehensive splenic tissue excision is crucial in AIHA management to obviate recurrent stemming from hypertrophic remnants. In scenarios of AIHA recurrence tied to an enlarged accessory spleen, LEAS stands as a viable and effective therapeutic modality.

Mefenamic acid triggered autoimmune hemolytic anemia in a child: a rare case report

Autoimmune hemolytic anemia (AIHA) is characterized by the abnormal production of antibodies that bind to antigens on the surface of red blood cells (RBC), resulting in RBC destruction. Here we describe a rare case of mefenamic acid-induced AIHA in a 3-year-old boy who developed acute hemolysis after ingestion of mefenamic acid for febrile illness. The aim is to draw the attention of pediatricians to one of the side effects of mefenamic acid, the drug which is very commonly used as an antipyretic.

Immunohematological evaluation of red cell alloimmunization and statistical assessment of various adsorption techniques in warm autoimmune hemolytic anemia

Adsorption techniques are widely applied to detect underlying masked alloantibodies in warm autoimmune hemolytic anemia (WAIHA). We established various adsorption techniques with an aim to detect alloimmunization in WAIHA This study conducted over a period of nine years included 298 patients of WAIHA. Complete immunohematological evaluation was performed on these 298 samples following departmental protocols. Clinical and laboratory details of patients were obtained from patient files. Various adsorption methods were performed and statistically evaluated in the study. Out of 479 cases of autoimmune hemolytic anemia, WAIHA comprised of 62.2 % (N = 298). A total of 139 (46.6 %) serum samples revealed autoantibodies. Adsorption study was performed in 101 (72.7 %) indicated samples and 24 (23.8 %) of these showed 26 alloantibodies. Among the patients subjected to adsorption study hemolytic marker were significantly deranged in the alloimmunization group (p < 0.01). Polyethylene glycol (PEG) adsorption was the quickest (52.2–54.6 min) of all adsorption techniques with minimum (1.3–1.5) numbers of adsorptions needing for complete removal of serum antibodies. The LISS-papain (LP) technique was found to be more sensitive and specific compared to the other two techniques. The agreement between PEG adsorption and LP adsorption was found to be ‘perfect’ (96.4 %) with a Cohen’s kappa (k) value of 0.9. We conclude that identification of alloantibody specificities underlying a warm autoantibody is critical for a safe and effective transfusion. All WAIHA patients with history of blood transfusion, pregnancy or both should be subjected to adsorption study. Selection of a suitable adsorption technique depends on multiple important factors.

A Rare Case of Autoimmune Hemolytic Anemia after Implantation of a Drug Eluting Stent to Coronary Artery

A Rare Case of Autoimmune Hemolytic Anemia after Implantation of a Drug Eluting Stent to Coronary Artery

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

Autoimmune hemolytic anemia (AIHA) is defined by increased erythrocyte turnover mediated by autoimmune mechanisms. While corticosteroids remain first-line therapy in most cases of warm-antibody AIHA, cold agglutinin disease is treated by targeting the underlying clonal B-cell proliferation or the classical complement activation pathway. Several new established or investigational drugs and treatment regimens have appeared during the last 1-2 decades, resulting in an improvement of therapy options but also raising challenges on how to select the best treatment in individual patients. In severe warm-antibody AIHA, there is evidence for the upfront addition of rituximab to prednisolone in the first line. Novel agents targeting B-cells, extravascular hemolysis, or removing IgG will offer further options in the acute and relapsed/refractory settings. In cold agglutinin disease, the development of complement inhibitors and B-cell targeting agents makes it possible to individualize therapy, based on the disease profile and patient characteristics. For most AIHAs, the optimal treatment remains to be found, and there is still a need for more evidence-based therapies. Therefore, prospective clinical trials should be encouraged.

Acute kidney injury following autoimmune hemolytic anemia due to simultaneous use of ciprofloxacin and hydrochlorothiazide: A case report and review of the literature

AbstractIntroductionRare cases of autoimmune hemolytic anemia (AHA) associated with using ciprofloxacin or hydrochlorothiazide (HCTZ) alone have been reported before. However, simultaneous use of both drugs could lead to a severe clinical condition. This study presents the combination of acute kidney injury (AKI) and AHA following the simultaneous use of ciprofloxacin and HCTZ for three days.Case DescriptionA 42‐year‐old Iranian woman presented to the emergency department with symptoms of fatigue, lethargy, nausea and vomiting, ataxia, oliguria, dark urine, and jaundice. The patient reported using HCTZ due to high blood pressure and ciprofloxacin for a urinary tract infection three days before presentation. Early laboratory findings revealed hemolytic anemia with a hemoglobin of 7 g/dl, the strongly positive direct and indirect Coombs test, high level of lactate dehydrogenase (820 IU/L), and hyperbilirubinemia (total: 3 mg/dL and direct: 1.2 mg/dL). Furthermore, hyperkalemia (5.2 mEq/L), hyperphosphatemia (6.2 mg/dL), high levels of BUN (100 mg/dL), and creatinine rise (6.8 mg/dL) were found. Urine analysis showed 2+ blood, 4‐6 red blood cells, and cola‐colored urine. Based on the findings, drug‐induced AHA, followed by AKI, was diagnosed. Following, the drugs were stopped and steroid therapy was initiated. The patient underwent four sessions of hemodialysis to improve the AKI.ConclusionHealthcare providers should be aware of the life‐threatening adverse effects of commonly used drugs such as ciprofloxacin or HCTZ. The timely diagnosis of the offending drugs leads to avoiding the persistence of the risk factor and the deterioration of the patient's clinical condition.

Real-world data from India on clinical practices in the management of autoimmune haemolytic anaemia: A survey-based cross-sectional assessment.

Autoimmune haemolytic anaemia (AIHA) is a decompensated acquired haemolysis caused by the host's immune system acting against its own red cell antigens. The aim of this national survey is to capture real-world data of clinical practices in AIHA by collecting responses from clinical haematologists across India. In this cross-sectional study, a structured, 26-question online survey was conducted in India by few members of the special interest group in immunohaematology between January and March, 2022. The final survey consisted of questions covering place of work, amount of AIHA cases being evaluated by the haematologist over preceding years, basic demographic, clinical and laboratory features of the patients being treated under them etc. Descriptive statistical analysis was performed during the assessment. The survey response rate was 48.2% (53/110), 69.8% (37/53) have diagnosed and managed more than 10 AIHA cases in the last 3years with a female preponderance. There was considerable variability in response. While 56.6% (30/53) of respondents do have the access to the facilities to subtype AIHA cases; 32.1% (17/53) of clinicians would prefer administering high dose steroids for 6weeks or more in non-responding patients, and only 45.3% (24/53) would assess the risks of thrombosis in AIHA. There is unanimous agreement among the participants that health-related quality of life should be taken into consideration in patients and the need for a national registry of patients with AIHA in India. The current national survey showed that some aspects of AIHA management were consistent; others were less so, but also significant variations were observed in certain clinical practices, where the evidence base is limited. A joint effort is needed to establish a national patient registry by including both clinical haematologists and transfusion medicine specialists which could potentially standardise AIHA management and future research in India.

A case of Evans syndrome

Evans syndrome is an autoimmune disorder described by Robert Evans in 1951 specifying that a link exists between primary thrombocytopenic purpura and acquired haemolytic anaemia. It is a rare autoimmune disorder characterised by the simultaneous or sequential development of autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) with or without immune neutropenia. Approximately, Evans syndrome represent 5-10% of warm autoimmune haemolytic anaemia cases and 2-5% of ITP cases. It is basically a diagnosis of exclusion. We present a 50-year-old female presented with anaemia, jaundice and petechia. Patient indirect bilirubin was raised, Coombs test was positive, lactate dehydrogenase and reticulocyte count were raised. Based on the Coombs positive haemolytic anaemia and thrombocytopenia patient was diagnosed with Evans syndrome. ANA profile was positive for SS-A suggestive of underlying autoimmune disorder. Evans syndrome is difficult to diagnose and treat. Typically, corticosteroids and other immunosuppressive medications are used to manage the syndrome.

Autoimmune haemolytic anaemia and immune thrombocytopenia following SARS-CoV-2 and non-SARS-CoV-2 vaccination: 32 Years of passive surveillance data.

Autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) are two uncommon haematologic autoimmune conditions that can rarely arise secondary to vaccination. Prior studies using the US Centers for Disease Control's (CDC) Vaccine Adverse Event Reporting System (VAERS) have demonstrated this infrequency, but contemporary data as well as comparison with current information regarding SARS-CoV-2 vaccination has not been assessed. In this study, we reviewed VAERS database reports from 1990 to 2022 to characterize the incidence and clinical and laboratory findings of non-SARS-CoV-2-associated AIHA and ITP and SARS-CoV-2 vaccine-associated AIHA and ITP. We discovered a total of 863 AIHA and ITP reports following vaccination with 15 non-SARS-CoV-2 and four SARS-CoV-2 vaccines submitted to the CDC VAERS database. AIHA and ITP reporting was low for both groups, with a large proportion excluded due to a lack of clinical details. ITP was reported the most frequently in both groups and was significantly more common with measles-mumps-rubella (MMR) vaccination (p < 0.001) in the non-SARS-CoV-2 group. AIHA and ITP cases were higher in the SARS-CoV-2 vaccine group, though ultimately still very infrequent. Autoimmune haematologic disease is vanishingly rare after immunization and rates are lower than in the general population according to passive reporting.

Splenectomy as an effective treatment for macrothrombocytopenia in Takenouchi-Kosaki syndrome.

Takenouchi-Kosaki syndrome (TKS) is a rare congenital disease caused by a de novo heterozygous mutation in the CDC42 gene. Its characteristic clinical features are macrothrombocytopenia, developmental delay, dysmorphic facial features, and deafness. Splenectomy has been contraindicated for inherited thrombocytopenia, and there is little information on treatment of macrothrombocytopenia in TKS. In a previously reported case of autoimmune hemolytic anemia (AIHA) with TKS, we observed that AIHA initially resolved with prednisolone, but gradually became refractory to drug therapy. After splenectomy, both anemia and macrothrombocytopenia improved. This is a novel positive effect of splenectomy for thrombocytopenia in TKS, although further studies are required to assess the effectiveness and safety of splenectomy.

Autoimmune Hematological Toxicities of Immune Checkpoint Inhibitors: A Real-World Pharmacovigilance Database Analysis

BACKGROUND: Autoimmune hematological toxicities are rarely reported from the use of checkpoint inhibitors. However, there have been several cases of autoimmune hemolytic anemia, immune thrombocytopenia, hemophagocytic lymphohistiocytosis (HLH), and immune mediated cytopenias that have been reported in patients who were treated with checkpoint inhibitors. We performed a retrospective analysis of data of adverse effects of drugs that has been made available to public by the FDA. METHODS: The FDA has made data on adverse effects of various treatments available to the public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the autoimmune hematological toxicities of various checkpoint inhibitor therapies available at FAERS for the years 2020-2022. RESULTS: We reviewed the reported side effects of PD-1 inhibitors (pembrolizumab, nivolumab, cemiplimab, dostarlimab), PDL-1 inhibitors (atezolizumab, avelumab, durvalumab), and CTLA-4 inhibitors (ipilimumab) from FAERS. A total of 5,195 hematological toxicities from immunotherapies were reported from 2020-2022. Out of those, 483 (9.3%) were autoimmune hematological toxicities. The most common autoimmune complications were autoimmune hemolytic anemia (21.9%), immune thrombocytopenia (36%), autoimmune neutropenia (4.1%), HLH (36.2%) and thrombotic/idiopathic thrombocytopenic purpura (ITP/TTP) (1.8%). Nivolumab had the highest incidence of autoimmune hematological events out of all immune checkpoint inhibitors. Since cemiplimab and dostaralimab are relatively newly being utilized for treatment, there has not been much reported data. CONCLUSIONS: Out of the reported cases of hematological adverse reaction to check point inhibitor, 9.3% were autoimmune toxicities. There was no statistical difference in rate of autoimmune toxicities caused by PD1, PDL1 or CTLA 4 inhibitors. As utilization of newer immune checkpoint inhibitors increase, we would need to re-evaluate incidence of autoimmune hematological adverse reactions. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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.