Hemolytic Anemia Research Articles

Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.

Serological analysis of autoantibody mimicking anti-Rh(e) specificity: a case report

Mimicking antibodies are described as autoantibodies with the “wrong” specificity, possessing both specificity and panreactivity. We report the case of a female patient with suspected hemolytic anemia in whom an autoantibody mimicking anti-Rh(e) specificity was found in both plasma and red blood cell samples. Mimicking antibodies are not usually identified in the clinic; however, it is still necessary to determine the specificity of mimicking antibodies to avoid antigen-positive blood transfusions and achieve maximum transfusion compatibility.

Methylene blue for hemolytic crisis in patients with met-hemoglobinemia secondary to hemoglobin volga: A case series.

There is a rare subset of patients with a genetically abnormal hemoglobin structure initially discovered in the Volga region of Europe known as Volga anemia. Key features of this condition include compromised delivery of oxygen to peripheral tissues and altered red blood cells that have a higher likelihood of being broken down or hemolyzed, which can lead to significant hemolytic anemia. Methylene blue is a dye that acts as a reducing agent of oxygen and is commonly used in toxic states that lead to methemoglobin build-up. This paper explores the pathophysiology of this genetic condition and documents three cases across two patients-a father and son-when methylene blue was used during an anemic crisis.

When and why is red blood cell genotyping applicable in transfusion medicine: a systematic review of the literature.

This review aims to provide a better understanding of when and why red blood cell (RBC) genotyping is applicable in transfusion medicine. Articles published within the last 8 years in peer-reviewed journals were reviewed in a systematic manner. RBC genotyping has many applications in transfusion medicine including predicting a patient's antigen profile when serologic methods cannot be used, such as in a recently transfused patient, in the presence of autoantibody, or when serologic reagents are not available. RBC genotyping is used in prenatal care to determine zygosity and guide the administration of Rh immune globulin in pregnant women to prevent hemolytic disease of the fetus and newborn. In donor testing, RBC genotyping is used for resolving ABO/D discrepancies for better donor retention or for identifying donors negative for high-prevalence antigens to increase blood availability and compatibility for patients requiring rare blood. RBC genotyping is helpful to immunohematology reference laboratory staff performing complex antibody workups and is recommended for determining the antigen profiles of patients and prospective donors for accurate matching for C, E, and K in multiply transfused patients. Such testing is also used to determine patients or donors with variant alleles in the Rh blood group system. Information from this testing aides in complex antibody identification as well as sourcing rare allele-matched RBC units. While RBC genotyping is useful in transfusion medicine, there are limitations to its implementation in transfusion services, including test availability, turn-around time, and cost.

Economic analysis of foregoing Rh immunoglobulin for bleeding in pregnancy

ObjectivesTo perform cost analyses of foregoing RhD blood type testing and administration of Rh immunoglobulin (RhIg) for bleeding in pregnancy at <12 weeks gestation in the United States. Study DesignWe created a decision-analytic model comparing the current standard treatment pathway for patients who have threatened, spontaneous, or induced abortion in the United States, with a new pathway foregoing RhD testing and administration of RhIg for those who are RhD-negative at <12 weeks gestation, assuming that the risk of sensitization is 0%. We derived population and cost estimates from current literature and calculated the number needed to treat, and number needed to screen, to avoid one case of fatal hemolytic disease of the fetus and newborn. We performed sensitivity analyses assuming Rh-sensitization risks of 1.5% and 3% and varying the subsequent pregnancy rates from 44-100%. ResultsThe annual savings to healthcare payers in the United States of foregoing RhD testing and RhIg administration to RhD-negative patients with bleeding events at <12 weeks is $5.5 million/100,000 total pregnancies, assuming that the risk of sensitization is 0%. In the sensitivity analyses with sensitization risk 1.5% and subsequent pregnancy rate 84.3%, foregoing Rh testing and RhIg administration <12 weeks would save $2.8 million/100,000 pregnancies, with a corresponding number needed to treat of 7,322 and number needed to screen of 48,816. At a 3% sensitization rate, the current standard treatment pathway is the most economical. ConclusionsThere is an opportunity to save the United States healthcare payers as much as $5.5 million/100,000 pregnancies by withholding RhIg in specific situations and conserving it for use later in pregnancy. ImplicationsCost analyses support foregoing RhD blood type screening and RhIg administration at <12 weeks gestation if the sensitization rate is <3%. By de-implementing this low value care, payers in the United States can save as much as $5.5 million/100,000 pregnancies and conserve RhIg for use later in pregnancy.

Exploring the Interplay between Asthma and Hemoglobinopathies: A Comprehensive Review.

Asthma, a prevalent chronic respiratory condition characterized by inflammation of the airways and bronchoconstriction, has demonstrated a potential association with hemoglobinopathies such as thalassemia and sickle cell disease (SCD). Numerous studies have highlighted a higher prevalence of asthma among thalassemia patients compared to the general population, with rates ranging around 30%. Similarly, asthma frequently coexists with SCD, affecting approximately 20-48% of patients. Children with SCD often experience heightened lower airway obstruction and airway hyper-reactivity. Notably, the presence of asthma in SCD exacerbates respiratory symptoms and increases the risk of severe complications like acute chest syndrome, stroke, vaso-occlusive episodes, and early mortality. Several studies have noted a decrease in various cytokines such as IFN-γ and IL-10, along with higher levels of both IL-6 and IL-8, suggesting an overactivation of pro-inflammatory mechanisms in patients with hemoglobinopathies, which could trigger inflammatory conditions such as asthma. The exact mechanisms driving this association are better elucidated but may involve factors such as chronic inflammation, oxidative stress, and immune dysregulation associated with thalassemia-related complications like chronic hemolytic anemia and iron overload. This review aims to comprehensively analyze the relationship between asthma and hemoglobinopathies, with a focus on thalassemia and SCD. It emphasizes the importance of interdisciplinary collaboration among pulmonologists, hematologists, and other healthcare professionals to effectively manage this complex interplay. Understanding this link is crucial for improving care and outcomes in affected individuals.

Off-label use of tramadol combined with Lacasera® soft drink: A sub-acute toxicological study using Wistar rats to evaluate the effects of combination on human basic haematological parameters and weight changes

Tramadol is a synthetic opioid that is used to treat moderate to severe pain in both acute and chronic conditions. Tramadol is predominantly used off-label for premature ejaculation and euphoria among male youth in Nigeria, especially when dissolved in Lacasera® soft drink, which gives it a pleasant taste. Research has not yet examined the effects of this combination on hematological parameters, despite the fact that this type of abuse is common among young people and poses a public health risk. A 28-day subacute study was conducted with Wistar rats weighing 160-180g. The rats were separated into 8 groups of 6 each. The control groups: 1 and 2 were treated with Lacasera® and deionized water respectively. Groups 3, 4 and 5 received 35mg/kg per day, 70.7mg/kg per day and 106mg/kg per day of Tramadol dissolved in deionized water respectively. Groups 6, 7 and 8 received similar doses of Tramadol dissolved in Lacasera®. Blood samples were analyzed using auto-analyzer and standard methods. The data was analyzed using a statistical tool software (SPSS version 27). All results were presented as mean ± SD. Values were considered significant at p&lt;0.05. Hematological analysis of groups treated with Lacasera®-Tramadol combination shows dose-dependent significant decreases (p&lt;0.05) in PCVs, RBCs, and Hbs. WBCs and platelets increased in groups that received Lacasera®-Tramadol combination. The study concludes that regular or infrequent users of Lacasera® without Tramadol are unlikely to experience serious hematological complications. However, chronic Tramadol-Lacasera® users will experience increased toxicity over time, leading to hemolytic anemia.

Incidence and Risk Factors of Cholestasis in Newborns with Hemolytic Disease-A Case-Control Study.

Background/Objectives: One of the rare causes of cholestasis may be hemolytic disease of the fetus and newborn (HDFN). Methods: We retrospectively analyzed 88 medical records of HDFN newborns with cholestasis and 186 records of children with HDFN without cholestasis and conducted an observational, case-control, retrospective study. Results: Factors influencing the risk of cholestasis were lower gestational age at birth (36.83 ± 1.9 vs. 37.57 ± 1.8, p = 0.002), Rh or Kidd HDFN (80.7% vs. 53.2%), and the need for intrauterine transfusion (27.3 vs. 11.8%). The subjects had lower hemoglobin concentrations at birth (14.01 ± 3.8 vs. 16.39 ± 2.8 g/dL) and during whole hospital stay, higher cord blood total bilirubin concentration (4.26 ± 1.8 vs. 2.39 ± 1.4 mg/dL), higher maximum bilirubin concentration (15.27 ± 5.8 vs. 10.24 ± 3.4 mg/dL), and more frequent liver ultrasound abnormalities (19.9 vs. 6.3%). They also required more extended hospitalization due to higher rates of postnatal blood transfusion (33 vs. 3.8%), more frequent need for exchange transfusion (8.8% vs. 2.2%), more extended time and higher risk of phototherapy (94.3 vs. 59.1%), and higher usage of immunoglobulins (55.7 vs. 8.1%), parenteral nutrition (45.5 vs. 12.9%), and antibiotics (14.8 vs. 4.8%). Conclusions: The risk factors for cholestasis in children with HDFN are lower gestational age at delivery, Rh and Kidd serological type of HDFN, and the need for intrauterine transfusions.

Plasma exchange is the hope for critically ill children with life-threatening autoimmune hemolytic anemia

BackgroundAutoimmune hemolytic anemia (AIHA) is a rare disease in children, sometimes associated with acute, life-threatening, rapidly progressive course requiring prompt management. The aim of our study is to describe the role and outcome of plasma exchange in the acute management of pediatric patients with AIHA requiring transfusion and refractory to high doses of corticosteroids.MethodsThis was a descriptive retrospective report of all patients admitted to the pediatric intensive care unit (PICU) of Children’s University Hospital who received PE for acute intractable AIHA resistant to management with pulse steroids starting from June 2017 to June 2022. The demographic data, vitals, and laboratory investigations at PICU admission and upon discharge were gathered. The number of PE sessions needed for each patient, volume used for exchange, type of replacement, IV access used, complications, and outcome were reported.ResultsThis series included 19 patients, 10 males, and 9 females, with a median age and weight of 76 months (IQR 18–121), and 20.9 kg. Improvement of the mean hemoglobin was observed from 5.3 ± 1.8 to 9.9 ± 2.6 g/dl at discharge. The average number of PE sessions was 2.4 sessions with no adverse effects encountered. The mean PICU stay was 16.6 days. Mortality occurred in 2 patients (10.5%) due to their primary illness, while 7 patients (36.8%) were in need of further immunotherapy, and 5 patients (28%) showed relapse.ConclusionPE may be used as a safe and successful therapy in children with severe acute life-threatening AIHA not responding to steroids, or if well-matched PRBCs are unavailable for transfusion.

Clinical and biochemical characteristics, and outcome in 33 patients with ceftriaxone-induced liver injury.

To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.

Continuous blood exchange in rats as a novel approach for experimental investigation

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.

Genetic profile of RHCE, Kell, Duffy, Kidd, Diego and MNS hybrid glycophorins blood groups in ethnic northeastern Thais: Alleles, genotypes and risk of alloimmunisation.

Antibodies against blood group antigens play a key role in the pathophysiology of haemolytic transfusion reactions (HTRs) and haemolytic disease of the fetus and newborn (HDFN). This study aimed to determine the frequencies of alleles, genotypes, and risk of alloimmunisation of clinically significant blood group systems in ethnic northeastern Thais. In total, 345 unrelated, healthy, ethnic northeastern Thais were tested using the in-house PCR-sequence specific primers (PCR-SSP) method for simultaneously genotyping of RHCE, Kell, Duffy, Kidd, Diego and MNS glycophorin hybrids and results confirmed by Sanger sequencing. In this cohort, the alleles RHCE*C (81.0%) and RHCE*e (84.8%) were more prevalent than RHCE*c (19.0%) and RHCE*E (15.2%). The most common predicted haplotype combinations of the RHCE alleles were C+c-E-e+(R1R1) (59.4%) followed by the C+c+E+e+ (R1R2) (20.6%) and C+c+E-e+ (R1r) (11.3%). The KEL*01 allele was not found in this study. The frequencies of FY*01 and FY*02 were 88.3% and 11.7%, respectively. The genotype FY*02/02 was found in four samples (1.2%). The frequencies of JK*01 and JK*02 were 52.5% and 47.5%, respectively. Homozygous JK*02/02 was found in 81 samples (23.5%). The frequencies of DI*01 and DI*02 were 0.6% and 99.4%, respectively. In total, 64 samples (18.6%) were found to carry the MNS glycophorin hybrids. Our results indicated a possible high risk of c, E, Fyb, Jka, Jkb and Mia alloimmunisation in these populations. Moreover, methods established for genotyping clinically significant blood groups in this study can now be utilised in routine clinical application.

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.

Donor/recipient Rh-mismatched allogeneic hematopoietic stem cell transplantation: transfusion strategy and allo-immunization to red blood cell antigens.

In the case of donor/recipient rhesus (Rh)-incompatibility after allogeneic hematopoietic stem cell transplantation (alloHSCT), the transfusion policy in France is to transfuse red blood cells (RBC) in the donor's Rh phenotype from the day of transplantation, leading to a risk of allo-immunization, either of donor or recipient origin. In this single-center retrospective study, the incidence of donor/recipient Rh incompatibility was 7.1% over an 8-year period including 1012 alloHSCT. Six of 58 evaluable patients (10.3%) developed alloantibodies to RBC antigens within one year of alloHSCT. None of these allo-immunizations were directed against the donor-mismatched Rh antigens and none could have been prevented by the transfusion of recipient and donor Rh-compatible RBC units. None of these allo-immunizations led to immune-mediated hemolytic anemia. We observed a statistically significant higher incidence of chronic GVHD among patients with anti-RBC allo-immunization. In the context of donor/recipient Rh incompatibility, the transfusion of packed RBC units in the donor's Rh phenotype from the day of alloHSCT is feasible and not associated with a high risk of allo-immunization. The generalization of this strategy could be discussed even when donor and recipient Rh phenotypes could be respected, to allow the preservation of units of infrequent phenotypes for other indications.

Infantile pyknocytosis, a neonatal hemolytic anemia with Heinz bodies: A cohort study.

Infantile pyknocytosis (IP) is a rare, probably misestimated, cause of non-immune neonatal hemolytic anemia evolving in two phases: an initial phase with severe jaundice, followed by a second phase with hemolytic anemia, which may require neonatal intensive care. The diagnosis of IP is based on the transient presence on blood smear of hyperdense, contracted, and/or spiculated red blood cells (pyknocytes), associated with the spontaneous resolution of clinico-biological features and the exclusion of other causes. If the etiology remains undetermined, some contributing factors, such as oxidative stress, have been proposed. We report the description of 16 patients with IP aiming at clarifying the circumstances associated with the development of this acquired disorder. In the acute phase, the mean hemoglobin nadir and pyknocyte count were 7.8g/dL and 11%, respectively, and strikingly, Heinz bodies were evident in 50% of the newborns, but in 100% after prolonged incubation (4hours). A high proportion of Mediterranean or African ancestry was noted in newborns, as well as a significant number of peripartum events, such as respiratory distress. If the etiology of IP is certainly multifactorial, our series reinforces the role of oxidative stress, which may, at least in part, find origin in desaturation episodes in newborns.

Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization.

Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.

#2989 Superposition of atypical hemolytic syndrome and tubulointerstitial nephritis, a case report

Abstract Background and Aims Hemolytic uremic syndrome is a heterogeneous group of diseases that have in common the development of thrombotic microangiopathy with diffuse endothelial damage, resulting in the classic triad composed of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury, on the other hand, tubulointerstitial nephritis is characterized by the presence of inflammatory infiltrates and edema and of the interstitial compartment that causes deterioration of renal function. Method The following is the case of a patient with acute kidney injury of etiology composed of thrombotic microangiopathy and tubulointerstitial nephritis. Results 27-year-old female patient without significant history, began 3 weeks prior to admission with fever, chills, asthenia, nausea and vomiting of food content, approximately 5 episodes per day for 3 days, presenting intermittent episodes of jaundice of the mucous membranes and conjunctivae, with progressive increase of the symptoms to the point of preventing daily activities, she was admitted for study, detecting hemolytic anemia, thrombocytopenia and severe acute kidney injury, so she was referred to our center was decided for evaluation by Nephrology and Hematology. In our institution, urinary sediment with dysmorphic erythrocytes was documented, peripheral blood smear without the presence of schistocytes, positive Coombs 4 crosses, renal ultrasound with data compatible with acute kidney injury, and supportive management with hemodialysis was initiated. Due to suspicion of autoimmune glomerulopathy, an autoantibody panel was indicated with negative antinuclear antibodies, anti-double-stranded DNA, anti-Sm, anti-B2 glycoproteins, and lupus anticoagulant, with normal complement values, stool culture, and negative stool Shiga protein assay, angiotomography of the abdomen where the integrity of renal circulation is verified, so renal biopsy with immunohistochemical study is performed, finding data compatible with thrombotic microangiopathy and acute tubulointerstitial nephritis. The patient is maintained with supportive care, steroids and hemodialysis as required with progressive recovery of renal function until renal replacement therapy is weaned, she is discharged with a steroid regimen and clinical nephrology and hematology follow-up. Conclusion Acute kidney injury is a complex and multifactorial entity, which requires a comprehensive approach in order to identify the best therapeutic option and to offer a better outcome in the renal function of these patients. The case of our patient presented a sudden deterioration of renal injury composed of two entities with different pathophysiology, demonstrating that, although the approach to these two entities converge in certain etiologies, it is imperative that the clinician does not forget the wide variety of factors that contribute to the development of renal injury.

#760 Monogenic lupus with ANCA associated vasculitis-phenotype and ANCA positivity due to DNASE1L3 mutations: case report and review of the literature

Abstract Background and Aims Monogenic systemic lupus erythematosus (SLE) accounts for 7-10% of cases of early-onset SLE. DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells and its deficiency, enhance autoantibody production and type I interferon responses and cause different autosomal recessive phenotypes including SLE and hypocomplementemic urticarial vasculitis syndrome (HUVS) [1]. In some cases patients can have a mixed SLE-AAV phenotype. Kidney involvement in patients with DNASE1L3 mutations is poorly characterised. Method We present the case report of a 7-years-old boy with monogenic SLE due to DNASE1L3 mutations who developed severe glomerulonephritis leading to kidney failure. Results The patient had a history of urticaria and arthralgia and presented with fever, haemolytic anaemia, lymphadenopathy, hepato-splenomegaly, erythematous- macular and necrotic skin lesions, and interstitial lung disease. He also had acute kidney injury (serum creatinine 5.4 mg/dL), nephrotic- range proteinuria (3.9 g/24 h) and microhaematuria. Immunological tests revealed low C3 and C4, positive anti-nuclear antibody (ANA) and myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), with negativity of anti-extractable nuclear antigen antibodies (anti-ENA) and anti-double stranded DNA (anti-dsDNA). Kidney biopsy showed pauci-immune (mesangial C3+ and IgG+) necrotising crescentic glomerulonephritis. The patient proved refractory to standard immunosuppression with cyclophosphamide and steroids. Two years later, due to renal function decline, a new kidney biopsy was performed and showed diffuse necrotising glomerulonephritis with endo- and extra-capillary proliferation; intense mesangial and subendothelial full-house deposits were evident on immunofluorescence. The patient did not respond to other lines of immunosuppression (mycophenolate mofetil, tacrolimus, azathioprine, rituximab), including the JAK inhibitor ruxolitinib. Kidney failure progressed to end stage at the age of 15 years, when the patient began haemodialysis. The kidney presentation, immunological profile and the first kidney biopsy led to diagnosis of AAV. However, the diagnosis was questioned due to the refractory course, the systemic clinical presentation and the second kidney histology (consistent with lupus nephritis). High interferon signature was detected and in the suspicion of a monogenic lupus nephritis Whole Exome Sequencing was performed and revealed homozygous DNASE1L3 variants (c.290_291delCA p.T97Ifs*2); thus, a final diagnosis of DNASE1L3 monogenic SLE was made. DNASE1L3 serum levels were normal but the DNAse enzymatic activity was low. Conclusion Renal involvement is one of the most frequent manifestations of DNASE1L3-related lupus; in the literature 32 cases of DNASE1L3-associated lupus nephritis are described. ANCA are positive in about 55% of these cases and are associated with a mixed lupus-AAV phenotype. All cases are characterized by resistance to common immunosuppressors and poor renal prognosis [2]. DNASE1L3 regulates neutrophil extracellular trap (NET) clearance and when this function is reduced the permanence of NETs induces endothelial damage and autoantibody formation. This pathogenic pathway is shared both by SLE and by AAV. There is no association between specific mutations and antibody positivity or clinical manifestations.

#3060 Assessment of differences in management and outcomes of severe hypophosphatemia secondary to refeeding syndrome

Abstract Background and Aims Refeeding syndrome is a severe, potentially life-threatening condition characterized by fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving parenteral or enteral artificial refeeding. This condition may present with hypokalemia, hypomagnesemia, thiamine deficiency and changes in glucose and fat metabolism, but the hallmark of the syndrome is hypophosphatemia. The rise in insulin during refeeding may lead to a significant uptake and utilization of phosphorus into the cells, leading to a deficit in intracellular and extracellular phosphorus. The best method for phosphate repletion has not yet been determined. In this study we describe the different management strategies and outcomes of severe hypophosphatemia secondary to refeeding syndrome observed at our centre. Method We performed a retrospective observational study of patients admitted at out tertiary hospital from December 2022 and May 2023 who presented severe hypophosphatemia (defined as serum phosphate level &amp;lt;1.2 mg/dl) secondary to refeeding syndrome. We collected demographic data, comorbidities, changes in electrolytes and kidney function and treatments received during in-hospital admission. Our outcomes were development of complications associated with severe hypophosphatemia (convulsions, myopathy, fractures, haemolytic anemia, and major cardiovascular events) and death. Results We identified 16 cases of severe hypophosphatemia secondary to refeeding syndrome during the study period, with a mean phosphate level of 0.81 ± 0.26 mg/dl. Mean age was 54.7 ± 16.4 years, and females were predominant (62.5%), and all were associated with parenteral nutrition. 18.8% of patients had had previous episodes of severe hypophosphatemia, 25% presented diarrhoea as well and 18.8% had also received intravenous iron previous to the episode. At presentation, mean serum creatinine was 0.64 ± 0.3 mg/dl, mean potassium levels were 3.5 ± 0.9 mmol/l, mean sodium 141.7 ± 6.3 mmol/l, mean calcium was 8.62 ± 0.37 mg/dl and mean magnesium was 2.05 ± 0.45 mg/dl. Most patients (75%) were treated by discontinuation of parenteral nutrition and intravenous phosphate, while 18.8% of patients were only treated by temporary discontinuation of parenteral nutrition and only 1 patient (6.3%) was treated with oral phosphate supplementation. Regarding complications, 18.8% of patients presented myopathy, 12.5% presented convulsions, 25% presented major cardiovascular events, and 18.8% of patients died during hospitalization. Conclusion Refeeding syndrome is a potential fatal condition that frequently presents with severe hypophosphatemia, however it frequently passes unrecognized. Prompt detection and management is essential, especially in patients receiving parenteral nutrition, to prevent complications and death. Further research is needed to determine the best management strategy in refeeding syndrome to improve outcomes.

#626 C3 glomerulonephritis and thrombotic microangiopathy—a prospective observational study

Abstract Background and Aims Complement mediated TMA (cTMA) and complement component 3 glomerulonephritis (C3GN) are two distinct complement mediated kidney diseases. cTMA is characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. C3GN results from uncontrolled activation of the alternative complement pathway leading to the deposition of C3 in the glomerulus. We sought to describe characteristic differences between these two conditions in a large cohort of patients from Bengaluru, India. Method All cases of cTMA and kidney biopsy proven C3GN from 2019-2022 at a tertiary care centre in India were included. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. All patients received protocolized medical therapy; patients with C3GN were treated with steroids and cyclophosphamide, while those with complement mediated TMA received plasmapheresis in addition to cyclophosphamide and steroids. Protocolised medical management (renin-angiotensin-aldosterone inhibition and diuretics) was provided in both the cases. Demographic, clinical and lab parameters were reported and compared. Results A total of 25 cTMA cases and 19 C3GN cases were included in the study. Both C3GN (52.7%) and cTMA (48%) were more common in males. Patients with C3GN typically presented in the third decade of life while cTMA cases presented in the fourth decade. Secondary hypertension was common in the cTMA group (92% vs 78.9%, compared to C3GN). 60% of patients with cTMA had either recent or current infection compared to 21.1% of C3GN patients (P = 0.04). The majority of cTMA cases had IFTA of &amp;lt;25% (84%) compared to C3GN (57.9%) although this was not statistically significant. Both C3GN and cTMA most commonly presented as rapidly progressive kidney failure and acute kidney injury. A total of 76% of patients in the cTMA group required kidney replacement therapy as compared to 47.4% in the C3GN group (P = 0.009). 44% of cTMA cases had anti factor H antibody positivity compared to 15.8% of C3GN patients (P = 0.02). Finally, 44% of cases in cTMA group had complete recovery compared to 47.4% in C3GN group at the end of 2.8 years of followup. Conclusion Although both conditions result from dysregulation of the alternative pathway, there are several important clinical characteristic differences between patients with cTMA and C3GN including presence or absence of secondary hypertension, concurrent infection, anti-factor H positivity and requirement of kidney replacement therapy. This information may be helpful to inform both diagnosis and prognosis for patients presenting with a complement mediated kidney disease.