Hemolytic Anemia Research Articles

RhD alloimmunization – diagnostics, therapy and prophylaxis

Introduction: The success in preventing and treating Rh D alloimmunization is a major accomplishment in modern obstetrics. The widespread use of Rh D immune globulin has led to a decline in red cell alloimmunization. Despite evidence of its effectiveness, many cases of Rh D alloimmunization persist due to non-compliance with established protocols. Implementing routine anti-D prophylaxis (RAADP) during the third trimester is well-established but requires more careful. Aim of study: The aim of the study is to summarize the available knowledge about alloimmunization in pregnancy and methods of prophylaxis. The definition, patomechanism, methods of treatment and prophylaxis were summarized and described. Materials and methods: The literature available in PubMed database was reviewed using following keywords: “alloimmunization in pregnancy”, “serological conflict”, “fetal anemia”, “HDFN”, “prophylaxis of alloimmunization”. Conclusion: Advancements in diagnosing, treating, and preventing hemolytic disease of the fetus and newborn are notable. Quick, non-invasive diagnostics have facilitated more efficient treatment implementation. Prevention methods include specific and nonspecific prophylaxis, which can start during or after pregnancy. Numerous guidelines and studies exist regarding immunoglobulin use in pregnancy. However, medical staff education on managing hemolytic disease during pregnancy is crucial.

Biphasic Behavior of Anti-M Antibody and Hemolytic Disease of the Fetus and Newborn (HDFN)

Biphasic Behavior of Anti-M Antibody and Hemolytic Disease of the Fetus and Newborn (HDFN)

Duration of hemolysis among infants with hemolytic disease of the fetus and newborn.

Duration of hemolysis among infants with hemolytic disease of the fetus and newborn.

Mitapivat for Acquired Pyruvate Kinase Deficiency.

Pyruvate kinase (PK) activation is emerging as a promising treatment modality for numerous congenital hemolytic anemias of diverse pathophysiology, and one agent, mitapivat, is already licensed to treat patients with congenital PK deficiency. However, PK deficiency may also be acquired in the setting of clonal myeloid disorders and other pathologies, where it may result in severe hemolytic anemia and remains without known therapies. This case report describes the novel application of mitapivat therapy in a patient with acquired PK deficiency causing red cell transfusion dependence, liberating the patient from transfusions and resulting in marked improvement in symptoms and quality of life.

ORGAN-SPARING AND ORGAN- REMOVING SURGICAL PROCEDURES FOR PATHOLOGICAL CONDITIONS OF THE SPLEEN IN CHILDREN. QUESTIONS AND ANSWERS.

Introduction. Nowadays splenic surgery is a rather urgent problem in pediatric surgery. There are diseases where only splenectomy allows a child to live a full life. These are: sickle cell anemia (SCA), idiopathic thrombocytopenic purpura, hereditary spherocytosis (Minkowski- Chauff ard disease), thalassemia, and autoimmune hemolytic anemia. The spleen is involved in 25-30 % of cases of blunt abdominal trauma in children. The loss of more than 45 % of the circulating blood volume leads to an unstable hemodynamic state in the child. The question of surgical treatment and preservation of the spleen in hemoperitoneum due to its injury is of vital importance. Aim: To study the possibilities of surgical treatment of diseases and injuries of the spleen in children. Materials and methods. An analysis of surgical interventions for diseases and injuries of the spleen in children aged 2 to 17 years from 2019 to 2024 was performed. The study was conducted in the surgical departments of the «Clinical Center of Pediatric Medicine» of the «Okhmatdyt Hospital» of the «Western Ukrainian Specialized Center» (Lviv) and the «Chernivtsi City Children’s Clinical Hospital» (Chernivtsi). 27 children (17 girls, 10 boys) had spleen diseases and 43 children (23 girls, 20 boys) had spleen injuries. Splenectomy was performed for the following splenic diseases: sickle cell anemia (9 children), idiopathic thrombocytopenic purpura (4 children), hereditary spherocytosis (Minkowski- Chauff ard disease) (6 children), thalassemia (1 child), and autoimmune hemolytic anemia (1 child). Six children had splenic cysts: 3 children had posttraumatic cysts and 3 children had parasitic cysts. Twenty children underwent surgery for splenic injuries. The following surgical procedures were performed: laparoscopic abdominal cavity repair with spleen preservation followed by conservative therapy (13 children); laparoscopic splenectomy (2 children); laparotomy, splenic suture (2 children); and open splenectomy (3 children).Results. Conservative management of splenic injuries of varying degrees according to the American Association for the Surgery of Trauma (AAST) was performed in 23 (53.49 %) children. Resorption of hemoperitoneum in cases of conservative treatment of splenic injuries occurred 11-14 days after the start of treatment. Safe, full physical activity was resumed after 6 weeks of conservative treatment of splenic injury. Surgical procedures were performed in 20 (46.51 %) children using various techniques. 17 patients underwent laparoscopy. 2 children underwent laparoscopic splenectomy for grade IV AAST injury and hemodynamic instability. In 15 cases, treatment was started with conservative therapy, but during monitoring an increase in hemoperitoneum was observed, indicating the need for laparoscopy. Laparoscopy was performed in 13 children. A minimum of 100 ml and a maximum of 400 ml of blood was collected laparoscopically in the children. The abdominal cavity was examined and hemostasis was confi rmed. In cases where the spleen was «wrapped» with the omentum, the omentum was not separated from the spleen. The operation was completed by placing a drainage tube in the perisplenic space. In 2 children, grade IV AAST injuries were converted to an open procedure in which the spleen was sutured to stop bleeding and a drain was left near the splenic bed. Grade V AAST splenic injury in 3 children was an indication for left subcostal laparotomy and splenectomy. For splenic disease, laparoscopic splenectomy was performed in 12 (44.44 %) children, with high effi cacy in Minkowski- Chauff ard disease combined with gallstones (3 children) where simultaneous cholecystectomy was possible. Laparoscopic removal of splenic cysts was also justifi ed in 3 (11.11 %) children. However, removal of parasitic cysts required open splenectomy in 3 patients. Open splenectomy was performed in 9 children with splenic disease. In 5 children the inappropriateness of laparoscopy was due to severe perisplenitis, large spleen weight and young age of the children.Conclusions1. The morpho- functional structure of the spleen promotes spontaneous hemostasis, which is the basis for conservative treatment of spleen injuries in 53.49 % of children.2. The AAST classifi cation of splenic injuries from grade I to V, hemodynamic indicators and ultrasound monitoring of blood in the abdominal cavity can be used as a basis for choosing the method of treatment of closed blunt splenic injuries in children.3. Ineff ectiveness of conservative treatment, hemodynamic instability and increase of blood in the abdominal cavity in a child with splenic injury within 4 hours is an indication for laparoscopy.4. Splenic suturing and laparoscopic monitoring should be the preferred methods for treating closed splenic injuries in children to preserve the organ.5. The choice of surgical intervention for splenic diseases in children should be individualized and depend on the disease, the child’s age, the size of the spleen, and the presence of complications of the disease.

Promising role of Voxelotor in managing sickle cell disease in children: a narrative review.

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and intermittent vaso-occlusive crises. To date, four disease-modifying drugs have been approved for the treatment of SCD: hydroxyurea (an S-phase inhibitor), L-glutamine (an amino acid), crizanlizumab (a P-selectin inhibitor), and voxelotor (a hemoglobin S polymerization inhibitor). Preclinical studies suggested that voxelotor effectively treats SCD and sickle cell anemia (SCA). In a phase III trial, voxelotor-treated patients showed significantly elevated hemoglobin levels (>1 g/dL from baseline) compared to placebo-treated patients. The group that received voxelotor also showed a greater decrease in hemolytic markers but a comparable incidence of side effects. Six ongoing clinical trials also sought to ascertain the effectiveness and safety of high-dose voxelotor when administered to children younger than 12 years. Studies assessing their long-term efficacy and safety are needed to fully understand the role of voxelotor in treating SCD/SCA. In this review, we discuss the mechanisms, trials to date, and future treatment directions of voxelotor.

Monitoring and Management of Hemolytic Disease of the Fetus and Newborn Based on an International Expert Delphi Consensus.

The study aimed to develop structured, expert-based clinical guidance on the prenatal and postnatal management of hemolytic disease of the fetus and newborn. A Delphi procedure was conducted among an international panel of experts in fetal medicine, neonatology, and hematology. Experts were selected based on their expertise, relevant publications, and affiliations. The domains were (i) prenatal workup, (ii) prenatal monitoring and management, (iii) intrauterine transfusion, (iv) delivery, and (v) postnatal management. The pre-defined cut-off for consensus was ≥70% agreement. One hundred-seven experts representing 25 countries across six continents completed the first round, and 100 (93.5%) completed the subsequent rounds. 75.3% agreed on using cfDNA to determine fetal antigen status, particularly for RhD, Kell, and Rhc antigens. The critical titer, requiring fetal monitoring via ultrasound, is considered when the threshold of ≥16 is for non-Kell antigens. 70.0% agreed on the use of maternal IVIg in pregnancies with prior intrauterine transfusion (IUT) <24 weeks or fetal/neonatal death due to HDFN. The minimum GA for IUT is 16 to 18 weeks, and the maximum is 350/7 to 356/7 weeks. Postnatal management consensus was reached for the following: anemia labs should be investigated in the affected neonates before hospital discharge (92.0% agreement), and if they received IUT, the labs should be repeated within one week of discharge (84.0% agreement). 96.0% agreed that exchange transfusions should be centralized in hospitals with sufficient exposure and experience, and 92.0% agreed that the hemoglobin cut-off level to consider transfusion following hospital discharge is 7g/dL, and the newborns need to be monitored until 2-3 months of age (96.0% agreement).

Abstract 4128352: Association Between G6PD Deficiency and Congenital Heart Disease Incidence and Hospital Outcomes

Background: G6PD deficiency classically presents with hemolytic anemia, but associations have been described with atherogenesis and coronary artery disease. There are limited data that also suggest a link between G6PD deficiency and the development of congenital heart disease (CHD). Hypothesis: We hypothesize a higher incidence of CHD among individuals with G6PD deficiency as well as worse hospital outcomes for those with CHD and G6PD deficiency. Methods: We reviewed the Vizient® Clinical Data Base (a national, administrative database) from 10/2019-3/2024 for admissions of individuals aged 0-25 years with ICD-10 codes for moderate to severe CHD with and without and G6PD deficiency (D55.0, D75.A) to calculate and compare CHD incidence. Additional data included: demographics, hospital outcomes and costs. Hospital outcomes were compared using t-tests for normally distributed data, Mann-Whitney U test for non-normally distributed data and χ 2 for categorical data. Results: There were 213,708 admissions of individuals with CHD and &lt;1% had G6PD deficiency; findings in Table 1. Of the 6,363 admissions with G6PD, 289 (4.5%) had CHD and of 11,179,670 without G6PD, 213,419 (1.9%) had CHD ( p &lt;0.001). Patients with CHD and G6PD deficiency had male predominance and more Blacks (consistent with known G6PD deficiency epidemiology), longer length of stay and higher hospital costs than those without G6PD deficiency (Table 1). Conclusions: This review of a national database shows a higher incidence of CHD in admissions with G6PD deficiency as well as worse hospital outcomes (longer length of stay, higher costs) for those with CHD and comorbid G6PD deficiency. There were demographic differences, but these reflect the typical inheritance of G6PD deficiency. While there may be potential interplay between race/ethnicity and these outcomes as well, further investigation is needed.

Identifying Hemolytic Disease of the Fetus and Newborn within a Large Integrated Health Care System.

This study aims to identify hemolytic disease of the fetus and newborn (HDFN) pregnancies using electronic health records (EHRs) from a large integrated health care system. A retrospective cohort study was performed among pregnant patients receiving obstetrical care at Kaiser Permanente Southern California health care system between January 1, 2008, and June 30, 2022. Using structured (diagnostic/procedural codes, medication, and laboratory records) and unstructured (clinical notes analyzed via natural language processing) data abstracted from EHRs, we extracted HDFN-specific "indicators" (maternal positive antibody test and abnormal antibody titer, maternal/infant HDFN diagnosis and blood transfusion, hydrops fetalis, infant intravenous immunoglobulin [IVIG] treatment, jaundice/phototherapy, and first administrated Rho[D] Immune Globulin) to identify potential HDFN pregnancies. Chart reviews and adjudication were then performed on select combinations of indicators for case ascertainment. HDFN due to ABO alloimmunization alone was excluded. The HDFN frequency and proportion of each combination were fully analyzed. Among the 464,711 eligible pregnancies, a total of 136 pregnancies were confirmed as HDFN pregnancies. The percentage of the HDFN-specific indicators ranged from 0.02% (infant IVIG treatment) to 34.53% (infant jaundice/phototherapy) among the eligible pregnancies, and 32.35% (infant IVIG treatment) to 100% (maternal positive antibody test) among the 136 confirmed HDFN pregnancies. Four combination groups of four indicators, four combination groups of five indicators, and the unique combination of six indicators showed 100% of HDFN pregnancies, while 80.88% of confirmed HDFN pregnancies had the indicator combination of maternal positive antibody test, maternal/infant HDFN diagnosis, and infant jaundice/phototherapy. We successfully identified HDFN pregnancies by leveraging a combination of medical indicators extracted from structured and unstructured data that may be used in future pharmacoepidemiologic studies. Traditional indicators (positive antibody test results, high titers, and clinical diagnosis codes) alone did not accurately identify HDFN pregnancies, highlighting an unmet need for improved practices in HDFN coding. · A case ascertainment method was developed to identify HDFN from structured and unstructured data.. · The method used in this study may be used in future pharmacoepidemiologic studies.. · The study highlighted an unmet need for improved practices in HDFN coding..

Thrombosis in Paroxysmal Nocturnal Hemoglobinuria (PNH): From Pathogenesis to Treatment

Paroxysmal Nocturnal Hemoglobinuria (PNH) constitutes a rare bone marrow failure syndrome characterized by hemolytic anemia, thrombotic events (TEs), and bone marrow aplasia of variable degrees. Thrombosis is one of the major clinical manifestations of the disease, affecting up to 40% of individuals with PNH. Venous thrombosis is more prevalent, affecting mainly unusual sites, such as intrabdominal and hepatic veins. TEs might be the first clinical manifestation of PNH. Complement activation, endothelial dysfunction, hemolysis, impaired bioavailability of nitric oxide, and activation of platelets and neutrophils are implicated in the pathogenesis of TEs in PNH patients. Moreover, a vicious cycle involving the coagulation cascade, complement system, and inflammation cytokines, such as interleukin-6, is established. Complement inhibitors, such as eculizumab and ravulizumab (C5 inhibitors), have revolutionized the care of patients with PNH. C5 inhibitors should be initiated in patients with PNH and thrombosis, while they constitute a great prophylactic measure for TEs in those individuals. Anticoagulants, such as warfarin and low-molecular-weight heparin, and, in selected cases, direct oral anticoagulants (DOACs) should be used in combination with C5 inhibitors in patients who develop TEs. Novel complement inhibitors are considered an alternative treatment option, especially for those who develop extravascular or breakthrough hemolysis when terminal inhibitors are administered.

PECULIARITIES OF THE EXOCRINE SECRETORY FUNCTION OF THE PANCREAS IN NEONATES WITH PERINATAL PATHOLOGY

Introduction. Post-asphyxia syndrome in newborn infants due to experienced intrauterine hypoxia and asphyxia at birth remains a relevant issue in neonatology. The intestines and glands of internal and external secretion are target organs of pathologic hypoxic influence. Their ischemic damage can be a cause of digestive disorders against the background of multiple organ damage of a newborn child. Objective of this study is to determine peculiarities of the exocrine secretory functions of the pancreas in full-term neonates with perinatal pathology. Material and methods. One hundred fifty five Full-term neonates with the signs of perinatal pathology were examined. I group included 82 neonates with severe perinatal pathology, II group – 73 moderate pathology, 50 healthy infants constitute III control group. Inclusion criteria were gestational age more than 37 full weeks, clinical-paraclinical signs of maladjustment syndrome at birth and/or during the early neonatal period, parents’ written consent to participate in the study. Exclusion criteria were gestational age less than 37 full weeks; congenital defects; low body weight (size) at birth; signs of infectious processes. Clinical examination of patients and biochemical blood tests were carried out on the base of the clinical laboratory of the Municipal Non-Profit Institution «Municipal Clinical Maternity Home №2» of Chernivtsi Municipal Council, and German-Ukrainian laboratory «Bukintermed» (Chernivtsi). The study was conducted in accordance with the 'Rules of Ethical Principles of Conducting Scientific Medical Research with Human Participation,' approved by the Declaration of Helsinki (1964-2013), ICH GCP (1996), EU Directive No. 609 (24.11.1986), the Order of the Ministry of Health of Ukraine No. 690 (23.09.2009), and the approval of the Biomedical Ethics Board of Bukovinian State Medical University. For statistical analysis, licensed software programs were used, including Statistica (StatSoft Inc., Version 7), Microsoft Excel (AtteStat, Version 12.5), and MedCalc Software Ltd (Version 22.021). Results and discussion. The examination groups were representative according to their gestational age and anthropometric parameters at birth, and gender characteristics. A comprehensive clinical-paraclinical examination of infants showed that severe disorders of infants in I group were caused by the signs of severe (13.4 %) and moderate (13.4 %) asphyxia at birth, meconium aspiration syndrome (20.7 %), severe respiratory disorders (53.6 %), hypoxic-ischemic damage of the central nervous system (39.0 %), convulsive syndrome (13.4 %), birth trauma (7.3 %) etc. Moderate maladjustment in infants from II group were associated with the signs of perinatal damage of the central nervous system (65.8 %), hemolytic diseases of the newborns (27.4 %), neonatal jaundice (28.8 %), respiratory disorders (35.6 %) etc. The condition of neonates from ІІІ group was satisfactory during the period of early postnatal adaptation. The results of additional examination methods found certain peculiarities of the exocrine secretory function of the pancreas in full-term neonates with perinatal pathology. Thus, blood amylase activity in the first day of life in the infants from І group was 0.39 ± 0.03 Un/L, ІІ group – 0.29±0.02 Un/L, ІІІ group – 0.14±0,01 Un/L (рІ-ІІ = 0.016, рІ-ІІІ &lt; 0.0001, рІІ-ІІІ &lt; 0.0001). According to the examination group, activity of the enzyme in the blood of infants at the end of their first week of life was 17.8 ± 0.81, 15.28 ± 0.22 and 14.81±0.06 Un/L respectively (рІ-ІІ = 0.006, рІ-ІІІ = 0.009, рІІ-ІІІ = 0.0435). The study found similar tendencies in changes of lipase activity in the blood of full-term infants. During the first day of life it was 0.35±0.01 Un/L in I group, ІІ group – 0.31±0.01 Un/L, ІІІ group – 0.32 ± 0.01 Un/L (рІ-ІІ = 0.003, рІ-ІІІ = 0.01, рІІ-ІІІ &gt; 0.05). Activity of the enzyme in the blood of infants at the end of their first week of life was 19.7±0.22, 19.1±0.13 and 18.9±0.37 Un/L respectively (рІ-ІІ = 0.021, рІ-ІІІ &gt; 0.05, рІІ-ІІІ &gt; 0.05). Conclusion. The results obtained were indicative of a reliable increase of amylase and lipase activity in the blood of full-term neonates in all the examination groups in the dynamics of observation. It is associated with physiological stimulation of the exocrine secretory function of the pancreas in the early neonatal period. Attention should be paid to a direct correlation between an increased activity of the enzymes and severity of perinatal pathology both in the first day of life and at the end of the first week. It can be indicative of an excessive activation of pancreatic function due to pathologic hypoxic damage.

Identification and functional analysis of novel SPTB and ANK1 mutations in hereditary spherocytosis patients

Hereditary spherocytosis (HS) is the most prevalent form of congenital hemolytic anemia, being caused by genetic mutations in genes encoding red blood cell cytoskeletal proteins. Mutations in the ANK1 and SPTB genes are the most common causes of HS.; however, pathogenicity analyses of these mutations remain limited. This study identified three novel heterozygous mutations in 3 HS patients: c.1994 C > A in ANK1, c.5692 C > T, and c.3823delG in SPTB by whole-exome sequencing (WES) and validated by Sanger sequencing. To investigate the functional consequences of these mutations, we studied their pathogenicity using in vitro culture erythroblast derived from CD34 + stem cells. All three mutations lead to the generation of a premature stop codon. Real-time PCR assay revealed that the two SPTB mutations resulted in reduced SPTB mRNA expression, suggesting a potential role for the nonsense-mediated mRNA degradation pathway. For the ANK1 mutation, gene expression was not reduced but was predicted to produce a truncated version of the ANK1 protein. Flow cytometry analysis of red blood cell-derived microparticles (MPs) revealed that HS patients had higher MP levels compared to normal subjects. This study contributes to the current understanding of the molecular mechanisms underlying mutations in the ANK1 and SPTB genes in HS.

A Thrilling Case of Anemia

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that presents with triad of peripheral blood cytopenias, hemolytic anemia and thrombosis. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations. GPI anchor protein deficiency is due to acquired somatic mutations in phosphatidylinositol glycan class A (PIGA) gene.Terminal complement inhibition with eculizumab and allogeneic bone marrow transplantation (BMT) are the only widely effective therapies for patients with classical PNH. Compared to eculizumab and ravulizumab that block the fifth component of complement (C5), pegcetacoplan blocks the third component of complement (C3).

A case report of severe drug-induced immune hemolytic anemia caused by piperacillin

Piperacillin is a beta-lactamase inhibitor frequently used in the treatment of urinary tract infections. It is a broad-spectrum antibiotic with strong antibacterial action against Pseudomonas aeruginosa and Enterobacter, especially extended-spectrum beta-lactamase-producing Enterobacteria and Enterococcus. Side effects of piperacillin include allergic reactions, rashes such as urticaria, leukopenia, interstitial nephritis, asthma attacks, serological reactions, candida infection, and bleeding with more severe reactions resulting in anaphylactic shock. Anemia and hemolytic anemia are rare adverse reactions to piperacillin, with an incidence of 0.01–0.10%. We report herein the case of a severe postoperative immune hemolytic reaction to piperacillin. Fortunately, we quickly recognized and identified the drug reaction caused by piperacillin, immediately stopped the use of piperacillin, and performed a blood transfusion. The patient recovered and was subsequently discharged from the hospital.

Coexistent sickle cell anemia and autoimmune hemolytic anemia in two adolescents

Coexistent sickle cell anemia and autoimmune hemolytic anemia in two adolescents

Danicopan (Voydeya)

Canada’s Drug Agency (CDA-AMC) recommends that Voydeya be reimbursed by public drug plans as an add-on to ravulizumab or eculizumab for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have residual hemolytic anemia due to extravascular hemolysis (EVH) if certain conditions are met. Voydeya should only be covered to treat adult patients with a diagnosis of PNH, who have met the public drug plan reimbursement criteria for initiating complement 5 inhibitor (C5i) treatments (ravulizumab or eculizumab) before receiving C5i treatment, and who have been on a stable dose of C5i treatment for 6 months or more, in addition, patients should also have persistent anemia caused by EVH, and an absolute reticulocyte count of 120 × 109/L or greater. Voydeya should only be reimbursed if prescribed by a hematologist with experience managing PNH. The cost of Voydeya should be negotiated so that Voydeya plus a C5i as a regimen does not exceed the drug program cost of treatment with pegcetacoplan for the treatment of adult patients with PNH who have residual hemolytic anemia due to EVH.

Extent of iron induced organ damage in patients with hematological disorders.

Objective: To determine the extent of iron induced organ damage in patients of Haematological disorders who are transfusion dependent, presenting in the emergency department of SZH, Lahore. Study Design: Cross Sectional study. Setting: Department of Emergency, Shaikh Zayed Hospital, Lahore. Period: December 25, 2020 to June 24, 2021. Methods: A total of 100 patients aged 10-60 years, of both genders, diagnosed with haematological disorders, and receiving multiple blood transfusions were included in this study. Demographic details were noted including name, age, sex, diagnosis, duration of receiving transfusions and number of transfusions received per month. Patients were evaluated clinically for organ damage including pulmonary, hepatic, renal, and cardiac organs using Denver MOF score. Results: Mean age of patients was 35.33±14.27 years. Mean duration of receiving transfusion was 6.69±2.71 months. There were 67 (67%) males and 33 (33%) female patients. Primary diagnosis was Autoimmune Haemolytic Anemia (AIHA) in 18 (18.00%) patients, Aplastic anemia in 34 (34%) patients, Thalassemia in 37 (37%) patients and Myelodysplastic syndrome (MDS) in 11 (11%) patients. Multiple organ damage was found in 23 (23%) patients. Pulmonary damage was diagnosed in 21 (21%) patients, hepatic damage in 21 (21 %) patients, renal damage in 20 (20%) patients and cardiac damage in 15 (15%) patients. Conclusion: There is a high frequency of multi-organ damage in patients of Haematological disorders requiring chronic blood transfusions. In this study, multi-organ damage was diagnosed in 23% patients requiring chronic blood transfusion.

Heterozygous Beta-Thalassaemia in Pregnancy: Two Rare Causes of Severe Fetal Anemia Requiring Intrauterine Blood Transfusions.

In this article, we present two cases of severe fetal hemolytic anemia based on a beta-thalassaemia trait inherited from a single parent. These cases, presented at 20 and 28weeks' gestation, necessitated intra-uterine blood transfusions. This occurrence is remarkable because it challenges the common assumption that beta-thalassaemia typically has no prenatal implications regarding fetal anemia. Both fetuses inherited a rare heterozygous mutation from their mother, resulting in gamma-thalassaemia-related anemia. In the first case, the anemia was related to a deletion in the beta locus control region (βLCR) and in the second case, a deletion on chromosome 11p15.4 was the cause. These mutations not only affect the beta chain production, but also the gamma chain production, leading to a reduction in the synthesis of HbF, ineffective erythropoiesis and consequently, perinatal hemolytic anemia. Clinicians should be vigilant regarding these rare mutations in families with a history of beta-thalassaemia as the fetal clinical consequences can be severe and intra-uterine blood transfusions may prove life-saving for these fetuses.

Autoimmune haemolytic anaemias.

Adult autoimmune haemolytic anaemias (AIHAs) include different subtypes of a rare autoimmune disease in which autoantibodies targeting autoantigens expressed on the membrane of autologous red blood cells (RBCs) are produced, leading to their accelerated destruction. In the presence of haemolytic anaemia, the direct antiglobulin test is the cornerstone of AIHA diagnosis. AIHAs are classified according to the isotype and the thermal optimum of the autoantibody into warm (wAIHAs), cold and mixed AIHAs. wAIHAs, the most frequent type of AIHAs, are associated with underlying conditions in ~50% of cases. In wAIHA, IgG autoantibody reacts with autologous RBCs at 37 °C, leading to antibody-dependent cell-mediated cytotoxicity and increased phagocytosis of RBCs in the spleen. Cold AIHAs include cold agglutinin disease (CAD) and cold agglutinin syndrome (CAS) when there is an underlying condition. CAD and cold agglutinin syndrome are IgM cold antibody-driven AIHAs characterized by classical complement pathway-mediated haemolysis. The management of wAIHAs has long been based around corticosteroids and splenectomy and on symptomatic measures and non-specific cytotoxic agents for CAD. Rituximab and the development of complement inhibitors, such as the anti-C1s antibody sutimlimab, have changed the therapeutic landscape of AIHAs, and new promising targeted therapies are under investigation.

High malaria parasitemia in an Italian man and severe delayed hemolytic anemia.

Parenteral artesunate has become the choice treatment of cases of high parasitemia malaria. We report the case of an Italian man with a high malaria parasitemia who promptly improved with intravenous artenusate, but who developed a delayed severe hemolytic anemia associated with intravenous artesunate treatment, requiring blood trasfusions.