Sickle Cell Beta-thalassemia Research Articles

How do we manage hyperhemolysis syndrome.

Hyperhemolysis syndrome (HHS) is a catastrophic anemia characterized by destruction of both donor and patient red blood cells (RBC). HHS occurs after transfusion and can cause significant morbidity and mortality. Given the difficulty in diagnosing and managing this process, we provide a detailed overview of our treatment protocol. Members of the Transfusion Medicine and Hematology faculty at our institution collaborated in an iterative process to produce a consensus approach to patients with HHS. We present diagnostic criteria for HHS: recent transfusion within past 7 days (up to 21 days), rapid hemoglobin decline to below the pretransfusion level (usually hemoglobin drop >25% from pretransfusion), a significant decrease in HbA% (in patients with sickle cell disease or beta thalassemia), low or decreasing reticulocyte count in a patient with worsening anemia, and laboratory evidence of hemolysis. We also describe an in-depth approach to management focusing on optimizing hematopoiesis while dampening the immune response. We provide a comprehensive approach to the diagnosis and management of HHS based on contemporary literature and clinical experience designed to optimize outcomes for patients.

A retrospective survey on follow-up of splenectomy patients due to β-thalassemia and Sickle cell Anemia in Karbala, Iraq during 2010-2023

Background: Hemoglobinopathy is considered a common monogenetic genetic disorder worldwide. Splenectomy is considered a therapeutic strategy in patients with hemoglobinopathy. The aim of current study was to provide a survey on the splenectomy and 5 years follow-up in different clinical forms of β-thalassemia (intermedia, Major) and Sickle cell Anemia (SCA) patients who referred to Hereditary Blood Disease Center in the Karbala Teaching Hospital for Children in Karbala, Iraq. Materials and Methods: In this retrospective study we tried to evaluate 126 hemoglobinopathy and thalassemia patients from Karbala City, Iraq. All cases of splenectomy due to hemoglobinopathy and thalassemia during 2010-2023 who referred to the Hereditary Blood Disease Center in the Karbala Teaching Hospital for Children in Karbala, Iraq were included. Patient data was collected at three-time points. The first was after the splenectomy, the second during 1-5 years, and the third step after 5 years. Clinical and laboratory data were retrieved from the patient’s file. Results: The mean age of splenectomy of included patients was 14.1±7.5 years. From 126 cases, 103 (81.74%) were β-Thalassemia, 13 (10.32%) were SCA, and 10 (7.94%) were Sickle cell beta-thalassemia. The mean age in SCA was significantly less than two other groups (mean age in β-Thalassemia, SCA and Sickle cell beta thalassemia were 18.2±8.7, 24.2±12.7 and 25.2±9.5, respectively) (p=0.008). Platelet and WBC count represents a significant increase during 1-5 years after splenectomy in comparison with 1 year after splenectomy (for Platelet and WBC p=0.03 and 0.001, respectively). Conclusion: splenectomy is considered the last therapeutic option in hemoglobinopathy patients. All Hemoglobinopathy patients represented significant improvement after splenectomy. Because there was no suitable treatment in the past, splenectomy was considered a therapeutic solution. It should be said that periodic follow-up of splenectomy patients in hemoglobinopathy plays an important role in improving the management of these diseases.

Anti-sickling effect of Vigna subterranean (L.) Verdc on sickle cell beta thalassemia

Sickle cell disease affects millions of people worldwide and has been recognized as a global health concern by WHO. Presently, there is no cure for sickle cell disease. Treatment options which include bone marrow, stem cell transplantation, blood transfusions, and hydroxyurea are not only expensive but have their side effects. Medicinal plants are often employed in the treatment of diseases because of the therapeutic effects of the secondary metabolites in them. Vigna subterranean an important leguminous crop in Africa, is used in some parts of the world for the treatment and management of sickle cell disease. However, there are no established link between the use of Vigna subterranean and their pharmacological effects. The present study investigated the therapeutic effect of Vigna subterranean on a variant of sickle cell disease known as sickle cell beta thalassemia. Parameters such as reversibility test, polymerization test, osmotic fragility test, deoxygenation test, beta synthesis and oxy-haemoglobin concentration were used to study the anti-sickling potentials of sickle cell beta thalassemia. The result showed that the plant extract reversed the sickled cells, reduced the rate of polymerization, maintained the stability of the cell membrane, increased beta globin synthesis and increased the oxy-haemoglobin concentration. This suggests that Vigna subterranean possesses anti-sicking properties and could be used as an effective therapeutic for the treatment and management of sickle cell beta thalassemia.

Evaluation of anti-sickling effects of two varieties of Cajanus cajan (L.) Huth on sickle cell beta thalassemia

Ethno-pharmacological relevance: Globally, the prevalence of sickle cell disease is on the rise, with developing countries experiencing particularly alarming mortality rate compared to developed nations. The World Health Organization (WHO) and United Nations (UN) have acknowledged sickle cell disease as a significant global public health concern. Unfortunately, a cure for this condition is yet to be discovered, and existing allopathic treatments, while offering relief, come with serious side effects. In recent times, there has been a growing interest in exploring the potential of medicinal plants for treating sickle cell disease due to their content of secondary metabolites that may impact the disease's mechanisms. Cajanus cajan, a crucial grain legume in rain-fed agriculture in semi-arid tropics, has been traditionally used in folk medicine to manage various illnesses and is suggested to possess anti-sickling properties.Aim of the study: The present study investigated two varieties of C. cajan for their effectiveness in treating sickle cell beta thalassemia, a variant of sickle cell disease. Materials and methodsThe study was divided into four groups consisting of the untreated group (group 1), group treated with standard drug (group 2), group treated with white C. cajan (group 3) and group treated with brown C. cajan (group 4). The effects of the two variety of C. cajan were measured by polymerization test, reversibility test, osmotic fragility test, deoxygenation and beta globin synthesis test. ResultThe results revealed that both varieties of C. cajan demonstrated a reduction in polymerization rates, reversed sickled red blood cells, increased the oxygen affinity of Hb-S/β, elevated the Fe2+/Fe3+ ratio, and maintained the membrane stability of red blood cells. Notably, the white variety exhibited superior anti-sickling properties compared to the brown variety. ConclusionThis suggests that this significant leguminous crop could be utilized for the treatment and management of sickling disorders, particularly in low-income countries where conventional treatments may be financially inaccessible to patients.

Splenic abscess, a rare complication in a case of sickle cell thalassemia

Sickle cell disease (SCD) is an inherited autosomal recessive haemoglobinopathy. Sickle cell beta thalassemia is a variant syndrome of SCD characterised by the compound heterozygosity for sickle and beta thalassemia genes. We present a case of 12 year old male child diagnosed case of sickle cell thalassemia at the age of 2 years with complaints of fever, yellowish discolouration of eyes and drowsiness. USG abdomen was done suggestive of splenomegaly, multiple ill-defined, heterogeneously hypo-echoic, areas scattered throughout the splenic parenchyma with no vascularity within likely representing as splenic micro-abscesses. Child was started on antibiotics covering anaerobic and gram-positive organisms (vancomycin, meropenem, amikacin and metronidazole). Currently child is doing well with huge relieve to his symptoms.

A Rare Case of Compound Heterozygous Sickle Cell Beta Thalassaemia with High HbF and Normal HbA2 Levels Detected on HPLC

Compound heterozygous Sickle Haemoglobin (HbS) beta (β) thalassaemia arises from the mutations associated with sickle cell and β thalassaemia and significantly affects populations in low income countries like India. Elevated levels of Haemoglobin A2 (HbA2) represent the primary indicator for identifying carriers of β thalassaemia. However, it’s worth noting that sometimes, High Performance Liquid Chromatography (HPLC) encounters challenges in confirming a final diagnosis when levels of HbA2 and HbS fall outside the diagnostic range. A nine-year-old male and his sister 11-year-old female patient presented with high-grade fever and jaundice since two weeks. Following admission, Complete Blood Count (CBC) and HPLC of both children were done. Hb of male and female child revealed 1.8 g/dL and 1.5 g/dL, respectively. HPLC of male child revealed Haemoglobin F (HbF) 27.4%, HbS 56.3%, HbA2 3.8% and of female child revealed HbF 39.2%, HbS 43.5%, HbA2 3%. HPLC reports of both children were suggestive of differential of compound heterozygous HbS β thalassaemia and HbS homozygous. Later, HPLC of their parents was also done. HPLC of father was suggestive of thalassaemia trait and of mother suggestive of sickle cell trait, following which final diagnosis of both children was given as compound heterozygous HbS β thalassaemia. Diagnosing these compound heterozygous haemoglobinopathies can be challenging. As their is resemblance in clinicopathological features of sickle cell anaemia and β thalassaemia disorders, it is important to carefully differentiate between them although prognosis is better than thalassaemia major or sickle cell anaemia.

Modifying Our Genes: Theology, Science and “Playing God”

Modifying Our Genes: Theology, Science and “Playing God”

Rational Engineering of Minimally Immunogenic Nucleases for Gene Therapy

Genome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. On the horizon for FDA approval next year are several of the first treatment tools involving CRISPR based gene editing for sickle cell anemia and beta thalassemia (Frangoul et al. 2021). However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use(Charlesworth et al. 2019; Chew 2018; Mehta and Merkel 2020). Here we report reduced immunogenicity (Red)(i)-variants of two clinically-relevant nucleases, SaCas9 and AsCas12a. Through MHC-associated peptide proteomics (MAPPs) analysis, we identified putative immunogenic epitopes on each nuclease(Sekiguchi et al. 2018). Then, we used computational modeling to rationally design these proteins to evade the immune response(King et al. 2014). SaCas9 and AsCas12a Redi variants were substantially less recognized by adaptive immune components, including reduced binding affinity to MHC molecules and attenuated generation of cytotoxic T cell responses, while maintaining wild-type levels of activity and specificity. In vivo editing of PCSK9 with SaCas9.Redi variant was comparable in efficiency to wild-type SaCas9, but significantly reduced undesired immune responses. This demonstrates the utility of this approach in engineering proteins to evade immune detection and expand in vivo clinical use for a wide assortment of hematological disorders.

Abstract 10 Experience with Enrollments and Releases Within a Medical Needs Program at a Large U.S. Private Cord Blood Bank

Abstract Introduction Medical Needs / Directed Donor programs provide families with access to cord blood for potential future use. In situations where a diagnosis, potentially treatable with cord blood, exists in an immediate relative of the newborn, these programs often allow families to preserve newborn stem cells at little to no cost. Objectives The objective of this study was to examine indications for enrollment and unit releases in a medical needs program at a large U.S. private newborn stem cell bank. Methods Enrollment data over a 24-year period was analyzed. Data was categorized by indications for enrollment and indications for which units were released. Results There was a total of 7,034 enrollments within the specified timeframe. Most enrollments were for indications treatable by hematopoietic stem cell transplant given the program did not include experimental indications until 2019. Approximately one-third of enrollments (33.4%) for transplant indications were for various types of leukemia. The experimental indications most frequently represented in enrollments were autism (44.3%) and cerebral palsy (38.4%). For all cord blood units stored under the medical needs program, the majority (70%) of releases were intended for use in transplant medicine. The most frequently represented transplant indication for releases was hemoglobinopathies including sickle cell anemia and beta thalassemia (44.6%). Approximately one-third (36.1%) of transplant releases were related to leukemia. Autism and cerebral palsy were the two most frequently represented experimental indications for units released at 39% and 36%, respectively. Discussion Clinical indications were mostly consistent between enrollments and releases through this cohort. This suggests the structure of the program is effective in identifying families who have a higher likelihood of utilizing their cord blood unit for a transplant or experimental infusion. Cord blood banks should continue to re-evaluate the eligibility criteria for their medical needs programs in light of relevant updates in the potential utility of newborn stem cells including changes in transplant medicine indications and treatment procedures, as well as clinical trials and experimental protocols using related cord blood units. Future research related to pathways of referral to medical needs programs may inform education gaps among women’s health providers.

Correlation of Transfusion Dependence and Its Associated Sequelae to Hematological and Biochemical Parameters in Patients With Sickle Cell Disease and Beta Thalassemia Major in Khobar: A Retrospective Study.

Sickle cell disease (SCD) and beta thalassemia major (βTM) are multisystemic, genetically inherited diseases. They are caused by mutations of hemoglobin, which ultimately cause abnormal functioning of the red blood cells. The morbidity and mortality rates of these diseases are significant, as they may result in severe complications, some of which are quite fatal; hence, early diagnosis and treatment are crucial. The purpose of this study is to collect patients' data in terms of their manifestations and overall clinical picture and correlate them to the laboratory parameters with emphasis on their transfusion dependence and its sequelae in King Fahd Hospital of the University (KFHU), Al-Khobar, Saudi Arabia. After obtaining ethical approval from the institutional review board and in collaboration with the blood bank, patients' data were retrospectively collected from the hospital's database and categorized into two disease groups. Accordingly, data related to the biological and demographic information, clinical picture pattern, laboratory investigations, and therapeutic measures, with emphasis on blood transfusion as a treatment option, were gathered and analyzed. Eventually, the aforementioned data aspects were assessed for the probability of correlations, which were proven to be present to some level as an answer to our cohort study's question. Such findings, which will be depicted later in this study, might represent a ground for having a more comprehensive and extensive approach in terms of the general evaluation of patients with SCD and βTM based on the established level of correlation. During the course of conducting our research, we encountered some limitations, including the sample size and scarce data available during the process of data collection.

A Comprehensive Review of Pregnancy in Sickle Cell Disease.

Sickle cell hemoglobinopathies encompass a range of qualitative and quantitative hemoglobin disorders that are inherited genetically. This group of disorders includes sickle cell beta thalassemia, sickle cell trait, and sickle cell disease (SCD). Globally, SCD is the most common disorder. Even epidemiological data suggests the majority of diseases, as well as traits, are concentrated in Sub-Saharan Africa, North-East Africa, the Middle East, and India. The physiological changes in pregnancy predispose to an increased risk of catastrophic events like a vaso-occlusive crisis, thromboembolic events, and their related sequelae, leading eventually to villous infarction, necrosis, and fibrosis leading to compromising uteroplacental circulation. Conversely, the mother may exhibit exacerbated symptoms of gestational hypertension, placental abruption, preterm labor, and venous thromboembolism. Although this disease is manageable, it has the potential to adversely impact maternal and child health on a national level. The chances of severe complications in the pregnant state affecting both mother and fetus attract due attention of health services towards redefining and researching this disease and its management frequently. The literature review on the following situation advocates the general treatment to be observed under the headings of preconceptual care, strengthened antenatal care, strict intranatal care, and compliant post-natal care. Preconceptually, genetic screening of couples, with education on the adverse effects of the disease, comes as the first line of management. Newer facilities like preimplantation genetic diagnosis and celocentesis may even allow for early diagnosis as well as help patients who do not wish to terminate the pregnancy by selective transfer of unaffected embryos. This may be combined with an extensive evaluation of the psychosocial aspect and socioeconomic status of couples who administer vaccines as prophylaxis for preventable diseases. Strengthening antenatal care is associated with routine blood investigations for every registered antenatal patient with adequate awareness about the conditions that precipitate the crisis. All patients should be prophylactically treated with appropriate doses of aspirin, iron, folic acid, and multivitamins. Radiological examinations by ultrasonography may be used to monitor placenta previa, abruption, or preterm labor. Later in pregnancy, it should be recommended to performbiophysical profiling and assessment of umbilical artery flow. Intranatal care deals with strict-term institutional delivery of all sickle cell-diseased mothers with a preference for vaginal delivery. Post-natal care requires a precise assessment of blood loss during labor to initiate transfusion therapy as soon as needed. Exclusive breastfeeding, with the importance of early initiation of it, must be emphasized. Screening of neonates as quickly as possible must be done for hemoglobinopathies. Through this review, authors are trying to make aware of the complications that can be faced during pregnancy in SCD patients, its prevention, and its treatment according to various new guidelines and research available.

48. Follicular Density and Ovarian Histology in Individuals with Sickle Cell Disease and Beta Thalassemia

48. Follicular Density and Ovarian Histology in Individuals with Sickle Cell Disease and Beta Thalassemia

394 - Determining the Safety and Efficacy of Prophylactic Defibrotide Administration in Children, Adolescents, and Young Adults with High-Risk Sickle Cell Disease (SCD) or Beta Thalassemia Major Following Myeloimmunoablative Conditioning (MAC) and Haploidentical Stem Cell Transplantation Utilizing CD34+ Selection and T-Cell (CD3) Addback (IND127812)

394 - Determining the Safety and Efficacy of Prophylactic Defibrotide Administration in Children, Adolescents, and Young Adults with High-Risk Sickle Cell Disease (SCD) or Beta Thalassemia Major Following Myeloimmunoablative Conditioning (MAC) and Haploidentical Stem Cell Transplantation Utilizing CD34+ Selection and T-Cell (CD3) Addback (IND127812)

MBD2a-NuRD Binds to the γ-Globin Gene Promoter and Uniquely Forms a Complex Required for Bcl11a Mediated Silencing of Hb F Expression

A mechanistic understanding of γ-globin silencing is of clinical importance because reversal of silencing in adult erythroid cells results in high level expression Hb F which is therapeutic in sickle cell anemia and beta thalassemia. We describe here studies to elucidate the mechanism by which MBD2a-NuRD is an obligate partner of Bcl11a in silencing of HbF. We have previously shown that depletion of MBD2 or disruption of the MBD2-NuRD chromatin remodeling complex, but not MBD3-NuRD complex results in high levels of Hb F despite a concomitant 2-3 fold increase in expression of Bcl11a, a major silencing transcription factor (Yu etal. Haematologica, 2019). At the same time, Bcl11a can interact with both the MBD3 and MBD2 NuRD complexes. To elucidate the specific role of MBD2-NuRD, Chromatin Immunoprecipitation-qPCR(ChIP-qPCR) assays carried out in both adult erythroid phenotype HUDEP-2 and primary progenitor derived adult erythroid cells showed binding at the γ-globin gene promoter. To clarify the role of MBD2-NuRD in establishing closed chromatin configuration at the γ-globin gene loci, we carried out ATAC seq assays which showed that MBD2 knockout resulted in the same pattern of chromatin opening as reported for Bcl11a knockout in HUDEP-2 cells, consistent with our previous data showing ~40-50% Hb F in MBD2 knockout cells. In order to examine the effect of MBD2-NuRD on nucleosome positioning over the γ-globin gene promoter, NOME-SEQ assays were performed in HUDEP 2 cells which showed a nucleosome positioned at -110 to + 36 relative to the transcription start site (TSS) in MBD +/+ cells but not MBD2 KO HUDEP-2 cells, such that the NFY-A transcriptional activator binding site but not the Bcl11a repressor binding site is occluded. MBD2 exists in two isoforms in erythroid cells, resulting from alternative translation initiation sites. MBD2a contains an arginine rich (GR) domain which is absent in MBD2b and MBD3. Addback of MBD2a but not MBD2b in MBD2 KO HUDEP-2 cells resulted in silencing of γ-globin gene expression. Editing of the endogenous MBD2 gene such that predominantly MBD2b was expressed relieved silencing. To understand how the GR domain contributes to silencing we carried out unbiased proteomic analysis of MBD2a vs MBD2b NuRD complexes, which identified only 3 proteins uniquely associated with MBD2a. One of these, PRMT5, has been implicated in silencing of HbF. Knockdown of PRMT5 resulted in a`from <1% to ~15% γ-globin RNA in parental HUDEP-2 cells and a 4-5 fold increase in primary human progenitor derived erythroid cells, but caused no significant further increase in MBD2 KO HUDEP-2 cells. ChIP qPCR assays showed that PRMT5 and its obligate binding partner MEP50 occupy the γ- promoter in parental HUDEP-2 cells and primary erythroid cells but not in MBD2 KO HUDEP-2 cells. Furthermore, knockdown of PRMT5 resulted in frequent displacement of the nucleosome positioned at -110 to + 36 relative to the TSS. In order to determine the role that the GR domain might have in occupancy of MBD2a-NuRD at the γ-promoter, in vitro binding studies where done, which showed a requirement for both CpG methylation and the GR domain for high affinity binding of the methyl cytosine binding domain of MBD2 to the proximal γ-globin gene promoter sequences. We conclude that MBD2a-NuRD is required for silencing of Hb F due to its ability to localize at the methylated γ-globin gene promoter in conjunction with Bcl11a and recruit PRMT5, thereby stably positioning a nucleosome that blocks binding of the transcriptional activator NFY-A. These results reinforce the concept that targeted disruption of this specific complex has therapeutic potential to increase HbF in sickle cell anemia and β thalassemia.

Persistence of Enrollment Among Commercial Enrollee Populations with Rare Hematologic Diseases: Implications for Long-Term Outcome Assessment and Value-Based Agreements

Background: Innovative therapies, including gene therapies for incurable hematologic conditions, have highlighted the need for long-term assessment of outcomes. Administrative claims are an important source for observing patients over time, but enrollment "churn" across health plans can limit the length of meaningful follow-up analysis. This analysis examined a large, United States (US) dataset with complete enrollment data for health plan members in order to assess continuous enrollment (CE) among commercial populations with and without rare hematologic diseases. Methods: From January 1, 2016 to December 31, 2021 (identification period), a matched-cohort analysis was used to compare enrollment data for commercial members using the Optum Research Database. Members were grouped into the following disease cohorts based on diagnosis codes on non-diagnostic medical claims and/or treatment during the identification period: sickle cell anemia (SCA), beta thalassemia (beta-thal), and hemophilia (HA or HB). SCA was defined using ≥2 claims, on different dates, with an SCA diagnosis code. Beta-thal was defined using ≥1 claim with a beta-thal diagnosis code and ≥2 claims, on different dates, for blood transfusion or luspatercept. Hemophilia was defined using ≥1 claim with a HA/HB diagnosis code and ≥2 claims, on different dates, for on-demand or prophylaxis treatment specific to HA/HB (factor VIII and IX concentrates and emicizumab-kxwh). Members without these rare diseases were eligible for the control cohort if they had at least 1 medical claim during the identification period. The date of the first identifying claim defined the index date. Persistence of CE (medical and pharmacy) was measured in months (30-days), from the index date to the earlier of the disenrollment date or end of data. Rare disease and control cohorts were matched 1:3 without replacement on age, gender, index year, geographic region, fully-insured/administrative services only coverage, and subscriber/dependent status. Member characteristics were descriptively summarized overall, and results were stratified by cohort, index year, and age group (at index). Results: Overall, among ~25.7 million members, 3,459 were identified with a rare hematologic disease of interest (Table 1). Per rare disease cohort, 2,168 with SCA, 422 with beta-thal, and 869 with HA/HB were identified; the average age (standard deviation, SD) was 29.0 (15.1), 36.8 (20.7), and 24.5 (16.0) years in each cohort, respectively. The average (standard deviation [SD]) CE length in months among those with rare disease compared with respective controls was shorter in SCA (19.2 [17.8] vs. 20.4 [18.4]), longer in beta-thal (22.5 [18.1] vs. 20.6 [18.1]), and longer in HA/HB (23.7 [19.4] vs. 21.0 [19.2]) (Table 2). This pattern was consistent across all index years stratifications and among pediatric patients and adults <45 years old. Conclusions/Implications: Continuous enrollment time was overall shorter among members with SCA compared with their controls but longer for those with beta-thal and hemophilia compared with their controls. Even among those with the earliest index year (thus maximum possible follow-up time of ~72 months), average persistence of enrollment ranged from 25-31 months across disease cohorts and their controls. Notably, these findings reflect average enrollment for commercial members, in the setting of no minimum enrollment requirements. By contrast, claims-based research often requires a minimum duration of CE for a particular study population, which often increases the average CE observed. CE varied not only from matched controls, but also across SCA, beta-thal, and HA/HB cohorts, supporting the need to specifically evaluate enrollment in eligible treatment populations. Value-based agreements traditionally have involved commercial populations and have contracted on short-term (6-12 month) outcomes. Providers, payers, and manufactures will need to assess current data assets, available follow-up, and innovative data-sharing solutions that allow for patient portability (e.g., multi-payer platforms) to measure long-term outcomes. These methodological considerations will provide the foundation for aligning risk-sharing interests so that patients may access and benefit from these innovative therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Fertility preservation for pediatric patients with hemoglobinopathies: Multidisciplinary counseling needed to optimize outcomes.

Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are clinically significant include sickle cell disease, alpha thalassemia, and beta thalassemia. Advancements in disease-modifying and curative treatments for the common hemoglobinopathies over the past thirty years have led to improvements in patient quality of life and longevity for those who are affected. However, the diseases, their treatments and cures pose infertility risks, making fertility preservation counseling and treatment an important part of the contemporary comprehensive patient care. Sickle cell disease negatively impacts both male and female infertility, primarily by testicular failure and decreased ovarian reserve, respectively. Fertility in both males and females with beta thalassemia major are negatively impacted by iron deposition due to chronic blood transfusions. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for SCD and transfusion dependent beta thalassemia. Many of the conditioning regimens for HSCT contain chemotherapeutic agents with known gonadotoxicity and whole-body radiation. Although most clinical studies on toxicity and impact of HSCT on long-term health do not evaluate fertility, gonadal failure is common. Male fertility preservation modalities that exist prior to gonadotoxic treatment include sperm banking for pubertal males and testicular cryopreservation for pre-pubertal boys. For female patients, fertility preservation options include oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation requires controlled ovarian hyperstimulation (COH) with ten to fourteen days of intensive monitoring and medication administration. This is feasible once the patient has undergone menarche. Follicular growth is monitored via transvaginal or transabdominal ultrasound, and hormone levels are monitored through frequent blood work. Oocytes are then harvested via a minimally invasive approach under anesthesia. Complications of COH are more common in patients with hemoglobinopathies. Ovarian hyperstimulation syndrome creates a greater risk to patients with underlying vascular, pulmonary, and renal injury, as they may be less able to tolerate fluids shifts. Thus, it is critical to monitor patients undergoing COH closely with close collaboration between the hematology team and the reproductive endocrinology team. Counseling patients and families about future fertility must take into consideration the patient's disease, treatment history, and planned treatment, acknowledging current knowledge gaps.

The spectrum of thalassemia syndromes and abnormal haemoglobins in adult patients based on HPLC in a tertiary care centre of Punjab, India

In the present study adult patients with anemia were analysed for thalassemia syndromes and other haemoglobino pathies by using high performance liquid chromatography. A total of 102 Patients’ blood samples were evaluated for complete blood count, RBC indices, reticulocyte count and peripheral blood film for morphology. For the confirmation and characterization of hemoglobinopathy, ‘BIORAD VARIANT II’ of HPLC instrument with CDM software was utilized. 60.8% of the patients were females while the remaining 39.2% were males. The results of this study showed that 79.4% of patients were having a normal hemoglobin while 17% patients showed the prevalence of thalassemia trait. Two cases of hereditary persistence of fetal hemoglobin (HPFH) were seen and one case each of sickle cell-beta thalassemia (HbSThal) and hemoglobin D-Iran (HD-Iran) were seen. It was observed that 65.4% of the patients without thalassemia trait had normocytic normochromic type of anemia. In contrast, all the patients with thalassemia trait and HbSThal had microcytic hypochromic anemia. This association was statistically significant with hemoglobinopathies mostly having microcytic hypochromic. The present findings show high performance liquid chromatography forms a rapid, accurate, and reproducible tool for the early detection and management of hemoglobinopathies and variants.

Splenectomy perspective for non-malignant hematological disorders: A cross-sectional study in the Eastern Province of KSA

ObjectivesSplenectomy is considered a therapeutic modality for several hematological diseases, although complications are possible. This study assessed the effects of splenectomy on various hematological disorders and the roles of prophylactic measures on postoperative outcomes. MethodsThis was a cross-sectional study performed in KSA on adult patients with underlying non-malignant hematological disorders who had undergone splenectomy. ResultsThis study examined 179 patients with various hematological disorders, 38 (21.1%) of whom had undergone a splenectomy. Of those 38 patients, more than two-thirds (73.7%) had an open splenectomy. The average hospital stay was 2–7 days, and no significant difference was observed between the open and laparoscopic approaches. Approximately 95% of the patients showed overall improvements in their condition after splenectomy. However, 26.3% of patients reported a recurrence or need for further treatment 1 year or more after splenectomy. Approximately 16% of patients had an increased incidence of postoperative infectious complications, particularly patients with sickle cell disease and beta thalassemia. More than half the patients who developed complications had not received vaccination preoperatively, whereas 44.4% of vaccinated patients experienced complications (p = 0.04). ConclusionSplenectomy is considered a universal line of treatment for most non-malignant hematological diseases. Although splenectomy is an effective treatment, the reasons why patients with the same disease can have different responses remains unclear. Infection is a common postoperative complication, and vaccinations are underused. This study emphasizes the roles of patient education, scheduled vaccinations and proper selection of patients in the use of splenectomy for the treatment of non-malignant hematological diseases.

438 - Determining the Safety and Efficacy of Prophylactic Defibrotide Administration in Children, Adolescents, and Young Adults with High-Risk Sickle Cell Disease (SCD) or Beta Thalassemia Major Following Myeloimmunoablative Conditioning (MAC) and Haploidentical Stem Cell Transplantation Utilizing CD34+ Selection and T-Cell (CD3) Addback (IND127812)

438 - Determining the Safety and Efficacy of Prophylactic Defibrotide Administration in Children, Adolescents, and Young Adults with High-Risk Sickle Cell Disease (SCD) or Beta Thalassemia Major Following Myeloimmunoablative Conditioning (MAC) and Haploidentical Stem Cell Transplantation Utilizing CD34+ Selection and T-Cell (CD3) Addback (IND127812)

Current applications for measuring pediatric intima-media thickness.

Intima-media thickness is a known subclinical radiologic marker of the early manifestations of atherosclerotic disease. It is the thickness of the vessel wall, most often the carotid artery. Intima-media thickness is measured on conventional US manually or automatically. Other measurement techniques include radiofrequency US. Because there is variation in its measurement, especially in children, several recommendations have been set to increase the measurement's validity and comparability among studies. Despite these recommendations, several pitfalls should be avoided, and quality control should be performed to avoid erroneous interpretation. This article summarizes current literature in relation to the clinical applications for intima-media thickness measurement in children with known risk factors such as obesity, liver steatosis, hypercholesterolemia, diabetes, hypertension, systemic inflammatory diseases, cancer survival, kidney and liver transplant, and sickle cell disease or beta thalassemia major. Most potential indications for intima-media thickness measurement remain in the research domain and should be interpreted combined with other markers. The objective of diagnosing an increased intima-media thickness is to start a multidisciplinary treatment approach to prevent disease progression and its sequelae in adulthood.