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Babesia species are intraerythrocytic piroplasms that can result in disease characterized by hemolytic anemia and thrombocytopenia. Of the 5 species that are known to infect canids in the United States, Babesia conradae is most frequently diagnosed in California, and Babesia vogeli is prevalent in the US. Despite the recent re-emergence of B. conradae, the mechanism of transmission is not known. Coyotes (Canis latrans) have been a proposed reservoir of disease, and previous work has shown that dogs with known aggressive interactions with coyotes are at greater risk for infection. This study aimed to determine the prevalence of B. conradae in wild coyote populations in California to assess the viability of coyotes as a potential source of infection for domestic dogs. Four hundred and sixty-one splenic samples were obtained during post-mortem examination of coyote carcasses from Southern California, Fresno, and Hopland. Demographic data including age, sex, cause of death, and urbanity were collected for each coyote. DNA was extracted from samples and amplified using real-time PCR with primers specific for the B. conradae ITS-2 gene. The 18S gene was amplified and sequenced using conventional PCR primers specific to the Babesia genus from any coyotes positive for B. conradae. In total, 22 coyotes tested positive for B. conradae in Fresno (n = 15), Orange (n = 4), San Bernardino (n = 1), and Los Angeles counties (n = 1) with an overall prevalence of 4.8%. Coyotes from Fresno (P

Theileria equi (T. equi) is an apicomplexan parasite that causes severe hemolytic anemia in equids. Presently, there is inadequate knowledge of the immune responses induced by T. equi in equid hosts impeding understanding of the host parasite relationship and development of potent vaccines for control of T. equi infections. The objective of this study was to evaluate the host-parasite dynamics between T. equi merozoites and infected horses by assessing cytokine expression during primary and secondary parasite exposure, and to determine whether the pattern of expression correlated with clinical indicators of disease. Our findings showed that the expression of pro-inflammatory cytokines was very low and inconsistent during both primary and secondary infection. There was also no correlation between the symptoms observed during primary infection and expression of the cytokines. This suggests that the symptoms might have occurred primarily due to hemolysis and likely not the undesirable effects of pro-inflammatory responses. However, IL-10 and TGF-β1 were highly expressed in both phases of infection, and their expression was linked to antibody production but not moderation of pro-inflammatory cytokine responses. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis (HS) is one of the most common causes of hereditary hemolytic anemia. The current diagnostic guidelines for HS are mainly based on a combination of physical examination and laboratory investigation. However, some patients present with complicated clinical manifestations that cannot be explained by routine diagnostic protocols. Here, we report a rare HS case of mild anemia with extremely high indirect bilirubin levels and high expression of fetal hemoglobin. Using whole exome sequencing analysis, this patient was identified as a heterozygous carrier of a de novo SPTB nonsense mutation (c.605G > A; p.W202*) and a compound heterozygous carrier of known UGT1A1 and KLF1 mutations. This genetic analysis based on the interpretation of the patient's genomic data not only achieved precise diagnosis by an excellent explanation of the complicated phenotype but also provided valuable suggestions for subsequent appropriate approaches for treatment, surveillance and prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoximeinduced hemolysis observed in a patient in China. Case description: A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion. Conclusion: This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing. [ABSTRACT FROM AUTHOR]

A single 300 mg dose of tafenoquine (an 8-aminoquinoline), in combination with a standard 3-day course of chloroquine, is approved in several countries for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged ≥ 16 years. Despite this, questions have arisen on the optimal dose of tafenoquine. Before the availability of tafenoquine, a 3-day course of chloroquine in combination with the 8-aminoquinoline primaquine was the only effective radical cure for vivax malaria. The World Health Organization (WHO)-recommended standard regimen is 14 days of primaquine 0.25 mg/kg/day or 7 days of primaquine 0.5 mg/kg/day in most regions, or 14 days of primaquine 0.5 mg/kg/day in East Asia and Oceania, however the long treatment courses of 7 or 14 days may result in poor adherence and, therefore, low treatment efficacy. A single dose of tafenoquine 300 mg in combination with a 3-day course of chloroquine is an important advancement for the radical cure of vivax malaria in patients without glucose-6-phosphate dehydrogenase (G6PD) deficiency, as the use of a single-dose treatment will improve adherence. Selection of a single 300 mg dose of tafenoquine for the radical cure of P. vivax malaria was based on collective efficacy and safety data from 33 studies involving more than 4000 trial participants who received tafenoquine, including over 800 subjects who received the 300 mg single dose. The safety profile of single-dose tafenoquine 300 mg is similar to that of standard-dosage primaquine 0.25 mg/kg/day for 14 days. Both primaquine and tafenoquine can cause acute haemolytic anaemia in individuals with G6PD deficiency; severe haemolysis can lead to anaemia, kidney damage, and, in some cases, death. Therefore, relapse prevention using an 8-aminoquinoline must be balanced with the need to avoid clinical haemolysis associated with G6PD deficiency. To minimize this risk, the WHO recommends G6PD testing for all individuals before the administration of curative doses of 8-aminoquinolines. In this article, the authors review key efficacy and safety data from the pivotal trials of tafenoquine and argue that the currently approved dose represents a favourable benefit–risk profile. [ABSTRACT FROM AUTHOR]

A 66-year-old man presented with hemolytic anemia, which required frequent blood transfusion, 6 months after surgical repair of an ascending aortic pseudoaneurysm. Hemolysis was attributed to luminal stenosis caused by graft kinking by laboratory test, CT and four-dimensional magnetic resonance imaging. First, an Excluder cuff was placed at the stenotic site under rapid pacing, but it migrated distally. Thereafter a Palmaz XL stent was placed at the stenotic site, which led to resolution of anemia. In this case, a Palmaz XL stent was successfully used to treat hemolytic anemia caused by graft kinking following ascending aortic surgery. [ABSTRACT FROM AUTHOR]

Faba bean (Vicia faba L.), is a popular legume crop due to its high protein content (22-38.2%), dietary fibre (12%), medicinal and nutritional values and environmental benefits. It is considered as an excellent source of protein, particularly in developing countries where people cannot afford to buy meat. It also has antioxidant, anti-inflammatory, antiviral, anticancer, anti-diabetic and antiatherosclerotic effects. But the presence of some key anti-nutritional factors, such as vicine and convicine, tannins, phytic acid etc. restricts the potential utilization of this crop as food and feed. Vicine and convicine are the thermostable, glucosidic aminopyrimidine derivatives that accumulate in the cotyledons of faba bean during seed development and maturity and cause "Favism" or haemolytic anaemia upon consumption by individuals having deficiency of glucose 6-phosphate dehydrogenase enzyme. As globally millions of people are genetically predisposed to such condition, it is highly desirable to eliminate these compounds from faba bean without compromising yield and other quality characteristics. In this review, we have highlighted the recent advancement in the field of genomics and molecular marker technologies for an easy and efficient selection of faba bean with low vicine and convicine content and the strategies to deploy these efficient tools in the future molecular breeding programs in faba bean. [ABSTRACT FROM AUTHOR]

Complement inhibitors are the mainstay of paroxysmal nocturnal hemoglobinuria (PNH) treatment. The anti‐C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life‐long intravenous fortnightly drug. Additionally, suboptimal response may occur in up to 2/3 of patients with persistent anemia due to incomplete control of intravascular hemolysis, development of upstream C3‐mediated extravascular hemolysis (EVH), or concomitant bone marrow failure. Ravulizumab, a longer half‐life anti‐C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti‐C5 concentrations. More recently, several other anti‐C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti‐C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti‐factor B) and danicopan (anti‐factor D). These drugs efficiently target EVH and are able to improve anemia and transfusion need in suboptimal responders to anti‐C5. The route and schedule of administration (twice weekly subcutaneously for pegcetacoplan and twice or thrice oral daily dosing for iptacopan and danicopan, respectively) are very convenient but pose novel issues regarding adherence. Additionally, both anti‐C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review, we will recapitulate PNH physiopathology, clinical presentation, and diagnosis and describe available and developing drugs that will lead to a precision medicine approach for this rare though heterogenous disease. [ABSTRACT FROM AUTHOR]

Summary: The hexokinase (HK) enzyme plays a key role in red blood cell energy production. Hereditary non‐spherocytic haemolytic anaemia (HNSHA) caused by HK deficiency is a rare disorder with only 12 different disease‐associated variants identified. Here, we describe the clinical features and genotypes of four previously unreported patients with hexokinase 1 (HK1)‐related HNSHA, yielding two novel truncating HK1 variants. The patients' phenotypes varied from mild chronic haemolytic anaemia to severe infantile‐onset transfusion‐dependent anaemia. Three of the patients had mild haemolytic disease caused by the common HK1 promoter c.‐193A>G variant combined with an intragenic HK1 variant, emphasizing the importance of including this promoter variant in the haemolytic disease gene panels. HK activity was normal in a severely affected patient with a homozygous HK1 c.2599C>T, p.(His867Tyr) variant, but the affinity for ATP was reduced, hampering the HK function. In cases of HNSHA, kinetic studies should be considered in the functional studies of HK. We reviewed the literature of previously published patients to provide better insight into this rare disease and add to the understanding of genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

Danicopan (Voydeya®) is an oral complement factor D inhibitor that is being developed by Alexion AstraZeneca Rare Disease as add-on treatment to ravulizumab or eculizumab for patients with clinically significant extravascular haemolysis. Danicopan recently received approval in Japan for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH) when used in addition to a complement component 5 (C5) inhibitor. Subsequently, the European Medicines Agency adopted a positive opinion recommending the granting of marketing authorisation for danicopan for the treatment of patients with PNH who continue to have residual haemolytic anaemia despite treatment with a complement C5 inhibitor. This article summarizes the milestones in the development of danicopan leading to this first approval for PNH. [ABSTRACT FROM AUTHOR]

Iptacopan (FABHALTA®) is an oral complement Factor B inhibitor developed by Novartis Pharmaceuticals for the treatment of complement-mediated diseases. Acting upstream of complement 5 in the alternative pathway, iptacopan inhibits both terminal complement-mediated intravascular haemolysis and complement 3-mediated extravascular haemolysis. On 5 December 2023, iptacopan received approval in the USA for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH). This article summarizes the milestones in the development of iptacopan leading to this first approval for PNH. [ABSTRACT FROM AUTHOR]

Objective: Pistacia vera is commonly used in traditional medicine to treat various disorders. This study aims to investigate the antianemia and hepatoprotective effects of Pistacia vera pericarp extract (PVPE) in a rat model of phenylhydrazine (PHZ)-induced anemia. Materials and Methods: PVPE was prepared using the maceration method. The extract was administered at doses of 20, 80, and 160 mg/kg for 28 days to normal and PHZ-treated rats. The effects of PVPE were evaluated in terms of changes in biochemical, histological, hematological, and molecular biomarkers in the liver and blood. Results: Administration of PVPE to the anemic animals significantly restored these deleterious effects on hematological parameters compared to the anemic group. Kupffer cell activation was seen in the liver tissue of the anemic rats. Administration of PVPE mitigated these deleterious effects. Conclusion: PVPE has potent antioxidant activity and may represent a promising treatment for anemia and liver protection in clinical settings. [ABSTRACT FROM AUTHOR]

Background: No tick‐borne pathogens (TBPs) causing haemolytic anaemia in cattle have been reported, except Theileria orientalis and complete blood count (CBC) profile is the only haematological parameter to determine the severity of regenerative haemolytic anaemia. Objectives: To identify the causative agents of TBP‐induced haemolytic anaemia and determine haematological parameters that indicate haemolytic anaemia in grazing cattle. Methods: Eighty‐two Korean indigenous cattle (Hanwoo) were divided into two groups: grazing (n = 67) and indoor (n = 15) groups. CBC and serum biochemistry were performed. PCR was conducted using whole blood‐extracted DNA to investigate the prevalence of TBPs. Results: TBP‐induced haemolytic anaemia was observed in the grazing group. In grazing cattle, co‐infection (43.3%, 29/67) was most frequently detected, followed by T. orientalis (37.6%, 25/67) and Anaplasma phagocytophilum infections (1.5%, 1/67). In indoor cattle, only co‐infection (20%, 3/15) was identified. Grazing cattle exhibited regenerative haemolytic anaemia with marked monocytosis, mild neutropenia, and thrombocytopenia. According to grazing frequency, the 1st‐time grazing group had more severe anaemia than the 2nd‐time grazing group. Elevations in indirect bilirubin and L‐lactate due to haemolytic anaemia were identified, and correlations with the respective markers were determined in co‐infected grazing cattle. Conclusions: Quantitative evaluation of haematocrit, mean corpuscular volume, and reticulocytes (markers of regenerative haemolytic anaemia in cattle) was performed for the first time. Our results show that, in addition to T. orientalis, A. phagocytophilum is strongly associated with anaemia. The correlation between haemolytic anaemia severity and haematological parameters (indirect bilirubin, reticulocytes, and L‐lactate) was confirmed. [ABSTRACT FROM AUTHOR]

Transplacental-derived anti-D IgG in RhD-negative pregnant women can trigger an immune response to Rh D-positive red cells in fetuses and newborns. We assessed the effect of anti-D titers in RhD-negative pregnant women on fetuses and newborns. The clinical data of 142 singleton RhD-sensitized pregnancies were retrospectively collected. The pregnant women received routine prenatal care and the newborns had standard care. Based on the tertile categories of the pregnancies, the maximum titers of anti-D IgG in the pregnant women were divided into three groups ranging from low to high as follows: low-titer group (anti-D titer: 1:4–1:128, n = 57); medium-titer group (anti-D titer: 1:256–1:512, n = 50); and high-titer group (anti-D titer: 1:1024–1:4096, n = 35). The frequencies of major neonatal complications did not significantly differ among the three groups. The high-titer group had the highest frequency of pregnancies requiring intrauterine transfusion (IUT) and number of IUTs among the three groups. The high-titer group had a significantly higher frequency of newborns treated with top-up transfusion, number of top-up transfusions, frequency of newborns treated with exchange transfusion (ET), and number of ETs when compared to the low-titer group. Higher anti-D titers in RhD-negative pregnant women predict more severe fetal and neonatal hemolytic anemia. Increasing maternal anti-D titers results in an increased need for IUTs, and neonatal top-up transfusions and ETs. Methods for reducing titers of anti-D IgG in RhD-sensitized pregnant women warrants further investigation. [ABSTRACT FROM AUTHOR]

Anaemia is a leading cause of morbidity and mortality in both males and females of all ages. Anaemia was induced by intraperitoneal (i.p.) administration of phenylhydrazine (60 mg/kg) for a period of 3 days. Anaemic rats were allotted to five (5) groups; group I served as the negative control, group II served as the positive control received Astyfer syrup (0.15 mg/kg p.o), groups III-V served as the test groups that received Tapinanthus globiferus methanol extract, ethyl acetate and n-hexane fractions (100, 200 and 400 mg/kg, p.o.), respectively. Packed cell volume (PCV), haemoglobin concentration (HB) and red blood cell count (RBC) were analysed as indices of anaemia at 7-day intervals for 21 days. The mean cell volume (MCV) and mean cell haemoglobin concentration (MCHC) were calculated accordingly. Leaf extract and fractions of Tapinanthus globiferus significantly (P<0.001) increased the PCV, the HB concentration and the RBC, which had been originally decreased by phenylhydrazine (P<0.001) administration within one week of treatment. The extract and fractions were compared with rats administered with the positive and vehicle-treated group. The results suggested that Tapinanthus globiferus leaves have haematinic activities. [ABSTRACT FROM AUTHOR]

Paravalvular leak (PVL) is an uncommon complication of prosthetic valve implantation, which can lead to infective endocarditis, heart failure, and hemolytic anemia. Surgical reintervention of PVLs is associated with high mortality rates. Transcatheter PVL closure (TPVLc) has emerged as an alternative to surgical reoperation. This method provides a high success rate with a low rate of complications. This article reviews the pathogenesis, clinical manifestation, diagnosis, and management of PVL and complications following TPVLc. Besides, we presented a case of a patient with severe PVL following mitral valve replacement, who experienced complete heart block (CHB) during TPVLc. The first TPVLc procedure failed in our patient due to possible AV‐node insult during catheterization. After 1 week of persistent CHB, a permanent pacemaker was implanted. The defect was successfully passed using the previous attempt. Considering the advantages of TPVLc, procedure failure should be regarded as a concern. TPVLc should be performed by experienced medical teams in carefully selected patients. [ABSTRACT FROM AUTHOR]

Systemic Lupus Erythematosus (SLE) is a clearly heterogeneous autoimmunity disorder with an unknown etiology that largely affects several body regions. Interleukin-15 (IL-15) is a cytokine that plays a vital role in the immune regulation and has been related in the pathogenesis of SLE disease. Hemolytic anemia is one of the hematological features of SLE, where the immune system breaks erythrocytes (red blood cells), causing anemia. The aim of this research is to evaluate IL-15 in SLE patients and their correlation with hemolytic anemia to see if this can be used as a biomarker for hemolytic anemia in SLE patients. This study analyzed the demographic and clinical presentation of 200 cases with whole blood and serum from this disease. ELISA and qPCR were also used to measure the amount of IL-15 at the gene and serum of SLE disease association hemolytic anemia. The results showed that IL-15 contributes to the immune response in hemolytic anemia from SLE. The data demonstrated that the gene and serum concentration of IL-15 in SLE disease patients associated with hemolytic anemia were higher than non-hemolytic anemia. In conclusion, the level of serum IL-15 was confirmed to be significantly higher in SLE patients associated with hemolytic anemia, not only in SLE disease patients. [ABSTRACT FROM AUTHOR]

Rationale: Passenger lymphocyte syndrome (PLS) may complicate minor ABO mismatched lung transplantation (LuTX) via donor-derived red cell antibody-induced hemolysis. Objectives: To ascertain the incidence and specificity of PLS-relevant antibodies among the study population as well as the dynamics of hemolysis parameters and the transfusion requirement of patients with or without PLS. Methods: In this cohort study, 1,011 patients who received LuTX between January 2010 and June 2019 were studied retrospectively. Prospectively, 87 LuTX (July 2019 to June 2021) were analyzed. Postoperative ABO antibody and hemolytic marker determinations, transfusion requirement, and duration of postoperative hospital care were analyzed. Retrospectively, blood group A recipients of O grafts with PLS were compared with those without. Measurements and Main Results: PLS affected 18.18% (retrospective) and 30.77% (prospective) of A recipients receiving O grafts, 5.13% of B recipients of O grafts, and 20% of AB patients receiving O transplants. Anti-A and anti-A1 were the predominant PLS-inducing antibodies, followed by anti-B and anti-A,B. Significantly lower hemoglobin values (median, 7.4 vs. 8.3 g/dl; P = 0.0063) and an approximately twice as high percentage of patients requiring blood transfusions were seen in PLS. No significant differences in other laboratory markers, duration of hospital stay, or other complications after LuTX were registered. Conclusions: Minor ABO incompatible LuTX recipients are at considerable risk of developing clinically significant PLS. Post-transplant monitoring combining red cell serology and hemolysis marker determination appears advisable so as not to overlook hemolytic episodes that necessitate antigen-negative transfusion therapy. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary pyropoikilocytosis (HPP) is the most common cause of non‐thalassemic severe inherited hemolytic anemia in Thai population. Up to 90% of affected patients harbor biallelic mutations of SPTB Providence (SPTB c.6055T>C), SPTB Buffalo (SPTB c.6074T>G), and SPTB Chiang Mai (SPTB c.6224A>G). This study aimed to develop a simple assay for mass screening of the three common SPTB mutations and to study their carrier frequencies in a healthy Thai population. Methods: We combined multiplex amplification refractory mutation system‐PCR (ARMS‐PCR) and high‐resolution melting (HRM) curve analysis to create a one‐step single‐tube assay. The primers were designed to generate products with different melting temperatures in the presence of 6055C, 6074G, and 6224G. Internal control primers were added for quality control. Residual samples from blood donors and healthy adolescents were collected and tested for the three common SPTB mutations using the newly developed assay. Results: Optimized multiplex ARMS‐PCR/HRM curve assay yielded well‐separated melt curves to detect the three SPTB mutations with 4‐h turnaround time. The assay was validated in screening of 2261 non‐repetitive blood donors and 89 adolescents, in which 10 (0.43%), 2 (0.09%), and 3 (0.13%) individuals were identified as carriers of SPTB Providence, SPTB Buffalo, and SPTB Chiang Mai, respectively. All mutated SPTB and 20 random wild‐type samples were confirmed using Sanger sequencing with 100% accuracy. Conclusion: The novel ARMS‐PCR/HRM curve assay is simple, accurate, and time‐effective for mass screening of the common SPTB mutations. This can be employed to prevent HPP birth in a Thai population. [ABSTRACT FROM AUTHOR]

Background: Hemoglobinopathies are common inherited blood disorders in our Mediterranean area. The main structural hemoglobin variants are hemoglobin S and hemoglobin C, due to their prevalence. We conducted this retrospective study to investigate and characterize hemoglobin C patients referred to the National Center for Thalassemia and Genetic Counseling and the management of hemoglobin C disease in Damascus. Materials and Methods: The study included patients referred to the National Center for Thalassemia and Genetic Counseling in Damascus between 2000 and 2022 for hemoglobin C detection. Gender, age, geographical origin, hemoglobin electrophoresis profile, and blood transfusion were considered for hemoglobin C patient classification. Blood transfusion in five consecutive years and linear regression with hemoglobin S and C values were determined. Results: 30 (14 males and 16 females) out of 624 patients between 3 and 46 years old (mean ± SD: 17.3 ± 9.7 years) showed hemoglobin C disease. Only eight patients (one male and seven females) received blood transfusions, and the remaining patients (13 males and 9 females) did not receive any transfusion. Only one patient with 100% hemoglobin C was detected; 19 showed HbSC, and 10 had HbAC. There was a significant correlation between hemoglobin S and geographical origin (P-value=0). Conclusion: A Homozygote hemoglobin C patient has mild hemolytic anemia, whereas the hemoglobin C 100% patient has only a one-time blood transfusion (he was 17 years old) in our study. The inherited combination of hemoglobin C and S is less severe than hemoglobin S alone. There is a significant relationship between hemoglobin S and geographical origin (p-value=0). [ABSTRACT FROM AUTHOR]

A subtype of cutaneous lupus erythematosus known as lupus erythematosus tumidus (LET) is characterized by sun-exposed areas that typically display urticaria-like papules and plaques. For LET, systemic therapy with antimalarials – particularly hydroxychloroquine (HCQ) – is the first line of treatment. Even though the safety profile of these medications appears to be high, there have been very few reports of side effects in the literature, including hemolytic anemia, retinal toxicity, maculopapular rash, gastrointestinal disturbance, and blue-gray discoloration of the skin or mucous membranes. Here, we report a unique instance of a 46- year-old LET smoker who, following HCQ treatment, developed a generalized myopathy. [ABSTRACT FROM AUTHOR]

Congenital erythropoietic porphyria (CEP) is an autosomal recessive inherited metabolic disorder caused due to deficiency of the enzyme uroporphyrinogen III cosynthase, resulting in large amounts of type I isomers, which massively accumulate in erythroid cells and then leak into plasma. CEP clinically presents as lifelong mutilating photosensitivity, erythrodontia, and hemolytic anemia. We report two brothers born out of consanguineous marriage with a diversity of features, i.e., mild and severe variants of CEP with hemolytic anemia and supported by genetic analysis. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension in sickle cell disease (SCD) is a complex phenomenon resulting from multiple overlapping etiologies, including pulmonary vasoconstriction in the setting of chronic hemolytic anemia, diastolic dysfunction, and chronic thromboembolic disease. The presence of pulmonary hypertension of any cause in SCD confers a significant increase in mortality risk. Evidence to guide the management of patients with sickle cell disease and chronic thromboembolic pulmonary hypertension (CTEPH) is scant and largely the realm of case reports and small case series. Centered on a discussion of a complex young patient with hemoglobin hemoglobin SC who ultimately underwent treatment with pulmonary thromboendarterectomy, we review the available literature to guide management and discuss and overview of treatment of CTEPH in SCD, considering the unique considerations and challenges facing patients suffering from this multisystem disease. [ABSTRACT FROM AUTHOR]

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. Objective: This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term "anaemias haemolytic immune" according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). Results: There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. Conclusions: Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA. [ABSTRACT FROM AUTHOR]

Ceftriaxone is widely used in pediatric outpatient care for its efficacy against respiratory and digestive system infections, yet its increasing association with severe immune hemolytic reactions requires heightened vigilance from pediatricians. This report details a rare and severe case of ceftriaxone-induced severe immune hemolytic anemia (IHA), hemolytic crisis, myocardial injury, liver injury, renal calculi, and cholecystolithiasis in a previously healthy 3-year-old child. The child, treated for bronchitis, experienced sudden pallor, limb stiffness, and altered consciousness following the fifth day of ceftriaxone infusion, with hemoglobin (Hb) levels precipitously dropping to 21 g/L. Immediate cessation of ceftriaxone and the administration of oxygen therapy, blood transfusion, intravenous immunoglobulin (IVIG), and corticosteroids led to a gradual recovery. Despite initial improvements, the patient's condition necessitated extensive hospital care due to complications including myocardial injury, liver injury, renal calculi, and cholecystolithiasis. After a 12-day hospital stay and a 3-month follow-up, the child showed complete normalization of Hb and liver function and resolution of calculi. In children, ceftriaxone infusion may trigger severe, potentially fatal, hemolytic reactions. Pediatricians must promptly recognize symptoms such as pallor, limb stiffness, and unresponsiveness, indicative of ceftriaxone-induced severe IHA, and immediately discontinue the drug. Effective management includes timely blood transfusion, respiratory support, IVIG administration, and corticosteroids when necessary, along with rigorous vital signs monitoring. Continued vigilance is imperative, even after cessation of ceftriaxone, to promptly address any residual adverse effects. [ABSTRACT FROM AUTHOR]

Background: Glucose-6-phosphate isomerase deficiency is a rare genetic disorder causing hereditary nonspherocytic hemolytic anemia. It is the second most common glycolytic enzymopathy in red blood cells. About 90 cases are reported worldwide, with symptoms including chronic hemolytic anemia, jaundice, splenomegaly, gallstones, cholecystitis, and in severe cases, neurological impairments, hydrops fetalis, and neonatal death. Case presentation: This paper details the case of the first Danish patient diagnosed with glucose-6-phosphate isomerase deficiency. The patient, a 27-year-old white female, suffered from lifelong anemia of unknown origin for decades. Diagnosis was established through whole-genome sequencing, which identified two GPI missense variants: the previously documented variant p.(Thr224Met) and a newly discovered variant p.(Tyr341Cys). The pathogenicity of these variants was verified enzymatically. Conclusions: Whole-genome sequencing stands as a potent tool for identifying hereditary anemias, ensuring optimal management strategies. [ABSTRACT FROM AUTHOR]

Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients. METHODS In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. RESULTS In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusions; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients received no transfusion; none of the patients in the second trial received transfusions. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan. CONCLUSIONS Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia -- in whom iptacopan showed superiority to anti-C5 therapy -- and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.) [ABSTRACT FROM AUTHOR]

Hemoglobin (Hb) Volga is a rare, unstable β-chain hemoglobin variant (β27 Ala→Asp), causing chronic hemolytic anemia. This study presents two members of a Danish family, splenectomized due to Hb Volga at and with multiple thrombotic events. The proband was diagnosed with Hb Volga 9 years old and splenectomy was performed as a part of treatment. Throughout his life, he experienced multiple superficial thrombophlebitis, two episodes of distal deep venous thrombosis (DVT) on lower extremities (age 32 and 33) and a transient ischemic attack (TIA) presented as amaurosis fugax (age 51). Thrombophilia investigation was normal. The proband's son was diagnosed with Hb Volga and underwent splenectomy at the age of 6. Despite anticoagulation therapy, he suffered from multiple venous thromboembolic events in his youth and died of chronic pulmonary embolism (PE)/pulmonary hypertension combined with infection. Given the observed propensity for multiple thromboses in these two patients, a literature review was conducted investigating reported occurrence of thrombotic events in individuals with Hb Volga. Currently 25 cases of Hb Volga are reported worldwide. The clinical symptoms primarily described are related to hemolytic anemia. Splenectomy is reported in 15 patients. Thromboses have previously been reported in only three patients who were also splenectomized. These cases involved DVT and PE, myocardial infarction, and an unspecified thrombotic event. The proband represents the first reported Hb Volga case with both venous and arterial thrombotic disorders. The exact mechanism underlying thrombotic tendency in patients with Hb Volga remains unknown, but it is probably associated with splenectomy. [ABSTRACT FROM AUTHOR]

In this report, we describe a 6-year-old girl with a medical history of pallor, mild icterus, anemia, blood transfusion and abnormal hemoglobin variant analysis on capillary electrophoresis. She was referred for further analysis. DNA sequencing of the proband revealed a de novo mutation in Codon 88 (CTG > CCG) of the β-globin gene (HBB: c.266T > C) in a heterozygous state compatible with hemoglobin Santa Ana, an unstable hemoglobin. This is the first case of Hb Santa Ana from Iran associated with moderate to severe anemia who underwent splenectomy with clinical improvement. [ABSTRACT FROM AUTHOR]

Background. Hemolytic uremic syndrome (HUS) may present atypically without the full triad of classical HUS. Eculizumab has been shown to be efficacious in complement-mediated atypical HUS and some cases of Shiga-toxin (ST) associated HUS. We report the utility of eculizumab in enteroaggregative E. coli (EAEC) associated HUS. Case summary. A female toddler presented with hemolytic anemia, oliguric acute kidney injury (AKI) without thrombocytopenia, and peripheral schistocytes. The stool examination for ST was negative but positive for EAEC. She required several hemodialysis sessions and received one dosage of eculizumab with rapid reversal of AKI and hemolytic markers. A kidney biopsy revealed acute tubular injury and segmental glomerular basement membrane splitting. Genetic testing was negative for complement mutations or deficiencies. A follow-up six months later showed persistently normal renal function and hematological markers. Conclusion. The clinical and histological manifestations of non-ST-associated diarrheal HUS and the role of eculizumab in this condition warrant future larger studies. [ABSTRACT FROM AUTHOR]

Background: Relapse is a clinical concern in dogs diagnosed with immune‐mediated hemolytic anemia (IMHA), thrombocytopenia (ITP), or polyarthritis (IMPA). The average time to relapse is unknown, and evidence that vaccination is associated with disease relapse is lacking. Hypothesis/Objectives: Compare the incidence of relapse in groups of dogs with IMHA, ITP, or IMPA over a 24‐month period after diagnosis and compare proportions of dogs that received vaccines in those dogs that did and did not relapse. Animals: One hundred sixty client‐owned dogs (73 with IMHA, 55 with ITP, 32 with IMPA). Methods: Medical records of dogs were reviewed with the goal of following cases for a minimum of 2 years. Incidence of relapse was calculated for each disease, and relapse rates in dogs that were or were not vaccinated after diagnosis were compared. Results: Relapse rates at 12 months differed significantly among disease groups (P =.02), with a higher rate for IMPA (35%) compared to IMHA (11%) or ITP (11%). Relapse rate at 24 months was 41% for IMPA, 18% for IMHA, and 23% for ITP. Ninety percent of IMPA relapses occurred in the first 12 months after diagnosis, compared with 56% for IMHA and 50% for ITP. Vaccine administration after diagnosis was not associated with relapse (P =.78). Conclusions and Clinical Importance: Risk of disease relapse in IMPA is highest in the first year after diagnosis, with a higher relapse rate compared with IMHA and ITP. The role of vaccination in disease relapse remains unclear. [ABSTRACT FROM AUTHOR]

Posttransplant thrombotic microangiopathy (PT-TMA) can be caused by calcineurin inhibitors (CNIs), ischemic injury, infections, or antibody-mediated rejection (ABMR). Delayed recognition can result in allograft loss. We describe the first reported case of successful reversal of refractory PT-TMA with eculizumab in India. It highlights the importance of prompt diagnosis and benefit from an early initiation of eculizumab therapy in refractory cases. [ABSTRACT FROM AUTHOR]

Objectives: To establish epidemiology, healthcare costs, and labor market attachment in patients with paroxysmal nocturnal hemoglobinuria (Pt‐PNH) in Denmark. Methods: Data were from Statistics Denmark and the Danish Health Data Authority national population registers (2005–2021). Descriptive baseline statistics characterized the Pt‐PNH analytic population; ordinary least squares and adjusted Cox proportional hazards regressions measured outcomes in the Pt‐PNH versus Danish general population matched comparators. Results: Overall PNH incidence in Denmark was n = 11 during 2007–2009, n = 25 during 2016–2018 and n = 7 during 2019–2020; prevalence increased from n = 13 in 2006 to n = 62 in 2021. Of the overall n = 85 Pt‐PNH; n = 24 were treated with complement‐5 inhibitors (Pt‐C5i) and n = 61 not treated with C5i (Pt‐nC5i). Versus respective comparators, all patients had significantly greater annual per‐patient costs (from inpatient hospital admissions, outpatient contacts, PNH treatments; indirect costs from lost earnings + transfer payments; post‐diagnosis for Pt‐PNH and Pt‐nC5i, post‐treatment initiation for Pt‐C5i). The Pt‐C5i incurred the greatest healthcare and indirect cost differences (€709 119; €152 832, respectively) followed by the Pt‐PNH (€189 323; €29 159, respectively) and Pt‐nC5i (€95 548; €4713, respectively). The Pt‐PNH versus comparators also had an increased hazard of death (2.71 [95% CI, 1.63 − 4.51]). Conclusion: Although a rare disease, PNH is associated with significant patient, healthcare system, and societal burdens in Denmark. [ABSTRACT FROM AUTHOR]

Objective: Snakebite envenomation‑related thrombotic microangiopathy (TMA) is observed in a subset of patients with venom‑induced consumption coagulopathy (VICC). The study was planned to determine the prevalence of TMA among patients with hemotoxic envenomation admitted to a medical college hospital in Himachal Pradesh, India. Methods: This was a hospital‑based open cohort observational study conducted on patients diagnosed with hemotoxic envenomation. The study period was of 1 year and patients were recruited using a nonprobability sampling method. Hemotoxic envenomation was defined as prolonged bedside 20‑min whole blood clotting time (20 WBCT) following a history of snake bites. TMA was defined as the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury (AKI). Results: A total of 56 patients (32 females and 24 males) were included in the study. The prevalence of TMA was (7/56) 12.5%. Out of the seven patients with TMA, four (57.1%) patients improved without renal replacement therapy and three (42.9%) patients took referrals for getting nephrology services outside the state and hence were lost in follow‑up. AKI was developed in 17 (30%) patients. Conclusion: The study demonstrated that TMA is not an uncommon entity. Investigation protocol for TMA should be included in all patients with VICC. [ABSTRACT FROM AUTHOR]

Background: Nutritional deficiencies are the most common cause of anemia in the tropical countries. Deficiencies of vitamin B12 and folate can cause severe anemia and cytopenias due to ineffective hematopoiesis and can sometimes minor hemolytic anemia. Vitamin D deficiency is likely to play an important role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections such as tuberculosis in India. Aim is to study Vitamin B12 and Vitamin D levels in factory employees. Objective is to evaluate Vitamin D and Vitamin B12 levels in factory employees and identify groups vulnerable for these deficiencies. Materials and Methods: Present cross-sectional study was performed in 714 factory employees from Chhatrapati Sambhaji Nagar district of Maharashtra for a period of 2 months. Vitamin D3 and vitamin B12 levels were estimated on Vitross 5600 dry chemistry with immunochemistry by Chemiluminescent Immunoassay platform from plain vacutainer samples. Statical analysis done by using Unpaired t Test. All the patients were in the fasting state. Results: 714 employees were examined for vitamin D and B12. Out of which 676 were males and 38 were females. Age range of employees were from 20 to 60 years. Out of which 18% males had deficiency, 73% males had insufficiency and only 9% males had sufficient levels of Vitamin D in males. For Vitamin B12 67.45% males had deficiency and 33% males had sufficient levels. For females: 37% females had deficiency, 53% had insufficiency and 11% had sufficient levels of Vitamin D3.42.1% females had deficiency and 58% females had sufficient levels of Vitamin B12. [ABSTRACT FROM AUTHOR]

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An 11‐year‐old neutered male Jack Russell Terrier was presented to Yuki Animal Hospital for regenerative anemia during the treatment of hypoadrenocorticism. A blood smear examination showed spherocytes, polychromatic erythrocytes, and erythrocyte ghosts. The direct agglutination test was positive at 37°C. The dog was then diagnosed with immune‐mediated hemolytic anemia (IMHA). Although prednisolone and mycophenolate mofetil were administered, the hematocrit and reticulocyte count decreased, and nonregenerative anemia developed. A bone marrow examination was performed to diagnose the cause of the nonregenerative anemia. Histologic and cytologic bone marrow examination revealed a normocellular to hypercellular medulla with severe erythroid hypoplasia. No proliferation of lymphocytes or lymphoblast‐appearing cells was observed. This dog was diagnosed with pure red cell aplasia (PRCA). Despite treatment with immunosuppressive agents, the patient died of thrombosis. Although these associations were unclear, this is the first report of PRCA diagnosis following IMHA and while treating hypoadrenocorticism. [ABSTRACT FROM AUTHOR]

ABSTRACT: The state of Santa Catarina is the largest national producer of onions. The consumption of onion (Allium cepa) by domestic animals can cause hemolytic anemia and hyperhemoglobinemia of Heinz bodies in erythrocytes. The epidemiological data and the pathological clinical picture were obtained during a visit to the property where the disease occurred. A herd of 54 beef cattle from a property in the municipality of Bom Retiro/SC, was placed in an onion crop, which had not been completely harvested because it was outside the desired standard for trade. The animals remained in this field for eight days. At the end of this period, all of them presented apathy, anorexia, brown urine and mucous membranes and an onion odor on expiration. The macroscopic changes observed were pale mucous membranes, blood with decreased viscosity and increased clotting time, liver with an evident lobular pattern and remains of onion in the rumen. The carcass gave off a strong onion odor. By histological analysis, there was central lobular coagulation necrosis in bridging in the liver. In the kidneys, there were intracytoplasmic hyaline droplets in tubular epithelial cells and a deposit of eosinophilic material in the lumen of the tubules. For the diagnosis of onion poisoning, epidemiological data associated with clinical signs, such as pale mucous membranes with evidence of hemoglobin pigmentation (brown mucosa) and hemoglobinuria, should be taken into account. This article seems to be the first report of onion poisoning in cattle in Brazil.

The elephant trunk procedure, an endovascular strategy for retrograde type A acute aortic dissection, is associated with several complications, hemolytic anemia being a rare one. We performed endovascular stent-graft insertion in a patient who developed hemolytic anemia. Transesophageal echocardiography (TEE) detected turbulent jet flow and stenosis position, which was not detected by angiography and intravascular ultrasound (IVUS). This imaging technique proved effective for malperfusion diagnosis and enabled us to confirm its resolution after the endovascular procedure. Intraoperative TEE is a useful adjunct to angiography and IVUS for diagnosis and therapeutic assessment during endovascular repair of a stenosed elephant trunk.

Abstract Background The administration of high-dose intravenous immunoglobulin (IVIG) is a standard treatment for the management of Kawasaki disease (KD). IVIG is known to be a highly effective and safe treatment. Case presentation We report the development of hemolytic anemia in seven children receiving repeated doses of IVIG. The children were aged 3–44 months and included 4 girls and 3 boys. All children received 10% IVIG and a second course of immunoglobulin because they did not respond to the first course of immunoglobulin. Two received high-dose aspirin (50 mg/kg), and five received low-dose aspirin (5 mg/kg). Two patients required additional methylprednisolone pulse therapy (30 mg/kg) after the second dose of immunoglobulin, and three patients received oral prednisolone therapy for defervescence. Three patients showed coronary artery dilation during hospitalization and normalized within two months. Pretreatment hemoglobin averaged 11.3–14.2 g/dL, and post-hemolytic anemia hemoglobin ranged from 7.4 to 9.6 g/dL, with a difference of 1.7–6.8 g/dL. Reticulocytes were increased to 3.3–13.2%. Peripheral blood smears showed normochromic normocytic anemia, and anisopoikilocytosis. All children were positive for warm-type antibodies with IgG+, C3d- in direct antiglobulin test, and the blood group was A + in five and B + in two. None of the patients received immunomodulatory therapy or red blood cell transfusions. They were followed for a year and all recovered. Conclusion Especially, in non-O blood group KD patients who are refractory to initial IVIG and require a second dose of IVIG or 10% formulation the possibility of immune hemolytic anemia should be carefully considered, and close follow-up should be maintained after therapy.

The article reports on the launch of a revised classification scheme of glucose-6-phosphate dehydrogenase (G6PD) deficiency by World Health Organization (WHO). Topics mentioned include the clinical manifestations of G6PD, the need to gather information on phenotype-genotype associations for each variant, and the assessment of the G6PD activity of each variant from hemizygotes and from rare homozygotes.

Atypical Haemolytic Uraemic Syndrome (aHUS) is a rare type of thrombotic microangiopathy that occurs without Shiga toxin producing bacteria. It is a condition related to complement regulation, which may be genetic or acquired. The complement system’s alternative pathway is commonly implicated, with around 6-10% of cases being caused by autoantibodies directed against factor H. While it typically affects children between 9 to 13-years-old, it can also occur in adults. Many patients do not have circulating Complement Factor H-related proteins 1 and 3 due to a homozygous deletion involving CFHR1 and CFHR3. Authors hereby report a case of a six-month-old female child who was diagnosed with Ventricular Septal Defect (VSD) at one and a half months of age. She presented with pneumonia and subsequently developed haemolytic anaemia with thrombocytopenia, oliguria, and acute kidney failure. She was diagnosed with Antifactor H antibody-mediated HUS. She was treated with plasma therapy, but the patient succumbed due to multiorgan dysfunction. [ABSTRACT FROM AUTHOR]

The article describes the case of a 24-year-old male patient who developed acute hemolytic anemia following arsenic poisoning. Topics include his medical history of the patient, differential diagnosis, confirmation of an ischemic stroke of the brain following a neurological consultation, and a discussion on arsenic poisoning.

Sickle cell disease (SCD) is a hemoglobinopathy inherited in an autosomal recessive pattern arising from a mutation causing substitution of valine for glutamic acid in the sixth amino acid of the β-globin chain. The clinical manifestation of SCD varies from acute pain, chronic anemia, to multi-organ infarct and failure. SCD is known to be rare in Indonesia. However, we recently encountered a SCD patient presenting with recurrent pain and hypesthesia since a year ago. The diagnosis of SCD in this patient was established based on the results of peripheral blood smear and hemoglobin electrophoresis. The patient had previously been diagnosed with thalassemia at the age of 19 years old due to a history of icterus, thus delaying prompt treatment. This further emphasizes the challenges in distinguishing SCD, which is relatively rare in Indonesia compared to thalassemia, especially considering the complexity and the variability in the phenotypic presentation of SCD. The patient was then given supportive therapy consisting of blood transfusion and symptomatic treatment, as well as consideration to administer hydroxyurea if the patient’s clinical condition worsens.

Monika Oliver,1 Christopher J Patriquin2 1Department of Medicine, University of Alberta; Division of Hematology, University of Alberta Hospital, Edmonton, Alberta, Canada; 2Department of Medicine (Hematology), University of Toronto, Division of Medical Oncology & Hematology, University Health Network, Toronto, Ontario, CanadaCorrespondence: Christopher J Patriquin, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G2C4, Canada, Tel + 1-416-340-5233, Fax + 1-416-340-3799, Email christopher.patriquin@uhn.caAbstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired clonal abnormality, which renders hematopoietic cells exquisitely sensitive to complement-mediated destruction. Classical features of PNH include intravascular hemolytic anemia, increased thrombotic risk, and manifestations related to end-organ damage (eg fatigue, chest pain, dyspnea, renal failure, and pulmonary hypertension). With supportive care alone, mortality rate of patients with PNH is approximately 35%. The anti-C5 monoclonal antibody, eculizumab, was the first targeted therapy approved for PNH, and led to improved hemoglobin, quality of life, reduced transfusion need, reduced thrombosis, and greater overall survival. More recently, therapeutics such as longer acting anti-C5 (ravulizumab) and anti-C3 (pegcetacoplan) medications have been approved, along with other novel therapeutics in late-stage clinical trials. Biosimilars of eculizumab are also now available. Proximal inhibitors (against C3, factor B, and factor D) have shown significant improvements in hemoglobin and transfusion-avoidance in patients who remain anemic despite C5 inhibition. Despite these novel therapies, some unmet challenges remain, including management of breakthrough hemolysis, clinically significant iatrogenic extravascular hemolysis, optimal management in pregnancy, and infection risk mitigation as new targets in the complement system are blocked. In addition, the use of self-administered subcutaneous and oral therapies raises concerns around treatment adherence and the risks of uncontrolled terminal complement. Given the ultra-rare nature of PNH, development is underway of a centralized international registry to capture and analyze the data as they mature for various new therapies and characterize the clinical challenges related to PNH management.Keywords: complement, hemolysis, hemolytic anemia, PNH, thrombosis

Hemolytic crises and aplastic crises in hereditary spherocytosis (HS) are most commonly triggered by viral infections. We present the case of an adolescent girl with HS who developed unexpected and life-threatening complications of her inherited hemolytic anemia as a consequence of anorexia nervosa and severe malnutrition.