Acute Hemolysis Research Articles

Ofloxacin Induced Hemolysis in G6PD-deficient Patient: A Rare Cause of Pigment Nephropathy

Thrombotic microangiopathy (TMA) commonly presents as a triad of acute kidney injury (AKI), jaundice, and hemolysis; however, tropical infections such as malaria, dengue, leptospira, and drugs like antimalarials can also have a similar presentation. They can cause AKI for many reasons including pre-renal causes but an important yet not relatively uncommon genetic cause of hemolytic anemia, that is, glucose 6-phosphate deficiency (G6PD) manifesting as jaundice, hemolysis, and AKI secondary to pigment nephropathy after receiving offending drugs needs to be worked up while evaluating such patients. Ofloxacin is not usually included in the lists of unsafe drugs in G6PD deficiency. Herein, we report a patient developing intravascular hemolysis secondary to G6PD deficiency associated with ofloxacin administration presenting as a rare cause for pigment nephropathy.

Aspirin Therapy in Cardiovascular Disease with Glucose-6-Phosphate Dehydrogenase Deficiency, Safe or Not?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, which may present as acute hemolysis, neonatal jaundice, or chronic hemolysis. Ingestion of fava beans, as well as infection and certain drugs, are the most typical causes of acute hemolysis in people with G6PD deficiency. Aspirin, the cornerstone in current therapies for the prevention of cardiovascular disease (CVD), is occasionally reported to induce acute hemolysis in G6PD-deficient individuals. G6PD deficiency is typically asymptomatic and many CVD patients with this enzyme defect start to take long-term aspirin therapy without G6PD activity examination; however, no consensus on the safety of aspirin in this population has been reached. A few studies have reported on this issue and produced contradictory results. In this review, we discuss the possible mechanisms of aspirin-induced hemolysis, and summarize clinical evidence regarding the safety of aspirin in subjects with G6PD deficiency.

Study of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Genotype Polymorphism of G6PD B and G6PD (A+/A-) in Patients Treated for Plasmodium vivax Malaria in a Tertiary Care Hospital in North East India.

IntroductionGlucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency is the most common enzymopathy in humans, and its distribution has been historically described to be closely associated with that of malaria. North East India provides optimal conditions for transmission of malaria and bears a considerable burden of Plasmodium vivax (P. vivax) malaria. Primaquine, a mainstay in the treatment of vivax malaria, may trigger episodes of acute hemolysis in patients with G6PD deficiency. The present study sought to delineate the frequency and genotypes of G6PD deficiency among patients suffering from vivax malaria infections. MethodsBlood specimens from 80 individuals diagnosed with vivax malaria underwent enzyme assay for G6PD deficiency. Samples with deficient phenotype underwent isolation of DNA using a genomic DNA isolation kit (Qiagen India Pvt. Ltd., New Delhi, India). The genomic DNA underwent amplification, serial denaturation, annealing, extension, final extension followed by digestion with restriction endonucleases Nla III and Fok I. The digested products were subjected to horizontal agarose electrophoresis for the separation of digested fragments. Samples without nucleotide 376 adenine→guanine (A→G) mutation were classified as G6PD B. Those with the mutation were further classified into G6PD A(+) and G6PD A(-) based on the presence of Nla III site.ResultsTwenty-seven out of 80 individuals (33.75%) with P. vivax malaria were found to have G6PD deficiency, of which a majority (n=24) had G6PD B genotype. Three individuals had Asparagine→Aspartic Acid mutation at position 376 (A→G), of which G6PD A(+) and G6PD A(-) were present in two and one cases, respectively.ConclusionG6PD deficiency was noted in about a third of patients with vivax malaria. Since primaquine therapy is contraindicated in this group of patients, there is a rationale for looking into screening patients with vivax malaria from the region prior to primaquine therapy. Further large scale studies may substantiate this and help in better genotypic and geographic characterization of G6PD deficiency in the region.

Metabolomic Characterization of Red Blood Cell Differentiation

Background: Erythropoiesis is the highly coordinated multi-step process by which multipotent hematopoietic stem cells differentiate into mature enucleated red blood cells (RBCs). As erythroid cells become more terminally differentiated, they undergo changes in morphology and gene expression, start synthesizing hemoglobin, commit to an irreversible loss of proliferation, and eventually expulse their nuclei and other cytoplasmic organelles. Thus, RBCs must rely on their proteome and metabolome for proper function. The RBC proteome is estimated to contain 2,800 proteins, including a variety of receptors and transporters that allow RBCs to uptake xenobiotics or endogenous metabolites as they circulate for ∼120 days. Furthermore, they are metabolically active with glycolysis, nucleotide catabolism, and glutathione metabolism as the major pathways supporting cell survival and function. However, it is unclear how the metabolome is altered during erythropoiesis, what role metabolites play in normal erythropoiesis, and if dysregulation of metabolites contributes to diseases of ineffective erythropoiesis, such as sickle cell anemia and thalassemia. Methods: Four models of erythropoiesis were used in this study. 1) Mice were treated with phenylhydrazine (Phz) to induce acute hemolysis followed by erythropoietic recovery, leading to an increase in circulating reticulocytes. 2) Mice were lethally irradiated and transplanted with wild-type or sickle cell bone marrow, leading to anemic profiles in sickle cell chimeras. 3) The mouse erythroleukemic (MEL) cell line was treated with DMSO to induce differentiation. 4) The human erythroleukemic (K562) cell line was treated with sodium butyrate to induce differentiation. For the in vivo mouse models, blood was collected from control and treated animals, and complete blood count (CBC) analysis was performed. For the in vitro cell culture models, the mRNA levels of β-globin were measured by Q-RT-PCR in control and differentiated cells, and the degree of hemoglobinization was determined visually and via staining for heme. In addition, metabolites were extracted from the collected RBCs and erythroleukemic cell lines, and a Snapshot LC/MS metabolomic platform was used to identify commonly altered metabolites. Results: We first validated our four models of erythropoiesis. Treatment with Phz decreased the number of total RBCs while increasing the RBC distribution width, indicating an increased number of reticulocytes (more immature RBCs) in circulation. Similar results were seen in the sickle cell chimeras. Treatment of MEL and K562 cells with DMSO and sodium butyrate, respectively, resulted in increased expression of β-globin, increased levels of heme, and increased red color. Then, using our Snapshot metabolomic platform, we identified global changes in RBC metabolism during erythropoiesis. Analyses of the commonly altered metabolites in the in vitro and in vivo models revealed an increase in amino acid, mitochondrial, and urea cycle metabolism during erythropoiesis. L-aspartate levels were particularly upregulated, especially in DMSO-treated MEL cells. We are now investigating the role of aspartate in the regulation of erythropoiesis. Conclusions: We defined how the metabolome was altered in multiple in vitro and in vivo models of erythropoiesis and identified global changes in RBC metabolism between the different models. Specifically, we found that L-aspartate was upregulated during RBC differentiation in all four models. Aspartate is an amino acid that plays a role in many processes in cells, including nucleotide biosynthesis, redox homeostasis, and amino acid biosynthesis. We hypothesize that aspartate metabolism is critical for RBC differentiation and that its dysregulation exacerbates disease of ineffective erythropoiesis, such as sickle cell anemia and β-thalassemia. We are currently testing its role in inducing hemoglobinization and in regulating the commitment of erythroid progenitor cells to an irreversible loss of proliferation. Overall, we believe that understanding the precise mechanisms by which cellular metabolism plays a role in proper RBC differentiation may lead to better therapies for diseases of ineffective erythropoiesis, such as sickle cell anemia and thalassemia. Disclosures No relevant conflicts of interest to declare.

Safety and efficacy of low-dose aspirin in ischemic stroke patients with different G6PD conditions.

Aspirin is the first recommended antiplatelet agent to prevention secondary stroke, but its safety and efficacy in stroke patients with glucose-6-phosphate dehydrogenase deficiency remain unclear. We sought to evaluate its safety and efficacy in ischemic stroke patients with and without glucose-6-phosphate dehydrogenase deficiency. Patients with ischemic stroke receiving aspirin (100 mg/day) for three months were recruited for a multicenter, prospective, cohort study. Blood glucose-6-phosphate dehydrogenase activity was examined after stroke. Safety outcomes including acute hemolysis, moderate-to-severe bleeding, and death (vascular, all-cause), and efficacy outcome indicated as stroke recurrence were evaluated at three months. Risk factors associated with moderate-to-severe bleeding and all-cause death were determined using multivariate or Cox regression analysis. Among the included 1121 patients, 81 of 130 glucose-6-phosphate dehydrogenase deficient and 576 of 991 glucose-6-phosphate dehydrogenase normal patients received aspirin for three months. Acute hemolysis was observed in one of the glucose-6-phosphate dehydrogenase deficient and in none of the glucose-6-phosphate dehydrogenase normal patients (p = 0.876). The rates of moderate-to-severe bleeding were 2.5% and 0.3% (p = 0.045), and the percentages of all-cause death were 6.2% and 1.4% (p = 0.008) in the glucose-6-phosphate dehydrogenase deficient and glucose-6-phosphate dehydrogenase normal patients. Stroke recurrence rate was similar in the two groups (2.5% vs. 1.7%; p = 0.608). Glucose-6-phosphate dehydrogenase deficiency was significantly associated with increased risk of moderate-to-severe bleeding (adjust p = 0.048) and all-cause death during aspirin use (adjust p = 0.008). Long-term low-dose aspirin therapy might relate to worse safety outcomes in patients with glucose-6-phosphate dehydrogenase deficiency and large clinical trials are needed to further confirm these findings.

Experimental vascular protective shield combined with vacuum sealing drainage prevents pressure on exposed vessels and accelerates wound repair.

The sustained negative pressure created by vacuum sealing drainage (VSD) on exposed vascular wounds can result in blood vessel compression, embolism, or necrosis. The objective of this research was to explore the ability of an experimental vascular protective shield combined with VSD to protect exposed vessels of the lower limbs and accelerate wound repair. (I) The vascular protective shield was prepared; (II) the material was subjected to acute toxicity and hemolysis tests; (III) and 30 New Zealand rabbits were divided into three groups: the control, VSD-only, and combined shield-VSD groups (with ten rabbits in each group). The wound-healing rate, myocardial function, wound histopathology, expression of angiogenesis markers, and exposed vascular compression of these three groups were compared on day 7. (I) The internal structure of the material was smooth; and (II) no toxicity or death was observed in mice of any group. The hemolysis rate in the combined shield-VSD group was very low. (III) The combined shield-VSD group showed a higher wound-healing rate, and higher levels of cluster of differentiation 31 (CD31), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF), than the other groups (P<0.05), along with a better tissue healing rate. (IV) Left ventricular pressure fluctuations in the combined shield-VSD group were smaller than those in the VSD-only group (P<0.05). (V) Blood vessels in the control and combined shield-VSD group were not damaged, but were damaged in the VSD-only group. The experimental vascular protective shield exhibited exceptional biosafety. The combination of this shield with VSD reduces influences on systolic and diastolic capacities of myocardium and avoids multiple compressions of exposed vessels, thus contributing to early vascularization of wounds and wound repair.

Circulating FH Protects Kidneys From Tubular Injury During Systemic Hemolysis.

Intravascular hemolysis of any cause can induce acute kidney injury (AKI). Hemolysis-derived product heme activates the innate immune complement system and contributes to renal damage. Therefore, we explored the role of the master complement regulator Factor H (FH) in the kidney's resistance to hemolysis-mediated AKI. Acute systemic hemolysis was induced in mice lacking liver expression of FH (hepatoFH−/−, ~20% residual FH) and in WT controls, by phenylhydrazine injection. The impaired complement regulation in hepatoFH−/− mice resulted in a delayed but aggravated phenotype of hemolysis-related kidney injuries. Plasma urea as well as markers for tubular (NGAL, Kim-1) and vascular aggression peaked at day 1 in WT mice and normalized at day 2, while they increased more in hepatoFH−/− compared to the WT and still persisted at day 4. These were accompanied by exacerbated tubular dilatation and the appearance of tubular casts in the kidneys of hemolytic hepatoFH−/− mice. Complement activation in hemolytic mice occurred in the circulation and C3b/iC3b was deposited in glomeruli in both strains. Both genotypes presented with positive staining of FH in the glomeruli, but hepatoFH−/− mice had reduced staining in the tubular compartment. Despite the clear phenotype of tubular injury, no complement activation was detected in the tubulointerstitium of the phenylhydrazin-injected mice irrespective of the genotype. Nevertheless, phenylhydrazin triggered overexpression of C5aR1 in tubules, predominantly in hepatoFH−/− mice. Moreover, C5b-9 was deposited only in the glomeruli of the hemolytic hepatoFH−/− mice. Therefore, we hypothesize that C5a, generated in the glomeruli, could be filtered into the tubulointerstitium to activate C5aR1 expressed by tubular cells injured by hemolysis-derived products and will aggravate the tissue injury. Plasma-derived FH is critical for the tubular protection, since pre-treatment of the hemolytic hepatoFH−/− mice with purified FH attenuated the tubular injury. Worsening of acute tubular necrosis in the hepatoFH−/− mice was trigger-dependent, as it was also observed in LPS-induced septic AKI model but not in chemotherapy-induced AKI upon cisplatin injection. In conclusion, plasma FH plays a key role in protecting the kidneys, especially the tubules, against hemolysis-mediated injury. Thus, FH-based molecules might be explored as promising therapeutic agents in a context of AKI.

&lt;p&gt;Clinical Characteristics of &lt;em&gt;Acalypha indica&lt;/em&gt; Poisoning&lt;/p&gt;

BackgroundAcalypha indica is a tropical plant used as a herbal medicine in various parts of the world, including Thailand. In glucose-6-phosphate dehydrogenase (G6PD)-deficient patients, acute hemolysis has been reported following the ingestion of this plant. Methemoglobinemia was reported in the present study.Patients and MethodsDescriptive data of patients who suffered from Acalypha indica toxicity reported from different hospitals to the Ramathibodi Poison Center were retrieved from 2011 to 2019.ResultsEight patients were included, mostly male with a median age of 61.5 years. The plant was ground for fresh juice or boiled before consuming as herbal medicine. All patients presented with dark urine. Most had jaundice and fever, and all reported hemolysis. Seven out of eight patients were diagnosed as methemoglobinemia. Methemoglobin level was confirmed in five patients with the highest level of 23.9%. Early symptoms occurred within 24 hours of the last ingested dose.DiscussionIn previous case reports of Acalypha indica ingestion, acute hemolysis was mostly observed in G6PD-deficient patients, consistent with the current findings. However, our patients also demonstrated methemoglobinemia, with some constituents in this plant (quinine, 2-methyl anthraquinone and tectoquinone) implicated as the cause in previous studies. Further studies are crucial to validate these findings.ConclusionWe report a case series in which acute hemolysis and methemoglobinemia after Acalypha indica ingestion were observed. This study presents methemoglobinemia as the other toxicity caused by this plant.

Intravascular hemolysis triggers ADP-mediated generation of platelet-rich thrombi in precapillary pulmonary arterioles.

Patients with hereditary or acquired hemolytic anemias have a high risk of developing in situ thrombosis of the pulmonary vasculature. While pulmonary thrombosis is a major morbidity associated with hemolytic disorders, the etiological mechanism underlying hemolysis-induced pulmonary thrombosis remains largely unknown. Here, we use intravital lung microscopy in mice to assess the pathogenesis of pulmonary thrombosis following deionized water-induced acute intravascular hemolysis. Acute hemolysis triggered the development of αIIbβ3-dependent platelet-rich thrombi in precapillary pulmonary arterioles, which led to the transient impairment of pulmonary blood flow. The hemolysis-induced pulmonary thrombosis was phenocopied with intravascular ADP- but not thrombin-triggered pulmonary thrombosis. Consistent with a mechanism involving ADP release from hemolyzing erythrocytes, the inhibition of platelet P2Y12 purinergic receptor signaling attenuated pulmonary thrombosis and rescued blood flow in the pulmonary arterioles of mice following intravascular hemolysis. These findings are the first in vivo studies to our knowledge to suggest that acute intravascular hemolysis promotes ADP-dependent platelet activation, leading to thrombosis in the precapillary pulmonary arterioles, and that thrombin generation most likely does not play a significant role in the pathogenesis of acute hemolysis-triggered pulmonary thrombosis.

A 3 Year Old with Hypoxia other Treatments Besides Oxygen

Background: Glucose-6-phosphatase Dehydrogenase (G6PD) deficiency causes acute hemolysis when exposed to oxidative stress. Methemoglobinemia has been associated with G6PD deficiency, and recognition is important to avoid further complications. Case Presentation: A 3-year-old healthy boy presents to the pediatric emergency department with acute onset of difficulty in breathing, perioral cyanosis and hypoxia not responding to oxygen therapy. Transfusion of packed red blood cells was given with improvement of symptoms. Laboratory results were significant for anemia and methemoglobinemia. Further tests revealed deficiency in glucose-6-phosphatase dehydrogenase enzyme. Discussion: G6PD deficiency can cause acute hemolytic anemia. Cyanosis can be exacerbated by the presence of methemoglobinemia. Management must include transfusion of packed red blood cells and avoidance of methylene blue to prevent further hemolysis. Conclusion: G6PD deficiency can manifest after exposure to oxidative stressors with acute onset hemolytic anemia and hypoxia. Occasionally methemoglobinemia could be present contributing to worsening symptoms.

Acute Hemolytic Transfusion Reaction Due to Anti-c Rhesus Antibody in a Patient With Subdural Hematoma: A Case Report Emphasizing the Shortcoming of Spin Cross-Match

The Rh blood group system is a complex blood group which includes different antigen specificities such as c antigen. Anti-c antibody is associated with both acute and delayed hemolytic transfusion reactions as well as hemolytic disease of the newborn (HDN). Rh mediated hemolytic transfusion reactions (HTR) are mostly immunoglobulin G (IgG) mediated and results in extravascular hemolysis and delayed HTR (DHTR). However, we are presenting a case of acute intravascular hemolytic transfusion reaction due to anti-c in a patient with acute subdural hematoma. A 77-year-old woman was referred to our hospital with a loss of conscious and left-sided hemiparesis. After an emergency MRI, she was diagnosed with Acute Subdural hematoma, and an emergency craniotomy was performed. Since Acute Subdural hematoma is a neurosurgery emergency, laboratory technician performed an Immediate-spincrossmatchedd for blood bag to preserve time. During the transfusion of the first packed cell, the patient developed severe hypotension and tachycardia. Thus, the transfusion was stopped. Laboratory results raised the suspicion of an Acute Intravascular Hemolysis. Antibody identification revealed that the patient had an irregular blood phenotype (C2+/c-/E-/e3+/K-), and the presence of alloantigen-c Rh antibody confirmed the suspicion of HTR. In patients with multi transfusion history and pregnant women, pre-transfusion screening of irregular antibodies must be performed. The immediate spincrossmatchh must be prevented in patients with a history of multi transfusions, even in emergency situations.

Pathogen genomic surveillance of typhoidal Salmonella infection in adults and children reveals no association between clinical outcomes and infecting genotypes

BackgroundIndia is endemic for enteric fever, and it is not known whether the variations in clinical manifestations between patients are due to host, environmental or pathogen factors.Blood culture surveillance was conducted at St. John’s Medical College Hospital, Bangalore, between July 2016 and June 2017. Clinical, laboratory and demographic data were collected from each case, and bacterial isolates were subjected to whole genome sequencing. Comparative analysis between adults and paediatric patients was carried out to ascertain differences between adult and paediatric disease.ResultsAmong the 113 cases of blood culture-confirmed enteric fever, young adults (16–30 years) and children < 15 years accounted for 47% and 37% of cases, respectively. Anaemia on presentation was seen in 46% of cases, and 19% had an abnormal leucocyte count on presentation. The majority received treatment as inpatients (70%), and among these, adults had a significantly longer duration of admission when compared with children (p = 0.002). There were atypical presentations including arthritis, acute haemolysis and a case of repeated typhoid infection with two separate S. Typhi genotypes. There was no association between infecting genotype/serovar and treatment status (outpatient vs inpatient), month of isolation, duration of admission, patient age (adult or child), antimicrobial susceptibility, Widal positivity or haematologic parameters.ConclusionsAmidst the many public health concerns of South India, enteric fever continues to contribute substantially to hospital burden with non-specific as well as uncommon clinical features in both paediatric and adult populations likely driven by host and environmental factors. Robust clinical surveillance as well monitoring of pathogen population structure is required to inform treatment and preventive strategies.

Red Cell Shearing between Transcatheter Heart Valves? Acute Hemolysis after Emergency TAVR-in-TAVR

A 72-year-old man with end-stage renal failure on hemodialysis and prior (21 months) transcatheter aortic valve replacement (TAVR) using a 29 mm Evolut R (Medtronic), presented with refractory card...

Gene Mutants and Their Clinical Characteristics of G6PD Deficiency Among Children in Luzhou Area

To study the gene mutants of G6PD deficiency and their clinical featuers among children in Luzhou area. 732 children with suspected G6PD deficiency in Luzhou area from March 2017 to July 2019 were selected, which were examined for G6PD enzyme activity and gene mutation. The G6PD enzyme activity was detected by ultraviolet rate quantification, and the gene mutation was detected by melting curve analysis-based PCR assay, and the clinical characteristics of different mutants when acute hemolysis happens were analyzed. 387 positive specimens were detected in 732 specimens, among which the gene mutation and the enzyme activity decrease was found in specimens 326, 49 specimens showed gene mutation but without the enzyme activity decrease, and 12 specimens without gene mutation but with the enzyme activity decrease. Among 375 positive samples with gene mutation, c.1376G＞T, c.1388G＞A, c.1024C＞T and c.95A＞G were the most common. The enzyme activity of c.1376G＞T and c.1388G＞A was statistically significantly different with c.1024C＞T. The most common incentives of acute hemolysis was broad bean, the reticulocyte count was statistically significantly different among c.1376G＞T, c.1388G＞A and c.95A＞G. The hemoglobin level of c.1376G＞T was statistically significantly different from with c.95A＞G. Moreover, c.1376G＞T, c.1388G＞A was lower than c.1024 C＞T. When acute hemolysis occurs, the reticulocyte count and hemoglobin changes were different between different mutation types, while the patients age, hospitalization time, blood transfusion, total bilirubin, and urine color recovery time of the patients were not statistically different. The common mutants of G6PD deficiency among children in Luzhou area are c.1376G＞T, and c.1388G＞A, c.1024C＞T. Favism is the most common clinical manifestation of G6PD deficiency.

Perioperative Events of Laparoscopic Cholecystectomy in Patients with Hemoglobinopathies

Background: Hemoglobinopathies are common genetic disorders affecting the synthesis of one of the globin chains of hemoglobin molecule. Laparoscopic cholecystectomy is the standard procedure for treatment of patients with normal hemoglobin and symptomatic gall stones, but doubt is still to date regarding safety of this procedure in patients with hemoglobinopathy. Aims:1. To assess the safety of laparoscopic cholecystectomy for hemoglobinopathic patients, 2. To describe the perioperative events that might happen before, during or after this procedure. Patients and Methods: This is a record-based comparative study conducted over a period of seven years, involved 62 hemoglobinopathic patients and 148 patients with normal hemoglobin variant. All underwent laparoscopic cholecystectomy and comparison done regarding perioperative events. Results: The overall complication rate was 56.5% in hemoglobinopathic patients and 21.6% in the other group and the difference was statistically significant (P- value ˂0.001). Vaso-occlusive crisis occurred in 9 patients (14.5%), respiratory complications (atelectasis and bronchitis) in (9.7%), acute chest syndrome in (4.8%) and hemolysis in (4.8%). Conclusions: 1. Laparoscopic cholecystectomy is safe in well prepared hemoglobinopathic patients but it is associated with significantly higher rate of disease related complications, namely acute chest syndrome, hemolysis and vaso-occlusive crises.2- Hemoglobinopathic patients require special pre, intra and post-operative care which should be offered by the surgeon, the physician and the anesthetist

Naphthalene Toxicity in Clinical Practice.

Naphthalene ingestion and skin or inhalational exposure (accidental or deliberate) is an under-recognized cause of a severe toxidrome in regions where it is commonly used (e.g., mothballs in households). This review is an update for the clinicians to understand the pharmacology, clinical features, laboratory evaluation, and treatment for naphthalene toxicity. High-quality literature for the past eight decades was collected and reviewed in this article. Several landmark articles were reviewed using PubMed, EMBASE Ovid, and the Cochrane Library, which have essential implications in the current toxicology practice. Naphthalene toxicity usually occurs abruptly and leads to acute hemolysis, methemoglobinemia, renal failure, respiratory depression, and acute brain dysfunction that are difficult to manage. The toxicity is more marked in patients with G6PD deficiency and associated with high morbidity and mortality. The management should mainly focus on high-quality supportive care; however, severe methemoglobinemia (>20-30%) requires specific therapy with intravenous methylene blue. Methylene blue is a highly effective agent but contraindicated in severe G6PD deficiency.

Acute fulminant hemolysis after transcatheter mitral valve replacement for mitral annular calcification

Transcatheter mitral valve replacement (TMVR) is emerging as an alternative treatment strategy to surgery for patients with severe mitral annular calcification (MAC) who are not candidates for traditional mitral valve surgery. Paravalvular leak (PVL) is common following TMVR for severe MAC and can lead to heart failure symptoms and/or intravascular hemolysis, the latter of which usually is clinically stable. We report the case of a 67-year-old woman with symptomatic severe aortic stenosis and mitral stenosis with MAC in the setting of prior chest irradiation who was treated initially with transcatheter aortic valve replacement followed by TMVR at a later date (Sapien S3 system; Edwards Lifesciences). Immediately following TMVR, she developed acute profound hemolysis which manifested with hemoglobinuria, transfusion-dependent anemia, and acute renal failure requiring renal replacement therapy. She was treated with post-dilation balloon valvuloplasty after failed transcatheter PVL closure 10 days following TMVR with resulting improvement in the PVL. The hemolytic anemia resolved and renal function recovered without the need for continued hemodialysis 2 months later and stabilization of glomerular filtration rate at 6 months. This case highlights a potential severe complication of TMVR in MAC and suggests that improvement in hemolysis and late recovery of renal function may occur following treatment of PVL.

Pattern of Hemolytic Anemia Among Egyptian Pediatric Emergency Department Patients.

The emergency department is considered the backbone of the medical service offered in any hospital. Yet, the data on the frequency of pediatric hematological presentation is scanty. Anemia occurs in 9% to 14% of pediatric emergency department (ED) patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects more than 400 million people worldwide. Unfortunately, we do not have screening program for G6PD deficiency in Egypt. The aim of this study is to assess the burden of hemolytic crisis among Egyptian children visiting ED. This is a prospective cross-sectional study among children presenting with acute hemolytic crisis in the ED of New Children Hospital, Cairo University from March to June 2016. Cases underwent full history taking, clinical examination, and laboratory tests based on clinical judgment of the resident. We categorized the presenting hemolytic anemias into 3 groups: G6PD deficiency, acute hemolysis in previously diagnosed patients with chronic hemolytic anemia, and acute undiagnosed hemolytic anemia. Our study included 143 patients, 109 males (76.22%) and 34 females (23.76%), with a mean age 36 months (range, 3-188 months), who presented with hemolytic anemia in the ED. Seventy-six cases (53.1%) were diagnosed as G6PD deficiency, 36 (25.2%) were diagnosed as chronic hemolytic anemia, and 31 (21.7%) were diagnosed as undiagnosed acute hemolytic anemia. Hemolytic anemia is very common presentation in ED. G6PD deficiency is the most common cause, representing 53.1% of the hemolytic anemia.

Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case\u2013control study in Congolese children

BackgroundBlackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children.MethodsThis is a case–control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping.ResultsA total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87–829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06–0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF.ConclusionThis pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.

Ispitivanje i upoređivanje troškova G6PD enzimskog skrining testa za novorođenu decu u odnosu na troškove lečenja pacijenata sa favizmom hospitalizovanih usled hemolize

Objective. We compared the glucose-6-phosphate dehydrogenase (G6PD) deficiency screening costs in neonates and treatment costs for patients with favism who were referred to the government hospitals of Isfahan with acute hemolysis. Methods. In this retrospective study, 116 patients with favism were selected, and their clinical data and treatment costs were recorded in Iranian Rials (IRR) and United States Dollars (USD). The costs of neonatal G6PD screening tests were estimated based on quantitative and qualitative screening kits by referring to each hospital's laboratories. Approximately 84760 births occurred in Isfahan province from October 2014 to October 2015. Results. Based on our results, 73 patients (62.9%) were males, and 43 of them (37.1%) were females. The causes for hemolysis were the consumption of broad beans in 78.4%, infection in 19.8%, and drugs (erythromycin and sodium cephalothin) in 1.7% of patients. The majority of patients (46.6%) received a single blood transfusion, and 18.9% received two or more transfusions, while 34.5% had received no blood transfusions. The mean and standard deviation of patients' medical expenses were 7,472,005±7,329,847 IRR (276.74±271.47 USD). The total cost of treatment for patients was 869,162,324 IRR (32,191.19 USD). The screening cost for all newborns from October 2014 to October 2015 with qualitative kits was 754,364,000 IRR (27,939.40 USD) and with the quantitative kits was 960,330,800 IRR (35,567.80 USD). Conclusion. The costs of the qualitative screening test for G6PD deficiency are lower than the costs of treatments of favism patients in Isfahan.