Acute Hemolysis Research Articles

Eculizumab Utilization in Hemolytic Uremic Syndrome (HUS) Presenting with Acute Hemolysis

Background: Hemolytic uremic syndrome (HUS) is thrombotic microangiopathy in which microthrombi are formed, consisting mainly of platelets, which will occlude the arterioles and capillaries leading to a triad of intravascular hemolysis, thrombocytopenia, and acute kidney failure. Case Presentation: A 2-year-old boy presented to our outpatient clinic with persistent diarrhea streaked with blood, vomiting, signs of dehydration, and an ingested throat. The complete blood count (CBC) revealed acute hemolysis with mild normocytic hypochromic anemia, anisopoikilocytosis, fragmented red blood cells, and moderate thrombocytopenia. The patient experienced a drastic course which was dramatically improved after the administration of eculizumab. Conclusion: Eculizumab is a recombinant humanized monoclonal antibody against complement component C5; that effectively blocks the cleavage of complement factor C5 and, subsequently, the complement membrane attacks complex C5B-9.78. While on eculizumab, our patient's kidney function improved significantly after the first dose with a creatinine of 0.56 mg/dl.

Blood Group Discrepancy in a Donor Due to a Rare Ax/Aweak Subgroup Phenotype with ABO*AW.31.01/*O.01.75 Genotype

ABSTRACT The most crucial blood group system in transfusion medicine is still the ABO system. Any unresolved discrepancy could result in the patient receiving blood that is incompatible and could trigger acute intravascular hemolysis. ABO subgroups are one of the astounding differences in blood grouping. The amount of A and B antigens carried by red blood cells and present in secretion varies depending on the ABO subgroup phenotype. Clinically, A1 and A2 are the two most frequently observed subtypes. Many weaker A subgroups have been described, including A3, Axe, am, and el. This example involves an Indian male donor who was initially misclassified as a Group O individual before being identified as an Ax/Aweak subgroup phenotypically. The next-generation sequencing defined the genotype of this case as ABO*AW.31.01/*O.01.75.

A fatal case of acute copper sulphate poisoning presenting with methaemoglobinemia and intravascular haemolysis: a case report

Copper sulphate is a common industrial chemical that is rarely used for suicide. Ingestion of more than one gram of copper sulphate causes features of toxicity, mainly severe gastrointestinal tract erosions, methaemoglobinemia, acute kidney injury, intravascular haemolysis, and acute hepatitis. A dose of more than 10g is lethal. The management is mainly supportive. Copper chelation with penicillamine, edetate calcium disodium (EDTA) and British anti-Lewisite (BAL) can be used to minimize the toxicity. Exchange transfusion for severe methemoglobinemia has been attempted with variable success.We report a lethal case of poisoning with 75g of copper sulphate resulting in severe methaemoglobinemia, intravascular haemolysis, gastrointestinal bleeding and multi-organ failure. Exchange transfusion was carried out without success and the patient succumbed to death on the third day of the poisoning. Though it is rare, the fatality of copper sulphate poisoning necessitates proper knowledge about manifestations and management options.

Severe acute kidney injury related to haemolysis after pulsed field ablation for atrial fibrillation.

Pulsed field ablation (PFA) has been proposed as a novel alternative to radiofrequency (RF) and cryoablation in the treatment of atrial fibrillation (AF). Following the occurrence of two cases of acute kidney injury (AKI) secondary to haemolysis after a PFA procedure, we evaluated haemolysis in a cohort of consecutive patients. Two cases of AKI occurred in last May and June 2023. AKI was secondary to acute and severe haemolysis after a PFA procedure. From June 2023, a total of 68 consecutive patients (64.3 ± 10.5 years) undergoing AF ablation with PFA were enrolled in the study. All patients had a blood sample the day after the procedure for the assessment of haemolysis indicators. The pentaspline PFA catheter was used with a total number of median applications of 64 (54; 76). Nineteen patients (28%) showed significantly depleted haptoglobin levels (<0.04 g/L). A significant inverse correlation was found between the plasma level of haptoglobin and the total number of applications. Two groups were compared: the haemolysis+ group (haptoglobin < 0.04 g/L) vs. the haemolysis- group. The total number of applications was significantly higher in the haemolysis+ group vs the haemolysis - group respectively 75 (62; 127) vs 62 (54; 71) P = 0.011. More than 70 applications seem to have better sensitivity and specificity to predict haemolysis. Intravascular haemolysis can occur after certain procedures of PFA. Acute kidney injury is a phenomenon that appears to be very rare after a PFA procedure. However, caution must be exercised in the number of applications to avoid severe haemolysis.

Evaluation of Safety and Efficacy of Amniotic Mesenchymal Stem Cells for POI in Animals.

The efficacy of human amniotic mesenchymal stem cell (hAMSC) ovarian injection in improving ovarian function in primary ovarian insufficiency (POI) patients has been shown in some reports. However, the safety and efficacy of hAMSC vein injection remains unclear. In this study, we evaluated the safety and efficacy of hAMSC intravenous injection in cynomolgus macaques and SD rats and provided evidence for clinical trials. The hAMSCs were transplanted three times in SD rats at low, medium, and high doses. The animal behavior and biochemical and biophysical parameters were routinely monitored on a 2-month period posttransplantation, and histopathologic examinations were also performed. Experiments on the acute toxicity, allergy test, and hemolysis test showed that hAMSCs possess good biocompatibility. Our results showed that the maximum tolerated dose of hAMSCs in SD rats was 4.0 × 107 cells/kg. The maximum safe dose with three injections of hAMSCs in SD rats was 5.0 × 106 cells/kg. In addition, the results demonstrated that hAMSCs may restore POI rat ovarian function after two injections of 2.5 × 106 cells/kg or 5.0 × 106 cells/kg, which improved the disturbed estrous cycle, hormone levels, and ovarian lesions induced by pZP3. In conclusion, the preclinical results suggested that the transplantation of hAMSCs may be safe and efficacious for SD rats at doses of 5.0 × 106 cells/kg and lower.

Prevalence and molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Senoi Malaysian Orang Asli population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder characterized by reduced G6PD enzyme levels in the blood. This condition is common in populations exposed to malaria; an acute febrile disease caused by Plasmodium parasites. G6PD-deficient individuals may suffer from acute hemolysis following the prescription of Primaquine, an antimalarial treatment. The population at risk for such a condition includes the Senoi group of Orang Asli, a remote indigenous community in Malaysia. This study aimed to elucidate the G6PD molecular heterogeneity in this subethnic group which is important for malaria elimination. A total of 662 blood samples (369 males and 293 females) from the Senoi subethnic group were screened for G6PD deficiency using a quantitative G6PD assay, OSMMR2000-D kit with Hb normalization. After excluding the family members, the overall prevalence of G6PD deficiency in the studied population was 15.2% (95% CI: 11-19%; 56 of 369), with males (30 of 172; 17.4%) outnumbering females (26 of 197; 13.2%). The adjusted male median (AMM), defined as 100% G6PD activity, was 11.8 IU/gHb. A total of 36 participants (9.6%; 26 male and 10 female) were deficient (<30% of AMM) and 20 participants (5.4%; 4 male and 16 female) were G6PD-intermediate (30-70% of AMM). A total of 87 samples were genotyped, of which 18 showed no mutation. Seven mutations were found among 69 genotyped samples; IVS11 T93C (47.1%; n = 41), rs1050757 (3'UTR +357A>G)(39.1%; n = 34), G6PD Viangchan (c.871G>A)(25.3%; n = 22), G6PD Union (c.1360C>T)(21.8%; n = 19), c.1311C>T(20.7%; n = 18), G6PD Kaiping (c.1388G>A)(8.0%; n = 7), and G6PD Coimbra (c.592C>T)(2.3%; n = 2). Our analysis revealed 27 hemizygote males, 18 heterozygote females, 7 homozygote females, and 2 compound heterozygote females. This study confirms the high prevalence of G6PD deficiency among the Senoi Malaysian Orang Asli, with a significant degree of molecular heterogeneity. More emphasis should be placed on screening for G6PD status and proper and safe use of Primaquine in the elimination of malaria among this indigenous population.

Use of nebulized ketamine for subarachnoid block in paediatric patient with g6pd deficiency: A case report

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect with male predominance. Patients with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency may face acute haemolysis precipitated by infection, certain medications and some of the anaesthetic drugs. Ketamine helps in providing anxiolysis, analgesia and sedation. Here, we report successful use of nebulized ketamine in a child to give subarachnoid block with G6PD deficiency undergoing below umbilical procedure.

52-Week Open-Label Extension Data from a Phase 2 Study Evaluating the Safety and Efficacy of Pozelimab and Cemdisiran Combination Therapy in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Switched from Eculizumab

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired disorder, leading to impaired expression of complement-regulating proteins on the surface of hematopoietic cells. Complement component C5 inhibitors are part of the standard of care for patients with PNH; however, these are generally intravenous treatments. Pozelimab and cemdisiran are investigational agents with a small volume subcutaneous (SC) once every 4 weeks maintenance regimen that may be self-administered. Both inhibit terminal complement through complementary mechanisms of action. Cemdisiran is an N-acetylgalactosamine-conjugated small interfering RNA that suppresses liver production of C5, while pozelimab is a fully human monoclonal antibody inhibitor of C5. The efficacy and safety of the combination of pozelimab and cemdisiran was evaluated in an open-label, single-arm study in patients with PNH who switched from eculizumab therapy (NCT04888507). The completed safety and efficacy data of the optional 52-week open-label extension period (OLEP) are presented. Methods: Patients who completed the 32-week open-label treatment period (OLTP) were offered to participate in an optional 52-week OLEP. Patients were adults with PNH who had switched from stable eculizumab therapy to the combination (pozelimab 400 mg and cemdisiran 200 mg) SC every 4 weeks in the OLTP. The study enrolled two patients who were previously treated with higher doses of eculizumab (1200 mg or 1500 mg every two weeks). The results of the 32-week OLTP have been previously presented; the results of the subsequent 52-week OLEP are presented here. Results: All five patients who completed the OLTP were enrolled in and completed the OLEP. After completing the OLEP, all patients transitioned to an expanded access program to continue the combination of pozelimab and cemdisiran. At baseline of the OLTP, lactate dehydrogenase (LDH) was well controlled on eculizumab and remained controlled during the 32-week OLTP. During the 52-week OLEP, no patient had an LDH greater than 1.5 x the upper limit of normal (ULN; Figure) at any of the scheduled study visits or met the protocol criteria for breakthrough hemolysis (either by central or local laboratory values; defined as an increase in LDH [LDH ≥2 x ULN if pre-treatment LDH ≤1.5 x ULN, or LDH ≥2 x ULN subsequent to initial achievement of LDH ≤1.5 x ULN if pre-treatment LDH &amp;gt;1.5 x ULN] with concomitant signs or symptoms associated with hemolysis). The two patients who previously received higher doses of eculizumab also maintained control of LDH levels throughout the OLTP and OLEP. Four of five patients remained transfusion free, but one patient required a blood transfusion while hospitalized with an acute complement-activating condition. This patient experienced two serious and severe treatment-emergent adverse events of respiratory infection and consequently acute hemolysis that did not meet the trial criteria for breakthrough hemolysis but was reported as an adverse event based on clinical judgement. The investigator and sponsor assessed these events as not treatment related. CH50, a measure of terminal complement activity at fixed time points, remained suppressed throughout the study in all patients. No other serious or severe adverse events were reported. There were no meningococcal infections, thrombotic events, or TEAEs leading to death. Conclusions: Results suggest that, in patients with PNH transitioning from eculizumab treatment, the combination of pozelimab and cemdisiran was generally well tolerated and provided long term sustained control of intravascular hemolysis without any breakthrough hemolysis events. Findings support the ongoing development of pozelimab and cemdisiran combination therapy.

A Paradoxal Reaction from Intravenous Immunoglobulin

Introduction: Intravenous immunoglobulin (IVIG) is among the commonly used agents for many autoimmune conditions, such as chronic inflammatory demyelinating polyneuropathy (CIDP), a progressive neurologic disorder that is characterized by weakness and sensory loss. While rare, adverse effects stemming from IVIG have been noted, these usually occur during or right after the infusion. Hematopoietic adverse events leading to anemia have been documented but are extremely rare. Two cases of IVIG-associated thrombocytopenia have been reported. We present a case of IVIG-induced thrombocytopenia in a patient with CIDP. Case Presentation: A 73-year-old female presented with severe back pain, absent reflexes, worsening sensory loss, and proximal and distal weakness resulting from her CIDP. She received 1000 mg of IV methylprednisolone and 2 grams per kilogram of IVIG (Gamunex) to manage her presenting symptoms. Patient symptoms improved and was subsequently discharged from the hospital. Following the treatment regiment in the hospital she had 2 subsequent infusions of IVIG in the outpatient setting, scheduled 2 weeks apart. On follow up, her platelet count dropped from 333,000 noted at time of hospital discharge to 35,000, 9 days after her second outpatient infusion of IVIG. No known antiplatelet antibodies were found; a formal thrombocytopenic workup for underlying causes was negative. Her count was restored once IVIG was withheld. No other treatment was implemented, and no other changes were made. Discussion: In a retrospective study of patients receiving IVIG, headache and fatigue were the most common adverse reactions. Less frequently, observed events were back pain and changes in blood pressure (mostly tachycardia). Serious complications such as anaphylaxis, infection or cardiac infarction have been noted. Hematological effects such as Coombs negative hypochromic anemia, autoimmune pure red cell aplasia, acute hemolysis, thrombosis, and embolism were stated to be extremely rare. These side effects generally occurred within 6 h after the start of the infusion, and lowering the infusion rate led to an improvement in the symptoms. However, rare late-onset adverse effects (LAe) have been described, none of which describe thrombocytopenia as a possibility. The temporal association between IVIG administration and the rapid decline in this patient's platelet count suggested a possible link. A comprehensive workup excluded common causes of cytopenia, such as viral infections (hepatitis B&amp;C) and nutritional deficiencies (folic acid and copper). The exact mechanism underlying IVIG-induced thrombocytopenia remains unclear. Proposed mechanisms include immune-mediated destruction of platelets or drug-dependent antibody formation. Prompt recognition and appropriate management are crucial to prevent complications associated with severe thrombocytopenia. Our case highlights the significance of monitoring platelet counts in individuals receiving IVIG. Physicians and other providers should know the potential risk of IVIG-induced thrombocytopenia and promptly evaluate any unexplained platelet count decline after infusion. Further research is needed better to understand this rare complication's pathogenesis and risk factors. Heightened vigilance and early intervention can ensure optimal outcomes for IVIG therapy patients. While our patient had no complications from the developed thrombocytopenia, subsequent infusions will be needed for her inevitable CIDP flares. Closer observation and frequent lab draws will be needed to mitigate any future IVIG-associated thrombocytopenia.

Hemolysis and Free Heme Impact Therapeutic Activity of Anti-CD20 Antibody

Hemolysis is a process of destruction of erythrocytes that can occur in different hereditary or acquired pathologies. It is accompanied by release of hemoglobin and heme, which both manifest potent pro-oxidative and pro-inflammatory activities. If released in large quantities hemoglobin and heme can directly contribute to systemic inflammation and tissue injury in hemolytic diseases. Moreover, it was demonstrated that heme binds to a significant fraction (ca. 10 %) of human antibodies (Abs) and this binding can result in considerable functional changes. Thus, heme-bound human IgG acquire reactivity towards a large set of unrelated proteins, including autoantigens. In a previous study we observed that 14 % of a repertoire of 117 clinical-stage therapeutic mAbs are able to bind heme and as a result they acquired autoreactivity and polyreactivity. Among these Abs some are specific for CD20 and used in lymphoma therapy (e.g. Rituximab). Importantly, therapeutic mAbs can be administered in patients with ongoing hemolysis. Thus, it is of critical importance to decipher molecular mechanism and functional consequences of interaction of heme with therapeutic mAbs and understand how the therapy of lymphoma can be affected by underling hemolysis and heme release. The present study has the following objective: to elucidate the effect of heme on the therapeutic activity of anti-CD20 therapy in in vitro and in vivo models of B cell lymphoma. Effect of heme on anti-CD20 therapeutic Abs was assessed by i) binding assays - ELISA, western blot; protein microarrays; absorbance spectroscopy; surface plasmon resonance, and ii) molecular modeling. The impact of heme on functional and therapeutic activity of Rituximab was analyzed by i) site-directed mutagenesis; ii) flow cytometry; iv) in vitro and in vivo models of human B cell lymphoma. Our data reveled molecular and functional details about the interaction of heme with Rituximab and other anti-CD20 Abs. Thus, we characterized the interaction of Abs with heme, and identified in case of Rituximab the putative binding site for heme that overlapped with antigen binding site. By using a protein array with &amp;gt;9800 human proteins, we identified the target proteins of heme-bound Rituximab. A mouse model of human B cell lymphoma revealed that the therapeutic activity of Rituximab was compromised following exposure to cell free heme under condition of acute intravascular hemolysis. Our study delineates that a fraction of currently used therapeutic mAbs show high sensitivity to heme and their therapeutic activity can be compromised under hemolytic conditions. This finding suggests that therapeutic interventions that reduce free heme and /or intravascular hemolysis should precede therapy with these Abs. Moreover, we identified sequence features of Abs that determine the sensitivity to heme. This finding can help to reduce sensitivity of heme of therapeutic Abs by protein engineering.

A Case Report of a Patient with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan Who Underwent Major Surgery

Paroxysmal Nocturnal Hemoglobinuria (PNH) is characterized by intravascular hemolysis, thrombosis and bone marrow failure. The appearance of the anti-C5 monoclonal antibody eculizumab revolutionized the treatment of PNH, controlling hemolysis and the incidence of thrombosis. However, some patients persist with anemia, due in part to extravascular C3-mediated hemolysis. More recently, the anti-C3 monoclonal antibody pegcetacoplan, which blocks the most proximal part of the complement cascade, has been marketed in Europe, achieving improvements in anemia in these patients. However, intercurrent infectious episodes or surgical interventions can trigger a hemolytic flare, so dose adjustments are necessary to prevent their occurrence. There is hardly any published information or established consensus on how to treat these patients. We present this case as an example of a successful treatment of a patient diagnosed with PNH under treatment with pegcetacoplan who has undergone major surgery. A 67 year-old man was diagnosed with aplastic anemia in 1997 and treated with immunosuppression (cyclosporine and oxytosone). In 2000, he presented his first intravascular hemolytic crisis with HPN clone detection. He presented several intravascular hemolytic crises for which he was treated with erythropoiesis-stimulating agents, corticosteroids and transfusions. In 2010, due to deterioration of renal function because of acute hemolysis episode, he started treatment with eculizumab. A reduction in the number of hemolytic crises was observed. However, he required an increase in the dose and frequency of administration of eculizumab due to pharmacokinetic breakthrough hemolysis. After one month of treatment, a positive direct coombs test appeared and presented anemia due to extravascular hemolysis, for which he again required treatment with corticosteroids on specific occasions. For this reason, in December 2022, he started treatment with pegcetacoplan at the usual dose of 1080 mg twice a week subcutaneously (sc). Prior to the start of pegcetacoplan, the patient had hemoglobin levels of 10.3 g/dL, hyperbilirubinemia of 3.2 mg/dL (indirect 2.6 mg/dL), consumed haptoglobin, elevated lactate dehydrogenase (LDH) of 281 U/L and reticulocytosis of 5-6%. Subsequently, since the beginning of pegcetacoplan, he presented clinical improvement, stable hemoglobin (12-13 g/dL) and normalization of reticulocytes, LDH and bilirubin levels. The haptoglobin has remained low until the present time. In June 2023, the patient underwent major surgery consisting of radical prostatectomy due to a benign prostatic hypertrophy. Suspecting that it might provoke a hemolytic crisis due to surgical stress, the dose of pegcetacoplan was increased as recommended by clinical experts to a dose of 1080 mg every 72 hours sc from one week prior to surgery until one week after. The procedure was carried out without incident and without an increase in hemolysis parameters. This is the first case report of a patient with PNH treated with pegcetacoplan undergoing major surgery in Spain. In this patient, the perioperative dose increase was successful in preventing the development of a hemolytic crisis.

Abstract 12507: Impella versus Intra-Aortic Balloon Pump in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Meta-Analysis

Background: Acute myocardial infarction complicated by cardiogenic shock (AMICS) requires mechanical circulatory support, with IABP and Impella being commonly used options. The IABP's survival benefit is uncertain, and guideline recommendations differ. Studies comparing Impella and IABP have yielded mixed results and reported varying complication rates. Aim: This meta-analysis aims to comprehensively evaluate the effectiveness and safety of Impella versus IABP in AMICS. Methods: A systematic search was conducted in PubMed, EMBASE, Cochrane, and clincialtrials.gov from inception to April 2023 to identify studies comparing Impella and IABP in AMICS. A meta-analysis was performed to assess the short-term mortality as the primary efficacy endpoint, along with major bleeding, limb complications, acute kidney injury (AKI), stroke, and hemolysis as safety endpoints of interest. Results: A total of 10 studies (2 RCTs, 8 observational) with 6,634 patients were included in the final analysis. No significant difference was found in 30-day mortality (OR=1.03; 95% CI=0.74-1.42; p=0.87), in-hospital mortality (OR=1.14; 95% CI=0.45-2.85; p=0.79) and all-cause mortality (OR=1.00; 95% CI=0.55-1.81; p=0.99) between Impella and IABP. However, the analysis revealed a higher risk of major bleeding with Impella compared to IABP (OR=2.12; 95% CI=1.32-3.42; p=0.002) and an increased likelihood of limb complications (OR=3.86; 95% CI=1.57-9.48; p=0.003). There was no significant difference in the incidence of AKI (OR=0.91; 95% CI=0.56-1.48; p=0.70) and stroke (OR=0.72; 95% CI=0.42-1.24; p=0.24) between the two groups. Notably, the risk of hemolysis was significantly higher in the Impella group (OR=11.35; 95% CI=1.99-64.69; p=0.006). Conclusion: Impella and IABP showed similar short-term mortality, AKI, and stroke rates in AMICS patients. However, Impella was associated with a higher risk of major bleeding, limb complications, and hemolysis.

Double-edged functions of hemopexin in hematological related diseases: from basic mechanisms to clinical application.

It is now understood that hemolysis and the subsequent release of heme into circulation play a critical role in driving the progression of various diseases. Hemopexin (HPX), a heme-binding protein with the highest affinity for heme in plasma, serves as an effective antagonist against heme toxicity resulting from severe acute or chronic hemolysis. In the present study, changes in HPX concentration were characterized at different stages of hemolytic diseases, underscoring its potential as a biomarker for assessing disease progression and prognosis. In many heme overload-driven conditions, such as sickle cell disease, transfusion-induced hemolysis, and sepsis, endogenous HPX levels are often insufficient to provide protection. Consequently, there is growing interest in developing HPX therapeutics to mitigate toxic heme exposure. Strategies include HPX supplementation when endogenous levels are depleted and enhancing HPX's functionality through modifications, offering a potent defense against heme toxicity. It is worth noting that HPX may also exert deleterious effects under certain circumstances. This review aims to provide a comprehensive overview of HPX's roles in the progression and prognosis of hematological diseases. It highlights HPX-based clinical therapies for different hematological disorders, discusses advancements in HPX production and modification technologies, and offers a theoretical basis for the clinical application of HPX.

A Study of Glucose-6-Phosphate Dehydrogenase Deficiency among Children attending the Emergency Hospital in Zakho City Kurdistan Region, Iraq

Background: G6PD deficiency, which affects 400 million individuals globally, is an X-linked hereditary enzymopathy that causes acute hemolysis after exposure to specific oxidative agents such as fava beans, more than 37 drugs, and infections viral or bacterial. Neonatal jaundice worsened by kernicterus is one of the condition's significant consequences. It can be prevented by avoiding the oxidative factors that cause a hemolytic episode alongside neonatal screening programs for early detection of afflicted individuals. Objectives: This research aimed at investigating the variability in clinical and biochemical manifestations among children with G6PDD. This is the first study to be carried out in the Zakho area. Methods: A cross-sectional study was used, recruiting 112 children attending Zakho Emergency Hospital from January 2022 to April 2023. Laboratory aids involved in obtaining CBC, liver enzyme activities, and blood grouping were all investigated. The IBM SPSS 26 program was used to analyze the obtained data. Results: There was no statistically significant difference between male and female patients in terms of age, time of admission, hemoglobin level, WBC count, and liver enzymes. The majority of cases who visited Zakho Emergency Hospital within 72 hours of exposure to the triggering agent were males (67.9%), with the most common clinical features being jaundice, dark urine, and abdominal pain. Conclusion: In this study, the three main symptoms in G6PD deficient patients with acute hemolysis were pallor, jaundice, and black urine. These signs appeared several hours or even days after consuming fava beans. The primary clinical symptoms and the patient's gender, family history, or prior newborn jaundice were not related, according to our research.

Evaluation of the prevalence of glucose-6-phosphate dehydrogenase deficiency in Al-Qassim region of Saudi Arabia

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder that is more common in males, is the most prevalent blood enzyme deficiency, affecting 5% of the population worldwide. Its prevalence in Saudi Arabia varies greatly from one region to another (4.7% to 12%), and no related data are available for the country’s Al-Qassim region.MethodsThis was a retrospective medical record-based study. Eligible patients were those who visited Dr. Sulaiman Al-Habib Hospital in Al-Qassim, Saudi Arabia, between June 2021 and November 2022, and underwent the test for G6PD enzyme deficiency. The study sample consisted of (n = 313) randomly selected Saudi patients. G6PD enzyme activity was evaluated using spectrophotometry.ResultsThe prevalence of G6PD deficiency was 2.9%. The proportion of male patients (100%) was significantly higher than that of female patients. 88.9% of patients with G6PD deficiency experienced episodes of acute hemolysis and reported a history of favism, whereas 77.8% of the patients had a family history of favism.ConclusionThe prevalence of G6PD deficiency was low in Al-Qassim region of Saudi Arabia.

Mefenamic acid triggered autoimmune hemolytic anemia in a child: a rare case report

Autoimmune hemolytic anemia (AIHA) is characterized by the abnormal production of antibodies that bind to antigens on the surface of red blood cells (RBC), resulting in RBC destruction. Here we describe a rare case of mefenamic acid-induced AIHA in a 3-year-old boy who developed acute hemolysis after ingestion of mefenamic acid for febrile illness. The aim is to draw the attention of pediatricians to one of the side effects of mefenamic acid, the drug which is very commonly used as an antipyretic.

Intravascular hemolysis triggers NAFLD characterized by a deregulation of lipid metabolism and lipophagy blockade.

Intravascular hemolysis is a common feature of different clinical entities, including sickle cell disease and malaria. Chronic hemolytic disorders are associated with hepatic damage; however, it is unknown whether heme disturbs lipid metabolism and promotes liver steatosis, thereby favoring the progression to nonalcoholic fatty liver disease (NAFLD). Using an experimental model of acute intravascular hemolysis, we report here the presence of liver injury in association with microvesicular lipid droplet deposition. Hemolysis promoted serum hyperlipidemia and altered intrahepatic triglyceride fatty acid composition, with increments in oleic, palmitoleic, and palmitic acids. These findings were related to augmented expression of transporters involved in fatty acid uptake (CD36 and MSR1) and deregulation of LDL transport, as demonstrated by decreased levels of LDL receptor and increased PCSK9 expression. Hemolysis also upregulated hepatic enzymes associated with cholesterol biosynthesis (SREBP2, HMGC1, LCAT, SOAT1) and transcription factors regulating lipid metabolism (SREBP1). Increased LC3II/LC3I ratio and p62/SQSTM1 protein levels were reported in mice with intravascular hemolysis and hepatocytes stimulated with heme, indicating a blockade of lipophagy. In cultured hepatocytes, cell pretreatment with the autophagy inductor rapamycin diminished heme-mediated toxicity and accumulation of lipid droplets. In conclusion, intravascular hemolysis enhances liver damage by exacerbating lipid accumulation and blocking the lipophagy pathway, thereby promoting NAFLD. These new findings have a high translational potential as a novel NAFLD-promoting mechanism in individuals suffering from severe hemolysis episodes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The Effect of Respiratory Viral Infections on Breakthrough Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolysis and thrombosis and is associated with significant morbidity and mortality. Although complement inhibitors have significantly changed the outcomes in PNH patients, breakthrough hemolysis (BTH) may still occur as a response to stress factors such as pregnancy, surgery, and infections. Despite the well-described association between bacterial infections and hemolysis in PNH patients, little is known about the effect of respiratory viruses on triggering hemolytic episodes. This is the first study, to our knowledge, addressing this question. We retrospectively analyzed 34 patients with PNH disease between 2016 and 2018, who were on eculizumab treatment and who presented with respiratory symptoms and were subsequently tested for 10 respiratory viruses (influenza A, influenza B, parainfluenza, respiratory syncytial virus, adenovirus, rhinovirus, and human metapneumovirus). NTS+ patients had higher inflammatory markers, with the majority requiring antibiotics. Acute hemolysis, along with a significant drop in hemoglobin, was noted in the NTS+ group, with three of them requiring a top-up transfusion and two requiring an extra dose of eculizumab. Furthermore, the time from the last eculizumab dose was longer in the NTS+ patients who had BTH, than those who did not. Our data indicate that respiratory virus infections pose a significant risk for BTH in PNH patients on complement inhibitor treatment, underlining the need for regular screening and close monitoring of patients with respiratory symptoms. Furthermore, it implies a higher risk for patients who are not established on complement inhibitors, suggesting the necessity for greater vigilance in these patients.

A Case of Acute Intravascular Hemolysis During Dialysis: A Quiz

A Case of Acute Intravascular Hemolysis During Dialysis: A Quiz

The potential role of vitamin E in patients with glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis.

As an antioxidant, vitamin E (VitE) may benefit the erythrocytes by protecting glutathione from oxidation by free radicals and peroxide-generating processes. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines when reporting this systematic review. We searched 6 electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) until May 8, 2022. We included all relevant studies. According to the study design, the Cochrane assessment tool (Risk of Bias 2), Risk Of Bias In Non-randomized Studies - of Interventions checklists, and National Institutes of Health tools were used to assess the risk of bias.Continuous data were pooled as a mean difference (MD) with a relative 95% confidence interval. The protocol was registered on PROSPERO (CRD42022333848). Six studies were included in the meta-analysis with a total of 181 patients. Compared with the control group, VitE significantly improved the hemoglobin level for chronic hemolysis (MD = 2.72 g/dL, P < .0001) and for acute hemolysis (MD = 1.18 g/dL, P < .0001). It also decreased the reticulocyte level for chronic hemolysis (MD = -1.39 P < .0001) and for acute hemolysis (MD = -1.42%, P < .0001). For before and after studies, the use of VitE significantly improved the level of packed cell volume (MD = 0.56%, P < .00001), red blood cell half-life (MD = 2.19 days, P < .0001), and decreased the reticulocytes level (MD = -1.41%, P < .00001). Among patients with glucose-6-phosphate dehydrogenase deficiency, VitE might provide benefits such as increasing the hemoglobin, packed cell volume levels, red blood cell half-life, and decreasing the reticulocyte level, so reducing hemolysis. Further high-quality, well-designed randomized controlled trials are recommended.