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Acute renal failure (ARF) with severe loin pain and patchy renal vasoconstriction is a rare syndrome described as an anaerobic exercise-induced acute kidney injury (AKI) without rhabdomyolysis. The characteristic computed tomography (CT) finding is multiple patchy wedge-shaped delayed contrast enhancement in the kidney. The syndrome is named as a clinical syndrome of ARF with severe loin pain after anaerobic exercise (ALPE). A 16-year-old Japanese boy was admitted to our hospital for vomiting and severe loin pain after Japanese fencing. He had kidney dysfunction with slightly increased serum creatine phosphokinase and was eventually diagnosed with ALPE based on the characteristic finding on delayed renal CT scans. He had no predisposing factors for ALPE, such as renal hypouricemia or analgesic use prior to the exercise; however, he had pigmenturia at the onset, which is an unusual finding for ALPE. The pigmenturia proved to be hemoglobinuria due to intravascular hemolysis, indicated by increased serum levels of indirect bilirubin and lactate dehydrogenase, an undetectable level of serum haptoglobin, and absence of red blood cells and myoglobin in the urine. The hemolysis following strenuous steps on a hard floor suggested that the phenomenon was march hemoglobinuria. Our patient is the first reported example in which ALPE developed in the setting of hemoglobinuria due to mechanical intravascular hemolysis.

Background March hemoglobinuria is caused by a hemolytic mechanism due to transient hematuria after physical exercise which, although rare, may lead to acute kidney injury. We report a case of a patient with march hemoglobinuria induced by kendo, which was diagnosed by the presence of Berlin blue iron staining in the proximal tubules through renal biopsy. Case presentation A 15-year-old male complained of fever (37 °C), general malaise, and nausea after hard kendo sessions. Laboratory findings revealed indirect bilirubin dominant hyperbilirubinemia (total bilirubin 3.8 mg/dL), high lactate dehydrogenase (LDH), and acute kidney injury (serum creatinine: 3.11 mg/dL and estimated glomerular filtration rate: 26 mL/min/1.73m2). Urine test was positive for occult blood but without hematuria. Renal biopsy was performed to clarify the cause of renal injury, which showed minor glomerular abnormalities. Meanwhile, hemosiderin deposition was identified in the proximal tubules by Berlin blue iron staining, and lysosomes were observed to contain granular iron. In addition to clinical background of strenuous kendo exercise, renal biopsy led to a definitive diagnosis of march hemoglobinuria. Conclusions March hemoglobinuria is a hemolytic disease that can occur after intense exercise, especially kendo. Considering its rarity due to the lack of critical symptoms, it is important to note that occult blood-positive findings may be indicative of march hemoglobinuria if the patient underwent strenuous exercise. Therefore, clinicians should be aware of this possibility to provide timely and appropriate treatment.

A 7-y-old male Labrador Retriever dog was presented because of acute onset of dark-colored urine after a hunting session the day prior. Moderate hemoglobinemia was observed, associated with transient hemoglobinuria and hematuria with no concurrent evidence of underlying urinary tract disease. The patient’s clinical signs resolved within 36 h post-exercise without specific treatment. The concurrent occurrence of exertional hemolysis and hematuria in a dog is uncommon; these conditions are commonly reported separately in human athletes.

Aim: Favism is characterized as acute anemia, due to Glucose-6-phosphate dehydrogenase (G6PD) deficiency as a result of fava beans intake. It is associated with paleness, jaundice, and hemoglobinuria. In this study, signs, symptoms and therapeutic findings of the patients with hemolysis due to G6PD deficiency were investigated in Shahid Madani Hospital of Khorramabad, Lorestan. Methods: This is a single-center cross-sectional descriptive study that was conducted on all children with G6PD deficiency-induced hemolysis. Results: 308 children (64.3% male and 35.7% female) were included in this study. The most common complaint was jaundice (82.5%) and the most common cause of hemolysis was the intake of fava bean (85.7%). 68% of the children were treated with hydration/fluid therapy. Blood transfusion was conducted in 36.36% of the cases and the mean of blood administered was 18.9 cc/kg. Conclusion: In this study, hydration therapy was performed in most of the children presenting favism. Also, the incorrect calculation of the amount of blood needed for transfusion increased the frequency of blood transfusions and prolonged hospitalization time.

Aims Accidental contact with the Lonomia obliqua caterpillar is a common event in southern Brazil. Envenomed victims present consumption coagulopathy, which can evolve to acute kidney injury (AKI). In the present study, we searched for AKI biomarkers and changes in molecular pathway signatures through urine proteomic analysis. Methodology Male Wistar rats were injected with L. obliqua venom (1.5 mg/kg, via s.c.) or 0.9 % NaCl and distributed into metabolic cages. After 24 h, urine was obtained, and the set of differentially regulated proteins was analyzed by MudPIT technology in an OrbiTRAP mass spectrometer. Results L. obliqua venom leads to an increase in urine output and water and electrolyte excretion and to an increase in the albumin to creatine ratio in urine. The proteomic analysis revealed an up-regulation of tubular injury biomarkers, such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C, in urine from envenomed rats. Several components related to the heme scavenging system were up-regulated or exclusively identified in urine from envenomed animals. There was an increase in urinary heme levels and hemoglobin subunits, hemopexin, haptoglobin, and biliverdin reductase. Similarly, kinin- and angiotensin-generating/degrading peptidases, such as kallikreins, neprilysin, plasmin, dipeptidyl peptidase IV, cathepsin D, kininogen, and neutral, basic, glutamyl, and acidic aminopeptidases, were also up-regulated in urine. Conclusions L. obliqua envenomation induced tubular and glomerular injury, probably involving heme/hemoglobin toxicity and an imbalance in the kinin/angiotensin generating/degrading system.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired clonal haematological disease characterized by complement-mediated haemolysis, bone marrow failure and venous thrombosis. Anticomplement therapy eculizumab improves survival and reduces complications. Severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2) disease 2019 (COVID-19) is associated with high incidence of both venous and arterial thrombosis in hospitalized patients with pneumonia. Deep venous thrombosis (DVT) as the presenting symptom of COVID-19 is a rare event. We describe a well-controlled PNH patient on eculizumab for more than 5 years who presented with DVT, while on warfarin, as the first sign of COVID-19. To our knowledge, this is the first described case of DVT in a PNH patient with COVID-19.

Background Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. Methods This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb Discussion This study evaluates the potential benefit of a universal radical cure for both P. vivax and P. falciparum in different endemic locations. If found safe and effective universal radical cure could represent a cost-effective approach to clear otherwise unrecognised P. vivax infections and hence accelerate P. vivax elimination. Trial registration NCT03916003. Registered on 12 April 2019.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement-mediated intravascular hemolysis and thrombosis. The increased incidence of PNH-driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement-mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti-thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in-part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.

Objective To document a case of transient AB blood type indicated by immunochromatography in a type B cat following administration of an incompatible type A transfusion. Case summary A 7-month-old neutered male domestic longhair cat was evaluted for anemia, pigmenturia, and intravascular hemolysis 1 day after receiving a feline whole blood transfusion. Neither blood donor nor patient had been blood-typed or crossmatched. The cat presented in shock with a severe non-regenerative anemia, hyperlactatemia, hyperbilirubinemia, hemoglobinemia, hemoglobinuria, and a positive saline slide agglutination test. Immunochromatographic blood typing tests initially indicated the cat had type AB blood, but crossmatch tests with blood from type A and type B donors suggested that the cat was type B. The cat was transfused with type B packed red blood cells without apparent complications and clinically improved. The cat's blood type reverted to type B once all the previously transfused type A cells were cleared from circulation. Furthermore, the original donor was subsequently identified as a Siamese cat and confirmed to have type A blood. While the cause of the original anemia remained unknown, the cat completely recovered and regained a normal hematocrit. New or unique information provided This is the first documented report of transient AB blood type diagnosed using immunochromatography after a transfusion mismatch and shows the utility of crossmatching or back-typing to identify the cat's correct blood type during the hemolytic transfusion reaction.

HbE/Beta thalassemia (HbE/β-thalassemia) is one of the common genetic disorders in South East Asia. It is heterogeneous in its clinical presentation and molecular defects. There are genetic modifiers which have been reported to influence the disease severity of this disorder. The aim of this study was to determine the genetic polymorphisms which were responsible for the disease clinical diversity. A case-control study was conducted among Malay transfusion-dependent HbE/β-thalassemia patients. Patients who were confirmed HbE/β-thalassemia were recruited and genotyping study was performed on these subjects. Ninety-eight patients were selected and divided into moderate and severe groups based on clinical parameters using Sripichai scoring system (based on hemoglobin level, spleen size, growth development, the age of first transfusion and age of disease presentation). Forty-three (44.9%) and 55 (56.1%) patients were found to have moderate and severe clinical presentation, respectively. Genotyping analysis was performed using Affymetrix 6.0 microarray platform. The SNPs were filtered using PLINK and Manhattan plot by R software. From the GWAS results, 20 most significant SNPs were selected based on disease severity when compared between moderate and severe groups. The significant SNPs found in this study were mostly related to thalassemia complications such as rs7372408, associated with KCNMB2-AS1 and SNPs associated with disease severity. These findings could be used as genetic predictors in managing patients with HbE/β-thalassemia and served as platform for future study.

Intravascular hemolysis is relatively rare but can lead to acute kidney injury (AKI), from increased destruction of erythrocytes and release of free hemoglobin. Since hemolysis and hemoglobinuria are known causes of acute kidney injury we sought to define clinicopathologic findings and outcomes of patients with hemolysis-associated hemoglobin cast nephropathy through a retrospective analysis of 27 cases. The mean patient age was 47 years (range 19-79) and the female-to-male ratio was 1.3:1. All patients presented with AKI with a mean serum creatinine of 8.0 (range 2.9-17.0) mg/dL. Etiologies included autoimmune hemolytic anemia (30%), medication (26%), paroxysmal nocturnal hemoglobinuria (7%), procedural/mechanical causes (7%), transfusion of incompatible blood (4%), toxin ingestion (4%), disseminated intravascular coagulation (4%), and hemoglobinopathy (4%). All biopsies showed acute tubular injury and pigmented, proteinaceous casts characterized by positive hemoglobin immunohistochemistry. After a mean follow-up of nine months (range 0.5-26), the mean serum creatinine was 1.3 (range 0.6-3.3) mg/dL, with 78% of patients returning to normal kidney function. Thus, based on our clinicopathologic case series, hemolysis-associated hemoglobin cast nephropathy is an important entity for clinicians and pathologists to recognize as treatment hinges upon elimination of the pathogenic driver of intravascular hemolysis.

Defects in the regulatory components of the complement system can lead to inflammatory diseases. We present a patient who had four episodes of demyelination in the central nervous system as the only manifestation of inherited CD59 deficiency. Relapsing encephalopathy partially responsive to intravenous immunoglobulin and steroid treatments on the background of parental consanguinity suggested an inherited immune dysregulation. Next generation sequencing revealed homozygous mutation in the CD59 gene, confirmed by lack of CD59 expression on flow cytometry. Inherited CD59 deficiency is a rare autosomal recessive condition characterized by chronic hemolysis, recurrent strokes, and relapsing peripheral demyelinating neuropathy mimicking Guillain–Barré syndrome or chronic inflammatory demyelinating polyneuropathy. Recurrent central nervous system demyelinating episodes as the only manifestation has not been reported to date in inherited CD59 deficiency. This entity should be considered in the differential diagnosis of patients with early-onset recurrent neurological diseases with central or peripheral origin.

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease presenting with variable and various clinical findings. PNH might be overlooked and diagnosis may be delayed due to low awareness about PNH. This is the first multicenter study in Turkey, investigating the efficiency of diagnostic screening of PNH by multiparameter flow cytometry (FCM) according to consensus guidelines. Methods We evaluate the efficiency of consensus clinical indications for PNH testing with FCM in 1689peripheral blood samples from 20 centers between January 2014 and December 2017. Results Overall, at the 20 centers contributing to this study, PNH clone were detected in 62/1689 samples (3.6%) by FCM test. 75.8% (n = 47) of patients with PNH clone had aplastic anemia, 3.2% (n = 2) had Coombs (-) hemolytic anemia, 6.5% (n = 4) had unexplained cytopenia, 3.2% (n = 2) had MDS with refractory anemia, 1.6% (n = 1) had hemoglobinuria and 9.7% (n = 6) had others (elevated LDH, splenomegaly, etc.). In contrast, we detect no PNH clone test in patients who were screened for unexplained thrombosis. Conclusions Our study showed that current clinical indications for PNH testing are highly efficient and diagnostic screening of suspected patients for PNH with FCM is recommended. However, advanced screening algorithms are required for patients presenting with unexplained thrombosis and normal complete blood count.

Objectives Sclerotherapy is an essential component of the treatment for venous malformations, and ethanolamine oleate (EO) is known as a useful sclerosing agent. However, macroscopic haemoglobinuria (MH) and subsequent renal impairment are severe complications after sclerotherapy using EO. The present study aimed to clarify the MH risk factors for better peri-operative management of venous malformations. Methods Data collected during 130 procedures involving 94 patients who were undergoing sclerotherapy using EO for venous malformation were retrospectively analysed. Pre-operative and operative variables, including sex, age, pre-operative body mass index, location, depth, type of lesion, size, number of procedures, type of drainage vein, ratio of sclerosant to air, and injected total dose of 5% EO per body weight (BW), were examined. Univariable analysis and multivariable logistic regression were performed to determine the possible risk factors for MH. Results Following sclerotherapy, MH occurred in 27.7% of patients, but no patient developed post-operative renal impairment because of aggressive hydration and haptoglobin administration. On univariable analysis, diffuse lesion, lesion size ≥50 cm2, and total injected dose of 5% EO ≥ 0.18 mL/kg were found to be the MH risk factors. Multivariable logistic regression analysis identified a total injected dose of 5% EO ≥ 0.18 mL/kg as the significant independent factor contributing to MH risk. Conclusions Macroscopic haemoglobinuria is a reversible complication if immediate and appropriate interventions with aggressive hydration and haptoglobin administration are performed; therefore, it should be closely monitored following sclerotherapy, especially when using 5% EO ≥ 0.18 mL/kg.

The main important clinical signs in acute kidney injury (AKI) after sever Hemiscorpius lepturus envenomation in patients is associated with proteinuria, hemolysis and hemoglobinuria. Unfortunately, our limited knowledge of molecular cell death mechanism in H. lepturus induced AKI restricts the development of desirable therapeutics. So, in the present study, the potential role of necroptosis and ferroptosis in H. lepturus induced AKI were investigated in male albino mice. The animals were administrated by SC injection of venom (1, 2.5, 5 and 10 mg/kg) based on LD50 determination. After 1 and 7 days, urinalysis, stereological assessments and gene expression of Ngal, Tnf-α, Tlr-4, Ripk3, Mlkl and Acsl4 were evaluated by real time PCR. Our data revealed that upregulation of renal Ngal expression is associated with the gene over expression of Tnf-α, Tlr-4, Ripk3 and Mlkl in venom treated kidneys. We observed that the Malondialdehyde (MDA) level was increased in dose-dependent manner similar to Acsl4 gene over expression suggesting a main role of ferroptosis in hemoglobinuria mediated AKI following envenomation. Moreover, transcriptional enhancement of Tlr-4and Tnf-α receptor can cause phosphorylation of Ripk3-Mlkl complex, collapse of membrane potential and DAMPs release which intensified the inflammation cytokines in kidney. Taken together, it supposes co-existence of two separate pathways of regulated necrosis and inflammatory environment provides a promising outlook in prevention and management of hemoglobinuria induced AKI following envenomation in clinical practice.

In this study, we aimed at disclosing the main features of paroxysmal nocturnal hemoglobinuria (PNH) clones, their association with presentation syndromes, and their changes during follow-up. A large-scale, cooperative collection (583 clones from 529 patients) of flow cytometric and clinical data was entered into a national repository. Reason for testing guidelines were provided to the 41 participating laboratories, which followed the 2010 technical recommendations for PNH testing by Borowitz. Subsequently, the 30 second-level laboratories adopted the 2012 guidelines for high-resolution PNH testing, both upon order by the local clinicians and as an independent laboratory initiative in selected cases. Type3 and Type2 PNH clones (total and partial absence of glycosyl-phosphatidyl-inositol-anchor, respectively) were simultaneously present in 54 patients. In these patients, Type3 component was sevenfold larger than Type2 (p 0.001). Frequency distribution analysis of solitary Type3 clone size (N = 442) evidenced two discrete patterns: small (20% of peripheral neutrophils) and large ( 70%) clones. The first pattern was significantly associated with bone marrow failure and myelodysplastic syndromes, the second one with hemolysis, hemoglobinuria, and thrombosis. Pediatric patients (N = 34) showed significant preponderance of small clones and bone marrow failure. The majority of PNH clones involved neutrophils, monocytes, and erythrocytes. Nevertheless, we found clones made exclusively by white cells (N = 13) or erythrocytes (N = 3). Rare cases showed clonal white cells restricted only to monocytes (6 cases) or neutrophils (3 cases). Retesting over 1-year follow-up in 151 cases showed a marked clone size increase in 4 cases and a decrease in 13, demonstrating that early breaking-down of PNH clones is not a rare event (8.6% of cases). This collaborative nationwide study demonstrates a clear-cut difference in size between Type2 and Type3 clones, emphasizes the existence of just two classes of PNH presentations based on Type3 clone size, depicts an asymmetric cellular composition of PNH clones, and documents the possible occurrence of changes in clone size during the follow-up.

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a clonal disease of blood cells caused by the lack of glycosyl phosphatidyl inositol anchored proteins bound to the cell membrane. In consequence, erythrocytes lead to intravascular hemolysis upon complement activation, which promotes high risk of thrombosis, intravascular hemolytic anemia, and bone marrow failure in patients. The mechanisms of thrombosis in PNH are still poorly understood. Treatment with eculizumab reduces intravascular hemolysis and thrombotic risk, but not in all cases. Exosomes are extracellular vesicles released by cells and whose secretion is closely related to the inflammatory status. They participate in cell communication by activating signaling pathways and transferring genetic material and proteins to host cells. In consequence, exosomes may serve as surrogate biomarkers for the prognosis and/or diagnosis of a disease. Isolation of exosomes was carried out from healthy controls and from three groups of PNH patients, i.e. i) with no eculizumab treatment; ii) under treatment with eculizumab that have not suffered thrombosis; and iii) under treatment with eculizumab but that have suffered thrombosis. The miRNAome and proteome was analyzed using plasma focus miRNAs PCR panel and LC-MS analysis respectively. We found differential expression of miRNAs miR-148b-3p, miR-423-3p, miR29b-3p, miR15b-5p, let-7e-5p, miR126-3p, miR-125b-5p and miR-376c-3p as well as hemoglobin, haptoglobin, protein S and C4-binding protein in healthy controls vs PNH patients. Our results warrant further research and provide new information on the content of exosomes that could play a role in the hypercoagulable state in this disease.

The haematological benefit of standard-of-care anti-C5 treatment for haemolytic paroxysmal nocturnal haemoglobinuria is limited by residual intravascular haemolysis or emerging C3-mediated extravascular haemolysis. Therefore, the aim of this phase 2 study was to assess the safety, tolerability, pharmacokinetics and pharmacodynamics, and activity of the new complement factor B inhibitor, iptacopan, in patients with paroxysmal nocturnal haemoglobinuria who have active haemolysis despite anti-C5 therapy.In this multicentre, open-label, single-arm, phase 2 trial, we enrolled adult patients (aged 18-80 years) with paroxysmal nocturnal haemoglobinuria who showed signs of active haemolysis despite receiving eculizumab treatment. Patients were enrolled at Federico II University Hospital (Naples, Italy), Hôpital Saint-Louis (Paris, France), and University Hospital Essen (Essen, Germany). For enrolment, patients were required to show lactate dehydrogenase more than 1·5-times the upper limit of normal and a paroxysmal nocturnal haemoglobinuria type 3 erythrocyte or granulocyte clone size of 10% or greater. Patients with bone marrow failure, on systemic steroid or immunosuppressive drugs, or with severe comorbidities were excluded from the study. Iptacopan was given orally as an add-on therapy at a dose of 200 mg twice daily. The primary endpoint was the effect of iptacopan on the reduction of chronic residual intravascular haemolysis measured as change in lactate dehydrogenase from baseline value to week 13. At 13 weeks, patients could opt into a long-term study extension (ongoing), allowing for modifications of standard treatment. This trial is registered at ClinicialTrials.gov, NCT03439839.Between May 31, 2018, and April 9, 2019, ten patients had twice daily 200 mg iptacopan. Iptacopan resulted in marked reduction of lactate dehydrogenase from baseline versus at week 13 (mean 539 IU/L [SD 263] vs 235 IU/L [44], change from baseline -309·2 IU/L [SD 265·5], 90% CI -473·77 to -144·68, p=0·0081), associated with significant improvement of haemoglobin concentrations (mean 97·7 g/L [SD 10·5] vs 129·5 g/L [18·3] change from baseline 31·9 g/L [14·5], 90% CI 23·42-40·28, p0·0001). All biomarkers of haemolysis improved on iptacopan treatment. Observed haematological benefits were maintained longer than the 13-week study period, throughout the study extension, including seven patients who stopped concomitant standard-of-care treatment and continued iptacopan as monotherapy. There were no deaths or treatment-related serious adverse events during the study period. Of three non-related serious adverse events, two occurred in the same patient (one during run-in and before exposure to iptacopan).Iptacopan at a chronic dose of 200 mg twice daily was well tolerated without any major drug-related safety findings and shows lactate dehydrogenase reduction and haemoglobin normalisation in most patients with paroxysmal nocturnal haemoglobinuria at week 13 and beyond, even in monotherapy. On the basis of these data, iptacopan will be tested as monotherapy in pivotal trials investigating its haematological benefit in a broader paroxysmal nocturnal haemoglobinuria population.Novartis Institutes for Biomedical Research.

A man in his early 50s presented with jaundice, mild shortness of breath on exertion and dark urine. He had had coryzal symptoms 2 weeks prior to admission. Medical history included obstructive sleep apnoea and hypertension. His initial blood tests showed a mild hyperbilirubinaemia and acute kidney injury stage 1. Chest X-ray and CT pulmonary angiogram were negative for features suggestive of COVID-19. He later developed a drop in haemoglobin and repeat bloods showed markedly raised lactate dehydrogenase and positive direct antiglobulin test. These results were felt to be consistent with a haemolytic anaemia. A nasopharyngeal swab came back positive for COVID-19. We suspect the cause of his symptoms was an autoimmune haemolytic anaemia secondary to COVID-19 which has recently been described in European cohorts.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hemopoietic stem cell disorder characterized by the triad of hemolytic anemia, thrombosis, and impaired bone marrow function. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. Patient concerns: A 27-year-old Caucasian man with PNH presented to the Emergency Department of our hospital with acute onset shortness of breath, cough and blood in urine. Diagnosis: The patient was diagnosed with acute hemolytic exacerbation of PNH complicated with moderate COVID19 pneumonia. Outcomes: The patient was initiated with an anticoagulant unfractionated heparin, dexamethasone, and cefuroxime injection. His symptoms quickly resolved, and he was discharged after 5 days. Conclusion: The complement system activation is a critical component in the sequalae of COVID19 infection. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. Notably, C5a concentration was noted to be higher in patients with COVID19 infection. The use of complement inhibitors to attenuate immune mediated damage in COVID19 nevertheless represents a very interesting theoretical approach. However, careful consideration as to which patients may benefit will be required and the outcome of clinical trials needed.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life‐threatening hematologic disease characterized by chronic complement‐mediated hemolysis and thrombosis. Despite treatment with eculizumab, a C5 inhibitor, 72% of individuals remain anemic. Pegcetacoplan (APL‐2), a PEGylated C3 inhibitor, has the potential to provide more complete hemolysis control in patients with PNH. This open‐label, phase Ib study was designed to assess the safety, tolerability, and pharmacokinetics of pegcetacoplan in subjects with PNH who remained anemic during treatment with eculizumab. Pharmacodynamic endpoints were also assessed as an exploratory objective of this study. Data are presented for six subjects in cohort 4 who received treatment for up to 2 years. In total, 427 treatment‐emergent adverse events (TEAEs) were reported, 68 of which were possibly related to the study drug. Eight serious TEAEs occurred in two subjects; three of these events were considered possibly related to the study drug. Pegcetacoplan pharmacokinetic concentrations accumulated with repeated dosing, and steady state was reached at approximately 6‐8 weeks. Lactate dehydrogenase levels were well controlled by eculizumab at baseline. Pegcetacoplan increased hemoglobin levels and decreased both reticulocyte count and total bilirubin in all six subjects. Improvements were observed in Functional Assessment of Chronic Illness Therapy Fatigue scores. Two subjects discontinued for reasons unrelated to pegcetacoplan. All four subjects who completed the study transitioned to pegcetacoplan monotherapy following eculizumab discontinuation and avoided transfusions. In this small study, pegcetacoplan therapy was generally well‐tolerated, and resulted in an improved hematological response by achieving broad hemolysis control, enabling eculizumab discontinuation.

Background Blackwater 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. Methods This 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. Results A 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. Conclusion This 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.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. Methods: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indica-tions for PNH testing using FCM in peripheral blood samples and compared the results of older patients and pa-tients aged 18 - 64 years. Results: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unex-plained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydroge-nase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). Conclusions: Our results showed that the current clinical indications for PNH screening with FCM were also effi-cient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment. © 2020 Verlag Klinisches Labor GmbH. All rights reserved.

Spontaneous ureter rupture (SUR) is a rare condition that can present mimicking many acute abdominal diseases. There is no probable explanation of the theoretical mechanism of spontaneous ureter rupture in the literature. Mostly calculus can cause spontaneous ureter rupture with ureteral obstruction. If left untreated, it can lead to life-threatening complications. Herein we report a case of SUR that was occurred due to urinary stone disease in a male patient who presented with abdominal pain. A non-contrast enhanced and a late phase contrast-enhanced abdominal computed tomography (CT) demonstrated the urinary stone disease and contrast extralumination from the proximal part of the left ureter. We also aimed to emphasize the clinical and CT imaging findings of SUR. © 2018 Elsevier Inc.

CD59 is involved in lymphocyte signal transduction and regulates complement-mediated cell lysis by inhibiting the membrane attack complex. In the cases reported so far, congenital isolated CD59 deficiency was associated with recurrent episodes of hemolytic anemia, peripheral neuropathy, and strokes. Here, we report on a patient from a consanguineous Turkish family, who had a first episode of hemolytic anemia at one month of age and presented at 14 months with acute Guillain-Barré syndrome (GBS). The child suffered repeated infection-triggered relapses leading to the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Although partly steroid-responsive, the polyneuropathy failed to be stabilized by a number of immunosuppressive agents. At the age of 6 years, he developed acute hemiparesis and showed progressive stenosis of proximal cerebral arteries, evolving into Moyamoya syndrome (MMS) with recurrent infarctions leading to death at 8 years of age. Post-mortem genetic analysis revealed a pathogenic p.(Asp49Valfs*31) mutation in CD59. Re-analysis of brain biopsy specimens showed absent CD59 expression and severe endothelial damage. Whereas strokes are a known feature of CD59 deficiency, MMS has not previously been described in this condition. Therefore, we conclude that in MMS combined with hemolysis or neuropathy CD59 deficiency should be considered. Establishing the diagnosis and targeted therapy with eculizumab might have prevented the lethal course in our patient.

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Babesia venatorum was isolated from a captive reindeer calf in Switzerland. The clinical signs consistent with acute babesiosis included hemolytic anemia and hemoglobinuria. The diagnosis was made based on visualization of intraerythrocytic parasites in the stained blood smears and confirmed by PCR analysis of the 18S rRNA gene, with subsequent species identification within Babesia confirmed by sequencing. The reindeer calf was initially treated with supportive care and an antiprotozoal drug (imidocarb dipropionate) but died a few days after hospitalization. Babesia venatorum is also known as Babesia sp. EU1 and can infect different mammalian species, including humans. The current case report aims to increase awareness among veterinarians and reindeer owners about the presence and the associated risk of this zoonotic pathogen. Considering the high morbidity and possible mortality associated with acute babesiosis, captive reindeer should receive tick prevention measures and be tested for subclinical infections in endemic area.

Paroxysmal nocturnal hemoglobinuria (PNH) can occur as a hemolytic form or small PNH clone found in a patient with bone marrow failure. Methods Describe Brazilian retrospective PNH cohort and identify the impact of disease burden on long-term follow-up. Results 167 patients, mean age at diagnosis 28.4 (7.1–71.2 years), four years mean interval between onset of cytopenia/aplasia diagnosis and PNH clone detection. Patients were divided into 15 Classic PNH, 55 Hemolytic PNH with bone marrow hypoplasia (PNH/AA), and 97 Subclinical PNH (sc-PNH). Hypocellular bone marrow was found in 89.2%; 55 had hemoglobinuria and 22 thrombosis during monitoring. WBC PNH clone correlated with RBC PNH clone, LDH and cytopenia. Subclinical patients had lower median lower RBC clone (2.0% vs 24.0% vs 57.8%) and WBC clone (11.7% vs 58.8% vs 81.2%) than PNH/AA and Classic PNH, respectively. PNH granulocyte clone was 89.1% in thrombotic patients. Ten-year overall survival 80.4% and mortality in transplanted patients 9.6%. Sepsis was mortality cause in subclinical PNH (16/18, 88.8%), and thrombosis in hemolytic PNH (11/13, 84.6%). Conclusion Large PNH clones and LDH burden were associated with increased hemolysis and thrombosis risks, while young patients were associated with small PNH clones and subclinical form of the disease. Knowledge of the patient profile, the low risk associated with HSCT, and the use of long-term IST may be instrumental in the clinical management of PNH in restricted-resources countries.

Clostridium haemolyticum causes bacillary hemoglobinuria (BH), an infectious and usually fatal disease that occurs mostly in cattle, which is clinically characterized by jaundice, hemoglobinuria, and anemia. The trematode Fasciola hepatica has been commonly reported as the main predisposing factor that triggers this condition. The authors evaluated 20 naturally occurring cases of bovine BH to characterize the pathology and pathogenesis of the disease. Grossly, the most consistent finding was a large, frequently single focus of necrosis surrounded by a red to purple halo, observed most frequently on the parietal surface of the right and left hepatic lobes. Other findings were jaundice, dark-brown discoloration of kidneys, and red urine in the urinary bladder. Microscopically, characteristic lesions were locally extensive, necrotizing hepatitis with thrombosis and numerous intralesional Gram-positive rod-shaped bacteria, and acute renal tubular necrosis. By immunohistochemistry, many hepatocytes outside the necrotic focus in the liver were positive for activated caspase 3, suggesting that those cells were undergoing apoptosis. Ultrastructural evaluation revealed hepatocyte necrosis, hemolysis, and clumps of vegetative and sporulating bacilli within the liver. Polymerase chain reaction for the C. haemolyticum beta toxin gene was positive in randomly selected liver samples. No gross or microscopic lesions indicative of fascioliasis were detected in the liver of any animal, suggesting that other yet undetermined predisposing factors were associated with these cases of BH.

Serum lactate dehydrogenase (LDH) is the standard measure for detection of hemolysis and thus surveillance for device thrombosis in patients on continuous-flow left ventricular assist device (CF-LVAD) support. Significant hemolysis has been defined as LDH ≥600 IU/L. However, LDH testing requires phlebotomy, precluding frequent home monitoring. Simple dipstick urinalysis (UA) for urine hemoglobin (U-Hb) overcomes this limitation. This study correlated U-Hb and LDH levels and evaluated the performance of UA for detection of significant hemolysis in patients with CF-LVADs.U-Hb and LDH were measured concurrently 956 times in 221 patients with CF-LVADs. Statistics were computed to determine accuracy of UA in detecting LDH ≥600 IU/L, with a positive result being any detected U-Hb. All analyses were performed with and without excluding for 1) conditions associated with tissue damage, which are known to increase LDH, and 2) suspected or confirmed urinary tract infections or hematuria, which are known to cause hemoglobinuria for reasons other than hemolysis.Mean LDH for absent/mild/severe U-Hb was 360 IU/L/467 IU/L IU/L/777 IU/L without exclusions, 354 IU/L/444 IU/L IU/L/651 IU/L after excluding non-hemolytic LDH elevations, 370 IU/L/513 IU/L IU/L/1,357 IU/L after excluding urinary tract infections and hematuria, and 367 IU/L/470 IU/L IU/L/1,217 IU/L when both exclusions applied (all p0.001). Absent U-Hb had a negative predictive value for LDH ≥600 IU/L of90% for all analyses.Serum LDH is significantly associated with U-Hb levels. Absence of U-Hb appears to efficiently exclude significant hemolysis in patients with CF-LVADs. Because it can be performed by patients at home, hemoglobinuria monitoring may enable more intense surveillance and earlier diagnosis of device thrombosis.

Item does not contain fulltext Disease characteristics of patients enrolled in the International PNH Registry were assessed during two follow-up periods based on hemolytic status while untreated with eculizumab: Non-hemolytic cohort: follow-up time defined as time from disease start until last reported untreated lactate dehydrogenase (LDH) value /=1.5xULN at or post-disease start, to most recent untreated follow-up. A total of 1012 patients met criteria for the Non-hemolytic cohort and 1565 patients for the Hemolytic cohort; median (min, max) years of follow-up were 2.2 (0.0, 54.2) and 1.2 (0.0, 37.2) years, respectively. Annual rate of thrombotic events (TEs) was lower in the Non-hemolytic than Hemolytic cohort (0.01 events/person-year vs. 0.03 events/person-year; p

We performed a review of case records of children diagnosed with hepatic venous outflow tract obstruction at our center in last 10 years. Out of 11 cases identified, 6 had variable blocks in the hepatic venous system and 4 had combined hepatic venous and inferior vena cava (IVC) block. One child with paroxysmal nocturnal hemoglobinuria (PNH) had isolated IVC involvement. Angioplasty was attempted in 3 patients; among them 2 had successful outcome. Seven children with advanced liver disease underwent transplantation, which was successful in six. With availability of modalities like interventional radiology and transplantation, the overall prognosis of hepatic venous outflow tract obstruction seems to be good when managed in a well-equipped center.

We herein report the first case of Mediterranean glucose-6-phosphate dehydrogenase (G6PD) variant from Bangladesh. A boy had been admitted to hospital and was diagnosed with uncomplicated Plasmodium vivax infection and treated with 30 mg/kg body weight (BW) chloroquine for 3 days and 4.8 mg/kg BW primaquine (PQ) to be taken over 14 days. The boy was discharged but represented 4 days later with severe hemoglobinuria and fatigue. Hemoglobin was measured at 6.0 g/dL and serum bilirubin was at 5.6 mg/dL, although malaria microscopy was negative. The boy had taken the 4-fold recommended daily dose of PQ and was treated with two fresh blood transfusions. Subsequent molecular analysis showed the boy to have the Mediterranean G6PD variant and a G6PD activity of 0.93 U/gHb.

Introduction:l’objectif de ce travail était d’analyser les aspects épidémiologiques, diagnostiques, thérapeutiques et évolutifs de l’hémoglobinurie chez l’enfant au CHU Pédiatrique Charles-De-Gaulle de Ouagadougou. Méthodes:il s’est agi d’une étude transversale à visée descriptive sur la période allant du 01 juillet au 31 décembre 2014. Ont été inclus dans l’étude, tous les enfants âgés de zéro à 15 ans hospitalisés dans le Service de Pédiatrie Médicale du CHU Pédiatrique Charles-de-Gaulle, chez qui une hémoglobinurie macroscopique a été diagnostiquée pendant la période de l’étude. Résultats:trente-huit patients ont été inclus dans l’étude. La fréquence hospitalière de l’hémoglobinurie était de 1,9%. L’âge moyen des patients était de 80,8 ± 44,1 mois (extrêmes = 21 et 168). Il s’agissait de 23 garçons (60,5%) et 15 filles (39,5%). Les principaux signes cliniques étaient: la fièvre (86,8%), les urines foncées « coca cola » (86,8%), la pâleur (63,2%), l’hépatomégalie (50%). Le débit de filtration glomérulaire (DFG) était inférieur à 80 mL/min/1,73m2chez 23 patients (69,7%); 21 patients avaient un déficit en G6PD. Les principales étiologies présumées de l’hémoglobinurie étaient: le paludisme grave, les infections bactériennes et virales, le déficit en G6PD, la fièvre bilieuse hémoglobinurique. Les traitements administrés étaient: les dérivées de l’artémisinine, les antibiotiques et les antipyrétiques. Le recours à la dialyse a été nécessaire chez un patient. Conclusion:l’hémoglobinurie est un symptôme qui pose surtout un problème de diagnostic étiologique dans notre contexte. Sa gravité réside dans le fait qu’elle peut provoquer une IRA sévère.

Background The aim of this work was to determine the frequency of ascorbic acid-positive urine samples and to evaluate the potential risk on patient safety. Materials and methods A total of 27,856 samples submitted for urinalysis in previous year were retrospectively analysed from the laboratory information system. Urinalysis was done on Iris IQ200 analyzer using 11-parameter iChem Velocity test strips. Risk analysis combined the impact of potentially erroneous results (due to ascorbic acid interference) on patient safety (severity – S) with their frequency (occurrence – O). Potential risk was identified as high, intermediate and low. Results One thousand one hundred and ninety-nine (4.3%) and 1646 (5.9%) samples were mildly (20 mg/dL, 1+) and highly positive (40 mg/dL, 2+) for ascorbic acid, respectively. Severity (S1 to S5) was assigned to four possible errors: false-negative glucose (U-Glc: S2), blood (U-Hb: S5), nitrite (U-Nit: S4) and bilirubin (U-Bil: S1). Based on the frequency of errors, occurrence was categorized as: O2 for U-Glc, and O3 for U-Bil, U-Nit and U-Hb. The risk analysis matrix revealed that false-negative U-Hb was associated with potentially high risk, false-negative U-Nit with intermediate risk, while false-negative U-Glc and U-Bil were associated with low risk on patient safety. Conclusions Positive ascorbic acid can cause potentially high risk for patient safety by missing positive blood in urine.

Objectives We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of Chinese paroxysmal nocturnal hemoglobinuria (PNH) patients, and assessed the efficacy and safety of glucocorticoid in PNH patients. Methods The clinical data of 92 PNH cases in our hospital were analyzed, including clinical manifestation, laboratory examination, treatment efficacy, and survival. Results The main clinical manifestations of these patients included hemoglobinuria, anemia, fatigue, dyspnea, headache, abdominal pain, and erectile dysfunction. Glucocorticoid is still the first‐line treatment for PNH patients to control hemolytic attack, and the short‐term remission rate (12 months) is 79.01% (64/81). Meanwhile, the overall survival (OS) of 10 years after diagnosis was estimated as 70.77% (46/65). Moreover, Cox proportional risk model for multivariate analysis showed that the increase in LDH multiple, thrombosis complications, and complicated with bone marrow failure were the independent adverse prognostic factors affecting the survival of PNH patients. Conclusion Paroxysmal nocturnal hemoglobinuria patients in mainland China have various clinical features, while lower incidences of thrombosis and renal damage. Thrombosis and bone marrow failure are two complications with worse prognosis.

Objective Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disorder of the hematopoietic stem cells that involves all blood cells. The primary aim of this study was to assess the role of whole-blood exchange (WBE) in treating patients with PNH. Methods A 32-year-old male patient was admitted our hospital because of severe anemia. His clinical test results indicated serious hemolysis, with positive anti-I on pretransfusion antibody screening tests. Because immunosuppressive therapy was ineffective and red blood cell (RBC) transfusion may aggravate hemolytic symptoms, the COBE Spectra blood cell separator was used for WBE. Results We performed WBE, where 1789 mL of the patient’s blood was removed and replaced with 12 U of packed RBCs, along with 150 mL of frozen plasma and 200 mL of normal saline (total volume, 1883 mL), representing an exchange of 42.5% of the patient’s total blood volume (approximately 4209 mL). The WBE treatment was considered successful. Rapid improvement in clinical signs and symptoms were observed after the WBE transfusion. The patient was discharged from the hospital on the third day after treatment. Conclusion Whole-blood exchange may be an applicable emergency treatment for rescuing PNH patients with severe or life-threatening hemolysis.