[Eculizumab in patients with paroxysmal nocturnal hemoglobinuria: a real-world study in China].

Objective: To evaluate the efficacy and safety of eculizumab in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in China. Methods: Data from PNH patients who received at least 3 months of full-dose eculizumab and were followed for at least 3 months between December 2022 and July 2023 were retrospectively collected. We evaluated changes in clinical and laboratory parameters after 1, 2, 3, and 6 months of eculizumab treatment. The rates of breakthrough hemolysis (BTH), extravascular hemolysis (EVH), and the occurrence of adverse reactions were also monitored. Results: The study included nine patients, six males and three females, with a median age of 54 (28-69) years. 5 of the patients had classic PNH, while 4 had PNH/AA. The number of episodes of hemoglobinuria was 5 (1-25) per month before eculizumab. 4 patients required blood transfusion, 5 had thrombosis and one had renal impairment before eculizumab. The median time to eculizumab was 6 (3-7) months and the followup period was 3 (3-6) months after treatment. The number of episodes of hemoglobinuria following eculizumab was 0 (0-1). During the followup period, no additional thrombotic events occurred. LDH at any time after eculizumab was lower than at baseline, and some patients' HGB increased. All transfused patients became transfusion-independent after receiving eculizumab. The FACIT-Fatigue score improved by an average of 17.3 points following treatment. 2 patients developed BTH and improved with symptomatic treatment. There were three adverse events that caused mild symptoms. There are no serious adverse events or deaths. Conclusion: Eculizumab can effectively control the hemolytic-related symptoms of PNH in China, reducing the need for blood transfusions to some extent, while also demonstrating a higher safety profile.

A rare case of dialysis associated reaction presenting with urticarial vasculitis and haemoglobinuria.

Dialysis associated reactions presenting with urticarial vasculitis is rarely reported in medical literature. We report a 61-year-old gentleman who developed sudden onset dyspnea with diffuse erythema within 20 min of haemodialysis. Patient was started on Azilsartan 3 days prior to this clinical event. Labs revealed features of hemolysis and urine was positive for hemoglobinuria. All dialysis related factors responsible for this reaction were ruled out. Due to non-resolution of skin rash, skin biopsy was attempted which revealed fibrinoid necrosis of occasional vessels with predominant lymphocytic infiltration suggestive of drug induced urticarial vasculitis. Complement levels were normal. He was managed with steroids, anti-histaminic, discontinuation of azilsartan and change of dialyzer membrane. This case highlights a rare dermatological presentation of Type A dialysis associated reaction involving azilsartan with differential diagnosis and treatment strategies.

How the United States syphilis epidemic may portend a resurgence of an unusual hematologic condition: The connection between syphilis and paroxysmal cold hemoglobinuria.

The connection between syphilis and paroxysmal cold hemoglobinuria.

Cold Agglutinin Disease in a Rhesus Macaque (Macaca mulatta).

Cold agglutinin disease (CAD) is a condition involving anemia and its related symptoms; it is caused by autoantibodies that bind and agglutinate red blood cells in areas susceptible to hypothermia, such as extremities exposed to cold temperatures. CAD is rare, with 5 to 20 human cases per million individuals. In this report, we describe a case of CAD in a previously healthy and experimentally naïve adult Indian rhesus macaque that was housed indoors and presented with blood in the urine. After our observations of hemoglobinuria and anemia led us to suspect CAD, we demonstrated that the macaque's blood agglutinated at reduced temperatures. We also noticed that the provision of cold foraging treats triggered episodes of hemoglobinuria. Further investigation revealed that serum from the macaque agglutinated RBCs in vitro with high thermal amplitude (at or below 30 °C) and had an antibody titer of 8 to 32. The serum contained autoantibodies of the immunoglobulin M (IgM) isotype; agglutinins of the IgG isotype were not detected. The cold-dependent IgM autoantibodies in the serum from the affected macaque reacted against a common RBC antigen because RBCs collected from other macaques were bound and agglutinated by the affected animal's IgM under cold conditions. This in vitro binding activity was reversible when the test temperature was returned to normal body temperature (37 °C). These findings demonstrated cold-dependent RBC-specific IgM agglutinins and led us to a diagnosis of CAD. This is the first documented case of spontaneous CAD in a rhesus macaque.

Plasma exchange in acute hemolytic reaction due to ABO-incompatible erythrocyte concentrate transfusions: Single center experience.

OBJECTIVES: Acute hemolytic transfusion reaction (AHTR) due to ABO-incompatible erythrocyte concentrate (EC) is one of the most catastrophic complications of transfusion. Since the hemolysis is intravascular; hemoglobinemia and hemoglobinuria result in disseminated intravascular coagulation (DIC), acute renal failure, shock, and sometimes death. BACKGROUND: Treatment of AHTR is mostly supportive measures. Today there are no clear suggestions about plasma exchange (PE) in these patients. METHODS/MATERIALS: Here we report our experience with six patients diagnosed with AHTR due to ABO-incompatible EC transfusion. RESULTS: We performed PE in 5 of these patients. Although all of our patients were geriatric and most of them had significant comorbidities four out of five patients recovered without an incident. CONCLUSION: Although PE is considered a last-chance treatment when other measures fail in the literature, our experience above indicates that it must be evaluated in every patient with AHTR early in the course. If the patient has cardiac and renal comorbidities, large volume EC is transfused, DAT is negative, plasma color is red and there is macroscopic hemoglobinuria, we suggest performing PE.

Inherited CD59 deficiency, where neurology and genetics intertwine.

OBJECTIVES: To describe the clinical phenotype of eight children diagnosed with CD59 deficiency and their ultimate neurological outcome. METHODS: The data of our cases were extensively reviewed both clinical and ancillary tests; investigations included: neuroimaging, neurophysiological studies, and laboratory tests. RESULTS: All patients presented during early infancy with Guillain-Barre syndrome later they suffered repeated relapses leading to the diagnosis of chronic axonal neuropathy. Recurrent stroke and acute necrotizing encephalopathy were described, 2 patients in each group. One girl developed acute disseminated encephalomyelitis while one boy developed acute transverse myelitis. Overt hemolytic anemia requiring blood transfusion reported in six patients. CONCLUSION: Inherited CD59 deficiency is an autosomal recessive disorder which can have devastating neurological consequences. First line immunotherapy including intravenous immunoglobin, corticosteroids, and plasma exchange may have transient beneficial effect. Reports of targeted therapy with eculizumab might be lifesaving. Genetic counseling is crucial.

Hospital-based surveillance of severe paediatric malaria in two malaria transmission ecological zones of Burkina Faso.

BACKGROUND: In the current context of tailoring interventions to maximize impact, it is important that current data of clinical epidemiology guide public health programmes and health workers in the management of severe disease. This study aimed at describing the burden of severe malaria at hospital level in two areas with distinct malaria transmission intensity. METHODS: A hospital-based surveillance was established in two regional hospitals located in two areas exposed to different malaria transmission. Data on paediatric severe malaria admissions were recorded using standardized methods from August 2017 to August 2018 with an interruption during the dry season from April to June 2018. RESULTS: In total, 921 children with severe malaria cases were enrolled in the study. The mean age was 33.9 (± 1.3) and 36.8 (± 1.6) months in lower malaria transmission (LMT) and higher malaria transmission (HMT) areas (p = 0.15), respectively. The geometric mean of asexual P. falciparum density was significantly higher in the LMT area compared to the HMT area: 22,861 trophozoites/µL (95% CI 17,009.2-30,726.8) vs 11,291.9 trophozoites/µL (95% CI 8577.9-14,864.5). Among enrolled cases, coma was present in 70 (9.2%) participants. 196 patients (21.8%) presented with two or more convulsions episodes prior to admission. Severe anaemia was present in 448 children (49.2%). Other clinical features recorded included 184 (19.9%) cases of lethargy, 99 (10.7%) children with incoercible vomiting, 80 (8.9%) patients with haemoglobinuria, 43 (4.8%) children with severe hypoglycaemia, 37 (4.0%) cases where child was unable to drink/suck, 11 (1.2%) cases of patients with circulatory collapse/shock, and 8 cases (0.9%) of abnormal bleeding (epistaxis). The adjusted odds of presenting with coma, respiratory distress, haemoglobinuria, circulatory collapse/shock and hypoglycaemia were significantly higher (respectively 6.5 (95%CI 3.4-12.1); 1.8 (95%CI 1.0-3.2); 2.7 (95%CI 1.6-4.3); 5.9 (95%CI 1.3-27.9); 1.9 (95%CI 1.0-3.6)) in children living in the HMT area compared to those residing in the LMT area. Overall, forty-four children died during hospitalization (case fatality rate 5.0%) with the highest fatalities in children admitted with respiratory distress (26.0%) and those with hypoglycaemia (25.0%). CONCLUSION: The study showed that children in the HMT area have a higher risk of presenting with coma, shock/dehydration, haemoglobinuria, hypoglycaemia, and respiratory distress. Case-fatality rate is higher among patients with respiratory distress or hypoglycaemia. Hospital surveillance provides a reliable and sustainable means to monitor the clinical presentation of severe malaria and tailor the training needs and resources allocation for case management.

March hemoglobinuria progressed to acute kidney injury after kendo practice: a case report.

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.

Exertional hemolysis and hematuria in a Labrador Retriever dog.

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.

Optic neuritis in CD59 deficiency: an extremely rare presentation.

BACKGROUND: CD59 is the principal cell inhibitor of complement membrane attack on cells. Stroke, peripheral neuropathy, and recurrent central nervous system attacks have been reported in patients with inherited CD59 deficiency. In this paper, we report a patient with CD59 deficiency associated with two attacks of demyelinating peripheral neuropathy and the third attack as an isolated optic neuritis. CASE: An 8-month-old girl whose sibling died at 12th month of age with recurrent weakness episodes responsive to intravenous immune globulin treatment, presented with weakness in legs and poor sucking. Weakness episodes with neurogenic electromyography suggested CD59 deficiency. Immunophenotypic analysis with flow cytometry showed CD59 deficiency. Sanger sequencing of CD59 gene revealed a homozygous c146delA (p.Asp49Valfs*32) mutation. First two attacks were treated with intravenous immunoglobulin therapy without any sequalae. Third attack was an isolated optic neuritis which could not be explained by any other entity. The patient had no response to intravenous immunoglobulin but benefited from pulse steroid therapy. Eculizumab was started every two weeks in order to prevent possible advanced attacks and to reduce their severity. CONCLUSION: Although it is a rarely reported disease, better recognition of CD59 deficiency by pediatric neurologists is necessary because it is curable. In addition to different presentations reported, optic neuritis may also be a manifestation of CD59 deficiency.

Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas-a randomized controlled trial (PRIMA).

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<5g/dl and <7g/dl) and/or the risk for blood transfusion, the incidence risk of ≥ 25% fall in haemoglobin with and without haemoglobinuria, and the incidence risk of ≥ 25% fall in haemoglobin to under 7g/dl with and without haemoglobinuria. 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.

Discolored Urine in Horses and Foals.

This article describes the most common causes of urine discoloration. The review includes a description of the most common disorders causing hematuria, highlighting clinical presentation, treatments, and pathophysiology. Causes of hemoglobinuria and myoglobinuria together with their mechanisms of renal injury are also reviewed.

Changes to blood parameters after postparturient hemoglobinuria in 11 Holstein-Friesian cows.

This study reviewed a case series of 11 Holstein-Friesian (HF) cows with postpartum hemoglobinuria (PPH) from one dairy herd. The first clinical signs of PPH appeared in the animals during the second or third lactation, between 21 and 30 days after calving. The clinical signs, including depression, diminished appetite, a dark red to brown color in the urine, pale mucous membranes, and a decrease in milk yields were observed in these 11 animals. Three of the cows developed jaundice of the mucous membranes and five had dry, parched feces. PPH was confirmed on laboratory test results of blood and urine samples. Anemia, serum hypophosphatemia (Pi = 0.79 mmoL/L), and increased liver function analytes (total bilirubin, total protein, and urea concentrations) were observed in all animals. Animals were treated with intravenous phosphorus supplementations for the first 2 days after clinical signs were noted, and then oral supplementations were administered. After the clinical signs resolved and the treatments were discontinued, the animals still had mild anemia; however, the phosphorus concentration increased to 1.40 mmoL/L. Gamma-glutamyltransferase activity increased compared with activities measured before treatments and total bilirubin concentrations decreased slightly; however, the concentrations were still more than twice the upper limit of the normal RI. These animals were diagnosed with liver damage that had developed over the course of PPH, indicating the need for the further monitoring and treatment of cows during the postparturient period, even if clinical signs are no longer present.

Acute renal failure with severe loin pain and patchy renal vasoconstriction in a patient with march hemoglobinuria.

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.

Recurrent Blistering Skin Lesions and Reversible Monocular Abducens Paralysis in a Patient with CD59 Deficiency.

Congenital CD59 deficiency is an autosomal recessive disease characterized by mild-to-moderate chronic intravascular hemolysis, relapsing demyelinating peripheral neuropathies, and recurrent ischemic central nervous system strokes. We report a 2-year-old Turkish girl with a history of two episodes of Guillain-Barré syndrome-like acute weakness, reversible monocular abducens paralysis, and recurrent blistering skin lesions during periods of upper respiratory tract infections. Reversible monocular abducens palsy and recurrent blistering skin lesions have not been reported previously in cases of congenital CD59 deficiency.