Case Report: A Case of Primaquine-Induced Hemoglobinuria in Glucose-6-Phosphate Dehydrogenase Deficient Malaria Patient in Southeastern Bangladesh.

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.

Risk Factors for Macroscopic Haemoglobinuria After Sclerotherapy Using Ethanolamine Oleate for Venous Malformations.

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.

Acute Kidney Injury following Ingestion of Henna Leaf Extract: A Case Report from Myanmar.

Alternative medicine is gaining popularity worldwide. In Asia, particularly Southeast Asia, herbal medicine plays an important role in healthcare. A 34-year-old man from Yangon, Myanmar, was admitted to the medical ward of our hospital after ingesting a herbal remedy of boiled henna leaves (Dan Ywet in Burmese). He developed hemoglobinuria leading to acute kidney injury (AKI). The insult was severe, and he underwent 5 sessions of hemodialysis. His condition improved and within 7 weeks of injury, he made a full recovery. However, he was lost to follow-up when renal function became normal. Our diagnosis was AKI from hemoglobinuria secondary to henna leaf extract nephrotoxicity in G6PD deficiency. This case highlights the steps required to achieve the International Society of Nephrology's goal of 0 preventable deaths from AKI by 2025 and the efforts needed to increase public knowledge about herbal remedies and AKI, medication adherence, and compliance with follow-up.

A patient presented with dark brown urine after mothballs powder ingestion.

We report a case who presented with dark brown urine and malaise after mothballs powder ingestion.

Successful reduction of plasma free-hemoglobin using therapeutic plasma exchange: A case report.

Massive intravascular hemolysis may overwhelm hemoglobin (Hgb) clearance mechanisms leading to accumulation of excess plasma free-Hgb and subsequent acute kidney injury. We present the case of a 44-year-old male with cardiac failure necessitating placement of a subcutaneous left ventricular assist device. Following insertion, the patient developed mechanical hemolysis and an acute decline in renal function. Three therapeutic plasma exchange procedures were performed resulting in a dramatic decrease in plasma free-Hgb levels and stabilization of renal function. This demonstrates that therapeutic plasma exchange can be used to decrease plasma free-Hgb in cases of intravascular hemolysis, possibly protecting the patient from hemoglobinuric acute kidney injury.

Severe intravenous immunoglobulin-induced hemolysis with pigment nephropathy managed with red cell exchange.

We report on the use of red cell exchange in a case of severe intravenous immune globulin induced hemolysis and pigment nephropathy. Renal impairment and hemoglobinuria were not ameliorated by supportive measures including hydration. Partial red cell exchange with group O blood reduced hemoglobinuria and appeared to stabilize renal function. This is the first report on the use of red cell exchange in this clinical setting. J. Clin. Apheresis 31:464-466, 2016. © 2015 Wiley Periodicals, Inc.

[Current management of thalassemia intermedia]. / Prise en charge actuelle des thalassémies intermédiaires.

Thalassemia intermedia is a clinical entity where anemia is mild or moderate, requiring no or occasional transfusion. Non-transfusion-dependent thalassemia encompasses 3 main clinical forms: beta-thalassemia intermedia, hemoglobin E/beta-thalassemia and alpha-thalassemia intermedia (HbH disease). Clinical severity of thalassemia intermedia increases with age, with more severe anemia and more frequent complications such as extramedullary hematopoiesis and iron overload mainly related to increased intestinal absorption. Numerous adverse events including pulmonary hypertension and hypercoagulability have been associated with splenectomy, often performed in thalassemia intermedia patients. The potential preventive benefit of transfusion and chelation therapies on the occurrence of numerous complications supports the strategy of an earlier therapeutic intervention. Increasing knowledge about pathophysiological mechanisms involved in thalassemia erythropoiesis and related iron overload is currently translating in novel therapeutic approaches.

Hemoglobinuria and acute kidney injury requiring hemodialysis following intravenous immunoglobulin infusion.

Intravenous immunoglobulin (IVIG), a product initially developed for patients with immunodeficiencies, now has multiple other indications and increasing off-label use. IVIG generally is well tolerated, with few adverse effects. Antibody-mediated (Coombs-positive) hemolysis is known to occur after IVIG infusion, but often is subclinical and previously has not been reported to lead to acute kidney injury (AKI). The predominantly known mechanism of AKI after IVIG infusion has been osmotic nephrosis, primarily associated with sucrose-containing formulations. We present a case of a bone marrow transplant recipient who was treated with a sucrose-free IVIG product and subsequently developed Coombs-positive hemolysis leading to AKI requiring hemodialysis, who ultimately died secondary to infectious complications. The severity of this case emphasizes the importance of identifying populations who may be at increased risk of pigment-mediated kidney injury before consideration of IVIG therapy.

Conservative treatment of hemolytic complication following coil embolization in two adult cases of patent ductus arteriosus.

Two adult cases of relatively large patent ductus arteriosus (PDA) were treated by coil embolization, but were complicated by hemolysis that was successfully managed by medical treatment. Case 1 was a 67-year-old woman and Case 2 was a 71-year-old woman with a PDA of minimal diameter of 5.3 mm and 5.5 mm, respectively. The approach was via the pulmonary artery and 2 coils were delivered simultaneously into the ductus, known as the 'kissing coil technique'. Although immediately after the procedure only a small residual shunt was revealed by aortogram, hemolysis occurred for several hours after the procedure in both cases. A hemolytic complication usually needs additional coil embolization or surgical treatment, but in these 2 cases it was successfully treated by haptoglobin infusion to prevent nephropathy and by antiplasmin infusion to promote thrombus formation. Hemolytic complications of coil embolization of PDA can managed by medication when the residual shunt is minimal and the degree of hemolysis is mild.

Repression of aberrant splicing in human beta-globin pre-mRNA with HbE mutation by antisense oligoribonucleotide or splicing factor SF2/ASF.

Hemoglobin (Hb) E is the most common Hb variant among Southeast Asian populations. The mutation in codon 26 (GAG to AAG) of the beta-globin gene (beta E) induces alternative splicing, resulting in the production of normally and aberrantly spliced beta-globin mRNA. Compound heterozygosity for beta-thalassemia and HbE, beta-thalassemia/HbE disease, could lead to a severe thalassemia phenotype. Repression of aberrant splicing from the beta E mutation could ameliorate the severity in such patients. We showed that the aberrant splicing was partially repressed in cells treated with antisense oligoribonucleotide targeted to the aberrant 5' splice site. The maximum effect of the antisense oligoribonucleotide was observed at a concentration of 0.4 mumol/L, 36 hours after the treatment in our experiment. We also analyzed the effect of the transient and stable expression of SF2/ASF on aberrant splicing in cells expressing the beta E-globin gene. Partial repression of the aberrant splicing was also observed in both expression systems. Our results imply that antisense oligoribonucleotide treatment and SF2/ASF expression are possible therapeutic applications for beta-thalassemia/HbE disease.

The form of iron oxide deposits in thalassemic tissues varies between different groups of patients: a comparison between Thai beta-thalassemia/hemoglobin E patients and Australian beta-thalassemia patients.

Mössbauer spectra of 12 beta-thalassemia/hemoglobin E spleen samples from Thai patients who had not received multiple blood transfusions and chelation therapy and seven beta-thalassemia spleen samples from Australian patients who had received multiple blood transfusions and chelation therapy were recorded with sample temperatures of 78 K. Each spectrum was found to consist of a superposition of a relatively intense central doublet characteristic of high-spin Fe(III), a low intensity sextet of peaks due to magnetic hyperfine-field splitting, and occasionally a doublet that could be attributed to heme iron. A significant (P=0.01) difference (Kolmogorov-Smirnov statistic of 0.71) between the distributions of sextet signal intensity as a fraction (Fs) of the total non-heme iron Mössbauer spectral signal for the two groups of patients was detected. The distribution of Fs for the Thai beta-thalassemia/hemoglobin E spleens had a mean value of 0.128 (S.D. 0.035) while that for the Australian beta-thalassemia spleens had a mean of 0.27 (S.D. 0.12). No significant difference between the distributions of non-heme iron concentrations in the tissues for the two groups of patients was detected by atomic absorption spectrometry. This study shows that the Australian beta-thalassemia patients had a higher fraction of their non-heme spleen iron in a goethite-like form than the Thai beta-thalassemia/Hb E patients.

Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in beta-thalassemia/hemoglobin E disease.

Hydroxyurea (HU) is one of several agents that have been shown to enhance hemoglobin (Hb) F levels in patients with sickle cell disease and may be useful as a therapy for beta-globinopathies. However, limited information exists on the effects of HU in patients with thalassemia. Accordingly, we examined the hematologic effects of orally administered HU in 13 patients with beta-thalassemia/Hb E, including four patients who had been splenectomized. These patients were treated with escalating doses (final range, 10 to 20 mg/kg/d) for 5 months and were observed in the outpatient hematology clinic every 2 to 4 weeks. Complete blood counts including reticulocyte counts, amounts of Hb E and Hb F, G gamma:A gamma and alpha:non-alpha globin biosynthetic ratios were evaluated before and during treatment. Almost all patients responded with an average increase of 33% in Hb F levels, from a mean (+/- SD) of 42% +/- 11% to 56% +/- 8% (P < .0001), and a reciprocal decline in the percentage of Hb E from 59% +/- 9% to 49% +/- 8% (P < .001). Reticulocytosis was decreased from a mean (+/- SD) of 18.0% +/- 15.6% to 11.7% +/- 9.1% (P < .05); there was also a slight (10%) but statistically significant increase in hemoglobin levels and an improved balance in alpha:non-alpha globin chains ratios. The side effects were minimal in most patients, although these patients tended to tolerate a lower dose of HU before significant myelosuppression than has been our previous experience in sickle cell disease. One splenectomized patient died of sepsis during the trial. We conclude that increased Hb F production in beta-thalassemia/Hb E patients, with an improvement in the alpha:non-alpha globin ratios and, probably, the effectiveness of erythropoiesis, can be achieved using HU. Longer trials of HU in this population, including at other doses and in combination with other agents, appear warranted.

Haptoglobin therapy for acute favism: a Japanese boy with glucose-6-phosphate dehydrogenase Guadalajara.

We report the case of a 2-year-old Japanese boy with acute favism who was treated with human haptoglobin products. He had been exhibiting chronic nonspherocytic haemolytic anaemia until the diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency when 14 months old. He suffered a favic crisis at 24 months of age, when the administration of haptoglobin was effective for relieving bilirubinaemia and haemoglobinuria. Serum-free Hb rapidly decreased to normal levels despite the sustained level of serum lactate dehydrogenase. His G6PD gene was G6PD Guadalajara. This is the first application of haptoglobin therapy for acute favism and the first reported case of Japanese G6PD deficiency with typical favic crisis. Haptoglobin treatment might be helpful for managing the haemolytic crisis in the disease.

Study of hematopoietic progenitor cells in thalassemia after bone marrow transplantation.

The hematopoietic committed progenitor cells (BFU-E and CFU-GM) in blood and bone marrow were studied in thalassemic patients before and after bone marrow transplantation. Eighteen transplants were performed in 17 patients with thalassemia. Five were homozygous beta-thalassemia and 12 were beta-thalassemia/hemoglobin E disease. The age ranged from 1.2-14 years (median = 3.4 years). The conditioning regimen comprised busulfan 3.5-4 mg/kg/day for 4 days and cyclophosphamide 50 mg/kg/day for 4 days. Cyclosporin in combination with methotrexate were administered post transplant for GVHD prophylaxis. Before transplantation, BFU-E and CFU-GM in the blood of the patients were significantly higher compared with normal (p < 0.05) but were normal in the bone marrow. Only the CFU-GM in the bone marrow of the successful cases after transplantation recovered to the normal level at the first month through the 12th month whereas the BFU-E were low. Both CFU-GM and BFU-E in the blood were lower than normal after follow up to the 12th month. Inspite of the low number of progenitor cells, there was hematological recovery in the blood of the patients. It may be due to the capacity of the hematopoiesis react to stress which could be amplified the differentiation compartment or the shortened-transit time through the stem cell compartment.