Severe autoimmune hemolytic anemia complicating hereditary spherocytosis treated successfully with glucocorticoids and cyclosporine: a case report.

BACKGROUND: Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which this intractable disease was treated successfully with glucocorticoids and cyclosporine. CASE PRESENTATION: A 25-year-old female patient with hereditary spherocytosis developed severe autoimmune hemolytic anemia after respiratory syncytial virus infection. Her hemoglobin level was 26 g/L and various anti-red blood cell antibodies were detected in her serum, making blood matching difficult. Glucocorticoid monotherapy was ineffective. With the addition of cyclosporine (50 mg/12 h), the patient's hemoglobin level increased significantly and the symptoms associated with anemia were greatly relieved. CONCLUSION: In patients with severe autoimmune hemolytic anemia, especially when the presence of multiple anti-red blood cell antibodies and alloantibodies interferes with blood matching, a glucocorticoid-cyclosporine regimen may be tried.

Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis.

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.

Flow Cytometric Analysis of Erythrocytes Osmotic Fragility in Hereditary Spherocytosis: A Case-Controlled Study Evaluating the Best Anticoagulant, Sample Pre-Treatment and NaCl Concentration for Reliable Screening of this Red Blood Cell Membrane Disorder.

BACKGROUND: The cytometric flow osmotic fragility test (FC-OFT) was recently introduced. However, the test is still under development and some variables have not yet been fully tested. METHODS: The osmotic fragility of hereditary spherocytosis (HS) cases and healthy controls were evaluated by FC-OFT using a series of tubes containing decreasing concentrations of NaCl. The analyses were executed in fresh and incubated (37°C for 24 h) blood samples anticoagulated with EDTA and heparin. The percentages of residual red blood cells were used to plot the osmotic fragility curves. The OF curves of each tested condition were compared using the median corpuscular fragility (MCF). ROC curve analyses identified the most accurate NaCl concentrations for differentiation between HS cases and healthy controls. RESULTS: FC-OFT curves assumed a sigmoidal dose-response shape and the MCF of cases and controls were different in all instances. MCF comparisons revealed that incubation and anticoagulant have major and minor effects on the FC-OFT, respectively. One hundred percent of sensitivity and specificity was obtained from 5.5 to 6.0 g/L of NaCl in EDTA-treated fresh blood, from 6.0 to 8.0 g/L of NaCl in EDTA-treated incubated blood, and in none of the tested NaCl concentration in heparinized blood. CONCLUSIONS: EDTA is the anticoagulant of choice for the assay. Incubation at 37°C for 24 h increased its diagnostic capability. The most reliable NaCl concentration for the discrimination of HS case from controls was 6.0 g/L of NaCL in fresh EDTA-treated blood, and was 7.5 g/L of NaCl in incubated EDTA-treated blood. © 2018 International Clinical Cytometry Society.

Previously undiagnosed hereditary spherocytosis in a patient with jaundice and pyelonephritis: a case report.

BACKGROUND: Hereditary spherocytosis is autosomal dominant inherited extravascular hemolytic disorder and is the commonest cause of inherited hemolysis in northern Europe and the United States. The classical clinical features of hereditary spherocytosis are anemia, jaundice, and splenomegaly. However, all of these classical features are not always revealed in the case of mild hemolysis or when hemolysis is well compensated. Patients with hereditary spherocytosis may remain undiagnosed for years if their hemolysis is mild. CASE PRESENTATION: A 42-year-old Asian woman presented to our clinic with a sudden onset of high fever with shaking chills and jaundice, suggesting septicemia; however, following detailed investigation, the patient was diagnosed with pyelonephritis and accelerated hemolysis of hereditary spherocytosis due to infection. CONCLUSIONS: It is important to note that transient anemia or jaundice can sometimes be the only initial presenting symptoms in cases of undiagnosed latent hereditary spherocytosis. This case also highlights the fact that physicians should consider concomitant hemolytic disease in patients in whom jaundice and infections that rarely cause jaundice coexist.

Hereditary Spherocytosis with Splenomegaly and Cholelithiasis in a Young Male of Western Region of Nepal - A Case Report.

Hereditary spherocytosis is an autosomal dominant congenital hemolytic anemia due to defect in RBC membrane protein that commonly presents with intermittent jaundice, anemia, abdominal pain, splenomegaly and sometimes cholelithiasis. Due to the membrane defect, there is increased fragility, hemolytic anemia, marked splenomegaly and hyperbilirubinemia. This is a report of an 11 years old male diagnosed case of hereditary spherocytosis who presented with jaundice, splenomegaly and cholelithiasis. He underwent elective open splenectomy and cholecystectomy after prophylactic immunization for capsulated organisms and was advised lifelong oral penicillin prophylaxis post-splenectomy.

Loss of transfusion dependency following deferasirox treatment of iron overload in a woman with myelofibrosis and spherocytosis - a case report.

BACKGROUND: Many patients with primary myelofibrosis (PMF), a myeloproliferative neoplasm, become transfusion dependent due to anemia. In these patients, transfusion dependency is associated with shortened survival. CASE REPORT: We report on a 67-year-old woman who was diagnosed with PMF. Cytogenetic testing revealed a karyotype 46,XX, del(20)(q11.2), consistent with a myeloproliferative disorder. Although offered to her because of severe anemia and leukocytosis, the patient did not consent to allogeneic hematopoietic stem cell transplantation. After having received a cumulative number of more than 70 packed red blood cell transfusions, iron chelation therapy with deferiprone was initiated to treat iron overload and switched to deferasirox after 3 months. Within 2 months of deferasirox treatment, serum ferritin concentrations were significantly reduced, the patient lost transfusion dependency for 17 months, and normal hemoglobin concentrations were recovered. CONCLUSION: Iron chelation treatment with deferasirox resulted in an improvement of hematologic parameters and loss of transfusion dependency.

A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia.

Hemolysis can saturate the hemoglobin (Hb)/heme scavenging system, resulting in increased circulating cell-free Hb (CF-Hb) in hereditary and acquired hemolytic disease. While recent studies have suggested a central role for intravascular hemolysis and CF-Hb in the development of vascular dysfunction, this concept has stimulated considerable debate. This highlights the importance of determining the contribution of CF-Hb to vascular complications associated with hemolysis. Therefore, a novel Hb-binding peptide was synthesized and linked to a small fragment of apolipoprotein E (amino acids 141-150) to facilitate endocytic clearance. Plasma clearance of hE-Hb-b10 displayed a rapid phase t(1/2) of 16 min and slow phase t(1/2) of 10 h, trafficking primarily through the liver. Peptide hE-Hb-B10 decreased CF-Hb in mice treated with phenylhydrazine, a model of acute hemolysis. Administration of hE-Hb-B10 also attenuated CF-Hb in two models of chronic hemolysis: Berkeley sickle cell disease (SS) mice and mice with severe hereditary spherocytosis (HS). The hemolytic rate was unaltered in either chronic hemolysis model, supporting the conclusion that hE-Hb-B10 promotes CF-Hb clearance without affecting erythrocyte lysis. Interestingly, hE-Hb-B10 also decreased plasma ALT activity in SS and HS mice. Although acetylcholine-mediated facialis artery vasodilation was not improved by hE-Hb-B10 treatment, the peptide shifted vascular response in favor of NO-dependent vasodilation in SS mice. Taken together, these data demonstrate that hE-Hb-B10 decreases CF-Hb with a concomitant reduction in liver injury and changes in vascular response. Therefore, hE-Hb-B10 can be used to investigate the different roles of CF-Hb in hemolytic pathology and may have therapeutic benefit in the treatment of CF-Hb-mediated tissue damage.

Excessive bilirubin elevation in a patient with hereditary spherocytosis and intrahepatic cholestasis.

Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.

Steroid therapy may be effective in augmenting hemoglobin levels during hemolytic crises in children with hereditary spherocytosis.

BACKGROUND: The course of hereditary spherocytosis (HS) may be subject to hemolytic episodes, sometimes requiring blood transfusion. The aim of this study was to evaluate the efficacy of a short course of steroid therapy in elevating hemoglobin levels during hemolytic crisis. PROCEDURE: The files of all patients followed for HS from 1968 to 2009 at our hospital were reviewed. Outcome of hemolytic crises was compared between steroid-treated and untreated patients; patients given packed red blood cell transfusion(s) or erythropoietin treatment were excluded. A good outcome was defined as an increase of at least 20% in hemoglobin level from the nadir within 1 week. RESULTS: Of the 118 patients with HS who attended our hospital during the study period, 20 were treated with steroids and 9 received no treatment. Mean nadir hemoglobin level in both groups was 6.9 g/dl. The study group had a total of 50 steroid-treated hemolytic crises of which 37 (74%) responded favorably to treatment. Treatment failure was significantly associated with a low dose (<1 mg/kg/day) or short duration (<1 week) of treatment. The nine untreated patients had 16 hemolytic crises, of which 25% had a good outcome. Steroid therapy was significantly more effective than no therapy in increasing hemoglobin level (P = 0.015) in these hemolytic crises. CONCLUSION: Steroid therapy may be effective in augmenting hemoglobin levels during hemolytic crises in patients with moderate HS and eventually will result in a reduced need for RBC transfusion.

Propolis influence on erythrocyte membrane disorder (hereditary spherocytosis): a first approach.

Propolis is a resinous substance collected from plants by bees. Its composition depends on the vegetation, the season, and the source area. It usually contains many chemical compounds such as polyphenols, steroids and amino acids. The hereditary spherocytosis (HS) is a type of anaemia characterized by microcytic and hyperchromic red cells, spherical in shape and without central pallor. Clinically, subjects present from asymptomatic conditions to severe haemolytic anaemia. In this study it was evaluated the effect of two propolis extracts in the osmotic fragility of HS patient red blood cell (RBC) membrane. It was found that propolis decreases the erythrocytes membrane fragility, being the effect of Bornes propolis more pronounced than Fundão propolis'. This effect was related with the higher phenolic content of the former propolis. The results obtained in vitro suggest that the membrane fragility increases under oxidative stress conditions for the patient RBC's and the protection effect of propolis is due to its antioxidant properties. These results open doors for future investigations in order to elucidate the mechanisms, identify the main compounds involved in this fragility protection of the erythrocyte membrane. This is the first work reporting an evaluation of the propolis effect in a blood disease.

Oxidative stress contributes to hemolysis in patients with hereditary spherocytosis and can be ameliorated by fermented papaya preparation.

In the present study, we questioned the role of oxidative stress in hereditary spherocytosis (HS), where red blood cells (RBC) have a shortened survival due to primary deficiency in membrane proteins. Using flow cytometry techniques, we showed that RBC derived from 17 HS patients of seven families generate more reactive oxygen species, membrane lipid peroxides, and less reduced glutathione than normal RBC. Following in vitro incubation of HS-RBC from seven patients with a fermentation bioproduct of Carica papaya (fermented papaya preparation (FPP)) with known antioxidative properties, oxidative stress markers were significantly reduced. Similar results were obtained following treatment with FPP for 3 months of 10 adult HS patients, as well as decreased tendency to undergo hemolysis. The hemoglobin levels increased by >1 g/dl, mean corpuscular hemoglobin concentration decreased by >1 g/dl, and the reticulocyte count decreased by 0.93%. Concomitantly, lactic dehydrogenase decreased by 17% and indirect bilirubin by 50%. A significant decrease in malonyldialdehyde was also detected. These data indicate that oxidative stress plays an important role in the pathophysiology of HS which can be ameliorated by an antioxidant such as FPP. Additional clinical trials with FPP and other antioxidants are warranted.

Hereditary spherocytosis.

Hereditary spherocytosis is a congenital haemolytic anaemia due to defect in spectrin-a RBC membrane protein and is transmitted as autosomal dominant. Due to this defect there is presence of characteristic spherical cell in peripheral blood smear and osmotic fragility is increased. Haemolytic anaemia, reticulocytosis, jaundice and splenomegaly are present. This article reports a case of a 9 year old boy who presented with a history of prolonged jaundice since the age of 4 years and recurrent pain in the right upper quadrant of abdomen. Clinical examination revealed jaundice, enlarged liver and marked splenomegaly. Investigations confirmed the diagnosis of hereditary spherocytosis by the presence of spherocytes in blood smear, raised reticulocytes and increased osmotic fragility. The patient was subjected to splenectomy after vaccination against coccobacillus and was discharged after proper advice and on post splenectomy antibiotic prophylaxis.

[Recombinant Human Erythropoietin (r-HuEPO) therapy in a newborn with hereditary spherocytosis]. / Utilisation de l'érythropoïétine chez un nouveau-né atteint de sphérocytose héréditaire.

UNLABELLED: The newborn with hereditary spherocytosis can develop severe anemia, requiring red blood cell transfusions. Therapy with r-HuEPO has been proposed to avoid transfusions. CASE REPORT: Hereditary spherocytosis was diagnosed in a newborn who had severe and early jaundice. He was treated with r-HuEPO, and did not require red blood cells transfusion. CONCLUSION: Recombinant erythropoïetin might be an interesting alternative to red blood cells transfusions during the neonatal period in newborns with hereditary spherocytosis.

[Recombinant erythropoietins--an alternative therapy to red cell blood transfusions in infants with hereditary spherocytosis]. / Zastosowanie erytropoetyny w leczeniu sferocytozy wrodzonej o ciezkim przebiegu klinicznym u niemowlecia--alternatywa dla transfuzji masy erytrocytarnej?

Hereditary spherocytosis is the most frequently occurring haemolytic anaemia. Some patients manifest clinical signs during the neonatal period and require transfusion. A case of hereditary spherocytosis in neonate is presented. The use of rhEPO during the first months may be an alternative therapy to red cell transfusion.

Moyamoya syndrome with spherocytosis: effect of splenectomy on strokes.

A 3-year-old male patient with hereditary spherocytosis who developed moyamoya syndrome, presenting hemiplegia, and slurred speech is reported. Transient ischemic attacks occurred repeatedly with hemolytic crises. Magnetic resonance imaging and angiography revealed bilateral occlusion of the internal carotid and middle cerebral arteries with the formation of moyamoya vessels and multiple infarctions in the basal ganglia. Although splenectomy can increase the risk of stroke, no stroke occurred after splenectomy. On aspirin and dipyridamole therapy the patient has been free of neurologic deficits and progression of the vasculopathy for 5 years. This rare observation suggests that anemic hypoxia more greatly contributes to the progression of moyamoya syndrome than postsplenectomy thrombocytosis or reduced deformability of spherocytes.