Hemolytic Jaundice Research Articles

Successful Allogeneic Hematopoietic Stem Cell Transplantation of a Patient Suffering from Type II Congenital Dyserythropoietic Anemia A Rare Case Report from Western India.

The most frequent form of congenital dyserythropoiesis (CDA) is congenital dyserythropoietic anemia II (CDA II). CDA II is a rare genetic anemia in humans, inherited in an autosomally recessive mode, characterized by hepatosplenomegaly normocytic anemia and hemolytic jaundice. Patients are usually transfusion-independent except in severe type. We are here reporting a case of severe transfusion-dependent type II congenital dyserythropoietic anemia in a 5-year-old patient who has undergone allogeneic hematopoietic stem cell transplantation (HSCT) at our bone marrow transplantation centre. Patient has had up until now more than 14 mL/kg/month of packed cell volume (PCV), which he required every 15 to 20 days to maintain his hemoglobin of 10 gm/dL and hematocrit of 30%. His pre-HSCT serum ferritin was 1500 ng/mL and he was on iron chelating therapy. Donor was HLA identical sibling (younger brother). The preparative regimen used was busulfan, cyclophosphamide, and antithymocyte globulin (Thymoglobulin). Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD) prophylaxis. Engraftment of donor cells was quick and the posttransplant course was uneventful. The patient is presently alive and doing well and he has been transfusion-independent for the past 33 months after HSCT.

KLF1 Null Neonates Display Hydrops Fetalis and a Deranged Erythroid Transcriptome

We describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of >500 genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We interrogated recently published KLF1 ChIP-seq to determine directly regulated KLF1 genes in man. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. KIF23 mutations result in CDA type III so our finding provides a direct link btween CDA IV adn CDA III. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. DisclosuresNo relevant conflicts of interest to declare.

Thrombotic, thrombocytopenic purpura (ADAMTS-13 deficiency): a rare neonatal presentation

Abstract Congenital ADAMTS-13 deficiency is rare, with only between 150 and 200 living cases described internationally. It can present in the neonatal period with thrombocytopenia that may be associated with thrombosis rather than haemorrhage, microangiopathic haemolytic anaemia (MAHA) and jaundice requiring exchange transfusion. We report a case of a large cerebral infarction resulting from severe ADAMTS-13 deficiency in the immediate neonatal period. The diagnosis of ADAMTS-13 deficiency should be considered in babies with haemolytic anaemia, jaundice, thrombocytopenia and a negative direct antiglobulin (Coombs) test (DAT). It is important to diagnose and treat early in order to prevent further brain and kidney damage.

Severe Hemolytic Jaundice in a Neonate with a Novel COL4A1 Mutation

We report our experience with a preterm infant with severe hemolytic jaundice who required exchange transfusion just after birth. The patient was negative for alloimmune hemolysis as a result of maternal-fetal blood type incompatibility, and tests for inherited defects in erythrocyte metabolism, membrane function, and hemoglobin synthesis were normal. We also performed a bone marrow examination, but could not identify the cause of hemolysis. The patient had several other complications, including porencephaly, epilepsy, elevated serum levels of creatine kinase, and persistent microscopic hematuria. Later, we detected a genetic mutation in COL4A1, which was recently found to be associated with hemolytic anemia. We therefore believe that all of the patient's clinical features, including hemolytic anemia, were due to the mutation in COL4A1. Genetic testing for COL4A1 mutations is recommended in neonates who exhibit hemolytic disease of unknown etiology, especially when other complications compatible with COL4A1-related disorders are present.

Role of Subgroup Incompatibility in Newborn Jaundice Requiring Exchange Transfusion

We aimed to determine the role of exchange transfusion related complications, treatment, and etiology as well as subgroup incompatibility in patients subject to ET (exchange transfusion) due to newborn jaundice. 82 patients hospitalized due to newborn jaundice and exposed to exchange transfusion between August 2007 and August 2011 were retrospectively studied. Before ET mean total serum bilirubin was 29,2±9,83. The most frequent cause of ET was ABO incompatibility (31%) followed by Rh incompatibility (19%) and subgroup incompatibility (17%), respectively. In 46% of all patients and in 71% of the patients presenting with subgroup incompatibility , direct combs test was detected to be (+). 49% of the patients were administrated with intravenous immunoglobulin. 5 of the patients who were exposed to ET presented with hydrops fetalis. Of these patients 3 had Rh, 1 had ABO while the other had subgroup incompatibility. Although ABO and Rh incompatibility are substantial underlying reasons of severe jaundice requiring exchange transfusion, particularly widespread use of RhoGAM thereby enabling the prior identification and precautions, ET need was reduced compared to previous cases. On the contrary, SGU related severe hemolytic jaundice relatively enhanced, however.

Disfunción hepática constitucional (enfermedad de Gilbert), a propósito de once casos estudiados en el Hospital Obrero de Lima.

Presentamos once casos de Disfunción Hepática Constitucional (Enfermedad de Gilbert), estudiados en el Servicio de Gastroenterología del Hospital Obrero de Lima. Ubicamos esta enfermedad dentro del grupo de las Ictericias Crónicas no Hemolíticas por defectos congénitos en el metabolismo de la bilirrubina. Se señala, de acuerdo con los nuevos conceptos sobre el metabolismo de la bilirrubina, que el mecanismo patogénico de esta enfermedad está en relación con una deficiente actividad de la glucoroniltransferasa, enzima encargada de la conjugación de la bilirrubina con el ácido glucorónico.

Profile of acute severe malaria with hepatopathy

Background: The single most dreaded complication in severe malaria is cerebral malaria, but extracerebral serious complications are becoming frequent in endemic areas, which include hepatic dysfunctions with jaundice. Materials and Methods: This prospective case series study was undertaken to observe the clinical profile in 81cases of complicated malaria presenting with jaundice out of 344 hospitalized patients diagnosed with acute severe malaria. Liver function tests were assessed and the patients were followed up to 4 weeks. Results: 85% cases with jaundice had Plasmodium falciparum ( Pf ) infection. Significant findings included a predominantly hemolytic jaundice (mean bilirubin 7.6 mg%, unconjugated 4.83 mg%, conjugated 2.79 mg%), raised ALT > AST (mean 101.2 vs.74.7 iu) and a mean prothrombin time of 3 sec > control. Acute renal failure was common (77%). No residual hepatic dysfunctions were detected in survivors on follow-up. Mortality was 10%, mostly due to delayed diagnosis and associated serious co-morbid conditions. Conclusion: Differentiating fulminant viral hepatitis with multi-organ failure and early treatment of associated complications are crucial to reduce mortality in malaria presenting with jaundice. Hemolytic jaundice with mild and relatively early reversibility of hepatocellular dysfunction usually points towards complicated Pf malaria. Histologically, there is mild hepatic derangement. Acute renal failure is commonly associated. Vivax malaria can also cause hepatic dysfunctions. Mere presence of jaundice does not increase mortality compared to those without jaundice

G6PD Deficiency and G6PD (Mediterranean and Silent) Polymorphisms in Egyptian Infants with Neonatal Hyperbilirubinemia

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited cause of neonatal hemolytic anemia and jaundice. We investigated the prevalence of G6PD deficiency (Mediterranean and silent) polymorphisms in Egyptian infants with neonatal hyperbilirubinemia. Methods: Fifty full-term infants with neonatal jaundice were included. All patients were subjected to a routine hematologic evaluation, total and indirect serum bilirubin levels, direct Coombs test, qualitative evaluation of G6PD enzyme activity, and detection of G6PD Mediterranean and silent mutations by the polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) technique. Results: There were 21 (42%) patients who were G6PD deficient; 29 (58%) had normal activity of the enzyme. Among the G6PD deficient patients, 7/21 (33.3%) had Mediterranean mutation and 6/21 (28.6%) had silent mutation. Conclusion: Our findings, together with other reports, provide data on the prevalence of the Mediterranean variant in Egyptian infants. Further characterization of the G6PD variants requires molecular studies, including analysis of the entire G6PD coding sequence.

The umbilical cord alpha-fetoprotein levels for predicting hyperbilirubinemia in term neonates

Objective: The aim of this study was to investigate the possible relationship between cord bloodalpha-fetoprotein (AFP) level and development of subsequent neonatal hyperbilirubinemia.Study design: The term newborns born between March 2005 and October 2005 were included in the study. Infants with Coombs-positive ABO and/or Rh incompatibility and/or hemolytic jaundice, asphyxia, congenital anomaly and signs of bleeding were excluded from the study. Cord blood AFP levels were measured in 504 full term newborns in this period. Infants were followed-up for possible neonatal hyperbilirubinemia. The capillary bilirubin level (CBL) was examined expeditiously in newborns developing jaundice and in other infants at the time discharge while the screening test was being performed.Results: The mean umbilical cord AFP level was 49.1 ± 44.9 mg/L (range 1.1–396.2 mg/L), mean CBL was 5.8 ± 3.1 mg/dL (range 1–19.4 mg/dL), and the mean bilirubin detection time was 37 ± 23.2 hours (range 12–144 h) of age. Although a significant positive correlation was found between umbilical cord AFP and CBL levels, it was weak (r = 0.187, p < 0.001). Comparison of AFP levels in terms of bilirubin percentile values appropriate for postnatal age also showed a significant weak positive correlation (r = 0.113, p < 0.001).Conclusion: The umbilical cord AFP levels may not be used as a strong predictor for the determination of newborns at risk for hyperbilirubinemia.

The effect of clofibrate in near term newborns with non hemolytic jaundice

The aim of this study was to evaluate the efficacy of clofibrate in reducing total serum bilirubin levels in near term neonates with non hemolytic jaundice. A randomized controlled study was carried out in the neonatal ward of Children's Hospital, Tabriz, Iran, over one year period. Sixty eight healthy near term infants with non hemolytic hyperbilirubinemia were randomized to receive phototherapy plus clofibrate (n=35) or phototherapy and placebo (n=33). There were no significant differences in the weight, gender, modes of delivery and age of neonates between two groups. Similarly, the mean total serum bilirubin (TSB) level at the time of admission was not significantly different between the two groups (19.72±1.79 versus 20.05±2.82 mg/dl, P=0.57). The mean TSB 48 h after phototherapy (8.06±1.34 versus 10.94±2.87 mg/dl P=0.02) and the mean duration of phototherapy (64.32±12.48 versus 87.84±29.76 h P<0.0001) was significantly lower in clofibrate treated group. Clofibrate is an effective adjunctive drug in neonatal hyperbilirubinemia and results to lower TSB level and reduced duration of phototherapy in near term newborns. Key words: Clofibrate, near term neonate, non hemolytic jaundice, phototherapy.

A neonate with Coombs-negative hemolytic jaundice with spherocytes but normal erythrocyte indices: a rare case of autosomal-recessive hereditary spherocytosis due to alpha-spectrin deficiency

The diagnosis of hereditary spherocytosis (HS) in a newborn infant is generally made on the basis of a positive family history, spherocytes on blood film and Coombs-negative hemolytic jaundice of variable severity with an elevated mean corpuscular hemoglobin concentration (MCHC) and a low mean corpuscular volume (MCV). In general, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) quantification of erythrocyte membrane proteins is not needed to make the clinical diagnosis of HS. However, we observed that a neonate with no family history of HS, but with abundant spherocytosis on repeated blood films, Coombs-negative hemolytic jaundice and normal MCHC and MCV measurements, where SDS-PAGE revealed alpha-spectrin deficiency, a rare autosomal-recessive variety of HS that generally has a severe clinical phenotype.

Hepatic manifestations in hematological disorders.

Liver involvement is often observed in several hematological disorders, resulting in abnormal liver function tests, abnormalities in liver imaging studies, or clinical symptoms presenting with hepatic manifestations. In hemolytic anemia, jaundice and hepatosplenomegaly are often seen mimicking liver diseases. In hematologic malignancies, malignant cells often infiltrate the liver and may demonstrate abnormal liver function test results accompanied by hepatosplenomegaly or formation of multiple nodules in the liver and/or spleen. These cases may further evolve into fulminant hepatic failure.

α-HUS Patient as a Renal Transplant Recipient - A Case Report

Background: α-HUS is a rare cause of ESRD. The problem arises during selecting patients for renal transplantation, in whom ESRD developed due to α-HUS. In such cases, genetic testing should be performed (C3, CFH-, CFI- and MCP deficiency). A risk of recurrence of α-HUS after kidney transplantation (ktx) is the highest in the first 6 months and depends on the type of defect (the highest risk ˜ 80% for CFH and CFI mutations, ˜ 20% MCP). CNI-avoidance regimen does not reduce the risk of recurrence. In our country living donation for ESRD-patient with α-HUS is not recommended. Kidney transplantation from a cadaveric donor is acceptable, although there is a high risk of recurrence of the primary disease and graft failure. We present the cases of three brothers with ESRD in course of α-HUS with family HUS-history; two of them were transplanted, but due to the lack of real opportunities, genetic testing proving α-HUS was not performed. Description: The first brother, 21-year-old, with no previous signs of disease, suddenly developed hemolytic anemia, jaundice and AKI. Died in 4 weeks. Six years later, the second brother, aged 27, developed the same signs and symptoms. Renal biopsy revealed TMA. We conducted plasmapheresis (17 sessions) but with no renal improvement. Patient was referred to hemodialysis. Two years later, the third brother developed HUS and AKI. Due to thrombocytopenia renal biopsy was not performed. Plasmapheresis and FFP infusions were started, but renal function did not improved and hemodialysis were continued. The patient was highly motivated to ktx so he was referred to pretransplant assessment. Unfortunately, genetic testing for α-HUS is not available in our country due to economical reason we did not perform genetic testing abroad. Patient was informed about the increased risk of graft loss and underwent ktx from cadaveric donor with immunosupressive regimen: steroids+tacrolimus+MMF. Three months after ktx in protocol biopsy we found no signs of TMA. Currently, 14 months after ktx, graft function is stable, tacrolimus concentration is 4-5 ng/ml, serum creatinine concentration is 1,7 mg/dl. Then, the second brother underwent ktx from cadaveric donor (immunosupressive regimen: steroids+tacrolimus +MMF+basiliximab) with immediate graft function. After three months of follow-up graft function remains stable, serum creatinine concentration is 1,3 mg/dl, tacrolimus concentration is 5-6 ng/ml, protocol biopsy in 3 months after ktx revealed normal kidney structure. Discussion: The cases illustrate the difficulties in application for ktx α-HUS-patient. We did not manage to perform necessary α-HUS genetic testing, what became a serious concern. Uneventful course after ktx might be determined by the presence of mild defects of complement or other cause, what is elusive for the authors. Conclusion: The lack of widespread access to specialized α-HUS genetic testing impeded qualification for ktx and forces the doctor to make decisions based on clinical experience and personal intuition.

Refeeding syndrome in a small‐for‐dates micro‐preemie receiving early parenteral nutrition

This report describes a small-for-date extremely low birth weight infant who manifested bradycardic events, respiratory failure, and hemolytic jaundice during her first week of life. These complications were attributed to severe hypophosphatemia and hypokalemia. Inadequate supply and refeeding syndrome triggered by early aggressive parenteral nutrition were responsible for electrolyte abnormalities.

Amniotic fluid embolism: incidence, risk factors, and impact on perinatal outcome

To extend our previous work on AFE in Canada by including stricter criteria for case identification and by examining risks for stillbirth, neonatal mortality and serious maternal and neonatal morbidity. Population-based cohort study. Canada. In all, 4,508,462 hospital deliveries from fiscal year 1991/92 to 2008/09. To reduce false-positive diagnoses, we restricted our analysis to AFE cases with cardiac arrest, shock or severe hypertension, respiratory distress, mechanical ventilation, coma, seizure, or coagulation disorder. Linkage of maternal and neonatal records, available since 2001/02, enabled us to examine the effects of AFE on neonatal outcomes. Detailed demographic and clinical data facilitated control for a broad array of potential confounding variables. Amniotic fluid embolism, in-hospital neonatal death, asphyxia, mechanical ventilation, bacterial sepsis, seizure, nonimmune haemolytic or traumatic jaundice and length of hospital stay. A total of 292 AFE cases were identified, of which only 120 (40%) were confirmed after applying our additional diagnostic criteria, yielding an AFE incidence of 2.5 per 100,000 deliveries. Of the 120 confirmed cases, 33 (27%) were fatal. Significant modifiable risk factors included medical induction, caesarean delivery, instrumental vaginal delivery, and uterine or cervical trauma. Amniotic fluid embolism was associated with significantly increased risks of stillbirth and neonatal asphyxia, mechanical ventilation, sepsis, seizures and prolonged length of hospital stay. Amniotic fluid embolism remains a rare but serious obstetric outcome, with several important modifiable risk factors and major implications for maternal, fetal and neonatal health.

A Chinese family carrying novel mutations in SEC23B and HFE2, the genes responsible for congenital dyserythropoietic anaemia II (CDA II) and primary iron overload, respectively

A Chinese family carrying novel mutations in <scp><i>SEC23B</i></scp> and <scp><i>HFE2</i></scp>, the genes responsible for congenital dyserythropoietic anaemia <scp>II</scp> (<scp>CDA II</scp>) and primary iron overload, respectively

Hemolytic Disease of the Newborn Caused by Irregular Blood Subgroup (Kell, C, c, E, and e) Incompatibilities: Report of 106 Cases at a Tertiary-Care Centre

To determine the clinical spectrum of hemolytic disease due to irregular blood subgroup incompatibility in hospitalized neonates. The medical records of the all hospitalized newborn patients diagnosed with indirect hyperbilirubinemia due to subgroup incompatibility in Kell, C, c, E, and e systems were included in the study. Data from 106 newborns with hemolytic jaundice due to irregular blood subgroups were retrospectively evaluated, and clinical and laboratory findings were compared between patients . The treatment modalities given to the patients of each subgroup types and the laboratory findings and treatment modalities of the cases according to Coombs tests results were also analyzed. Fetal affection of the hemolysis and also fetal losses due to irregular red-cell alloimmunization were not detected in prenatal course, as there was no follow-up of these pregnancies. The mean postnatal hospitalizing age was 6.1 ± 5.2 days after birth. The mean total bilirubin level and the mean hemoglobin value on hospitalization were 343.7 ± 63.3 µmol/L (=20.1 ± 3.7 mg/dL) and 14.9 ± 3.4 g/dL, respectively. Of 106 patients identified with irregular subgroup incompatibility, 40 infants (37.7%) were associated with C, 22 (20.8%) with c, 30 (28.3%) with E, 9 (8.5%) with e, and 5 (4.7%) with Kell subgroup system. Positive Coombs tests (either direct and/or indirect) occurred in 28.3% of the study cases. Hydrops fetalis was determined in 5 of 106 neonates (4.7%). Twenty-two of 106 (20.8%) patients required total exchange transfusion. Positive Coombs test in cases required total exchange transfusion was 63.6%. Our data expose the magnitude and spectrum of the potential developing severe hemolytic disease and immune hydrops due to irregular subgroup incompatibility. Minor group antibody screening is recommended both in the mother and the high-risk infants with hyperbilirubinemia and hemolytic disease of the newborn.

Light-emitting diode phototherapy for unconjugated hyperbilirubinaemia in neonates

Phototherapy is the mainstay of treatment of neonatal hyperbilirubinaemia. The commonly used light sources for providing phototherapy are special blue fluorescent tubes, compact fluorescent tubes and halogen spotlights. However, light emitting diodes (LEDs) as light sources with high luminous intensity, narrow wavelength band and higher delivered irradiance could make phototherapy more efficacious than the conventional phototherapy units. To evaluate the effect of LED phototherapy as compared to conventional phototherapy in decreasing serum total bilirubin levels and duration of treatment in neonates with unconjugated hyperbilirubinaemia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 1), MEDLINE (1966 to April 30, 2010) and EMBASE (1988 to July 8, 2009). Handsearches of the proceedings of annual meetings of The European Society for Paediatric Research and The Society for Pediatric Research were conducted through 2010. Randomised or quasi-randomised controlled trials were eligible for inclusion if they enrolled neonates (term and preterm) with unconjugated hyperbilirubinaemia and compared LED phototherapy with other light sources (fluorescent tubes, compact fluorescent tubes, halogen spotlight; method of administration: conventional or fibreoptic). We used the standard methods of The Cochrane Collaboration and its Neonatal Review Group for data collection and analysis. Six randomised controlled trials met the inclusion criteria for this review. Four studies compared LED and halogen light sources. Two studies compared LED and compact fluorescent light sources. The duration of phototherapy (six studies, 630 neonates) was comparable in LED and non-LED phototherapy groups (mean difference (hours) -0.43, 95% CI -1.91 to 1.05). The rate of decline of serum total bilirubin (STB) (four studies, 511 neonates) was also similar in the two groups (mean difference (mg/dL/hour) 0.01, 95% CI -0.02 to 0.04). Treatment failure, defined as the need of additional phototherapy or exchange blood transfusion (1 study, 272 neonates), was comparable (RR 1.83, 95% CI 0.47 to 7.17). Side effects of phototherapy such as hypothermia (RR 6.41, 95% CI 0.33 to 122.97), hyperthermia (RR 0.61, 95% CI 0.18 to 2.11) and skin rash (RR 1.83, 95% CI 0.17 to 19.96) were rare and occurred with similar frequency in the two groups. LED light source phototherapy is efficacious in bringing down levels of serum total bilirubin at rates that are similar to phototherapy with conventional (compact fluorescent lamp (CFL) or halogen) light sources. Further studies are warranted for evaluating efficacy of LED phototherapy in neonates with haemolytic jaundice or in the presence of severe hyperbilirubinaemia (STB ≥ 20 mg/dL).

Clinical Course and Prognosis of Hemolytic Jaundice in Neonates in North East of Iran

Background: Hemolytic jaundice is the most serious cause of hyperbilirubinemia among neonates. It may develop to kernicterus due to misdiagnosis or inappropriate treatment. The aim of this study is to determine the prevalence rate of hemolytic jaundice, predisposing factors and assessment of treatment and complications in hemolytic jaundice. Methods: This prospective descriptive study has been performed on 1568 newborns with jaundice as their chief complaint, in a seven-year period at Ghaem hospital in Mashhad, Iran. 795 neonates were included in our study (237 infants with hemolytic jaundice and 558 infants with idiopathic jaundice). Complete physical examinations and laboratory tests were performed and data were recorded. Statistical analysis was carried out, using SPSS 11.5 statistical package. Results: In the present study, significant differences were determined between two groups of hemolytic and idiopathic jaundice for total serum bilirubin, hematocrit, time of jaundice appearance, age of admission, hospitalization period and incidence of kernicterus (p<0.001). Newborns with ABO incompatibility (17%), Rh disease (7%), G6PD deficiency (6%) and minor blood group immunization (2%) were developed to hyperbilirubinemia, respectively. Among the newborns affected with kernicterus, 12 cases were placed in group with ABO hemolytic disease (9%), 3 cases were in Rh isoimmunization group (5.5%), 4 cases were in G6PD deficiency group (8.9%) and 9 cases were idiopathic (1.6%). Conclusion: Jaundice due to hemolysis is associated with a higher serum bilirubin and more complications like kernicterus. ABO incompatibility was the most common reason of hemolytic jaundice among neonates in north east of Iran. Special attention to ABO incompatibility and G6PD enzyme screening may decrease complications and improve the prognosis.

Clinical and Hematological Studies on Hemolytic Icterus of Foals

Clinical and Hematological Studies on Hemolytic Icterus of Foals