Hematological and molecular analysis of patients with G6PD deficiency revealed coexistent hereditary spherocytosis and alpha thalassemia

Introduction. Though, in developed countries, laparoscopy is now a gold standard for splenectomy, we are lacking in this aspect in the eastern world. Splenectomy has mostly been performed by open surgery in our region. This is our effort to introduce laparoscopic splenectomy in our country.Methods. This is a retrospective cohort study done in patients presenting to hematology and surgery department of our hospital who underwent laparoscopic splenectomy for hematological diseases from January 2013 to December 2016.Results. There were 50 patients (38 females, 12 males). The diagnoses were idiopathic thrombocytopenic purpura in 31, (steroid/azathioprine-resistant, steroid dependent), hereditary spherocytosis in 9, alpha-thalassemia in 3, beta-thalassemia in 2, autoimmune hemolytic anemia in 4, and isolated splenic tuberculosis in 1. Average platelet counts preoperatively were62000±11000/mm3 (range 52000-325000/mm3). The mean operative time was130±49minutes (range 108-224 min). The mean postoperative stay was4±2.11days (range 3-9 days). Laparoscopic splenectomy could be completed in 45 (90%) patients.Conclusion. Laparoscopic splenectomy could be successfully contemplated in patients with hematological diseases, especially if spleen is normal or only mildly enlarged, and is an advantageous alternative to open splenectomy. Absence of ideal resources has not limited our progress in minimal access approach.

Download Full-text

Recurrent acute splenic sequestration crisis due to interacting genetic defects: hemoglobin SC disease and hereditary spherocytosis

Blood ◽

10.1182/blood.v75.1.266.266 ◽

1990 ◽

Vol 75 (1) ◽

pp. 266-270 ◽

Cited By ~ 28

Author(s):

TE Warkentin ◽

RD Barr ◽

MA Ali ◽

N Mohandas

Keyword(s):

Hereditary Spherocytosis ◽

Genetic Defects ◽

Mechanical Instability ◽

Splenic Sequestration ◽

Alpha Thalassemia ◽

Unusual Occurrence ◽

Distinguishing Features ◽

Hemoglobin Sc Disease ◽

Reduced Surface ◽

In Cells

Abstract A 14-year-old boy with hemoglobin SC disease and alpha-thalassemia-2 experienced five episodes of acute splenic sequestration crisis (ASSC), while two of his siblings with identical globin genotypes (SC and - alpha/alpha alpha) had no such experience. To determine if an additional red blood cell (RBC) defect was responsible for the unusual occurrence of frequent ASSCs, we performed detailed rheologic characterization and membrane protein analysis on RBCs from the proband and other members of his family. Reduced surface area, increased mechanical instability, and decreased spectrin content of the membrane, distinguishing features of RBCs in hereditary spherocytosis, were observed in cells from the proband and his mother, but not in cells from other family members. These findings are consistent with the dominant inheritance of spherocytosis by the proband. We suggest that the combined effects of SC disease and spherocytosis in the proband resulted in decreased RBC deformability and led to increased splenic trapping, intrasplenic sickling, and consequently, recurrent sequestration crisis. Marked clinical and hematologic improvement occurred from splenectomy. Thus, inheritance of interacting genetic defects, sickling hemoglobinopathy, and hereditary spherocytosis appear to be responsible for the unusual clinical manifestation of recurrent ASSC in this patient.

Download Full-text

Prospective Newborn Screening for Sickle Cell Disease and Other Inherited Blood Disorders in Central Malawi

International Journal of Public Health ◽

10.3389/ijph.2021.629338 ◽

2021 ◽

Vol 66 ◽

Author(s):

Gerald Tegha ◽

Hillary M. Topazian ◽

Portia Kamthunzi ◽

Thad Howard ◽

Zondwayo Tembo ◽

...

Keyword(s):

Sickle Cell Disease ◽

Newborn Screening ◽

Sickle Cell ◽

Early Identification ◽

G6pd Deficiency ◽

The United States ◽

Sub Saharan Africa ◽

Cell Disease ◽

Hematological Disorders ◽

Alpha Thalassemia

Objectives: Newborn screening in the United States and Europe allows early identification of congenital disorders but does not yet exist in most low-resource settings, especially in sub-Saharan Africa. Newborn screening can identify multiple inherited hematological disorders, but feasibility and effectiveness for Africa are not fully determined.Methods: Surplus dried blood spot collected in Central Malawi through the HIV Early Infant Diagnosis surveillance program were repurposed and tested by isoelectric focusing for sickle cell disease and trait. Additional genetic testing identified G6PD deficiency and alpha thalassemia.Results: Testing of 10,529 cards revealed an overall sickle cell trait prevalence of 7.0% (range 3.9–9.7% by district); 10 of 14 infants identified with sickle cell disease (prevalence 0.1%) were located and received care at a specialized clinic. Subsequent testing of 1,329 randomly selected cards identified alpha thalassemia trait in 45.7% of samples, and G6PD deficiency in 20.4% of males and 3.4% of females, with 29.0% of females as heterozygous carriers.Conclusion: Inherited hematological disorders are common in Central Malawi; early identification through newborn screening can improve clinical outcomes and should be supported throughout Africa.

Download Full-text

Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

Antioxidants ◽

10.3390/antiox9090863 ◽

2020 ◽

Vol 9 (9) ◽

pp. 863

Author(s):

Fatou Gueye Tall ◽

Cyril Martin ◽

El hadji Malick Ndour ◽

Camille Faes ◽

Indou Déme Ly ◽

...

Keyword(s):

Oxidative Stress ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

G6pd Deficiency ◽

Clinical Severity ◽

Oxidative Stress Biomarkers ◽

Antioxidant Genes ◽

Stress Biomarkers ◽

Alpha Thalassemia ◽

The Impact

Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs2333227) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD, CAT, GPx) and clinical severity in 301 Senegalese SCA hydroxyurea-free children at steady-state (median age 9.1 years, sex ratio H/F = 1.3). Plasma oxidative stress biomarkers were compared with those of a control group (AA). CAT activity, AOPP, and MDA levels were higher in SCA than in AA individuals while XO, GPX, and MnSOD activities were lower. The presence of alpha-thalassemia decreased MDA level and MPO activity but no effect of the HbF QTL or G6PD deficiency was observed. SCA children who experienced their first hospitalized complication before 3 years old had higher MnSOD and CAT activities than the other children while those with no hospitalized VOC in the previous 2 years presented higher GPX activity. Age of the first hospitalized complication and AOPP levels were affected by the MPO rs2333227 SNP. Our results suggest that alpha-thalassemia modulates oxidative stress in SCA, presumably because of a reduction in the MPO activity.

Download Full-text

G6PD deficiency, absence of α-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia

Blood ◽

10.1182/blood-2008-03-143891 ◽

2008 ◽

Vol 112 (10) ◽

pp. 4314-4317 ◽

Cited By ~ 98

Author(s):

Françoise Bernaudin ◽

Suzanne Verlhac ◽

Sylvie Chevret ◽

Martine Torres ◽

Lena Coic ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

G6pd Deficiency ◽

Odds Ratio ◽

Multivariate Logistic Regression Analysis ◽

Multivariate Logistic Regression ◽

Alpha Thalassemia ◽

Independent Risk Factors ◽

First Time

AbstractStroke is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). This study aimed at defining predictive factors for abnormally high velocities (≥ 2 m/sec) based on the Créteil pediatric sickle cell anemia (SCA) cohort composed of 373 stroke-free SCA children. α genes and β-globin haplotypes were determined. Biologic parameters were obtained at baseline. α-thalassemia was present in 155 of 325 and G6PD deficiency in 36 of 325 evaluated patients. TCD was abnormal in 62 of 373 patients. Multivariate logistic regression analysis showed that G6PD deficiency (odds ratio [OR] = 3.36, 95% confidence interval [CI] 1.10-10.33; P = .034), absence of alpha-thalassemia (OR = 6.45, 95% CI 2.21-18.87; P = .001), hemoglobin (OR per g/dL = 0.63, 95% CI 0.41-0.97; P = .038), and lactate dehydrogenase (LDH) levels (OR per IU/L = 1.001, 95% CI 1.000-1.002; P = .047) were independent risk factors for abnormally high velocities. This study confirms the protective effect of alpha-thalassemia and shows for the first time that G6PD deficiency and hemolysis independently increase the risk of cerebral vasculopathy.

Download Full-text

Hereditary Hemolytic Anemias Other Than Thalassemia: Single Center Experience

Blood ◽

10.1182/blood-2019-121702 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4855-4855

Author(s):

Gul Nihal Ozdemir ◽

Mehmet Akif Kilic

Keyword(s):

Family History ◽

Pyruvate Kinase ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

G6pd Deficiency ◽

Chelating Agents ◽

Hereditary Spherocytosis ◽

Conflicts Of Interest ◽

Single Center ◽

Pyruvate Kinase Deficiency

Aim: The aim of this study was to evaluate the demographic information, clinical and hematologic findings and treatment response of patients diagnosed with hereditary hemolytic anemias other than thalassemia at a single center. Materials and Methods: A total of 157 children with a diagnosis of hereditary hemolytic anemia except thalassemia were included. Patients' files were reviewed retrospectively. Demographic, clinical and laboratory characteristics, family history, complications, history of splenectomy and cholecystectomy, splenectomy response, use of chelating agents and other treatments, first transfusion age and transfusion frequency of patients were evaluated. Mean, standard deviation, median and 25-75 percentile values were used when descriptive analysis were presented. Mann Whitney U and Kruskal Wallis Tests were used for nonparametric groups. Pearson Chi Square and Fisher Tests were used when categorical comparisons were made. A value of P <0.05 was considered statistically significant. Results: Of the 157 patients , 101 patients (64,3%) had hereditary spherocytosis, 39 patients had (24,8%) glucose-6 phosphate dehydrogenase deficiency (G6PD), 15 patients had (9,6%) sickle cell anemia and 2 patients had (1.3%) pyruvate kinase deficiency. Sixty-one patients (38,9%) were girls and 96 were boys (61,1%). Median age of diagnosis was 10 months (range 1-188 months). Of 97 patients whom family history was questioned, 63 (64.9%) had family history. Most common complaint at diagnosis was paleness. Eighty-two patients had splenomegaly. Twenty-two patients (14%) had cholecystectomy and 56 patients (35.7%) had splenectomy on follow-up. The most frequent indication for splenectomy was hereditary spherocytosis. Fifty-eight (36.9%) patients required regular transfusion. Mean ferritin level of all was 506.3±1175.0. Patients with pyruvate kinase had the highest ferritin levels. Erythropoietin was used for 1 patient with hereditary spherocytosis in infancy without a response. Ten of 15 patients with sickle cell anemia were using hydroxyurea. Thirteen percent of all were using chelating agents. Conclusion: Hereditary spherocytosis and G6PD deficiency were the most common hereditary hemolytic anemias except thalassemia in our center. Family history was more frequent in hereditary spherocytosis compared to other hereditary hemolytic anemias. Patients with G6PD deficiency were diagnosed earlier than other hereditary hemolytic anemias. Hereditary spherocytosis was the most common indication for splenectomy and eliminated/decreased transfusion requirement in 96%. Patients with other hemolytic anemias had lower iron load compared to thalassemia except pyruvate kinase deficiency patients. Disclosures No relevant conflicts of interest to declare.

Download Full-text

G6PD deficiency-induced hemolysis in a Chinese diabetic patient: a case report with clinical and molecular analysis

Acta Diabetologica ◽

10.1007/s00592-010-0236-y ◽

2010 ◽

Vol 50 (1) ◽

pp. 89-92 ◽

Cited By ~ 3

Author(s):

Xue-Jiang Gu ◽

Shuo-Ping Chen ◽

Sheng-Jie Ge ◽

Le-Qun Zheng ◽

Da-Wang Wang ◽

...

Keyword(s):

Case Report ◽

Diabetic Patient ◽

Molecular Analysis ◽

G6pd Deficiency

Download Full-text

Hereditary spherocytosis in association with severe G6PD deficiency: report of an unusual case

Clinica Chimica Acta ◽

10.1016/j.cccn.2004.02.021 ◽

2004 ◽

Vol 344 (1-2) ◽

pp. 221-224 ◽

Cited By ~ 2

Author(s):

Prabhakar S Kedar ◽

Roshan B Colah ◽

Kanjaksha Ghosh ◽

Dipika Mohanty

Keyword(s):

G6pd Deficiency ◽

Unusual Case ◽

Hereditary Spherocytosis

Download Full-text

High LDH Level, G6PD Deficiency and Absence of alpha-Thalassemia Are Significant Independent Risk Factors of Abnormally High Cerebral Velocities in Patients with Sickle Cell Anemia.

Blood ◽

10.1182/blood.v110.11.430.430 ◽

2007 ◽

Vol 110 (11) ◽

pp. 430-430 ◽

Cited By ~ 1

Author(s):

Francoise Bernaudin ◽

Suzanne Verlhac ◽

Lena Coïc ◽

Cecile Arnaud ◽

Annie Kamdem ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

G6pd Deficiency ◽

Intensive Therapy ◽

Univariate Analysis ◽

Beta Globin ◽

Alpha Thalassemia ◽

Cerebral Mri ◽

Independent Risk Factors

Abstract Background Predicting the severity of sickle cell anemia (SCA) is important for providing better informed genetic counseling and for better targeting of intensive therapies. Stroke is the most severe complication in children with SCA and is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). We attempted to define the risk factors associated with high velocities. Methods This study concerned the Créteil pediatric SCA cohort, composed of newborn patients, screened and followed at our Center since birth, and of patients secondarily referred to the Center because of the severity of their disease. Time-averaged mean of maximum velocities (TAMMX) higher than 200 cm/sec were considered as abnormal, resulting in initiation of a transfusion program initiated</DEL>. Cerebral MRI/MRA was done after the age of 5 years or earlier in case of abnormal TCD. Alpha </DEL>genes and beta-globin haplotypes were determined. Baseline biological parameters (G6PD activity; WBC, PMN, Reticulocytes, Platelets counts; Hemoglobin, Hematocrit, HbF, LDH levels; MCV; SpO2) were obtained a minimum of 3 months away from a transfusion, one month from a painful episode, after 18 months of age and, before intensive therapy. Results SS children (390; 189 F, 201 M) were annually explored by TCD (n=2286) since 1992, and followed for a total of 1962 patient-years. The follow-up before initiation of intensive therapy was 1032 patient-years. Nineteen patients experienced an overt stroke. TCD was abnormal in 65 of 390 patients (17%). MRI (n=850) was performed in 268 patients, was abnormal in 86 cases and showed silent infarcts in 67 of 249 patients (27%). Silent infarcts were seen in 33% of patients with abnormal TCD. Alpha genes study, available in 336 patients, demonstrated alpha-thalassemia in 158 patients (47%): 31 had a deletion of 2 genes (7.9%) and 127 of 1 gene (32.6%). G6PD deficiency was present in 26 of 228 evaluated patients (11%). Beta-globin haplotypes studied in 316 patients were Car/Car in 125 (40%), Ben/Ben in 76 (24%), Sen/Sen in 30 (9%) and, “other” in 85 (27%). Univariate analysis showed that the risk of abnormally high velocities was not related to sex, beta-globin haplotypes, pain and acute chest syndrom rates, WBC, PMN, platelets counts, HbF level and SpO2 but was significantly associated with the absence of alpha-thalassemia (p< 0.001), G6PD deficiency (p=0.012), low Hb and Ht levels (p< 0.001), high reticulocyte count (p=0.008), high MCV (p=0.004) and high LDH level (p<0.001). Multivariate logistic regression analysis showed that absence of alpha-thalassemia [OR= 14.5, 95% CI (2.6–79.7)], (p=0.002); G6PD deficiency [OR=6.7, 95% CI (1.7–26.1)], (p=0.006) and, LDH > 1200 UI/L [OR=4.5, 95% CI (1.5–13.5)], (p=0.007) were independent risk factors of abnormally high velocities. Conclusion This study confirms that the risk of high velocities in patients with SCA is significantly decreased by the presence of alpha-thalassemia. It shows for the first time that hemolysis is a more significant risk factor than the degree of anemia and that absence of alpha-thalassemia, G6PD deficiency and hemolysis are significant independent risk factors of cerebral vasculopathy in patients with SCA.

Download Full-text