Sickle Cell Hemoglobinopathies Research Articles

A qualitative secondary evaluation of statewide follow-up interviews for abnormal newborn screening results for cystic fibrosis and sickle cell hemoglobinopathy

A qualitative secondary evaluation of statewide follow-up interviews for abnormal newborn screening results for cystic fibrosis and sickle cell hemoglobinopathy

Structural and Functional Correlation in Sickle Cell Retinopathy Using Spectral-Domain Optical Coherence Tomography and Scanning Laser Ophthalmoscope Microperimetry

To correlate macular structural changes by spectral-domain optical coherence tomography (SD-OCT) with functional changes by scanning laser ophthalmoscope (SLO) microperimetry testing in patients with sickle cell hemoglobinopathies. Prospective, investigational study. Patients with electrophoretic confirmation of sickle cell hemoglobinopathies and normal subjects underwent SD-OCT and microperimetry testing with the OPKO Spectral OCT/SLO instrument. Based on SD-OCT findings, patients were grouped into those with focal macular thinning (Group A) and those without (Group B). Main outcome measure were mean retinal sensitivities measured by microperimetry and mean macular thicknesses in the 9 Early Treatment Diabetic Retinopathy Study (ETDRS)-like subfields. Thirty-seven eyes of 19 patients with sickle cell hemoglobinopathies (SS, SC, and S-thalassemia) and 34 eyes of 34 age-similar normal controls were included. Mean age and mean logMAR best-corrected visual acuity between Groups A and B were not statistically different (39.7 years vs 36.5 years, P = .64 and 0.015 vs 0.016, P = .93, respectively). Group A had significantly thinner retinas compared to Group B in the parafoveal superior (P = .019), parafoveal temporal (P < .004), parafoveal inferior (P = .003), perifoveal superior (P = .04), perifoveal temporal (P = .0005), and perifoveal inferior (P = .045) subfields. The overall mean microperimetry retinal sensitivities of Group A were significantly less than those of Group B (14.2 dB vs 16.5 dB, P = .00005). However, there was no statistical difference between Group B and controls (16.5 dB vs 16.7 dB, P = .63). Sickle cell patients with focal macular thinning present on SD-OCT have significantly decreased retinal sensitivities compared to those without focal thinning or normal controls based on mean microperimetry sensitivities, despite similar age and visual acuity. Microperimetry is a sensitive measurement of macular function in patients with sickle cell hemoglobinopathies.

Outcome of patients (pts) with renal medullary carcinoma (RMC) treated in the era of targeted therapies (TT): A multicenter experience.

386 Background: RMC is a rare, highly aggressive primary neoplasm of the kidney that almost exclusively afflicts young black pts with sickle cell hemoglobinopathies, primarily sickle cell trait. The primary objectives of this study were to evaluate the clinical characteristics and treatment outcome of RMC pts. Methods: We retrospectively reviewed the medical records of pts diagnosed with RMC at four US institutions between 2000 and 2010. Overall survival (OS) was determined from initial diagnosis to date of death or last follow up (F/U). The time interval from date of metastasis to death or last F/U (OSm) was also determined. Kaplan-Meier methods were used to estimate OS and OSm. Results: 20 RMC pts were identified. All pts were black; 14 (70%) were males; 18 had sickle cell trait, 1 had sickle thalassemia and 1 not tested. 19 presented with stages III or IV; 7 (35%) had nephrectomy. Nineteen pts had ≥ 2 metastatic sites. Twelve pts had performance status [PS] 0/1; eight pts had PS 2/3. For the OS analysis, data on 16 pts were available and for the OSm analysis, data on 20 pts were available. The median follow up time for the OS analysis was 722 days. Thirteen of 16 pts died with median OS of 421 days [95%CI: 225–546]. Sixteen of 20 pts died in the OSm analysis with median OSm of 378 days [95%CI: 225–487]. Frontline therapy consisted of TT [sunitinib (5), bevacizumab + erlotinib (1), imatinib (2)], chemotherapy (C) [platinum/gemcitabine or taxane (7), gemcitabine/doxorubicin (2)], C + TT [gemcitabine/cisplatinum/bevacizumab (2), imatinib/doxorubicin (1)]. Three pts achieved a partial response (PR) in first-line (2 with C, 1 with C + TT). Twelve pts received second-line systemic therapies; 4 achieved PR (1 with bevacizumab/erlotinib, 2 with C, 1 with C + TT). Among 15 pts who had TT at any time during their treatment course, only 1 pt had PR. Conclusions: The prognosis of RMC pts remains poor despite initial palliation with systemic therapy. Collaborative multi-institutional efforts are needed to better understand the biology of this disease and improve treatment strategies. No significant financial relationships to disclose.

Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies

Sickle cell anemia is the best known hereditary blood disorder; there are serious complications associated with the condition. Diagnosis and early intervention reduce morbidity and mortality. These benefits have resulted in the widespread use of newborn screening education programs. In Brazil, the National Neonatal Screening Program established by decree 822/01 included sickle cell disease in the list of diseases tested in the so called "heel prick test". Since then, national studies of the results of this program have been periodically published. To review the literature in order to assess the prevalence of sickle cell trait and sickle cell anemia from data of national neonatal screening studies on hemoglobin S (Hb S). A bibliographic review was carried out using the key words: sickle cell anemia & hemoglobinopathies & neonatal screening & Brazil in the Bireme and SciELO databases. Original Brazilian studies presenting data on prevalence of the sickle cell trait (Hb AS) and sickle cell anemia (Hb SS) based on neonatal screening for Hb S were analysed. Twelve original national studies were identified with prevalences varying from 1.1% to 9.8% for the sickle cell trait and from 0.8 to 60 per 100,000 live births for sickle cell disease in different Brazilian regions. Conclusion: Neonatal screening for Hb S is a very useful method to assess the prevalence of sickle cell trait (Hb AS) and sickle cell anemia (Hb SS) in Brazil. There is a heterogeneous distribution of this disease with the highest prevalence in the northeastern region and the lowest prevalence in the south.

PERIPHERAL VASCULAR ABNORMALITIES IN β-THALASSEMIA MAJOR DETECTED BY ULTRA WIDE-FIELD FUNDUS IMAGING.

To describe peripheral retinal vascular abnormalities in two patients with β-thalassemia major. Visual acuity testing, slit-lamp biomicroscopy, dilated fundus examination, ultra wide-field fundus photography, and fluorescein angiography were performed in two consecutive patients with β-thalassemia major. Both patients had excellent visual acuity (20/20 and 20/25). Anterior segment examination was unremarkable. There were no lenticular changes noted in either patient. Dilated fundus examination was only remarkable for peripheral neovascular changes with preretinal hemorrhage in one patient and white without pressure in the other patient. Ultra wide-field fluorescein angiography revealed peripheral ischemia, vascular remodeling, active neovascularization, and arteriovenous anastomosis at the junction of perfused and nonperfused peripheral retina. One patient had sea fan neovascularization with active vitreous hemorrhage requiring peripheral laser photocoagulation. As with patients with sickle cell disorder, patients with β-thalassemia major may require surveillance for peripheral vascular abnormalities, with treatment of these abnormalities before they result in permanent visual loss.

Heparin and prednisone-associated priapism: two case reports

Priapism is a prolonged penile erection that is not associated with sexual stimulation. In this report, two patients who developed priapism 2-4 h after an oral prednisone and intravenous heparin infusion are described. Low-flow (ischaemic) priapism is usually associated with sickle cell disease, haemoglobinopathies, neoplastic syndrome, anticoagulant therapy (heparin and warfarin), psychotropic medication, sildenafil citrate (Viagra) or idiopathic causes. Here we report two cases of prolonged low-flow priapism induced by heparin and prednisone. Treatments were successfully conducted after the priapism, while the exact mechanism remains unclear.

Hb S [β6(A3)Glu→Val, GAG>GTG] in Mexican Mestizos: Frequency and Analysis of the 5' β-Globin Haplotype

Between 1978 and 2009, we studied 1,863 Mexican Mestizo patients with clinical data compatible with a hemoglobinopathy. Of these patients, 382 had some hemoglobin (Hb) abnormality (20.5%), 128 had a sickle cell hemoglobinopathy, representing a general frequency of 6.9%, which is similar to the percentage observed in previous studies on Mexican Mestizos. We analyzed the 5' β-globin haplotype (5'Hp) in 79 unrelated βS chromosomes (26 βS/βS, 14 βS/βThal, nine βS/βA and four βS/βD), and four haplotypes were observed: 72.2% CAR 24.1% Benin, 2.5% Senegal and 1.2% Cameroon; the last two are reported for first time in Mexico. In some Latin American populations such as Brazil, the Bantu haplotype predominates, while in others such as Jamaica, the Benin haplotype is the most frequent, showing heterogeneity of African genes as a consequence of different regions involved in the slave trade.

β-Globin Gene Haplotypes Linked with the Hb D-Punjab [β121(GH4)Glu→Gln, GAA>CAA] Mutation in Eastern India

Hb D-Punjab [β121(GH4)Glu→Gln] is prevalent in the northern states of the Indian subcontinent. Due to inadequate data from Asian countries, the origin and spread of the Hb D-Punjab mutation are uncertain. In a study of sickle cell hemoglobinopathies, we detected the Hb D-Punjab mutation in 25 subjects from 11 unrelated Agharia families. Twelve cases were Hb S [β6(A3)Glu→Val]/Hb D-Punjab compound heterozygotes and 13 were Hb D trait carriers. In 76.0% of the cases, the βD gene was linked to haplotype I, whereas 24.0% had a novel haplotype. None of the haplotypes matched the βA haplotype of the local population. In view of the ancestral origin of the subjects and the high prevalence of the βD gene in the states of northern India, we suggest a North Indian origin for the βD mutation in our population. The finding of a novel haplotype in eastern India supports the hypothesis of a multicentric origin of this mutation.

Tourniquet Use and Sickle Cell Hemoglobinopathy: How Should We Proceed?

The use of tourniquets for upper and lower extremity operative procedures is controversial in patients with sickle cell hemoglobinopathies. The authors used Ovid and MEDLINE®, PubMed, and CINAHL® to detect English-language reports of any surgical procedure where a tourniquet was used on a patient with sickle cell disease or trait. Four papers met the search criteria and were reviewed. These studies included 96 patients with hemoglobin SS, SC, and sickle cell trait (AS). The investigations differed in tourniquet type, perioperative care, operative procedure, and patient genotype distribution. Twelve of 96 sickle cell patients (12.5%) experienced postoperative complications (8 SS/SC and 4 AS) detailed in two of the four studies. Nonetheless, the available limited evidence suggests that with proper perioperative management and necessary precautions, tourniquets can be used with relative safety in most patients with sickle cell disease.

Microalbuminuria represents a feature of advanced renal disease in patients with sickle cell haemoglobinopathy

Chronic renal failure (CRF) occurring in sickle cell disease has a dismal outcome. The systematic screening for microalbuminuria representsthe touchstone to prevent CRF in patients with diabetes mellitus. Microalbuminuria has also been demonstrated in patients with sickle cell disease. Whether this has the same prognostic significanceas it does in diabetes mellitus has never been clearly stated. The purpose of the present study was to determine the prevalence ofmicroalbuminuria and to establish the clinical significance of microalbuminuria in patients with sickle cell disease. Patients with sickle cell disease of both sexes and all ages were consecutivelyrecruited at the haematology outpatient clinic of the Yopougon Teaching Hospital, Abidjan, Ivory Coast. in a prospective study fromJuly to September 2004. In each patient characteristics such as age, gender, ethnic group, weight, height, blood pressure, type of haemoglobinopathy , glomerular filtration rate, complications related to the disease and current treatment were collected. Microalbuminuria wasassessed in all the patients. Statistical analysis was performed to identify factors related to microalbuminuria. The prevalence ofmicroalbuminuria was 17.3% in our study population. Glomerular filtration rate was significantly lower in the microalbuminuric group thanin the normoalbuminuric group both on univariate analysis (p

P71 Management of patients with sickle cell haemoglobinopathy receiving oro-facial head and neck surgery in a district general hospital

P71 Management of patients with sickle cell haemoglobinopathy receiving oro-facial head and neck surgery in a district general hospital

Osteocalcin and bone-specific alkaline phosphatase in Sickle cell haemoglobinopathies

Osteocalcin or bone gamma-carboxyglutamic acid (gla) protein and Bone-specific alkaline phosphatase (b-AP) total protein levels were evaluated as indicators of bone turnover in twenty patients with sickle cell haemoglobinopathies and in twenty normal healthy individuals. The serum bone-specific alkaline phosphatase total protein level was measured by immunoradiometric (IRMA) method. The concentrations of serum bone-specific alkaline phosphatase total protein were higher in the study group than in the control group [P < 0.05]. The serum osteocalcin (BGP) showed no significant difference with the control healthy subjects. There was no correlation between the serum osteocalcin and serum bone-specific alkaline phosphatase total protein in the patient group. In conclusion, serum bone-specific alkaline phosphatase total protein determined or measured by IRMA can be considered a sensitive marker of bone turnover and could be especially useful as valuable non-invasive biochemical marker for identifying sickle cell patients with bone complications.

Development of warm auto- and allo-antibodies in a 3-year old boy with sickle cell haemoglobinopathy following his first transfusion of a single unit of red blood cells.

Alloimmunisation is a very common problem for blood banks; foreign red blood cell (RBC) antigens induce the formation of antibodies in a manner that depends on the immunogenicity of the antigen as well as on genetic and environmental factors. Alloimmunisation is estimated to occur in 0.3% to 38% of the population1, but it can occur in almost 50% of multiply transfused patients2, such as those with sickling haemoglobinopathies and thalassaemia. Autoantibodies, which are antibodies directed against a patient’s self-antigens, are less widely recognised as a complication of multiple transfusions3 but may be clinically significant. Autoantibodies may make it difficult to identify co-existing alloantibodies, delaying the identification of appropriately matched blood products, since most warm autoantibodies react with most donor RBC. In addition, autoantibodies can be associated with clinically significant warm autoimmune haemolytic anaemia3. In this report, we describe the case of a child with sickle cell anaemia who developed both auto- and alloantibodies following a transfusion of a single unit of packed RBC.

Time to Recognize an Overlooked Trait

In this era of identifying genetic risk factors for kidney disease, it may be appropriate to revisit one of the most common genetic disorders: Sickle cell hemoglobinopathies. Although sickle cell disease is a rare cause of ESRD, there is only a limited literature examining sickle cell trait (HbAS) in advanced kidney disease. In fact, in the most recent US Renal Data System report describing the primary cause of incident ESRD from 2003 through 2007, sickle cell trait accounted only for 29 of 536,877 cases.1 Progressive chronic kidney disease (CKD) leading to ESRD is often not included in the description of kidney injury resulting from sickle cell trait.2 Considering that the reasons behind the racial disparity of progression of kidney disease and ESRD remain unknown, it seems an obvious hypothesis to consider a widely known genetic disorder such as sickle cell trait. In this issue of JASN , Derebail et al. 3 describe the prevalence of HbAS in a sample of black patients who had ESRD and were receiving either hemodialysis or peritoneal dialysis. They then compare this observed prevalence with that of newborn screening programs in local counties and report the prevalence of HbAS in maintenance dialysis patients to be twice that of the newborn screening programs. The authors also characterize the prevalence of heterozygous hemoglobin …

Renal medullary-like carcinoma in an adult without sickle cell hemoglobinopathy

A 42-year-old white man with no significant prior medical history presented with macroscopic hematuria of 2 months' duration. His family history was notable for a maternal grandfather with kidney cancer. Urinalysis, CT, microscopic examination of tumor, immunohistochemical analysis of tumor, hemoglobin electrophoresis, molecular cytogenetic analysis, gene sequencing. Renal medullary-like carcinoma in an adult without sickle cell trait, sickle cell disease or other hemoglobinopathies. The patient underwent laparoscopic nephrectomy to remove the tumor and received adjuvant sorafenib (400 mg per day) as part of the E2805 ASSURE (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) trial. Metastatic recurrence of the tumor occurred 9 months after nephrectomy, for which the patient underwent tumor debulking and retroperitoneal lymph node dissection, followed by chemotherapy consisting of gemcitabine (2,000 mg/m(2)) and doxorubicin (50 mg/m(2)), both given on day 1 of a 14-day cycle. After six cycles of drug treatment, the patient had achieved a partial response. The patient was managed by active surveillance for 4 months, when he developed further symptoms and disease progression was detected. Third-line systemic therapy in the form of 21-day cycles of cisplatin (80 mg/m(2) on day 1) and etoposide (100 mg/m(2) on days 1-3) has recently been initiated.

Sickle cell hemoglobinopathies in district Bhopal

Sickle cell hemoglobinopathies in district Bhopal

Low dose, oral epsilon aminocaproic acid for renal papillary necrosis and massive hemorrhage in hemoglobin SC disease

Renal papillary necrosis in sickling hemoglobinopathies can lead to significant complications, including hemorrhage, obstruction, and infection. Despite its frequency, there are limited therapies for protracted hemorrhage. In the past, massive hemorrhage was managed with nephrectomy. Here, we report a patient with hemoglobin SC disease and prolonged, life-threatening hemorrhage from papillary necrosis successfully treated with oral, low-dose epsilon aminocaproic acid (EACA). Although further study is warranted, this case illustrates the need to consider EACA in the conservative management of renal papillary necrosis and significant hemorrhage in sickle cell hemoglobinopathies.

Survival benefit in bevacizumab-based therapy in sickle cell trait patients diagnosed with renal medullary carcinoma

e16096 Background: Renal medullary carcinoma (RMC) is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, primarily sickle cell trait. This is a rare and highly aggressive tumor that is shown to be most resistant to chemotherapy. In an effort to evaluate treatment outcomes, we retrospectively examined those patients diagnosed with RMC who were treated with and without bevacizumab based regimens. Methods: We reviewed the genitourinary medical oncology database at M. D. Anderson Cancer Center for patient diagnosed between 1999–2008 with histology proven RMC. Vital statistics of birth and death dates were noted. In addition, detailed chemotherapy regimen as well as medical and radiological data were also obtained. Results: All patients had metastatic disease (stage IV) to at least one distant site at presentation. Distant sites included bone, liver or lungs. A sample of five black males 5/9 (53%) were treated with therapy that included a 2 or 3 drug combinations of Adriamycin, Taxol, Gemzar, cisplatin, or Gleevac. Median survival was 12.7 months (3.2–22.2) while median age was 31 year (28–59). Only 4/9 (47%) patients received bevacizumab based therapy in a 2 or 3 drug combinations with Gemzar, Xeloda, cisplatin, or Taxol. In this group, 50% were females, median age of 36 years (33–39) and median survival of 18.5 months (15.5–22.8). Conclusions: Sickle cell trait was confirmed for all in this group diagnosed with RMC. 8/9 of these patients were black and 1/9 South-Asian. The group that received bevacizumab based therapy had a median survival of 5.8 months longer. Future studies, including genetic studies on the tumor types are essential to determining the SNP profiles of renal cell carcinoma in black patients. Furthermore, a prospective multicenter trial should be developed to evaluate the efficacy of bevacizumab based regimens in renal medullary carcinoma in this population. No significant financial relationships to disclose.

Cardiorenal Risk Prevalence in Sickle Cell Hemoglobinopathy

Introduction: The spectrum of kidney functional and structural alterations in sickle cell hemoglobinopathy (SCH) is broad. Also, morbidity and mortality from end organ dysfunction, especially cardiorenal dysfunction, are substantial. Consequently, screening an SCH population prospectively for surrogate markers of cardiorenal risk such as albuminuria and intima-media thickness (IMT) was the aim of this cross-sectional study. Patients and Methods: We screened 165 patients with SCH over 4 months at the Primary Care Department, King Abdulaziz Armed Forces Hospital, Saudi Arabia. The 133 who fulfilled the inclusion criteria have been referred for further investigations. Anthropometric evaluation of body mass index (BMI) and blood pressure (BP), determination of 24-hour urine albuminuria, fasting lipids, computed atherogenic risk ratio (ARR), estimated glomerular filtration rate (eGFR), common carotid artery (CCA) IMT measurements, and hemoglobin (Hb) electrophoresis were done. Results: Increased urinary albumin excretion (UAE) rate [380 (272.2–489.6) mg/day; mean and 95% confidence interval (95% CI) of mean] was detected in 24% of SCH patients (6 males and 26 females). Microalbuminuria (168.8 ± 59.7 mg/day) was noted in the majority (63.6%) while macroalbuminuria (752.7 ± 205.4 mg/day) was detected in a smaller percentage (36.4%). Patients with sickle cell disease (SCD) contributed about 66.6% of subjects with microalbuminuria and 100% of those with macroalbuminuria, while most individuals with sickle cell trait (89%) were normoalbuminuric (p < 0.0001). Preclinical atherosclerosis (increased CCA IMT and/or atheromatous plaques) was noticed in 68.8% of SCH individuals with increased UAE (ANOVA p = 0.003). The microalbuminuric and macroalbuminuric patients had comparable BMI, BP values and lipid profiles. However, the microalbuminuric sicklers were significantly younger (28.4 ± 6.7 vs. 34.0 ± 7.2 years, p = 0.04), less anemic (Hb: 9.13 ± 2 vs. 7.47 ± 0.8 g/dl, p = 0.015), with lesser atherosclerosis (IMT; 0.68 ± 0.1 vs. 0.78 ± 0.1 mm, p = 0.004) and higher eGFR (83.3 ± 17.2 vs. 61 ± 10.7 ml/min/1.73 m², p = 0.0004) compared to those with macroalbuminuria. UAE correlated positively with age (r = 0.591, p = 0.0001), systolic BP (r = 0.483, p = 0.005), IMT (r = 0.399, p = 0.024) and negatively with Hb (r = –0.409, p = 0.02), and eGFR (r = –0.620, p = 0.0001). By univariate analysis, the significant indicators of UAE in SCH patients were age (p = 0.05), BMI (p = 0.041), IMT (p = 0.018) and eGFR (p = 0.016). Also, increased risk (odds ratio) of albuminuria was noted with SCD, age, anemia, abnormal eGFR, obesity, and ARR. Conclusions: Markers of cardiorenal risk such as albuminuria and IMT are common findings in SCH patients of Arabic descent and could be useful screening tools to identify sicklers at risk for cardiovascular and renal events.

Efficient Erythroid Differentiation of a PGD-Derived Human Pluripotent Stem Cell Line Affected with Sickle Cell Hemoglobinopathy

The technology of preimplantation genetic diagnosis (PGD) screens IVF-derived cleavage-stage embryos or oocytes from parents with inherited disorders, and is routinely used to avoid births with severe genetic disorders. More than one hundred testable genetic conditions, including severe hematologic diseases such as beta thalassemia, sickle cell anemia, and Fanconi anemia can be PCR-screened from either a micro-manipulated blastomere, or a pre-fertilization ovarian polar body. Derivation of human embryonic stem cell (hESC) lines from diseased IVF blastocysts has recently been reported, and these PGD-hESC are untested yet potentially valuable tools for investigating cellular and molecular events of human embryogenesis in diseased states. For example, a great deal of interest has recently been generated in treating hematologic diseases with genetically-corrected hematopoietic stem cells (HSC) derived from patient-specific pluripotent stem cells. Generation of hematopoietic progenitors from PGD-hESC affected with genetic syndromes may thus provide novel opportunities for testing cell-based and gene therapeutic strategies. An important candidate for such cell-based therapy includes sickle cell disease (SSD) hemoglobinopathy, a classic inherited single gene disorder resulting from the substitution of glutamic acid by valine at position 6 of the beta chain of hemoglobin. Human pluripotent stem cells derived from PGD-selected blastocysts or induced pluripotency (iPS; e.g., using patient's somatic cells), will serve as critical reagents for testing such therapeutic strategies. In these studies, we report the characterization and erythropoietic differentiation of a novel PGD-hESC line affected with SSD hemoglobinopathy. The sickle point mutation was confirmed in this PGD-hESC line with direct genomic sequencing of the beta globin locus. This hESC line possesses typical pluripotency characteristics and forms multilineage teratomas in vivo. SSD-hESC can be efficiently differentiated to the hematopoietic lineage under serum-free conditions, and gave rise to robust primitive and definitive erythropoieses. The expression of embryonic, fetal and adult globin genes in SSD PGD-hESC derived erythroid cells was confirmed by qRT-PCR, intracytoplasmic FACS, and in situ immunostaining of PGD-hESC teratoma sections. Moreover, we defined culture conditions for massive, long-term liquid culture expansion of sickle affected erythroid progenitors that remained in an undifferentiated erythroblastic phenotype for at least two months. These sickle erythroblasts were continuously maintained as a primary cell line that could be frozen and thawed without loss of viability. In vitro-expanded sickle erythroblasts expressed CD71+CD36+ and CD71+CD235a+ phenotypes, and underwent developmentally appropriate embryonic, fetal, and adult hemoglobin switching over a period of several months. Moreover, hESC-derived erythroblasts were readily infected with Plasmodium falciparum malaria parasites, thus demonstrating their potential utility in studying the effects of this important pathogen in normal and diseased erythropoiesis. These data demonstrate the utility of using patient-specific, hemoglobinopathic hESC for generating significant numbers of erythroid progenitors for molecular, developmental, gene therapeutic, pharmacologic, and microbiological studies. We are currently conducting a comparative erythropoietic differentiation study using SSD PGD-hESC vs. SSD iPS that were generated from somatic fibroblasts using defined pluripotency factors.