scholarly journals First report of reversal of organ dysfunction in sickle cell anemia by the use of hydroxyurea: splenic regeneration

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 1951-1953 ◽  
Author(s):  
S Claster ◽  
E Vichinsky
Keyword(s):  
Immune System ◽  
Organ Dysfunction ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Organ Damage ◽  
Germinal Centers ◽  
Quadrant Pain ◽  
Significant Impairment ◽  
Splenic Regeneration

Much of the morbidity associated with sickle cell anemia (SCA) is due to ongoing infarction resulting in organ dysfunction. Because the spleen is often the first organ damaged in this illness, there is a significant impairment of the immune system in these patients. Hydroxyurea (HU) has been shown to increase fetal hemoglobin (HbF) and decrease painful episodes in patients with this disease. It is unclear whether HU can prevent organ damage. We treated two SCA patients with HU for several years and found evidence of reversal of previously documented splenic dysfunction. Patient no. 1 was treated for 30 months with an increase in HbF to 30%. HU was stopped because of cytopenia. She developed left upper quadrant pain. A splenectomy was performed due to the possibility of splenic abscesses. A pathologic review found no evidence of infection and an enlarged spleen that showed active germinal centers. Patient no. 2 was treated for 24 months with HU before developing splenomegaly. His HbF levels were 25% to 30%, his pit counts averaged 2%, and his liver spleen scans showed uptake. These two cases show that chronic HU therapy may reverse splenic dysfunction in certain patients and suggest that this drug may have efficacy beyond the elimination of pain in SCA.

scholarly journals Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0141706 ◽  
Author(s):  
Courtney D. Fitzhugh ◽  
Matthew M. Hsieh ◽  
Darlene Allen ◽  
Wynona A. Coles ◽  
Cassie Seamon ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Organ Damage

STUDIES OF CONGENITAL HEMOLYTIC SYNDROMES

PEDIATRICS ◽  
1958 ◽  
Vol 22 (5) ◽  
pp. 910-922
Author(s):  
Marion E. Erlandson ◽  
Irving Schulman ◽  
Gertrude Stern ◽  
Carl H. Smith
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Severe Form ◽  
Intermediate Form ◽  
Transfusion Therapy ◽  
Effective Synthesis ◽  
Cooley's Anemia ◽  
Compensation Index

Rates of destruction of erythrocytes and of effective production of erythrocytes and hemoglobin have been determined in 10 patients with homozygous Cooley's anemia. The method employed was based upon survival of Cr51-labeled cells in patients in whom a state of equilibrium of erythrocytes was present. While a marked hemohytic defect is present, this defect does not, by itself, determine the degree of anemia present. Rates of effective production of erythrocytes are increased above normal but are not increased to the same degree found in patients with other hemolytic diseases. Rates of effective synthesis of hemoglobin were found to be less than those obtained for production of erythrocytes. The rates of production of fetal hemoglobin in these patients are remarkably elevated but cannot be directly correlated with the rate of destruction of erythrocytes, rate of production of erythrocytes, or the degree of anemia present. The hemolytic defect in patients with intermediate Cooley's anemia was comparable to that in the majority of the patients with the severe form of disease. However, the most marked hemolytic defects were among patients with the severe and not with the intermediate form of disease. Production of erythrocytes and hemoglobin did not differ significantly in the two forms of this disease. Results in two splenectomized patients did not differ significantly from results in the non-splenectomized group of patients. However, since pre-splenectomy data were not available, no statement may be made as to possible individual benefit derived from the operation. The final status of each patient is determined by the particular balance obtained between rates of destruction and production. Neither production nor destruction alone determines the degree of anemia. The compensation index, as a measure of final status in each patient, was lowest in the severe form of Cooley's anemia. It is presumed to be lower still in many patients who could not be studied because transfusion therapy was in progress. The compensation index is somewhat higher in patients with intermediate Cooley's anemia and in two splenectomized individuals not requiring frequent transfusions. Values in these patients approach the higher levels found in patients with sickle cell anemia and congenital spherocytosis.

Clinical epidemiology of individuals with Sickle cell anemia using Hydroxyurea at Muhimbili National Hospital, Dar Es Salaam, Tanzania

2020 ◽  
Vol 31 (1) ◽  
pp. 106-119
Author(s):  
Elisha Osati ◽  
Edward Kija ◽  
Florence Urio ◽  
Magdalena Lyimo ◽  
Siana Nkya ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Severe Pain ◽  
Clinical Epidemiology ◽  
Fetal Hemoglobin ◽  
Dar Es Salaam ◽  
Acute Chest Syndrome ◽  
Muhimbili National Hospital ◽  
National Hospital

Background: The pathophysiology of sickle cell disease (SCD) is complex and involves nitric oxide depletion, increased inflammation/adhesion molecules and vaso-occlusion in addition to the chronic hemolytic anemia. This pathophysiology results in systemic clinical complications including recurrent episodes of severe pain, stroke, acute chest syndrome (ACS) and an increased susceptibility to infection. SCD severity varies among individuals and fetal hemoglobin (HbF) is known as a major modulator of the disease. To date, hydroxyurea (HU) is a known intervention that acts by increasing HbF in individuals with SCD. The increase in HbF reduces the risk of ‘sickling’ events and improves clinical outcomes. This is the first study on the use of HU in individuals with SCA in Tanzania.Methods: A case-control study to determine the proportion, indications, clinical and laboratory outcomes of SCD patients with HU use was conducted at Muhimbili National Hospital in Dar Es Salaam, Tanzania.Results: Forty-two patients with Sickle cell anemia (SCA) on HU treatment and 32 patients with SCA not on HU treatment were enrolled. The proportion of HU use by individuals with SCA at Muhimbili National Hospital was 10 per 1000. The mean HbF % was 9.8 ± 2.4 vs 6.2 ±1.4 for controls (P <0.001). Thirty (71.4%) were enrolled for HU treatment due to central nervous system (CNS) events, frequent painful crises 11(26.2%) and recurrent anemia 1(2.4%). Thirty-two SCA patients (76.2%) reported improvements after being on HU for at least six months. Of these, 91% reported no history of severe pain that required hospitalizations since they started HU. Twenty patients (66.7%) out of those with CNS events reported not to have experienced convulsions after HU initiation.Conclusions: HbF was higher in patients who were on HU and had positive correlation with clinical outcomes. Further clinical trials are required to evaluate more effects of HU use among SCA individuals in Tanzania. Keywords: Sickle cell anemia, HU, Fetal hemoglobin, Tanzania.

MODULATION OF FETAL HEMOGLOBIN IN SICKLE CELL ANEMIA

Hemoglobin ◽  
2001 ◽  
Vol 25 (2) ◽  
pp. 195-211 ◽  
Author(s):  
Martin H. Steinberg
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin

ANTXR1 Intronic Variants Are Associated with Fetal Hemoglobin in the Arab-Indian Haplotype of Sickle Cell Disease

2018 ◽  
Vol 140 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Zhara A. Al-Ali ◽  
Rana K. Fallatah ◽  
Esra A. Aljaffer ◽  
Eman R. Albukhari ◽  
Neriman Sadek Al-Ali ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Real Time Pcr ◽  
Genetic Variants ◽  
Fetal Hemoglobin ◽  
Genetic Mutations ◽  
Cell Disease ◽  
Hbf Level ◽  
Intronic Variants

Disease severity of sickle cell anemia is highly variable, and it is commonly accepted that fetal hemoglobin (HbF) levels play a major role as an ameliorating factor. Investigation of genetic variants have identified several genes to be the principal influencers of HbF regulation. Here, we further elucidated the association of rs4527238 and rs35685045 of ANTXR1 genes in the context of HbF level variance in sickle cell anemia patients of the Arab-Indian haplotype. Samples from 630 sickle cell anemia patients were analyzed for the mutations at 2 specific locations of the ANTXR1 gene by TaqMan®-based real-time PCR. The CC genotype (p = 0.018) of rs4527238 and the TT genotype (p = 0.048) of rs35685045 of ANTXR1 were found to be significantly associated with low HbF expression. The frequency of the CC genotype of rs4527238 was observed to be high in the low HbF patient group compared to the high HbF group (p = 0.009). Likewise, the frequency of the TT genotype of rs35685045 was also high among the low HbF group (p = 0.017). The ANTXR1 genetic mutations and the association with HbF expression in the Arab-Indian haplotype sickle cell patients revealed that the ANTXR1 gene may be a major HbF modulator leading to potential therapeutic options that should be further explored.

scholarly journals High fetal hemoglobin production in sickle cell anemia in the eastern province of Saudi Arabia is genetically determined

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1404-1410 ◽  
Author(s):  
BA Miller ◽  
M Salameh ◽  
M Ahmed ◽  
J Wainscoat ◽  
G Antognetti ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Cell Disease ◽  
Chromosome 11 ◽  
Eastern Province ◽  
Genetically Determined ◽  
Hemoglobin Production

Abstract Homozygous sickle cell disease in the eastern province of Saudi Arabia is clinically mild. Circulating fetal hemoglobin levels of 16.0 +/- 7.4% were found in these anemic patients, but only 1.09 +/- 0.97% in their sickle trait parents. To determine whether these sickle cell anemia patients inherit an increased capacity to synthesize fetal hemoglobin, a radioimmunoassay of fetal and adult hemoglobin was performed on erythroid progenitor (BFU-E)-derived erythroblasts from Saudi Arabian sickle cell patients and their parents. Mean fetal hemoglobin content per BFU-E-derived erythroblast from Saudi Arabian sickle cell patients was 6.2 +/- 2.4 pg/cell or 30.4 +/- 8.6% fetal hemoglobin (normal 1.1 +/- 0.7 pg/cell and 5.1 +/- 1.8%). Linear regression analysis of % HbF in peripheral blood versus % HbF per BFU-E- derived cell showed a positive correlation with an r of 0.65. The variance of the intrinsic capacity to produce HbF may account for almost 40% (r2) of the variance of circulating fetal hemoglobin but other factors, particularly selective survival of F cells, must also contribute significantly. Despite virtually normal HbF levels in sickle trait parents of these Saudi patients, mean fetal hemoglobin production per BFU-E-derived erythroblast in these individuals was elevated to 3.42 +/- 1.79 pg/cell or 16.1 +/- 6.4% fetal hemoglobin, and the magnitude of fetal hemoglobin production found in parents correlated with that of the patients. These data indicate that the high fetal hemoglobin in Saudi sickle cell disease is genetically determined but expressed only during accelerated erythropoiesis. Further evidence of such genetic determination was provided by analysis of DNA polymorphisms within the beta-globin gene cluster on chromosome 11. This revealed a distinctive 5′ globin haplotype (+ + - + +) on at least one chromosome 11 in all high F SS and AS tested. The precise relationship of this haplotype to HbF production in this population remains to be defined.

Genetics of fetal hemoglobin in tribal Indian patients with sickle cell anemia

2015 ◽  
Vol 165 (6) ◽  
pp. 696-703 ◽  
Author(s):  
Aparna A. Bhanushali ◽  
Pradip K. Patra ◽  
Smarnika Pradhan ◽  
Suraj S. Khanka ◽  
Sujata Singh ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Indian Patients

scholarly journals Optimizing hydroxyurea therapy for sickle cell anemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 436-443 ◽  
Author(s):  
Russell E. Ware
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Maximum Tolerated Dose ◽  
Sub Saharan Africa ◽  
Future Research ◽  
Published Evidence ◽  
Treatment Indications ◽  
Hydroxyurea Treatment ◽  
Hydroxyurea Therapy

Abstract Hydroxyurea has proven efficacy in numerous clinical trials as a disease-modifying treatment for patients with sickle cell anemia (SCA) but is currently under-used in clinical practice. To improve the effectiveness of hydroxyurea therapy, efforts should be directed toward broadening the clinical treatment indications, optimizing the daily dosage, and emphasizing the benefits of early and extended treatment. Here, various issues related to hydroxyurea treatment are discussed, focusing on both published evidence and clinical experience. Specific guidance is provided regarding important but potentially unfamiliar aspects of hydroxyurea treatment for SCA, such as escalating to maximum tolerated dose, treating in the setting of cerebrovascular disease, switching from chronic transfusions to hydroxyurea, and using serial phlebotomy to alleviate iron overload. Future research directions to optimize hydroxyurea therapy are also discussed, including personalized dosing based on pharmacokinetic modeling, prediction of fetal hemoglobin responses based on pharmacogenomics, and the risks and benefits of hydroxyurea for non-SCA genotypes and during pregnancy/lactation. Another critical initiative is the introduction of hydroxyurea safely and effectively into global regions that have a high disease burden of SCA but limited resources, such as sub-Saharan Africa, the Caribbean, and India. Final considerations emphasize the long-term goal of optimizing hydroxyurea therapy, which is to help treatment become accepted as standard of care for all patients with SCA.

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