Hydroxyurea Therapy for Sickle Cell Disease in Low-Income Countries

: Sickle Cell Disease (SCD) is an inherited disorder of red blood cells that is caused by a single mutation in the βglobin gene. The disease, which afflicts millions of patients worldwide mainly in low income countries, is characterized by high morbidity, mortality and low life expectancy. The new pharmacological and non-pharmacological strategies for SCD is urgent in order to promote treatments able to reduce patient’s suffering and improve their quality of life. Since the FDA approval of HU in 1998, there have been few advances in discovering new drugs; however, in the last three years voxelotor, crizanlizumab, and glutamine have been approved as new therapeutic alternatives. In addition, new promising compounds have been described to treat the main SCD symptoms. Herein, focusing on drug discovery, we discuss new strategies to treat SCD that have been carried out in the last ten years to discover new, safe, and effective treatments. Moreover, nonpharmacological approaches, including red blood cell exchange, gene therapy and hematopoietic stem cell transplantation will be presented.

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Sickle cell disease has emerged as a public health concern. Some drugs may conflict with curative therapies, yet they may be useful as a bridge to HSCT and gene therapy

10.31219/osf.io/6kufh ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Low Income ◽

Low Income Countries ◽

Health Concern ◽

Haematopoietic Stem Cell ◽

Cell Disease ◽

Public Health Concern ◽

Disease Modifying Drugs ◽

Matched Sibling

Sickle cell disease has resurfaced as a health-care priority in high-income nations and low-income countries (LMICs). Transplantation results with haploidentical haematopoietic stem cell transplantation (HSCT) are improving, increasing the likelihood of a curative treatment for the majority of patients. The indications for HSCT and for disease-modifying drugs, for example, must be determined. There are still a few things to think about, including biomarkers for systemic vasculopathy. Some medications may compete with curative treatments, but they might potentially be an important bridge treatment to HSCT. One of the most difficult hurdles yet ahead is reaching out to general practitioners and haematologists to bridge the awareness gap about curative alternatives such as matched sibling donor HSCT so that patients and their families may be identified early.

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Treatment for children with severe aplastic anemia and sickle cell disease in low income countries in Latin America: A report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO): Part III

Pediatric Blood & Cancer ◽

10.1002/pbc.20988 ◽

2007 ◽

Vol 48 (5) ◽

pp. 598-599 ◽

Cited By ~ 3

Author(s):

Scott C. Howard ◽

Judy A. Wilimas ◽

Andronica Flores ◽

C. Pacheco ◽

Gladis de Reyes ◽

...

Keyword(s):

Latin America ◽

Sickle Cell Disease ◽

Aplastic Anemia ◽

Sickle Cell ◽

Low Income ◽

International School ◽

Low Income Countries ◽

Severe Aplastic Anemia ◽

Cell Disease ◽

Pediatric Hematology

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SICKLE CELL DISEASE AND INFECTIONS IN HIGH- AND LOW-INCOME COUNTRIES

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2019.042 ◽

2019 ◽

Vol 11 (1) ◽

pp. 02019042 ◽

Cited By ~ 4

Author(s):

Giovanna Cannas

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Host Defense ◽

Low Income ◽

Defense Mechanisms ◽

Developed Countries ◽

Infectious Complications ◽

Low Income Countries ◽

Cell Disease ◽

Salmonella Infections

Infections, especially pneumococcal septicemia, meningitis, and Salmonella osteomyelitis, are a major cause of morbidity and mortality in patients with sickle cell disease (SCD). SCD increased susceptibility to infection, while infection leads to SCD-specific pathophysiological changes. The risk of infectious complications is highest in children with a palpable spleen before 6 months of age. Functional splenectomy, the results of repeated splenic infarctions, appears to be an important host-defense defect. Infection is the leading cause of death, particularly in less developed countries. Defective host-defense mechanisms enhance the risk of pneumococcal complications. Susceptibility to Salmonella infections can be explained at least in part by a similar mechanism. In high-income countries, the efficacy of the pneumococcal vaccine has been demonstrated in this disease. A decreased in infection incidence has been noted in SCD patients treated prophylactically with daily oral penicillin. Studies in low-income countries suggest the involvement of a different spectrum of etiological agents.

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The Effect of Hydroxyurea Therapy in Bahraini Sickle Cell Disease Patients

Indian Journal of Hematology and Blood Transfusion ◽

10.1007/s12288-015-0529-y ◽

2015 ◽

Vol 32 (1) ◽

pp. 104-109 ◽

Cited By ~ 3

Author(s):

Durjoy K. Shome ◽

Abdulla Al Ajmi ◽

Ameera A. Radhi ◽

Eman J. Mansoor ◽

Kameela S. Majed

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Hydroxyurea Therapy

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Newborn Screening for Sickle Cell Disease Using Point-of-Care Testing in Low-Income Setting

PEDIATRICS ◽

10.1542/peds.2018-4105 ◽

2019 ◽

Vol 144 (4) ◽

pp. e20184105 ◽

Cited By ~ 3

Author(s):

Ofelia A. Alvarez ◽

Tally Hustace ◽

Mimose Voltaire ◽

Alejandro Mantero ◽

Ulrick Liberus ◽

...

Keyword(s):

Sickle Cell Disease ◽

Newborn Screening ◽

Sickle Cell ◽

Low Income ◽

Point Of Care ◽

Cell Disease ◽

Point Of Care Testing ◽

Low Income Setting

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Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Anemia

Blood ◽

10.1182/blood.v112.11.4819.4819 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4819-4819

Author(s):

Rodolfo D Cancado ◽

Maria Cristina A Olivato ◽

Newton Nunes Lima Filho ◽

Orlando Campos ◽

Carlos Chiattone

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Pulmonary Artery ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Systolic Pressure ◽

Pulmonary Artery Systolic Pressure ◽

Cell Disease ◽

Risk Of Death ◽

Hydroxyurea Therapy

Abstract Pulmonary hypertension develops in most forms of hereditary and chronic hemolytic anemia, including sickle cell disease, thalassemia, hereditary spherocytosis, and paroxysmal nocturnal hemoglobinuria, suggesting that there is a clinical syndrome of hemolysis-associated pulmonary hypertension. Retrospective studies from tertiary care referral centers suggest a prevalence of pulmonary hypertension in adults with sickle cell disease ranging from 20 to 40%. Despite the fact the elevations in pulmonary artery pressures are slight, morbidity and mortality are high. In adult sickle cell anemia patients, pulmonary hypertension is emerging as a major risk factor for death. We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 80 consecutive patients (20 men and 60 women; mean [±SD] age, 30 ± 10.8 years) between 1/20/2006 and 1/20/2008. The genotype on the basis of hematologic and hemoglobin characteristics was hemoglobin SS in all patients. Pulmonary hypertension was prospectively defined as a tricuspid regurgitant Jet velocity (TFJV) of at least 2.5 m per second. Patients were followed for a mean of 18 months (6–24 months), and data were censored at the time of death or loss to follow-up. Doppler-defined pulmonary hypertension occurred in 37.5 percent of patients (30/80). Multiple logistic-regression analysis, with the use of the dichotomous variable of a tricuspid regurgitant jet velocity of less than 2.5 m per second or 2.5 m per second or more, identified age, female sex, deferasirox therapy, left ventricular mass index, pulmonary artery systolic pressure, reticulocytes, white-cell count, platelet count, lactate dehydrogenase (a marker of hemolysis), blood urea nitrogen, creatinine, uric acid and self-reported history of cardiovascular complication, billiary stones, retinopathy and acute chest syndrome, as significant independent correlates of pulmonary hypertension. The hemoglobin level, fetal hemoglobin level, hydroxyurea therapy and serum ferritin level were unrelated to pulmonary hypertension. Hazard rate for death according to the TFJV of at least 2.5 m per second, as compared with a velocity of less than 2.5 m per second, was associated with an increased risk of death (0.00 versus 2.54; P=0.998). Mortality rate in 24 months was 6.7% (2/30) for patients with TRJ velocity ≥ 2.5 m/sec versus 0.0% (0/50) for patients without pulmonary hypertension. Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Large trials evaluating the effects of treatment for pulmonary hypertension in the sickle cell anemia population are indicated.

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Overlapping Onset and Sequential Progression of Vasculopathy in Multiple Organs in Sickle Cell Disease

Blood ◽

10.1182/blood.v128.22.3660.3660 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3660-3660

Author(s):

Shruti Chaturvedi ◽

Djamila Ghafuri ◽

Adetola A. Kassim ◽

Michael DeBaun

Keyword(s):

Pulmonary Hypertension ◽

Magnetic Resonance ◽

Sickle Cell Disease ◽

Mortality Rate ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Age Of Onset ◽

Cell Disease ◽

Multiple Organs ◽

Hydroxyurea Therapy

Abstract Background: Sickle cell disease (SCD) is associated with vasculopathy in multiple vital organs, which ultimately leads to complications such as stroke, proliferative retinopathy, chronic kidney disease and pulmonary hypertension. Existing studies focus on single organ specific vasculopathy without an emphasis on shared mechanisms and simultaneous progression of vasculopathy in multiple organs. We conducted this retrospective cohort study to determine the onset and progression, as well as sequence of involvement of vasculopathy in the central nervous system (CNS), eye, kidney and lungs of adults with SCD. Methods: Our institutional practice is to perform annual magnetic resonance imaging with magnetic resonance angiography (MRI/MRA, for CNS vasculopathy and silent cerebral infarcts), echocardiography (for tricuspidregurgitant jet velocity > 2.5 m/sec, a surrogate of pulmonary hypertension), retinal examination, and measurement of urinaryalbumin:creatinine ratio, and serum creatinine in all adults with SCD. All patients were followed until death or last clinical encounter. Data were summarized as counts and proportions. Multivariable logistic regression was used to identify associations of number of organs affected with mortality. Results: We identified 280 adults with SCD followed for a median period of 66 months (interquartile range [IQR] 15.7 to 112 months). Median age was 31.1 (IQR 25.4 to 39.7) years and 49.6% were female. Over half (51.8%) were on hydroxyurea therapy. The prevalence of vasculopathy in different organs was: CNS, 37.8%; retinopathy 26.1%, proteinuria, 20.7% (nephropathy 5.71%); and pulmonary hypertension, 15.36%. There was no evidence of vasculopathy in 103 (36.8%) individuals. Of the remaining 177 (63.2%) adults, vasculopathy was present in one, two, three and all four end organs in100, 55, 18, and 4 individuals respectively. Median age of onset was earliest for CNS vasculopathy [25.42 (IQR 19.31, 38.85)] years followed by retinopathy [28.41 (IQR 23.04, 35.79)] years, proteinuria [31.25 (IQR 25.6, 46.0)] years, and pulmonary hypertension [33.08 (IQR 23.83, 47.17)] years (Figure 1). Mortality rate was 1.69 per 100 patient-years. Patients with vasculopathy affecting 3 or 4 organs had a significantly higher mortality rate than those with 0-2 organs affected by vasculopathy [odds ratio 5.50 (95%CI 4.49-20.35), p=0.007], adjusted for phenotype, age, sex, hydroxyurea therapy, and smoking status. Conclusion: Vasculopathy in SCD occurs in multiple organs simultaneously, with a predisposition to affectthe CNS first. These data strongly support that multiple vasculopathy is common, and when present in at least three organs, is associated with earlier mortality. Disclosures No relevant conflicts of interest to declare.

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