scholarly journals Cardiovascular complications in patients with sickle cell disease

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 423-430 ◽  
Author(s):  
Mark T. Gladwin
Keyword(s):  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Single Point ◽  
Systolic Pressure ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Pulmonary Artery Systolic Pressure ◽  
Single Point Mutation ◽  
Cell Disease

Abstract Sickle cell disease (SCD) is an autosomal recessive disease in which homozygosity for a single point mutation in the gene encoding the β-globin chain produces hemoglobin S molecules that polymerize within the erythrocyte during deoxygenation; the result is sustained hemolytic anemia and vaso-occlusive events. As patients live to adulthood, the chronic impact of sustained hemolytic anemia and episodic vaso-occlusive episodes leads to progressive end-organ complications. This scenario culminates in the development of 1 or more major cardiovascular complications of SCD for which there are no approved or consensus therapies. These complications include elevated pulmonary artery systolic pressure, pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, sudden death, and chronic kidney disease with associated proteinuria, microalbuminuria, and hemoglobinuria. In patients with advancing age, cardiopulmonary organ dysfunction and chronic kidney injury have significant effects on morbidity and premature mortality. Over the last 15 years, a number of tests have been validated in multiple replicate cohort studies that identify patients with SCD at the highest risk of experiencing pulmonary and systemic vasculopathy and death, providing for screening strategies tied to targeted, more aggressive diagnostic and therapeutic interventions.

Abstract 65: Anemia-related Heart Failure in Sub-saharan African Sickle Cell Disease Patients

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Adebayo C Atanda ◽  
Yahya Aliyu ◽  
Oluwafunmilayo Atanda ◽  
Aliyu Babadoko ◽  
Aisha Suleiman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Hemoglobin Level ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Jet Velocity ◽  
Sub Saharan

Introduction: Anemia has been implicated in heart failure. Existing literatures, involving predominantly African-Americans, suggests that Sickle Cell Disease (SCD) maybe linked to various cardiovascular complications including pulmonary hypertension and left venticular dysfunction. Peculiarly, our study involves exclusively Sub-Saharan population. Method: We conducted a cross sectional observational study of 208 hydroxyurea-naive consecutive SCD patients aged 10-52 years at steady state and 94 healthy non-matched controls who were studied in an out patient clinic in Sub-Saharan Africa. SCD patients were required to have electrophoretic or liquid chromatography documentation of major sickling phenotypes. Control group was required to have non-sickling phenotypes. Cardiac measurements were performed with TransThoracic Echo according to American Society of Echocardiography guidelines. Hemoglobin level was also obtained. Results: Hemoglobin level in SCD group (8.5+/- 1.5) was significant (P<0.001) compared to control (13.8+/- 1.7). Although SCD group had significantly higher values of left ventricular (LV) size, there was no qualitative evidence of LV dysfunction. SCD group had higher values of Ejection Fraction but not statistically significant. There was no evidence of LV wall stiffening to impair proper filling in SCD group, with the ratio of early to late ventricular filling velocities, E/A ratio elevated (1.7+/-0.4 compared to 1.6+/- 0.4; P=0.010). Right ventricular systolic pressure was determined using the formula of 4x Tricuspid Reugurgitant jet (TRV) square as an indirect measurement of Pulmonary arterial systolic pressure. SCD patients had significantly higher mean±SD values for tricuspid regurgitant jet velocity than did the controls (2.1±0.6 vs. 1.8±0.5; p= 0.001). Within the SCD group, there was no clear pattern of worsening diastolic function with increased TRV. Furthermore, E/A had a significant positive relationship with jet velocity in bivariate analysis (R=0.20; P=0.013). Conclusions: We were unable to demonstrate existence of anemia-associated left ventricular dysfunction in Sub-Saharan African with SCD. Further studies is required to highlight the reason behind this finding.

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

Blood ◽  
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.

scholarly journals Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management

2012 ◽  
Vol 2012 ◽  
pp. 1-55 ◽  
Author(s):  
Samir K. Ballas ◽  
Muge R. Kesen ◽  
Morton F. Goldberg ◽  
Gerard A. Lutty ◽  
Carlton Dampier ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Point Mutation ◽  
Sickle Cell ◽  
Globin Gene ◽  
Single Point ◽  
Acute Chest Syndrome ◽  
Single Point Mutation ◽  
Cell Disease ◽  
Exon 1 ◽  
Abnormal Hemoglobin

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of theβglobin gene resulting in the substitution of glutamic acid by valine at position 6 of theβglobin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

Normal Pulmonary Artery Pressure in Sickle Cell Patient with Severe Iron Deficiency Anemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3785-3785
Author(s):  
Oswaldo Castro ◽  
Adriana Medina ◽  
Peter Gaskin
Keyword(s):  
Sickle Cell Disease ◽  
Iron Deficiency ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Serum Bilirubin ◽  
Systolic Pressure ◽  
Deficiency Anemia ◽  
Pulmonary Artery Systolic Pressure ◽  
Cell Disease ◽  
Iron Deficient

Abstract One-third of adults with sickle cell disease (SCD) have echocardiographic (ECHO) evidence of pulmonary hypertension (PHTN), a complication associated with early mortality. Because the pulmonary artery pressures in most SCD patients with PHTN are only mildly elevated, the question arises whether such increases are primarily a reflection of the high cardiac output state that accompanies the anemia. Recently we treated a 45 year-old woman with homozygous sickle-cell disease and profound iron deficiency due to heavy menstrual flow. Two ECHOs were done while she was severely iron deficient (Hb 5 g/dl, MCV 57 fl, reticulocytes 72,407/mm3, serum bilirubin 0.5 mg/dl, iron 29 mcg/dl, transferrin 376 mg/dl, and ferritin 3.6 ng/ml). Her pulmonary artery systolic pressure (PAs) was calculated from the tricuspid regurgitant jet velocity (TRV) using the Bernoullie equation: 4(TRV3) + central venous pressure (assumed at 10 mm Hg). The PAs was normal, 24 mm Hg, even though the patient also had M-mode evidence of left ventricular diastolic dysfunction and a small pericardial effusion. Treatment with intravenous iron and red cell transfusion partially improved her iron deficiency and anemia (Hb 7 g/dl, MCV 67 fl, serum bilirubin 0.7 mg/dl, iron 54 mcg/dl, transferrin 322 mg/dl, and ferritin 33.9 ng/ml) but also increased her hemolytic rate: though LDH data are unavailable, the reticulocyte count rose to 117,900/mm3. Repeat ECHO exams at this time showed that her pulmonary artery systolic pressures increased to 35–36 mm Hg. These values are at or near the lower range of pulmonary artery systolic pressures (36–70 mm Hg) measured in SCD patients in whom PHTN was diagnosed at cardiac catheterization. The figure compares hematologic values, and pulmonary artery systolic pressure in our iron deficient SS patient at baseline and during treatment. This experience, though anecdotal, suggests that the PHTN in SCD is unrelated to the anemia per se and, by implication, also unrelated to the high cardiac output. The patient’s mild pulmonary systolic hypertension actually developed with improvement of her anemia. Our hypothesis is that when the patient’s iron deficiency was most severe, the low MCHC decreased Hb S polymerization and decreased hemolysis, as in other iron deficient SCD patients. Her relatively low hemolytic rate may have prevented the mild PHTN, which developed once treatment improved her iron deficiency but increased hemolysis. Our hypothesis is consistent also with an emerging new paradigm in sickle cell disease pathophysiology: a strong link between hemolysis-related nitric oxide system (NO) dysfunction and risks for pulmonary hypertension, leg ulcers, priapism, and death. In this context it is interesting that iron deficiency anemia up-regulates vascular nitric oxide synthase in animals. In humans iron deficiency increases NO production even in the absence of anemia. Hence, this patient’s iron depletion may have contributed to the maintenance of her low pulmonary pressures also by a direct NO-mediated vascular effect. Figure Figure

scholarly journals Selenium Deficiency in a Mouse Model of Sickle Cell Disease Resulted in Increased Oxygen Consumption and Aberrant Mitochondrial Retention (OR11-05-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lenny Hong ◽  
Ramasamy Jagadeeswaran ◽  
Robert Molokie ◽  
Donald Lavelle ◽  
Angela Rivers ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Sickle Cell Disease ◽  
Mouse Model ◽  
Sickle Cell ◽  
Globin Gene ◽  
Single Point ◽  
Selenium Deficiency ◽  
Single Point Mutation ◽  
Cell Disease ◽  
Deficient Diet

Abstract Objectives Sickle Cell Disease (SCD) is caused by a single point mutation in the β-globin gene, resulting in the polymerization of the altered hemoglobin βS in hypoxic conditions, affecting millions of people worldwide. Previous studies have shown that there are lower selenium levels and reduced activity of the antioxidant selenoprotein GPX1 in SCD patients. The objective of this study was to investigate the consequences of selenium deficiency in a SCD mouse model. Methods Humanized SCD (HbSS) mice (Townes model) and wild type (HbAA) mice were purchased from Jackson Laboratories (Bar Harbor, ME). Mice were fed either a selenium-deficient (<0.01 mg/kg) or a selenium adequate (0.1 mg/kg) diet for 4 weeks. Hematological testing was performed using the ADVIATM 120 analyzer (Bayer Corporation, NY). Mitochondrial retention and reactive oxygen species (ROS) were measured by flow cytometry with a BD LSRFortessaTM analyzer using Kaluza analysis software (Beckman Coulter, CA). The oxygen consumption rate (OCR) was measured from isolated red blood cells (RBCs) in real time using the Seahorse Extracellular Analyzer (Agilent, CA). Results RBCs normally eject their mitochondria before reaching maturity. However, a previous study demonstrated that there was increased RBC mitochondrial retention in SCD mice and patients when compared to controls. Feeding SCD mice a selenium deficient diet resulted in increased retention of mitochondria in RBCs (26% + 6.9%, 5% + 3.5%, n = 3, P < 0.01), decreased hemoglobin levels (5.7 + 0.17 g/dl, 7.0 + 0.83 g/dl, n = 3, P < 0.05), and an increased OCR of the RBCs (P < 0.01) in these animals when compared to SCD mice fed a selenium adequate diet. Conclusions Providing humanized SCD mice a selenium deficient diet resulted in increased mitochondrial retention in mature RBCs, decrease hemoglobin levels, and increased RBC oxygen consumption. RBC retention of mitochondria is associated with increased ROS and hemolysis, potentially contributing to the pain and vaso-occlusive crises that occur in the disease. These studies indicate that selenium deficiency may contribute to the severity of symptoms experienced by patients with SCD. Funding Sources This work is supported by a grant from the NIH.

scholarly journals BIBLIOMETRIC ANALYSIS OF GLOBAL SICKLE CELL DISEASE RESEARCH FROM 1997 – 2017

2019 ◽  
Author(s):  
Henshaw Okoroiwu ◽  
Francisco López-Muñoz ◽  
F. Javier Povedano-Montero
Keyword(s):  
United States ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Scientific Literature ◽  
Single Point ◽  
World Health ◽  
Single Point Mutation ◽  
Cell Disease ◽  
Growth Trend ◽  
Disease Research

Abstract Background: Sickle cell disease (SCD) is an autosomal recessive genetic disease caused by single point mutation in the β-globin chain of the hemoglobin. It has been recognized by World Health Organization as a public health priority since 2006. Methods: Scopus database was used in this study with the search descriptors: “sickle cell” and “sickle cell disease”. We applied common bibliometric indicators to evaluate the trend in scientific literature in sickle cell disease research. Results: We retrieved a total of 19,921 scientific literatures in the repertoire from 1997 to 2017. Price law was fulfilled in the trend of production of scientific literature in SCD as the growth of scientific literature was more exponential (r = 0.959) than linear (r = 0.9449). We observed a duplication time of 4.55 years. The Bradford core was made up of 69 journals with Blood at the top, publishing the most number of articles. The most productive institutions were mostly United States agencies and hospitals. United States was the most productive country. National Institute of Health was the most productive institution and also had the highest number of citation. Vichinsky E was the most productive author while the most cited article was published by Circulation. Conclusion: The growth of scientific literature in SCD was found to be high. However, the exponential growth trend shows a “yet-to-be-explored” area of research. This study will be useful for physicians, researchers, research funders, policy cum decision makers.

scholarly journals Sickle Cell Anemia: A review on the most severe form of Sickle Cell Disease

Bionatura ◽  
2019 ◽  
Vol 02 (Bionatura Conference Serie) ◽  
Author(s):  
María Belén Paredes ◽  
María Eugenia Sulen
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Globin Gene ◽  
Single Point ◽  
Clinical Manifestations ◽  
Severe Form ◽  
Single Point Mutation ◽  
Cell Disease ◽  
Hemoglobin S

Sickle cell disease (SCD) is a group of hereditary disorders caused by a single point mutation in the β-globin gene. This mutation results in the formation of a mutated hemoglobin S (HbS) and the consequent sickle phenotype of erythrocytes. SCD is common in regions of malaria endemicity. However, changes in population dynamics enabled the movement of the mutated gene to other areas such as North America and Europe. Sickle cell anemia (SCA) is the most severe form of SCD and affects millions of people around the globe. The clinical manifestations of SCA arise primarily from the polymerization of deoxygenated hemoglobin S (deoxyHbS) leading to vascular occlusion and hemolytic anemia. Clinical complications of the disease are derived from deoxyHbS polymerization, but there are several therapeutic strategies to reduce the severity of the symptoms. Gene therapy has arisen as a new therapeutic approach aimed to cure rather than to treat the symptomatology of SCA by targeting the altered β-globin gene for gene correction.

scholarly journals Effects of vaccines in patients with sickle cell disease: a systematic review protocol

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e021140
Author(s):  
Alison Beriliy Wiyeh ◽  
Leila Hussein Abdullahi ◽  
Ambroise Wonkam ◽  
Charles Shey Wiysonge ◽  
Mamadou Kaba
Keyword(s):  
Systematic Review ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Single Point ◽  
Ethical Review ◽  
Advisory Group ◽  
Single Point Mutation ◽  
Common Disease ◽  
Cell Disease ◽  
Increased Risk

IntroductionSickle cell disease (SCD) is an inherited haematological disorder caused by a single point mutation (Glub6Val) that promotes polymerisation of haemoglobin S and sickling of erythrocytes. Inflammation, haemolysis, microvascular obstruction and organ damage characterise the highly variable clinical expression of SCD. People with SCD are at increased risk of severe infections, hence the need for vaccination against common disease-causing organisms in this population. We aim to review the evidence on the efficacy and safety of vaccines in people with SCD.Methods and analysisThe present systematic review will examine the current data as indexed in PubMed, CENTRAL, EMBASE and EBSCOHost. We will consult Strategic Advisory Group of Experts practice statements, conference abstracts, reference lists of relevant articles, WHO ICTRP trial registry and experts in the field. Two authors will independently screen search outputs, select studies, extract data and assess risk of bias; resolving discrepancies by discussion and consensus between the two authors or arbitration by a third author when necessary. We will perform a meta-analysis for clinically homogenous studies. Evidence from clinically diverse studies will be aggregated using narrative synthesis of the findings. In either case, we will use the GRADE approach to assess the strength of the available evidence.Ethics and disseminationThe study draws on data that are readily available in the public domain, hence no formal ethical review and approval is required. The findings of this review will be disseminated through conference presentations and a publication in a peer-reviewed journal.PROSPERO registration numberCRD42018084051.

Diastolic Dysfunction Is an Independent Risk Factor for Death in Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 206-206 ◽  
Author(s):  
Vandana Sachdev ◽  
Roberto F. Machado ◽  
Yukitaka Shizukudu ◽  
Yesoda Rao ◽  
Stanislav Sidenko ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Sickle Cell ◽  
Systolic Pressure ◽  
Pulmonary Artery Systolic Pressure ◽  
Cell Disease

Abstract Background. Pulmonary hypertension, defined by an elevated pulmonary artery systolic pressure measured by Doppler-echocardiogram, has been identified as the major predictor of death in the adult sickle cell disease population. While diastolic dysfunction is also observed in this population, the prevalence in unselected patients, the association with high pulmonary artery systolic pressure, and the attributable mortality remain unknown. Methods. Diastolic function parameters, pulmonary artery systolic pressures and right and left ventricular size and function were measured prospectively in 215 subjects with sickle cell disease. Associations between these parameters, lab and echocardiographic variables and prospective mortality were determined. Results. Diastolic dysfunction, measured by conventional and tissue-Doppler echocardiography, was present in 19% of patients with sickle cell disease. Diastolic dysfunction and pulmonary hypertension were both present in approximately 11% of patients and diastolic dysfunction accounted for approximately 10–20% of the variability in tricuspid regurgitant jet velocity. Importantly, Cox Proportional Hazards analysis revealed that diastolic dysfunction, as reflected by low E/A ratio, was associated with prospective mortality with a risk ratio of 1.9 (95%CI 1.0 to 3.7; p=0.028), even after adjustment for tricuspid regurgitant jet velocity. While pulmonary hypertension remained the dominant determinant of mortality risk, even after adjustment for measures of diastolic function (adjusted rate ratio of 5.3; 95% CI= 1.9 to15.0; p<0.001), the risk was additive such that patients with both risk factors had an odds ratio for death of 10.1 (95% CI= 3.2 to 31.9; p<0.001). Conclusions. Diastolic dysfunction and pulmonary hypertension due to other causes each contribute independently to prospective mortality in patients with sickle cell disease. Patients with both risk factors have an extremely poor prognosis. These data support the implementation of Doppler-echocardiographic screening of adult patients with sickle cell disease to identify individuals at high risk of death for intensified therapy. Figure Figure

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