Pulmonary Artery Hypertension in Children with Sickle Cell Disease: Is Chronic Transfusion Protective?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1210-1210
Author(s):  
Kristin Joyce ◽  
Craig Sable ◽  
Brenda Martin ◽  
Caterina P. Minniti
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Vena Cava ◽  
Systolic Pressure ◽  
Pulmonary Artery Hypertension ◽  
Right Atrial ◽  
Cell Disease ◽  
Systemic Pressure

Abstract Background Studies in adults with sickle cell disease (SCD) suggest an increased prevalence of pulmonary artery hypertension (PAHTN) with associated increased morbidity and mortality. These findings have not been validated in children. Methods The digital echocardiography (echo) database at Children’s National Medical Center was searched for echos performed on patients with SCD from 1999 to 2006. Patients on chronic transfusions undergo regularly scheduled studies; other patients are referred for a variety of indications including murmurs, cardiomegaly, hypoxia, chest pain, and respiratory distress. Echo reports and digital images were reviewed and the following information was recorded: Chronic transfusion, date of study, blood pressure, cardiac structure, ventricular function, presence of tricuspid regurgitation (TR), and velocity of TR. The estimated right ventricular (RV) pressure was calculated using modified Bernoulli equation (adding 5 mm Hg for estimated right atrial pressure if the inferior vena cava was not dilated). The ratio of RV systolic pressure to systemic systolic blood pressure was calculated. All studies with TR velocities of < 3 m/sec or a RV to systemic ratio of less than one third were considered to be normal. Results: The SCD database has 1060 patients ages 0 to 21 years; 166 echos were performed in 104 routine patients and 72 echos in 47 children while on chronic transfusions. TR could be measured in 56 routine and 20 transfusion studies. Comorbidities were present in 11 studies (7 patients) in the routine group: structural heart disease (4 ), constrictive pericarditis (1 ), significant obstructive airway disease (1 ), and pneumonia requiring mechanical ventilation (1 ). There were no comorbidities in the transfusion group. The mean TR velocity, estimated RV pressure, and RV to systemic pressure ratios were higher in the routine group; however when patients with comorbidities were removed, this difference was no longer statistically significant. Routine (n=55) Routine/no comorbidities (n=44) Transfused (n=20) 1p = 0.01 transfused vs. routine; p = 0.11 transfused vs. routine/no comorbidities 2p < 0.01 transfused vs. routine; p = 0.09 transfused vs. routine no comorbidities 3p = 0.01 transfused vs. routine; p = 0.13 transfused vs. routine/no comorbidities 1TR velocity (m/sec) 2.54 ± 0.48 2.30 ± 0.30 2.30 ± 0.30 Range 1.67–3.93 Range 1.67–3.19 Range 1.70–2.76 2RV pressure (mm Hg) 31.8 ±10.5 29.2 ± 6.6 26.5 ± 5.6 Range 16.2–67.8 Range 16.2–45.7 Range 16.6–36.4 3RV/systemic pressure ratio 0.29 ± 0.11 0.26 ± 0.064 0.23 ± 0.065 Range 0.16–0.78 Range 0.16–0.41 Range 0.14–0.38 There were 6 routine studies (2 when patients with comorbidities were removed) and no transfusion studies with a TR velocity above 3.0 m/sec. There were 23 routine studies (18 when patients with comorbidities removed) and 6 transfusion studies with a TR velocity between 2.5 and 3.0 m/sec. The ratio of RV to systemic pressure was greater than one third in 11 routine patients (5 when patients with comorbidities were removed) and 1 transfusion patient. Conclusions PAHTN is present in a small number of children with SCD and may be exacerbated by other medical problems. Chronic transfusion may be protective against PAHTN. Prospective analysis of this population is warranted.

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.

Pulmonary Artery Occlusion Pressure May Overdiagnose Pulmonary Artery Hypertension in Sickle Cell Disease

CHEST Journal ◽  
2011 ◽  
Vol 140 (4) ◽  
pp. 881A
Author(s):  
Sunil Sharma ◽  
Renuka Kadali ◽  
Ramesh Daggubati ◽  
Jimmy Efird ◽  
Hadi Chohan ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Pulmonary Artery Occlusion Pressure ◽  
Artery Occlusion ◽  
Pulmonary Artery Hypertension ◽  
Occlusion Pressure ◽  
Cell Disease

Genomic Approaches to Identifying Risk for Pulmonary Artery Hypertension among Individuals with Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1442-1442
Author(s):  
Damian Silbermins ◽  
Laura M. De Castro ◽  
Jude C Jonassaint ◽  
Shiaowen David Hsu ◽  
Marilyn J. Telen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Whole Blood ◽  
Gene Signature ◽  
Pulmonary Artery Hypertension ◽  
Gene Set Enrichment Analysis ◽  
Cell Disease ◽  
Gene Signatures

Abstract Pulmonary artery hypertension (PAH) occurs in 30–50% of adult patients with sickle cell disease (SCD), with mortality ranging from 16 to 50% and a median survival of 25 months. Our objective was to use gene expression profiling to develop a gene signature predictor for PAH through the analysis of gene expression of blood cells from SCD patients with or without PAH. We hypothesized that these gene signatures could allow us to identify patients at risk for PAH, as well as to generate hypotheses as to the pathophysiology of PAH in SCD. We used Affymetrix U133A2 GeneChip to determine the RNA expression of both whole blood and leukocytes using PAXgene and Leukolock methods, respectively. The study population included patients homozygous for HbS or with HbSβ0 thalassemia. Subjects with PAH were ≥18 years old, in steady state, and had PAH either by 2D echo (TR jet ≥ 2.7 m/sec) or right-sided catheterization (mean PA pressure ≥ 30 mmHg). Patients were excluded if they were pregnant, had co-existing rheumatologic conditions or other inflammatory diseases, were on chronic transfusion therapy or had had a vaso-occlusive episode in the previous 4 weeks. The control subjects were patients with SCD but without PAH (TR jet ≤ 1.8 m/sec or mean PA pressure <25 mmHg). Hierarchical clustering based on the gene expression pattern from 7 patients with PAH and 6 controls showed a trend for the clustering of SCD patients with PAH away from SCD patients without PAH. This trend was present for the gene expression in both whole blood and leukocytes. A Bayesian regression analysis was then performed to identify a set of predictor gene signatures for the PAH phenotype (Figure 1) in SCD. Finally, using gene set enrichment analysis, we found that the leukocytes from patients with PAH were highly enriched in the gene sets deriving from hematopoietic stem cells, corroborating the hypothesis of hyperhemolysis and higher blood cell turnover in this population. Other pathways showing upregulation in PAH were PTEN, TGFβ, cyclin D1, WNT and PPAR. Although these data are preliminary, they suggest that PAH in SCD does indeed have a distinct gene signature profile that may become useful in identifying risk for PAH prospectively, as well as in directing further investigation into the pathogenesis of PAH in SCD. Figure Figure

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 Pulmonary Artery Occlusion Pressure May Overdiagnose Pulmonary Artery Hypertension in Sickle Cell Disease

2013 ◽  
Vol 36 (9) ◽  
pp. 524-530 ◽  
Author(s):  
Sunil Sharma ◽  
Jimmy Efird ◽  
Renuka Kadali ◽  
Sanjay Mehra ◽  
Hadi Chohan ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Pulmonary Artery Occlusion Pressure ◽  
Artery Occlusion ◽  
Pulmonary Artery Hypertension ◽  
Occlusion Pressure ◽  
Cell Disease

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

scholarly journals Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Richard K. D. Ephraim ◽  
Patrick Adu ◽  
Edem Ake ◽  
Hope Agbodzakey ◽  
Prince Adoba ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Total Cholesterol ◽  
Sickle Cell ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipoprotein Cholesterol ◽  
Cell Disease ◽  
Cross Sectional

Background.Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients.Methods.A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8–28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8–38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C.Results.Total cholesterol (TC) (p=0.001) and high-density lipoprotein cholesterol (HDL-C) (p<0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP,p=0.01, OR: 0.74 (CI: 0.6–0.93); DBP,p=0.023, OR: 1.45 (CI: 1.05–2.0)].Conclusion.Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

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.

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