Reduction of the Six-Minute Walk Distance in Children with Sickle Cell Disease Is Correlated with Silent Infarct: Results From a Cross-Sectional Evaluation in a Single Center in Belgium.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2107-2107
Author(s):  
Rudy Chapusette ◽  
Laurence Dedeken ◽  
Phu-Quoc Le ◽  
Catherine Heijmans ◽  
Christine Devalck ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Exercise Capacity ◽  
Sickle Cell ◽  
P Value ◽  
Cell Disease ◽  
Walk Distance ◽  
Cross Sectional ◽  
History Of ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Abstract 2107 The 6-minute walk test (6MWT) evaluates the sub-maximal functional exercise capacity and can be used together with the tricuspid regurgitant jet velocity (TRV) and pro-BNP to screen pulmonary hypertension in adults with sickle cell disease (SCD). A reduced 6-minute walk distance (6MWD) is observed in adults with SCD with chronic pain, hip avascular necrosis and osteopenia. In children with SCD, baseline elevated TRV is associated with a decline in age-standardized 6MWD. The aim of our study is to explore the submaximal exercise capacity of children with SCD followed at the Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium and to analyze the factors affecting the 6MWT and the 6MWD. Since September 2011, all patients with SCD above 6 years of age were screened with the 6MWT as part of their follow-up in order to test if their functional capacity was altered. The age-standardized predicted value of the 6MWD was established as reported by Geiger. The 6MWT was considered as normal if the 6MWD was more than 80% of the age-standardized predicted value, moderately decreased between 60–80%, and severely altered less than 60%. Baseline hematological values, clinical events, cerebro-vascular disease, cardio-pulmonary parameters and disease-modifying treatment (DMT) were compared between those with normal and abnormal 6MWT and according to the 6MWD. Forty-six patients (20 boys and 26 girls) with a median age of 12 yrs were investigated. Forty-three were HbSS or HbSβ°, 2 HbSC and 1 HbSβ+. Thirty-two patients had a normal 6MWT and 14 an abnormal 6MWT. Only one patient had a severely altered test. These 2 groups were similar for age, sex, genotype and history of vaso-occlusive crisis or acute chest syndrome (ACS) as well as for the number of patients receiving DMT (either hydroxyurea (HU) or chronic transfusion). The proportion of patients with normal, conditional or abnormal transcranial doppler was also similar in both groups. Silent infarct (SI) on routine cerebral magnetic resonance imaging was found in 42.9% in the group with abnormal 6MWT versus only 19.4% in the group with normal 6MWT (p= 0.087). Pulmonary functional test, blood pressure, heart rate, systolic function and TRV were identical in both groups and only one patient had TRV >2.5m/sec. Baseline pulse oxymetry was slightly but significantly decreased in patients with abnormal 6MWT (98 versus 100%; p=0.022). Biological parameters were not statistically different between both groups. The 6MWD was not modified according to Hb, MCV, HbF, LDH and reticulocytes count or previous history of clinical event, except for the presence of SI (Table 1). Patients with or without SI were similar for age, sex, previous ACS or painful crisis as well as for hemolytic parameters (LDH: 945 versus 825 UI/l, p=0.832; reticulocytes: 273 versus 329 × 103/μl, p=0.548) and basal Hb (9.7 versus 8.8 g/dl, p=0.06). However patients without SI had significantly higher HbF and MCV values, and lower PMN count reflecting that most of them were treated with HU. In this cross-sectional study, the majority of children with SCD have a normal 6MWT. Abnormal 6MWT was not predicted by any clinical or biological features despite a trend to more SI in the group of children with abnormal test. In this series with only one high TRV patient, the sole factor which influences the 6MWD is the presence of SI. The lower exercise capacity of children with SCD with silent stroke may reflect some subclinical motor or sensitive impairment. Our data suggest also that HU might prevent SI which needs to be confirmed by larger prospective studies. Table 1. 6-minute walk distance (6MWD) in 46 SCD children according to their biological values and clinical complications Mean 6MWD in meters (SD) p value Mean Age in years (SD) p value Hemoglobin (g/dl) · ≥ 9 (N = 24) 531.5 (95.4) 0.173 11.2 (2.8) <0.001 · < 9 (N = 22) 569.8 (92.2) 14.5 (2.7) MCV (fL) · ≥ 90 (N = 24) 536.1 (100.7) 0.251 12.6 (3.5) 0.518 · < 90 (N = 22) 568.3 (86.8) 13.2 (2.8) HbF (%)* · ≥ 10% (N = 30) 544.0 (101.7) 0.360 13.2 (3.5) 0.352 · <10% (N = 15) 570.1 (81.8) 12.6 (2.4) LDH (UI/l) · ≥ 1000 (N = 14) 526.8 (86.5) 0.229 11.8 (3.0) 0.105 · < 1000 (N = 32) 562.3 (97.4) 13.4 (3.1) Previous ACS* · Yes (N = 38) 548.6 (98.3) 0.625 13.5 (3.1) 0.453 · No (N = 7) 566.9 (85.5) 12.5 (4.2) Silent Infarct · Yes (N = 12) 502.5 (113.9) 0.035 12.1 (2.2) 0.374 · No (N = 34) 568.9 (82.0) 13.2 (3.4) * Missed information for 1 patient. Disclosures: No relevant conflicts of interest to declare.

Non-Cardiopulmonary Factors Affecting the Six-Minute Walk Distance in Patients with Sickle Cell Disease: Results From the Walk-PHaSST Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1074-1074 ◽  
Author(s):  
Ruchika Goel ◽  
Kathryn L. Hassell ◽  
Roberto F Machado ◽  
Robyn J. Barst ◽  
Nancy Yovetich ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
P Value ◽  
Cell Disease ◽  
Walk Distance ◽  
Factors Affecting ◽  
History Of ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Abstract 1074 Non-Cardiopulmonary Factors Affecting the Six-Minute Walk Distance in Patients with Sickle Cell Disease: Results from the Walk-PHaSST Study. INTRODUCTION: The six-minute walk (6MW) test is frequently used to assess exercise capacity. Patients with sickle cell disease (SCD) can have decreased 6MW distance (6MWD) compared to controls. The 6MWD in conjunction with the TR-jet velocity (TRV) and NT-proBNP have recently been proposed to have a greater predictive value for screening SCD patients suspected of having pulmonary hypertension (PH) than TRV alone. (Parent et al, NEJM, 365; 1, 2011 365 (1):44–53). The American Thoracic Society guidelines recommend caution in controlling for sources of variability in the 6MWD (Am J Respir Crit Care Med 166. 111–117, 2002). Age and height are known confounders of the 6MWD. However, non-cardiopulmonary factors including skeletal-mechanics and pain may also impact the 6MWD. AIM: This study explores whether non-cardiopulmonary factors affect the 6MWD in SCD patients. METHODS: We analyzed data from subjects screened for the walk-PHaSST trial. Walk-PHaSST was a multi-center, placebo-controlled, double-blind, 16-week trial evaluating the safety and efficacy of oral sildenafil for the treatment of Doppler-defined PH (TRV '2.7m/s) in subjects with SCD aged >12 years. The primary endpoint in the trial was change in 6MWD. During screening, subjects were evaluated by self-reported medical history, physical examination, blood sampling, echocardiography and 6MWD. Univariate and multivariable linear regression was performed. A two sided p value <0.05 was considered significant. RESULTS: Of the 673 subjects screened, 671 had a 6MW test. The median (inter-quartile range) of 6MWD was 438m (503 – 381m = 122 m). On univariate analysis, there was no statistically significant effect of the SCD genotype on the 6MWD (p=0.26). Further, when combining the severe genotypes (HbSS and HbSβ0 thalassemia) vs the less severe genotypes, there was no significant difference in the 6MWD (p=0.22). By multivariable linear regression (Table 1), after adjusting for age, gender and TRV, the presence of the following (self-reported by subjects) were independently associated with an estimated decrease in the 6MWD: a) chronic pain (n = 260/671, 38.9%) by 24.3m (95% CI: 9.1–39.4m, p-value <0.01), b) history of avascular necrosis (AVN) of the hip (N =127/671, 18.9%) by 27.8m (95% CI: 9.2–46.4m, p-value <0.01), and c) osteopenia (N = 46/671,6.9% ) by 31.2m (95% CI: 2.7.-59.6m, p-value <0.05) There were no significant two-way interactions between chronic pain, AVN of the hip and/or osteopenia. History of leg ulcers, osteomyelitis and rheumatoid arthritis were not significant predictors of the 6MWD. DISCUSSION: In this multi-center study of patients with SCD, history of self-reported: 1) chronic pain 2) AVN of the hip and 3) osteopenia were independently associated with decreased functional capacity (as assessed by the 6MW test), after adjusting for age, gender, and TRV. While the 6MWD in patients with SCD is significantly related to cardiac function (i.e., PH and LV diastolic dysfunction), the potential effects of pain, osteonecrosis and osteopenia on 6MWD suggest that if using the 6MW test as the primary endpoint in future trials, one should consider documentation of the presence of these factors and use a stratified randomization based on a composite of these non-cardiopulmonary variables. Disclosures: Hassell: NIH:. Gladwin:Patents filed related to treating hemolysis.: Patents & Royalties.

scholarly journals Reduction of the Six-Minute Walk Distance in Children with Sickle Cell Disease Is Correlated with Silent Infarct: Results from a Cross-Sectional Evaluation in a Single Center in Belgium

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e108922 ◽  
Author(s):  
Laurence Dedeken ◽  
Rudy Chapusette ◽  
Phu Quoc Lê ◽  
Catherine Heijmans ◽  
Christine Devalck ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Single Center ◽  
Cell Disease ◽  
Walk Distance ◽  
Cross Sectional ◽  
Minute Walk Distance ◽  
Minute Walk

Association of Hemolysis with Clinical Manifestations of Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2482-2482
Author(s):  
Mehdi Nouraie ◽  
Caterina Minniti ◽  
Craig Sable ◽  
Andrew D. Campbell ◽  
Sohail R Rana ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Hemoglobin Concentration ◽  
Left Ventricular ◽  
P Value ◽  
Z Score ◽  
Cell Disease ◽  
History Of ◽  
Minute Walk

Abstract Background: Sickle cell disease shares common complications such as vasculopathy and organ dysfunction involving the heart, the lungs, the liver and the kidneys with other hemolytic conditions. We hypothesized that a hemolytic vasculopathy may underlie some of these complications. Distinguishing whether a complication is due to hemolysis or to the degree of anemia has been a challenge. Methods: A prospective, multicenter study of 310 children and adolescents with sickle cell disease in steady state was conducted. The associations of measures of hemolysis and of hemoglobin concentration with disease complications were assessed. Principle component analysis was used to develop a hemolytic index from the measurements of reticulocyte count, lactate dehydrogenase, aspartate aminotransfersae and total bilirubin. In order to determine the independent associations of hemolysis with the clinical manifestations of sickle cell disease, we computed correlation coefficient of the hemolytic index with these manifestations that controlled for hemoglobin concentration. P values were adjusted for multiple comparisons. Results: Hemolysis and hemoglobin had no significant correlation with number of the severe pain episodes, acute chest syndrome and priapism. The hemolytic index correlated with history of stroke (r= 0.19, p=0.026), white blood cell count (r=0.22, p&lt;0.001), tricuspid regurgitation velocity (r=0.25, p&lt;0.001), left ventricular mass index (r=0.33, 0&lt;0.001), left ventricular internal diastolic z score (r=0.30, p&lt;0.001) and hemoglobin oxygen desaturation (r=−0.30, p&lt;0.001) but not independently with platelet count and creatinine and six-minute-walk Correlation of clinical outcomes with hemolytic index and hemoglobin concentration in sickle cell cases N Hemolytic index (r and P value) Hemoglobin (r and P value) Hemolytic index adjusted for hemoglobin (partial r and P value) 1 Square roots 2Natural Log 3Adjusted for patient’s height p values are adjusted for 13 comparisons. Number of severe pain episodes in the last year 283 −0.05 (0.4) 0.06 (0.3) −0.02 (0.7) History of acute chest or pneumonia 278 0.11 (0.09) −0.63 (&lt;0.0001) 0.06 (0.3) History of priapism History of stroke 137 0.13 (0.1) −0.63 (&lt;0.0001) 0.06 (0.5) 277 0.14 (0.3) 0.003 (1.0) 0.19 (0.026) Platelet count 1 283 0.32 (&lt;0.0001) −0.35 (&lt;0.0001) 0.11 (0.07) White blood cells 2 283 0.46 (&lt;0.0001) −0.47 (&lt;0.0001) 0.22 (&lt;0.001) Creatinine 1 282 −0.34 (&lt;0.0001) 0.45 (&lt;0.0001) −0.07 (0.2) Systolic blood pressure 283 0.01 (0.8) 0.16 (0.07) 0.14 (0.2) Tricuspid regurgitant jet velocity 264 0.35 (&lt;0.0001) −0.27 (&lt;0.001) 0.25 (&lt;0.001) Left ventricular internal diastolic diameter z score 282 0.53 (&lt;0.0001) −0.50(&lt;0.001) 0.30 (&lt;0.001) Left ventricular mass index1 215 0.51 (&lt;0.0001) −0.44 (&lt;0.001) 0.33 (&lt;0.001) O2 saturation 273 −0.49 (&lt;0.0001) 0.42 (&lt;0.001) −0.30 (&lt;0.001) Six-minute-walk (m)3 228 −0.03 (0.6) 0.17 (0.1) 0.07 (0.3) Conclusion: These observations support the hypothesis that a hemolytic vasculopathy independent of the degree of anemia contributes to the pathogenesis of stroke and pulmonary hypertension and to the development of increased systemic vascular resistance. They also raise the possibility that leukocytosis may in part serve as a predictor of poor outcome by its association with hemolysis. Therapeutic interventions that reduce the rate of hemolysis need to be studied for their potential benefit in decreasing the risk and severity of vasculopathy and the resulting organ damage.

Pulmonary Hypertension in Sickle Cell Disease: Cardiopulmonary Evaluation and Response to Chronic Phosphodiesterase 5 Inhibitor Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 235-235 ◽  
Author(s):  
Roberto F. Machado ◽  
Sabrina E. Martyr ◽  
Anastasia Anthi ◽  
Gregory J. Kato ◽  
Lori A. Hunter ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Functional Capacity ◽  
Cell Disease ◽  
Walk Distance ◽  
Jet Velocity ◽  
Minute Walk Distance ◽  
Minute Walk ◽  
Tricuspid Regurgitant Jet Velocity

Abstract Pulmonary hypertension (PH) is a risk factor for mortality in Sickle Cell Disease, but it is unclear whether pulmonary hypertension is a marker or a direct cause of mortality. To better understand the pathophysiology of pulmonary hypertension in patients with sickle cell disease we performed evaluations of cardiopulmonary function in sickle cell disease patients with pulmonary hypertension (n= 15, mean age = 41 ± 2.4 years, males = 7, HbSS = 15, mean Hb = 8.3 ± 0.2 g/dl, mean tricuspid regurgitant jet velocity = 3.2 ± 0.11 m/s) compared to matched controls with sickle cell disease without pulmonary hypertension (n=11, mean age=40.2 ± 2.5 years, males=4, HbSS=11, mean Hb=8.5 ± 0.3 g/dl, mean tricuspid regurgitant jet velocity = 2.28 ± 0.07 m/s). To evaluate if specific therapy for pulmonary hypertension has any impact on systolic pulmonary artery pressure (PAP), estimated by tricuspid regurgitant jet velocity (TRJ), and functional capacity, measured by six-minute walk test (a well validated surrogate of functional capacity and response to therapy in patients with other causes of pulmonary hypertension), we treated 14 patients with sickle cell disease and pulmonary hypertension (mean age = 40 ± 2.5 years, males = 3, HbSS = 14, mean Hb = 8.8 ± 0.6 g/dl, mean TRJ = 3.4 ± 0.1 m/s) with sildenafil for at least three months. When compared to controls pulmonary hypertension patients had lower maximal oxygen consumption (VO2 max (% predicted), +PH: 44 ± 4, −PH: 55 ± 4; P=0.41), walked shorter six-minute walk distance (meters, +PH: 308.5 ± 53.8, −PH: 427.1 ± 44.6; P=0.03), demonstrated greater degree of interstitial lung disease by chest CT (P &lt; 0.05), and more perfusion impairments measured by ventilation perfusion scan (P &lt; 0.05). Six-minute walk distance correlated directly with maximal oxygen consumption (R=0.6; P=0.01), and inversely with mean pulmonary arterial pressure (R= −0.5; P=0.03) and tricuspid regurgitant jet velocity (R= −0.6;P=0.002), suggesting that the test is an adequate surrogate of functional capacity and response to therapy in pulmonary hypertension patients with sickle cell disease. Chronic treatment with sildenafil (up to 100 mg TID) decreased pulmonary arterial pressure (PAP mmHg, baseline: 50 ± 4.4, sildenafil: 41 ± 2.5; P=0.04) and increased six-minute walk distance (meters, baseline: 394 ± 31, sildenafil: 476 ± 26: P= 0.02). Sildenafil was well tolerated with only 2 patients stopping the drug due to headaches. We also observed 3 episodes of transient eyelid edema not requiring discontinuation of drug. Priapism was not observed in the 3 males treated (2 on exchange transfusion therapy, 1 with erectile dysfunction). In conclusion, we find that in patients with sickle cell disease, 1) pulmonary hypertension, though relatively mild, is associated with severe impairments in cardiopulmonary function, 2) traditional markers of functional capacity such as six-minute walk test can be utilized in this population as a therapeutic endpoint for clinical trials, 3) and therapy with sildenafil seems to have a favorable impact on pulmonary pressures and functional capacity.

Hemolysis-Associated Elevation in Tricuspid Regurgitation Velocity Predicts Reduction in Six-Minute Walk Distance After Two Years of Follow up in Children and Adolescents with Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 574-574
Author(s):  
Victor R. Gordeuk ◽  
Lori Luchtman-Jones ◽  
Andrew D. Campbell ◽  
Sohail R Rana ◽  
Mehdi Nouraie ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Sickle Cell ◽  
Cell Disease ◽  
Walk Distance ◽  
Six Minute Walk Test ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Abstract 574 Background. Elevated tricuspid regurgitation velocity (TRV) as determined by echocardiography correlates with elevated systolic pulmonary artery pressure and is associated with increased morbidity and mortality in adults with sickle cell disease. The importance of elevated TRV in children and adolescents with sickle cell disease is not known. The Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study is an ongoing, longitudinal and observational multicenter study of children with sickle cell disease. Methods. Baseline echocardiography and six-minute walk test were performed prospectively in 361 children and adolescents with sickle cell disease at steady state and then repeat studies were performed in 209 after a median of 22 months of follow up (range 10 months to 36 months), also at steady state. A hemolytic component was derived by principal component analysis of baseline values for reticulocyte count, lactate dehydrogenase, aspartate aminotransferase and total bilirubin. Results. TRV or six-minute walk test were measured at both baseline and follow-up in 193 patients. Twenty-one of these 193 patients had elevated TRV of 2.60 m/sec or higher at baseline. Elevated baseline TRV was associated with high hemolytic rate in 15 patients, defined as hemolytic component above the median for the population studied, and with lower hemolytic rate in six patients. Elevated baseline TRV with high hemolytic rate predicted elevated TRV at follow up (odds ratio 7.7; 95% confidence interval [CI] 2.5 to 24.2; P <0.001) but elevated baseline TRV with lower hemolytic rate did not (odds ratio 1.6; 95% CI 0.2 to 14.1; P = 0.7). Elevated baseline TRV with high hemolytic rate also predicted a decline in the six-minute walk distance by 10% or more at follow-up (hazard ratio 3.9; 95% CI 1.4 to 10.7; P = 0.009). In contrast, higher cardiac output as measured by the left ventricular end diastolic dimension z-score was associated with reduced risk for a decline in the walk distance (hazard ratio 0.7; 95%CI 0.6 to 0.9; P = 0.006). Conclusion. Steady-state TRV elevation in association with a high hemolytic rate occurs on screening in about 8% of children and adolescents with sickle cell disease and is predictive of elevated TRV and reduced six-minute walk distance after approximately two years of follow. Such children may be at risk for adverse clinical consequences of pulmonary hypertension as young adults. Further studies are indicated to identify the molecular mechanisms and to develop appropriate medical management for children and adolescents with this complication. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Influence of haematological profile on the exercise capacity of children with sickle cell disease in Kano

2021 ◽  
Vol 13 (2) ◽  
pp. 79-83
Author(s):  
O. Adeyinka ◽  
U.M. Badaru ◽  
J.M. Nuhu ◽  
R.Y. Ahmad ◽  
B. Bello ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Exercise Capacity ◽  
Sickle Cell ◽  
Negative Influence ◽  
Full Blood Count ◽  
Cell Disease ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Haematological Profile ◽  
Minute Walk

The Exercise Capacity (ExC) of children with sickle cell disease (SCD) may be influenced negatively by both haematological and environmental factors.This study aimed to assessthe influence of haematological profile on the ExC of children with SCD in Kano and to ascertain the safety of conducting 6 minute walk test (6MWT) on those children. In the cross-sectional survey, 162 children were recruited from Murtala Mohammed SpecialistHospital, Kano. Each of them walked to-and-fro for 6 minutes on a 10 meter marked level floor at their own walking pace in order to determine their actual 6 minute walk distance (6MWD). The actual 6MWD was compared with a predicted one in order to determine their ExC.  Full blood count was used to evaluate haematological profiles. The data wereanalysed with Pearson product moment correlation and unpaired t test, at a level of significance of p<0.05 using SPSS version 20. Results showed that seventy (70) males (43.2%) and ninety two (92) females (56.8%) with mean age of 10.7±3.27 years took part in the study. The actual 6MWD was 366.20 m ± 59.88m (95%CI=356.91m - 375.49m) which was 59.17% of the predicted one. ExCcorrelated with each of White blood cell count (WBC)(r= - 0.22; p=0.005), Sex (r= - 0.27; p=0.001) and age (r=0.19; p=0.013). None of the participants experienced exercise-induced vaso-occlusive crisis during or immediately after the 6MWT.It was concluded that infection (signified by increased WBC count) and female gender have negative influence on  ExC. 6MWT is safe to be performed by children with SCD.

Splenectomy Is Not Associated With Higher Tricuspid Regurgitant Jet Velocity In Patients With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1002-1002
Author(s):  
Tanvi Adsumilli ◽  
Hillel Cohen ◽  
Jane A. Little ◽  
Deepa Manwani
Keyword(s):  
Sickle Cell Disease ◽  
Linear Regression ◽  
Sickle Cell ◽  
Categorical Variables ◽  
Cell Disease ◽  
Walk Distance ◽  
Jet Velocity ◽  
Minute Walk Distance ◽  
Minute Walk ◽  
Tricuspid Regurgitant Jet Velocity

Abstract Introduction An elevated tricuspid regurgitant jet velocity (TRV) has been associated with hemolysis and increased mortality in sickle cell disease (SCD). An elevated TRV is also associated with decreased exercise capacity as measured with the six minute walk distance (6MWD). Vascular complications including pulmonary arterial hypertension (PAH) and thrombosis have been reported to occur at an increased rate following splenectomy in various disorders, including chronic hemolytic anemias or those associated with ineffective erythropoiesis, such as thalassemia. The risk of elevated TRV, already high in patients with thalassemia (33%), is significantly increased with splenectomy (unadjusted O.R 5.3, 95% CI 2.1-13.5). We wanted to evaluate the independent association of splenectomy with TRV in a cohort of patients with homozygous SS disease (HbSS). Methods We performed a retrospective cross sectional analysis of the association between splenectomy and an elevated TRV. 41 splenectomized HbSS patients were identified within the 482 HbSS patients ≥12 years of age from the multi-centered Walk-PHASTT study of pulmonary hypertension; this study incorporated a cardiovascular phenotype, including echocardiogram and 6-minute walk distance (6MWD) as part of the observational phase of the study. This sample size achieved > 99% power to detect a 15% difference in TRV in the 2 groups at a significance level of 0.05 using a 2 sided two sample t-test. Other parameters compared between groups included 6MWD, age, blood pressure, body surface area, urine albumin, blood urea nitrogen, ferritin, creatinine, white blood cell count, platelet count, hematocrit, hemoglobin, bilirubin, lactate dehydrogenase, aspartate aminotransferase, absolute reticulocyte count (ARC), absolute neutrophil count and hydroxyurea use. Continuous variables were analyzed with linear regression and 2-sided t-tests and categorical variables were analyzed with Chi-square test. Multivariable linear regression models were constructed using variables significantly associated with TRV in bivariate analyses. Results There were no significant differences in mean± SD TRV (2.62± 0.42 vs 2.62± 0.43, p=0.99) or 6MWD (446± 84 vs 440± 97, p=0.74) between the 2 groups. A history of splenectomy was associated with significantly higher ARC, hemoglobin and hematocrit. When adjusted for hemoglobin and ARC an association of TRV with splenectomy was still not observed (p=0.82). Conclusion Surgical asplenia is not associated with higher TRV compared with presumed auto-infarction of the spleen in a large cohort of adult patients with HbSS. Platelet and WBC counts were also not higher in the splenectomized patients, making it less likely that the thrombotic risk is greater in splenectomized patients compared to the high baseline risk in HbSS patients. The overall greater risk of elevated TRV with asplenia in HbSS cannot be addressed here, because most patients are functionally asplenic even absent surgical resection. However, these results suggest that, distinct from thalassemia, surgical asplenia does seem to not confer additional risk for elevated TRV in HbSS, an important consideration when weighing the risks and benefits of splenectomy. Disclosures: No relevant conflicts of interest to declare.

Genetic Polymorphisms Associated with Priapism in Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 789-789
Author(s):  
Laine Elliott ◽  
Allison E. Ashley-Koch ◽  
Jude Jonassaint ◽  
Jennifer Price ◽  
Jason Galloway ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Linkage Disequilibrium ◽  
Sickle Cell Disease ◽  
Candidate Genes ◽  
Sickle Cell ◽  
P Value ◽  
Cell Disease ◽  
P Values ◽  
History Of ◽  
Male Patients

Abstract Priapism, a painful and prolonged erection, has been reported to occur in 30–45% of male patients with sickle cell disease (SCD). However, little is known about the pathological processes and genetic risk factors that contribute to the occurrence of priapism. The identification of genetic variables that are associated with priapism may therefore help define both critical pathophysiologic mechanisms not otherwise apparent, as well as patients at increased risk. We examined genetic variation in our sample of 199 unrelated, adult (&gt;18 years), male patients with Hb SS and Hb Sβ0-thalassemia, 83 (42%) of whom reported a history of priapism. Candidate genes for association with priapism were identified based on their involvement in adhesion, coagulation, inflammation, and cell signaling. Additionally, we examined genes involved in NO biology (NOS2, NOS3, SOD1, SLC4A1). Finally, we also examined polymorphisms in the KLOTHO gene, which has previously been associated with priapism. We examined a total of 389 SNPs in 48 candidate genes. Except for the gene encoding the β2 adrenergic receptor, SNP genotyping was performed by TaqMan, using Assays-on-Demand or Assays-by-Design genotyping products (Applied Biosystems). Allele tests were used to detect genetic associations with priapism. Strong evidence of association was found for SNP rs7526590 in the transforming growth factor-β receptor, type III (TGFBR3) gene (p=.00058), SNP rs10244884 in the aquaporin (AQP1) gene (p=.00068), and SNP rs3768780 in the integrin αV (ITGAV) gene (p=0.00090). A second ITGAV SNP (rs3768778), in linkage disequilibrium (r2=.59) with the first, also showed association with priapism (p=.00888). The A1 subunit of coagulation factor XIII (F13A1) had four SNPs (hcv1860621, rs1032045, rs1674074, rs381061) with p-values less than 0.010 (p-values = 0.00156, 0.00415, 0.00648, and 0.00712, respectively). The linkage disequilibrium among these F13A1 SNPs is negligible (r2 &lt;.15). We also adjusted for multiple testing using the Benjamini-Hochberg procedure (significance threshold &lt;.10). SNP rs7526590 in TGFBR3, SNP rs10244884 in AQP1 and SNP rs3768780 in ITGAV each had a false discovery rate (FDR) p-value of .09834. SNP rs1674074 in F13A1 had an FDR p-value of .12733. The other SNPs in F13A1 had large FDR p-values, close to .30. We did not detect an association between priapism and genetic variation in the Klotho gene, as was previously reported by Nolan et al. (2005). Specifically, SNPs rs2249358, rs211234 and rs211239 showed a virtually identical distribution of genotypes for individuals with and without a history of priapism. However, our population is not identical to the previous study, which included patients as young as 10 years old. In conclusion, our data support the hypothesis that genetic variation is associated with risk for priapism among males with SCD and suggest that genes involved in the TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important.

Chronic Pain Is An Independent Predictor of Lower 6 Minute Walk Distance In Patients with Sickle Cell Disease: Results From Walk-PHaSST Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2658-2658
Author(s):  
Lakshmanan Krishnamurti ◽  
Ruchika Goel ◽  
Oswaldo Castro ◽  
Robyn J. Barst ◽  
Erika Berman Rosenzweig ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Exercise Capacity ◽  
Sickle Cell ◽  
Acute Pain ◽  
Research Funding ◽  
History Of ◽  
Pain Crisis ◽  
The Mean ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Abstract 2658 Introduction: Six minute walk distance (6MWD), is a measure of exercise capacity commonly used as an endpoint in pulmonary hypertension (PH) clinical trials. Many patients with sickle cell disease (SCD) have acute pain crises or chronic pain syndromes that impair their quality of life. While patients with SCD who are undergoing screening for PH are generally screened in steady state, i.e., when they have not had a recent pain crisis, the impact of chronic pain on exercise capacity in this group of patients has not been previously evaluated. Methods: walk-PHaSST was a multi-center screening study designed to identify subjects with SCD at increased risk for symptomatic PH, defined by a tricuspid regurgitant velocity (TRV) ≥ 2.7 m/sec and 6MWD between 150–500 meters, for enrollment in a double-blind placebo controlled trial of sildenafil. The primary endpoint was the change in 6MWD after 16 weeks of treatment. We examined the relationship between subjects' self-reported acute and chronic pain and baseline 6MWD in the screened SCD patients in walk-PHaSST. Results: For 90% of subjects, the information about pain was reported by the patient or parent/family member. Documentation of pain management and utilization of services was verified from medical records in 10% of subjects. Ninety four percent of all subjects reported having a history of acute sickle cell pain crises; 6% reported never having had an acute pain crisis. For the subjects who reported a history of acute pain crises, the ‘typical’ acute pain rating on a scale of 0 to 10 was ≥ 7 (maximum 10) for 77% of this subset of subjects. A total of 342 (50%) subjects reported not having had any pain crises in the preceding week. Of 720 subjects screened medical history and 6 MWD was available in 673 patients. Of these 633 (94%) subjects did not report having had a pain crisis requiring an emergency department visit or hospitalization in the preceding week. A total of 39% of subjects reported chronic sickle cell related pain; no rating was reported for chronic pain. 88% of patients reported using medications for pain control while 15% reported using non-drug therapy including physical therapy in 3%, alternative therapy in 2%, acupuncture in 2% and hypnosis in < 1% of patients. The mean 6MWD for the screened population was 439 meters (median 438 m, range 123–713 m). A total of 171/673 (26%) subjects had a 6MWD >500 meters, which was above the screening cut-off for enrollment in the main interventional trial. By univariate analysis, subjects reporting chronic pain had a significant lower odds ratio for walking > 500 meters (OR 0.637, 95% C.I 0.44–0.99); a similar observation was seen with those subjects with a history of acute pain crises (OR 0.47, 95% C.I 0.24–0.91). Multivariable logistic regression analysis revealed a significant inverse relationship between chronic pain but not acute pain and 6MWD after adjusting for age, TRV, gender, hematocrit and smoking history (See Table 1). The mean 6MWD decreased by 27 meters with self reported chronic pain after adjusting for TRV, age, gender, hematocrit and 6MWD. Conclusions: TRV is a known predictor of 6MWD. However, these data suggest that patient self reported sickle cell related chronic pain is also an independent predictor of 6MWD. This relationship raises interesting questions about the potentially confounding effects of pain on exercise capacity as assessed by the 6MW test. Further study is warranted to investigate an association between chronic pain and exercise capacity in SCD as well as exploration of appropriate endpoints for future clinical trials in patients with SCD and suspected symptomatic PH. Disclosures: Barst: Pfizer: Consultancy, Research Funding. Rosenzweig:Pfizer: Research Funding. Badesch:Pfizer: Honoraria, Research Funding. Hassell:Novartis: Research Funding.

scholarly journals Improvement of the Six-Minute Walk Test in Children with Sickle Cell Disease over Time

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1085-1085
Author(s):  
Geoffrey Bourg ◽  
Laurence Dedeken ◽  
Phu-Quoc Le ◽  
Laurence Rozen ◽  
Safiatou Diallo ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Hemoglobin Level ◽  
Walk Test ◽  
Cell Disease ◽  
Walk Distance ◽  
Six Minute Walk Test ◽  
Clinical Events ◽  
Minute Walk Distance ◽  
Minute Walk ◽  
Over Time

Abstract The six-minute walk test (6MWT) was introduced in adults and children suffering from pulmonary or cardio-vascular conditions to assess their sub-maximal functional exercise capacity. In sickle cell disease (SCD), a reduced 6-minute walk distance was observed in adults with chronic pain, hip avascular necrosis and osteopenia ; and in children with low hemoglobin level, low fetal hemoglobin, a baseline elevated TRV. In a previous study (Dedeken et al., PLoS One 2014), we also showed that abnormal 6MWT was significantly associated with the presence of silent infarct. The aim of our study is to explore the evaluation of the 6MWT over time and to confirm the correlation with the cerebral vasculopathy in a larger cohort. This study was conducted at Hôpital Universitaire des Enfants Reine Fabiola (Brussels, Belgium) and included SCD children older than 6 years, regularly followed between 2011 and 2017 and who had at least two 6MWT. The age-standardized predicted value of the 6-minute walk distance (6MWD) was established as reported by Geiger. The 6MWT was considered as normal if the 6MWD was more than 80% of the age-standardized predicted value. Baseline hematological values, clinical events, cerebro-vascular disease, cardio-pulmonary parameters and disease-modifying treatment (DMT) were compared between those with normal and abnormal 6MWT and according to the 6MWD and between the 1st and the 2nd 6MWT overtime. 118 patients have been assessed twice and had at first evaluation a 6MWD of 90.6% (Range 49-119%), with an abnormal test found in 5.1%. The characteristics of the patients are detailed in the Table 1. The changes of the 6MWD and the biological data over time are detailed in Table 2. After 4 years of follow-up, 77.1% of patients were treated with Hydroxyurea (HU) and 16.6% patients were chronically transfused. In parallel with the increased HU prescribing rate, we have observed a significant increase of the Hb and the MCV and a decrease of reticulocytes and hemolysis parameters. The first 6WMT was performed at the median age of 10.3 years and the last one at the median age of 14.1 years. The median 6MWD increased over time including for non-chronically transfused patients. Girls performed less well in the 6MWT (93% for girls vs. 95.7% for boys; P = 0.03). Acute chest syndrome was significantly more frequent in boys (62%) compare to girls (38.7%). Nevertheless, no other differences were founded between boys and girls regarding biological values, clinical events or DMT. 26.5% of our patients have silent infarcts at a median age of 14.6 years. The 6MWD was the same in patients with and without silent infarcts (92.5% vs. 95% ; P=0.17) even when chronically transfused patients were excluded (94% vs. 95% ; P= 0.20). Patients with silent infarcts have a significant lower hemoglobin level and higher reticulocytes count, neutrophils count, LDH and MCV. In conclusion, the 6MWD observed in our cohort characterized by a very high rate of HU treatment is much higher than published in others series and improved over time. With only 5% of SCD patients having a 6MWD < 80% of the normal predicted value at last evaluation, we were not able anymore to confirm a correlation between the presence of silent infracts and abnormal 6MWT. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document