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Russell E. Ware - One of the best experts on this subject based on the ideXlab platform.
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Spleen Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial.
Blood, 2008Co-Authors: Russell E. Ware, Renee C. Rees, Rathi V. Iyer, Barry L. Shulkin, Eglal Shalaby-rana, Sharada A. Sarnaik, Ofelia A. Alvarez, James F. Casella, C. Frederic Strife, John H. MillerAbstract:BABY HUG is an NHLBI/NICHD-sponsored Phase III randomized double-blinded placebo-controlled clinical trial (NCT00006400) to test the hypothesis that hydroxyurea can prevent chronic organ damage in very young children with sickle cell anemia (SCA). Renal and splenic Function measures are the co-primary endpoints. Renal disease in SCA begins early in life with impaired urine concentration and acidification, along with glomerular hyperfiltration; some patients will progress to microalbuminuria, glomerulosclerosis, macroalbuminuria, and even renal failure. In BABY HUG, glomerular filtration rate (GFR) elevation was selected as a primary endpoint, to be measured quantitatively by plasma clearance of injected 99mTc-DTPA and also estimated by the Schwartz equation where GFR = (height × 0.55)/(serum creatinine), with creatinine measured by HPLC to .01 mg/dL precision. Of 233 enrolled subjects, 193 completed screening and were randomized to study treatment. Quantitative GFR measurement was successful in most cases: 176 of 182 (97%) of DTPA clearance studies were adequate and 157 subjects had both baseline DTPA and Schwartz GFR values available for analysis. The average age at GFR measurement was 13.7 ± 2.6 months (range 9–19 months) and 59% of subjects were female. Baseline mean (± 1SD) hematological parameters included hemoglobin = 9.0 ± 1.4 gm/dL, absolute reticulocytes = 295.3 ± 137.4 × 109/L, WBC = 14.3 ± 5.8 × 109/L, and fetal hemoglobin (HbF) = 25.6 ± 8.8%. Baseline past medical history included dactylitis (34%), splenic sequestration (7%), and acute chest syndrome (5%). The average baseline quantitative GFR measurement determined by DTPA clearance was elevated at 125.4 ± 34.4 mL/min/1.73m2, (range 40.2 – 300.9 mL/min/1.73m2, normal value 100 ± 20 mL/min/1.73m2). The average baseline GFR estimate by Schwartz equation was substantially higher at 193.9 ± 53.8 mL/min/1.73m2, range 65.8 – 350.0 mL/min/1.73m2. In univariate analysis, the DTPA GFR value was positively correlated with the Schwartz GFR estimate (r=0.22, p=0.0059, slope=0.145) as well as age, weight, height (all p≤.001) but not with hemoglobin, HbF, WBC, reticulocytes, previous sickle cell-related events, or measures of splenic Function including liver-Spleen scan and quantitation of pitted erythrocytes and micronuclei. The Schwartz GFR estimate was positively correlated with age, height, WBC, and splenic Function, and negatively correlated with hemoglobin and HbF. Using a quantitative GFR threshold of 120 mL/min/1.73m2 and an age threshold of 15 months, higher GFR values were observed in older infants, p=0.026. These data indicate that renal dysFunction measured by GFR elevation may begin early in life in SCA; quantitative GFR measurement is feasible but highly variable in this very young patient population; (3) the Schwartz and DTPA GFR values are strongly correlated, but the Schwartz estimate is usually greater and only modestly agrees with the quantitative DTPA GFR value. These baseline GFR measurements in BABY HUG support the hypothesis of age- and disease-related glomerular hyperfiltration in SCA. BABY HUG should yield important information regarding the ability of hydroxyurea to prevent renal damage among infants with SCA.
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preservation of Spleen and brain Function in children with sickle cell anemia treated with hydroxyurea
Pediatric Blood & Cancer, 2008Co-Authors: Jane S. Hankins, Winfred C. Wang, Kathleen J Helton, Beth M Mccarville, Russell E. WareAbstract:Introduction Chronic organ damage is an insidious process in patients with sickle cell anemia (SCA). Although hydroxyurea prevents acute vaso-occlusive events, its effects on the preservation of organ Function remain undefined. Patients and Methods We retrospectively reviewed our single institution experience with children with SCA treated with hydroxyurea for clinical disease severity, who had optional radionuclide liver-Spleen (LS) and brain magnetic resonance imaging (MRI)/with angiography (MRA) performed before and during therapy. Studies were reviewed by pediatric radiologists blinded to treatment status. Demographic and laboratory predictors were modeled using logistic regression. Results A total of 43 children had Spleen Function measured both at baseline and on therapy. After a median of 2.6 years (range, 0.2–8.6 years) of hydroxyurea at maximum tolerated dose (MTD), six patients (14%) completely recovered splenic Function and two (5%) had preserved splenic Function. These eight children had a greater hemoglobin (Hb) concentration on hydroxyurea therapy than those without splenic Function (9.1 vs. 8.6 gm/dl, P = 0.01). Of 25 children with brain MRI/MRA studies performed before initiating hydroxyurea and on therapy, 24 (96%) had no change in brain ischemic lesions compared with pre-treatment studies, after a median of 2.9 years of treatment. Conclusion These retrospective data suggest that hydroxyurea at MTD possibly preserves Spleen and brain Function in children with SCA, and can even result in recovery of splenic Function. Higher final Hb concentration during therapy is a significant laboratory predictor of improved splenic Function. Pediatr Blood Cancer 2008;50:293–297. © 2007 Wiley-Liss, Inc.
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Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study.
Blood, 2005Co-Authors: Jane S. Hankins, Zora R. Rogers, Peter A. Lane, Russell E. Ware, Lynn W. Wynn, J. Paul Scott, Winfred C. WangAbstract:The long-term efficacy and toxicity of hydroxyurea for infants are undefined, and its role in preventing organ dysFunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on Spleen Function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and biannual imaging studies. Hematologic indices were compared with predicted age-specific values and event rates compared with historic rates. All 21 subjects completing the original trial enrolled in the extension study: median age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with Hb S/beta0-thalassemia. Seventeen patients completed 4 years of hydroxyurea, and 11 completed 6 years. After 4 years, hydroxyurea was associated with increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs), and platelets (P < .01). Patients experienced 7.5 acute chest syndrome (ACS) events per 100 person-years, compared with 24.5 events per 100 person-years among historic controls (P = .001). Treated patients had better Spleen Function than expected and improved growth rates. Infants with SCA tolerate prolonged hydroxyurea therapy with sustained hematologic benefits, fewer ACS events, improved growth, and possibly preserved organ Function.
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Long-term hydroxyurea therapy for infants with sickle cell anemia : the HUSOFT extension study. Commentary
Blood, 2005Co-Authors: Jane S. Hankins, Zora R. Rogers, Peter A. Lane, Winfred C. Wang, Russell E. Ware, Lynn W. Wynn, J. Paul Scott, Thomas Luft, Eugene Maraskovsky, Max SchnurrAbstract:The long-term efficacy and toxicity of hydroxyurea for Infants are undefined, and its role In preventing organ dysFunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on Spleen Function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and biannual imaging studies. Hematologic indices were compared with predicted age-specific values and event rates compared with historic rates. All 21 subjects completing the original trial enrolled In the extension study: median age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with Hb S/β 0 -thalassemia. Seventeen patients completed 4 years of hydroxyurea, and 11 completed 6 years. After 4 years, hydroxyurea was associated with increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs), and platelets (P
Winfred C. Wang - One of the best experts on this subject based on the ideXlab platform.
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Biomarkers of splenic Function in infants with sickle cell anemia: baseline data from the BABY HUG Trial
Blood, 2011Co-Authors: Zora R. Rogers, Beatrice Files, Rathi V. Iyer, Barry L. Shulkin, Eglal Shalaby-rana, John H. Miller, Stephen D. Dertinger, Winfred C. Wang, Zhaoyu Luo, Peter A. LaneAbstract:We evaluated Spleen Function in 193 children with sickle cell anemia 8 to 18 months of age by 99mTc sulfur-colloid liver-Spleen scan and correlated results with clinical and laboratory parameters, including 2 splenic biomarkers: pitted cell counts (PIT) and quantitative Howell-Jolly bodies (HJB) enumerated by flow cytometry. Loss of splenic Function began before 12 months of age in 86% of infants in association with lower total or fetal hemoglobin and higher white blood cell or reticulocyte counts, reinforcing the need for early diagnosis and diligent preventive care. PIT and HJB correlated well with each other and liver-Spleen scan results. Previously described biomarker threshold values did define patients with abnormal splenic Function, but our data suggest that normal Spleen Function is better predicted by PIT of ≤ 1.2% or HJB ≤ 55/106 red blood cells and absent Function by PIT ≥ 4.5% or HJB ≥ 665/106. HJB is methodologically advantageous compared with PIT, but both are valid biomarkers of splenic Function. This trial was registered at www.clinicaltrials.gov as #NCT00006400.
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Spleen Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial.
Blood, 2008Co-Authors: Zora R. Rogers, Renee C. Rees, Beatrice Files, Rathi V. Iyer, Barry L. Shulkin, Eglal Shalaby-rana, John H. Miller, Stephen D. Dertinger, Peter A. Lane, Winfred C. WangAbstract:Abstract The Pediatric Hydroxyurea [HU] Phase III Clinical Trial [BABY HUG], an NHLBI and NICHD sponsored double-blind placebo-controlled 14 center trial (NCT00006400), was designed to critically assess the efficacy of HU in preventing chronic organ damage in infants with sickle cell anemia [SCA]. The Spleen is among the first organs damaged in SCA, but loss of Function is variable among patients and difficult to measure. Pretreatment splenic filtrative Function as determined by uptake on 99mTc sulfur colloid liver-Spleen [LS] scan was compared to surrogate markers of Spleen Function: pocked erythrocyte [PIT] counts and flow cytometric quantitation of Howell-Jolly Bodies [HJB]. Splenic uptake of 99mTc sulfur-colloid was qualitatively interpreted by structured consensus of 3 pediatric nuclear medicine physicians. Results were correlated with age, total hemoglobin [Hb], fetal hemoglobin[HbF], white blood cell [WBC], platelet [PLT], absolute neutrophil count [ANC], reticulocyte count [RETIC], Spleen volume [SVOL] on ultrasound, maximum TCD velocity [TCD], glomerular filtration rate determined by 99mTc-DTPA [GFR], steady state oxygen saturation [O2], as well as clinical features of SCA (presence of a palpable Spleen at screening, history of splenic sequestration, dactylitis, other vaso-occlusive event or transfusion). A logarithmic transformation was applied to each parameter (except age) to improve linearity with other variables and stabilize the variance of the transformed data. LS scans were available for 205 (89 male; mean age 13 mos, range 8–18 mos) of the 233 subjects who were recruited without regard to disease severity. To date 170 scans have been adjudicated into 1 of 3 categories of uptake: normal (n=21, 12.4%), reduced (n=124, 72.9%) and absent (n=25, 14.7%). Both surrogate markers of Spleen Function, PIT and HJB, increased with decreasing splenic Function [p<.001] and correlated well with each other [R2=.57, p<.001]. Patients with absent splenic uptake had a significantly higher mean age (14.6 mos) than those with normal (12.3 mos) or reduced uptake (12.5 mos) [p=.001]. Higher PIT, HJB, WBC, RETIC, TCD and lower Hb or HbF values were significantly associated with decreased LS scan uptake [p<.001]. PLT [p=.002] and ANC [p=.02] were also differentiated by categorical Spleen Function, while DTPA and O2 were not. SVOL was also not associated with Spleen Function as assessed by LS scan, PIT, or HJB, but was associated with a palpable Spleen at screening [p=.001]. Patients with diminished Spleen Function on LS scan were more likely to have a history of splenic sequestration [p=.027], dactylitis [p=.025], transfusion [p=.014], and vaso-occlusive events [p=.005]. Higher PIT and HJB values were associated with a history of splenic sequestration [p≤.001], palpable Spleen at screening [p≤.003] and transfusion [p<.001]. No child with a normal Spleen scan had a palpable Spleen at screening or a history of splenic sequestration or transfusion. This is the largest structured assessment of Spleen Function in SCA reported to date. Baseline data from the BABY HUG trial confirms that loss of Spleen Function begins in the first year of life and is associated with indicators of disease severity such as lower Hb and HbF, higher WBC, and history of splenic enlargement. We conclude that a palpable Spleen may not be a Functional one, and that Spleen volume is unrelated to Function. Surrogate assessments, PIT and HJB, correlate well with LS scan results and may obviate the need for radionuclide exposure to determine splenic Function. With these 3 methods to assess Spleen Function the BABY HUG trial is well positioned to determine whether HU impacts the loss of Spleen Function and the utility of surrogate markers to monitor that effect.
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preservation of Spleen and brain Function in children with sickle cell anemia treated with hydroxyurea
Pediatric Blood & Cancer, 2008Co-Authors: Jane S. Hankins, Winfred C. Wang, Kathleen J Helton, Beth M Mccarville, Russell E. WareAbstract:Introduction Chronic organ damage is an insidious process in patients with sickle cell anemia (SCA). Although hydroxyurea prevents acute vaso-occlusive events, its effects on the preservation of organ Function remain undefined. Patients and Methods We retrospectively reviewed our single institution experience with children with SCA treated with hydroxyurea for clinical disease severity, who had optional radionuclide liver-Spleen (LS) and brain magnetic resonance imaging (MRI)/with angiography (MRA) performed before and during therapy. Studies were reviewed by pediatric radiologists blinded to treatment status. Demographic and laboratory predictors were modeled using logistic regression. Results A total of 43 children had Spleen Function measured both at baseline and on therapy. After a median of 2.6 years (range, 0.2–8.6 years) of hydroxyurea at maximum tolerated dose (MTD), six patients (14%) completely recovered splenic Function and two (5%) had preserved splenic Function. These eight children had a greater hemoglobin (Hb) concentration on hydroxyurea therapy than those without splenic Function (9.1 vs. 8.6 gm/dl, P = 0.01). Of 25 children with brain MRI/MRA studies performed before initiating hydroxyurea and on therapy, 24 (96%) had no change in brain ischemic lesions compared with pre-treatment studies, after a median of 2.9 years of treatment. Conclusion These retrospective data suggest that hydroxyurea at MTD possibly preserves Spleen and brain Function in children with SCA, and can even result in recovery of splenic Function. Higher final Hb concentration during therapy is a significant laboratory predictor of improved splenic Function. Pediatr Blood Cancer 2008;50:293–297. © 2007 Wiley-Liss, Inc.
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Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study.
Blood, 2005Co-Authors: Jane S. Hankins, Zora R. Rogers, Peter A. Lane, Russell E. Ware, Lynn W. Wynn, J. Paul Scott, Winfred C. WangAbstract:The long-term efficacy and toxicity of hydroxyurea for infants are undefined, and its role in preventing organ dysFunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on Spleen Function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and biannual imaging studies. Hematologic indices were compared with predicted age-specific values and event rates compared with historic rates. All 21 subjects completing the original trial enrolled in the extension study: median age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with Hb S/beta0-thalassemia. Seventeen patients completed 4 years of hydroxyurea, and 11 completed 6 years. After 4 years, hydroxyurea was associated with increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs), and platelets (P < .01). Patients experienced 7.5 acute chest syndrome (ACS) events per 100 person-years, compared with 24.5 events per 100 person-years among historic controls (P = .001). Treated patients had better Spleen Function than expected and improved growth rates. Infants with SCA tolerate prolonged hydroxyurea therapy with sustained hematologic benefits, fewer ACS events, improved growth, and possibly preserved organ Function.
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Long-term hydroxyurea therapy for infants with sickle cell anemia : the HUSOFT extension study. Commentary
Blood, 2005Co-Authors: Jane S. Hankins, Zora R. Rogers, Peter A. Lane, Winfred C. Wang, Russell E. Ware, Lynn W. Wynn, J. Paul Scott, Thomas Luft, Eugene Maraskovsky, Max SchnurrAbstract:The long-term efficacy and toxicity of hydroxyurea for Infants are undefined, and its role In preventing organ dysFunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on Spleen Function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and biannual imaging studies. Hematologic indices were compared with predicted age-specific values and event rates compared with historic rates. All 21 subjects completing the original trial enrolled In the extension study: median age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with Hb S/β 0 -thalassemia. Seventeen patients completed 4 years of hydroxyurea, and 11 completed 6 years. After 4 years, hydroxyurea was associated with increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs), and platelets (P
Jane S. Hankins - One of the best experts on this subject based on the ideXlab platform.
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preservation of Spleen and brain Function in children with sickle cell anemia treated with hydroxyurea
Pediatric Blood & Cancer, 2008Co-Authors: Jane S. Hankins, Winfred C. Wang, Kathleen J Helton, Beth M Mccarville, Russell E. WareAbstract:Introduction Chronic organ damage is an insidious process in patients with sickle cell anemia (SCA). Although hydroxyurea prevents acute vaso-occlusive events, its effects on the preservation of organ Function remain undefined. Patients and Methods We retrospectively reviewed our single institution experience with children with SCA treated with hydroxyurea for clinical disease severity, who had optional radionuclide liver-Spleen (LS) and brain magnetic resonance imaging (MRI)/with angiography (MRA) performed before and during therapy. Studies were reviewed by pediatric radiologists blinded to treatment status. Demographic and laboratory predictors were modeled using logistic regression. Results A total of 43 children had Spleen Function measured both at baseline and on therapy. After a median of 2.6 years (range, 0.2–8.6 years) of hydroxyurea at maximum tolerated dose (MTD), six patients (14%) completely recovered splenic Function and two (5%) had preserved splenic Function. These eight children had a greater hemoglobin (Hb) concentration on hydroxyurea therapy than those without splenic Function (9.1 vs. 8.6 gm/dl, P = 0.01). Of 25 children with brain MRI/MRA studies performed before initiating hydroxyurea and on therapy, 24 (96%) had no change in brain ischemic lesions compared with pre-treatment studies, after a median of 2.9 years of treatment. Conclusion These retrospective data suggest that hydroxyurea at MTD possibly preserves Spleen and brain Function in children with SCA, and can even result in recovery of splenic Function. Higher final Hb concentration during therapy is a significant laboratory predictor of improved splenic Function. Pediatr Blood Cancer 2008;50:293–297. © 2007 Wiley-Liss, Inc.
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Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study.
Blood, 2005Co-Authors: Jane S. Hankins, Zora R. Rogers, Peter A. Lane, Russell E. Ware, Lynn W. Wynn, J. Paul Scott, Winfred C. WangAbstract:The long-term efficacy and toxicity of hydroxyurea for infants are undefined, and its role in preventing organ dysFunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on Spleen Function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and biannual imaging studies. Hematologic indices were compared with predicted age-specific values and event rates compared with historic rates. All 21 subjects completing the original trial enrolled in the extension study: median age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with Hb S/beta0-thalassemia. Seventeen patients completed 4 years of hydroxyurea, and 11 completed 6 years. After 4 years, hydroxyurea was associated with increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs), and platelets (P < .01). Patients experienced 7.5 acute chest syndrome (ACS) events per 100 person-years, compared with 24.5 events per 100 person-years among historic controls (P = .001). Treated patients had better Spleen Function than expected and improved growth rates. Infants with SCA tolerate prolonged hydroxyurea therapy with sustained hematologic benefits, fewer ACS events, improved growth, and possibly preserved organ Function.
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Long-term hydroxyurea therapy for infants with sickle cell anemia : the HUSOFT extension study. Commentary
Blood, 2005Co-Authors: Jane S. Hankins, Zora R. Rogers, Peter A. Lane, Winfred C. Wang, Russell E. Ware, Lynn W. Wynn, J. Paul Scott, Thomas Luft, Eugene Maraskovsky, Max SchnurrAbstract:The long-term efficacy and toxicity of hydroxyurea for Infants are undefined, and its role In preventing organ dysFunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on Spleen Function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and biannual imaging studies. Hematologic indices were compared with predicted age-specific values and event rates compared with historic rates. All 21 subjects completing the original trial enrolled In the extension study: median age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with Hb S/β 0 -thalassemia. Seventeen patients completed 4 years of hydroxyurea, and 11 completed 6 years. After 4 years, hydroxyurea was associated with increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs), and platelets (P
Azu Owunwanne - One of the best experts on this subject based on the ideXlab platform.
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influence of α thalassemia trait on Spleen Function in sickle cell anemia patients with high hbf
American Journal of Hematology, 1996Co-Authors: Adekunle D. Adekile, M. Tuli, Mohammad Z. Haider, S. Mohannadi, K Alzaabi, Azu OwunwanneAbstract:Spleen Function was studied in a group of 20 Kuwaiti SS patients (aged 2-12 years), using 99mTc-labeled tin colloid scintigraphy. They were screened for the alpha-thalassemia determinants which are prevalent in the Arabian Peninsula [-alpha (3.7 kb) deletion, alpha2-globin gene polyadenylation signal (AATAAA => AATAAG) mutation, and 5' IVS-I splice junction pentanucleotide (GAGGTGAGG => GAGG) deletion] with a combination of polymerase chain reaction and allele-specific oligonucleotide (ASO) hybridization techniques. The patients were divided into three groups depending on the result of their colloid uptake. Group I consisted of 7 patients (35.0%) with normally visualized Spleens, Group II consisted of 5 (25.0%) with partial visualization, and in Group III there were 8 (40.0%) in whom the Spleen was not visualized at all. The significant distinguishing features among those in Groups I and III were mean corpuscular volumes (MCVs) of 74.1 +/- 5.1 and 90.1 +/- 6.6 fl (P<0.0001) and mean corpuscular hemoglobins (MCHs) of 22.4 +/- 2.7 and 27.5 +/- 4.0 pg (P<0.05), respectively. The overall frequency of alpha-thalassemia determinants in the study was 35.0%; however, the frequencies in Groups I, II, and III were 57.1, 30.0, and 18.8%, respectively. alpha-Thalassemia trait, therefore, appears to be associated with normal splenic Function in these patients.
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Influence of α-thalassemia trait on Spleen Function in sickle cell anemia patients with high HbF
American Journal of Hematology, 1996Co-Authors: Adekunle D. Adekile, M. Tuli, Mohammad Z. Haider, K. Al-zaabi, S. Mohannadi, Azu OwunwanneAbstract:Spleen Function was studied in a group of 20 Kuwaiti SS patients (aged 2-12 years), using 99mTc-labeled tin colloid scintigraphy. They were screened for the alpha-thalassemia determinants which are prevalent in the Arabian Peninsula [-alpha (3.7 kb) deletion, alpha2-globin gene polyadenylation signal (AATAAA => AATAAG) mutation, and 5' IVS-I splice junction pentanucleotide (GAGGTGAGG => GAGG) deletion] with a combination of polymerase chain reaction and allele-specific oligonucleotide (ASO) hybridization techniques. The patients were divided into three groups depending on the result of their colloid uptake. Group I consisted of 7 patients (35.0%) with normally visualized Spleens, Group II consisted of 5 (25.0%) with partial visualization, and in Group III there were 8 (40.0%) in whom the Spleen was not visualized at all. The significant distinguishing features among those in Groups I and III were mean corpuscular volumes (MCVs) of 74.1 +/- 5.1 and 90.1 +/- 6.6 fl (P
Adekunle D. Adekile - One of the best experts on this subject based on the ideXlab platform.
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PRESENTED AT THE INTERNATIONAL CONFERENCE ON HEMOGLOBIN DISORDERS KUWAIT, February 5-7th, 2011 LIMITATIONS OF Hb F AS A PHENOTYPIC MODIFIER IN SICKLE CELL DISEASE: STUDY OF KUWAITI ARAB PATIENTS
2011Co-Authors: Adekunle D. AdekileAbstract:Sickle cell disease is characterized by phenotypic heterogeneity and many genetic modifiers have been identified with elevated Hb F being the most recognized ameliorating factor. Kuwaiti sickle cell disease patients carry the India/Arab chromosomal haplotype, which is associated with elevated Hb F (on average ∼22%) on account of the Xmn1 site in the Gγ-globin gene promoter. Most patients had either Hb SS or Hb S-β0-thalassemia (β0-thal) and there are a few Hb SD compound heterozygotes. We have carried out longitudinal clinical studies of these patients to document the pattern of morbidity, Spleen Function, brain and hip magnetic resonance imaging (MRI) for prevalence of silent brain infarcts and avascular necrosis of the femoral head (AVNFH), respectively. In addition, pulmonary Function, SPECT (single photon emission computerized tomography) brain cerebral blood flow and response of selected patients to hydroxyurea (HU) treatment were also studied. The Hb SS and Hb S-β-thal patients have a generally mild phenotype compared to sickle cell disease in other populations and most patients do not have their first pain crisis until about the age of 4 years. Spleen Function is retained till late childhood; pneumococcemia and other severe bacterial infections are rare. Overt stroke and silent brain infarcts are uncommon in childhood (∼3% prevalence) although SPECT reveals cerebral blood flow deficits in ∼30%. Avascular necrosis of the femoral head is, however, common with a prevalence of ∼26% in children and 50% in adults. There is brisk response to HU in patients with frequent pain crises, with marked increases in Hb F levels. Patients who are compound heterozygotes for Hbs S and D-Los Angeles, have the most severe phenotype despite Hb F levels of >20% and Hb S
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influence of α thalassemia trait on Spleen Function in sickle cell anemia patients with high hbf
American Journal of Hematology, 1996Co-Authors: Adekunle D. Adekile, M. Tuli, Mohammad Z. Haider, S. Mohannadi, K Alzaabi, Azu OwunwanneAbstract:Spleen Function was studied in a group of 20 Kuwaiti SS patients (aged 2-12 years), using 99mTc-labeled tin colloid scintigraphy. They were screened for the alpha-thalassemia determinants which are prevalent in the Arabian Peninsula [-alpha (3.7 kb) deletion, alpha2-globin gene polyadenylation signal (AATAAA => AATAAG) mutation, and 5' IVS-I splice junction pentanucleotide (GAGGTGAGG => GAGG) deletion] with a combination of polymerase chain reaction and allele-specific oligonucleotide (ASO) hybridization techniques. The patients were divided into three groups depending on the result of their colloid uptake. Group I consisted of 7 patients (35.0%) with normally visualized Spleens, Group II consisted of 5 (25.0%) with partial visualization, and in Group III there were 8 (40.0%) in whom the Spleen was not visualized at all. The significant distinguishing features among those in Groups I and III were mean corpuscular volumes (MCVs) of 74.1 +/- 5.1 and 90.1 +/- 6.6 fl (P<0.0001) and mean corpuscular hemoglobins (MCHs) of 22.4 +/- 2.7 and 27.5 +/- 4.0 pg (P<0.05), respectively. The overall frequency of alpha-thalassemia determinants in the study was 35.0%; however, the frequencies in Groups I, II, and III were 57.1, 30.0, and 18.8%, respectively. alpha-Thalassemia trait, therefore, appears to be associated with normal splenic Function in these patients.
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Influence of α-thalassemia trait on Spleen Function in sickle cell anemia patients with high HbF
American Journal of Hematology, 1996Co-Authors: Adekunle D. Adekile, M. Tuli, Mohammad Z. Haider, K. Al-zaabi, S. Mohannadi, Azu OwunwanneAbstract:Spleen Function was studied in a group of 20 Kuwaiti SS patients (aged 2-12 years), using 99mTc-labeled tin colloid scintigraphy. They were screened for the alpha-thalassemia determinants which are prevalent in the Arabian Peninsula [-alpha (3.7 kb) deletion, alpha2-globin gene polyadenylation signal (AATAAA => AATAAG) mutation, and 5' IVS-I splice junction pentanucleotide (GAGGTGAGG => GAGG) deletion] with a combination of polymerase chain reaction and allele-specific oligonucleotide (ASO) hybridization techniques. The patients were divided into three groups depending on the result of their colloid uptake. Group I consisted of 7 patients (35.0%) with normally visualized Spleens, Group II consisted of 5 (25.0%) with partial visualization, and in Group III there were 8 (40.0%) in whom the Spleen was not visualized at all. The significant distinguishing features among those in Groups I and III were mean corpuscular volumes (MCVs) of 74.1 +/- 5.1 and 90.1 +/- 6.6 fl (P