Elective Cholecystectomy Decreases the Morbidity of Cholelithiasis and Cholecystectomy in Pediatric Sickle Cell Disease.

Abstract Abstract 1544 Poster Board I-567 PURPOSE Cholelithiasis frequently occur in sickle cell disease, are easily diagnosed by ultrasound, and are associated with hospital admissions for abdominal pain. Elective cholecystectomy is controversial in sickle cell disease despite small series which suggest that elective cholecystectomy decreases the morbidity of the procedure. Therefore we examined the impact of cholecystectomy on morbidities associated with cholelithiasis and cholecystectomy in sickle cell disease. METHODS: Records of 191 consecutive pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy between January 1999 and May 2009 were retrospectively reviewed. The cholecystectomies were classified into 3 groups 1) elective: no pre-operative symptoms, cholelithiasis on screening ultrasound, pre-planned surgical preparation; 2) symptomatic: pre-operative symptoms of cholelithiasis on ultrasound, pre-planned surgical preparation; 3) emergent: hospitalization for acute cholecystitis symptoms, cholelithiasis on ultrasound, no pre-planned surgical preparation. We compared the morbidity of cholelithiasis and cholecystectomy by examining pre-operative hospitalizations, cholecystectomy hospitalization, and post-operative hospitalizations. RESULTS: Patients with sickle cell disease underwent a total of 191 cholecystectomies over a ten year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required an emergent cholecystectomy had a longer post-operative hospitalization time than elective cholecystectomy (7.3 vs 4.3 P< 0.001). Prior to hospitalization for the cholecystectomy, patients needing emergent and elective cholecystectomy had similar number of total of hospital admission days (5.2 vs 5.6 P=0.73). However, the emergent cholecystectomy population required more hospital admission days prior to surgery for abdominal pain than the elective patients (1 vs 0.37, P=0.01). After the cholecystectomy, emergent patients required more total hospital admission days (7.2 vs 2.9, P=0.002) and more admission days for abdominal pain (0.5 vs 0.2, P=0.049) than patients that underwent elective cholecystectomy. In 18 patients with the most severe abdominal pain (>2 inpatient admission days) prior to hospitalization for cholecystectomy, 11 (61%) were not admitted after cholecystectomy for pain. Patients receiving chronic blood transfusions prior to surgery had a reduced need for emergent cholecystectomy as compared to non-transfused patients (8% vs 25%, P= 0.056 by chi-square). Patients receiving hydroxyurea had a similar rate of need for an emergent cholecystectomy as compared to patients not on hydroxyurea (22% vs 13% P= NS). No differences in degree of anemia or reticulocytosis were identified in patients requiring emergent vs. elective cholecystectomy (Hb: 8.7 vs 8.6 g/dL; Reticulocyte percent: 10.9% vs 10.4%). The morbidity of patients in the symptomatic cohort was intermediate between the elective and emergent cohorts without demonstrating statistical significance. CONCLUSIONS: This represents the largest reported series of pediatric cholelithiasis and cholecystectomy in sickle cell disease to date. This data strongly suggests that elective cholecystectomy decreases morbidity associated with cholelithiasis and cholecystectomy in sickle cell disease. Disclosures No relevant conflicts of interest to declare.

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Gallstones in Sickle Cell Disease: A Single Institution Experience

Blood ◽

10.1182/blood.v124.21.4939.4939 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4939-4939

Author(s):

Thomas Coats ◽

Kate Gardner ◽

Swee Lay Thein

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Surgical Complications ◽

Conflicts Of Interest ◽

Acute Cholangitis ◽

Biliary Tree ◽

Ultrasound Scan ◽

Cell Disease ◽

Time Period ◽

Elective Cholecystectomy

Abstract Background: There is an increased incidence of gallstones in patients with sickle cell disease (SCD), due to haemolysis. Complications of gallstones include cholecystitis, pancreatitis and cholangiopathy and gallstones can trigger an acute sickle cell crisis. It is not known whether patients with asymptomatic gallstones would benefit from elective cholecystectomy to avoid such complications. Method: Electronic patient records of all 767 adult SCD patients attending clinic at King’s College Hospital, London between 1st Jan 2003 and 31st Dec 2013 were retrospectively reviewed to identify cases of gallstones. Medical records and steady state blood values were analysed in all those patients with an ultrasound of the biliary tree during this time period. Results: Amongst the cohort of 767 patients with SCD, 481 (62.7%) were HbSS, 244 (31.8%) HbSC, 35 (4.6%) HbSB+, 6 (0.8%) HbSB0 and 1 (0.1%) HbSHFPH genotype. 43% were male. Mean age at the end of the study period was 36.6 +/- 12.5 years. 344 patients had an ultrasound scan of the biliary tree during the time period of the study. 38 of the 344 patients scanned had had a cholecystectomy prior to 2003. Of the remaining 306 patients with an ultrasound scan, 134 had gallstones identified within the gallbladder. The 134 patients with gallstones comprised 119 (88.8%) HbSS, 12 (9.0%) HbSC, 2 (1.5%) HbSB+ and 1 (0.7%) HbSB0. 39.6% were male. Mean age at the end of the study period was 35.4 +/- 12.2 years. Of the 134 patients with gallstones identified during the study, 35 developed serious complications directly relating to cholelithiasis (5 pancreatitis, 4 acute cholangitis, 8 choledocholithiasis and 18 isolated cholecystitis) and 8 of these patients required sphincterotomies +/- stone removal with endoscopic retrograde cholangio-pancreatogram. 34 of the 134 patients with gallstones went on to have a cholecystectomy during the 11 year study period. Of these 34, 3 had recorded surgical complications following cholecystectomy (2 bile leaks, 1 hepatic injury). All 3 cases had gallstone-related complications prior to the cholecystectomy. Discussion: Our findings of cholelithiasis in 134 of the 306 of sickle cell disease patients scanned, is similar to incidence reported in the literature. Notably, we documented a high incidence of complications associated with cholelithiasis. Furthermore, there were higher than expected rates of surgical complications in cholecystectomy undertaken following the development of a complication relating to gallstones. These findings make routine screening for cholelithiasis followed by elective cholecystectomy for positive cases an attractive approach. Disclosures No relevant conflicts of interest to declare.

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The Impact of a Multidisciplinary Sickle Cell and Gynecology Clinic

Blood ◽

10.1182/blood.v128.22.1319.1319 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1319-1319

Author(s):

Vardya A Tasha

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Reproductive Age ◽

Cell Disease ◽

Time To Event ◽

University Hospitals ◽

Contraception Use ◽

Before And After ◽

The Impact

Abstract Background: Contraception and pregnancy planning are critically important for patients with sickle cell disease (SCD). However, rates of contraceptive utilization are often suboptimal and unplanned pregnancy remains a problem among this patient population. In an effort to improve care, a multidisciplinary hematology and gynecology clinic was initiated at University Hospitals Case Medical Center in which women of reproductive age received comprehensive care in single visits. Objective: To determine the impact on pregnancy, contraception use and sexually transmitted infections (STIs) diagnoses of a multidisciplinary hematology and gynecology clinic for women with SCD. Methods: A retrospective cohort study of women seen in University Hospitals Hematology Clinic for sickle cell disease from 2011 to 2015. Baseline demographics as well as the subsequent outcomes of pregnancies, contraception use and STIs were collected. Total differences in outcomes before and after the multidisciplinary clinical were evaluated with Fisher's exact test. Longitudinal differences in pregnancies and STIs were analyzed with time-to-event analyses. For outcomes of interest p charts were constructed with upper and lower control limits. Results: A total of 133 women total were identified as reproductive age women with sickle cell disease from 2011 to 2015. The percentage of SCD patients using birth control before and after the multidisciplinary clinic increased from 12.3% to 37% (p=0.0001). The p chart for contraception use is provided bellow and was highly significant. No significant differences in pregnancy or STIs were identified in time-to-event analysis and p charts, though the total number of STIs before and after the intervention was limited (eighteen). Conclusion: Incorporating a multidisciplinary approach with combined hematology and gynecology care for women with sickle cell disease has the potential to improve access to contraception use in this population. Figure Figure. Disclosures No relevant conflicts of interest to declare.

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The Impact of Local Air Quality on the Number of Hospital Admissions with Acute Pain in Sickle Cell Disease within an Urban Environment.

Blood ◽

10.1182/blood.v108.11.3790.3790 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3790-3790

Author(s):

Deborah Yallop ◽

Edward R. Duncan ◽

Ellie Norris ◽

Gary Fuller ◽

Nikki Thomas ◽

...

Keyword(s):

Air Quality ◽

Sickle Cell Disease ◽

Environmental Factors ◽

Sickle Cell ◽

Acute Pain ◽

Hospital Admissions ◽

Clinical Severity ◽

Cell Disease ◽

Low Levels ◽

The Impact

Abstract The clinical severity of sickle cell disease (SCD) is dependent on genetic and environmental variables. The impact of environmental factors on disease is a major public health issue and air pollution has been consistently correlated with poor health outcomes. Environmental factors in SCD have been poorly studied. We have retrospectively studied the numbers of daily admissions with vaso-occlusive sickle cell pain to King’s College Hospital, London, in relation to local daily air quality measurements. We analysed 1047 patient episodes over 1400 days (1st January 1998 to 31st October 2001). Statistical time series analysis was performed using cross-correlation function (CCF), where the observations of one series are correlated with the observations of another series at various lags and leads, values >0.05 being significant. This showed a significant association between increased numbers of admissions and low levels of nitric oxide (NO) (CCF=0.063), low levels of carbon monoxide (CO) (CCF=0.064) and high levels of ozone (O3) (CCF=0.067). There was no association with sulphur dioxide (SO2), nitric dioxide (NO2) or dust. The significant results were further examined using quartile analysis. This confirmed that increased numbers of hospital admissions were associated with high levels of O3 (oneway ANOVA p=0.039) and low levels of CO (oneway ANOVA p=0.042). Low NO levels were also associated with increased admissions, not however reaching statistical significance on quartile analysis (oneway ANOVA p=0.158). O3 levels show marked seasonal variation, with high levels occurring in summer months in the UK. We have previously shown a trend towards increased admissions in the summer months with acute sickle related pain, whereas other groups, which are primarily based in rural tropical climates, found increased admissions in cold, rainy months. The adverse effect of high O3 levels may explain this difference. There is no direct evidence to explain the mechanism by which high O3 levels leads to vaso-occlusion in SCD but high levels of O3 have been linked to reduced respiratory function, which may in turn precipitate vaso-occlusion. Independent studies have shown high CO levels are linked to increased respiratory and cardiovascular admissions. Paradoxically we found that high CO levels were linked to decreased admission numbers and may be protective against acute pain in SCD. CO may confer benefit by forming carboxyhaemoglobin that cannot polymerise resulting in decreased sickling. Previous studies have shown prolonged red cell survival in vivo following administration of CO to patients with SCD. Our study also suggests higher levels of atmospheric NO are linked to fewer admissions. NO is known to be central in the pathophysiology of vaso-occlusion and sickle cell patients are thought to have functional deficiency of NO. Many groups have reported inhaled NO as beneficial in the treatment of sickle pain. Our study suggests air quality has a significant effect on acute pain in SCD and that patients should be counselled accordingly. Based on these findings it would be appropriate to warn patients that high O3 levels might precipitate complications of SCD. The potential beneficial effect of CO and NO is intriguing and requires further investigation.

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A Multicentre Study of Environmental Factors on the Severity of Sickle Cell Disease

Blood ◽

10.1182/blood.v124.21.4841.4841 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4841-4841

Author(s):

Sanjay Tewari ◽

Fred Piel ◽

Valentine Brousse ◽

Baba PD Inusa ◽

Paul Telfer ◽

...

Keyword(s):

Sickle Cell Disease ◽

Environmental Factors ◽

Sickle Cell ◽

Hospital Admissions ◽

Conflicts Of Interest ◽

Acute Chest Syndrome ◽

Electronic Patient Records ◽

Cell Disease ◽

Hospital Data ◽

Significant Difference

Abstract Background: Sickle cell disease (SCD) is a very variable condition, with some patients being asymptomatic and others admitted frequently to hospital. Genetic factors have been extensively investigated but only explain a small amount of the variability to date. Environmental factors are undoubtedly important, but have not been studied in depth, at least in part because of the difficulty of conducting these studies. We have analysed the role of climatic, environmental and temporal factors in determining the frequency of hospital admissions in children with SCD to 4 large sickle cell centres in London and Paris. Participants and Methods: Clinical data were collected from 1st January 2007 to 31st December 2012. Inclusion criteria were children with SCD (HbSS and HbSC) between the ages of 0 and 17 years, admitted to hospital with acute pain, acute chest syndrome or fever. All children lived within 4 miles radius (London) or 10km (Paris) of the hospital. Data were collected using specific electronic patient records of SCD patients. Data were collected on the reason for admission, date and length of admission. Daily air quality records were collected from sites around Paris and London, including details of black smoke, particulate matter, nitric oxide, carbon monoxide, sulphur dioxide and ozone. Daily meteorological records were obtained from weather stations in London and Paris including wind speed, temperature, rainfall and humidity. Statistical analysis including time series studies were conducted using R software version 3.1.1. Results: There were a total of 2717 admissions over the six year study period. Overall for the London hospitals there was a mean of 0.39 admissions/patient/year, with 1406 admissions for pain, 153 for acute chest syndrome and 417 for fever. The rate of admission/patient/year by cause for HbSS and HbSC across the London hospitals is shown in table below: Table 1. Rates of admission/patient/year by cause Sickle genotype/cause of admission All London hospitals Institution A Institution B Institution C HbSS (Pain) 0.31 0.18 0.40 0.43 HbSS (Fever) 0.09 0.03 0.15 0.11 HbSS (acute chest syndrome) 0.04 0.03 0.04 0.04 HbSC (pain) 0.07 0.03 0.08 0.10 HbSC (fever) 0.03 0.01 0.04 0.05 HbSC (acute chest syndrome) 0.004 0.008 0.002 0.002 Overall admission numbers were significantly higher on Mondays and Tuesdays in London but there was no such variation in Paris (Table 2). Table 2. Mean number of admissions on days of week in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Weekday Monday 0.75** 0.35 Tuesday 0.77** 0.36 Wednesday 0.66 0.36 Thursday 0.64 0.32 Friday 0.60 0.32 Saturday 0.51 0.20 Sunday 0.57 0.27 There was no seasonal variation in admission numbers in London, but significantly higher numbers of patients admitted in Paris during autumn and winter. Table 3. Mean number of seasonal admissions in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Season Autumn 0.70 0.35** Spring 0.60 0.31 Summer 0.64 0.25 Winter 0.62 0.34** Conclusion In London, there is a 2-3 fold variation in admission rates for the same complications between different hospitals. Similarly there is a significant difference on the effects of season and weekday between Paris and London. These results are statistically stronger than many effects which are identified in genetic and therapeutic studies, and show the importance of environmental and cultural factors, which are potentially modifiable. The effect of weather and pollution on hospital admissions is currently being analysed. Disclosures No relevant conflicts of interest to declare.

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Sickle Cell Disease in Central India: High Prevalence of Sickle/Beta Thalassemia and Severe Dsiease Phenotype

Blood ◽

10.1182/blood.v126.23.4588.4588 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4588-4588 ◽

Cited By ~ 1

Author(s):

Dipty Jain ◽

Vinit Warthe ◽

Roshan Colah ◽

Graham Roger Serjeant

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Hospital Admissions ◽

Conflicts Of Interest ◽

Central India ◽

Beta Thalassemia ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Beta Thalassaemia ◽

Alpha Thalassaemia

Abstract Objectives: To assess the clinical, haematological and molecular features of sickle cell disease in central India where the disease has been reported to be more severe than the mild clinical course usually observed in the Asian haplotype of homozygous sickle cell (SS) disease. Methods: A cross-sectional assessment of 91 consecutive patients with sickle cell disease attending clinics at the Akola Government Medical College, Akola, Maharastra State, India. Results: Of the 91 patients, who were predominantly of the scheduled caste community, 49 had SS disease, 6 had sickle cell-HbD Punjab, and 36 had sickle cell-beta thalassaemia. Of the patients with sickle cell-beta thalassaemia, the beta thalassemia mutation was IVS1-5 G>C mutation in 25 patients (69%) while the rest had one of seven other molecular mutations identified (Table1). Contrary to commonly held beliefs, alpha thalassaemia occurred in only 9/90 (10%) of subjects but fetal haemoglobin (HbF) levels were markedly elevated with mean and median levels of 24.4%. All except 3 SS disease patients had the Xmn1(+/+) polymorphism. These patients exhibited many of the severe manifestations of sickle cell disease. Comparison of SS disease and sickle cell-beta thalassaemia showed no differences in the prevalence of dactylitis, bone pain crisis, acute chest syndrome, haemoglobin level, reticulocyte counts or hydroxyurea usage but patients with sickle cell-beta thalassaemia had significantly more hospital admissions, blood transfusions, and greater frequencies of splenomegaly and hepatomegaly. Conclusions: Many of the patients with sickle cell disease in central India appear to have relatively severe manifestations. This appears to be due to much lower frequencies of alpha thalassaemia and more frequent sickle cell-beta thalassaemia. There is a need for assessment of the indications and policies for blood transfusion and for hydroxyurea. Table 1. Beta Thalassemia mutations associated with HbS/Beta Thalassemia in Akola Mutation Expression Number IVS 1-5 (G>C) severe b+ 22 IVS 1-1 (G>A) bo 3 Cd 15 (-T) bo 2 Cd 30 (G>C) bo 2 Cd 15 (G>A) bo 1 Cd 39 (C>T) bo 1 Cd 41/42 (-CTTT) bo 1 619 bp deletion bo 1 Total 36 Disclosures No relevant conflicts of interest to declare.

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Temperature and Humidity Effects on Acute Vaso-Occlusive Pain Episodes in Sickle Cell Disease

Blood ◽

10.1182/blood.v126.23.992.992 ◽

2015 ◽

Vol 126 (23) ◽

pp. 992-992

Author(s):

Fuad El Rassi ◽

Eldrida Randall ◽

Sidney F. Stein ◽

Hanna Jean Khoury ◽

James R. Eckman ◽

...

Keyword(s):

Sickle Cell Disease ◽

Hospital Admission ◽

Acute Care ◽

Sickle Cell ◽

Hospital Admissions ◽

Admission Rate ◽

Emergency Department Visits ◽

Cell Disease ◽

Temperature And Humidity ◽

The City

Abstract Background: Sickle cell patients suffer from painful vaso-occlusive episodes (VOE) that interrupt patients' lives and productivity and lead to emergency department visits and hospitalizations and, on occasion, death. The VOE in sickle cell disease (SCD) accounts for 90% of hospital admissions for patients with SCD and constitute a financial burden on both patients and hospitals. Efforts to prevent pain crises have failed to establish a causal relationship in about 40% of reported cases. The remaining 60% of known causes of VOE are related to dehydration, febrile illness, and infections. The Emory University Sickle Cell Center at Grady Memorial hospital has been providing specialized services for SCD patients for 30 years. The center includes a 24/7 acute care unit (ACU) that is staffed by SCD providers who specialize in the management of VOE. The patients are started on intravenous narcotics and fluids within 30 minutes of presenting to the ACC. After eight hours of management, the patient is then either discharged home if the VOE is controlled or admitted to the hospital for continued management. Annually, around 3000 ACU visits are recorded with a 17% hospital admission rate. When patients are questioned on the reason for their presentation, “weather change” is frequently reported as the trigger of the VOE. A review of the literature reveals scant data to support the hypothesis that weather-related changes trigger sickle cell pain crises. Methods: In a retrospective evaluation of patient visits over the last 4 years, we identified temperature and humidity measurements for that period of time and attempted to correlate them with the frequency of ACU visits. We used the “weatherspark” website that records weather changes for the city of Atlanta because > 90% of our patients reside in the city. Results: The four-year review of weather data and ACU visits did not show a direct correlation between graphs of temperature and humidity, and the number of ACU visits. The annual number of visits to the ACU was 2930, 2467, 3195 and 3370 for the years 2011, 2012, 2013 and 2014 respectively. The average admission rate was 16.6% overall, and the admission rate in the years 2011, 2012, 2013 and 2014 was 12.4%, 14.9%, 19.6% and 19.6% respectively. The attached figure has an example of the year 2013 charts for temperature, humidity, sickle cell acute care visits and hospital admission graphs. Conclusion: The retrospective analysis does not reflect a direct correlation between the temperature and humidity graphs and the number of ACU visits and hospital admissions. Given the volume of data analyzed, it is unlikely that there is any correlation between temperature and humidity variations and either acute care visits or admissions. Atlanta, GA- ACU visits, Hospital admissions, Temperature and Humidity Charts for 2013: DATA from weatherspark.com Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

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Effect of PSI697, a Small Molecule Inhibitor of P-Selectin, in the Townes Model of Sickle Cell Disease

Blood ◽

10.1182/blood.v126.23.3391.3391 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3391-3391 ◽

Cited By ~ 1

Author(s):

Reema Jasuja ◽

Sunita Patel Hett ◽

Neelu Kaila ◽

Debra Pittman

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Small Molecule ◽

Blood Cells ◽

Conflicts Of Interest ◽

Cell Disease ◽

Tissue Ischemia ◽

Multicellular Aggregates ◽

Surgical Preparation ◽

Platelet Aggregates

Abstract Chronic vaso-occlusion is a major cause of morbidity and mortality in patients with sickle cell disease (SCD). Persistent vaso-occlusion can damage lungs, liver, kidneys or brain and ultimately lead to end-organ dysfunction. Vaso-occlusive pain crisis is a complex multistep process, initiated by adhesion of fragile sickle erythrocytes and rigid neutrophils to hypoxic and inflamed endothelium. Large multicellular aggregates of blood cells, including platelets and sickled erythrocytes, form on these adherent activated neutrophils in the microcirculation, ultimately causing vascular occlusion and tissue ischemia. Inflammatory mediators, such as P-selectin, play a key role in mediating these heterocellular interactions and attract additional leucocytes to the site of occlusion. P- and E-selectin mediate rolling and tethering of blood cells on the endothelium. Here, we explore cellular and animal models of sickle cell disease to assess PSI-697, an orally active small molecule antagonist of P-selectin. PSI-697 inhibits P-selectin binding to P-selectin glycoprotein ligand-1 (PSGL-1) with an IC50 of 50-125 µM (Bedard et al, JPET, 2008). Townes SCD mice were used to assess the efficacy for PSI-697 in preventing vaso-occlusion in SCD. Mice were randomized to treatment with vehicle or PSI-697. Animals were treated in a prophylactic setting prior to the surgical preparation. Surgical preparation induces a well described acute inflammatory response in the microcirculation associated with neutrophil adhesion to the endothelium and formation of multicellular aggregates. Alexa-488 labeled Ly-6G neutrophil antibody and Dylight-649 labeled CD42c platelet antibody were injected to quantify adherent neutrophils and neutrophil-platelet aggregates. Cremaster microvasculature was observed by intravital microscopy. Mice treated with 100 mg/kg of P-selectin inhibitor PSI-697 showed a 55% reduction in adherent neutrophils and a 78% decrease in the number of neutrophil-platelet aggregates compared to vehicle treated animals. Neutrophils showed ~7 fold increase in rolling velocity in mice treated with P-selectin inhibitor. Our results demonstrate that prophylactic administration of PSI-697, a small molecule P-selectin antagonist, improved parameters associated with vaso-occlusion in Townes SCD mice. Disclosures No relevant conflicts of interest to declare.

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Impact of Hydroxyurea on Sickle Cell Patients Managed in a Community Medical Center

Blood ◽

10.1182/blood.v126.23.3411.3411 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3411-3411

Author(s):

Shailja Shah ◽

Adaeze Nwosu-Iheme ◽

Alice J. Cohen

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Hospital Admissions ◽

Conflicts Of Interest ◽

Comprehensive Care ◽

Cell Disease ◽

Major Barrier ◽

Care Clinic ◽

Ed Visits ◽

Clinic Visits

Abstract Background: Sickle Cell Disease (SCD), including the subtypes of HbSS(SS) or Hb S beta zero thalassemia(SB0) are characterized by frequent vasoocclusive pain crises (VOC) requiring numerous visits to emergency departments and admissions to the hospital. A NHLBI expert panel recommends that patients(pts) with SCD receive hydroxyurea(H) therapy to improve clinical outcomes. H, approved by the FDA in 1998 for treatment of clinically severe SCA is the only disease modifying agent for sickle cell disease. Its primary mechanism of action is induction of fetal hemoglobin (HbF) which in turn causes inhibition of sickling. As a part of our adult sickle cell comprehensive care program, aggressive education and counseling has been utilized to ensure that eligible adults with SCD are treated with H. The clinical benefits of this program were tracked for its impact on blood parameters and utilization of health care services. Methods: Pts with SS/SB0 over the age of 18 years attending a comprehensive SCD program were tracked for use of H, clinic and ED visits, hospitalizations and transfusions over a period of 12 months. Lab parameters monitored included WBC, Hemoglobin(Hb), MCV , platelets(plts), Hb F level. Dose of H in the steady state is reported in mg/kg . Education about the benefits and side effects was provided utilizing a newly created video, one on one counselling and educational group programs. As part of the yearly visits, H education and compliance were reinforced. Pts were excluded if attempting pregnancy, currently pregnant or breast feeding. Results: We identified 169 pts of which 135 were evaluable with complete data. 89/135 (66%) were on H and 46/135 (34%) not on H. The major barrier to not taking H was patient refusal. Pts on H were divided into two groups, Hb F < 15%(n=54) and Hb F >15% (n=35); 66/89 (75%) were SS , 22/89(25%) SB0. As expected, MCV and HB were higher in pts on H and WBC and plts were lower in pts on H and correlated with higher HbF levels (See Table 1). Table 1. Not on H(n=46) Pts on H with HbF<15% ( n=54) Pts on H with HbF >15%( n=35) WBC(K/uL) 11.3 9.6 8.8 HB(g/dl) 8.4 8.4 9.1 MCV(fL) 90.7 102 113.3 Platelets(K/uL) 367 320 308 HbF (%) 5.5 7.6 18.8 H dose (mg/kg) N/A 22.6 18.6 The number of ED visits was significantly lower on H. Admissions trended lower on H but were not statistically different (see Table 2). Table 2. Pts on H Pts not on H P value ER visits (mean) 1.36 3.15 0.0206 Hospital Admissions (mean) 3.05 3.41 0.6261 Clinic Visits (mean) 6.10 5.89 0.7382 Pts on H had similar ED, clinic visits and admissions with HbF levels of <15% and >15%. The number of pts transfused were as follows: pts not on H 25/46(54%); on H 40/89(45%); and pts with HbF<15% -28/54(52%), while HbF>15%- 12/35(34%). Conclusion: Aggressive education in a community comprehensive care clinic has allowed for a majority of eligible patients with SS/SB0 to utilize H. Use of H has significantly reduced ED visits suggesting uncomplicated VOC can be reduced utilizing H in a community setting .Transfusions were reduced in patients on H especially those with HbF >15%. Mean H dosing did not correlate with higher HbF levels, which raises the question of compliance in some pts. Continued education, monitoring of prescriptions filled and possible higher doses of H may be beneficial in reducing hospitalizations. Disclosures No relevant conflicts of interest to declare.

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Sickle-Cell Disease and Malaria: Evaluation of Seasonal Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine in Senegalese patients—a Randomized Placebo-Controlled Trial

Blood ◽

10.1182/blood.v116.21.1633.1633 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1633-1633 ◽

Cited By ~ 1

Author(s):

Saliou Diop ◽

Moussa Seck ◽

Youssou Bamar Gueye ◽

Fabienne Soudre ◽

Awa Oumar Touré Fall ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Malaria Incidence ◽

Controlled Trial ◽

Intermittent Preventive Treatment ◽

Public Health Problem ◽

Preventive Treatment ◽

Cell Disease ◽

The Impact

Abstract Abstract 1633 Malaria is a real public health problem in Africa, more than 300 million new cases and approximately two million deaths arise every year. Sickle-cell disease (SCD) patients are at high risk of developing malaria which is a major contributor to morbidity and mortality in this disease. In Senegal, malaria transmission is high during rainy season, between July and October, and it was noted that sickle-cell crisis are frequent during this period. Then we carried out a double-blind randomized controlled trial to compare the impact of monthly sulfadoxine-pyrimethamine (SP) during the high-transmission season versus placebo on malaria incidence and morbidity of sickle-cell anemia. Sixty (60) SCD patients were randomized either to receive three intermittent preventive treatment (ITP) with SP or placebo using the random permutation table with nine elements. The drug was administrated as follows: sulfadoxine 25 mg/kg and pyrimethamine 1.25 mg/kg and this treatment was given once during the following months: September, October, and November. Overall four episodes of malaria disease were diagnosed, all these cases in the placebo arm. Thus, overall prevalence was 6.6% and there was no other case of malaria in the SP arm during the study period. Parasitological diagnosis confirmed the presence of Plasmodium falciparum in all four cases. No patient death was encountered during the study. SP treatment was well tolerated as only one patient (1.6%) in the SP arm reported pruritis. A significant reduction of patients’ complaints (p= 0.002) and blood requirements (p = 0.001) was noted in the SP group; whereas, no impact was observed on vaso-occlusive crisis and hospitalization occurrence. Malaria prophylaxis by monthly intake of SP during the transmission period of the parasite reduced the prevalence of malaria and was safe in SCD patients leaving in malaria endemic area. Disclosures: No relevant conflicts of interest to declare.

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Optimizing Hydroxyurea Use in Children with Sickle Cell Disease: Least Tolerated Dose Is Effective

Blood ◽

10.1182/blood.v118.21.4851.4851 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4851-4851

Author(s):

Sharef Waadallah Sharef ◽

Maya Al-Hajri ◽

Ismail Beshlawi ◽

Amer Qais Al-Shahrabally ◽

Yasser Wali

Keyword(s):

Abdominal Pain ◽

Side Effects ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Annual Number ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Starting Dose

Abstract Abstract 4851 Background: Hydroxyurea (HU) is an antimetabolite that effectively ameliorates the course of sickle cell disease (SCD). Starting dose is usually 20 mg/kg/day and the dose is escalated up to 35 mg/kg/day in most of the centers. In Oman, due to high level of consanguinity, ethnic neutropenia affects around 10% of population rendering higher doses difficult to maintain in most of the patients. Materials and Methods: 161 patients (age 2–16 years, 61% male and 39% female) with SCD at Sultan Qaboos University Hospital, Muscat, Oman, were started on HU for clinically severe course (defined as: annual vaso occlusive crisis admissions more than 3, and/or occurrence of acute chest syndrome) with starting dose of 15 mg/kg and a mean dose of 18 mg/kg/day. All patients were included in the study except for 19 patients who were excluded for various reasons (8 lost follow up, 6 stopped HU by parents, and 5 stopped due to side effects: dizziness, abdominal pain, and myelosuppression). Remaining 142 patients were followed up for median treatment duration of 4 years (range, 1.5–10 years). Patients were assessed for clinical and laboratory response to HU. Results: There was significant reduction in the annual number of admissions due to vaso occlusive crisis (P <0.001, Wilcoxon Signed Ranks Test) with a mean of 4.7 and 1.5 before and after HU use respectively. There was also observed clinical improvement regarding the incidence of acute chest syndrome. Only 12 out of 39 patients initiated on HU for acute chest syndrome had a recurrent attack during a follow up period of 3–7 years. The laboratory parameters were consistent with previous reports: significant increase in hemoglobin level, fetal hemoglobin (HbF) level, Mean Corpuscular Volume, whereas significant decrease in platelet, absolute neutrophil, and absolute reticulocytic counts. All 142 patients tolerated the treatment well. Observed side effects included abdominal pain, dizziness, rash, tremor in one patient each. Of note, 21 patients (11.1%) developed neutropenia (ANC<1000 × 10̂9/l) while 7 patients (3.7%) had thrombocytopenia (<100 × 10̂9/l) which interrupted the treatment for period ranging from 3 weeks to 3 months only. Conclusion: In SCD patients with background of ethnic neutropenia, lower starting dose and limited range of dose escalation of HU ensured safety and yet did not affect efficacy. Disclosures: No relevant conflicts of interest to declare.

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