Causes of Death in Sickle Cell Disease Adult Patients: Old and New Trends

Abstract Introduction: The treatment of sickle cell disease has advanced in recent years. Infant mortality has decreased with the introduction of systematic antibiotics, the preventive care cerebral vasculopathy and therapeutic education for families. It seemed interesting to update causes of death in adult sickle cell patients. Materiel and method: We retrospectively reviewed the records of patients treated in our national referral center (Henri Mondor Hospital) which died between January 2001 and 2013. Basic biological parameters, chronic and acute complications present in these patients as well as their treatment, median age at death, causes and circumstances of death were identified when the information was available. Results: During the study period, 96 patients among 2478 patients followed died. The median age at death was 36 years (mean age 37.1 + / - 10.6 years) (range: 16-69 years). The main characteristics of the population are summarized in Table 1. Abstract 2716. Table 1:General characteristics of patients during study periodSickle cell diseaseSSSCSβ0thal.Sβ+thal.TotalNumber1556670871532478Deaths71176296Mean age (years)35.1944.474130.537.1Sex ratio0.970.7210.95Mean Hemoglobin level (g/dl)8.711.68.911.59.3Mean LDH level (UI/ml)389.6229.9346.8250392.16Patients with treatment n (%)45 (63.4%)2 (11.8%)3 (50%)0 (0%)50 (52%)Transfusion program n (%)26 (36.6%)0 (0%)2 (33.3%)0 (0%)28 (29.2%)Hydroxycarbamide n (%)27 (38%)1 (5.9%)3 (50%)0 (0%)31 (32.3%)Erythropoietin n (%)18 (25.4%)1 (5.9%)0 (0%)0 (0%)19 (19.8%)Mean number of complication per patient (among 4)2.431.712.331.52.28 An offset to the right of population curves is observed compared to 10 years ago. (Figure 1) Main causes of death were: acute organ failure in a context of chronic organ impairment (22.9%), acute chest syndrome (16.7%), infection (16.7%), cerebral hemorrhage (10.4%), drug overdose (7.3%), acute right heart failure (5.2%) and delayed hemolysis transfusion related (4.2%). Six deaths occurred during pregnancy. History of chronic kidney failure (p = 0.01) and positive irregular antibodies (p = 0.04) appeared to be a risk factor for premature death. A trend was noted for history of heart disease (p = 0.07) and a history of delayed hemolysis transfusion related (DHTR) (p = 0.13). Discussion: The median age of death does not seem to improve since the study published by Platt et al (Mortality in sickle cell disease. Life expectancy and risk factors for early death. Platt OS,N Engl J Med. 1994 Jun 9;330(23):1639-44.); however our cohort appears to age, we observed an increase in the number of patients aged over 45. The causes of death have evolved compared to data available from previous studies, chronic organ failures are the leading cause of mortality especially in patients with renal impairment. The prevention of the onset of these complications is one of the new challenges especially renal diseases which were associated with premature mortality. DHTR and brain hemorrhages are new entities probably previously under-diagnosed. Pregnancy remains a risk period, which should strengthen its monitoring. Figure 1: Patients’ age evolution between 2000 and 2011. Figure 1:. Patients’ age evolution between 2000 and 2011. Disclosures No relevant conflicts of interest to declare.

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Leg Ulcers among Patients with Sickle Cell Disease on Hydroxyurea Therapy.

Blood ◽

10.1182/blood.v104.11.1676.1676 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1676-1676

Author(s):

Suresh Mendpara ◽

Betsy Clair ◽

Mudusar Raza ◽

Lisa Daitch ◽

David Smith ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Therapeutic Agent ◽

Acute Chest Syndrome ◽

Prior History ◽

Leg Ulcers ◽

Cell Disease ◽

Number Of Patients ◽

Transfusion Requirements ◽

History Of

Abstract Leg ulcers remain a debilitating complication of Sickle Cell Disease (SCD): significant pain, tendency to polymicrobial infection, difficult to heal, and tendency to recur in ~ 50% of patients. According to CSSCD data, 2.5% of 2075 patients had leg ulcers at study entry; overall incidence was 9.97 per 100-person years in patients without concomitant alpha thalassemia (thal), and 5.73 per 100 person years in those with alpha thal. Hydroxyurea (HU) is an approved therapeutic agent for adults with SCD; it has been shown to decrease frequency of pain crises and acute chest syndrome and decrease transfusion requirements. Recently, HU was associated with a 40% reduction in mortality. There have been reports of an association between HU therapy and leg ulcers in patients with myeloproliferative disorders (MPD) and more recently with SCD. A retrospective study from the Mayo Clinic (Best et al, Ann. Intern. Med., 128:29, 1998) found that among 115 patients with various forms of MPD, 14 developed leg ulcers after an average HU exposure of 6 years; all ulcers healed after stopping HU, and 2 patients had recurrences of their ulcers after resuming HU. Chaine et al (Arch. Dermatol, 137: 467, 2001) reported that 5/17 (29%) patients with SCD on HU developed leg ulcers. If HU, the most effective available therapeutic agent for SCD is indeed causative of leg ulcers, this should raise serious concerns. In an effort to further clarify this problem, we performed a retrospective analysis. 421 adult SCD patients (age 16–60) formed the subject of this study. 152 were treated with HU for a minimum of 6 months. 269 patients were not exposed to HU. A total of 25 patients (5.9%) had leg ulcers; 17 were treated with HU, 8 were not. Thus, the frequency of leg ulcers was 11.2% among HU treated patients, as opposed to 2.9% among those who did not receive HU therapy (p<0.001). However, of the 17 patients with ulcers, 16(94%) had a history of ulcers prior to HU exposure. Only one patient developed ulcers for the first time after starting HU therapy. 6/17 patients experienced healing of their ulcers despite continuing HU. Among the patients treated with HU, those who had ulcers were more anemic (pre-treatment Hb 7.4 vs 8.2 g/dl, p=0.01) and were older (mean age 40.5 vs 33.0, p<0.001), confirming previous observations. Logistic regression analyses showed that only age and prior history of leg ulcers were significant risk factors for the development of ulcers in patients with SCD under HU therapy. Our data on a large number of patients does not suggest that HU therapy alone is causative of leg ulcers in SCD patients. The supporting evidence for this conclusion comes from our observations that 1) a vast majority of patients (16/17; 94%) who developed leg ulcers after starting HU had a previous history of ulcers. This is also true of the report by Chaine et al, where 4/5 patients with leg ulcers had a prior history; 2) in 6/17 patients (35.3%) ulcers healed with conventional therapy despite continuation of HU. Furthermore, it should be noted that patients with leg ulcers represent a more severe group and are thus more likely candidates for HU therapy. We conclude that HU therapy alone is not causative of leg ulcers in patients with SCD. In addition, HU does not appear to prevent recurrence of leg ulcers in patients with a prior history; nor does it expedite ulcer healing. Other as yet unknown factors, some of which are likely genetic, play an important role in determining the risk for developing leg ulcers.

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To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

Transfusion Medicine and Hemotherapy ◽

10.1159/000512644 ◽

2021 ◽

pp. 1-5

Author(s):

Justin E. Juskewitch ◽

Craig D. Tauscher ◽

Sheila K. Moldenhauer ◽

Jennifer E. Schieber ◽

Eapen K. Jacob ◽

...

Keyword(s):

Pregnant Woman ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pregnancy Termination ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Childbearing Age ◽

Procedural Complications ◽

History Of ◽

Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

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Prevalence of Pulmonary Hypertension (PHTN) in Sickle Cell Disease (SCD) Adolescents with Pulmonary Complications.

Blood ◽

10.1182/blood.v104.11.3759.3759 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3759-3759

Author(s):

Onyinye C. Onyekwere ◽

Andrew Campbell ◽

James Williams ◽

Peter Gaskin ◽

Sohail Rana ◽

...

Keyword(s):

Sickle Cell Disease ◽

Pulmonary Artery ◽

Sickle Cell ◽

Pulmonary Complications ◽

Acute Chest Syndrome ◽

University Of Michigan ◽

Cell Disease ◽

Hemoglobin F ◽

Howard University ◽

History Of

Abstract Despite the high prevalence of PHTN in adults with SCD, the prevalence in the pediatric population with SCD is not known. We hypothesized that elevated pulmonary artery pressures may be found in SCD adolescents with history of pulmonary complications, such as acute chest syndrome (ACS), obstructive sleep apnea (OSA), asthma, and reactive airway disease. Thirty such sickle cell disease adolescents were screened at Howard University or University of Michigan for PHTN with Doppler echocardiography. We defined PHTN as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/sec (corresponding to a pulmonary artery systolic pressure greater than 35 mm Hg). PHTN was found in 16 SCD patients (53.3%) and 5 (16.7%) had TRV > 3.0 m/sec. Clinical findings according to the presences or absence of PHTN are shown in the table. Potential factors contributing to PHTN in patients with SCD include chronic hemolysis and chronic hypoxia. Our results suggest that PHTN is common among SCD adolescents with a history of pulmonary complications. Consideration should be given to screening such patients for PHTN and exploring treatment options. Further studies are urgently needed to clarify the prevalence and mechanisms of PHTN in adolescents with SCD. Clinical and demographic data of 30 SCD adolescents with pulmonary findings who underwent echocardiography at Howard University Hospital or University of Michigan PHTN (N = 16) No PHTN (N = 14) P Age in years (mean +/− SD) 15.9 +/− 3.2 17.4 +/− 2.3 0.17 Females (no. and %) 5 (31.3) 7 (50) 0.5 Hemoglobin SS Phenotype (no and %) 14 (87.5 11 (78.6) 0.5 Hemoglobin concentration (mean +/− SD) 8.0 +/− 2.1 9.3 +/−1.9 0.11 White blood cells (mean +/− SD) 10.9 +/− 2.9 9.7 +/− 3.7 0.4 Platelet (mean +/− SD) 475 +/− 172 364 +/− 240 0.17 Hemoglobin F percent (mean +/− SD) 5.1 +/− 3.5 6.4 +/− 5.5 0.6 Lactate dehydrogenase (mean +/− SD) 505 +/− 162 264 +/− 50 0.002 Total bilirubin (mean +/− SD) 4.1 +/− 2.6 3.4 +/− 2.6 0.5 Creatinine concentration (mean +/− SD) 0.6 +/− 0.2 0.7 +/− 0.2 0.18 Aspartate transaminase (mean +/− SD) 48 +/− 27 36 +/− 16 0.18 Alanine transaminase (mean +/− SD) 51 +/− 37 39 +/− 20 0.3

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Corrected QT Interval Is Related to Markers of Hemolysis and Tricuspid Regurgitant Jet Velocity in a Young Cohort with Sickle Cell Disease.

Blood ◽

10.1182/blood.v110.11.2258.2258 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2258-2258

Author(s):

Robert I. Liem ◽

Luciana T. Young ◽

Alexis A. Thompson

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Qt Interval ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Qtc Prolongation ◽

Corrected Qt Interval ◽

Conduction Abnormalities ◽

History Of ◽

Tricuspid Regurgitant Jet Velocity

Abstract Recent evidence suggests that prolongation in QT interval may be a frequent finding in patients with sickle cell disease (SCD). Few studies, however, have examined the relationship between conduction abnormalities and other cardiac complications, such as left ventricular hypertrophy (LVH) and tricuspid regurgitant jet velocity (TRJV) elevation, in this population. Moreover, long QT may be a marker of increased mortality in conditions, other than SCD, associated with LVH. We therefore sought to evaluate QT interval and its relationship to echocardiographic findings, laboratory parameters and disease severity in a cohort of children and young adults with SCD. Methods We prospectively evaluated the corrected QT interval (QTc) on standard 12-lead ECG in a cross-sectional, convenience sample of 73 subjects (41 males, mean age 14.2±3 years, range 10 to 24) with Hb SS, SC and S-β0 thalassemia undergoing screening for TRJV elevation. Subjects on chronic transfusions were excluded and all studies were performed at baseline on the same day. A review of available medical records was also performed. Results In our cohort, QTc (mean 436±24 ms, range 387 to 531) was prolonged > 440 ms in 30/73 (41%) of subjects at steady state. We also found TRJV elevation ≥ 2.5 m/s in 24/73 (33%) and LVH by ECG or echocardiographic criteria in 32/73 (44%) subjects. Using Pearson’s correlation coefficient, we observed significant correlations between QTc and TRJV (r=0.38, p=0.002), WBC (r=0.37, p=0.001) and several markers of hemolysis, including LDH (r=0.46, p=0001), Hb (r=-0.32, p=0.005), retic (r=0.29, p=0.013), plasma Hb (r=0.27, p=0.03) and AST (r=0.38, p=0.001). Using Student’s t-test for independent samples, only TRJV (2.55±0.33 vs. 2.34±0.26 m/s, p=0.006), LDH (450±166 vs. 329±143 U/L, p=0.001), WBC (10.6±4.7 vs. 8.6±3.3×109/L, p=0.048), retic (14.4±9.2 vs. 10.6±6.1%, p=0.039) and AST (50±22 vs. 38±15 U/L, p=0.009) were significantly higher and Hb (9.1±1.3 vs. 9.9±1.7 g/dL, p=0.04) lower in subjects with QTc > 440 ms compared to those with QTc ≤ 440 ms. We found no significant relationship between QTc and age, LV mass, platelet count or fetal Hb. By χ2 analysis, a larger proportion of subjects with QTc > 440 ms also had a history of acute chest syndrome (p=0.007), gallstones (p=0.047), exchange transfusion (p=0.04) and to a less significant degree, TRJV elevation (p=0.112). Prolonged QTc was not affected by sex, hydroxyurea use or a history of LVH, frequent pain, asthma, splenectomy, priapism and tonsilloadenoidectomy. Given sample size limitations and data reduction methods, we found by logistic regression analysis that the combination of TRJV and history of acute chest syndrome best predicted QTc prolongation, correctly identifying 80% of cases and resulting in positive and negative predictive values of 76% and 81%, respectively. Conclusions We conclude that QTc prolongation is common in a prospectively screened cohort of young sickle cell patients at baseline and is associated with evidence of hemolysis and to a lesser degree, TRJV elevation. Our results contrast with findings in other conditions that link QTc prolongation primarily to LVH. Future studies will be critical to further define QTc variability, pathophysiologic determinants as well as the clinical consequences of conduction abnormalities, which may or may not relate to TRJV elevation, in the sickle cell population.

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Sickle Cell Disease Mortality in the United States: Age at Death and Contributing Causes.

Blood ◽

10.1182/blood.v110.11.81.81 ◽

2007 ◽

Vol 110 (11) ◽

pp. 81-81 ◽

Cited By ~ 6

Author(s):

Carlton Haywood ◽

Sophie Lanzkron

Keyword(s):

Sickle Cell Disease ◽

Cause Of Death ◽

Sickle Cell ◽

Causes Of Death ◽

College Education ◽

Age At Death ◽

Cell Disease ◽

Time Period ◽

Icd 10 ◽

The U.S

Abstract BACKGROUND: In the early 1990’s, the Cooperative Study of Sickle Cell Disease (CSSCD) estimated a median life expectancy of 42 years for males, and 48 years for females with sickle cell anemia. We used death certificate data from the late 1990’s and early 2000’s to examine age at death and contributing causes of death for persons with sickle cell disease (SCD). METHODS: We used the National Center for Health Statistics Multiple Cause of Death (MCOD) files to examine age at death and contributing causes of death for persons in the U.S. with SCD during the years 1999 to 2004. The MCOD files contain data from all death certificates filed in the U.S. Each observation in the data has listed an underlying (primary) cause of death, as well as up to 20 conditions thought to contribute to the death. We used ICD-10 codes D570-D578 to identify all deaths attributed to SCD during the time period under study. Records with the ICD-10 code for sickle cell trait (D573) were excluded from further analyses. We used the Clinical Classification Software provided by the Healthcare Cost and Utilization Project to collapse all listed ICD-10 codes into smaller categories. Analyses of age at death were conducted using t-tests, median tests, ANOVA, and multiple linear regression as appropriate. RESULTS: From 1999 to 2004, there were 4553 deaths in the U.S. attributed to SCD (mean = 759/yr, sd = 42.6). SCD was listed as the primary cause in 65% of the deaths. 95% of the deaths were attributed to HbSS disease, and approximately 1% of the deaths were attributed to double heterozygous sickle cell disorders (SC/SD/SE/Thal). 50.4% of the deaths were among males. 64% of the decedents had a high school education or less. 54% of the decedents lived in the South. 68% of the decedents died as inpatients in a hospital. The mean age at death for the time period was 38.2 years (sd = 15.6). There was no change in the mean age at death during the time period. Females were older than males at death (39.4 vs. 36.9, p < 0.0001). Those with HbSS were younger than those with a double heterozygous disorder (38 vs. 47, p < 0.02). Having SCD listed as the primary cause of death was associated with younger age at death (36.8 vs. 40.7, p < 0.0001). Decedents with at least some college education were older at death than those with high school educations or less (40.9 vs. 37.0 p < 0.0001). There were no regional differences in mean age at death. In a multivariate model of age at death with the predictors gender, region, education, and whether or not SCD was listed as the primary cause of death, being female and having some college education remained associated with older age at death, while having SCD listed as the primary cause of death remained associated with younger age at death. Septicemia, pulmonary heart disease, liver disease and renal failure were among the top contributing causes of death for adults, while septicemia, acute cerebrovascular disease and pneumonia were among the top contributing causes of death for kids. CONCLUSIONS: Persons dying from SCD during 1999 to 2004 experienced ages at death that are not improved over those reported by the CSSCD, suggesting the continued need for societal efforts aimed at improving the quality of care for SCD, especially among adults with the condition. Educational attainment is associated with age at death among the SCD population, though it is not possible from the cross-sectional nature of this data to determine the causal directionality of this association.

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Does Treatment with Hydroxyurea and Opioids Affect Age of Death in Sickle Cell Disease Patients?

Blood ◽

10.1182/blood.v112.11.4808.4808 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4808-4808

Author(s):

Charlene M. Flahiff ◽

Jude C Jonassaint ◽

Charles R. Jonassaint ◽

Soheir S. Adam ◽

Marilyn J. Telen ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Treatment Modality ◽

Group Analysis ◽

Treatment Modalities ◽

Age At Death ◽

Cell Disease ◽

Number Of Patients ◽

Living Group ◽

Age Of Death

Abstract Hydroxyurea (HU) is used to treat sickle cell disease and has been shown to decrease painful episodes (Charache, 1995) and possibly vaso-occlusive episodes associated morbidity and mortality (Steinberg, 2003). Opioids are often prescribed in adult patients for daily management of their chronic pain. The aim of the current study was to determine the age at death and the effect of treatment with HU and/or opioids prior to death in patients who died from sickle cell disease (SCD) related complications and to compare these parameters to those in our current patients population. Methods: Age, daily treatment with opioids, and HU treatment were determined for 185 patients currently followed at the Duke Comprehensive Sickle Cell Center (DCSCC) and for 50 patients who died between 2002 and 2008 due to SCD complications and who were regularly followed at the DCSCC for their care. The two cohorts, living and deceased patients were divided based on their treatment modality into the following 4 groups: opioid only, HU only, both drugs, and neither drug. Non-parametric chi-square test was performed to determine whether the treatment modality distribution was different in the deceased group compared to the living group. Analysis of variance was done to determine the relationship between treatment group and age at death. Results and Discussion: The distribution of treatment modalities in the deceased group was significantly different than that of the living group. The opioids only group had the largest number of patients in the deceased cohort (44%), and this percentage was almost twice that of the living group (25%). (Fig. 1) Moreover, 72 % of the deceased patients were treated with opioids vs. only 53 % of the living patients, perhaps because the sicker patients are often treated with daily opioids. However, the age of death in the opioids only group was 44 ± 15.5 years. (Fig. 2) In the living group, treatment with both drugs or with no drugs were equivalent (28%), while in the deceased group, more patients were treated with both drugs (28%) compared to no drug treatment (18%). The HU only group had the lowest number of deaths (10%), and the percentage of patients in this group was nearly half that the one of the living group (19%). This group also was the oldest at death (58 ±16 years). Age at death was also significantly higher in this group than in each of the other 3 groups (p<0.05). The low use of HU in the deceased cohort, along with the higher age of death, support the reported effectiveness of this drug in reducing morbidity associated with SCD. The age of the living patients receiving treatment with both drugs was the same as that of the deceased. Similarly the age of the non treated living patients was comparable with that of the deceased group. Interestingly, the interaction of the 2 therapeutic interventions (HU and opiates) had a significant effect on the age at death (p=0.003). We conclude that opioid treatment, either alone or in conjunction with HU, appears to have a significant effect on the age at death and warrants further investigation.

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Implementation of a European Cohort to Follow Sickle Cell Children and Adults Treated with Hydroxycarbamide

Blood ◽

10.1182/blood.v124.21.564.564 ◽

2014 ◽

Vol 124 (21) ◽

pp. 564-564

Author(s):

Mariane De Montalembert ◽

Frédéric Galacteros ◽

Jean Antoine Ribeil ◽

Uwe Kordes ◽

Jean Benoit Arlet ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Safety Profile ◽

Conflicts Of Interest ◽

Subcutaneous Tissue ◽

Acute Chest Syndrome ◽

Control Group ◽

Cell Disease ◽

Skin Reactions ◽

Number Of Patients

Abstract Hydroxycarbamide (HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological cancer, and authorized since 2007 in Europe as orphan medicinal product for the prevention of recurrent vaso-occlusive crises including acute chest syndrome in adults and children older than 2 years with sickle cell disease (SCD). ESCORT-HU (European Sickle Cell Disease Cohort – Hydroxyurea) is a multicenter prospective non interventional study implemented in Europe to collect more information about the safety profile of HU and morbi-mortality in SCD patients treated with HU. The study responds to EMA (European Medicines Agency) request and has been approved by the Ethical of Necker Enfants Malades Hospital (Paris, France).The ongoing study involves the largest number so far of patients with SCD treated with HU. Primary endpoints of ESCORT HU are to determine frequency of adverse events, and possible consequent changes of HU treatment. Secondary endpoints are to evaluate morbi-mortality of the disease although in the absence of control group. From June 2008 to June 2014, 483 patients (255 females; 228 males) were enrolled from 3 European countries, Greece (24%), Germany (19%), and France (56%). 67% patients were adults, median aged 37.35 yrs (17-83.5) and 33% were children, median aged 11.06 yrs (2.6-16.9). genotypes were HbS/HbS in 71.4% cases, and compound heterozygotous HbS/β-thalassemia in 22.8 % (Table 1). 137 (28.4%) patients experienced 421 events (Table 2). 132 (32.2%) of these events may be attributed to HU. The safety profile is roughly similar in children and adults. As expected the most frequent side effects were firstly blood disorders (n=86 events, 42.4%) such as neutropenia or thrombocytopenia. In all cases, these cytopenias were rapidly resolved with the transitory stop of HU. 71 events related to skin and subcutaneous tissue disorders were observed, mostly cutaneous dryness, skin reactions, alopecia and nails or skin pigmentation; 4 patients had a leg ulcer (34.8%). Most of these events are ongoing or stabilized despit the decrease of HU. No secondary cancer has been reported until now. Even if HU is an old drug with a relatively well-known safety profile, some uncertainties remain in terms of long-term safety as well as tolerance in the youngest people. The main interest of ESCORT HU is to offer the possibility of safety surveillance of hydroxycarbamide in European sickle cell patients. Table 1 Demographic data Adults Children < 17 years old Total Number of patients 322 (67%) 161 (33%) 483 Females/Males 183/139 72/89 255/228 Median age (yrs) (range) 37.35 (17-83.5) 11.06 (2.6-16.9) 28.58 Genotype SS 206 (64%) 139 (86.3%) 345 (71.4%) SC 1 (0.3%) 3 (1.86%) 4 (0.8%) Sβ0 51 (15.8%) 11 (6.8%) 62 (12.8%) Sβ+ 46 (14.2%) 2 (1.2%) 48 (9.9%) Other 18 (5.5%) 6 (3.7%) 24 (4.9%) Treatment with HU before enrollment in ESCORT HU No of pts 232 83 315 (65%) Median duration (range) of HU treatment before ESCORT HU 8.2 yrs (0.5 ans-24 yrs) 3. 1 yrs ( 71 days – 8.9 yrs) 6.85 (71 days-24 years)] HU ESCORT Daily mean dose (mg/kg/d) 16.11 ± 4.79 19.63 ± 4.69 17.32 ± 4.94 Abstract 564. Table 2 The most frequent events of hydroxycarbamide in the two populations of SCD patients ADULTS CHILDREN No ofGerman(%) No of adults No ofEpisodes(%) No of children Total(% /411) Events Related to HU treatment (Siklos®)(%**) Blood and lymphatic system disorders (%) 32 (17.7) 22 54 (31.03) 28 86 (20.9) 56 (65.1) Skin and subcutaneous tissue disorders (%) 42 (23.2) 28 29 (16.7) 19 71 (17.3) 46 (64.8) Nervous system disorders Headache (24), Dizziness/vertigo (14), 32 (17.7) 23 12(6.9) 10 44 (10.7) 11 (25) Gastrointestinal disorders Nausea (14), diarrhea (8), other (14) 20 (11) 17 23 (13.2) 16 43 (10.4) 7 (16.3) Metabolic and nutrition disorders: vit D deficiency (17), weight gain (5) 13 (7) 11 18 (18.3) 18 36 (8.75) 4 (11.1) Fever 11 (6) 10 12(6.9) 7 23 (5.6) 1 (4.3) Cardiac disorders (hypertension, bradycardia, chest pain, cardiomegaly) 4 4 2 2 6 1 (16.6) General disorders : fatigue 5 5 0 0 5 0 Hepatobiliary disorders 2 2 0 0 2 0 Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Harmatoma, benign vulvar sebaceous cyst 2 2 0 0 2 0 Renal & urinary disorders 2 2 0 0 2 0 Reproductive system and breast disorders 3 3 0 0 3 0 Other 13 13 21 14 34 6 (17.1%) 181 80 /181(24.8%) 174 57 / 174(35.4%) 411 132/411 (32.2%) ** compared to the total number of “system organ class” events Disclosures No relevant conflicts of interest to declare.

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Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽

10.1182/blood.v97.11.3628 ◽

2001 ◽

Vol 97 (11) ◽

pp. 3628-3632 ◽

Cited By ~ 132

Author(s):

Alina Ferster ◽

Parvine Tahriri ◽

Christiane Vermylen ◽

Geneviève Sturbois ◽

Francis Corazza ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Significant Difference ◽

History Of ◽

Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P < .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

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Hematological Changes from Baseline in Children with Sickle Cell Disease Admitted for Acute Chest Syndrome Compared to Acute Pain Crisis

Blood ◽

10.1182/blood-2018-99-118977 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4909-4909

Author(s):

Timothy Klouda ◽

Nataly Apollonsky ◽

Deepti Raybagkar ◽

Bruce Bernstein

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Acute Pain ◽

Neutrophil Count ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

History Of ◽

Pain Crisis ◽

Hematological Changes

Abstract Title: Hematological Changes from Baseline in Children with Sickle Cell Disease Admitted for Acute Chest Syndrome Compared to Acute Pain Crisis Authors: Timothy Klouda1, Deepti. Raybagkar2, Bruce Bernstein1, Nataly Apollonsky2, Institutes:1Pediatrics, St Christopher's Hospital for Children, Philadelphia, PA, United States, 2Hematology, St Christopher's Hospital for Children, Philadelphia, PA, United States, Introduction: Children with Sickle Cell Disease suffer from multiple complications including acute pain crisis (VOC) and acute chest syndrome (ACS). Nearly 30% of children with SCD have had one episode of ACS, with the incidence higher in early childhood. The proposed pathophysiology of ACS is thought to be multi-factorial, with pulmonary fat embolism or infectious etiology being identified in a large number of patients. Increased sickling due to hypoxemia or pain has been shown to place patients at risk for ACS development., Studies have shown an increase in inflammatory markers including leukocytes and neutrophils, along with a decreased hemoglobin in SCD children who developed ACS, but no studies to date have compared laboratory changes during the acute illness to their baseline values. We hypothesized that children with SCD who are admitted for ACS will have a larger decrease in hemoglobin from baseline and a higher increase in white blood cell count from baseline when compared to those admitted for an acute pain crisis. Methods: Through retrospective chart review of patients with SCD admitted to St.Christopher's Hospital for Children we identified 45 patients with ACS. Laboratory data collected on admission from chart review included SCD genotype, age, BMI, hemoglobin, white blood cell count, absolute neutrophil count, absolute eosinophil count, platelets, reticulocyte count, hemoglobin F, vital signs and medication history. All 45 children had laboratory data collected from an acute pain crisis that occurred during a different admission for comparison. Collected data was compared to baseline laboratory data, collected during routine visit at sickle cell clinic within 1 year of admission. Changes in laboratory data from baseline during admission for ACS were compared to changes during admission for uncomplicated VOC. Results: Children with SCD who were admitted or developed ACS during admission had a larger increase in leukocyte count (6.99 vs 4.18, p=0.027) and neutrophil count (6.3 vs 3.74, p=0.04) from baseline compared to those admitted for VOC alone. Patients with ACS development also had a larger decrease in platelets (-124.74 vs -56.21, p=.047) from baseline when compared to VOC admissions. There was no statistically significant change from baseline labs when comparing hemoglobin (p=0.10), eosinophil count (p=.382), reticulocyte count (p=0.754), AST (p=0.061) and ALT (p=0.082) in the ACS and VOC groups. Children with a history of 2 or more lifetime ACS were more likely to have OSA (p=0.021), 3 or more VOCs in the past year (p=0.002), and a history of splenectomy, but it was not found to be statistically significant (p=0.155) Conclusion: Children with SCD who developed or were admitted with ACS had a significant increase in leukocyte and neutrophil count from baseline, and a decrease in platelets when compared to VOC admissions. There was no significant change from baseline in hemoglobin, reticulocyte and eosinophils detected. Future larger and multi-center prospective studies need to be performed to confirm the various changes identified in hematological markers seen in ACS vs VOC. Disclosures No relevant conflicts of interest to declare.

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Successful Management of Sickle Cell Disease Patient with Covid-19 Infection in a Low Resource Setting: Case Study

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i26a31475 ◽

2021 ◽

pp. 110-114

Author(s):

Akaba Kingsley ◽

Edu C. Betta ◽

Akaba Edakabasi ◽

Essien Ofonime ◽

Bibia Glory Philemon

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Disease Patient ◽

Sickle Cell Disease Patient ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Management Options ◽

Adequate Hydration ◽

History Of ◽

The Impact

Background: Sickle cell disease (SCD) patients have greater susceptibility to infections, they are reckoned to be vulnerable patients during the current COVID-19 pandemic. SCD patients are commonly affected by pulmonary complications such as acute chest syndrome (ACS), pulmonary embolism (PE) and pneumonia that contribute significantly to mortality risks. Aim: The study was aimed at showing the impact of SARS-COV viral pandemic on SCD patients. Presentation of Case: A 42-year-old male known sickle cell disease patient, who presented with a 5 days’ history of chest pain and difficulty in breathing with a pain score of 8/10. Pain was said to be localized and, subside on the ingestion of analgesics (Tab DF118/60mg and PCM 1000mg) with no known aggravating factor, but there was associated history of difficulty in breathing. The patient was being managed as a case of vaso-occlusive crises R/O acute chest syndrome, and was commenced on adequate hydration, oxygen saturation was between 95-85%. On examination, respiratory rate was 20 cycles per minute, pulse rate – 96 beats/minute, BP and chest examination were essentially normal. CBC showed the Packed Cell Volume of 31%, White Blood Cells 15.04 x 109/L, Neutrophils 7.51x103/µL Lymphocyte 6.50 x103/µL, Monocyte 0.76 x103/µL Eosinophils 0.20x103/µL, Basophils 0.05x103/µL, Platelet 358. The electrolytes (Na-135 mmol/L, K 3.5mmol/L, HCO3-20), urea -10 mmol/L and creatinine (88mmol/L) were normal, the chest x-ray showed cardiomegaly but the lung fields were clear. The patient was administered ceftriaxone (prophylactic antibiotics – 1 g daily). The patient tested positive to COVID-19 and was immediately transferred to the isolation centre for proper management. He was commenced on oral medication, azithromycin, dexamethasone, ivermectine, amoxicillin/clavulanic acid, vitamin C, clexane and the analgesic was changed to paracetamol and dihydrocodeine to alternate 3 hourly with accordance to the national guidelines. In addition, he was administered subcutaneous enoxaparin due to the hypercoagulability state of SCD. The patient’s health status improved within 24hours of commencement of the above medications and remained stable all through the period of isolation and a repeat covid-19 test was done 15 days of admission using and reverse transcriptase PCR and was discharged home according to the National protocol. Conclusion: Studies and clinical trials are essential to evaluate effective diagnostic and management options for SCD patients and other high-risk conditions like diabetes hypertension, cancer patients and so on that are associated with fatal complications when infected with COVID-19 and similar diseases.

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