Manifestations of HbSE sickle cell disease: a systematic review

Abstract Background Sickle cell disease (SCD) is commonly encountered in Africa and Middle Eastern countries. The causative mutation in the gene encoding the hemoglobin subunit β (HBB) leads to various genotypic variants of the disease. This results in varied phenotypes, with a spectrum of complications, from benign to fatal. Hemoglobin SS (HBSS) genotype is associated with most of these complications; hence, it is a severe form of SCD. On the other hand, rare genotypes such as hemoglobin SE (HBSE) are considered benign. There is limited literature about the clinical manifestations and characteristics of patients with HBSE. We pooled all available data describing the phenotypic manifestations of HBSE heterozygote worldwide to perform a systematic review. Methods We performed a systematic review according to PRISMA guidelines using PubMed, SCOPUS, and Google Scholar databases. Two independent reviewers (FA and IK) evaluated studies for eligibility and extracted data. We synthesized data on demographics, manifestations, and management of HBSE disease. PROSPERO Registration Number: CRD42021229877. Results We found 68 HBSE patients reported in the literature. 24 cases were extracted from case reports whereas 44 cases from case series and retrospective studies. Turkey reported the highest number of patients (n = 22). 32 (47%) of the patients were males. The mean age was 20.9 ± 18.26 years. The mean HBS and HBE percentages were 61.1% ± 7.25% and 32.3% ± 5.06%, respectively, whereas the mean hemoglobin was 11.64 ± 1.73 g/dl. Reported manifestations of HBSE disease included acute vaso-occlusive pain crisis (n = 22, 32.3%), splenomegaly (n = 11, 16.1%), hemolytic anemia (n = 10, 14.7%), infections (n = 8. 11.7%), bone infarction (n = 4, 5.8%), gallstones (n = 3, 4.4%), venous thromboembolism (VTE) (n = 2, 2.9%) and stroke (n = 2, 2.9%), and hematuria (n = 2, 2.9%). Death due to HBSE complications was reported in three patients. Conclusion HBSE is a rare genotypic variant of SCD. It has been considered a benign form; however, there are multiple reports of severe complications. Severe complications observed in HBSE disease include vaso-occlusive crisis, acute chest syndrome, stroke, bone marrow embolism, and death.

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Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq

Anemia ◽

10.1155/2015/195469 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Zeina A. Salman ◽

Meaad K. Hassan

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Readmission Rate ◽

Length Of Hospital Stay ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Opioid Use ◽

Asthma Symptoms ◽

The Mean ◽

High Readmission Rate

Objectives. Despite improvements in the management of sickle cell disease (SCD), many patients still experience disease-related complications requiring hospitalizations. The objectives of this study were to identify causes of hospitalization among these patients and factors associated with the length of hospital stay (LOS) and readmission.Methods. Data from 160 patients (<14 years old) with SCD who were admitted to the Basra Maternity and Children’s Hospital from the first of January 2012 through July 2012 were analyzed.Results. The main causes of hospitalization were acute painful crises (73.84%), infections (9.28%), acute chest syndrome (8.02%), and acute splenic sequestration crisis (6.32%). The mean LOS was4.34±2.85days. The LOS for patients on hydroxyurea (3.41±2.64days) was shorter than that for patients who were not (4.59±2.86days),P<0.05. The readmission rate (23.1%) was significantly higher among patients with frequent hospitalizations in the previous year (OR 9.352, 95% CI 2.011–43.49), asthma symptoms (OR 4.225, 95% CI 1.125–15.862), and opioid use (OR 6.588, 95% CI 1.104–30.336). Patients on hydroxyurea were less likely to be readmitted (OR 0.082, 95% CI 0.10–0.663).Conclusions. There is a relatively high readmission rate among patients with SCD in Basra. The use of hydroxyurea significantly decreases the LOS and readmission rate.

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Beneficial effects of adenotonsillectomy in children with sickle cell disease

ERJ Open Research ◽

10.1183/23120541.00071-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00071-2020

Author(s):

Ilaria Liguoro ◽

Michele Arigliani ◽

Bethany Singh ◽

Lisa Van Geyzel ◽

Subarna Chakravorty ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Arterial Oxygen Saturation ◽

Arterial Oxygen ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Beneficial Effects ◽

Admission Rates ◽

The Mean ◽

The Impact

Tonsillectomy and adenoidectomy (T&A) is frequently performed in children with sickle cell disease (SCD). Our aim was to evaluate the impact of this surgery on overnight oxygenation and rates of complications in these patients.Children with SCD who underwent T&A between 2008 and 2014 in two tertiary hospitals were retrospectively evaluated. Overnight oximetry and admission rates due to vaso-occlusive pain episodes (VOEs) and acute chest syndrome (ACS) in the year preceding and following the surgery were compared.19 patients (10 males, 53%) with a median age of 6 years (range 3.5–8) were included. A significant increase of mean overnight arterial oxygen saturation measured by pulse oximetry (SpO2) (from 93±3.6% to 95.3±2.8%, p=0.001), nadir SpO2 (from 83.0±7.1% to 88±4.1%, p=0.004) and a reduction of 3% oxygen desaturation index (from a median value of 5.7 to 1.8, p=0.003) were shown. The mean annual rate of ACS decreased from 0.6±1.22 to 0.1±0.2 events per patient-year (p=0.003), while the mean cumulative rate of hospitalisations for all causes and the incidence of VOEs were not affected.T&A improved nocturnal oxygenation and was also associated with a reduction in the incidence of ACS at 1-year follow-up after surgery.

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Adverse Events in Sickle Cell Patients with Nocturnal Hypoxia.

Blood ◽

10.1182/blood.v106.11.3793.3793 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3793-3793

Author(s):

Andrew D. Campbell ◽

Megumi Okumura ◽

Ndidi Unaka ◽

Sally Hutchinson ◽

Onyinye Onyekwere

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Sickle Cell Disease ◽

Adverse Events ◽

Sickle Cell ◽

Case Series ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Obstructive Sleep ◽

The Relationship

Abstract The relationship between hemoglobin dexoygenation and sickling is well known. However, the relationship between hypoxia and severity of disease in sickle cell patients has not been well established. Recently, nocturnal hypoxemia has been associated with higher incidence of CNS events including strokes, and elevated TCDs. We present our case series on 13 patients(12 SS, 1 SC) with sickle cell disease (SCD) who have nocturnal hypoxia. Approximately 75 patients were screened at the University of Michigan Sickle Cell clinic for nocturnal hypoxia either by symptoms of obstructive sleep apnea or by longitudinal baseline clinic 02 saturations (02 Sat <92%). Of the 13 hypoxic pts, median baseline O2 Sat 90%(n=13, mean 90) and the median nocturnal O2sat (Nctnl 02 sat) 84%(n=13, mean 80%) with 10/13 with moderate-severe nocturnal hypoxia (O2sats<85%)based on sleep studies. Multiple adverse events noted in the cohort were pulmonary hypertension (PHTN TRJV>2.5, n=9, median 2.74/mean 2.74,) frequent pain episodes(>3visits to ER or hospitalizations/year, n=7, with 5 pts >5/year ), recurrent acute chest syndrome( ≥ 3 episodes, n= 10), CNS events (n=3 silent infarcts, vascular stenosis), priapism( (n=4, among 6 males ). Also reported were possible causes of the underlying hypoxia including obstructive sleep apnea(OSA)(n=7 of 11 pts), asthma(n= 10 of 13 pts), and chronic lung disease( n=8). In conclusion, the persistence of nocturnal hypoxia in pediatric sickle cell disease could possibly contribute to the development of severe complications of sickle cell disease. Treatment of underlying hypoxia (ie nighttime oxygen, maximize asthma treatment, T&A for OSA)may help prevent complications and lead to the improvement clinical symptoms. Further, chronic nocturnal hypoxia may complicate pulmonary disease and accelerated the development of PHTN. More studies are needed to clarify the mechanism of hypoxia in SCD. Table I. Clinical &Demographic Data of 13 SCD Patients with Nocturnal Hypoxia. Age:(6–22y/o, mean 15) Sex: M=6 F=7 Clinical: Total Mild Mod Sev. Genotype: SS=12, SC=1 Mean Range Nctnl Hypoxia(<%) 13 3 5(<85) 5(<80) Baseline O2 Sat(%) 90 +3.0 86–97 Obstr Sleep Apnea 7 3 3 1 Nctnl 02 sat (%) 80+8.4 59–87 Pulm HTN 9 4 4 1 Total #Apneic Events(11) 65.6+80 6–256 Rest. Lung Ds. 8 2 5 1 Obstr. Apneic Events(7) 27+68.5 0–221 # of Episodes <3 3–4 >4 Hypopneic Events(9) 32.5+38 0–132 ACS 2 5 5 TRJet Velocity 2.74+.42 2–3.5 Severe Pain Crises/yr 1 2 5

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Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.4767.4767 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4767-4767

Author(s):

Giovanna Graziadei ◽

Alessia Marcon ◽

Martina Soldarini ◽

Ilaria Gandolfi ◽

Luisa Ronzoni ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Acute Chest Syndrome ◽

P Value ◽

Cell Disease ◽

Transfusion Therapy ◽

Clinical Complications ◽

Significant Difference ◽

The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

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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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Direct Oral Anticoagulants in Sickle Cell Disease, Where We Stand and Where We Are Heading: A Systematic Review

Blood ◽

10.1182/blood-2021-144694 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4188-4188

Author(s):

Waail Rozi Kashgary ◽

Elrazi Awadelkarim Awadelkarim Hamid Ali ◽

Alaa Rahhal ◽

Abdulrahman F Al-Mashdali ◽

Yousef Hailan ◽

...

Keyword(s):

Systematic Review ◽

Clinical Practice ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Observational Studies ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Case Series ◽

Cell Disease ◽

Bleeding Events

Abstract Introduction: Sickle Cell Disease (SCD) is a hemolytic disorder with an increased risk of venous thromboembolism (VTE). By the age of 40 years around 11-12% of sickle cell disease patients will have at least one episode of VTE. VTE among patients with SCD is associated with a two to four times increase in mortality compared to SCD patients without VTE. Nevertheless, the evidence guiding VTE management in SCD, specifically in terms of anticoagulant choice, is scarce. Therefore, we conducted a systematic review that evaluates the effectiveness and safety of direct oral anticoagulants (DOACs) in SCD with VTE. Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the English literature (PubMed, SCOPUS, and Google Scholar) for randomized controlled trials, observational studies, reviews, case series, and case reports for patients with SCD treated with DOAC for thromboembolic disease. We used the terms in combination: "Sickle cell disease" or "Sickle cell anemia", and "DOAC", "rivaroxaban", "apixaban", "dabigatran" "edoxaban". The search included all articles published up to 20th April 2021. Quality and risk of bias assessment were done by two independent authors for each included study. Results: A total of 7 articles were included; four observational studies, and three case series addressing this matter. Patel A et al. found that the use of DOACs, including rivaroxaban, dabigatran, and apixaban in comparison to vitamin K antagonists (VKAs) and low molecular weight heparin (LMWH) for the treatment of VTE in SCD among adults was associated with similar VTE recurrence rate and a better safety profile in terms of a significant reduction in major bleeding events. Similarly, Roberts MZ et al. reported that the use of DOACs for VTE treatment in SCD compared to VKAs resulted in similar effectiveness in terms of VTE recurrence, but the use of DOACs was associated with a similar safety in comparison to VKAs in contrary to the results reported by Patel A et al. in their retrospective study. With regards to the risk of major hemorrhagic events associated with the use of non-VKAs, Gupta VK et al. showed that among 55 patients with SCD treated with VKAs, DOACs, or injectable anticoagulants, only patients treated with VKAs had major bleeding events. Discussion: The current data demonstrated that the use of DOACs for VTE in SCD has similar effectiveness in the prevention of VTE recurrence in comparison to other anticoagulants, including VKAs and injectable anticoagulants with a better safety profile. However, given the absence of clinical practice guidelines for the treatment of VTE among patients with SCD, the clinical practice guidelines recommendations for VTE treatment can be applied to patients with SCD. According to the latest CHEST guidelines (2016) for the treatment of VTE, the use of DOACs is recommended in patients with VTE over VKAs. Similarly, the latest American Society of Hematology (2020) guidelines for VTE suggest the use of DOACs over VKAs, except among patients with renal insufficiency (creatinine clearance less than 30 mL/min), moderate to severe liver disease, or those with antiphospholipid syndrome. Conclusion: In view of the current evidence and based on the results observed; using DOACs was associated with lesser bleeding incidence and fewer complications comparing to VKAs. We think it is rational to use DOACs for VTE treatment among patients with SCD rather than use VKAs. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Comparison of Clinical Evolution of Children with Sickle Cell Disease before and after Treatment with Hydroxyurea at Saint Damien Hospital, Tabarre-Haiti,2013-2018

Blood ◽

10.1182/blood-2019-124105 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2306-2306

Author(s):

Nora St Victor Dély ◽

Ofelia A. Alvarez ◽

Vanessa J Dor ◽

Emmeline Lerebours

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Course ◽

Acute Chest Syndrome ◽

Blood Transfusions ◽

Cell Disease ◽

Clinical Evolution ◽

Before And After ◽

The Mean ◽

Painful Crisis

INTRODUCTION Sickle cell disease (SCD), an autosomal recessive hemoglobinopathy, is associated with a high morbidity and mortality rate, especially in low income countries. In Africa, 5% of deaths among children under five are attributable to SCD [59th World Health Assembly, WHO 2006]. This chronic disease greatly alters the quality of life of affected children. However, according to several published studies, SCD clinical course can be improved with the administration of hydroxyurea, an antimetabolite drug. [Nkashama, Pan African Medical Journal,2015] Saint-Damien, a pediatric hospital in Haiti, has a current cohort of 1248 sickle cell children. Forty of them (3 %) benefit from hydroxyurea administration since November 2015. In this hospital, data on how hydroxyurea modifies SCD clinical course are lacking, despite the advantage of this drug described in literature [Charache,New England Journal of Medicine,1995]. This study aims to compare the evolution of children treated at Saint Damien Hospital, before and after receiving hydroxyurea. METHODS A retrospective analytic study was conducted from November 2013 to June 2018 in the Sickle Cell Clinic at Saint-Damien Hospital. We included 40 children aged 2 to 15 years old treated with hydroxyurea. All of them benefit of the same treatment protocol: Initial dose of 10 mg per kg per day increase to maintenance dose of 25 mg per kg per day. Any child whose treatment has been permanently discontinued regardless of the cause was excluded. Epidemiological and clinical data were collected using Excel 2010. We compared children clinical evolution two years before and two years after hydroxyurea administration using these parameters: frequency and duration of hospitalizations, hospitalization frequency for specific complications (pain crisis, stroke and acute chest syndrome), and frequency of blood transfusions. We calculated frequencies, ratios and means using Epi Info. We realized statistical analysis to compare quantitative variables with a p value significant when less than 5%. RESULTS Gender ratio was 1:1. The mean age of children at enrollment on hydroxyurea was 8 years. Thirty-eight children of 40 (95 %) experienced at least one hospitalization before receiving the drug, compared with 17 (42.5%) after, p=0.025. The mean duration of hospitalization was 9 days before and 6 days after, p=0.0319. The average number of hospitalizations per child was decreased by 30 %. Seventy percent of children were hospitalized at least once due to painful crisis 2 years before receiving hydroxyurea, compare to 22.5 % after. Thirty-one children (77.5%) were transfused at least once before receiving the drug and 9 (22.5%) after receiving it. There was no cases of acute chest syndrome or stroke reported after hydroxyurea, unlike before the introduction of the drug. (Table 1) CONCLUSION The percentage of hospitalized children and the average length of hospitalization stay decreased significantly with hydroxyurea intake; as well as the frequency of painful crisis and blood transfusions. Hydroxyurea acts directly on the two main causes of hospitalization in the sickle cell, reducing the morbidity related to this pathology; and demonstrating the direct benefit of this drug at Saint Damien Hospital. Since our cohort is young, we have not been able to follow his evolution over a longer period of time. We plan to continue to observe this cohort. But these first results already allow us to recommend a broader use of hydroxyurea for pediatric patients with SCD in Haiti. Disclosures Alvarez: Forma Therapeutics: Consultancy; Novartis: Consultancy.

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Progression of Pulmonary Hypertension in Patients with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3187.3187 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3187-3187 ◽

Cited By ~ 3

Author(s):

Kenneth I. Ataga ◽

Charity Moore ◽

Susan Jones ◽

Oludamilola Olajide ◽

Dell Strayhorn ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Left Ventricular ◽

Right Atrial ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Original Cohort ◽

The Mean

Abstract Introduction: The prevalence of pulmonary hypertension (PHT) is high in patients with sickle cell disease (SCD). Although most patients have only mild increases in their pulmonary artery systolic pressure (PASP), the presence of PHT is strongly associated with an increased risk of death. While PHT seen in SCD is thought to progress over time, both the rate of development of PHT and the factors that affect disease progression remain unknown. Methods: The 41 subjects in this study were drawn from an original cohort of 60 patients followed in the Sickle Cell Clinic at UNC-Chapel Hill. All patients were previously evaluated for PHT (defined using an age-, sex-, and BMI-adjusted reference range). Of the 60 patients in the original cohort, six are now deceased and 13 others were not available for repeat evaluation. The PASP was determined using Doppler echocardiography and then applying the modified Bernoulli equation (PASP = 4V2 + right atrial pressure). Individuals were not studied if they: 1) showed clinical evidence of left ventricular failure; 2) had a recent acute illness (e.g., vaso-occlusive crisis); or 3) had experienced an episode of acute chest syndrome within the preceding 4 weeks. Means and standard deviations were calculated for all measures at the time of initial evaluation and at the time of follow-up. Results: Of the 41 subjects in our study, PHT was originally present in 12, while no evidence of PHT was present in 29. Of the 29 subjects who initially had no evidence of PHT, 4 (or 14%) have now developed PHT (mean follow-up period of 3.3 ± 0.4 years). In these 4 subjects, the mean PASP at the time of initial and follow-up evaluations respectively were: 37.0 ± 2.0 mm Hg vs. 55.8 ± 11.0 mm Hg. The patients who developed PHT during the course of the study had lower systolic BP (143 ± 12 mm Hg vs. 128 ± 12 mm Hg), lower fetal hemoglobin levels (6.2 ± 5.7 % vs. 4.2 ± 3.7 %), and higher platelet counts (276 ± 119 X 103/μL vs. 426 ± 96 X 103/μL) at the time of their follow-up analyses. By contrast, 3 of the 12 subjects (or 25%) who were thought to have PHT at the time of their original evaluations were found to have normal PASP determinations at the time of their repeat echocardiograms (mean follow-up period of 3.2 ± 0.6 years). In these latter 3 subjects, the mean PASP values at the time of the initial and follow-up evaluations respectively were: 40.0 ± 4.6 mm Hg vs. 33.7 ± 4.7 mm Hg. Conclusion: In this small group of patients with SCD, we found that PHT developed in 14% of subjects who had no evidence of PHT 3 years earlier. Based on this observation, it seems that periodic echocardiograms to screen for the development of PHT would be appropriate. On the other hand, our observation that some patients initially classified as having PHT failed to have elevated PASP measurements at the time of follow-up illustrates the limitation of a single echocardiographic evaluation in establishing this diagnosis. Because of the increase in PASP that occurs during acute vaso-occlusive episodes, and the difficulty usually encountered in distinguishing steady state from crisis, the initial elevation of the PASP in these patients could have resulted from sub-clinical crisis states. For these reasons, a patient found to have an elevated PASP at the time of a screening echocardiogram should have a repeat study, and perhaps a right heart catheterization, before the diagnosis of PHT is firmly established.

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Is Incentive Spirometry Effective in Preventing Post Surgical Acute Chest Syndrome in Sickle Cell Disease Patients?

Blood ◽

10.1182/blood.v112.11.4807.4807 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4807-4807

Author(s):

Adlette Inati ◽

Fouad Ziade ◽

Suzan Koussa ◽

Ali Taher

Keyword(s):

Postoperative Complications ◽

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Perioperative Care ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Clinical Events ◽

Number Of Patients ◽

Incentive Spirometry

Abstract Persons with sickle cell disease (SCD) are more likely to undergo cholecystectomy and splenectomy than are the general population. Even with meticulous care, surgical complications are seen in approximately 25% to 30% of patients. A chart review of SCD patients who had splenectomies and cholecystectomies and who were treated in 3 centers between1987–2007 was undergone. Data pertaining to clinical events, surgery, perioperative care and outcome were collected and analyzed. Since 1995, laparoscopic surgery was the modality used. Management consisted of preoperative transfusions in 83% of patients, general anesthesia, adequate hydration, temperature conservation, non sedating analgesia and supervised incentive spirometry exercises (after 1995) in all patients. The total number of patients was 120: 81 underwent splenectomy, 59 cholecystectomy and 20 both procedures. Of patients who underwent splenectomy, 43.2% were females and 56.8% males; 64.2% had sickle cell anemia (SCA) and 35.8% sickle-beta thalassemia (ST). For those undergoing cholecystectomy, 39.0% were females and 61.0% males; 79.7% had SCA and 20.3% ST. Patients undergoing splenectomy were significantly younger (mean age 9.28 years) than those undergoing cholecystectomy (mean age 15.28 years) (p=0.037). Median operative time was 50 minutes, and median hospitalization duration was 2 1/2 days. No major intra operative complications or fatalities were noted. Postoperative complications included acute chest syndrome (ACS) in 5 patients (4% of surgeries). The mean time to onset of symptoms of ACS was 36 hrs after surgery (range, 24–96 hr). All patients who developed this complication did not receive incentive spirometry or were noncompliant with this therapy. As for the relation between clinical events and splenectomy/cholecystectomy, bivariate analysis showed a significant association between splenectomy and regular blood transfusion (p=0.005). Borderline significance was found for the association of cholecystectomy with ACS, joint necrosis and stroke (0.05<p<0.10). Predictors of splenectomy were regular blood transfusion (OR=2.38, [1.36–4.17] 95%CI], ACS (OR= 3.42, [1.64–7.15] 95%CI) and ST as compared to SS (OR=1.89, [1.10–3.27] 95%CI). Predictors of cholecystectomy were regular blood transfusion (OR=2.02, [1.10–3.71] 95%CI and sepsis (OR=2.59, [1.04–6.45] 95%CI). Sensitive predictors of postoperative complications could not be studied due to the small number of complications. This survey shows that splenectomy and cholecystectomy can be performed in SCD patients with minimal morbidity and no mortality. The current rate (4%) of post surgical ACS is lower than previously reported and is probably due to strict adherence to meticulous perioperative care. The absence of post surgical ACS in patients treated with supervised incentive spirometry is suggestive of a beneficial effect of this therapy in preventing this serious complication. The small number of patients with post surgical ACS prevents us, however, from drawing definite conclusions about the preventive role of this treatment. Nevertheless, early use of this simple, available and inexpensive tool most likely minimizes surgical morbidity and mortality from ACS, decreases hospitalization time, cuts down expenses and can be helpful particularly in countries with limited resources. Prospective controlled studies are, however, warranted to evaluate the efficacy of incentive spirometry and other perioperative interventions in preventing complications in SCD patients undergoing surgery.

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Treatment patterns and economic burden of sickle-cell disease patients prescribed hydroxyurea: a retrospective claims-based study

Health and Quality of Life Outcomes ◽

10.1186/s12955-019-1225-7 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 8

Author(s):

Nirmish Shah ◽

Menaka Bhor ◽

Lin Xie ◽

Rashid Halloway ◽

Steve Arcona ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Economic Burden ◽

Medication Possession Ratio ◽

Treatment Patterns ◽

Care Utilization ◽

Acute Chest Syndrome ◽

Cell Disease ◽

The Mean

Abstract Background This study aimed to evaluate sickle-cell disease (SCD) treatment patterns and economic burden among patients prescribed hydroxyurea (HU) in the US, through claims data. Methods SCD patients with pharmacy claims for HU were selected from the Medicaid Analytic Extracts (MAX) from January 1, 2009 - December 31, 2013. The first HU prescription during the identification period was defined as the index date and patients were required to have had continuous medical and pharmacy benefits for ≥6 months baseline and 12 months follow-up periods. Patient demographics, clinical characteristics, treatment patterns, health care utilization, and costs were examined, and variables were analyzed descriptively. Results A total of 3999 SCD patients prescribed HU were included; the mean age was 19.24 years, most patients were African American (73.3%), and the mean Charlson comorbidity index (CCI) score was 0.6. Asthma (20.3%), acute chest syndrome (15.6%), and infectious and parasitic diseases (20%) were the most prevalent comorbidities. During the 12-month follow-up period, 58.9% (N = 2357) of patients discontinued HU medication. The mean medication possession ratio (MPR) was 0.52, and 22.3% of patients had MPR ≥80%. The average length of stay (LOS) for SCD-related hospitalization was 13.35 days; 64% of patients had ≥1 SCD-related hospitalization. The mean annual total SCD-related costs per patient were $27,779, mostly inpatient costs ($20,128). Conclusions Overall, the study showed the patients had significant unmet needs manifest as poor medication adherence, high treatment discontinuation rates, and high economic burden.

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