Manifestations Of Sickle Cell Disease Research Articles

Genitourinary manifestations of sickle cell disease.

Sickle cell disease is a common genetic disorder characterized by sickling of red blood cells under conditions of reduced oxygen tension. In turn, sickling leads to intravascular hemolysis and vaso-occlusive events with subsequent tissue ischemia-reperfusion injury affecting multiple organs, including the genitourinary system. Our review of the genitourinary manifestations of sickle cell disease focuses on sickle cell nephropathy, priapism, and other genitourinary complications such as papillary necrosis and renal medullary carcinoma.

Inflammatory targets of therapy in sickle cell disease.

Sickle cell disease (SCD) is a monogenic globin disorder characterized by the production of a structurally abnormal hemoglobin (Hb) variant Hb S, which causes severe hemolytic anemia, episodic painful vaso-occlusion, and ultimately end-organ damage. The primary disease pathophysiology is intracellular Hb S polymerization and consequent sickling of erythrocytes. It has become evident for more than several decades that a more complex disease process contributes to the myriad of clinical complications seen in patients with SCD with inflammation playing a central role. Drugs targeting specific inflammatory pathways therefore offer an attractive therapeutic strategy to ameliorate many of the clinical events in SCD. In addition, they are useful tools to dissect the molecular and cellular mechanisms that promote individual clinical events and for developing improved therapeutics to address more challenging clinical dilemmas such as refractoriness to opioids or hyperalgesia. Here, we discuss the prospect of targeting multiple inflammatory pathways implicated in the pathogenesis of SCD with a focus on new therapeutics, striving to link the actions of the anti-inflammatory agents to a defined pathobiology, and specific clinical manifestations of SCD. We also review the anti-inflammatory attributes and the cognate inflammatory targets of hydroxyurea, the only Food and Drug Administration-approved drug for SCD.

Fentanyl Buccal Tablet: A New Breakthrough Pain Medication in Early Management of Severe Vaso-Occlusive Crisis in Sickle Cell Disease.

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder. The principal clinical manifestations of SCD are the chronic hemolytic anemia and the acute vaso-occlusive crisis (VOCs), which are mainly characterized by ischemic/reperfusion tissue injury. Pain is the main symptom of VOCs, and its management is still a challenge for hematologists, requiring a multidisciplinary approach. We carried out a crossover study on adult SCD patients, who received two different types of multimodal analgesia during two separate severe VOCs with time interval between VOCs of at least 6months. The first VOC episode was treated with ketorolac (0.86mg/kg/day) and tramadol (7.2mg/kg/day) (TK treatment). In the second VOC episode, fentanyl buccal tablet (FBT; 100μg) was introduced in a single dose after three hours from the beginning of TK analgesia (TKF treatment). We focused on the first 24hours of acute pain management. The primary efficacy measure was the time-weighted-sum of pain intensity differences (SPID24). The secondary efficacy measures included the pain intensity difference (PID), the total pain relief (TOTPAR), and the time-wighted sum of anxiety (SAID24). SPID24 was significantly higher in TKF than in TK treatment. All the secondary measures were significantly ameliorated in TKF compared to TK treatment, without major opioid side effects. Patients satisfaction was higher with TKF treatment than with TK one. We propose that VOCs might require breakthrough pain drug strategy as vaso-occlusive phenomena and enhanced vasoconstriction promoting acute ischemic pain component exacerbate the continuous pain of VOCs. FBT might be a powerful and feasible tool in early management of acute pain during VOCs in emergency departments.

Relation between glutathione S-transferase genes (GSTM1, GSTT1, and GSTP1) polymorphisms and clinical manifestations of sickle cell disease in Egyptian patients

ObjectivesClinical manifestations of sickle cell disease (SCD) result from sickling of Hb S due to oxidation, which is augmented by accumulation of oxygen-free radicals. Deficiencies in normal antioxidant protective mechanism might lead to clinical manifestations of SCD like vaso-occlusive crisis (VOC) and acute chest syndrome (ACS). The glutathione system plays an important role in the removal of endogenous products of peroxidation of lipids, thus protecting cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphisms of glutathione S-transferase (GST) genes is expected to increase the severity of SCD manifestations. This report describes a case control study aimed at studying the ethnic-dependent variation in the frequency of GST gene polymorphisms among participants selected from the Egyptian population and to find out the association between GST gene polymorphisms and the severity of SCD manifestations.MethodsWe measured the frequency distribution of the three GSTs gene polymorphisms in 100 Egyptian adult SCD patients and 80 corresponding controls. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction (PCR). GSTP1 genotyping was conducted with a PCR-restriction fragment length polymorphism assay.ResultsThe GSTM1 null genotype was significantly associated with ACS and VOC (P = 0.03 and 0.01, respectively). The GSTT1 null genotype was associated with significantly increased requirement of blood transfusion (P = 0.01). Absence of both GSTM1 and GSTT1 genes was significantly associated with pulmonary hypertension (P = 0.04). The non-wild-type GSTP1 polymorphism was not associated with clinical manifestations of SCD.DiscussionSome GST gene polymorphisms were significantly associated with the worsening of the clinical manifestations of SCD.

Corrigendum to “Interleukin-1β and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia” [Blood Cells Mol. Dis. 54/3(2014), 244–249

Universidade Federal de Sao Paulo, Escola Paulista Med, Disciplina Hematol & Hemoterapia, BR-04037002 Sao Paulo, SP, Brazil

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea.

As hypoxia-induced inflammatory angiogenesis may contribute to the manifestations of sickle cell disease, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from patients with steady-state sickle cell anemia contained elevated concentrations of pro-angiogenic factors (angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly increasing endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice than in non-sickle cell disease mice, consistent with an up-regulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy had a pro-angiogenic profile and more significant effects on endothelial cell proliferation and capillary formation than plasma from patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factors and inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, individuals with sickle cell anemia or hemoglobin SC disease with retinopathy present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy to prevent the progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.

Sickle cell disease: renal manifestations and mechanisms.

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ(+)-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16-18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms.

High Foetal Haemoglobin in Sickle Cell Disease: Not so Protective?

High Foetal Haemoglobin in Sickle Cell Disease: Not so Protective?

Health-Related Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Sickle cell disease (SCD) is a hereditary hemoglobinopathy that affects over 100,000 people in the United States. Patients with SCD are known to experience suboptimal health-related quality of life (HRQoL). In addition to the physical manifestations of SCD, psychological and social stress, along with academic difficulties, secondary to the chronicity of the disease and its complications often affect patients with SCD. Although medical therapy of SCD has improved, allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapy. The objective of this study was to measure HRQoL before and after allo-HCT by assessing physical, psychological, and social functioning in patients with SCD who have undergone reduced-toxicity conditioning (busulfan/fludarabine/alemtuzumab) followed by allo-HCT. Patients < 21 years of age undergoing allo-HCT (matched siblings and unrelated donors) for SCD and their primary caregiver were enrolled using either the English or Spanish version of the PedsQoL 4.0. Data were collected at 3 time points: before allo-HCT and on days 180 and 365 after allo-HCT. The change in HRQoL from baseline was assessed with unadjusted and adjusted mixed-effects models in which subjects were treated as random effects, and variance component structure was used. Seventeen patients and 23 primary caregivers were enrolled and reported a mean overall HRQoL of 66.05 (SD, 15.62) and 72.20 (SD, 15.50) at baseline, respectively. In the patient-reported analysis with adjusted mixed-effects models, the estimated improvements in overall HRQoL were 4.45 (SE, 4.98; P = .380) and 16.58 (SE, 5.06; P = .003) at 180 and 365 days, respectively, after allo-HCT. For parent-reported overall HRQoL, the estimated improvements were 1.57 (SE, 4.82; P = .747) and 9.28 (SE, 4.62; P = .053) at 180 and 365 days, respectively, after allo-HCT. Similar results were found across the physical, social, and emotional HRQoL domains with mixed-effects models after adjustment of demographic and medical variables. In addition to the alleviation of clinical manifestations of SCD, these patients demonstrated significant improvement in most aspects of HRQoL by 1 year after allo-HCT. These data represent the trajectory of HRQoL during the initial year of follow-up within this population and should be integrated into the decision-making process when considering allo-HCT in patients with SCD.

Impact Assessment of Foetal Haemoglobin on Biochemical Markers of Liver Function in Sickle Cell Disease Patients

Background/objective: The role of foetal haemoglobin (HbF) on the modulation of clinical manifestations in sickle cell disease is well known but there is inconsistency as to the levels of HbF that may protective against the development of liver disease. This study evaluates the impact of HbF on biochemical markers of liver function in sickle cell disease (SCD) patients in steady clinical state. Materials and Methods: Liver function tests: aspartate amino transferase, alanine amino transferase, alkaline phosphatase, bilirubin and proteins as well as HbF were assayed in SCD patients using colorimetric methods. Results: Out of 100 SCD patients, 24% had high (>5%) HbF while 76% had low ( 5%) may be protective against the development of liver pathology in SCD patients in steady clinical state.

Interleukin-1β and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia.

Sickle cell anemia (SCA), a disorder characterized by both acute and chronic inflammation, exhibits substantial phenotypic variability. Interleukin-1 beta (IL-1β) and IL-6 are important in acute and chronic diseases, and their single nucleotide polymorphisms (SNPs) have been considered as predictors of prognosis in several inflammatory conditions. This study aims at exploring possible association of IL-1β and IL-6 SNPs as potential genetic modifiers and or predictors of SCA clinical and laboratory phenotypes. This cross-sectional study involved 107 SCA patients and 110 age, sex and ethnicity-matched healthy individuals. The SNPs were identified by PCR-RFLP for IL-1β (-511C>T and +3954C>T) and IL-6 (-597G>A and -174G>C) genes. Associations between these SNPs and the clinical and laboratory profiles of patients with SCA were then determined. Allelic and genotypic frequencies of IL-1β and IL-6 SNPs between patients with SCA and controls were similar and followed HWE. IL-1β +3954C>T SNP was associated with increased risk of osteonecrosis, elevated pulmonary arterial pressure and lower absolute reticulocyte count, while IL-6 -597G>A was associated with higher likelihood of retinopathy and leg ulcer. These data indicate that IL-1β and IL-6 gene SNPs are associated with SCA complications among Brazilian patients and may act as genetic predictors of SCA clinical heterogeneity.

Mass Spectrometry of Urine Proteins for Early Detection of Renal Complications in Sickle Cell Disease

PURPOSE: Sickle cell disease (SCD) is an autosomal recessive genetic disorder caused by a single G6V mutation in the β-globin gene. SCD patients have various complications including chronic renal failure and nephrotic syndrome which can develop in 30-50% of sickle cell patients. Currently there are no reliable methods to identify the risk for renal complications in the early stages for the subset of people who will develop renal failure. It is essential that new noninvasive prognostic biomarkers be discovered to help assess patients for risk of renal failure which may lead to early intentions and greater survival rates among SCD patients.METHODS: Urine samples were collected from 25SCD patients and 6 healthy controls. Trypsin digests of urine proteins were analyzed by nano LC coupled in-line to LTQ Orbitrap XL tandem mass spectrometer. Proteins identified with Proteome Discoverer software were further quantified using SIEVE 2.1 (Thermo).RESULTS: About 80 proteins were detected in urine. Among those, about 10 proteins were found at higher levels in SCD patients, including seruloplasmin, transferring and alpha-1-acid glycoprotein precursor.CONCLUSION: Several of the detected proteins may cause early changes in glomerular permeability and be a potential biomarker for early renal manifestations in SCD. Further studies are needed to form a more conclusive relationship between renal complications and the proteins present in urine of SCD patients.SUPPORT: NIH Research Grants 8G12MD007597 and P50HL118006-01. DisclosuresNo relevant conflicts of interest to declare.

Association of MBL2 polymorphism with Leg Ulcers Development in Sickle Cell Anemia Patients

Leg ulcers are the most common clinical manifestations of sickle cell anemia (SCA), a monogenic disease with huge clinical diversity among patients. They affect 8% to 10% of SCA patients, reaching a percentage greater than 50% in patients residing in tropical areas. These ulcers occur due to vascular occlusion, tissue hypoxia, hemolysis and genetic factors, presenting a slow healing, high recurrence rate and huge susceptibility to infection. Recently, some studies have shown a positive relationship between the complement system and the development of some vascular diseases and injuries such as leg ulcers in non-SCA patients. Mannan-binding lectin (MBL) is an important component of the humoral innate immune system, and MBL possesses several characteristics indicating that it may play an essential role in wound healing; modulating inflammation and contributing to the clearance of microorganisms and apoptotic cells. In a recent study of chronic leg and foot ulcer patients, serum MBL levels were significantly different between wounds of different etiologies, with chronic venous leg ulcers patients having a higher frequency of MBL deficiency. Polymorphisms in the MBL2 are associated with a reduction in the MBL protein serum levels, increasing risk of developing leg ulcers and also the maintenance of these wounds, compromising the integrity of the immune defence and its response to potential invading pathogens. Here, we aimed to determine the frequency of polymorphisms in the promoter region -221 (Y / X) and -550 (H / L) and exon 1 of the MBL2 and assess the clinical impact of these variants in a northeastern Brazilian SCA population who presented leg ulcers. Two-hundred seventy-five unrelated SCA patients were included. According the leg ulcers presence, the total cohort was classified in patients presenting current or prior history of leg ulcers (n=100) and SCA patients above 18 years with no history of leg ulcers (n=175). Molecular analysis was performed by qPCR. Our population was in Hardy-Weinberg equilibrium. The allelic frequency of haplotypes associated with high MBL production (HYA, LYA) was 54.5% for cases and 62.9% in controls. The genotypes related to low MBL production (HYO, LYO) in cases and controls was 27.5% and 18.6%, respectively. The frequency of genotype related to intermediate MBL production (LXA) was 18% in cases and 18.5% in controls. We had no statistically significant results when we analyzed only the polymorphisms (P>0.05). However, the phenotypic analysis between high and low MBL production revealed that patients with leg ulcers have lower MBL protein levels (P=0.019). We focused specifically on a possible role of MBL deficiency on healing complications, based on the facts that MBL deficiency is the most common immune disorder, and that a common causality for prolonged healing of these ulcers is infection or colonization by bacteria. In our study, MBL deficiency appears to increase the risk of developing leg ulcers in SCA patients. DisclosuresNo relevant conflicts of interest to declare.

Implementation of a Pediatric Observation Unit for Children with Sickle Cell Disease

▪Acute vaso-occlusive crisis (VOC), the most common manifestation of Sickle Cell Disease (SCD), is the number one cause for visits to the Emergency Department (ED). Pediatric patients differ from adult patients with SCD due to variations in opioid tolerance and age-specific complications. Many pediatric patients can be sent home after evaluation and treatment in an ED, however, others will need hospitalization for further pain management as well as continued evaluation.Observation Units (OUs), ED-associated units for evaluation and protocol management of short-term conditions (<24 hours), have successfully provided more rapid care while still maintaining quality. At our institution, using an OU-based protocol, we have demonstrated improved care with decreased resource utilization in an adult population with SCD experiencing VOC. However, there is limited data for the use of OU in pediatric patients with VOC. Our objective was to determine the feasibility of a pediatric OU for the evaluation and treatment of patients with uncomplicated VOC.A retrospective, descriptive chart review study was conducted on all pediatric patients (<18 years) with SCD between July 1, 2012 to June 30, 2013. The study was conducted in an academic pediatric tertiary care hospital (annual volume 27k/year). A medical record search was conducted using ICD-9 codes and SCD related DRG codes. The cohort was then limited to patients who received care in the academic ED or were transferred from another hospital for direct admission (DA). The cohort was limited to visits with pain related to VOC. Patients with a complication other than VOC were excluded as well as patients admitted to the intensive care unit. Cohort data as well as exclusion criteria are in table 1.Visits that were admitted to the floor (either as a direct admission or admitted from the ED) with a length of stay (LOS) less than 48 hours were included in the analysis. Patients were grouped into categories based on LOS: < 24 hours, <36 hours, and <48 hours Though the OU will only manage up to 24 hours, categories of LOS longer than 24 hours were included in order to capture elements that may lengthen a patients stay such as waiting time, time until disposition and discharge.Table 1Sample Size and Exclusion Criteria# of Patients treated for Sickle Cell Between 7/1/2012 - 6/30,2012197 patientsLimiting to patients seen in ED or having a DA119 patientsLimiting to confirmed diagnosis of SCD (multiple genotypes) = 6113 patientsLimiting to reason of visit to a pain complaint = 6107 patientsLimiting to reason of pain to VOC = 3104 patientsLimited or no data in EMR (left prior to treatment) = 3101 patientsExclusion of patients with visits only for complications of SCD* = 2180 patientsFinal Sample Size for analysis80 patients*Complications include acute chest syndrome, sepsis, splenic sequestration, fever, infiltrates, and infection80 patients had 160 visits for uncomplicated VOC from 7/1/2012 - 6/30/2012. Of the 160 visits, the patient was admitted53.8% (86) of the time. Of the 86 visits resulting in admission, 30 (34.9%) were DA and 56 (65.1%) were admitted from the academic ED. LOS of the admission by DA or from the academic ED is in table 2.Table 2LOS for AdmissionsDA to Floor30 total visitsLOS < 24 Hours5 (16.6%) visitsLOS < 36 Hours10 (33.3%) visitsLOS < 48 Hours17 (56.7%) visitsED to Floor56 total visitsLOS < 24 Hours4 (7.1%) visitsLOS < 36 Hours10 (17.9%) visitsLOS < 48 Hours21 (37.5%) visitsOU’s are ideal for the evaluation and management of patients requiring more than a few hours of ED treatment but less than 24 hours of hospital therapy. Our study shows that there is a large number of patients with SCD and VOC are admitted (53.8%). Based on our study, 44% of admissions have a LOS less than 48 hours. We believe that 48 hours is a reasonable cutoff for consideration of OU care as disposition decisions on the floor occur at 12-hour and sometimes 24-hour intervals leading to an increase in LOS beyond the actual treatment time. All patients, including DA patients, should be eligible for OU treatment if they meet inclusion criteria. This is evidenced by the finding that the LOS is shorter for DA patients (56.7%) versus admissions from the academic ED (37.5%).Overall, pediatric SCD patients would benefit from the presence of a pediatric OU by potentially decreasing the rate of inpatient admissions. An observation unit should therefore be strongly considered in centers with large volume SCD. DisclosuresNo relevant conflicts of interest to declare.

Desaturation Is Related to the Presence of Dense Red Blood Cells in Sickle Cell Patients and Is Reversed By Hydroxyurea

Production of abnormal hemoglobin (HbS) in sickle-cell disease (SCD) results in its polymerization in deoxygenated conditions and in sickled-RBC formation. Dense RBCs (DRBCs), defined as density >1.11 and characterized by increased rigidity, viscosity and HbS concentration (main polymerization factor), are absent in normal AA subjects, but present at percentages that vary from 1 SCD patient to another but remain stable throughout adulthood for each patient. Polymerized, but not nonpolymerized, HbS has reduced affinity for oxygen, demonstrated by the rightward shift of the oxygen-dissociation curve, leading to disturbances in oxygen transport. We recently described a correlation between %DRBCs and some clinical SCD manifestations. Notably, some SCD patients have unexplained, very low oxygen saturation (SpO2), without heart or lung dysfunctions. %DRBC variability within SCD patients could be the main pathophysiological explanation of those manifestations. This study was undertaken to determine whether a link exists between the %DRBCs and Hb affinity for oxygen, and to look for a potential clinical implication for SCD patients.92 patients (44.6 ± 7.7 years; 51 women and 41 men) were included in the study. Blood samples were obtained at steady state to measure hemorheological and hematological parameters. Using a Percoll-gradient fractionation method, total RBCs were separated into non-DRBCs (NDRBC) (d<1.11) and DRBCs (d>1.11) fractions. The %DRBCs was determined using the phthalate-gradient method. P50 in venous blood gases was measured with a radiometry analyzer. Oxygen-affinity curves of Hb dissociation and association in RBC fractions were obtained with dual wavelength spectrophotometry. All patients had a 6-minute walking test (6MWT) and 10 of them (38.1 ± 6.1 years; 6 men and 4 women) had done so before and after >6 months (>6M) on hydroxyurea (HU). Times <90% and <88% transcutaneous SpO2 of Hb and a SpO2 decrease ≥4% during the test (delta SpO2 >4%) were evaluated to investigate the physiological impact on patients during exertion. Patients, divided into quartiles according to their values (Q1: 0–25th centile, Q2–Q3: 25th–75th centiles, and Q4: >75th centile), were analyzed for the times <88% SpO2, <90% SpO2 and with delta SpO2 >4%, for the distance walked.DRBCs had increased MCHC and decreased %HbF and 2,3 DPG, leading to more polymerization and modulation of Hb affinity for oxygen, compared to NDRBCs. Moreover, dissociation and association curves of SS RBC fractions differed (compared to AA RBCs), with rightward shifts of NDRBCs and, more importantly, DRBC-association curves, thereby confirming the role of HbS polymerization in the loss of affinity (Fig 1). Bivariate analysis showed that the P50 was positively correlated with the %DRBCs (P<0.0001, r²=0.34), reflecting a link between the total Hb–oxygen affinity and %DRBCs in SCD patients. Conversely, P50 and %HbF were negatively correlated (P<0.0001, r²=0.25). The clinical impact of %DRBCs was studied with the 6MWT. Q4 patients for the times <90% SpO2 and <88% SpO2 had higher %DRBCs than Q1 patients (P=0.03 and P=0.04, respectively). No between-group differences were observed for the times <90% SpO2 and <88% SpO2 for Hb or %HbF. Finally, in agreement with our previous demonstration that HU strongly decreased the %DRBCs >M6 of therapy and that the %DRBCs impacted the time at low SpO2, the 10 SCD patients’ 6MWT results before and >M6 of HU therapy showed significantly decreased times <90% SpO2 (P=0.002) and <88% SpO2 (P=0.01) (Fig 2), and with delta SPO2 <4% (P=0.02). In conclusion, according to our results, the %DRBCs directly affects SCD patients’ SpO2 during exercise; HU improves oxygen affinity in correlation with the %DRBC decline. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

English

The Editor, Sir, Intracranial neurovascular manifestations in sickle cell disease include cerebral infarction, parenchymal and epidural haemorrhage, subarachnoid haemorrhage with single or multiple aneurysms, Moyamoya syndrome and posterior reversible ischemic encephalopathy.

How French paediatric emergency departments manage painful vaso-occlusive episodes in sickle cell disease patients.

The most common manifestation of sickle cell disease (SCD) is painful vaso-occlusive episodes (PVOE), and inappropriate treatment leads to unnecessary suffering and potentially fatal complications. This study describes how French paediatric emergency departments (EDs) manage PVOE and their knowledge, and implementation of the French National Authority for Health recommendations on the management of sickle cell patients. A questionnaire on managing PVOE was sent to all the 111 French paediatric EDs. We received responses from 81 (72.9%) of the EDs. Of those who responded to each individual question, 85% said that they had read the national recommendations, 71.6% said they used nalbuphine for moderate PVOE, and 85% used intravenous morphine for severe PVOE. The majority (91.7%) of EDs thought that intravenous morphine provided relief for severe PVOE, but only 30.9% thought that intravenous nalbuphine did. A 50:50 nitrous oxide/oxygen mix was used by 71.3% of departments to relieve procedural pain and by 48% to enhance analgesia when morphine was insufficient for severe pain. Most French EDs follow the national recommendations for PVOE. Nalbuphine was the most commonly used opioid for moderate PVOE and morphine for severe PVOE. A nitrous oxide/oxygen mixture was widely used for PVOE.

Sterile subperiosteal fluid collections accompanying orbital wall infarction in sickle-cell disease

Infarction of the orbital wall is an uncommon manifestation of sickle cell disease (SCD) that may mimic an infectious process. We report a patient with two separate orbital infarctions with different presenting symptoms involving different bones. Radiologic-guided sampling of a periosteal fluid collection in the first episode showed likely sterile inflammatory exudates. This case highlights the range of findings in orbital wall infarction in SCD as well as helpful clinical and imaging entities that may differentiate infarction from infection, allowing early diagnosis and appropriate management.

Addressing the global health burden of sickle cell disease.

A review of the clinical manifestations of sickle cell disease (SCD), available therapeutic interventions and a necessarily limited assessment of progress with their implementation in Nigeria (the country with the largest number of affected individuals worldwide) was recently published in this journal. Despite a disappointing dearth of targeted therapy for a condition whose molecular basis has been well understood for half a century, there is a wealth of evidence-based supportive interventions, including antibiotic and vaccination prophylaxis against early bacteraemic mortality, childhood stroke risk prevention, patient and population education and screening and community care provision that are simple and inexpensive to implement. There is a real opportunity for international collaboration to drive an improvement in healthcare provision for this condition.

Comparison of Patients from Nigeria and the USA Highlights Modifiable Risk Factors for Sickle Cell Anemia Complications

To identify factors that affect manifestations of sickle cell anemia we compared patients 11–30 years of age from University of Ibadan, Ibadan, Oyo, Nigeria (n = 214) and University of Illinois at Chicago, Chicago, IL, USA (n = 209). Paralleling findings in the general populations of the two countries, the Chicago patients were more often overweight or obese as defined by the Centers for Disease Control and Prevention (Atlanta, GA, USA) guidelines, and more often had elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA guidelines. The Ibadan patients did not receive the pneumococcal vaccine or hydroxyurea (HU) therapy as frequently as the Chicago patients. Consistent with lower rates of elevated BP and increased body mass index (BMI), stroke history was less frequent in the Ibadan patients ≥18 years old. Furthermore, in combined analyses, systolic and diastolic BP directly correlated with BMI, and elevated weight status independently associated with history of stroke. Our findings are consistent with the possibility that higher values for BMI and BP in Chicago sickle cell anemia patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, lower pneumococcal vaccination and HU therapy rates in Ibadan patients highlights the need for more improved vaccination coverage and for studies to define the role of HU therapy in Africa.