Frequency Of Painful Crises Research Articles

The experience, satisfaction, and Emergency Department utilization of pediatric patients with sickle cell disease during the Covid-19 pandemic

The COVID-19 pandemic has influenced how patients utilize healthcare. This study examines the utilization, experience, and satisfaction of patients with Sickle Cell Disease (SCD) in the pediatric Emergency Department (ED) during the COVID-19 pandemic compared to the care they had received before the pandemic. The authors surveyed fifty-eight participants ages 14 months to 20 years who presented to the ED for a complaint related to their SCD during the COVID-19 pandemic. The study analyzed five variables: race, SCD severity, hemoglobin (Hgb) genotype, who completed the questionnaire (patient versus parent/guardian), and whether the ED visit resulted in an admission to the hospital. Our results suggest that the COVID-19 pandemic significantly affected the decision of some patients as to whether and when to go to the ED. African Americans and those with severe disease did not wait longer than usual to go to the ED, possibly because these groups are more likely to have more serious and more frequent pain crises. Thus, their decision to present to the ED was driven more by their relatively worse symptoms, rather than such external factors as the pandemic. However, the pandemic did not significantly affect patients’ satisfaction with their ED visit or their baseline SCD symptoms. To our knowledge, this is the first study of how the COVID-19 pandemic has affected patients’ utilization of, experience in, and satisfaction with a pediatric hospital ED.

Age-related prescription medication utilization for the -management of sickle cell disease among Texas Medicaid patients.

Sickle cell disease (SCD) is associated with recurrent complications and healthcare burden. Although SCD management guidelines differ based on age groups, little is known regarding actual utilization of preventative (hydroxyurea) and palliative therapies (opioid and nonopioid analgesics) to manage complications. This study assessed whether there were agerelated differences in SCD index therapy type and SCD-related medication utilization. Texas Medicaid prescription claims from September 1, 2011 to August 31, 2016 were retrospectively analyzed for SCD patients aged 2-63 years who received one or more SCD-related medications (hydroxyurea, opioid, or nonopioid analgesics). The primary outcomes were SCD index drug type and medication utilization: hydroxyurea adherence, and days' supply of opioid, and nonopioid analgesics. Chi-square, analysis of variance, and Kruskal-Wallis tests were used. Index therapy percentages for included patients (N = 2,339) were the following: opioids (45.7 percent), nonopioids (36.6 percent), dual therapy-opioids and nonopioids (11.2 percent), and hydroxyurea (6.5 percent), and they differed by age-groups (χ2 = 243.0, p < 0.0001). Hydroxyurea as index therapy was higher among children (2-12:9.1 percent) compared to adults (26-40:3.7 percent; 41-63:2.9 percent). Opioids as index therapy were higher among adults (18-25:48.0 percent; 26-40:54.9 percent; 41-63:65.2 percent) compared to children (2-12:36.6 percent). Mean hydroxyurea adherence was higher (p < 0.0001) for younger ages, and opioid days' supply was higher for older ages. Texas Medicaid SCD patients had low hydroxyurea utilization and adherence across all age groups. Interventions to increase the use of hydroxyurea and newer preventative therapies could result in better management of SCD-related complications and reduce the frequency of pain crises, which may reduce the need for opioid use.

Sleep Patterns and Associated Clinical Correlates Amongst Ghanaian Individuals with Sickle Cell Disease

▪Background: Sickle cell disease (SCD) is the most commonly inherited blood disorder that affects 1 in 500 individuals of African descent worldwide and 70,000-80,000 individuals in the United States. While the molecular basis and progression of this condition has been well established, the association between sleep, stress and frequency of complications such as pain crises has not been well studied. In this study, we investigate how sleep behavioral patterns are associated with the severity and incidence of sickle cell crises amongst patients with SCD.Methods: Adult individuals with SCD were recruited from the Korle Bu Teaching Hospital in Accra, Ghana as participants for this study. No compensation was provided. Participants completed a questionnaire that assessed SCD disease severity such as frequency of pain crises and need for hospitalization. Self-reported sleep habits, including average hours of sleep both at baseline and during pain crisis were also evaluated. Medical records for each participant were also obtained to establish demographic and genotype information.Results: A total of 308 individuals with SCD were enrolled in the study. Patients were classified according to SCD genotype with 68.6% of individuals with severe genotype (hemoglobin SS or sickle/beta thalassemia), and 31% had mild genotype (hemoglobin SC, sickle/beta plus thalassemia disease). Regarding average sleep per night, 2.4% reported 0-2 hours, 14.4% reported 3-4 hours, 38.8% reported 5-6 hours, 36.8 reported 7-9 hours, and 7.7% reported 10 hours or more. During pain crises, 48% reported 0-2 hours of sleep and 91.1% reported 0-4 hours of sleep per night. A paired sample t-test of average hours of sleep at baseline versus sleep during pain crisis showed a significant decrease in hours of sleep while in pain crisis (t=20.16, p < 0.001). Furthermore, female gender was associated with decreased sleep during pain crises (p = 0.008) compared to their male counterparts. An analysis of all SCD Genotypes revealed average sleep per night at baseline was not associated with frequency of crises per year, pain crises requiring ER/doctor visits nor per pain crises per year requiring hospitalizations. However, within the mild genotype group alone, average hours of sleep during a pain crisis was significantly associated with number of crises per year (r = 0.299, p = 0.04), number of crises/year requiring ER/doctor visit (r = 0.256, p = 0.013), and crises/year requiring hospitalization per year (r = 0.246, p = 0.018). Sleep patterns and pain crises/year measures did not correlate amongst patients with severe genotype.Discussion: Per patient self-report, individuals with SCD experience significant disruption with sleep due to pain crises. Most of the individuals report a significant reduction in average amount of sleep during a pain crisis, suggesting that pain crisis likely plays a crucial role in quality of life amongst patients with SCD. In patient with milder genotypes, worse outcomes (frequent ER/doctor visits, frequent crises, and frequent hospitalizations) are associated with less sleep during a pain crisis. This association suggests that amongst those with mild genotypes, sleep amount likely reflects SCD morbidity. The lack of associated pain crises patterns and sleep within the severe genotype suggests most adult patient regardless of severity report a severe lack of sleep during painful crises. Leg ulcer associated with less sleep during painful crises may reflect the impact of leg ulcers on sleep patterns. A limitation of this study was that data was obtained from a single site which may not reflective of sleep patterns amongst individuals with SCD elsewhere. Future areas of exploration could include evaluation of sleep habits with a validated sleep questionnaire and compared with end organ complications of sickle cell disease. DisclosuresWilson:American Society of Hematology: Research Funding. Asare:Office of Research Innovation and Development (ORID) Research Fund/8/LMG-008, University of Ghana; Doris Duke Charitable Foundation; Burroughs Wellcome Foundation; Phillips Family Donation; Aaron Ardoin Foundation for Sickle Cell Anemia; Vanderbilt Univer: Research Funding. Olayemi:Office of Research Innovation and Development (ORID) Research Fund/8/LMG-008, University of Ghana; Doris Duke Charitable Foundation; Burroughs Wellcome Foundation; Phillips Family Donation; Aaron Ardoin Foundation for Sickle Cell Anemia; Vanderbilt Univer: Research Funding.

Frequency of Vasocclusive Crises and the Relationship of Vitamin D Deficiency to the Frequency of Pain Crises in Children with Sickle Cell Disease in an Aboriginal Tribal Region in Gadchiroli, India

▪BackgroundRecent reports suggest that the clinical phenotype of sickle cell disease (SCD) in India may not be as mild compared to African haplotypes as previously believed (Jain et. al. 2016). There is however a paucity of data from India.There are some reports of association between Vitamin D deficiency and pain in SCD, but these associations have not been studied in pediatric SCD patients form India. The objective of this community-based study was to determine the frequency of vaso-occlusive episodes (VOE) in Indian pediatric SCD patients and to determine the relationship of Vitamin D deficiency to the frequencies of VOE and other SCD complications.MethodsWe conducted a community based study in aboriginal tribal area in Gadchiroli district in Maharashtra State, India. After providing informed consent, patients completed a health history interview and underwent blood testing for serum 25-Hydroxy Vitamin D by Radioimmunoassay. The number of times in the previous year that their child had severe pain, associated with cessation of activity including play and school attendance which required treatment, in the past year, was obtained by parent self-report, and was defined as a VOC. Hospitalizations for VOE treatment and number of blood transfusions in the past year were also obtained by parent self-report. No medical record review was done. Descriptive statistics and tests of hypothesis were performed using STATA Ver. 13.ResultsWe screened 91 children (50% male) with a median age of 14 years (range 5-16, IQR 10-16). They reported a median 3 episodes of VOC/Year (IQR 2-4) and a median 2 Hospitalizations (IQR 1-2) and a median of 1 blood transfusion/ year (IQR 1-2). Median Vitamin D level was 26.4 (IQR 22.6-29.9) with 15 patients (16.5%) being Vitamin D deficient (<20ng/ml). On Student t-test with equal variance, Vitamin D deficient patients vs. Vitamin D replete patients revealed 4±0 vs. 2.5± 0.97 VOCs/year (p=0.0000), 2.3± 0.7 vs.1.60±0.7 (p=0.0006). Hospitalizations for VOC/year(P=0.010) and 1.9±0.7 vs 1.4 ±0.6 blood transfusions/year(P=0.0064). In a linear regression model, after adjusting for age and sex, higher vitamin D levels were associated with lower VOCs (P=0.0000, Model F statistic= 53.8).ConclusionsChildren with SCD in an aboriginal tribal region in Gadchiroli, India have reported pain frequencies similar to that described in reports from other parts of the world. This suggests that the phenotype of SCD in India may not be as mild as previously thought. In this population, Vitamin D deficiency is associated with significantly increased VOE, hospitalizations for VOE and blood transfusions. These data provide the rationale for larger studies to further elucidate the association of Vitamin D with pain events in SCD, and to determine the causes of Vitamin D deficiency and its impact on severity of SCD, so as to inform the development of suitable preventive and therapeutic strategies [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical epidemiology of individuals with Sickle cell anemia using Hydroxyurea at Muhimbili National Hospital, Dar Es Salaam, Tanzania

Background: The pathophysiology of sickle cell disease (SCD) is complex and involves nitric oxide depletion, increased inflammation/adhesion molecules and vaso-occlusion in addition to the chronic hemolytic anemia. This pathophysiology results in systemic clinical complications including recurrent episodes of severe pain, stroke, acute chest syndrome (ACS) and an increased susceptibility to infection. SCD severity varies among individuals and fetal hemoglobin (HbF) is known as a major modulator of the disease. To date, hydroxyurea (HU) is a known intervention that acts by increasing HbF in individuals with SCD. The increase in HbF reduces the risk of ‘sickling’ events and improves clinical outcomes. This is the first study on the use of HU in individuals with SCA in Tanzania.Methods: A case-control study to determine the proportion, indications, clinical and laboratory outcomes of SCD patients with HU use was conducted at Muhimbili National Hospital in Dar Es Salaam, Tanzania.Results: Forty-two patients with Sickle cell anemia (SCA) on HU treatment and 32 patients with SCA not on HU treatment were enrolled. The proportion of HU use by individuals with SCA at Muhimbili National Hospital was 10 per 1000. The mean HbF % was 9.8 ± 2.4 vs 6.2 ±1.4 for controls (P &lt;0.001). Thirty (71.4%) were enrolled for HU treatment due to central nervous system (CNS) events, frequent painful crises 11(26.2%) and recurrent anemia 1(2.4%). Thirty-two SCA patients (76.2%) reported improvements after being on HU for at least six months. Of these, 91% reported no history of severe pain that required hospitalizations since they started HU. Twenty patients (66.7%) out of those with CNS events reported not to have experienced convulsions after HU initiation.Conclusions: HbF was higher in patients who were on HU and had positive correlation with clinical outcomes. Further clinical trials are required to evaluate more effects of HU use among SCA individuals in Tanzania.&#x0D; Keywords: Sickle cell anemia, HU, Fetal hemoglobin, Tanzania.

Blood rheology biomarkers in sickle cell disease.

Sickle cell disease (SCD) is the most common inherited blood disorder, affecting approximately 100,000 patients in the U.S. and millions more worldwide. Patients with SCD experience a wide range of clinical complications, including frequent pain crises, stroke, and early mortality, all originating from a single-point mutation in the β-globin subunit. The RBC changes resulting from the sickle mutation lead to a host of rheological abnormalities that diminish microvascular blood flow, and produce severe anemia due to RBC hemolysis, and ischemia from vaso-occlusion initiated by sticky, rigid sickle RBCs. While the pathophysiology and mechanisms of SCD have been investigated for many years, therapies to treat the disease are limited. In addition to RBC transfusion, there are only two US Food and Drug Administration (FDA)-approved drugs to ameliorate SCD complications: hydroxyurea (HU) and L-glutamine (Endari™). The only curative therapy currently available is allogeneic hematopoietic stem cell transplantation (HSCT), which is generally reserved for individuals with a matched related donor, comprising only 10–15% of the total SCD population. Potentially curative advanced gene therapy approaches for SCD are under investigation in ongoing clinical trials. The ultimate goal of any curative treatment should be to repair the hemorheological abnormalities caused by SCD, and thus normalize blood flow and prevent clinical complications. Our mini-review highlights a set of key hemorheological biomarkers (and the current and emerging technologies used to measure them) that may be used to guide the development of novel curative and palliative therapies for SCD, and functionally assess outcomes.Impact statementSevere impairment of blood rheology is the hallmark of SCD pathophysiology, and one of the key factors predisposing SCD patients to pain crises, organ damage, and early mortality. As novel therapies emerge to treat or cure SCD, it is crucial that these treatments are functionally evaluated for their effect on blood rheology. This review describes a comprehensive panel of rheological biomarkers, their clinical uses, and the technologies used to obtain them. The described technologies can produce highly sensitive measurements of the ability of current treatments to improve blood rheology of SCD patients. The goal of curative therapies should be to achieve blood rheology biomarkers measurements in the range of sickle cell trait individuals (HbAS). The use of the panel of rheological biomarkers proposed in this review could significantly accelerate the development, optimization, and clinical translation of novel therapies for SCD.

Excellent Survival and Immune Reconstitution Following Matched/Mismatched Unrelated and Mismatched Related Transplantation in Adult Patients with Sickle Cell Disease: Updated Results from a Single Center Experience

Excellent Survival and Immune Reconstitution Following Matched/Mismatched Unrelated and Mismatched Related Transplantation in Adult Patients with Sickle Cell Disease: Updated Results from a Single Center Experience

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

Magnesium for treating sickle cell disease.

Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life. This is an updated version of the review. To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 03 February 2019.Date of last search of other resources (clinical trials registries): 04 April 2019. We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium. Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies. We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Of these, two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies in this comparison, mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence). Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.

CLINICAL AND HEMATOLOGICAL EFFECTS OF HYDROXYUREA THERAPY IN MANAGEMENT OF SICKLE CELL ANEMIA

Background: The most predominant form of haemoglobinopathy worldwide is sickle cell disease. The greatest burden of the disease lies in sub-Saharan Africa and Asia5.&#x0D; Objective: To evaluate the effectiveness of HU therapy in sickle cell disease as measured by decrease in crises rate, hospital admissions, days of hospitalization and number of blood transfusions.&#x0D; Methods: the study was conducted on 79 children of 1-16 year age. Out of which in only 75 patients Hydroxyurea therapy was started as they were found to be eligible. 16% of the patients responded to 15 mg/kg/ day of HU, 50.66% responded to 20 mg/kg/ day, 29.33% to 25 mg/kg/ day and only 4% needed a dose escalation to 30 mg/kg/ day for the response.&#x0D; Results: Our study showed a significant reduction in the VOC rate from 243 episodes to 46 episodes (p value &lt;0.001), the number of ACS reduced from 37 episodes to 5 episodes (p value &lt;0.001), also there is a significant decline in the rates of hemolytic crises from 63 episodes to 10 episodes per year, Significant increase in the HbF levels from 15.87±5.50% to 21.77.±4.06% (p value &lt;0.001). There was a definite and significant reduction in the number of hospitalization days from 7.76±4.76 to 3.79±2.29 days and in the number of admissions per year dropped significantly from 4.80 ± 1.41 to 1.42± 0.61 per year.&#x0D; Conclusion: Hydroxyurea reduced the frequency of painful crises and diminished the number of hospitalization, transfusion, and episodes of acute chest syndrome17.&#x0D; Keywords: Haemoglobin (Hb), Hydroxyurea (HU), Mean Corpuscular Volume (MCV), Pletelet Counts, Sickle Cell Disease (SCD), White Blood Cells (WBC).

Transcranial Doppler and Magnetic Resonance in Tanzanian Children With Sickle Cell Disease.

Background and Purpose- We determined prevalences of neurological complications, vascular abnormality, and infarction in Tanzanian children with sickle cell disease. Methods- Children with sickle cell disease were consecutively enrolled for transcranial Doppler; those with slightly elevated (>150 cm/s), low (<50 cm/s) or absent cerebral blood flow velocity (CBFv) were invited for brain magnetic resonance imaging and magnetic resonance angiography. Results- Of 200 children (median age 9; range 6-13 years; 105 [2.5%] boys), 21 (11%) and 15 (8%) had previous seizures and unilateral weakness, respectively. Twenty-eight (14%) had elevated and 39 (20%) had low/absent CBFv, all associated with lower hemoglobin level, but not higher indirect bilirubin level. On multivariable analysis, CBFv>150 cm/s was associated with frequent painful crises and low hemoglobin level. Absent/low CBFv was associated with low hemoglobin level and history of unilateral weakness. In 49 out of 67 children with low/absent/elevated transcranial Doppler undergoing magnetic resonance imaging, 43% had infarction, whereas 24 out of 48 (50%) magnetic resonance angiographies were abnormal. One had hemorrhagic infarction; none had microbleeds. Posterior circulation infarcts occurred in 14%. Of 11 children with previous seizure undergoing magnetic resonance imaging, 10 (91%) had infarction (5 silent) compared with 11 out of 38 (29%) of the remainder ( P=0.003). Of 7 children with clinical stroke, 2 had recurrent stroke and 3 died; 4 out of 5 had absent CBFv. Of 193 without stroke, 1 died and 1 had a stroke; both had absent CBFv. Conclusions- In one-third of Tanzanian children with sickle cell disease, CBFv is outside the normal range, associated with frequent painful crises and low hemoglobin level, but not hemolysis. Half have abnormal magnetic resonance angiography. African children with sickle cell disease should be evaluated with transcranial Doppler; those with low/absent/elevated CBFv should undergo magnetic resonance imaging/magnetic resonance angiography.

Lung Function Impairment in Pediatric Subjects with Sickle Cell Anemia from Nigeria Is Associatede with Associated Low Steady Haemoglobin

Low hemoglobin (Hb) level at steady state in subjects with sickle cell anemia (SCA) may indicate severe chronic hemolysis and might be related to a more severe course of disease.In this study we investigated the hypothesis that low hemoglobin at steady state may be associated with higher rate of lung function impairment in children and adolescents with SCA.MethodsIn this cross-sectional study black African subjects with SCA (Hb phenotype SS) aged 6 to 18 years followed at the Barau Dikko Teaching Hospital, Kaduna, Nigeria, underwent spirometry and anthropometry measures. A recent Hemoglobin level at steady state was recorded for each patient. Caregivers or patients were interviewed through a questionnaire investigating a history of asthma or acute chest syndrome (ACS) and frequency of pain crises in the last year that required analgesics for at least 24 hours. Exclusion criteria were: the lack of recorded complete blood count (CBC) performed in the last 6 months, respiratory symptoms or feeling unwell on the test day, SCA-related acute events (e.g., pain crises) in the last two weeks or a blood transfusion or an ACS episode in the last month. A portable Easy-on-PC spirometer (ndd, Zurich, Switzerland) was used. Data were included if at least two forced expiratory manoeuvres met the ATS/ERS acceptability and repeatability criteria adapted for children (Miller MR, ERJ 2005; Kirkby J, Pediatr.Pulmonol.2008). Spirometry z-scores and percentage of predicted for FEV1, FVC and FEV1/FVC were derived according to the GLI-2012 reference equations for African Americans (Quanjer PH, ERJ2012). Spirometry patterns were classified as normal, obstructive (zFVC ≥ 1.64 + zFEV1/FVC < -1.64), restrictive (zFVC < -1.64 + zFEV1/FVC ≥ -1.64) or mixed (zFVC < -1.64 + zFEV1/FVC < -1.64) and a FEV1 < 70% of predicted was considered indicative of lung end-organ disease (Kassim AA et al, Blood. 2015 Sep 24;126(13):1544-50). Group comparison between patients with Hb level < 7.5 g/dL versus Hb ≥7.5 g/dL were tested using unpaired t test, χ2 or Fisher's exact test as appropriate. The relationship between Hb values and spirometry outcomes was explored through logistic and linear regression models. P-value < 0.05 was adopted as representing a statistically significant difference. Analyses were conducted using the software STATA and Graphpad Prism 7.ResultsA total of 186 subjects with SCA were initially enrolled. Only one child was on hydroxyurea. After exclusions, data from 126 patients (mean ± SD age of 11.5 ± 3.1 yr., 53% boys) were retained for the final analysis. Mean ± SD Hb value was 7.8±0.9 g/dL (range 5.6 to 10.9). Frequency of low Hb (< 7.5 g/dL) at steady state was 30.9% (39/126).Mean FEV1 and FVC z-scores were lower and frequency of FEV1 < 70% of predicted was higher in patients in the low Hb group compared to those with Hb ≥7.5 g/dL though differences were not statistically significant (table 1). Prevalence of restrictive spirometry pattern, possibly suggesting restrictive lung disease, was significant higher in patients with Hb level < 7.5 g/dL (17/39, 43.5%) than in those with Hb ≥7.5 g/dL (20/87, 22.9%) (p = 0.01; table 1).The odds ratio for restrictive spirometry pattern in presence of Hb level <7.5 g/dL was 2.5 (95% CI 1.1 to 5.7; p = 0.03). In a linear regression model (figure 1) the FVC z-score resulted significantly related to the Hb level with an increase of 0.17 z-scores for each point of Hb (95% CI 0.01 to 0.34, p = 0.04; R2 = 0.03).Frequency of asthma, pain crises and previous acute chest syndrome did was similar between the two groups (data not showed)ConclusionsIn Nigerian pediatric patients with sickle cell anemia a hemoglobin level < 7.5 g/dL at steady state was associated with a 2.5 higher risk of presenting a restrictive spirometry pattern and with a higher frequency of end-organ lung disease (FEV1 < 70% of predicted). Low hemoglobin levels in wellbeing may depend on intense chronic haemolysis that could worsen microangiopathy, inflammation and ischemia and reperfusion injury in the lungs, potentially determining a precocious onset of restrictive lung disease.These preliminary data seem to indicate that a low Hb level at steady state in African pediatric patients with sickle cell anemia is associated with more severe lung impairment and should prompt respiratory assessment with lung function when found. [Display omitted] DisclosuresInusa:Novartis plc: Honoraria, Research Funding, Speakers Bureau; Astrazeneca: Consultancy.

Maximum Tolerated Dose Versus Fixed Low-Dose Hydroxyurea for Treatment of Adults with Sickle Cell Anemia - Retrospective Comparison of Two Studies

Background. Despite a large body of evidence that hydroxyurea is effective for sickle cell anemia (SCA), utilization with the “maximum tolerated dose” regimen has been low.1 Hydroxyurea therapy for SCA increases hemoglobin F, reduces pain crises, acute chest syndrome and blood transfusions, and possibly increases survival.2 The increase in hemoglobin F with hydroxyurea is related to the plasma level achieved, which depends on the dose.3 Hydroxyurea is typically initiated at 15 mg/kg/day followed by dose escalations up to 35 mg/kg/day if tolerated - the “maximum tolerated dose” approach used in the seminal Multicenter Study of Hydroxyurea (MSH) in the 1990's.4 With this approach, neutropenia and thrombocytopenia are limitations to achieving maximal dose and frequent blood count monitoring is required.These considerations limit the use of hydroxyurea in areas of the world where frequent blood monitoring is not feasible, and they also cause primary care providers in the US to hesitate to prescribe the medication.Methods. We recently reported a trial of hydroxyurea (500 mg/day orally) in 48 adults with SCA in Ibadan, Nigeria - a “fixed low-dose” approach.5 In the present report, we compare hematologic responses in 38 per protocol patients from the Ibadan study (received at least five of the planned six 4-weekly supplies of hydroxyurea)5 to the responses in 152 patients in the MSH study.6Results. Baseline hematologic values for the two studies are shown in Table 1. Over the first 12 to 14 weeks of hydroxyurea, responses in hemoglobin, mean corpuscular volume (MCV), and platelets were similar in the two studies (Figure 1). At end-of-study (24 weeks Ibadan and 104 weeks MSH) responses in hemoglobin F and complete blood count were similar, except that the decline in neutrophil count in the Ibadan cohort was significantly less than the decline in MSH after the Bonferroni correction for multiple comparisons (Table 1and Figure 2). At this time the median (range) dose of hydroxyurea per body weight was 10 (7-14) mg/kg per day in the 38 Ibadan patients versus 20 (2.5-35) mg/kg per day in the 119 patients who remained on hydroxyurea in the MSH study.6 We performed a review of the medical records in the Ibadan patients. There were seven acute non-infectious complications in the 38 patients while taking fixed low-dose hydroxyurea for 24 weeks (admission for pain or acute chest syndrome) versus 17 while being observed off hydroxyurea for 24 weeks (pain, acute chest syndrome, need for blood transfusion, heart failure or death) (Table 2). Incidence of infections was similar during 24 weeks of fixed low-dose hydroxyurea and during 24 weeks of observation off hydroxyurea (Table 2).Discussion. These findings suggest that a “fixed low-dose” regimen may have substantial clinical benefit. Such a regimen would have a low chance of inducing cytopenias, would be straightforward for primary care providers to prescribe and would be ideal to test in combination therapy regimens for SCA. It would also be cost-efficient and affordable, especially for patients in low and middle-income countries where access to health insurance is lacking. We propose that the clinical efficacy of “fixed low-dose” hydroxyurea for SCA should be investigated further. We believe that a randomized comparison of the efficacy and safety of the “fixed low-dose” and “maximum tolerated dose” regimens should be a high priority.ReferencesStettler N, McKiernan CM, Melin CQ, Adejoro OO, Walczak NB. Proportion of adults with sickle cell anemia and pain crises receiving hydroxyurea. JAMA 2015;313:1671-2.Platt OS. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 2008;358:1362-9.Charache S, Dover GJ, Moore RD, et al. Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood 1992;79:2555-65.Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 1995;332:1317-22.Tayo BO, Akingbola TS, Saraf SL, et al. Fixed Low-Dose Hydroxyurea for the Treatment of Adults with Sickle Cell Anemia in Nigeria. Am J Hematol 2018.Charache S, Barton FB, Moore RD, et al. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive “switching” agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) 1996;75:300-26. [Display omitted] DisclosuresHsu:Global Blood Therapeutics: Research Funding; Astra Zeneca: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ironwood: Research Funding; Emmi: Consultancy; Hilton Publishing: Consultancy; Gerson Lehman Group: Consultancy; Guidepoint: Consultancy.

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We also searched online trials registries for any ongoing trials (01 July 2018).Last search of the Group's Haemoglobinopathies Trials Register: 08 October 2018. Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. Both authors independently selected studies for inclusion, assessed study quality and extracted data. Of the 51 studies identified, three met the inclusion criteria, including 524 people with sickle cell disease aged between 12 and 65 years of age. One study tested the effectiveness of zinc sulphate as compared to placebo and the remaining two assessed senicapoc versus placebo. No deaths were seen in any of the studies (low-quality evidence). The zinc sulphate study showed a significant reduction in painful crises (in a total of 145 participants) over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (moderate-quality evidence). However, analysis was restricted due to limited statistical data. Changes to red blood cell parameters and blood counts were inconsistent (very low-quality evidence). No serious adverse events were noted in the study. The Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo showed that the high dose senicapoc showed significant improvement in change in hemoglobin level, the number and proportion of dense red blood cells, red blood cell count and indices and hematocrit value (very low-quality evidence). The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups (low-quality evidence). A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red blood cell survival (depending on dose), this did not lead to fewer painful crises.Given this is no longer an active area of research, this review will no longer be regularly updated.

Hemoglobin D in a Patient with Sickle Cell Disease (Genotype HbSS).

A 29-year-old Saudi Arabian male with known sickle cell disease presented to the hematology clinic at Vanderbilt University Medical Center for follow-up and disease management. The patient had a complex past medical history including frequent pain crises requiring hospitalization, chronic kidney disease, and cholangitis. He was reported to be homozygous for hemoglobin S (HbS)2, a β-globin variant caused by a point mutation at codon 6, which results in the substitution of valine for glutamine. Under some circumstances, HbS can polymerize within red blood cells (RBCs), forming rigid, sickle-shaped cells that produce many of the secondary complications of the disease. At Vanderbilt University Medical Center, the patient had been undergoing simple RBC transfusion therapy. As part of the routine laboratory tests performed before each scheduled transfusion, the patient's HbS concentration was measured with cation-exchange high performance liquid chromatography (HPLC) on a Bio-Rad Variant HPLC analyzer (Fig. 1). During the daily review of hemoglobin HPLC chromatograms, the clinical chemistry team noted that an additional hemoglobin variant …

Simple chronic transfusion therapy, a crucial therapeutic option for sickle cell disease, improves but does not normalize blood rheology: What should be our goals for transfusion therapy?

Sickle cell anemia is characterized by a mutation resulting in the formation of an abnormal beta-hemoglobin called hemoglobin S. Hemoglobin S polymerizes upon deoxygenation, causing impaired red blood cell deformability and increased blood viscosity at equivalent hematocrits. Thus, sickle cell disease is a hemorheologic disease that results in various pathologic processes involving multiple organ systems including the lungs, heart, kidneys and brain. Red blood cell mechanics and the perturbations on blood flow-endothelial interaction underlie much of the pathology found in sickle cell disease. Transfusion therapy is one of the few therapeutic options available to patients, acting as both primary and secondary prevention of stroke. Transfusion therapy, both simple and exchange, is also used for unremitting and frequent pain crises and pulmonary hypertension. Therefore, understanding basic rheologic changes following transfusion inform other therapeutic options that aim to mitigate this diffuse pathologic process. This review will aim to highlight transfusion effects on blood rheology.

Quality of life in adults with sickle cell disease: an integrative review of the literature.

To identify the available evidence in the literature on health-related quality of life in adults with sickle cell disease. integrative review of MEDLINE, CUMED, LILACS and SciELO databases, from articles developed in this area, published between 2005 and 2015, in English, Portuguese or Spanish. 22 articles were included, six scales were used to evaluate health-related quality of life scores: three generic and three specific. No specific scale for adults with sickle cell disease has been adapted to Brazilian Portuguese so far. Patients affected by frequent painful crises, with low adherence to treatment, had a compromised quality of life. Selected studies have shown that patients with sickle cell disease have worse scores than the general population. These indicators should be instrumental to the nurse in the proposal of interventions and strategies of assistance and socio-educational, with a view to improving the quality of life of this clientele.

Persistent idiopathic facial pain, a diagnosis and treatment of challenge. Case report

ABSTRACT BACKGROUND AND OBJECTIVES: Persistent idiopathic facial pain is a chronic disease with neuropathic origin, whose etiology is usually unknown; it is a medical condition that does not respond satisfactorily to drug therapy. It is also a disease with a major impact on patient quality of life and difficult to diagnose. This study aimed to report the diagnosis of a complex, persistent idiopathic facial pain, the pharmacological intervention taken and the adoption of integrative and complementary practices for the management of persistent idiopathic facial, as well as the clinical course and the impact of these actions on the patient’s quality of life. CASE REPORT: A female patient, 52, diagnosed 06 years ago as a carrier of persistente idiopathic facial pain associated with bruxism and temporomandibular disorders. The patient presented with a complaint of orofacial pain which did not meet the diagnostic criteria for temporomandibular disorders. The patient also presented myofascial and trigeminal neuralgia pain in the left buccal region which emerged after performing a root canal procedure. The therapeutic plan adopted was based on pharmacological therapy with pregabalin (450mg) in combination with venlafaxine hydrochloride (150mg), continuously. As additional measures, weekly acupuncture sessions, therapy sessions with psychologists, including hypnosis and meditation, as well as peripheral nerve and a venous block during crises and botulinum toxin application were applied. CONCLUSION: The therapeutic plan adopted led to a considerable improvement in the patient’s quality of life, evidenced by the reduction in pain intensity and a decrease in the frequency of painful crises. The need for interdisciplinary monitoring, as it is a multifactorial disease, as well as for the ongoing training of various categories of health professionals involved in the treatment of persistent idiopathic facial, given that it is a complication which is rare and difficult to diagnose, is observed.

Correlation Between the Frequency of Painful Crises in Sickle Cell Anemia and the Biomarkers of Inflammation, Endothelial Dysfunction, Coagulation Activation and Bone Metabolism

Objective: Sickle cell anemia is a widespread inherited hemolytic anemia, characterized by chronic hemolysis, infections, recurrent occlusion of the microcirculation and painful crises. In this cross-sectional study, we investigated the correlation between biomarkers of inflammation, endothelial dysfunction, coagulation activation and bone metabolism, with the frequency of painful crisis in sickle cell anemia adult patients, to understand the potential role of these biomarkers in the management of sickle cell anemia.&#x0D; Methods: Sixty-three sickle cell anemia patients were enrolled in this study. They were divided into three groups based on the frequency of pain crises to mildly, moderately, and severely affected. Twenty-five healthy volunteers were enrolled as controls. Plasma levels of different biomarkers were tested, including tumor necrosis factor alpha, soluble intercellular adhesion molecule-1, D-dimer, sclerostin, and nitric oxide.&#x0D; Results: Tumor necrosis factor alpha, soluble intercellular adhesion molecule-1, and D-Dimer plasma levels were significantly higher in sickle cell anemia patients when compared to the controls, while nitric oxide levels were notably lower in the patients' group. Sickle cell anemia patients with severe pain showed higher tumor necrosis factor alpha, soluble intercellular adhesion molecule-1 and D-dimer levels than those mildly and moderately affected with painful crisis. Positive correlations were observed between all measured biomarkers and the frequency of the painful crisis, except for nitric oxide, which showed a negative correlation.&#x0D; Conclusion: Tumor necrosis factor alpha, soluble intercellular adhesion molecule-1, nitric oxide, and D-dimer can be used to assess sickle cell anemia severity and prognosis, and thus may affect determining appropriate management strategies.

Distinct patterns of response to transfusion therapy for different chronic complications of sickle cell disease: A useful insight

Two main sub-phenotypes have been described in sickle cell disease: one with higher baseline haemoglobin and a higher rate of painful crises and one with lower baseline haemoglobin, increased markers of haemolysis and a higher incidence of pulmonary hypertension, priapism and leg ulcers. We compared the patterns of response to regular automated red cell exchange transfusion over a five-year period of 21 patients with recurrent painful crises from the first group and 3 patients with pulmonary hypertension and 5 with recurrent severe stuttering priapism form the second and found them to be distinctly different. Response for pain is slow and increases gradually over years. The most pronounced clinical benefit and the one that appears first is a reduction in the severity rather than the frequency of painful crises. In contrast to the slow and gradual response we see for pain, response of patients with pulmonary hypertension and priapism is immediate with significant clinical improvement even after the first transfusion. The response appears to be directly correlated to the HbS level as the symptoms of both conditions invariably recur rapidly when transfusions are delayed or discontinued but resolve again once they are re-instituted.