Predictors of impending acute chest syndrome in patients with sickle cell anaemia.

Acute chest syndrome (ACS) is a major complication of sickle cell anaemia (SCA) and a leading cause for hospital admissions and death. We aimed to study the spectrum of clinical and laboratory features of ACS and to assess the predisposing factors and predictors of severity. A retrospective case-control cohort was studied by retrieving patient information from electronic medical records after ethical approval. One hundred adolescents and adults with SCA and hospital admissions for ACS were identified through the discharge summaries, along with 20 additional patients presenting with VOC, but without ACS (controls). Among the patients with ACS, fever (\u3e38.5 °C), reduced oxygen saturation (\u3c95) and asplenia significantly differed when compared to those of controls (p \u3c 0.05, chi-squared test). The degree of severity was reflected in the use of non-invasive ventilation (NIV), simple and exchange transfusions, and the presence of bilateral pleural effusions and multi-lobar atelectasis/consolidation, which were significantly higher in the cases with ACS than in the controls. Lower haemoglobin (Hb) and high WBC counts were also significantly different between the two groups (p \u3c 0.05, Student’s t test). Using logistic regression, our study further demonstrated that asplenia, fever, and reduced O2 saturation, along with low Hb and leukocytosis, were important predictors for the development of ACS

Predictors Of Use Of Hydroxyurea And Its Impact On Clinical And Economic Outcomes Among Children With Sickle Cell Disease

Objective: The objective of this study was to assess the prevalence and predictors of use of hydroxyurea (HU) and its impact on clinical and economic outcomes in pediatric patients with sickle cell disease (SCD) enrolled in Medicaid. Methods: A cohort of patients with SCD was identified in 2006 using ICD-9-CM codes from Medicaid claims from 40 US states. Patients who filled three prescriptions of HU in within 6 months in 2007 were identified as HU users. HU users were then matched with non-users and the impact of HU use on the presence of crises and economic outcomes including presence of hospitalizations and emergency department visits were assessed using conditional logistic regression stratified on matched pairs. Length of stay and medical costs were compared in the matched sample using generalized linear models. An additional clinical outcome, number of crises, was evaluated in the unmatched sample of HU users and non-users using conventional multivariable regression. Estimates obtained using this approach, were then compared with those obtained by minimizing selection bias using regional variation and physician preference-based instrumental variables (IVs). Results: Prevalence of HU use in children with SCD enrolled in Medicaid was found to be 10.72%. Age, gender, race, disease severity, previous office visits, presence of a comprehensive sickle cell center within the state of residence, and prior opioid use were all found to be significant predictors of HU use in this population (p\u3c0.0001). HU users had a significantly greater likelihood of having a hospitalization (OR:2.09; 95% CI:1.28-3.43) and a longer LOS (β=0.49; 95% CI:0.14-0.84) compared to non-users. Even though the conventional multivariable model shothat HU users had a significantly greater number of crises compared to non-users (β=0.93; p\u3c0.0001), analysis using IVs found no statistically significant relationship (β=-2.75; p=0.2013). Conclusion: HU use is not very prevalent among children with SCD enrolled in Medicaid. Based on the identified predictors, it seems that physicians follow guidelines when prescribing HU in this population. Since this study failed to corroborate the benefit associated with the use of HU on clinical outcomes and resource utilization, physicians should be wary in prescribing HU in this population

HYDROXYUREA EFFECTIVENESS AND HEALTH-CARE UTILIZATION IN TENNESSEE MEDICAID POPULATION AND A META-ANALYSIS OF TOXICITIES RELATED TO HYDROXYUREA DOSING

The use of hydroxyurea (HU) reduces sickle cell disease (SCD)-related complications and health care utilization. Young adults transitioning to adult care have difficulty adhering to HU therapy (or may not be receiving HU) and have increased healthcare utilization when compared to their younger and older counterparts, due to various challenges. There is a lack of consensus about dosing strategies for HU due to fear of toxicities. We evaluated the association of different levels of HU adherence and healthcare utilization (hospitalizations, ED visits, and transfusions rates) among transitioning young adults (18 to 25 years) when compared to the pediatric (25 years) groups, using state-wide claims data. We concluded that HU prescription prevalence was suboptimal in all three age groups of our study. Among those who initiated HU, as the HU percent prescription adherence increased the rate of hospitalizations, ED visits, and transfusions decreased. Females between ages 19 to 25 years had lower HU prescription prevalence and HU percent prescription adherence when compared to males. We estimated the association between the proportion of time a patient suspends HU treatment and its association with health-care utilization among pediatric, transitioning younger and older adults. those who suspend their treatment for extended periods have two to five times increased rate of health-care utilization, particularly among young adults. Young males who discontinued their treatment had a significantly increased rate of health-care utilization than females. The results of the above two studies may provide evidence to support HU prescription and adherence.We performed a meta-analysis comparing hematological toxicities between fixed and escalated dosing strategies in studies published between 2010 to 2015. Our meta-analyses show that summarized neutropenia and thrombocytopenia incidence rates are higher when using escalated dosing than fixed dosing. Summarized hepatic and renal toxicities incidence rates were higher in fixed doses than the escalated doses. However, a small number of studies reporting toxicities related information, imprecise summarized incidence rates, and high heterogeneity between the studies may have affected our results. A randomized clinical trial to compare toxicities between fixed and escalated dosing strategies may help establishing a consensus of HU dosing method

American Society of Hematology 2020 guidelines for sickle cell disease: Prevention, diagnosis, and treatment of cerebrovascular disease in children and adults

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan.OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD.METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations.RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings.CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.</p

C-Reactive Protein Polymorphism and Serum Levels as an Independent Risk Factor in Sickle Cell Disease

This study explored the relationship of a dinucleotide repeat polymorphism in the intron of the CRP gene and serum CRP levels as independent risk factors for end-organ dysfunction (mild vs. severe) in adults with sickle cell disease. The pathogenesis of secondary complications of sickle cell disease is complex and poorly understood. Predicting the severity of these complications could assist in therapeutic decision-making. The study measured serum CRP levels and the number of CA intron repeats located on the CRP gene in 29 adults (31.74 ± 11.54 years) with sickle cell disease The hemoglobin genotypes were distributed as Hgb SS 48.6% (17 of n = 29), Hgb SC 20.0% (7 of n = 29), Sβ° 10.3% (3 of n = 29), and Sβ+ 6.9% (2 of n = 29). The sample was categorized as mild (n = 9) no end-organ dysfunction vs. severe (n = 21) documented end-organ dysfunction. The severe group was sub-categorized by specific organ dysfunctions, 9 with pulmonary hypertension, 6 with renal dysfunction and 6 with cerebral vascular accident. Examination of serum CRP levels found no significant association with severe end-stage organ dysfunction. There was no significant association between serum CRP level and the polymorphism. However, a significant negative correlation (rho = -0.401, p = 0.031) was found between glomerular filtration rates and CAhigh repeats (≥17). Previous studies have found an association of genetic variations in the CRP gene polymorphism to serum CRP levels. While this pilot study found no evidence of this association, the findings provide some rationale for further investigation of the repeat polymorphism in the CRP gene and its association with renal end-organ dysfunction

Pulmonary Complications and Lung Function Abnormalities in Children with Sickle Cell Disease

The pulmonary complications of sickle cell disease (SCD) have a high morbidity and mortality. Fatal pulmonary complications occur in 20% of adults; those with sickle chronic lung disease (SCLD) and pulmonary hypertension have a significantly increased mortality. Treatment of SCLD is only supportive. Recurrent acute chest syndrome (ACS) episodes are the major risk factor for SCLD, and ACS is the leading cause of death. Adults with SCD tend to have restrictive lung function abnormalities, whereas, in children, obstructive abnormalities are more frequent. Lung function abnormalities are common even in young children and may reflect their chronic anaemia and increased pulmonary capillary blood volume, which increases airway obstruction and may be responsible for their increased wheezing. Whether more aggressive treatment of anaemia would improve lung function and long-term outcomes merits testing. Children with SCD experience a decline in lung function, which is most rapid in younger children in whom ACS episodes are most common highlighting the importance of identifying effective strategies to prevent and optimally treat ACS

Hydroxyurea Treatment for Sickle Cell Disease

High fetal hemoglobin (HbF) levels inhibit the polymerization of sickle hemoglobin (HbS) and reduce the complications of sickle cell disease. Pharmacologic agents that can reverse the switch from γ- to β-chain synthesis — γ-globin chains characterize HbF, and sickle β-globin chains are present in HbS — or selectively increase the proportion of adult erythroid precursors that maintain the ability to produce HbF are therapeutically useful. Hydroxyurea promotes HbF production by perturbing the maturation of erythroid precursors. This treatment increases the total hemoglobin concentration, reduces the vaso-occlusive complications of pain and acute chest syndrome, and attenuates mortality in adults. It is a promising beginning for pharmacologic therapy of sickle cell disease. Still, its effects are inconsistent, trials in infants and children are ongoing, and its ultimate value — and peril — when started early in life are still unknown