BACKGROUND: Readmission to the hospital within 30 days is a measure of quality care; however, only few modifiable risk factors for 30-day readmission in adults with sickle cell disease are known. METHODS: We performed a retrospective review of the medical records of adults with sickle cell disease at a tertiary care center, to identify potentially modifiable risk factors for 30-day readmission due to vasoocclusive pain episodes. A total of 88 patients >=18 years of age were followed for 3.5 years between 2010 and 2013, for 158 first admissions for vasoocclusive pain episodes. Of these, those subsequently readmitted (cases) or not readmitted (controls) within 30 days of their index admissions were identified. Seven risk factors were included in a multivariable model to predict readmission: age, sex, hemoglobin phenotype, median oxygen saturation level, listing of primary care provider, type of health insurance, and number of hospitalized vasoocclusive pain episodes in the prior year. RESULTS: Mean age at admission was 31.7 (18-59) years; median time to readmission was 11 days (interquartile range 20 days). Absence of a primary care provider listed in the electronic medical record (odds ratio 0.38; 95% confidence interval, 0.16-0.91; P = .030) and the number of vasoocclusive pain episodes requiring hospitalization in the prior year were significant risk factors for 30-day readmission (odds ratio 1.30; 95% confidence interval, 1.16-1.44; P <.001). CONCLUSION: Improved discharge planning and ensuring access to a primary care provider may decrease the 30-day readmission rate in adults with sickle cell disease. Abstract source Full text

Data on the magnitude and risk factors for hypertension in sickle cell anaemia (SCA) are limited. A retrospective analysis of individuals with SCA aged >=15 years enrolled from 2004-2014 at Muhimbili National Hospital, Tanzania was conducted to determine the prevalence, incidence and risk factors for hypertension. A total of 1013 individuals with SCA were analysed, of whom 571(56%) were females. The median age [interquartile range] was 17 [15-22] years. Four hundred and forty-one (44%) of the patients had relative hypertension [systolic blood pressure (SBP) 120-139 mmHg or diastolic blood pressure (DBP) 70-89 mmHg], and 79 (8%) had hypertension (SBP >= 140 mmHg or DBP >= 90 mmHg). The incidence of hypertension was 64/1000 person years of observation and the 5-year survival rate was 0·71 [95% confidence interval (CI): 0·67-0·75]. In multivariate analysis, age>18 years, Hazard ratio (HR) 1·50 (95% CI: 1·03-2·18); pulse pressure, HR 0·64 (95% CI: 0·42 to 0·98); pulse rate, 1·02 (95% CI: 1·01-1·03); body mass index (BMI), HR 1·08 (95% CI: 1·03-1·13); blood transfusion, HR 2·50 (95% CI: 1·01-6·21) and haemoglobin, HR 1·12 (95% CI: 1·05-1·33) were independently associated with hypertension. In conclusion, despite the younger age, hypertension in this population was higher than that reported in others studies. Age, BMI, pulse pressure and haemoglobin were independently associated with hypertension in SCA. Abstract source Full text

BACKGROUND: Little is known about red blood cell (RBC) transfusion practices for children hospitalized for a sickle cell vaso-occlusive pain crisis (VOC). We hypothesized that transfusion would be associated with the development of acute chest syndrome (ACS), lower hemoglobin (Hb) concentration, and lack of hydroxyurea therapy. STUDY DESIGN AND METHODS: This is a secondary analysis of all children admitted for a sickle cell pain crisis enrolled in the Magnesium in Crisis (MAGiC) randomized trial; all had HbSS or S-β0 thalassemia. ACS development and transfusion administration were prospectively collected during the parent trial. All Hb values during the hospitalization were recorded, as was parent report of child receiving hydroxyurea. Relative risks (RRs) of transfusion were compared between groups. RESULTS: Of 204 enrolled children, 40 (19.6%) received a transfusion. Of the 30 children who developed ACS, 22 (73.3%) received transfusions compared to 18 of 174 (10.3%) without ACS: the RR of transfusion in children with ACS was 7.1 (95% confidence interval [CI], 4.4-11.5). Among those without ACS, the lowest Hb was most strongly associated with transfusions: RR was 3.1 (95% CI 2.0 - 4.7) for each 1 g/dL decrease in lowest Hb. In a binary recursive partitioning model for those without ACS, a lowest recorded Hb level of less than 6.3 g/dL was significantly associated with transfusion during admission (p < 0.01). Hydroxyurea use was not associated with transfusions in any analysis. CONCLUSION: ACS increased the RR of transfusion in children hospitalized for VOC sevenfold. In children without ACS, transfusion was associated with lowest Hb concentration, particularly Hb concentration of less than 6.3 g/dL. Abstract source Full text

BACKGROUND: Sickle cell trait may increase risk of venous thromboembolism, but this is not fully established. OBJECTIVES: We sought to determine the association of sickle cell trait with deep vein thrombosis and pulmonary embolism. METHODS: Middle-aged African Americans participating in a prospective, population-based cohort investigation, the Atherosclerosis Risk in Communities Study, were followed from 1987 through 2011 for incident hospitalized pulmonary embolism (n = 111) or isolated deep vein thrombosis (n = 138), verified by physician review of medical records. Sickle cell trait (heterozygosity for hemoglobin S, n = 268) was compared with no sickle cell trait (n = 3748). RESULTS: Over a median of 22 years of follow-up, 249 participants had an incident venous thromboembolism. The hazard ratio of venous thromboembolism was 1.50 (95% confidence interval [CI] 0.96-2.36) for participants with vs. without sickle cell trait, after adjustment for age, sex, ancestry, hormone replacement therapy (women), body mass index, diabetes, and estimated glomerular filtration rate. This hazard ratio was 2.05 (95% CI 1.12-3.76) for pulmonary embolism and 1.15 (95% CI 0.58-2.27) for deep vein thrombosis without pulmonary embolism. CONCLUSIONS: Sickle cell trait in African Americans carries a 2-fold increased risk of pulmonary embolism but does not elevate deep vein thrombosis risk. Because neonatal screening for sickle hemoglobin is being conducted in the United States, consideration should be paid to the increased pulmonary embolism risk of individuals with sickle cell trait. Abstract source Full text Full text (PMC)

Sickle cell disease (SCD) is the most common hereditary disease worldwide, presenting with anemia and intermittent severe pain. Pregnancy in a patient with SCD is associated with high levels of maternal and fetal morbidity and mortality; the maternal and fetal death rates during pregnancy can attain 11.4% and 20%, respectively. Patient care has improved over time. However, certain management issues remain unresolved; these include the optimum policy in terms of prophylactic blood transfusion, and the use of antiplatelet drugs. Such issues are attributable to the heterogeneous nature of clinical SCD features, and the limitations of uncontrolled and prospective trials. In this review, we seek to facilitate a better understanding of relevant issues via creation of a comparative data profile extracted from current studies. This report may also encourage the drafting of standard operating procedure for management of pregnancy in SCD patients. Abstract source Full text

Background: Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Surgical interventions are more common in people with sickle cell disease, and occur at much younger ages than in the general population. Blood transfusions are frequently used prior to surgery and several regimens are used but there is no consensus over the best method or the necessity of transfusion in specific surgical cases. This is an update of a Cochrane review first published in 2001. Objectives: To determine whether there is evidence that preoperative blood transfusion in people with sickle cell disease undergoing elective or emergency surgery reduces mortality and perioperative or sickle cell-related serious adverse events.To compare the effectiveness of different transfusion regimens (aggressive or conservative) if preoperative transfusions are indicated in people with sickle cell disease. Search Methods: We searched for relevant trials in The Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 23 March 2016.We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 18 January 2016. Selection Criteria: All randomised controlled trials and quasi-randomised controlled trials comparing preoperative blood transfusion regimens to different regimens or no transfusion in people with sickle cell disease undergoing elective or emergency surgery. There was no restriction by outcomes examined, language or publication status. Data Collection and Analysis: Two authors independently assessed trial eligibility and the risk of bias and extracted data. Main Results: Three trials with 990 participants were eligible for inclusion in the review. There were no ongoing trials identified. These trials were conducted between 1988 and 2011. The majority of people included had haemoglobin (Hb) SS SCD. The majority of surgical procedures were considered low or intermediate risk for developing sickle cell-related complications. Aggressive versus simple red blood cell transfusions One trial (551 participants) compared an aggressive transfusion regimen (decreasing sickle haemoglobin to less than 30%) to a simple transfusion regimen (increasing haemoglobin to 100 g/l). This trial re-randomised participants and therefore quantitative analysis was only possible on two subsets of data: participants undergoing cholecystectomy (230 participants); and participants undergoing tonsillectomy or adenoidectomy surgeries (107 participants). Data were not combined as we do not know if any participant received both surgeries. Overall, the quality of the evidence was very low across different outcomes according to GRADE methodology. This was due to the trial being at high risk of bias primarily due to lack of blinding, indirectness and the outcome estimates being imprecise. Cholecystectomy subgroup results are reported in the abstract. Results for both subgroups were similar.There was no difference in all-cause mortality between people receiving aggressive transfusions and those receiving conservative transfusions. No deaths occurred in either subgroup.There were no differences between the aggressive transfusion group and conservative transfusion group in the number of people developing:• an acute chest syndrome, risk ratio 0.84 (95% confidence interval 0.38 to 1.84) (one trial, 230 participants, very low quality evidence);• vaso-occlusive crisis, risk ratio 0.30 (95% confidence interval 0.09 to 1.04) (one trial, 230 participants, very low quality evidence);• serious infection, risk ratio 1.75 (95% confidence interval 0.59 to 5.18) (one trial, 230 participants, very low quality evidence);• any perioperative complications, risk ratio 0.75 (95% confidence interval 0.36 to 1.55) (one trial, 230 participants, very low quality evidence);• a transfusion-related complication, risk ratio 1.85 (95% confidence interval 0.89 to 3.88) (one trial, 230 participants, very low quality evidence). Preoperative transfusion versus no preoperative transfusion Two trials (434 participants) compared a preoperative transfusion plus standard care to a group receiving standard care. Overall, the quality of the evidence was low to very low across different outcomes according to GRADE methodology. This was due to the trials being at high risk of bias due to lack of blinding, and outcome estimates being imprecise. One trial was stopped early because more people in the no transfusion arm developed an acute chest syndrome.There was no difference in all-cause mortality between people receiving preoperative transfusions and those receiving no preoperative transfusions (two trials, 434 participants, no deaths occurred).There was significant heterogeneity between the two trials in the number of people developing an acute chest syndrome, a meta-analysis was therefore not performed. One trial showed a reduced number of people developing acute chest syndrome between people receiving preoperative transfusions and those receiving no preoperative transfusions, risk ratio 0.11 (95% confidence interval 0.01 to 0.80) (65 participants), whereas the other trial did not, risk ratio 4.81 (95% confidence interval 0.23 to 99.61) (369 participants).There were no differences between the preoperative transfusion groups and the groups without preoperative transfusion in the number of people developing:• a vaso-occlusive crisis, Peto odds ratio 1.91 (95% confidence interval 0.61 to 6.04) (two trials, 434 participants, very low quality evidence).• a serious infection, Peto odds ratio 1.29 (95% confidence interval 0.29 to 5.71) (two trials, 434 participants, very low quality evidence);• any perioperative complications, risk ratio 0.24 (95% confidence interval 0.03 to 2.05) (one trial, 65 participants, low quality evidence).There was an increase in the number of people developing circulatory overload in those receiving preoperative transfusions compared to those not receiving preoperative transfusions in one of the two trials, and no events were seen in the other trial (no meta-analysis performed). Authors' Conclusions: There is insufficient evidence from randomised trials to determine whether conservative preoperative blood transfusion is as effective as aggressive preoperative blood transfusion in preventing sickle-related or surgery-related complications in people with HbSS disease. There is very low quality evidence that preoperative blood transfusion may prevent development of acute chest syndrome.Due to lack of evidence this review cannot comment on management for people with HbSC or HbSβ(+) disease or for those with high baseline haemoglobin concentrations. Abstract source Full text Full text (PMC)

BACKGROUND: Pregnancy in women with sickle-cell disease (SCD) is associated with increased adverse outcomes. Findings on the association between SCD and adverse pregnancy outcomes are conflicting, and the results do not address whether these associations are similar in both low- and high-income countries. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate pregnancy outcomes associated with SCD. SEARCH STRATEGY: The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles on pregnancy outcomes in women with SCD. SELECTION CRITERIA: We used full research articles published in English that compared women with SCD with women who did not have SCD, as controls. DATA COLLECTION AND ANALYSIS: Data were abstracted and analysed using comprehensive Meta-analysis 2.2. The primary outcomes were intrauterine growth restriction and perinatal mortality. Secondary outcomes were rates of caesarean sections, pre-eclampsia, eclampsia, postpartum haemorrhage, maternal mortality, prematurity, and low birthweight. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs). MAIN RESULTS: Sixteen studies met all of the selection criteria and were included in the analysis. SCD was associated with intrauterine growth restriction (pooled OR 2.79, 95% CI 1.85-4.21), perinatal mortality (pooled OR 3.76, 95% CI 2.34-6.06), and low birthweight (pooled OR 2.00, 95% CI 1.42-2.83). SCD was also associated with an increased risk of pre-eclampsia (pooled OR 2.05, 95% CI 1.47-2.85), maternal mortality (pooled OR 10.91, 95% CI 1.83-65.11, P = 0.009), and eclampsia (pooled OR 3.02, 95% CI 1.20-7.58). CONCLUSION: Pregnancy in women with SCD is associated with increased risks of adverse perinatal and maternal outcomes in both low- and high-income countries. Abstract source Full text

Once a fatal disease of childhood, more than 95% of patients born today with sickle cell disease (SCD) in developed countries are expected to survive into adulthood, largely because of improvements in supportive and preventive care (newborn screening, penicillin prophylaxis, transcranial Doppler (TCD) screening). Hydroxyurea (HU) therapy, the only oral medication currently available to prevent SCD complications, has become more widespread over the past 20 y. The NHLBI recommends that HU be offered to all patients with HbSS beginning at 9 mo of age, and the recently published Abnormal TCD with Transfusions Changing to HU (TWiTCH) trial has shown HU as an acceptable alternative to transfusion therapy for patients at high risk of stroke. While hematopoietic stem cell transplant (HSCT) is a curative option for SCD, less than 25% of patients have a suitable donor. Alternative stem cell sources from unrelated donors and haplo-identical donors are currently under investigation as are gene therapy trials. This review will focus on early efforts to elucidate SCD pathophysiology as well as supportive and preventive care improvements. Findings from recent multi-center studies (Silent Infarct Transfusion (SIT) Trial and TWiTCH) will be summarized. Finally, HSCT trials and gene therapy will be reviewed. Abstract source Full text

RATIONALE: Patient factors associated with development of abnormal lung function in children with sickle cell anemia (SCA) have not been fully characterized. OBJECTIVES: To characterize lung function abnormalities among children with SCA and to determine whether these steady-state lung function results were associated with morbidity before or after testing among children with SCA. METHODS: This study was part of the prospective National Institutes of Health-funded Sleep and Asthma Cohort Study. Children with HbSS or Hb Sβ(o) (SCA) were enrolled without regard for sickle cell-related comorbidities or diagnosis of asthma. Lung function was measured by spirometry and plethysmography on the same day, when free of acute disease. Standardized asthma symptom questionnaires and review of the medical records were also performed. MEASUREMENTS AND MAIN RESULTS: A total of 149 children aged 6 to 19 years completed lung function testing, of whom 139 participants had retrospective morbidity data from birth to the test date, and 136 participants were followed prospectively for a median of 4.3 years from the test date. At baseline, percentages with normal, obstructive, restrictive, nonspecific, and mixed lung function patterns were 70, 16, 7, 6, and 1, respectively. Neither retrospective rates of pain nor acute chest syndrome was associated with lung function patterns. Furthermore, baseline lung function pattern was not predictive of future pain or acute chest syndrome episodes. CONCLUSIONS: The majority of children with SCA have lung function that is within the normal range. Abnormal lung function patterns were not associated with prior vasoocclusive pain or acute chest syndrome episodes, and baseline lung function patterns did not predict future vasoocclusive pain or chest syndrome episodes. Abstract source Full text Full text (PMC)

Vitamin D deficiency has emerged as a public health focus in recent years and patients with sickle cell disease (SCD) reportedly have a high prevalence of the condition. Our objectives were to summarize definitions of vitamin D deficiency and insufficiency used in the literature, and to determine the prevalence and magnitude of each in patients with SCD through a systematic review conducted according to PRISMA guidelines. From a PubMed search, 34 potential articles were identified and 15 met eligibility criteria for inclusion. Definitions of deficiency and insufficiency varied greatly across studies making direct comparisons difficult. This review provides evidence to suggest that suboptimal vitamin D levels are highly prevalent among those with SCD, far more so than in comparable non-SCD patients or matched control populations. Defining deficiency as vitamin D < 20 ng/mL, prevalence estimates in SCD populations range from 56.4% to 96.4%. When compared with results from the population-based National Health and Nutrition Examination Survey, however, the general African American population appeared to have a similarly high prevalence of vitamin D deficiency. African American patients with and without SCD were both substantially higher than that of Caucasians. What remains to be determined is whether there are adverse health effects for patients with SCD because of concurrent vitamin D deficiency. Abstract source Full text Full text (PMC)