Acute Splenic Sequestration Crisis Research Articles

Splenic filtration of red blood cells in physiology, malaria and sickle cell disease.

The human spleen clears the blood from circulating microorganisms and red blood cells (RBCs) displaying alterations. This review analyzes how generic mechanisms by which the spleen senses RBC, such pitting, trapping and erythrophagocytosis, impact the pathogenesis of twos major spleen-related diseases, malaria and sickle cell disease (SCD). Scintigraphy, functional histology, comparison of circulating and splenic RBC, ex-vivo perfusion of human spleens and in-silico modeling enable relevant exploration of how the spleen retains and processes RBC in health and disease. Iterative cross-validations between medical observations, in-vitro experiments and in-silico modeling point to mechanical sensing of RBC as a central event in both conditions. Spleen congestion is a common pathogenic process explaining anemia and splenomegaly, the latter carrying a risk of severe complications such as acute splenic sequestration crisis and hypersplenism in SCD. Sickling of hemoglobin S-containing RBC may contribute but not trigger these complications. Ongoing progress in the exploration and understanding of spleen-related complications in malaria and SCD open the way to optimized prognosis evaluation and therapeutic applications.

Rescue splenic artery embolization in an adult patient of sickle cell disease presented with acute splenic sequestration crisis.

Splenic sequestration crisis is a potentially fatal complication of sickle cell disease, mainly seen in young children. Only a few case series describe the acute splenic sequestration crisis in adults and its management, which primarily consists of supportive care and, in some cases, splenectomy. Splenic artery embolization has seldom been described in sickle cell disease. This is probably the first case in which an adult with sickle cell disease presented with an acute splenic sequestration crisis was managed successfully through splenic artery embolization. This 22-year-old female, a known case of sickle cell disease, presented with severe pain in the abdomen and low-grade intermittent fever for two days, secondary to an acute splenic sequestration crisis. The diagnosis of acute splenic sequestration was made based on clinical and blood parameters, ultrasonography, and computed tomography. Even with adequate supportive care and blood transfusions, the patient's condition worsened with a rapid fall in the hemoglobin and total platelet count. Considering splenectomy to be a high-risk procedure for this patient, a decision of rescue splenic artery embolization was taken, which was successful. Splenic artery embolization may be considered a lifesaving procedure in patients with acute splenic sequestration, where the risk of splenectomy can be high. Adequate post-procedure supportive care is vital for preventing complications.

Hydroxyurea is associated with later onset of acute splenic sequestration crisis in sickle cell disease: Lessons from the European Sickle Cell Disease Cohort-Hydroxyurea (ESCORT-HU) study.

Acute splenic sequestration crisis (ASSC) is a potentially life-threatening complication of sickle cell disease (SCD), typically occurring in young patients under 5 years of age, with a median age at first episode of less than 2 years. Because a beneficial effect of hydroxyurea (HU) on spleen perfusion and splenic function has been suspected, we hypothesized that HU treatment might be associated with later onset of ASSC in patients with SCD. To investigate this hypothesis, we analyzed data from the ESCORT-HU study on a large cohort of patients with SCD receiving HU, enrolled between January 2009 and June 2017 with a follow-up of 7309 patient-years of observation. The median age at ASSC of the 14 patients who experienced a first episode of ASSC during the study period was 8.0 [IQR: 5.0-24.1] years. The median age at HU initiation was significantly lower in these 14 patients (4.8 [IQR: 3.3-18.7] years) compared to the 1664 patients without ASSC (19.9 [8.8-33.4] years, p = .0008). These findings suggest that ASSC may occur at an unusually late age in patients receiving HU, possibly reflecting longer preservation of spleen perfusion and function secondary to early initiation of HU. Further studies are needed to better characterize the effects of HU on spleen perfusion/function and on the occurrence of ASSC in patients with SCD (ClinicalTrials.gov identifier: NCT02516579; European registry ENCEPP/SDPP/10565).

Sudden Death due to Acute Splenic Sequestration Crisis in Sickle Cell Disease: A Case Report with Active Post-mortem Follow up

Sudden Death due to Acute Splenic Sequestration Crisis in Sickle Cell Disease: A Case Report with Active Post-mortem Follow up

Splenic Sequestration in Febrile Pediatric Sickle Cell Disease Patients

Introduction: Acute splenic sequestration is a rare complication of pediatric sickle cell disease (SCD). Acute splenic sequestration crisis (ASSC) is characterized by an acute decrease in hemoglobin and is associated with an increased risk for hypovolemic shock, often requiring blood transfusion during acute episodes and splenectomy to prevent recurrent episodes. Recent studies have also shown that chronic splenomegaly and resultant anemia (described as chronic or subacute sequestration) with potential benefit of splenectomy. However, non-life-threatening splenic sequestration in febrile, hospitalized children with SCD is a frequent occurrence that has not been well-described in current literature. Aim: To estimate the change in WBC, Hemoglobin, platelet count from inpatient and outpatient baseline to lowest recorded value (LRV) for each febrile hospitalization in sickle-cell disease patients while controlling for hydroxyurea use and patient age. Methods: A retrospective chart review was performed on febrile, hospitalized children with a diagnosis of SCD who presented to a tertiary care hospital from 2018-2021. Data including the magnitude of fever, presence of splenomegaly and trends in laboratory parameters such as complete blood count, and chemistries were recorded. Demographics, hydroxyurea use, transfusions and sickle cell phenotype were also recorded. For our primary outcome we estimated the change in Hgb, platelets, and WBC count from inpatient (first day of hospitalization) and outpatient (most recent outpatient values) baselines to the lowest recorded value (LRV) for each hospital encounter. We employed mixed models to account for within-subject correlation and adjusted for hydroxyurea use and categorized patient age. The beta coefficient and corresponding 95% confidence interval (CI) were reported for the model intercept and predictors. Results: Sixty-six unique patients (ages 0-17) accounted for a total of 117 hospital encounters. There was a statistically significant drop in WBC per microliter (-5.40, 95% CI: -6.89 - [-3.91]) , Hgb g/dL (-0.95, 95% CI : -1.25 - [-0.66]), and platelets per microliter (-60.95, 95% CI : -83.18 - [-38.71]) from the inpatient baseline to the LRV. There was a statistically significant drop in estimated Hgb g/dL (-1.83, 95% CI : -2.23 - [-1.42]) and platelets per microliter (-130.50, CI: -169.59 - [-91.41]) from outpatient baseline to the LRV. Hospital encounters with hydroxyurea had a significantly greater drop in estimated platelets per microliter from inpatient baseline to LRV (-54.43 CI : -93.64 - [-15.22]) but significantly greater increase in estimated Hgb g/dL from inpatient baseline to the LRV (1.11 CI : 0.45 - 1.78) compared to hospital encounters without hydroxyurea. Hospital encounters over the age of 8 were associated with a significantly greater decrease in HGB g/dL (-0.59 CI : -1.04 - [-0.14]) from inpatient baseline to the LRV compared to hospital encounters under the age of 8. Conclusion: Our study demonstrated features consistent with acute, non-life-threatening splenic sequestration in febrile pediatric SCD patients, as evidenced by a statistically significant drop in platelets, Hgb, and WBC count from the inpatient baseline. The largest acute drop was observed in platelets, which presents the strongest argument for sequestration, as drops in Hgb may be explained by rehydration or hyperhemolysis, and changes in WBC count may be related to infection. Hydroxyurea use may delay auto-infarction of the spleen, thus predisposing to splenic sequestration at an age later than classically associated with sequestration. The preservation of splenic function probably explains greater decrease in platelet count for patients on hydroxyurea. Our study has treatment implications: children with SCD experiencing non-life-threatening acute splenic sequestration recover spontaneously without the need for blood transfusion in many cases, thus avoiding long-term complications such as RBC alloimmunization or iron overload. Also, as the drop in WBC, hemoglobin, and platelets are not due to myelosuppression, they should not lead to modification of hydroxyurea therapy. Splenectomy should be reserved for the most severe and life-threatening episodes of sequestration. Further research may assist in correlating sickle cell phenotype and history of blood transfusion with the magnitude of sequestration in this population.

Role of social disparity in 30-day readmissions and healthcare utilization in patients with history of sickle cell crisis in United States: Cross-sectional analysis from US national database.

e18666 Background: Factors like age, mental status, spirituality, financial security, and clinic attendance affect hospital admissions/readmissions in sickle cell disease patients. To further understand the predisposing factors associated with increased readmissions in sickle cell disease patients, this study examined the relationship between readmission rates and socioeconomic status of Sickle cell patients in the US. Methods: All adult hospitalized patients in the Nationwide Readmission Database (NRD) for the year 2019 were captured. The sample population included all patients with primary diagnosis of Sickle cell crisis, identified using ICD-10 codes (International Classification of Diseases, tenth edition). We used the Wilcoxon rank sum test to compare continuous variables and chi square test for categorical variables. Predictors of readmission were analyzed using multivariate logistic regression models. We used StataCorp LLC MP4 17 version to perform statistical analysis. Results: The sample size included 48,715 patients admitted with sickle cell crisis, of which 55.12% were females and 44.88% were males. The mean age of presentation was 32.84 years. The rate of all cause 30-day readmission in patients admitted with Sickle cell crisis was 27.19%. The total hospital charges for these readmitted patients during the year 2019 was 507 million dollars and total length of stay was 69,418 days (about 190 years). The most common causes of readmissions were Sickle cell crisis including Acute chest syndrome and splenic sequestration crisis, followed by sepsis due to MRSA and femoral fractures. After adjusting for confounders on multivariate analysis, compared to patients belonging to income category 1 ( < $46,000), patients in category 2 ($46,000-$58,999) had 11% lower risk (p-value 0.018) and category 3 had 16% lower risk (p-value 0.008) of 30-day readmission. However, there was no increased risk of death based on socioeconomic status (OR 1.03, p-value 0.875). Conclusions: Our study concludes that socioeconomically deprived Sickle cell crisis patients are at higher risk of readmissions. Factors like poor living situation, lack of means for transportation, potential lower level of education leading to decreased medication compliance and clinic follow ups could be attributed to these findings. Interventions targeting this population can help reduce healthcare burden and patient morbidity significantly. [Table: see text]

Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease

The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC-macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.

How does sickle cell disease affect the peri-operative outcome in patients undergoing total knee arthroplasty? A large-scale, National Inpatient Sample-based study.

In view of the vaso-occlusive pathophysiology affecting osseous micro-circulation, sickle cell disease (SCD) is well known to present with diverse skeletal and arthritic manifestations. With prolonged life-expectancy over the past decades, there has been a progressive increase in the proportion of SCD patients requiring joint reconstructions. Owing to the paucity of evidence in the literature, the post-operative complication rates and outcome in these patients following total knee arthroplasty (TKA) are still largely unknown. Based on the National Inpatient Sample (NIS) database (using ICD-10 CMP code), patients who underwent TKA between 2016 and 2019 were identified. The cohort were classified into two groups: A-those with SCD; and B-those without. The data on patients' demographics, co-morbidities, details regarding hospital stay including expenditure incurred, and complications were analyzed and compared. Overall, 558,361 patients underwent unilateral, primary TKA; among whom, 493 (0.1%) were known cases of SCD (group A). Group A included a significantly greater proportion of younger (60.14 ± 10.87 vs 66.72 ± 9.50years; p < 0.001), male (77.3 vs 61.5%; p < 0.001); and African-American (88.2 vs 8.3%B; p < 0.001) patients, in comparison with group B. Group A patients were also at a significantly higher risk for longer duration of peri-operative hospital stay (p < 0.001), greater health-care costs incurred (p < 0.001), and greater need for alternative step-down health-care facilities (p < 0.001) following discharge. Among the SCD patients, 24.7%, 20.9% and 24.9% developed acute chest syndrome, pain crisis and splenic sequestration crisis, respectively during the peri-operative period. Group A patients had a statistically greater incidence of acute renal failure (ARF; p = 0.014), need for blood transfusion (p < 0.001) and deep vein thrombosis (DVT; p = 0.03) during the early admission period. The presence of SCD substantially lengthens the duration of hospital stay and enhances health care-associated expenditure in patients undergoing TKA. SCD patients are at significantly higher risk for systemic complications including acute chest syndrome, pain crisis, splenic sequestration crisis, acute renal failure, higher need for blood transfusions and deep venous thrombosis during the initial peri-operative period following TKA.

Relationship between Genotype Variants and the Age of First Acute Splenic Sequestration in Patients with Sickle Cell Disease in a Tertiary Center of Saudi Arabia

BACKGROUND: Acute splenic sequestration crisis (ASSC) is one of the earliest life-threatening complications of sickle cell disease (SCD). Here, we aimed to identify the relation between the age of the first splenic sequestration episode and SCD variants. Episodes of acute splenic sequestration before 1 year of age are associated with a higher risk of recurrence. METHODS: We carried out a retrospective chart review study from the medical charts of SCD patients ≤12 years admitted to the Department of Pediatric Hematology King Saud Medical City, Riyadh with the first episode of ASSC and no other complications from January 2014 to December 2019. RESULTS: We included 47 patients (46.8% males, 53.2% females) diagnosed with SCD and having experienced their first ASSC in this review. The mean age of the patients at which the first episode of splenic sequestration happened was 3.26 years. The genotype distribution in the population was 74.5% HBSS, 21.3% HBS β0 thalassemia, and 4.3% HBSβ+ thalassemia. The crisis precipitated with fever in 74.5% of patients. Treatment included programmed blood transfusion (46.2%), splenectomy (29.8%). The recurrence rate after the first episode of ASSC was 59.6%. The high rate of recurrence was mainly due to the early age of presentation and poor compliance with suggested treatment. The use of hydroxyurea in 19.1% of patients showed a decrease of recurrence of ASSSC by 66.6% of patients. CONCLUSION: The study concluded that the HBSS variant of SCD had the earliest presentation with the first episode of ASSC but the differences were numerical without any statistical difference. Earlier age of presentation is associated with a higher rate of recurrence, but the difference was numerical not statistically significant. Our study shows hydroxyurea decreased recurrent splenic sequestrations; further research would help in establishing its role

Splenic Complications in Sickle Cell Disease: A Retrospective Cohort Review

▪Splenic dysfunction, particularly acute splenic sequestration crisis (ASSC), is a leading cause of death in the first decade of life of patients with sickle cell disease (SCD). Despite the severity of splenic disease in SCD, few large-scale studies have been performed to assess the natural progression of splenic complications, particularly in the less common sickle cell genotypes and with the onset of early use of hydroxyurea.We performed a retrospective chart review of patients with SCD born between January 2011 and December 2018 and treated at the Texas Children's Hospital Sickle Cell Center. We extracted data from our electronic medical record system to identify patients with documented splenic complications based on ICD9 and ICD10 codes. We then reviewed charts for these patients to confirm diagnoses and obtain additional information about these complications.We identified 688 patients treated for SCD at our center during the study period. Of these, 113 (16.4%) were diagnosed with one or more splenic complications. The overall prevalence of splenic complications was highest in patients with hemoglobin Sβ 0 thalassemia (Sβ 0) at 50.0%, compared to 20.7% in hemoglobin SS (SS) patients, 6.9% in hemoglobin SC (SC) patients, and 0% in hemoglobin Sβ + (Sβ +) patients and patients with other genotypes (Table 1). ASSC and splenectomy were likewise most prevalent in Sβ 0, less so in SS, and rare in SC, Sβ +, and other genotypes.To further delineate the incidence of ASSC, we performed an in-depth analysis of patients from our cohort for whom detailed information was available. Compared to patients with the SS genotype, the incidence rate ratio (IRR) for ASSC was significantly higher for Sβ 0 patients and significantly lower for SC patients (Table 2). The mean age of onset of ASSC was similar between SS, Sβ 0, and SC patients, but survival curves for time to the first event differed significantly between genotypes.We examined the association between early hydroxyurea therapy and ASSC in SS and Sβ 0 patients by comparing patients who initiated hydroxyurea therapy by the age of two years to those who initiated therapy after this age. ASSC were more frequent among patients initiated on hydroxyurea by the age of two years (Table 3, upper panel). We also compared patients on hydroxyurea to those not on this therapy and found a similar effect, with ASSC occurring more frequently among patients on hydroxyurea (Table 3, lower panel). Survival curves for time to first ASSC also diverged significantly between these groups of patients.Our data indicate that the prevalence and severity of splenic problems vary widely between different sickle cell genotypes in the first decade of life, with SC patients having relatively mild complications while Sβ 0 patients have the most severe and frequent complications. The association between hydroxyurea use and incidence of ASSC also suggests that hydroxyurea therapy may increase the risk of this complication of SCD, particularly when initiated before two years of age. [Display omitted] DisclosuresGeorge: Global Blood Therapeutics: Consultancy, Speakers Bureau; Wolters Kluwer: Patents & Royalties.

Morbidity Pattern in Sickle Cell Disease in Central Gujarat, India — Single Centre Perspective

INTRODUCTIONSickle cell disease (SCD) poses a considerable health burden in India. About 20 per cent of children with SCD die by the age of two and 30 per cent children with SCD among the tribal community die before they reach adulthood is reported in one ICMR survey. As they are vulnerable to mortality, require regular clinical follow up. This retrospective analysis study was, undertaken to evaluate the morbidity pattern in SCD patients observed in patients followed up at our centre METHODSSCD patients registered and followed up at HOCC between Jan 2011 to June 2017 were included in this study. At first visit to HOCC baseline CBC, PLT, RBC indices, LFT, Creatinine, S.Ferritin,Urine R/M,HPLC pattern,USG abdomen were noted. All 342 patients registered at HOCC were advised to take Hydroxyurea (dose adjusted according to CBC), Folic acid, B12, Multivitamin and Calcium. Vaccination given to selected patients. Out of these 342 patients, 57(16%) patients had 79 hospitalization events, 11 patients (3.2%) had recurrent hospitalizations. All patients were hospitalized in Sterling Hospital Vadodara.CBC PLT,RBC indices,LFT, RFT done on admission in all patients, Blood and urine culture, PS for MP, Dengue NS1,IgG,IgM, in all febrile patients, Viral markers ,CXR,USG Abdomen, MRI pelvis with HIP done in selected patients. All hospitalized patients received adequate hydration by IV fluids.Paracetamol, Contramol, Buprenorphine transdermal patch for pain relief. PCV transfusion to keep HB 8 to 10 gm%.Antibiotics if any evidence of infection, pre-emptive or based on culture report.Oxygen by nasal prongs or NRBM,NIV or Invasive Ventilator support to maintain SPO2 more than 95%.Exchange transfusion if no pain relief in vasoocclusive crisis in 48 hrs or has Acute Chest Syndrome, Splenic Sequestration or Hepatic cell crisis RESULTSSeventy nine hospitalization events of 57 SCD patients during study period were evaluated to analyse morbidity pattern. Out of 57 patients 47 (82%)patients were not taking regular treatment,10 patients (17%)inspite of regular treatment and follow up developed morbid events .Age range 7 yrs to 57 years, M:F ratio 2:1(Male 38,Female 19),5(8%) patients were pregnant ,Vaso-occlusive crisis was most common morbid event 46(58% ) followed by LRTI,ARDS,Acute chest syndrome 9(11%),Hepatic cell crisis 8(10%),Septicemia 6(7.5%),Splenic sequestration 3(3.7%), Aplastic crisis 2(2.5%),Dengue 2(2.5%),Vivax Malaria 2(2.5%),AVN 2(2.5%).Septic arthritis 1(1.2%),Majority of hospitalization observed in month of July and Aug followed by in September ,October, least admissions in the month of April and December,HB F level was more than 20% in 16 patients(28%) and between 10 to 20 % in remaining patients(72%).Duration of hospitalization less than 10 days in majority 69(87%),14 days in 10(12%),Ventilator support was required for 7(8.8%) ,O2 by NRBM in 2(2.5%) ,O2 by nasal prongs 1(1.2%),Blood and Urine Culture for gram negative bacterial growth detected in 6(7.5%),none of the patient had gram positive growth, Exchange transfusion was required for 19 patients(24%) Outcome was favourable in 75(94%),whereas 4 patients(5%) who were not on regular follow up and they reached hospital almost 72 hrs after initial symptoms of crisis succumbed ,Major cause of mortality was Hypoxia, Septicemia with multiorgan failure on day1 of admission in hospital with rapid deterioration within 24 hrs. CONCLUSIONSCD patients on Hydroxyurea and supportive therapy have significantly lower incidence of morbid events requiring hospitalization.Vaso-occlusive crisis is a major reason of hospitalization. Gram negative septicaemia is the leading cause of infective morbidity. Hepatic cell crisis observed predominantly in ethanol addicted patients, Mortality is highest with delayed treatment of ARDS, Acute chest syndrome. Four strong predictors of good outcome are adequate hydration, early control on infection, maintaining adequate oxygenation and early initiation of treatment before organ failure sets in. DisclosuresNo relevant conflicts of interest to declare.

The spectrum of splenic complications in patients with sickle cell disease in Africa: a systematic review.

The majority of the global population of sickle cell disease (SCD) patients resides in Africa. Individuals with this condition are at great risk of serious infections and early mortality secondary to splenic dysfunction without preventative measures. This review investigated the spectrum of splenic complications encountered in SCD among populations in Africa. We systematically searched several databases for all articles published through March 3, 2020. We included 55 studies from 14 African countries. This review reveals the difference in frequency of splenic complications in SCD in Africa when compared with their counterparts in the United State and Europe. While several studies (n=45) described splenomegaly with a prevalence of 12% to 73% among children, and 4% to 50% among adults with HbSS, the reported prevalence for acute splenic sequestration crisis (n=6 studies) and hypersplenism (n=4 studies) was <10% and <5% respectively. A total of 30 surgical splenectomy was reported across eight studies. Only two (3.7%) studies provided data on spleen function. A conflicting pattern was observed amongst studies that evaluated the relationship between splenomegaly and the presence of bacterial and malaria infections. This review reveals the paucity of studies describing the role of SCD-induced splenic dysfunction in morbidity and infection related mortality in Africa.

Effectiveness of Comprehensive Newborn Screening Program of Sickle Cell Disease on the Childhood Morbidity and Mortality of the Disease: A Systematic Review and Meta-Analysis

Sickle cell disease is a multisystem disorder associated with severe complications and premature death. To address the morbidity, disability, and mortality of inherited disorders, the implementation of newborn screening programmes are considered pivotal public health service intervention. Due to ethical consideration there are no RCTs that prove the benefits of comprehensive newborn screening (Lees, Davies and Dezateux, 2000). However, many evidences suggested early diagnosis and treatment can improve outcomes and survival of patients (Gaston et al., 1986; King et al., 2007). As such, an economic analysis reviewed many studies, cited that the pre-clinical diagnosis of SCD had twofold cost-effectiveness compared to symptomatic diagnosis (Grosse, Olney and Baily, 2005). The aim of this study was to assess the impact of the newborn screening program on the morbidity and mortality of disease among the children by assembling results from cohort studies. DESIGN AND METHODS The systematic review was performed in accordance with the PRISMA guidelines. Medline, EMBASE, and Cochrane Library were searched for cohort studies that addressed the sickle cell disease morbidity and mortality of the disease among children will consider eligible. The phenomena of interest were mortality, infection, stroke PICO have been translated to keywords and MeSH terms with search limit under 18 years old and date set until July 2020. Two reviewers assessed the quality of included cohort studies individually using Newcastle-Ottawa scale (NOS). Subsequently, the data were extracted in Microsoft Word. In case of disagreement, were settled by discussion. The incidence rates per 100 patient year and 95% confidence intervals were pooled to random-effects meta-analysis using RevMan5.4. Studies' heterogeneity identified by chi-squared test and the I2 statistic. RESULTS Eight studies included that met inclusion criteria two studies were from USA (Quinn et al., 2008 and Gill et al., 1995) , 1 from UK (Telfer et al., 2007), 1 from Belgium(Lê et al., 2010), 1 from Jamaica (King et al 2007), 1 from Africa (Rahimy et al, 2003), 1 from India (Upadhye et al., 2016) and 1 from Brazil (Rezende et al., 2018). The total number of participants in the 8 cohort studies were 2377 SCD patients (mean 297.1 and SE 73.9), that includes patients with the four common SCD genotypes: HbSS, HbSC, Hb Sβ+ and HbSβ0. The median age was 6.5 year (IQR: 4.95), with 9623 total years of follow up. The pooled incidence rate of SCD associated mortality per 100 patient year was 0.65 (95%CI 0.35-0.94; I2= 89%; p &amp;lt; 0.00001). While the infection incidence rate 17.74 (95%CI; 11.57-23.91; I2= 100%; p&amp;lt; 0.00001), Stroke 1.04(95% CI 0.60-1.47; I2= 78%; p&amp;lt; 0.0001), Acute chest syndrome 12.55(95% CI; 7.70-17.41; I2 =97%; p&amp;lt; 0.00001), Acute splenic sequestration crisis 1.95 (95% CI 1.31-2.59; I2= 69%; p=0.003) and Vaso-occlusive crisis 52.45(95% CI 45.67-59.14; I2= 92%; p&amp;lt; 0.00001). DISCUSSION In this systematic review and meta-analysis combining 8 cohort studies, pooled mortality rate was 0.65 per 100 patient-year, similar to (0.64) meta-analysis of 15 studies reported previously (Wastnedge, 2018). Furthermore, our study reported that the total infection rate was 17.7 per 100 patient-year. However, this result of infection cannot be considered a true gold standard and due to the variation in definitions used and other methodological heterogeneity. For example, Africa-based cohort study reported 23.2 per 100 patient-year attacks of malaria and fatal pneumococcal meningitis despite the use of antimalarial prophylaxis and anti-pneumococcal vaccine (Rahimy et al., 2003). Another notable result, Hemoglobin SC cohort study stated that the incidence of infections was, 62.2 episodes (59.8-64.6) per 100 patient-years. They assumed that might be due to higher impaired splenic function in HbSC patients compared to HbSS (Rezende et al., 2018). CONCLUSION This first systematic review and meta-analysis of cohort studies provided evidence supporting the sickle cell newborn screening program. However, still infection and pain episodes are the highest incidence symptoms. Despite children survival increasingly improved, disease burden remains at a peak in developing countries. One limitation of this study is high heterogeneity and this mainly due to countries disparity of included studies and variance in definition of events, particularly infection. Table Disclosures Inusa: Novartis: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Bluebird bio: Research Funding; AstraZeneca: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Vertex: Research Funding.

9 Acute Splenic Sequestration Crisis in an Infant With Sickle Cell Trait

9 Acute Splenic Sequestration Crisis in an Infant With Sickle Cell Trait

Prevalence of Complications of Sickle Cell Disease at Makkah Al-Mukaramah, Saudi Arabia, 2017

Background: The studies in the Middle East Arabs have found that there are specific risk factors making Sickle cell disease (SCD) more prevalent in that part of the world, which has the fast growing in the population and the increase in consanguinity marriage. Despite of that, there are no studies conducted in Makkah Al-Mukarramah or even in all Saudi Arabia (KSA) regions that, focusing on the complications of SCD and its related risk factors. Objectives: To determine the pattern of admission and estimate the prevalence of different complications of SCD among children in Makkah Al-Mukaramah, KSA, 2017. Patients and methods: A retrospective, analytic, noninterventional cohort study was carried out in Makkah Al- Mukaramah, KSA over a 6 months period (from first of June 2017 to end of December 2017). The study reviewed the medical files of all sickler patients who have been admitted to the pediatric departments of the involved hospitals in the given time. Records of patients having combined thalassemia disease and/or Glucose 6 Phosphate Dehydrogenase Deficiency (G6PD) were excluded from the study. The required data were collected by using hard copies of a well-designed, semi-structured, valid and reliable checklist. Results: The study included 145 medical files of pediatric patients with SCD. Their age ranged between one day to 14 years with a Mean ± SD of 7 ± 3.6 years. Males represent 54.5% of them. Almost two-thirds of patients (67.6%) were Saudis. All cases live outside Makkah (n=5) were diagnosed as Sickle cell anemia with Vaso-occlusive crisis (VOC) whereas 47.1% of those live in Makkah were diagnosed by VOC at admission. The most frequent complication was VOC (55.9%), followed by infection (9%). Overall, 41.4% of SCA pediatric patients were admitted once whereas 25.5% were admitted more than 5 times. Acute splenic sequestration crisis was reported among 3.1% of Saudi patients compared to 12.8% of non-Saudi patients. This difference was statistically significant. Other complications were not significantly related to patients` nationality. Conclusion: The most frequent complication of SCD was VOC. Primary prevention of the acute complications of SCD should base on health care provider with expertise in SCD, preferably hematologist. In addition to prevention of complications through the use of penicillin prophylaxis started in the newborn period, appropriate immunizations, and blood transfusions for those at risk for stroke.

The Effect of Splenectomy on Development of Cerebral Vasculopathy in Children with Sickle Cell Disease

Splenic complications are often seen in pediatric patients with sickle cell disease and could lead to an increase in morbidity and mortality. The most common splenic event is acute splenic sequestration crisis (ASSC) which has been often managed with surgical splenectomy. Although splenectomy has been the treatment of choice for years, the long term complications of splenectomy on vascular events has not been broadly assessed. It has been reported that splenectomy could lead to vascular complications and increased risk of thrombosis in chronic hemolytic conditions. As it was proposed, it could be partially due to the shift form extravascular hemolysis to intravascular leading to the scavenging of nitric oxide (Kato et al, 2007). In terms of cerebral vasculopathy in children with sickle cell disease, screening is usually done by measuring blood flow velocity in the main cerebral arteries using Transcranial Doppler Ultrasonography (TCD). In 2014 Peter Soh and Abdul Siddiqui reported an increased risk of cerebrovascular complications in splenectomized patients with sickle cell disease (3), but it has not been confirmed by other publications. The aim of our study is to evaluate how splenectomy affects cerebral blood flow measured by TCD in patients with homozygous HbS. The secondary aim is to evaluate if Hydroxyurea (HU) has a protective effect on the development of cerebral vasculopathy in splenectomized patients.We performed a retrospective chart review of patients with sickle cell disease Hb SS and Hb S beta thalassemia followed at the Marian Anderson Center at St. Christopher's Hospital for Children, Philadelphia between 1999 and 2016. In the final analysis we included TCD data on 153 patients, of which 36 had undergone splenectomy. A total of 516 TCD studies were collected, of which 145 patients had a history of splenectomy. Of the 516 TCD assessments in this sample, 70 (13.6%) patients were on HU of which 21 had undergone splenectomy.Pearson correlations were calculated to explore linear associations of mean cerebral blood flow velocities (CBFV) with age at the time of TCD assessment, time since splenectomy, and TCD values. Associations of CVFV with splenectomy and with HU administration for splenectomy patients were analyzed with analysis of covariance (ANCOVA). The association of time elapsed since splenectomy to TCD measure, adjusting for age at TCD assessment, was explored with multiple linear regression models. Statistical analysis was conducted with SPSS ver. 24.0.Age at the time of TCD was significantly correlated with mean right cerebral artery (RMCA) (r = -.199, p < .001), LMCA (r = -.181, p < .001), RDICA (r = -.110, p = .047), LDICA (r = -.142, p = .01) and Basilar (r = -.186, p = < .001) velocities. Tables 1 and 2 present estimated mean TCD values (calculated adjusting for age at the time of TCD). In analysis of all TCDs, the estimated mean (RMCA) velocity was significantly higher in patients with history of splenectomy than in patients without splenectomy, (Table 1). There was also significant difference in LDICA, RDICA and right posterior cerebral artery (RPCA) velocities, all of which were higher in splenectomized patients (Table 1). When analyzing the velocities according to time since splenectomy, there were significant associations between years since splenectomy (0-5, 5-10 and >10years) and with both RMCA and LMCA abnormalities. Analysis of TCD results in splenectomized patients on HU versus non-HU, indicates all estimated mean TCDs except for RPCA, are lower for the patients on HU (Table 1), with RMCA and LMCA statistically significant.Based on our analysis we conclude that in patients with homozygous HbS disease history of surgical splenectomy increases the risk for cerebral vasculopathy. It remains unclear if cerebral vasculopathy develops as a result of splenectomy or if there is a preexisting factor leading to the development of both complications. The other important finding of our study is a protective effect of hydroxyurea on the development of cerebral vasculopathy in splenectomized patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease.

A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient’s peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined.

Accuracy of Administrative Coding for Sickle Cell Disease

BackgroundAdministrative data are increasingly used in sickle cell disease (SCD) research to study large numbers of patients at low cost. However, the validity of research with these data depends on the accuracy of administrative coding, which has been understudied in SCD. In particular, the validity of ICD-9CM coding for SCD's clinical hallmark, vaso-occlusive crisis (VOC), has not been reported. Therefore, we aim to describe the accuracy of ICD-9CM coding for VOC, acute chest syndrome (ACS), and acute splenic sequestration crisis (ASSC) in addition to SCD genotypes.MethodsAdministrative coding for all acute care visits (emergency department [ED], inpatient observation, and inpatient hospitalization) in SCD patients was captured for the 2013 calendar year at Children's Medical Center Dallas (CMCD) by query of administrative records. SCD visits were identified using the ICD-9CM codes 282.4x and 282.6x in the primary or any of 14 secondary code positions. From the administrative data, VOC was defined by the use of the "in crisis" codes (282.42, 282.62, 282.64, or 282.69). ACS was defined by 517.3 and ASSC by 289.52. Genotypes were defined as HbSS - 282.61 or 282.62; HbSC - 282.63 or 282.64; and HbS-BetaThal - 282.41 or 282.42.For the chart review, all visits were independently evaluated by two reviewers with the senior author settling disagreements. Previously-published consensus definitions were used for the complications of interest: VOC was defined as new onset of pain lasting at last 4 hours for which there is no other explanation; ACS was defined by new pulmonary infiltrate on chest X-ray with associated fever or respiratory symptoms; and ASSC was defined as splenic enlargement leading to anemia (hemoglobin >2g/dL under baseline), typically with thrombocytopenia. The primary reviewers and senior author evaluated 10 cases for the purpose of consensus-building before beginning data abstraction.Data capture included demographics and cause of the visit. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of ICD-9CM coding for VOC, ACS, ASSC, and the SCD genotype were calculated. The LR+ and LR- were prevalence-weighted.ResultsFrom 448 patients, 1107 acute care visits were identified at CMCD in 2013. Patients had a median age of 8.2 years (range 0.1 - 33.9 years). Females accounted for 53% of visits. Inpatient hospitalization accounted for 374 visits (34%) whereas ED-only visits accounted for 681(61%) and inpatient observation 52 (5%). The prevalence of SCD genotypes included 69% HbSS, 19% HbSC, and 7% HbS-BetaThal. VOC, ACS, and ASSC were the "true cause" for 36% (n=402), 6% (n=68), and 1% (n=13) of acute care visits, respectively.The results of the primary analyses are displayed in the table. Agreement between reviewers for VOC and ACS was 91% (kappa = 0.80) and 99% (kappa = 0.92), respectively. When VOC was falsely coded (n=176), the most common true diagnoses were ACS (26%), fever (24%), chronic pain exacerbation (14%), and abdominal pain (10%). When ACS was falsely coded (n=21), VOC was the most common true diagnosis (71%). Of 25 (2.2%) patients incorrectly coded for SCD, 14 had sickle trait.ConclusionsICD-9CM coding for VOC demonstrated poor accuracy; however, coding for ACS and ASSC was remarkably sensitive and specific. Genotype coding lacked sensitivity with otherwise variable results. Unfortunately, coding for SCD in ICD-10 differs minimally from ICD-9CM. Therefore, these data provide an impetus to restructure ICD coding for SCD.Table 1Sensitivity (95% CI)Specificity (95% CI)PPV(95% CI)NPV(95% CI)Postive Likelihood Ratio(95% CI)Negative Likelihood Ratio(95% CI)VOC91.8(88.6-94.2)75.0(71.6-78.2)67.7(63.6-71.6)94.1(91.8-95.9)2.1(1.8-2.4)0.06(0.04-0.08)ACS92.6(83.0-97.3)98.0(96.9-98.7)75.0(64.1-83.5)99.5(98.8-99.8)3.0(2.0-4.4)0.004(0.002-0.01)ASSC92.3(62.1-99.6)99.8(99.3-100.0)85.7(56.2-97.5)99.9(99.4-100.0)6.0(1.6-22.0)0.0009(0.0001-0.006)HbSS genotype74.2(70.9-77.2)67.7(62.5-72.6)83.8(80.7-86.4)53.8(49.0-58.6)5.1 (4.2-6.1)0.9(0.8-1.0)HbSC genotype31.0(24.9-37.7)99.6(98.8-99.9)94.3(85.3-98.2)85.8(83.5-87.9)16.5(6.4-42.8)0.16(0.14-0.19)HbS-BetaThalgenotype57.1(45.4-68.2)99.6(98.9-99.9)91.7(79.1-97.3)96.9(95.6-97.8)11(4.3-28.2)0.03(0.02-0.05) DisclosuresMcCavit:Pfizer: Research Funding; Novartis: Speakers Bureau; Novartis: Speakers Bureau; Gensavis LLC: Research Funding; Pfizer: Research Funding.

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients’ charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

Infectious complications after surgical splenectomy in children with sickle cell disease

ObjectiveTo evaluate the frequency of infectious complications in children with sickle cell disease (SCD) after surgical splenectomy for acute splenic sequestration crisis. MethodsRetrospective cohort of children with SCD who were born after 2002 and were regularly monitored until July 2013. Patients were divided into two groups: cases (children with SCD who underwent surgical splenectomy after an episode of splenic sequestration) and controls (children with SCD who did not have splenic sequestration and surgical procedures), in order to compare the frequency of invasive infections (sepsis, meningitis, bacteremia with positive blood cultures, acute chest syndrome and/or pneumonia) by data collected from medical records. Data were analyzed by descriptive statistical analysis. Results44 patients were included in the case group. The mean age at the time of splenectomy was 2.6 years (1-6.9 years) and the mean postoperative length of follow-up was 6.1 years (3.8-9.9 years). The control group consisted of 69 patients with a mean age at the initial follow-up visit of 5.6 months (1-49 months) and a mean length of follow-up of 7.2 years (4-10.3 years). All children received pneumococcal conjugate vaccine. No significant difference was observed between groups in relation to infections during the follow-up. ConclusionsSurgical splenectomy in children with sickle cell disease that had splenic sequestration did not affect the frequency of infectious complications during 6 years of clinical follow-up.