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 two 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 to these complications without necessarily being the trigger. 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.

Acute Splenic Sequestration: A Rare and Severe Complication of Sickle Cell Anemia in Adults: About a Case Report

Acute splenic sequestration is a well-known complication of sickle cell disorders, marked by a sudden drop in hemoglobin levels and significant, painless splenomegaly. This condition is typically observed in children with homozygous sickle cell disease. However, it is rarely reported in adults with heterozygous sickle cell conditions. We describe the case of a 28-year-old patient with a history of hemoglobin SC disease who suffered an acute splenic sequestration crisis. We review the CT characteristics of splenic sequestration, including splenic enlargement and an irregular peripheral rim of hypoenhancing or hypoechoic tissue, and discuss differential diagnoses. While acute splenic sequestration is predominantly a severe complication in children, timely diagnosis and treatment particularly red blood cell transfusions can lead to full recovery.

Splenic complications in pediatric sickle cell disease: A retrospective cohort review.

To delineate the natural history of splenic complications other than loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children's Hospital. We determined the dates of diagnoses of splenic complications, the number of acute splenic sequestration crises (ASSC), and hydroxyurea treatment in pediatric patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC. The cumulative prevalence of splenic complications was 24.7% for splenomegaly, 24.2% for ASSC, 9.6% for hypersplenism, and 5.6% for splenectomy. The cumulative prevalence of splenic complications was highest in patients with hemoglobin Sβ0 (69.2%), intermediate in hemoglobin SS (33.3%), low in hemoglobin SC (9.0%), and non-existent in hemoglobin Sβ+. The overall event rate of ASSC was 8.3 per 100 patient-years. The event-rate was 28.4 for hemoglobin Sβ0, 10.9 for hemoglobin SS, and 3.5 for hemoglobin SC. Patients with hemoglobin SS and hemoglobin Sβ0 on hydroxyurea therapy had a significantly higher occurrence of ASSC than those who were not, with event rates of 14.2 and 3.1, respectively. The event rate was also higher for children who started hydroxyurea before age 2years than for those who started after this age (19.8 and 9.2, respectively). The prevalence and severity of splenic problems vary widely between different sickle cell genotypes, with hemoglobin Sβ0 having the most severe complications. Hydroxyurea therapy is associated with increased incidence of ASSC, particularly when initiated before 2years of age.

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.

The German sickle cell disease registry reveals a surprising risk of acute splenic sequestration and an increased transfusion requirement in patients with compound heterozygous sickle cell disease HbS/β-thalassaemia and no or low HbA expression.

Patients with sickle cell disease (SCD) in Germany exhibit a substantial genetic diversity in the β-globin genotype. Data collected by the national German SCD registry reflect this diversity and allowed us to analyze the phenotypes associated with different SCD genotypes. Our study focused on 90 patients with HbS/β-thalassaemia (HbS/β-thal) and compared these to patients with HbSS and HbSC. Patients with HbS/β-thal were classified into three groups: HbS/β0-thal (no HbA), HbS/β+-thal (HbA < 14%), and HbS/β++-thal (HbA≥14%). In comparison to HbSS, patients with HbS/β++-thal had higher Hb-levels, lower hemolytic activity and rarely required red blood cell transfusions. HbS/β0-thal and HbS/β+-thal closely resembled each other and are jointly referred to as HbS/β0/+-thal. Compared to HbSS, patients with HbS/β0/+-thal experienced a similar frequency of vasoocclusive crises and degree of hemolysis. However, the frequency of red blood cell transfusions (0.6 vs. 0.39/year, p = .0049) and splenic sequestration crises (42.4 vs. 15.5% of patients, p = 3.799e-05) was higher in HbS/β0/+-thal than in HbSS, but close to zero in HbS/β++-thal. In conclusion, the level of HbA expression determines the phenotype of HbS/β+-thal. HbS/β-thal expressing no or little HbA is hematologically similar to HbSS, but causes a previously unknown high risk of splenic sequestration.

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).

Avascular Bone Necrosis in Pediatric Patients with Sickle Cell Disease in Basrah, Iraq

BACKGROUND: Avascular necrosis (AVN) is regarded as a manifestation of severe sickle cell disease (SCD), with the femoral head being the most affected. OBJECTIVES: The main objectives of this study were to look for the frequency of AVN in pediatric patients with SCD, evaluate the clinical pattern and severity of AVN, and study the possible risk factors associated with AVN. MATERIALS AND METHODS: A cross-sectional study has been conducted on SCD patients, aged 6–18 years, who visited the Basrah Center for Hereditary Blood Diseases from the first of February 2021 to August 2021. Patients were screened for AVN by hip plain radiography and magnetic resonance imaging. The modified Ficat-Arlet staging system was used to classify different stages of AVN. RESULTS: The total number of screened patients was 291; 193 (66.3%) had sickle cell anemia, 71 (24.4%) with S/β0 thalassemia, 21 (7.2%) with S/β+ thalassemia, and 6 (2.1%) had S/D disease. Fifty-eight (19.9%) patients were found to have different stages of AVN; 7 (12.1%) were asymptomatic and 51 (87.9%) were symptomatic. The logistic regression analysis has revealed that frequent vaso-occlusive crises requiring hospitalization (B = 1.576, P = 0.003), acute splenic sequestration crises (B = 1.256, P = 0.003), homozygous sickle hemoglobin genotype (B = −0.208, P = 0.001), and low reticulocyte count (B = 1.452, P = 0.027) are significant variables associated with AVN. CONCLUSION: AVN was reported in a significant percentage of pediatric patients with SCD and was associated with selected indicators of disease severity. Further studies that evaluate the natural history, progress of AVN, and variations in selected variables over time like reticulocytes and the co-inheritance of α-thalassemia are important.

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

Identification of Risk Factors for Sickle Cell Crisis Readmissions: A Community Center Experience

Introduction: Sickle cell disease (SCD) exerts a significant morbidity and mortality burden worldwide, with 300,000 infants being diagnosed with SCD annually. The term sickle cell crisis (SCC) encompasses several acute conditions under its umbrella, namely vaso-occlusive crisis, aplastic crisis, splenic sequestration crisis, dactylitis, and acute chest syndrome. SCC has been established to be a known cause of readmissions across the year with studies showing 17% of the population returning two to three times annually. This has resulted in a high mean length of stay for this diagnosis (5.3 days) in comparison to an index hospitalization (4.9 days), with a mean cost of $8485 per admission. Readmissions owing to SCC have relayed a significant burden of 95,445 hospitalization days and a total charge of $609 million in the US. Despite the high morbidity and financial burden it imposes, limited studies have been performed studying the risk factors for readmissions in these patients. Despite the establishment of a framework of recommendations and guidelines, there appears to be a high incidence of readmissions and discrepancies in adherence to evidence based recommendations. We performed a retrospective study to evaluate the risk factors for patients hospitalized in three community hospitals between October 2021 and August 2022. Methods: The admissions database of a community health system across three hospitals was scanned for admissions with SCC between the time period October 2021 and August 2022. ICD9 and ICD-10 codes of SCC were used. 50 patients found with the admitting diagnosis code of SCC and 103 encounters were included. After excluding patients who left against medical advice before initiation of treatment, those with the wrong diagnosis and incomplete documentation, a cohort of 47 patients with 100 encounters was attained. Patient charts were reviewed and demographic variables such as age, gender and race were studied. Readmissions and the length of stay were assessed for risk factors with the help of a chi square test. Risk factors assessed included use of pain medications (opioids with non-steroid anti-inflammatory medications versus monotherapy), use of IV Fluid Boluses, placement of Hematology consult, having an established primary care physician and the use of hydroxyurea as a home medication. Results: 87% of the patient population was African American with equal gender distribution (Males 51%; Females 49%). 59% of the patient population lay in the age group of 18-35. 49% of the patient population was noted to have readmissions within the time frame studied with 29% of the patient population having a length of stay of more than 3 days. 100% of the patients without an established primary care physician (PCP) were noted to have readmissions in comparison to 3.6% of the patients with an established PCP (p&amp;lt; 0.01). Length of stay was less than 3 days for 91.3% of the patients treated with the combination of opioids and NSAID's for pain in comparison to 64.9% of the patients that were not treated with this combination (p= 0.014). It was noted however, that 37% of the population was on hydroxyurea outpatient and 44% of the cases had involved hematology for the inpatient management of these patients. IV Fluid boluses and their association with length of stays in our patient population was unequivocal. 52.7% of the patients on hydroxyurea had readmissions within 30 days as opposed to 28.6% of the patients not on the drug. This was likely explained by non-compliance to the medication. No deaths were reported in this patient cohort. Conclusion: Several risk factors for readmissions in SCC patients exist in the community setting. Our findings reported that lack of close outpatient follow up is associated with higher readmission rates. In addition, we also observed that the type of medical pain management (combination vs monotherapy) played a role in length of stay with combination therapy being linked to shorter hospitalization stay. Integrated education for various medicine specialties regarding management guidelines should be instituted. In addition, maximum utilization of social work and case management for ensuring close follow ups for this patient population may further mitigate readmissions of SCC patients in the community setting.

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 ( &lt; $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]

Clinical Profiles of Children With Sickle Cell Anaemia Presenting With Acute Clinical Events: A Single-Center Study.

Sickle cell disease is a common genetic disorder characterised by chronic haemolytic anaemia and vaso-occlusive crisis. Sickle cell anaemia (SCA) has both short-term effects in the form of acute clinical events and long-term repercussions seen with chronic multiorgan involvement. It is associated with significant morbidity and mortality. In India, the disease is largely undocumented. Thus, there is an urgent need to highlight the features of the disease so that locally appropriate models of care may be implemented. This study aims to evaluate acute clinical events in SCA and to provide data that may help to reduce the rate of morbidity and mortality associated with this disease by early interventions. A cross-sectional observational study was conducted between November 2020 and May 2022 at Indira Gandhi Government Medical College and Hospital, Nagpur, Central India. The inclusion criteria included previously diagnosed patients of SCA (homozygous sickle cell disease) on high-performance liquid chromatography (HPLC) between the age groups of six months and 12 years, presenting with acute clinical events. The exclusion criteria included patients younger than six months and older than 12 years of age, and all patients with other haemoglobinopathies and sickle cell trait. The study was approved by the Institutional Ethical Committee. All the data was entered into a well-designed Microsoft Office Excel spreadsheet (v 2019, Microsoft, Washington, USA). All the clinical, biochemical, and haematological data were tabulated and analysed. A total of 100 children with sickle cell disease diagnosed by HPLC were enrolled during the study period. About 215 acute clinical events among the 100 cases were recorded, for which they were admitted to the paediatric ward or PICU. The majority (35%, n=35) were seen in the age group of six to nine years (school-going age). About 52% were male and 48% were female (male-to-female ratio= 1.08:1). Pain was the most common symptom. The highest incidence of 36.75% (n=79) was seen with acute painful crises and was the most common indication of hospitalisation, followed by acute febrile illness (AFI) (34.42%, n=74), aplastic crisis (10.23%, n=22), splenic sequestration crisis (9.77%, n=21), hepatobiliary involvement (3.72%, n=8), acute chest syndrome and haemolytic crisis (each 1.86%, n=4), and stroke (1.40%, n=3). In cases of having foetal haemoglobin (HbF) ≥20%, the incidence of acute painful crisis (p=0.0001), hand-foot syndrome (p=0.047), aplastic crisis (p=0.033), splenic sequestration crisis (p=0.039), and AFI (p=0.035) was low as compared to cases having HbF ≤20% which was statistically significant. The incidence of acute painful crisis, hand-foot syndrome, and an aplastic crisis was significantly low in patients receiving hydroxyurea therapy as compared to patients who were not on hydroxyurea. Out of 100 cases, four died during the study period, three died because of splenic sequestration crisis with septic shock, and one died due to hepatic encephalopathy due to haemolytic crisis with septic shock. Acute clinical events in sickle cell disease can have significant morbidity and mortality in the paediatric age group. The nutritional status of sickle cell disease children must be given due importance. Early initiation of hydroxyurea must be encouraged to maintain higher HbF levels, which plays a significant role in reducing morbidity.

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.

Are Women at High Risk of Complications from Sickle Cell Disease: Insights from National Database Analysis

Introduction: Published data reporting gender-related differences in outcomes from sickle cell disease (SCD) is scarce, consisting of small single-center studies. Therefore, using a large sample size from a nationally representative database, we looked into the effect of gender on outcomes from SCD. Methods: We investigated the National Inpatient Sample 2019 using International Classification of Diseases-10 (ICD-10) codes to include adult SCD patients. Morbidity, disease complication, and resource utilization were compared, stratified by patients' gender. Analyses were performed using STATA (version 14.2), considering 2-sided P< 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using the Student's t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses. Results: A total of 97,244 patients were included (mean age 34.61 years, 57.26% females). Female patients had 24% lower odds of acute chest syndrome on presentation (Adjusted odds ratio (aOR) 0.76, 95% confidence interval (CI): 0.64 - 0.91, P<0.01). The rates of splenic sequestration crisis, posterior reversible encephalopathy syndrome, myocardial infarction, and gallbladder stones were comparable between the two groups. Males had higher odds of developing acute kidney injury during hospitalization (aOR 0.80, 95% CI: 0.70 - 0.92, P<0.01), but the rates of in-hospital mortality and other morbidity markers were not different between the two groups. Packed Red Blood Cell (pRBC) transfusion, total hospital costs, and length of stay were not statistically different between males and females. Discussion: Using a large sample size, we found that females are not at high risk of SCD complications or adverse hospitalization outcomes. Male patients have a higher risk of presenting with acute chest syndrome and developing acute kidney injury. This could be due to the estrogen protective effect or other factors. Despite menstrual losses, females did not have significantly higher pRBC transfusions or lower secondary hemochromatosis. Our study showed that gender does not represent an indicator of morbidity and mortality in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Documented Viral Illness at the Time of Splenic Sequestration Does Not Affect the Odds of Recurrence in Children With Sickle Cell Disease.

This retrospective study investigates the relationship between the presence of a documented viral infection in children with sickle cell disease during their first splenic sequestration crisis and their odds of recurrence. Forty-eight children were admitted to our hospital between 2008 and 2018 with a splenic sequestration crisis. Thirty-six had respiratory viral panels done on admission, 13 of whom were positive. Two additional children were diagnosed with parvovirus B19 infection by serology. The recurrence rate was 52% (17/33) for those deemed negative for viral illness compared with 33% (5/15) among those with a positive documented viral illness, which was not statistically different (P=0.35). HbSC genotype decreased, and reticulocytosis increased the odds of recurrence. Further research is needed to substantiate these findings.

Splenectomy in Sickle Cell Haemoglobinopathies from a Tertiary Hospital of Southern Odisha: A Retrospective Study

Introduction: Sickle Cell Disease (SCD) is a common haemoglobinopathy, where spleen is considered to be the first organ to be involved. Although it initially undergoes enlargement, but most often there occurs autosplenectomy. But in some cases, there is persistence of splenomegaly which may be associated with various complications. In these situations, splenectomy is considered as a good option to mitigate all these morbidities. Aim: To analyse the effect of splenectomy on haematological parameters and complications in patients of SCD in postoperative period. Materials and Methods: This was a retrospective study conducted at SLN Medical College and Hospital, Koraput, Odisha, India, from April 2019 to March 2021. Total 42 patients of SCD underwent splenectomy. The haematological parameters (Haemoglobin (Hb), Total Leucocyte Count (TLC) and Total Platelet Count (TPC)) and blood transfusion needs were compared in pre and postoperative periods and analysed statistically with Student’s t-test. Results: Primary indication of splenectomy was hypersplenism 31 (73.8%) followed by splenic sequestration crisis in 8 patients (19.05%) and splenic abscess in 3 patients (7.1%). Postsplenectomy haemoglobin improvement was around 5.2 gm% (p-value &lt;0.001). Postoperative complication was also minimal, seen in only eight patients, it was mostly due to surgical site infection and fever. Preoperative blood transfusion rate was 9.07±1.92. Blood transfusion requirement rates were also drastically reduced to 0.5±0.707 postsplenectomy in these patients (p-value &lt;0.001). Conclusion: Following splenectomy, the need of blood transfusion was grossly reduced and also, the incidence of its complication was reduced.

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

Crisis in Sickle Cell Disease: Review Article

Sickle cell disease is a very common inherited disorder of the hemoglobin. It is inherited in an autosomal recessive manner. Most affected are the people of African, Indian and Arabian origin. It occurs due to change in the single base pair gene wherein thymine replaces adenine in the 6th codon of the beta-globin gene. This result in the sickling shape of the red blood cells. Sickle cell disease includes a variety of phenotypes like the SS, AS, Sickle-thal, SC patterns, etc. Sickle cell- SS pattern also termed as sickle cell anemia is the most common of form of the disorder and is also responsible for the morbidity and mortality caused by the disorder. The sickling pattern of the red blood cells occludes the blood vessels and leads to a wide range of complication in the affected individuals. These complications can be seen in number of different systems of the body and also multiple systems at the same time. These complications are termed as crisis, which then include the vaso-occlusive crisis, acute chest syndrome, splenic sequestration crisis, etc. These crises can negatively affect the quality of life to a large effect, but are also largely controllable or rather delayed and effectively managed as far as possible with reduced effect in the normal well being. Hence the knowledge about these crisis and their treatment is an important aspect of medical practice, especially in the countries where this disorder is commonly seen. Here in this review article we aim to highlight the major crises seen in sickle cell disease and their treatment in brief.

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.