Sickle Cell Disease Related Complications Research Articles

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21–35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

Comparison of Devices That Measure Sickle Red Cell Deformability

Background With the emergence of novel pharmacologic and gene-based therapies, identifying the rheological and biophysical RBC abnormalities of sickle cell disease (SCD) not captured by clinical laboratory techniques is crucial. Ektacytometry (LORRCA), the current standard to assess RBC function, does not reflect mechanical stress that RBCs experience in capillary microvasculature in the body. The device is costly, requires a nitrogen gas tank, and its use is difficult to translate outside of large-scale laboratory settings. In comparison, the Microfluidic Impedance Red Cell Assay (MIRCA) is a low-cost, portable device that mimics capillary microvasculature with micropillar arrays spaced 3-12 µm apart. Thus, MIRCA measures mechanical deformability, which is more physiologic, mimicking RBCs squeezing through microvasculature. An impedance analyzer calculates the MIRCA Occlusion Index (OI), representing the % occlusion of the chip. Here we compare the MIRCA to the LORRCA, assessing the correlations of OI and Elongation Index maximum (EI) to conventional laboratory tests and SCD related complications. Methods Peripheral blood from 53 adult (n = 28) and pediatric (n = 25) individuals (HbSS = 35, HbSB0 = 6, HbSC = 5, HbSB0 = 1, and HbAA controls = 6) were obtained under an Emory University IRB approved protocol. Patients transfused &amp;lt; 90 days prior were excluded. Hospitalizations / emergency department (ED) visits for pain within 12 months of sample collection were determined by chart review. Samples were collected in EDTA, stored at 4°C up to 48 hours, centrifuged at 500g, washed, and resuspended to a 20% hematocrit to run on MIRCA, an oxygen gradient ektacytometer (LORRCA), and an ADVIA hematology analyzer. Polydimethylsiloxane (PDMS) fabricated MIRCA chips were bonded to a standard glass slide with pairs of gold-sputtered electrodes adjacent to each array. Chips were prepared by perfusing ethanol, 1X phosphate-buffered saline (PBS), and 3% bovine-serum albumin (BSA) in 1X PBS via syringe pump and were incubated overnight at 4°C prior to use. Baseline impedance was taken for a 2-minute perfusion of 1X PBS, then OIs were calculated from impedance values 10 minutes after sample introduction normalized to baseline. The data was analyzed using the Mann-Whitney U test, Spearman correlation, and linear regression. OriginPro (Northampton, MA, USA) and Stata 18 (College Station, TX, USA) were used for the analyses and a p &amp;lt; 0.05 was considered significant. Results The correlation coefficients for OI and EI with laboratory tests (Table 1) and to each other (Figure 1) were comparable (p &amp;lt; 0.05). HbSS/SB0 had higher OIs than HbSC/SB+ (median = 13.7% vs 6.8%, p &amp;lt; 0.01) and HbAA (median = 4.6%, p &amp;lt; 0.01). Patients with ≥ 1 vaso-occlusive events (VOE) in the past year had higher OIs and lower EIs compared to those without a VOE (median = 15.3% vs 9.6%, p &amp;lt;0.01; median = 0.4 vs 0.5, p = 0.02, respectively). Patients that received acute medical care (admission or ED visit) had higher OIs and lower EIs compared to those that did not (median = 15.7% vs 9.8%, p &amp;lt; 0.01; median = 0.4 vs 0.5, p = 0.02, respectively). In multiple linear regression, HbSS/SB0 (p &amp;lt; 0.01), adults (p = 0.01), and DRBC (p &amp;lt; 0.01) were associated with OI while HbSS/SB0 (p = 0.01), DRBC (p &amp;lt; 0.01), hemoglobin % (p = 0.04), absolute neutrophil count (p = 0.02), and VOE+ (p = 0.02) were associated with EI. The models explained 55.2% and 66.8% variability of OI and EI, respectively. Lower Akaike's information criterion (AIC, 186 vs -80) and Bayesian information criterion (BIC, 192 vs -71) of the EI model suggest a higher correlation to conventional laboratory values and clinical features compared to OI; OI may possibly be a unique biomarker that both laboratory tests and LORRCA fail to fully characterize. Conclusion MIRCA OI and LORRCA EI normoxic deformability are correlated to each other, and both show statistically comparable correlations to many parameters associated with SCD severity. Both OI and EI are significantly associated with SCD outcomes like VOE and acute care. Due to lower device size, cost, and relative ease-of-use, MIRCA may be more convenient for routine clinical use and for use in low resource settings where LORRCA costs and requirements hamper implementation. As the addition of chemical hypoxia to MIRCA is now underway, future work will examine OI under hypoxia and its associations with SCD-relevant outcomes like pain events, stroke and acute chest syndrome.

Prevalence and Antimicrobial Resistance Patterns of Pathogenic Bacterial Isolates of Hospitalized Sickle Cell Disease Patients Admitted in Our Tertiary Hospital in the Gambia

Background: Sickle Cell Disease (SCD) patients are predisposed to several SCD related complications such as vasocclusive crisis, asplenia, haemolytic crisis and bacterial infection. Despite several other complications encountered by SCD patients during the first few years of life, invasive bacterial infections caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and non-typhi Salmonella species have been reported to be the predominant cause of morbidity and mortality in sickle cell disease patients in many countries (Williams et al. 2009). This is because most SCD patients develop functional asplenism in their early years of life because of repeated episodes of sickling-induced splenic infarction which predisposes them to episodes of infections caused by encapsulated bacteria such as such as Streptococcus Pneumoniae, Haemophilus influenzae type b, and non-typhoidal Salmonella species. The two major prophylactic interventions are vaccination, and daily oral penicillin at least until the fifth year to protect the SCD populations from encapsulated bacterial infections. Aims The aim of this study was to determine the prevalence of invasive bacterial infections and their antimicrobial resistance patterns in SCD patients admitted at the Medical Research Council the Gambia (MRCG) Ward in the era of Pneumococcal Conjugate Vaccine and Haemophilus Influenzae b vaccination in the Gambia. Methods and Results This study was conducted in the clinical laboratory department of MRCG. We retrospectively generated haematological, and blood culture data from our electronic medical records from 2015 to 2022 of SCD patients admitted to MRCG Ward. Of 380 SCD patients, blood culture was requested for 159. Of the 159 admitted SCD, 11 patients had qualified positive blood cultures. Five different types of pathogens were isolated from these positive blood cultures: 4 Staphylococcus aureus, 3 Streptococcus pneumoniae, 2 Salmonella species, 1 Enterococcus species, and 1 Shigella boydii. No episode of bacteremia caused by Haemophilus influenzae type b was identified. The molecular serotyping of the Streptococcus pneumoniae isolates revealed non-vaccine serotypes 10A, 12F and 12F. From our AST result, two of the three Streptococcus pneumoniae were resistant to penicillin antibiotics. The Staphylococcus aureus isolates were penicillin resistant but cefoxitin sensitive, hence no methicillin (oxacillin) resistant Staphylococcus aureus was reported., Generally, the isolated pathogens were all sensitive to chloramphenicol, and vancomycin. Conclusion: Streptococcus pneumoniae and Staphylococcus aureus were the most common cause of bacteremia in these admitted SCD patients. The presence of non-typhoidal Salmonella and Shigella infection coupled with penicillin resistance should be considered during penicillin prophylaxis and empirical treatment regimens for SCD patients and future SCD management policies in the Gambia.

Partial Red Cell Exchange Is an Effective Tool for Adequately Reducing Hemoglobin S Levels in Patients with Sickle Cell Disease and Improving Patient Outcomes Including Reduction in Acute Care Utilization

Introduction: Red cell exchange (RCE) is a therapeutic procedure that aims to reduce the number of sickle-shaped red blood cells in circulation and replace them with healthy donor cells. The use of red cell exchange in sickle cell disease (SCD) is primarily aimed at preventing or treating acute complications such as acute chest syndrome, stroke or priapism. However, in patients with inadequate disease control and associated frequent hospitalizations requiring parenteral opioids, we have proposed that prophylactic partial RCE (pRCE) be incorporated into the treatment plan. Implementation of pRCE with resulting limitation of parenteral opioid use may potentially reduce hospitalizations and achieve overall better disease control. Use of pRCE for disease control remains limited as it is labor intensive and requires copious amounts of blood which can be challenging especially in this era of COVID19 pandemic blood shortage. For this reason, we have utilized pRCE at our institution. Here we demonstrate that pRCE with four to five units of packed red blood cells (pRBCs) is equally effective in reducing hemoglobin S to levels below 40% and SCD related complications including VOCs and hospitalizations. Methods and Results: In our center, we identified six individuals with frequent hospitalizations and significant daily oral morphine equivalent requirements. These patients were then placed on a monthly pRCE protocol. Patients with variable genotypes were enrolled including HbSS, HbSC and HbSβthal +. Each patient underwent pRCE initially utilizing four units. Hemoglobin S level was closely monitored and if the target level of &amp;lt;40% was not reached with four units, the number was increased to five units. It is important to note that partial exchange was utilized only in patients whose indication for RCE was pain and frequent hospitalizations rather than history of CVA. In addition to pRCE, each patient was placed on a restricted care protocol that comprised of the administration of only home oral opioids during acute care visits. Prior to initiation of both pRCE and restricted care plan, patients were educated at length and during frequent clinic visits regarding the difference between chronic pain management and acute vaso-occlusive crisis. As shown in Figure 1, partial exchange leads to adequate reduction of hemoglobin S levels immediately post exchange that remains suppressed over the four-week period to predominately below 40 percent. This reduction in hemoglobin S levels results in patient-reported improved sense of well-being and compliance with restricted care plans to limit acute care utilization and move SCD care to the outpatient setting. In fact, we saw a dramatic reduction in hospitalization among patients with sickle cell disease regardless of genotype, age and gender. As shown in Figure 2, for each patient placed on restricted care plan, acute care utilization was reduced compared to each patient's previous year's monthly admission rates. Conclusion: Prolonged uncontrolled SCD with frequent VOCs will undoubtedly result in high acute care utilization, high opioid requirements and risk of development of chronic pain with subsequent opioid induced hyperalgesia and opioid failure. Partial red cell exchange is an effective tool for addressing sickle cell disease complications and improving patient outcomes, particularly in patients with least disease control and highest acute care utilization.

Haploidentical Aß T Cell Depleted HSCT Represents an Alternative Treatment Option in Pediatric and Adult Patients with Sickle Cell Disease (SCD)

Background: Sickle cell disease (SCD) is the most prevalent inherited hemoglobinopathy worldwide, which is associated with considerable morbidity and early mortality. Although HSCT with a MD offers a curative treatment option with an excellent 2-y OS of 95%, availability of MDs is limited and therefore haploidentical HSCT is increasingly explored. Here we update our in vitro T-depleted haploidentical HSCT approach, which is currently explored in a multicenter international trial (NCT04201210). Methods: 29 pts with SCD or SCD-ß Thal (median age: 18 years; range: 2-32) received either a CD3 +/CD19 + (n=9) or aß/CD19 + (n=20) T-haplo-HSCT and were compared with 20 SCD-pts receiving a BM graft from a MSD (median age: 23 years; range: 9-39) at our center. Indication for T-haplo HSCT pts included severe or moderate SCD related complications such as recurrent pain crisis (&amp;gt;5/year), acute chest syndrome, neurological events, osteonecrosis or nephropathy, transfusion-refractory allo-immunization. After exchange transfusion, almost identical conditioning regimens consisting of treosulfan, thiotepa, fludarabine (FTT) and ATG-Grafalon were applied in almost all pts, with the only difference in the timing of ATG (upfront in T-haplo-HSCT, prior to day 0 in MSD-HSCT). Immunosuppression (IST) was maintained for a minimum of 180 days consisting of calcineurin inhibitors (mainly tacrolimus) and MMF. Results: The OS and DFS for MSD and T-haplo-HSCT was 95% and 83%, respectively (Table 1). The median follow-up was 49 months for MSD (range 5-118) and 67 months for T-haplo-HSCT (range 0.5-135). Neutrophil engraftment was achieved after a median of 29 days for MSD pts and 17 days for T-haplo-HSCT with a median of 2.8 x 10 8 TNC/kg (range: 0.65-4.11) and 12 x 10 6 CD3 +/CD19 + or ab/CD19 + depleted CD34 + cells/kg (range: 4.8-49.2), respectively. One pt received two T-haplo HSCT due to primary graft failure after HHV6 infection with effective engraftment after the second transplantation. One pt required a stem cell boost of the same donor with slow subsequent engraftment and one pt died of infectious complications after the fourth T-haplo HSCT. A mixed chimerism &amp;lt;80% was observed in 1/20 MSD-HSCT (median 94.9%; range 40.5-100%) and in 2/29 T-haplo-HSCT pts (median 97.8%; range: 35.7 -100%). No severe cases of &amp;gt;°III aGVD was observed in both populations. MSD pts reached T cell counts &amp;gt;200/µl on day +62 (median; range: 24-293) and T-haplo-HSCT pts on day +136 (median; range: 25-758). Viral reactivation occurred both in T-haplo HSCT (20/29) and in MSD-BMT (9/20). However, one pt in the T-haplo group developed kidney failure after prolonged BKV infection and four of the T-haplo pts died of complications associated with severe CMV or HHV6 infections that were accompanied by hyperinflammation, macrophage activation and acute respiratory distress despite antiviral and anti-inflammatory treatment. One pt of the MSD group died of late treatment related toxicity in combination with preexisting SCD comorbidity. The last fatality occurred in 2020 with now 16 additional pts being transplanted safely, not least also because of a consistent letermovir prophylaxis. Overall, the treosulfan-based conditioning regimen was well tolerated with only one VOD/SOS and one CNS infarction being observed in this high-risk population. 4/20 pts in the MSD group and none in the T-haplo group developed PRES early after conditioning. Conclusions: The safety and efficacy data of this pilot series of T-haplo-HSCT in SCD reveal that T-haplo-HSCT in advanced stage pediatric and adult SCD patients lacking a MSD is feasible. However, diligent viral monitoring and early treatment of viral reactivation, in particular HHV6 is mandatory as otherwise fatal infections may develop.

Contemporary Obstetric and Neonatal Outcomes in Sickle Cell Disease: A Retrospective Cohort Study.

Sickle cell disease is associated with adverse perinatal outcomes. Aspects of sickle cell disease in pregnancy, such as health care utilization and neonatal abstinence syndrome, are understudied. We aimed to describe contemporary sickle cell disease outcomes in a U.S. hospital system to improve perinatal counseling. We conducted a retrospective cohort study of patients with sickle cell disease who delivered at >20 weeks' gestation at two sites within the University of Pennsylvania Health System from May 1, 2017 to August 30, 2020. Descriptive statistics were utilized. Over the study period, 48 patients with sickle cell disease had 52 deliveries of 53 neonates. Sickle cell disease-related morbidity was prevalent prior to pregnancy; 27% had a history of avascular necrosis, and 58% had experienced acute chest syndrome. In the year prior to pregnancy, 52% used daily opioids. During pregnancy, more than half of patients were admitted at least once for sickle cell disease-related complications, spending a median 3 days admitted interquartile range (0-23); >10% spent >70 days of pregnancy admitted. New daily opioids were prescribed during pregnancy for 10% to manage pain crises. Acute chest syndrome was experienced by 23% of patients during pregnancy, and 8% required placement of long-term intravenous access. Preterm delivery <37 weeks occurred in 48%. The primary cesarean rate in nulliparas was 43%. Additionally, 50% experienced a hypertensive disorder of pregnancy, 35% underwent transfusion during delivery admission, and 10% had a perinatal venous thromboembolism. Finally, 53% of neonates were admitted to the intensive care unit. Low birth weight was noted in 34%, severe respiratory distress in 15% of infants, and neonatal abstinence syndrome in 21%. Sickle cell disease remains associated with significant perinatal morbidity and need for hospitalization. These data provide contemporary outcomes to target improvements in the care of patients with sickle cell disease. · SCD was associated with significant perinatal morbidity and healthcare utilization.. · Most patients with SCD required hospitalization during pregnancy.. · Neonates of patients with SCD experienced preterm birth, NICU admission, and neonatal abstinence syndrome..

Preoperative Transfusion in Sickle Cell Disease Children Undergoing Adenotonsillectomy.

To perform a systematic review and meta-analysis comparing two pre-operative transfusion regimens (conservative versus aggressive) in children with sickle cell disease(SCD) undergoing adenotonsillectomy in terms of post-operative complications, complications related to SCD and transfusion related complications. A literature review was performed through PubMed, EMBASE, Cochrane, and Ovid databases using the following phrases: (Adenotonsillectomy OR Tonsillectomy) AND (Sickle Cell Disease OR Sickle Cell Trait). Using predetermined inclusion and exclusion criteria, seven articles were selected for systemic review and two control trials were included in meta-analysis. Out of a total of 3,146 results, seven articles were selected for review and two controlled trials were included in the meta-analysis. There was no statistically significant difference in the rate of primary and secondary hemorrhage between the aggressive and conservative transfusion regimens (RR = 3.1, CI = 0.84-11.4, p-value = 0.089). The rate of sickle cell disease related complications including vaso-occlusive crisis and acute chest syndrome was also not statistically significant between the two transfusion groups (RR = 1.4, CI = 0.7-2.8, p-value = 0.339). Even though, the transfusion related complications did not reach statistical significance, there was a higher complication rate in the group receiving aggressive blood transfusion. In SCD children undergoing adenotonsillectomy, an aggressive transfusion regimen that focuses on reducing the Hemoglobin S ratio to below 30% has not been shown to be more effective in reducing post-operative complications when compared to a conservative transfusion regimen. Therefore, it is reasonable to utilize a conservative transfusion regimen, thereby reducing the transfusion-associated risks.

Real-World data on efficacy of L-glutamine in preventing sickle cell disease-related complications in pediatric and adult patients.

BackgroundL-glutamine has been shown to play an important role in the regulation of oxidative stress which is one of the key contributors to the pathophysiology of sickle cell disease (SCD). In a Phase 3 clinical trial, L-glutamine demonstrated a significant reduction in SCD-related complications including vaso-occlusive crises (VOCs), hospitalizations, and acute chest syndrome (ACS) compared to placebo in patients with SCD.ObjectiveThe primary objective was to confirm the efficacy of L-glutamine (Endari®) therapy in pediatric and adult patients with SCD at follow-up time points of 24, 48 and 72 weeks.MethodsIn the observational study, nineteen patients with SCD were treated orally with L-glutamine twice daily for 72 weeks. Clinical and laboratory parameters were measured at baseline and follow-up time points. Patients with severe VOC and ACS were hospitalized. Blood transfusion was given in case of ACS and uncontrolled pain associated with VOC despite administration of the highest dose of intravenous (IV) narcotic.ResultsCompared to baseline, patients had significantly fewer pain crises (median change from 3.0 to 0.0; P < 0.00001), hospitalizations (median change from 3.0 to 0.0; P < 0.00001), days of hospitalization (median change from 15.0 to 0.0; P < 0.00001), and blood transfusions (median change from 3.0 to 0.0; P < 0.00001) at 24, 48, and 72 weeks following L-glutamine therapy. Moreover, there was a drastic decrease in the number of ACS events during this time. A significant increase was observed in mean hemoglobin levels and hematocrit proportions from baseline to 72 weeks (P < 0.001). Conversely, compared to baseline, mean reticulocyte counts and lactate dehydrogenase (LDH) levels were considerably lower at follow-up time points (P = 0.003 and P < 0.001, respectively). No patient reported treatment-related adverse events.ConclusionAlthough the sample size was small, our data clearly demonstrated that L-glutamine therapy was safe and significantly improved clinical outcomes and hemolysis parameters in patients with SCD.

Red Cell Exchange: A Concise Review of Indications and Management

▪Sickle cell disease (SCD), a common hemoglobinopathy in the United States affecting approximately one in 500 African-Americans, is associated with numerous potential complications related to both anemia and the presence of hemoglobin S (HbS). Red blood cell (RBC) transfusion and exchange (RCE) to improve oxygen carrying capacity and to treat or decrease the risk of complications due to sickling has been an important part of treatment for many years. While some treatment guidelines exist, there is still significant variation in the management of SCD patients.Fifteen physicians in the active practice of apheresis from 12 institutions representing different geographic regions within the United States discussed how they manage RCE. Additionally, a literature review was performed and data from a prior practice survey were evaluated.Simple transfusion is recommended to treat symptomatic anemia with hemoglobin <9 g/dL. RCE is indicated to prevent or reverse complications arising from the presence of HbS.Indications for RCE in SCD : Common indications include treatment of stroke, acute chest syndrome, and sickle hepatopathy. Primary and secondary stroke prevention is an accepted, well studied indication, although optimal duration of treatment is unknown. RCE may be indicated prior to planned surgical procedures, may be necessary during pregnancy in women who have a history of severe SCD-related complications, and is indicated prior to stem cell mobilization. Pain crisis in the absence of other symptoms is generally not accepted as an indication. The role of RCE is not determined for pulmonary hypertension, end stage renal disease, and progressive sickle retinopathy.Goals of RCE : The most important goals are to reduce the level of HbS while also preventing development of hyperviscosity. In most situations, a target HbS of ≤30% and target hemoglobin <10 g/dL (or hematocrit <30%) will treat and/or prevent SCD related complications without causing hyperviscosity.Access: Peripheral veins are the preferred means of access when possible. Treatment of acute complications of SCD usually requires a temporary central venous catheter. Options for long-term access include tunneled central venous catheters, implantable ports, or arteriovenous fistulas.RBC units: These should be HbS negative and leukodepleted. Units are commonly matched for C, E, and Kell antigens to help prevent alloimmunization in addition to being negative for antigens against which the patient has already formed antibodies. RBC phenotyping commonly is performed and molecular typing may be indicated in selected patients.Complications: These include risks related to central venous access, transfusion reactions, iron overload, alloimmunization, transfusion-transmitted infection, development of warm autoantibodies, and hyperhemolysis syndrome.There are many issues that need to be taken into consideration when evaluating a patient with SCD for transfusion treatment. A prior practice survey indicated that there are variations in the clinical management of these patients. While every case must be evaluated individually, we have presented some common practices. DisclosuresBoggio:Grifols: Consultancy, Honoraria.

Evaluation of Sickle Cell Module for Quality of Life in Egyptian Children and Adolescents Patients: Impact of Psychiatric and Disease Specific Variables.

Sickle cell disease (SCD) impacts the physical, emotional, and psychological aspects of life. We aimed to study the quality of life (QoL) in Egyptian children and adolescents with SCD using the sickle cell module in relations to social, psychological and disease variables. A cross sectional study included 40 patients with SCD between 5 and 18years. Details of diagnosis, SCD related complications, socioeconomic status were revised. Psychological assessment was done using children depression inventory, revised Children's Manifest anxiety scale and Health related QoL for both patients and parents using a validated Arabic age specific version of sickle cell module. Significant better scores for communication problems in mothers with college degree was found compared with other academic levels with no significant difference in QoL in relation to father education and significant higher communication problems with high rate of hospitalization (P = .021). Pain score was higher in 8-13years compared with 13-18years age groups. Significant worse scores for worrying was found in females, P = 0.033; Depression was found in 90% of studied patients. The main determinants of QoL in patients with SCD were maternal education and frequency of hospitalization. Depression is of alarming frequency for intervention.

Caregivers’ level of knowledge and home- based practices for prevention of Sickle cell disease related complications among children attending Mnazi mmoja hospital in Zanzibar

BackgroundOptimal control of Sickle cell disease (SCD) related complications in children is enhanced when caregivers have good knowledge of factors leading to complications and effective home-based preventative interventions. Most SCD care programs incorporate caregivers’ education sessions but little is known on the knowledge level and adherence to recommended home based preventative interventions among caregivers of children with SCD. ObjectiveTo evaluate knowledge level and home-based care practices of caregivers of children with SCD attended at Mnazi mmoja Hospital in Zanzibar in relation to occurrence of disease complications. MethodsThis was a cross-sectional study of caregivers of children with SCD bringing their children to Mnazi mmoja Hospital in Zanzibar. Caregivers with children aged 6 months to 12 years were enrolled. SCD knowledge and home-based care practices were evaluated using pre-tested scales consisting of 27 and 22 items respectively. Descriptive statistics, bivariate correlation and logistic regression analysis were done using SPSS version 21. ResultsA total of 300 caregivers of children with SCD were enrolled, among the caregivers, 53.3% had inadequate SCD knowledge and 52% reported inappropriate home based care practices. Caregivers knowledge level (AOR 2.282, 95% CI [1.021, 5.103] p = 0.044) and home-based care practices (AOR 3.030, 95% CI [1.338, 6.862] p = 0.008) were significantly associated with occurrence of disease complications. ConclusionInadequate caregivers’ level of knowledge and poor adherence to home-based care practices are significantly associated with occurrence of SCD related complications. We recommend review of the modality and contents of health education given to caregivers to identify gaps to be improved for better Sickle cell disease control.

Outcomes of Red Cell Exchange in Pregnant Patients with Sickle Cell Disease: A Case Series

Background: Pregnant patients with sickle cell disease (SCD) have higher morbidity compared to patients without SCD. SCD during pregnancy can increase the risk of fetal and obstetrical complications including preterm birth, preeclampsia, and others. Moreover, during pregnancy SCD can become more severe resulting in more sickle cell vasoocclusive crisis. Prophylactic transfusion during pregnancy has been used in practice to reduce sickle cell pain crisis since hydroxyurea is contraindicated during pregnancy. However, using prophylactic red blood cell exchange (RBCX) has been a controversial topic. In this study, we aim to evaluate the outcomes of red blood cell exchange in pregnant patients with SCD Methods: This is a retrospective study. We evaluated the charts of three pregnant patients who were enrolled in the chronic RBCX program at the University of Nebraska Medical Center at the time of their pregnancy. Data was collected to assess the sickle cell disease related complications during pregnancy, outcomes of pregnancy, and safety of the red blood cell exchange. Results: A total of 19 exchange procedures were performed for three pregnant patients while being enrolled in the chronic red blood cell exchange program. Patients demographic is summarized in table 1. The indication for enrollment in the red cell exchange program were recurrent vasooclussive crisis in patient 1 and 3, avascular necrosis in patient 2. The pregnancies were uncomplicated except for preeclampsia in the third patient resulting on early delivery. Overall, the three patients had less frequent visits to the emergency room for sickle cell related complications after starting apheresis and during pregnancy (Figure 1). We believe that the modest improvement that was noticed for the third patient was due to late enrollment in the exchange transfusion program and her older age compared to the two other patients Conclusion: Our study shows that red blood cell exchange for SCD patients during pregnancy can be safe, feasible, and can reduce the visits to the emergency room due to SCD related complication. Further larger studies are warranted to confirm this. Disclosures Gundabolu: BioMarin:Consultancy;Bristol Myers Squibb pharmaceuticals:Consultancy.

Burden of Sickle Cell Disease: A Brazilian Societal Perspective Analysis

Introduction: Sickle cell disease (SCD) is a group of inherited disorders that shorten life expectancy. It is estimated that 300,000 children are born with the disease worldwide each year [1,2]. In Brazil is it estimated that 3,500 children are born with SCD each year [3]. The SCD is a multisystem disorder that leads to several complications (acute and chronic) including vaso-occlusive crisis [1,4]. SCD patients experience increase morbidity and mortality, the implications of which are known to impacts the whole society [2]. Although there is some knowledge about the clinical impacts of SCD, little is known about the societal costs. Due to the limited available, to the best of our knowledge there are no similar studies which have been conducted and published. The aim of this study is to estimate SCD societal costs based on a burden of disease model, utilizing the Brazilian societal perspective. Material and Methods: A burden of disease model (Figure 1) was built considering direct medical costs to adults and children and indirect costs, taking into account lost wages due to SCD related morbidity and death. Direct costs were estimated using a bottom-up strategy and micro-costing method, and indirect costs were estimated using a prevalence method. Disability-adjusted life years (DALYs) were calculated from the sum of years of life lost and disability. The rate and duration of SCD related complications (including death) was calculated using information from a Brazilian governmental healthcare public database (DATASUS). The prevalence of each complication was determined by literature data or medical experts. It is important to point that there is some uncertainty around the prevalence estimates. Direct costs for complications were captured from the Brazilian public healthcare system table of procedures and medications (SIGTAP). Indirect costs attributed to productivity loss were calculated using the human capital method. All values were reported in 2020 Brazilian real (BRL). Results: Considering a prevalence of 23.9 cases per 100,000 (50,000 patients in 2018) and a probability of death of 1.11% (560 deaths in 2018), the annual total SCD cost in Brazil was estimated at 1,519,473,501 BRL. Table 1 shows the contribution of the direct and indirect costs to the total cost for the SCD population in Brazil. Further, results were stratified by children and adults (56% and 44%, respectively). Indirect cost was the main driver of disease burden, estimated at 1,128,355,824 BRL. Approximately 40,829 DALYs were lost by SCD patients in 2018 (22,750 and 18,079 among adults and children, respectively). Direct medical costs represented 25.7% of total costs and were estimated at 391,117,677 BRL. Provision of standard of care was the main driver of direct costs in both populations (157,521,597 BRL for adults and 100,133,575 BRL for children). Chronic complication management was shown to be more expensive than acute complication management among adults, while the opposite was observed for children. Vaso-occlusive crisis was the acute complication most frequently observed in available literature and according to medical experts (75.0% among adults and 59.5% among children). Acute chest syndrome had the highest disability weight (0.33). Considering chronic complications, calculous chronic cholecystitis was considered the most frequent among adults (62.0%) and renal abnormalities (without failure) among children (20.0%). Conclusion: SCD patients generate a high economic burden for the Brazilian society greater than one point five billion BRL per year. Most of the cost is related to indirect burden due to increased mortality and morbidity. Investments in technologies and therapies that can decrease the impact of SCD on patients' lives by reducing morbidity and/or mortality are necessary.

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

Prognosis of patients with sickle cell disease and COVID-19: a French experience

Prognosis of patients with sickle cell disease and COVID-19: a French experience

Pulmonary disease burden in Hispanic and non-Hispanic children with sickle cell disease.

Pulmonary complications are the leading cause of morbidity and mortality in sickle cell disease (SCD) patients. Research in SCD has predominantly been conducted on African-Americans, and the disease burden of SCD in other races and ethnicities, including Hispanic patients, is not well characterized. To compare pulmonary disease burden between Hispanic and non-Hispanic ethnic groups among children with SCD. In a retrospective chart review on 566 SCD patients followed at the Children's Hospital at Montefiore, NY, we compared the pulmonary disease burden and disease management in Hispanic patients to their non-Hispanic counterparts. We also compared the contribution of demographic and clinical variables to acute chest syndrome (ACS), vaso-occlusive crisis (VOC), and hospitalizations for SCD related complications between the two ethnic groups. Hispanic patients had a greater proportion of ACS, and had lower forced expiratory volume (FEV1), forced vital capacity, and vital capacity, compared to non-Hispanics. Hispanic patients were more likely to be evaluated in pulmonary clinic and to be on inhaled corticosteroids, short-acting β agonizts, and leukotriene receptor antagonists. In addition, Hispanic children were more likely to be on hydroxyurea, and receive exchange transfusions. However, the association of asthma with the proportion of ACS did not differ between Hispanics and non-Hispanics. Hispanic children with SCD had differences in their pulmonary function profile and received more pulmonary evaluations than non-Hispanic children.

Preoperative transfusion versus no transfusion policy in sickle cell disease patients: a randomized trial.

Many children with sickle cell disease (SCD) indicated for adenotonsillectomy receive pre-operative transfusion therapy, either simple or exchange transfusion, in order to reduce surgical and sickle cell disease-related complications. This is a prospective randomized controlled clinical trial aiming to compare between preoperative simple transfusion and no transfusion in pediatric patients with sickle SCD admitted in Sultan Qaboos University Hospital, Muscat, Oman for adenotonsillectomy during the period from January 2014 through June 2018. They were randomly assigned into two arms (simple transfusion and no transfusion). Postoperative SCD-related complications have been encountered in 6 out of 138 patients (4.3%). There was no statistically significant difference between the two studied groups as regards the development of surgical or SCD-related complications (p = 0.6 and 0.8 respectively). The length of postoperative hospital stay was comparable in the two groups. (p = 0.607). SCD-related complications occurred exclusively in cases with homozygous sickle anemia (4 out of 81 = 4.9%). Sickle cell disease patients with a hemoglobin level above 7.5 g/dL do not need PRBCs transfusion prior to adenotonsillectomy. This approach did not increase the risk of postoperative surgical or SCD-related complications.

LAPAROSCOPIC CHOLECYSTECTOMY IN SICKLE CELL PATIENTS: A NONTRANSFUSIONAL PERIOPERATIVE MANAGEMENT.

Background: The objective of this study is to evaluate the outcome of novel perioperative management involving prophylactic antibiotic, Intra Venous fluids and Intermittent Nasal Oxygen and avoidance of preoperative blood transfusion for Laparoscopic Cholecystectomy.&#x0D; Methods: A prospective study included all sickle cell disease (SCD) and trait patients who underwent Laparoscopic Cholecystectomy from January 2007 to August 2010 at Acharya Vinoba Bhave Rural Hospital, attached to Datta Meghe Institute of Medical sciences university, Sawangi, Wardha. India&#x0D; Result: A total of 26 patients underwent Laparoscopic Cholecystectomy. There were two recorded episodes of acute painful crises and three patients had postoperative fever. There were no recorded episodes of Acute Chest syndrome.&#x0D; Conclusion: Laparoscopic Cholecystectomy can be safely performed for sickle cell anemia (disease and trait) patients, without preoperative blood transfusion. A defined perioperative regimen including use of antibiotic, IV fluids and Intermittent Nasal Oxygenation for these patients helps to reduce SCD related complications.&#x0D; Keywords: Laparoscopy, Cholecystectomy, Sickle Cell, Nontransfusion, Haemoglobinopathy.

Predictors of the Rowland Universal Dementia Assessment Scale (RUDAS) Performance in Adults with Sickle Cell Disease

Background: Sickle cell disease (SCD) patients are at significant risk for stroke and silent cerebral infarcts. At least 33% of adults have cognitive dysfunction. However, access to specialized assessments is limited, and there is currently an unmet need for a fast, easy to administer, screening tool for cognitive impairment in SCD. The Rowland Universal Dementia Assessment Scale (RUDAS) is a 6-item task-based questionnaire that evaluates executive function, memory, language, visual-spatial function, praxis and judgment. It has been validated in many cultures and neurocognitive diseases other than SCD. Hypothesis: Poor RUDAS performance is associated with the presence of SCD complications independent of age, socioeconomic and education factors. Methods: Study design: cross-sectional, two adult sickle cell comprehensive care centers in Canada. Inclusion criteria: out-patients ≥18 years-old; all SCD phenotypes. Exclusion criteria: inability to obtain informed consent and/or follow study instructions. Intervention: RUDAS was administered twice, 2-4 months apart, in French or English, based on the patient's preference. Survey on demographics and patient-reported outcomes (PROMIS® tools for Depression and Anxiety) were completed. Baseline characteristics, SCD complications, and laboratory results were collected. Statistical plan: t-tests, Fisher exact and chi-squared tests, for continuous and discrete variables respectively, were performed to identify possible association between RUDAS and biologic, socioeconomic, and cultural factors, SCD related complications, comorbid conditions, laboratory parameters, and use of disease-modifying therapy (Table). Associations with univariate P &lt;0.05 were included in the multiple linear regression model. Multicollinearity was assessed. Results: Of the 252 participants, 92 were from Centre Hospitalier de l'Université de Montréal in Montréal, 160 were from University Health Network in Toronto. Median age at time of survey was 31.5 years (IQR 25-44). Female to male ratio was 1.15. Sickle genotype was distributed as follows: SS 55% (N=138), SC 32% (N=80), other sickle genotypes 13% (N=34). Median RUDAS score was 26 (IQR 24-28), mean score ± standard deviation was 26.0±2.9. Suspected cognitive impairment (defined as RUDAS score &lt;23/30) was found in 12% (N=29) of the participants. On univariate analysis, RUDAS score declined significantly with age (P&lt;0.001), lower eGFR (P&lt;0.001), lower systolic blood pressure (P=0.022), and lower reticulocyte count (P=0.007), while higher level of education (P=0.012), employment and/or active enrolment in a study program (P&lt;0.001), and diagnosis of depression (P=0.009) were predictive of higher RUDAS scores (Table). Reticulocyte count, eGFR, and highest level of education remained independent predictors of RUDAS score on multiple linear regression (P=0.003, &lt;0.001, and 0.001 respectively; see Table for effect size). Center, language of administration, age and diagnosis of depression were not associated with RUDAS score on multiple regression. R2 of the model was 0.323. All variance inflation factors in the model were &lt;2.0. Conclusions: Reticulocyte count and eGFR, but not SCD genotype, being independent predictors of RUDAS suggests disease phenotype may contribute to neurocognitive decline and deserves further exploration. RUDAS does not appear to be influenced by age, language of administration, socioeconomic status, and depression, on multiple regression with mild collinearity. Interestingly, education was independently associated with RUDAS score, despite previous studies showing RUDAS was not biased by education. Recruitment is ongoing at two additional sites to further delineate these relationships and to explore the role of silent cerebral infarct in neurocognitive decline in SCD patients. RUDAS may be a promising tool to identify the patients at higher risk for cognitive impairment who may benefit from access to specialized neurocognitive, educational and social interventions. Disclosures Kuo: Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy.

Rheological Assessments of Sickle Cell Patients Post Allogeneic Hematopoietic Cell Transplant

Introduction: Mixed donor chimerism (MDC) occurs in nearly 35% of patients with sickle cell disease (SCD) post allogeneic hematopoietic cell transplant (alloHCT). Donor myeloid engraftment of &amp;gt;20% is considered necessary to support disease resolution. However, in a disease known for its clinical variability, we hypothesize that patients (pts) with a severe pre-HCT phenotype may have abnormal RBC rheology at a level of chimerism and %HbS believed to be consistent with a cure. RBC rheology is markedly abnormal in SCD; these abnormalities are associated with SCD related clinical complications. Even fully oxygenated, sickle RBC are less deformable than those of HbAA or HbAS individuals; upon deoxygenation, deformability further declines. Sickle RBC morphology reflects the tendency to polymerize, with characteristic sickle forms. Sickle RBC are more adherent to the endothelial cell lining of the vasculature than HbAA or HbAS RBCs. The goal of any cell-based therapy of curative intent should be normalize the red cell rheology. To determine if the rheology of blood from SCD pts post-HCT with varying degrees of donor chimerism fall into the HbSS range of values, we propose to functionally assess the peripheral blood from a series of 6 post alloHCT SCD patients using a battery of rheological tests measuring deformability, sickling, adherence, percent dense cells (%DRBC), and RBC morphology. Methods: Peripheral blood samples (EDTA) from 6 SCD pts post alloHCT with a matched sibling donor were collected and immediately analyzed using oxygenscan (Lorrca), artificial microvascular network (AMVN), microfluidic image acquisition, and an ADVIA hematology analyzer. The Lorrca with oxygenscan measures RBC deformability (elongation index EI), under a range of pO2 (150-0 mmHg). EImax is the deformability of the oxygenated sickle RBC; EImin is the deformability of deoxygenated RBCs. The point of sickling (PoS) is the pO2 at which RBC deformability rapidly declines. RBC adhesiveness is measured by the difference in rate of perfusion of RBC through the AVMN coated with adhesive proteins (adherent AVMN) and a non-adherent, uncoated AVMN. %DRBC was measured by an ADVIA hematology analyzer. Microscopic RBC images were acquired and classified to determine the fraction of sickled RBCs in well-oxygenated samples. Additional clinical data including Hb profile, donor chimerism, and symptoms were obtained via chart review. Reference ranges were generated as described above using n=45 HbSS samples ages 2-21, on hydroxyurea, chronic transfusion, or untreated; n=14 HbAS, and n=43 HbAA. Results: In Figure 1, we show the measurements obtained by the Lorrca with oxygenscan on 5 pts post-alloHCT with a range of donor chimerism, as well as typical values for HbAA, HbAS, and HbSS patients. Patient 1 and 3 exhibit normal rheology; both were transplanted with a HbAA donor, with high chimerism and no detectable HbS. Patient 2 has 40% whole blood chimerism, well above the 20% threshold described with myeloid chimerism, and a HbS less than 50%, yet their plot resembles that of an untransplanted HbSS pt; the donor to Patient 2 exhibits the expected HbAA deformability. Patients 5 and 6 exhibit rheology in the HbAS range; they have intermediate chimerism from a HbAS donor. Clinical details and biomarker panel values for all 6 pts analyzed are in Table 1, as well as ranges of values for HbSS and HbAS subjects generated in the Sheehan and Shevkoplyas labs. Patient 2 is the only subject with values in the HbSS range, and the only subject with SCD symptoms. Conclusions: Our rheological tests identified a pt with values consistent with a HbSS pt of moderate severity or treated with hydroxyurea despite variable donor chimerism above the 20% threshold and HbS &amp;lt;50% thought to be sufficient for cure. The pt reported pain events beginning two years prior, indicating a clinical correlation supporting the validity of the rheological tests we propose to use to distinguish cure from persistent SCD. Current post-HCT evaluation depends on chimerism and hemoglobin profiles, and would not detect the significant functional abnormalities visible by Lorrca with oxygenscan biomarkers that indicate that Patient 2 is at risk for SCD related complications. Our results suggest that this functional analysis may help with management of post alloHCT SCD pts, and may be even more essential to assessing new gene-based therapy approaches to curing patients with SCD. Disclosures Rab: RR Mechatronics: Research Funding. van Wijk:Agios Pharmaceuticals: Consultancy, Research Funding; RR Mechatronics: Research Funding. Shevkoplyas:SSS: Research Funding; New Health Sciences: Consultancy.