Further evidence for the benefit of therapeutic plasma exchange for acute multi‐organ failure syndrome refractory to red cell exchange in sickle cell disease

2021 ◽  
Author(s):  
Raheel S. Siddiqui ◽  
Debra A. Ferman ◽  
Patricia A. Shi
Keyword(s):  
Sickle Cell Disease ◽  
Organ Failure ◽  
Plasma Exchange ◽  
Sickle Cell ◽  
Therapeutic Plasma Exchange ◽  
Red Cell ◽  
Cell Disease ◽  
Multi Organ Failure

Case series supporting heme detoxification via therapeutic plasma exchange in acute multiorgan failure syndrome resistant to red blood cell exchange in sickle cell disease

Transfusion ◽  
2017 ◽  
Vol 58 (2) ◽  
pp. 470-479 ◽  
Author(s):  
James E. Louie ◽  
Caitlin J. Anderson ◽  
Katayoun Fayaz M. Fomani ◽  
Alonye Henry ◽  
Trevor Killeen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Plasma Exchange ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Multiorgan Failure ◽  
Case Series ◽  
Therapeutic Plasma Exchange ◽  
Cell Disease

Improved Survival of Children and Adolescents with Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1425-1425
Author(s):  
Charles T. Quinn ◽  
Kimberly Thomas ◽  
Zora R. Rogers ◽  
George R. Buchanan
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Sickle Cell Disease ◽  
Organ Failure ◽  
Sickle Cell ◽  
Adolescents And Young Adults ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Multi Organ Failure

Abstract The survival of children with sickle cell disease (SCD) has improved over the past several decades, especially for very young children. However, we know less about mortality during adolescence, and we do not accurately know the current proportion of children born with SCD who survive to adulthood. The first report from the Dallas Newborn Cohort (DNC), which included follow-up through June 2002, estimated overall survival at 18 years of age to be 85.6% (95% C.I.: 73.4 – 97.8) for individuals with sickle cell anemia (SS) or sickle-β0-thalassemia (Sβ0) (Blood2004;103:4023–7). The confidence interval of this estimate was wide because only 8 cohort subjects were 18 years old at the time. Here we update the survival analysis with 5 more years of accrual and follow-up to provide an accurate, contemporary estimate of mortality for patients with SCD through 18 years of age. The DNC includes all individuals with SS, Sβ0, sickle-hemoglobin C disease (SC), or sickle-β+-thalassemia (Sβ+) who were diagnosed by the newborn screening program of Texas (initiated November 1, 1983) and seen at least once in our center. Subjects were analyzed in two separate groups because of clinical similarity: SS/Sβ0 and SC/Sβ+. Overall survival was analyzed by the Kaplan-Meier method. Subjects were censored at the time of their last clinical encounter. Between July 2002 and July 2007 we identified 229 new members of the DNC and added 3,201 additional patient-years of follow-up. The cohort now includes 940 subjects (572 SS, 284 SC, 63 Sβ+, 21 Sβ0; 52.8% male), and it provides a total of 8,857 patient-years of follow-up (5,819 SS/Sβ0 patient-years, 3,039 SC/Sβ+ patient-years). Mean follow-up is 9.4 years (range 0.1– 20.6 years), and 97 subjects are now at least 18 years of age at last follow-up. To date, 92 subjects (9.8%) have been lost to follow-up (not seen for >5 years), and 33 subjects have died (30 SS/Sβ0, 3 SC/Sβ+). There were 7 new deaths in DNC patients since 2002, all of which occurred in patients who were 18 years of age or older. Of all deaths, 23 were SCD-related (5 acute chest syndrome, 5 sepsis, 4 multi-organ failure syndrome, 9 other), and 10 were apparently unrelated to SCD (4 trauma or accidental death, 6 unrelated medical conditions). All SC/Sβ+ deaths were apparently unrelated to SCD. Overall survival at 18 years was 93.9% (95% C.I. 90.3 – 96.2; 81 patients > 18 years of age) for SS/Sβ0 subjects and 98.4% (95% C.I. 94.4 – 99.5; 16 patients > 18 years) for SC/Sβ+ subjects. The overall incidence of death in the SS/Sβ0 and SC/Sβ+ subgroups was 0.52 and 0.10 per 100 patient-years, decreased from 0.59 and 0.24 in the original DNC analysis. Survival also appears to be improving across cohort eras (Figure). In conclusion, approximately 6% of children with SS or Sβ0 die during childhood, but almost all children with SC or Sβ+ live to become adults. Although early childhood mortality has greatly decreased, we show that many adolescents and young adults still die from SCD. Notably, acute chest syndrome and multi-organ failure have now surpassed sepsis as the leading causes of death. These data provide the accurate, contemporary foundation for the counseling of parents of newborns with SCD and for genetic counseling for prospective parents. Finally, given the marked decrease in early mortality we show here, new efforts to improve survival in SCD should focus on adolescents and young adults. Figure Figure

Erythrocytapheresis in Sickle Cell Disease and Multi-Organ Failure in the Intensive Care Unit.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4627-4627
Author(s):  
Shatha Y. Farhan ◽  
Ileana Lopez_Plaza
Keyword(s):  
Organ Failure ◽  
Sickle Cell ◽  
Carrying Capacity ◽  
Exchange Transfusion ◽  
Red Cell ◽  
Cell Disease ◽  
The Third ◽  
Multi Organ Failure ◽  
Liver And Kidney ◽  
Oxygen Carrying Capacity

Abstract Abstract 4627 Introduction Patients with sickle cell disease (SCD), including those with homozygosity for hemoglobin (Hb) S (SCD-SS) or compound heterzygosity for sickle and Hb C (SCD-SC), suffer from chronic variable intravascular hemolysis, microvascular ischemia and organ damage. Vaso-occlusion results from a dynamic combination of abnormalities in hemoglobin S structure and function, red blood cell membrane integrity, erythrocyte density, endothelial activation, microvascular tone, inflammatory mediators, and coagulation. HbC enhances, by dehydrating the SC red cell, the pathogenic properties of HbS, resulting in a clinically significant disorder, but somewhat milder sickle cell anemia. The management of SCD continues to be supportive and includes hydration, pain relief, blood transfusion and psychosocial support. However, transfused red cells will significantly increase blood viscosity, potentially reducing blood flow, if the Hb level rises above 10 g/dL. Therefore, if the goal is an acute reduction in the proportion of sickled red cells in addition to an increase in oxygen-carrying capacity, exchange transfusion is the therapy of choice. We report 3 cases of (SCD-SS) and (SCD-SC) disease with multi-organ failure syndrome who were admitted to our intensive care unit (ICU) between January and July 09 where Erythrocyatperesis was effective but somewhat delayed. Report The first patient is a 46-year old male with SCD-SC disease who presented with severe leg, back, and chest pain. He was treated with intravenous fluid and nasal oxygen supplementation. Chest pain was sustained with severe hypoxemia, elevated troponins and somnolence developed third day of hospitalization. Fourth day he became more lethargic, breathing at 35/ min. His labs showed acute liver and kidney injury. The patient was transferred to ICU. In spite of respiratory and medical support, his medical status worsened, so hematology team was consulted and red cell exchange transfusion was made with subsequent improvement in mental status. The second patient was a 45 year old patient with SCD-SC disease who was found at home confused, complaining of back, chest and extremities pain, with unsteady gait and labored breathing. In Emergency Department (ED) he was hypotensive with abdominal tenderness and hypoactive bowel movements. His labs showed acute hepatic and renal injury with severe metabolic acidosis. Patient was resuscitated with IV fluids and intubated. CT scan of the abdomen showed diffuse bowel inflammation. On the third day of admission, hematology team was consulted and Erythrocytapheresis was started. His mental status improved slowly but he continued to have a seizure disorder and had to be on hemodialysis. The third patient is a 46 year old with SCD-SS disease and chronic lower extremity ulcers who had recurrent admissions for hyperpigmented gallstones and endoscopic retrograde cholangiopancreatography with stent placements. He presented to ED with nausea, vomiting, diarrhea and fever for 3 days. He was found hypotensive, tachycardic, with respiratory distress and acute liver and kidney abnormalities on labs. He was intubated and started on fluids and antibiotics. Thirty hours post admission he underwent erythrocytapheresis. Conclusion Red cell exchange transfusions remain an effective but possibly underutilized and delayed therapy in acute sickle cell complications, especially acute chest and the multi-organ failure syndromes. It can provide needed oxygen carrying capacity while reducing the overall viscosity of the blood. Although the need for a central line and the requirement for sickle- negative, as-fresh-as-possible blood, matched for minor antigens are major reasons for delay, it seems that it is mostly delayed for clinical reasons, trying to rule out other disorders or contributing factors and when the apheresis starts the patients are in the hospital/ICU for days already. We conclude that in patients with sickle cell disorder (SS or SC) being hypoxic and with chest or multi-organ failure syndrome, red cell exchange transfusion is effective treatment modality and should be initiated as soon as possible. Disclosures: No relevant conflicts of interest to declare.

scholarly journals COVID-19 Infection and Outcomes at a Comprehensive Sickle Cell Center

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3105-3105
Author(s):  
Fuad El Rassi ◽  
Abeer N. Abouyabis ◽  
Ross M. Fasano ◽  
Morgan L. McLemore
Keyword(s):  
Chronic Pain ◽  
Sickle Cell Disease ◽  
Organ Failure ◽  
Acute Care ◽  
Sickle Cell ◽  
Fetal Hemoglobin ◽  
Red Cell ◽  
Cell Disease ◽  
Clinical Database ◽  
Virtual Visits

Abstract Introduction: The Grady Comprehensive Sickle Cell (SC) center is the largest adult sickle cell center in the United States (US) and has the first 24/7 acute care unit for management of sickle cell vaso-occlusive events (VOE). In 2019, the center provided 3077 sickle cell outpatient visits and 3695 acute care visits. When the COVID-19 pandemic reached the US, the center had a precipitous drop in the number of both outpatient clinic and acute care visits as state regulations for lockdown were passed. This report follows all the COVID-19 cases at a single adult center for sickle cell disease in one year. Methods: The clinical database has been tracking COVID-19 cases reported. Out of a total of 1343 patients, 55 patients contracted COVID-19 and were tracked in the clinical database with IRB approval. Results: Of the 55 patients with COVID-19, 28 were female and 27 were male. By genotype, 64% of patients were SS, 31% were SC and 5% were Sβ+ thalassemia. 35% of patient were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 31% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis. Chronic pain (defined as patients experiencing daily pain episodes for more than 4 days a week for the last 3 months) and calculation of daily morphine equivalents were reported in clinic follow-up and the narcotic database utilization. 47% of the patients had chronic pain and the median morphine equivalents was 90 mg daily (45-225mg). The rate of emergency department (ED) visits or hospitalizations for the sickle cell patients with COVID-19 was 80%. 49% of the SC patients' visits were related to VOE and 27% related to COVID-19 primarily. 20% of SC patients with COVID-19 were not seen in any emergency setting or required any hospitalization. The COVID-19 signs and symptoms experienced by the patients were as follows: 58% had pain as the main presenting symptom, followed by cough and fever (40%), dyspnea (31%), and pneumonia with chest x-ray evidence (25%). 2 patients developed acute respiratory distress syndrome (ARDS) and were intubated, and 2 patients died. 29% of the patients had lung findings on imaging and 16 of 55 patients required treatment with the use of Remdesivir in 9, dexamethasone in 8 and red cell products in 7 of the 16 patients. The 2 patients who died had both presented with COVID-19 infection in June and July 2020 respectively. One patient had presented in June 2020 with VOE and was found to have bilateral lung opacities but was asymptomatic and was discharged home to return few days later with clinical picture of multi-organ failure for which a red cell erythrocytapheresis was attempted. The second patient had presented in July 2020 with COVID-19 pneumonia and was treated with Remdesivir and convalescent plasma with development of multi-organ failure and ARDS. Discussion: Several reports were published regarding the rate of COVID-19 related mortality and morbidity in sickle cell disease. The Grady comprehensive sickle cell center experience differs in the fact that 16 out of 55 patients who had contracted COVID-19 required treatment and 2 of those 16 had died. In fact, the deaths occurred early in the course of the pandemic in June and July 2020 when 20 total cases were diagnosed (from March to Septemeber 2020). The remaining 35 cases registered zero deaths (October 2020 to March 2021) with the rate of complicated COVID-19 hospitalizations decreasing with better treatment available. In addition, the timeline for the COVID-19 cases reported fits the population timeline of 2 peaks respectively happening in the summer of 2020 and the Winter of 2021. During the initial peak, we have noted a decrease in the number of clinic and acute care visits respectively. This was anticipated given the statewide lockdown that was implemented. To circumvent that, the center adopted virtual visits to deliver healthcare needs. This measure has aided in protecting patients against COVID-19. Additionally, it is interesting that despite the second peak in the winter of 2021, there were no reported deaths among the patients who developed COVID-19. This finding can suggest that despite the concern for morbidity and mortality of sickle cell patients, their diligence and awareness to stay home during the pandemic has proven crucial in reducing morbidity and mortality and the option of virtual visits for healthcare delivery was key and should be utilized further in sickle cell care. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hyperhaemolysis in Sickle Cell Disease Is Not Necessarily a Transfusion Reaction

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4595-4595 ◽  
Author(s):  
Elizabeth A Jones ◽  
Louise Smith ◽  
Russell D Keenan
Keyword(s):  
Intensive Care ◽  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Organ Failure ◽  
Sickle Cell ◽  
Red Cell ◽  
Cell Disease ◽  
Sickle Cell Crisis ◽  
Life Threatening ◽  
Red Cell Transfusion

Abstract Hyperhaemolysis is a rare life threatening complication in sickle cell disease with rapidly dropping haemoglobin, intravascular haemolysis and haemoglobinuria leading to multi organ failure and death. The literature reports that hyperhaemolysis in sickle cell disease is a complication of red cell transfusion (Aragona et al., 2014 J. Pediatr. Hematol. Oncol.) and suggests management based on with holding further transfusion to avoid aggravating the haemolysis and using immunosuppression (Win 2009 Expert Rev. Hematol.). In the literature, all cases of hyperhaemolysis in addition to a recent blood transfusion, were in or had had a recent sickle cell crisis. We report a case of life threatening Hyperhaemolysis in a 5 year old child following a sickle cell crisis who had never previously been transfused. We suggest that, at least in this case, the hyperhaemolysis cannot be transfusion related. The theoretical case for management of withholding transfusion may not be sound and potentially dangerous. A female child with known sickle cell disease presented with temperature and chest pains, she had a Hb 72g/L (stable over a few years). She initially improved with oxygen, fluids and antibiotics. 36 hours after admission she acutely deteriorated with increasing pallor and dropping oxygen saturations. She started passing frank red urine which initially was considered to be haematuria but on investigation was haemoglobinuria. Her Hb dropped to 47g/L with no evidence of blood loss. Within hours of developing haemoglobinuria she required intensive care for respiratory support. She rapidly developed multi-organ failure requiring oscillatory ventilation, inotropes, and haemofiltration for renal support. She was managed with emergency red cell transfusion (her first ever) and within 12 hours of haemoglobinuria received a full red cell exchange transfusion. There were ongoing antibiotics for clinical respiratory infection and she was later confirmed to have influenza B. No steroids or other immune suppression were given. There was no evidence of acute bleeding to explain a drop in haemoglobin at any point. With maximum intensive care support including further transfusions she gradually improved and has made a full recovery. No deterioration was observed following transfusion. She has remained well since. She is now 13 years old and following such a dramatic episode she has remained on a transfusion programme with successful oral iron chelation. She has not experienced any further episodes of hyperhaemolysis and no red cell antibody has been detected at any time. This case demonstrates that hyperhaemolysis in sickle cell disease does not require a previous transfusion. We suggest that it is possible the previous reported cases are also not due to blood transfusion but are an acute form of haemolysis seen on the background of a chronic haemolytic disease. An increase in the rate of haemolysis may be related to other acute complications of sickle cell disease. We propose that the optimum management of hyperhaemolysis should include full supportive care including maintaining haemoglobin by transfusion. Immunosuppression in this case could have led to a worse outcome as influenza pneumonia was the likely initial trigger of the episode. Disclosures No relevant conflicts of interest to declare.

Plasma exchange in critically ill patients with sickle cell disease

2007 ◽  
Vol 37 (1) ◽  
pp. 17-22 ◽  
Author(s):  
C. Boga ◽  
I. Kozanoglu ◽  
H. Ozdogu ◽  
Emel Ozyurek
Keyword(s):  
Sickle Cell Disease ◽  
Plasma Exchange ◽  
Critically Ill ◽  
Sickle Cell ◽  
Critically Ill Patients ◽  
Cell Disease

scholarly journals Reconstruction of Sickle Cell Disease with Circulating Sickling Red Blood Cells in Novel Humanized Cytokines and Liver Mistrg Mice

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Yuanbin Song ◽  
Rana Gbyli ◽  
Liang Shan ◽  
Wei Liu ◽  
Yimeng Gao ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Mouse Model ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Red Cell ◽  
Cell Disease ◽  
Ineffective Erythropoiesis ◽  
Cd34 Cells

In vivo models of human erythropoiesis with generation of circulating mature human red blood cells (huRBC) have remained elusive, limiting studies of primary human red cell disorders. In our prior study, we have generated the first combined cytokine-liver humanized immunodeficient mouse model (huHepMISTRG-Fah) with fully mature, circulating huRBC when engrafted with human CD34+ hematopoietic stem and progenitor cells (HSPCs)1. Here we present for the first time a humanized mouse model of human sickle cell disease (SCD) which replicates the hallmark pathophysiologic finding of vaso-occlusion in mice engrafted with primary patient-derived SCD HSPCs. SCD is an inherited blood disorder caused by a single point mutation in the beta-globin gene. Murine models of SCD exclusively express human globins in mouse red blood cells in the background of murine globin knockouts2 which exclusively contain murine erythropoiesis and red cells and thus fail to capture the heterogeneity encountered in patients. To determine whether enhanced erythropoiesis and most importantly circulating huRBC in engrafted huHepMISTRG-Fah mice would be sufficient to replicate the pathophysiology of SCD, we engrafted it with adult SCD BM CD34+ cells as well as age-matched control BM CD34+ cells. Overall huCD45+ and erythroid engraftment in BM (Fig. a, b) and PB (Fig. c, d) were similar between control or SCD. Using multispectral imaging flow cytometry, we observed sickling huRBCs (7-11 sickling huRBCs/ 100 huRBCs) in the PB of SCD (Fig. e) but not in control CD34+ (Fig. f) engrafted mice. To determine whether circulating huRBC would result in vaso-occlusion and associated findings in SCD engrafted huHepMISTRG-Fah mice, we evaluated histological sections of lung, liver, spleen, and kidney from control and SCD CD34+ engrafted mice. SCD CD34+ engrafted mice lungs showed an increase in alveolar macrophages (arrowheads) associated with alveolar hemorrhage and thrombosis (arrows) but not observed control engrafted mice (Fig. g). Spleens of SCD engrafted mice showed erythroid precursor expansion, sickled erythrocytes in the sinusoids (arrowheads), and vascular occlusion and thrombosis (arrows) (Fig. h). Liver architecture was disrupted in SCD engrafted mice with RBCs in sinusoids and microvascular thromboses (Fig. i). Congestion of capillary loops and peritubular capillaries and glomeruli engorged with sickled RBCs was evident in kidneys (Fig. j) of SCD but not control CD34+ engrafted mice. SCD is characterized by ineffective erythropoiesis due to structural abnormalities in erythroid precursors3. As a functional structural unit, erythroblastic islands (EBIs) represent a specialized niche for erythropoiesis, where a central macrophage is surrounded by developing erythroblasts of varying differentiation states4. In our study, both SCD (Fig. k) and control (Fig. l) CD34+ engrafted mice exhibited EBIs with huCD169+ huCD14+ central macrophages surrounded by varying stages of huCD235a+ erythroid progenitors, including enucleated huRBCs (arrows). This implies that huHepMISTRG-Fah mice have the capability to generate human EBIs in vivo and thus represent a valuable tool to not only study the effects of mature RBC but also to elucidate mechanisms of ineffective erythropoiesis in SCD and other red cell disorders. In conclusion, we successfully engrafted adult SCD patient BM derived CD34+ cells in huHepMISTRG-Fah mice and detected circulating, sickling huRBCs in the mouse PB. We observed pathological changes in the lung, spleen, liver and kidney, which are comparable to what is seen in the established SCD mouse models and in patients. In addition, huHepMISTRG-Fah mice offer the opportunity to study the role of the central macrophage in human erythropoiesis in health and disease in an immunologically advantageous context. This novel mouse model could therefore serve to open novel avenues for therapeutic advances in SCD. Reference 1. Song Y, Shan L, Gybli R, et. al. In Vivo reconstruction of Human Erythropoiesis with Circulating Mature Human RBCs in Humanized Liver Mistrg Mice. Blood. 2019;134:338. 2. Ryan TM, Ciavatta DJ, Townes TM. Knockout-transgenic mouse model of sickle cell disease. Science. 1997;278(5339):873-876. 3. Blouin MJ, De Paepe ME, Trudel M. Altered hematopoiesis in murine sickle cell disease. Blood. 1999;94(4):1451-1459. 4. Manwani D, Bieker JJ. The erythroblastic island. Curr Top Dev Biol. 2008;82:23-53. Disclosures Xu: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Flavell:Zai labs: Consultancy; GSK: Consultancy.

scholarly journals Alkaline Phosphatase Is Associated with Red Cell Alloimmunization in the Pulmonary Hypertension and Hypoxic Response (PUSH) Sickle Cell Disease Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Victoria Brooks ◽  
Oluwalonimi Adebowale ◽  
Victor R. Gordeuk ◽  
Sergei Nekhai ◽  
James G. Taylor
Keyword(s):  
Risk Factors ◽  
Alkaline Phosphatase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Severe Disease ◽  
Case Control ◽  
Red Cell ◽  
Cell Disease ◽  
History Of

Background: Blood transfusion is a common therapy for sickle cell disease (SCD). Although, highly effective, a major limitation is development of alloantibodies to minor blood group antigens on donor red cells. Alloimmunization has a prevalence of 2-5% for transfusions in the general population, but it is significantly higher in SCD. Risk factors for alloimmunization have been poorly characterized, although number of lifetime transfusions is an important risk factor. Alloimmunization has been clinically observed in children with a prevalence of about 7%. With development of each antibody, blood donor matching becomes increasingly difficult and expensive with an increased risk for transfusion reactions and diminished availability of compatible red cell units for treatment of SCD. The ability to identify risk factors for developing alloantibodies would be beneficial for clinicians. To identify markers for alloimmunization in SCD, we have analyzed children and adults who developed this complication. Methods: We analyzed The Pulmonary Hypertension and Hypoxic Response in Sickle Cell Disease (PUSH) study, which enrolled n=468 pediatric and n=59 adult SCD subjects. In both children and adults, alloimmunization cases were defined as a history of at least 1 alloantibody. Controls in both cohorts were defined as subjects with no history of alloantibodies and receipt of more than 10 lifetime red cell transfusions. All others within the study who did not meet these criteria were assigned to a third comparison group. To identify differences between cases, controls and all others, we performed univariate analyses (using ANOVA or Kruskal Wallace where appropriate) for clinical parameters and laboratories. Case control comparisons were also performed for selected variables and plasma levels for 11 cytokines. Results were further analyzed using regression modeling. Results: The overall prevalence of alloimmunization was 7.3% among children (34/468 subjects; median age 12, range 3-20 years) compared to 28.8% in adults (17/59 subjects; median age 37, range 18-73 years). When only considering those with >10 lifetime transfusions, the prevalence was considerably higher at 29.3% and 54.8% in children and adults, respectively. At the same time, 8 pediatric (23.5%) and 5 adult (29.4%) alloimmunization cases had received fewer than 10 transfusions. In a 3-way pediatric cohort comparison (cases, controls and all others), risk factors associated with alloimmunization included SS genotype, older age and markers of more severe disease (higher ferritin, WBCs, platelets and total bilirubin). Comparison of cases to controls showed alkaline phosphatase (P=0.05) was significantly lower in cases, whereas AST (P=0.02) was significantly higher even with adjustment for age. Levels of plasma cytokines MCP-1 (P=0.01) and IFNgamma (P=0.08) were lower in cases from a subset of the pediatric cohort. In adults, only 4/59 (6.8%) subjects had never received a lifetime transfusion (all non-SS). In the adult 3-way comparisons, only SS genotype and higher ferritin were associated with alloimmunization. The adult case control analysis showed higher absolute monocyte count (P=0.02), absolute eosinophil count (P=0.04) and absolute basophil count (P=0.008) in association with alloimmunization cases. In addition, alkaline phosphatase was again significantly lower among cases (P=0.02) as seen in the pediatric cohort. There were no significant differences in cytokine levels among adults. Conclusions: When considering only transfused SCD patients, the prevalence of alloimmunization is higher than 30%. As seen in prior studies, higher lifetime red cell transfusions are an important risk factor especially among adults where most patients have received transfusions. Children who develop alloantibodies appear to have laboratory markers of more severe disease, but this is not observed in adults. A novel association observed across both pediatric and adult subjects is a significantly lower serum alkaline phosphatase in those with alloantibodies. The results of this study suggest a need for improved tracking of red cell transfusion therapy in the US for SCD patients due to a high prevalence of alloimmunization. Further study is also needed to elucidate the significance of the alkaline phosphatase association. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding; Imara: Research Funding.

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