Manual Chronic Partial Exchange In Children and Adolescents with Sickle Cell Disease: Impact on Clinical Outcome and Iron Overload

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4821-4821
Author(s):  
Michel Aloni ◽  
Alina Ferster ◽  
Phu-Quoc Le ◽  
Catherine Heijmans ◽  
Sophie Huybrechts ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Clinical Outcome ◽  
Iron Overload ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Red Cell ◽  
Cell Disease ◽  
Hb S ◽  
The Mean

Abstract Abstract 4821 Background: Red cell exchange transfusion is frequently used in the management of patients with sickle cell disease either electively or therapeutically to maintain an hemoglobin S (Hb S) level < 30–50%. This target is often difficult to maintain. In order to assess the effects of chronic partial exchange transfusion (CPET) a) on level of Hb and Hb S, b) on iron overload c) the need for chelation, d) on risk of long term adverse events and e) clinical outcome, we analyzed the data of sickle cell disease patients treated by long term CPET in our center. Methods/subjects: In the cohort of 163 SCD patients followed at University Children's Hospital at Brussels (Belgium), 10 benefit from CPET. Main reasons for CPET were neurologic disease (4), frequent ACS (3), previous severe hepatic cholestasis (2), leg ulcer (1) and pulmonary hypertension (1). The median age at start of treatment was 13 years (range 4 –19). These patients (6 males and 4 females) account for 248 exchanges during a median follow-up of 20 months (range 6– 36). These exchanges are until now performed manually and the volume exchanged is calculated taking into account the Hb level and the last HbS percentage. It is usually between 30 and 40 ml/kg BW. Except if severe anemia occurs, the goal of these exchanges is to keep a constant hematocrit level. All patients had a full red cell phenotype performed and received blood matched for ABO, Rhesus, Kell and Duffy antigens systems. The estimation of iron balance (iron intake- iron removed) was calculated yearly. Results: The pre-exchange Hb value was 9.5 g/dl (median; range: 7.7–10.9 g/dl) and the mean post value was 9.4/dl (range: 8.4– 11.1 g/dl). These values are not statistically different (p> 0.05). The majority of patients (9/10) are reached an HbS < 50% when measured 3–5 weeks after PET (just before the next procedure) with a median HbS value of 40% (range: 30–54). At start of CPET program, the median ferritin level was 439 ng/ml (range: 80 – 1704). Five patients had already a ferritin > 500 ng/mL due to numerous previous transfusions. At last evaluation, the median ferritin did not change significantly and was 531 ng/ml (range 84– 3840). The two patients with ferritin higher than 1000 ng/ml start chelation with good result for one. One The mean annual net RBC load were 1.72 ml RBC/kg/yr provided approximately 1.85 mg of iron/kg/yr. Individual data are given in table 1. CPET-treated patients exchanged showed clinical improvement with disappearance of SCD crisis and related complications. The procedure was well tolerated by most patients, and adverse effects were limited to mild hypotension (3/10). No autoimmune hemolysis or allo-immunisation was documented in this cohort. All children remained negative for HIV and hepatitis C virus infections. Conclusion: Manual CPET seems to be safe to prevent middle-term iron overload and the need of elation therapy in most of patients. CPET can therefore be recommended for SCD patients who required decreased in Hb S levels either prophylactically or therapeutically. Manual are safe, effective and easy to use when mechanized exchanges are not possible for technical reasons. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role of Automated Red Cell Exchange in Acute and Chronic Complications of Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3674-3674
Author(s):  
Shivi Jain ◽  
Adam Rock ◽  
Caitlin Lopes ◽  
Santosh L. Saraf ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Hematological Parameters ◽  
Red Cell ◽  
Cell Disease ◽  
Chronic Complications ◽  
The Mean ◽  
The Difference

Abstract Background. Automated red cell exchange transfusion (ARCET) is commonly used in patients with sickle cell disease, but objective data on its impact on acute and chronic complications are limited. Methods. Fifty-two sickle cell disease patients at the University of Illinois at Chicago underwent exchange transfusion from January 2011 to January 2016. Six patients were excluded due to incomplete data leaving 46 patients available for analysis. We collected data from the year before, year after and the year of ARCET to study the impact of red cell exchange on clinical, biological and hematological parameters. Results. There were 435 procedures with average of 9.45 per patient (range 4-14). The mean age of our cohort was 58.2 years. There were 22 (47.8%) males and 24 (52.2%) females. Genotypes include 42 (91.3%) HbSS, 1 (2.2%) HbSC, 1 (2.2%) HbSBeta+thalassemia and 2 (4.3%) HbSBeta0thalassemia. The most common indication for ARCET in our cohort was prior stroke in 32 patients (69.6%) and prevention of stroke in 7 patients (15.2%), followed by frequent vaso-occlusive crisis (VOC) 8 patients (17.4%), multiple acute chest syndrome 6 patients (13%), pulmonary hypertension 6 patients (13%) and chronic kidney disease 5 patients (8.9%). Iron overload, sickle hepatopathy, cardiomyopathy and seizure were some of the other indications. Twenty-five patients (54.3%) had more than one indication to undergo the ARCET. Thirty-one patients (67.4%) are still continuing the treatment. Thirty patients (65.2%) were on hydroxyurea (HU) prior to ARCET and 8 patients (17.4%) were still on HU while on ARCET. The mean frequency of ARCET was every 6 weeks. The mean pre and post ARCET values for hemoglobin(Hb), hematocrit (Hct), Hemoglobin S %(HbS), white cell count (wbc) and platelets(plt) are shown in Table 1. Paired t-test and Wilcoxon signed-rank test were used to analyze the clinical and hematological parameters. Analysis shows increase in mean Hb and Hct post ARCET and decrease in mean wbc, plt and HbS % post ARCET and the difference is statistically significant. (Table 3). Post ARCET body mass index (BMI) and weight are increased and the difference is statistically significant with p value 0.002 for BMI and 0.003 for weight. (Table 3). Ten (21.7%) patients showed decrease in the ferritin level post exchange. Thirty patients (65%) had VORTEX port whereas 29 patients (63%) had central venous access for procedures prior to Vortex placement (17/29, 59%). Nine patients (20%) had peripheral access mostly power port (for access) with one peripheral vein for return (6/9 67%). There were 10 access related complications and there were 3 port replacements due to septum damage and infection. There were 10 procedure related complications and 10 transfusion reactions as described in Table 2. ED admissions were decreased in 13(28.3%) patients from mean 7.69 to 2.92 admissions. The annual inpatient admissions showed a decrease in 18(39.2%) patients from mean 4.6 days pre ARCET to 1.6 admissions post ARCET. The acute care admissions showed an increase due to program expansion of our acute care center during this study period. Discussion. Our study shows that red cell exchange is an effective treatment modality for patients with sickle cell disease. It contributes to improvement in weight, increase in Hb and Hct and decrease in wbc, plt, HbS% and iron overload. It also decreases inpatient and ED admissions. The procedure is safe and tolerable with minimal complications. Long term studies are needed study the efficacy of this treatment modality and its contribution to improvement of quality of life and life expectancy in sickle cell disease patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support

2020 ◽  
Vol 4 (2) ◽  
pp. 327-355 ◽  
Author(s):  
Stella T. Chou ◽  
Mouaz Alsawas ◽  
Ross M. Fasano ◽  
Joshua J. Field ◽  
Jeanne E. Hendrickson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Practice Research ◽  
Evidence Based ◽  
Red Cell ◽  
Cell Disease ◽  
American Society

Background: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. Objective: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. Methods: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. Results: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. Conclusions: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.

scholarly journals How I treat and manage strokes in sickle cell disease

Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3401-3410 ◽  
Author(s):  
Adetola A. Kassim ◽  
Najibah A. Galadanci ◽  
Sumit Pruthi ◽  
Michael R. DeBaun
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Management Strategies ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Hematopoietic Stem ◽  
Neuro Imaging

Abstract Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD.

scholarly journals Fat Embolism Syndrome in Sickle Cell Disease

2020 ◽  
Vol 9 (11) ◽  
pp. 3601
Author(s):  
Dimitris A. Tsitsikas ◽  
Jessica Bristowe ◽  
Jibril Abukar
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complete Recovery ◽  
Neurological Impairment ◽  
Fat Embolism ◽  
Red Cell ◽  
Cell Disease ◽  
Embolism Syndrome ◽  
Severe Neurological Impairment

Fat embolism syndrome is a devastating complication of sickle cell disease resulting from extensive bone marrow necrosis and associated with high mortality rates, while survivors often suffer severe neurological sequelae. Despite that, the syndrome remains under-recognised and under-diagnosed. Paradoxically, it affects exclusively patients with mild forms of sickle cell disease, predominantly HbSC and HbSβ+. A significant number of cases occur in the context of human parvovirus B19 infection. We provide here a brief summary of the existing literature and describe our experience treating 8 patients in our institution. One patient had HbSS, 6 HbSC and 1 HbSβ+. All patients developed type I respiratory failure and neurological involvement either at presentation or within the first 72 h. The most striking laboratory abnormality was a 100-fold increase of the serum ferritin from baseline. Seven patients received emergency red cell exchange and 1 simple transfusion. Two patients (25%) died, 2 patients (25%) suffered severe neurological impairment and 1 (12%) mild neurological impairment on discharge, while 3 (38%) patients made a complete recovery. With long-term follow-up, 1 patient with severe neurological impairment and one patient with mild neurological impairment made dramatic improvements, making the long-term complete recovery or near complete recovery rate 63%. Immediate red cell exchange transfusion can be lifesaving and should be instituted as soon as the syndrome is suspected. However, as the outcomes remain unsatisfactory despite the increasing use of red cell exchange, we suggest additional therapeutic measures such as therapeutic plasma exchange and pre-emptive transfusion for high risk patients.

scholarly journals Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1136-1142 ◽  
Author(s):  
HC Kim ◽  
NP Dugan ◽  
JH Silber ◽  
MB Martin ◽  
E Schwartz ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Cell Disease ◽  
Donor Blood ◽  
Iron Load ◽  
Blood Usage ◽  
Hb S

Abstract Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.

Effectiveness, Time Utilization and Clinical Outcome of Partial Manual Red Cell Exchange in Patients with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2326-2326
Author(s):  
Kevin H.M. Kuo ◽  
David Barth ◽  
Richard Ward
Keyword(s):  
Sickle Cell Disease ◽  
Clinical Outcome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Venous Access ◽  
Iron Chelation Therapy ◽  
Red Cell ◽  
Cell Disease ◽  
Hemoglobin S

Abstract Abstract 2326 Introduction: Red cell exchange transfusion (RBCX) is used to treat and prevent selected complications from Sickle Cell Disease (SCD) where there is a need to reduce hemoglobin S level, blood viscosity, improve oxygen carrying capacity, and to avoid rapid iron overload from simple transfusions. Partial manual red cell exchange is sometimes employed in the chronic maintenance of low hemoglobin S levels. Data on the efficacy and clinical outcome of SCD patients on partial manual RBCX are limited. Methods: All partial manual RBCX from the University Health Network, a SCD comprehensive care center between April 1st, 2010 and April 30th, 2011 were retrospectively reviewed. Patients were exchanged at a frequency of 4 to 6 weeks where each session consists of two 500cc phlebotomy with an infusion of 500cc normal saline in between the phlebotomies, and transfusion of 2 units of packed red cells (pRBC). The procedure was repeated until pre-RBCX hemoglobin S (HbS) level <50% was reached (for patients without overt stroke for >4 years). Phlebotomy was reduced or omitted during episodes of symptomatic anemia at the discretion of the treating hematologist. Patients with poor venous access had indwelling line with chronic, therapeutic anticoagulation against line-related thrombosis. Results: Nineteen patients (16 HbSS, 2 HbSC, 1 HbSD) totalling 176 exchange sessions were reviewed. Indications for RBCX include primary and secondary stroke prevention (n = 14), recurrent painful vaso-occlusive crises intolerant or refractory to hydroxyurea (n = 3), pulmonary hypertension confirmed on right heart catheterization with hypoxia (n = 1), and prevention of intrahepatic cholestasis in a liver allograft (n = 1). Mean frequency of RBCX was 4.8 weeks (95% CI 3.9, 5.6 weeks). There were 2 transfusion-related (fever, pruritis) and 1 phlebotomy-related (pre-syncope) adverse events. There were 23 partial/cancelled phlebotomy sessions, mostly due to symptomatic anemia. Mean post-RBCX hematocrit was 0.296 (95% CI 0.280, 0.312) and pre-RBCX HbS level was 0.439 (95% CI 0.387, 0.490). Pre-RBCX HbS level of <50% was achieved in 74% of exchanges. Reasons for not achieving the target HbS level include: exchange interval >4.0 weeks, not on any transfusion regime prior to initiating partial manual RBCX, reduced or no phlebotomy in previous session, and non-adherence to treatment. Patients who were adherent to treatment had no recurrent events related to their initial indication for RBCX (one patient has possible Moyamoya formation but no clinically overt stroke), while 3 of the 6 patients who were not adherent had events during the study period (2 had painful vaso-occlusive crisis requiring hospital admission and 1 had new Moyamoya-like changes on cerebral angiogram). It took a median time of 90 minutes to phlebotomize 1,000cc whole blood and 176 minutes to transfuse two units of pRBC. There was no significant difference between the time required to phlebotomize or transfuse via peripheral vein versus an indwelling line (55 vs. 53 minutes/500cc; P = 0.7572 and 88 minutes vs. 88 minutes/unit; P = 0.9859). Eleven patients were also on iron chelation therapy for iron overload from previous simple transfusion, and patients who were adherent to RBCX (n = 7) had either a stable or reduction in ferritin level. Discussion: Patients who are adherent on partial manual RBCX can maintain a pre-RBCX HbS <50% with good clinical outcomes and low rates of adverse events, reduced blood consumption compared to automated RBCX, and obviate the need for ongoing iron chelation in those without pre-existing iron overload. In patients with iron overload, RBCX combined with iron chelation therapy can maintain iron balance. In patients with good peripheral venous access, indwelling lines do not confer an advantage to the speed of phlebotomy or transfusion. Patient with pre-RBCX HbS level >50% may benefit from a single session of automated RBCX to “reset” their HbS level before commencing chronic partial manual RBCX. Further prospective studies will aim to determine the rate of new or progressive silent infarcts and vasculopathy and reduction of iron balance via partial manual RBCX. Disclosures: Kuo: Novartis Canada: Research Funding.

Estimating Iron Burden in Simple Vs. Modified Manual Exchange Transfusions in Pediatric Sickle Cell Patients on Chronic Transfusions

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4850-4850
Author(s):  
Mansi Lalwani ◽  
Mary DeBarr ◽  
Ann O'Riordan Mary ◽  
Connie M Piccone ◽  
Brian W Berman
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Red Cell ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Packed Red Blood Cells ◽  
Transfusion Protocol

Abstract Abstract 4850 Introduction: Nearly 100,000 Americans are affected by sickle cell disease (SCD), making it one of the most prevalent genetic disorders in the United States. Individuals with SCD exhibit significant morbidity and mortality related to chronic hemolysis, vasculopathy, and vascular occlusion by red cell sickling. Currently, red cell transfusions are a primary therapy for some of the acute and chronic complications of SCD, including prevention and treatment of stroke. The benefits of transfusion therapy are well known; however, transfusional iron overload is an inevitable consequence. Excess iron in the circulation leads to the formation of reactive oxygen species which ultimately causes end-organ damage. It is well established that adult SCD patients with significant iron overload have a higher mortality. As a result, exchange transfusion protocols are utilized to try to decrease overall iron overload. In our center, a modified manual exchange (MME) protocol is used which involves therapeutic phlebotomy of approximately 5–7.5ml/kg followed by the infusion of 15–20ml/kg packed red blood cells. MME is performed in the outpatient setting every 4–6 weeks with a goal hemoglobin S of less than 30%. Objective: The primary objective of our study was to describe the benefits of a MME protocol compared with a simple transfusion protocol in patients experiencing both. The effects of MME versus simple tranfusion on systemic iron overload were evaluated using serum ferritin levels, net transfusion volume, and need for iron chelation therapy. Study Design/Methods: A retrospective chart review was performed on patients with SCD (type SS) less than 18 years of age who were on chronic transfusions and transitioned from a simple to a MME protocol. All patients included were on chronic transfusions for primary/secondary stroke prevention. Exclusion criteria included all patients on automated exchange transfusion protocols and those patients who started iron chelation therapy after January 1, 2008. Demographic as well as clinical and laboratory data were collected on each patient. A simple transfusion was defined as 20ml/kg packed red blood cells transfused every 4–6 weeks. The MME protocol was defined as above. Iron overload was assessed using indicators including net volume of blood transfused, serum ferritin, and the need for iron chelation during both time periods, and differences were calculated. The Wilcoxon signed rank test was used for the change in amount of blood transfused. Slopes of ferritin levels over time were estimated for each transfusion protocol separately using mixed model methods. The need for chelation therapy was tabulated for each patient. Results: A total of six patients were included in the study, 4 boys and 2 girls. Ages ranged from 6–14 years. Four patients had been on chronic transfusions for more than 2 years prior to the start of our study. The mean net volume transfused during simple transfusion and MME was 400ml and 290ml, respectively (p=0.03). The slope of ferritin rise was 0.18 (CI: 0.11, 0.84) for MME and 1.37 (CI: 0.56, 2.17) for simple transfusion. One patient was taken off chelation therapy completely after transitioning to MME and another patient was maintained on low-dose chelation while on MME. Conclusions: MME appears to reduce the amount of blood transfused, slow the rise of ferritin, and potentially reduce the need for additional medication. MME may provide a safe and cost effective approach for delaying or preventing iron overload in patients with sickle cell disease who require long term transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

Transfusional Iron Overload In An Adult Sickle Cell Disease Population: Epidemiology, Prevalence, and Management

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1005-1005 ◽  
Author(s):  
James Son ◽  
Hongyan Xu ◽  
Nadine J Barrett ◽  
Leigh G Wells ◽  
Latanya Bowman ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Organ Damage ◽  
Morbidity And Mortality ◽  
Genotype Distribution ◽  
Cell Disease ◽  
The Mean

Abstract Transfusional iron (Fe) overload remains a significant problem among patients with chronic, transfusion dependent anemias, especially in transfusion dependent ß-thalassemia (Thal) syndromes. If not treated vigorously with chelation, Fe overload in Thal is associated with significant organ damage, especially with chronic liver disease and cardiac abnormalities which can contribute to morbidity and mortality. In recent decades, the significance of Fe overload in sickle cell disease (SCD) has also been recognized especially among pediatric patients on chronic transfusion regimens predominantly for primary and secondary prevention of stroke. The prevalence and significance of this problem among adult SCD patients is less clear, although it is widely believed that episodic, mostly unnecessary transfusion practices play a more prominent role in this patient population. There have been reports of an association between iron overload and increased morbidity and mortality among adult SCD patients; it has also been speculated that the chronic inflammatory state that exists in SCD affords some degree of protection against severe organ damage through upregulation of hepcidin and sequestration of Fe in these patients. We performed a retrospective review of 635 adult SCD patients followed at our Center to define and ascertain the epidemiology, prevalence, etiology, and clinical correlates of transfusional Fe overload. Fe overload was defined as two consecutive serum ferritin values of > 1000 ng/ml. 80 patients (12.6%) met this criterion. Of these, 38 were male and 42 were female. Genotype distribution was: 73 SS, 3 S-β+ thal, 2 S-β0 thal and 2 SC. The mean age was 35.9 (range 18-69). Out of the 80 patients with transfusional Fe overload, 24 (30%) were/had been on a chronic transfusion regimen (23 for secondary or primary stroke prevention and one for childhood cardiomyopathy). Seventy percent of the patients (n=56) developed Fe overload from episodic transfusions predominantly performed at outlying community hospitals. The mean highest ferritin value was 4991 ng/ml (range 1,052-16,500). There was no correlation between ferritin levels and the number of hospitalizations or painful episodes (p=0.9). Thirty seven patients (46.2%) had a history of chelation therapy (with desferoxamine, deferasirox, or both). In 25 patients who have been on deferasirox for a period of 6 months or more, serum ferritin levels decreased from 4452.3 to 3876.6 ng/ml (p=0.3239). Our retrospective study shows that transfusional Fe overload is not rare among adults with SCD and develops predominantly as a result of episodic blood transfusions. This underscores the importance of the development and dissemination of evidence based guidelines, especially for episodic transfusions in SCD. A careful study of the extent and degree of organ damage associated with transfusional Fe overload in SCD and why less than half (46.2%) of patients are exposed to chelation therapy needs to be done. These studies should include liver iron concentration (LIC), cardiac iron and liver histology, when indicated, in parallel with serum hepcidin levels. The fact that the reduction in serum ferritin levels with deferasirox did not reach statistical significance in this cohort can be explained by the relatively small number of patients as well as by the short period (6 months) of exposure to chelation therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Alloimmunization in Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3251-3251
Author(s):  
Dipanjan Debnath ◽  
Hedy P Smith ◽  
Cathy Conry-Cantilena ◽  
Valentina Baez Sosa
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Health System ◽  
Sickle Cell ◽  
Organ Damage ◽  
Cell Disease ◽  
Academic Health ◽  
End Organ Damage ◽  
The Mean

Abstract INTRODUCTION Blood transfusion is an essential therapeutic and prophylactic component in the management of sickle cell disease (SCD) and associated complications. Prolonged transfusion therapy can lead to the development of antibodies to the donor's RBC antigens (alloimmunization), causing complications such as delayed hemolytic transfusion reactions, hyperhemolysis, worsening vaso-occlusive episodes, and end-organ damage. There have been only a few case series highlighting the impact of RBC alloimmunization on SCD morbidity and mortality, proposing a pathway involving RBC alloimmunization and decreased survival associated with hemolytic reactions or difficulty obtaining compatible blood when needed. However, apart from the consequences of iron overload, there is no long-term data for alloimmunization highlighting the clinical consequences, multiorgan damage, or associated morbidity in sickle cell patients. AIM The primary aim is to investigate the incidence of alloimmunization in SCD patients in an academic health system. The secondary aim is to elucidate the differences in demographics, frequency of vaso-occlusive crisis, end-organ damage, and inflammatory markers between alloimmunized and non-alloimmunized SCD patients. METHODS We conducted a retrospective multicentric descriptive study, including all sickle cell patients treated in an academic health system from January 1st, 2009, to December 31st, 2020, in Maryland, Virginia, and Washington, DC. An exemption from the Institutional Review Board for obtaining individual subjects' consent was procured. Patients included in the study were older than 18 years and diagnosed with sickle cell disease. Patients who did not have sickle cell disease were excluded from the study. Statistical analysis was reported using means for descriptive data, t-test for continuous variables, and chi-square for categorical variables. RESULTS A total of 94 patients with sickle cell disease were included in the study. Of these, 24 (25.5%) patients were found to have alloimmunization, whereas 70 (74.4%) patients did not. Of the alloimmunized patients, the average age, BMI and BSA were 30.15 years (p=0.037), 23.15 kg/m2 (p=0.040), and 1.65 m2 (p=0.003) compared to 37.07 years, 26.17 kg/m2 and, 1.84 m2 respectively among the non-alloimmunized group. 83% of the alloimmunized patients had sickle cell anemia (Hb SS), and 17% had a sickle thalassemia phenotype (p=0.005). A lower baseline hemoglobin (Hb) value of 8.01 g/dL was seen among alloimmunized patients compared to a higher Hb value of 9.63 g/dL (p=0.001) among the non-alloimmunized. Alloimmunized patients had an average of 5.55 alloantibodies. The average number of vaso-occlusive crises per year and related hospitalizations was statistically significantly higher in the alloimmunized group with 4.82 and 3.78, respectively, compared to 2.34 (p=0.035) 1.01 (p=0.0005) in the non-alloimmunized group. Similarly, the incidence of other sickle cell-related complications were higher among the alloimmunized patients, such as priapism (29% vs. 9%; p=0.0139), pulmonary hypertension (38% vs. 9%; p=0.0038) with no statistical difference in the iron overload (25% vs. 11%; p=0.150) or ferritin levels (. 83% of alloimmunized patients had a history of narcotic use vs. 34% among the non-alloimmunized (p=0.0001). Higher use of disease-modifying therapies including hydroxyurea (71% vs. 31%; p=0.0009) and voxelotor (13%vs0; p=0.0029), were also seen among alloimmunized patients. While no statistically significant difference was seen in the mean number of lifetime transfusions, there was a difference in the mean number of lifetime exchanges (3.67 vs. 0.0; p=0.0208). CONCLUSION The prevalence of alloimmunization in sickle cell patients in our study population (25.5%) was higher than in the literature (7- 59%) and the general population (2%). An increase in alloimmunization was associated with an increased number of exchanges but not with simple transfusions. Independent from the iron overload, alloimmunization was associated with increasing end-organ damage and sickle cell complications such as priapism, pulmonary hypertension. Strategies to decrease alloimmunization are needed to prevent these complications. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparison between Automated Erythrocytopharesis (AECP) and Manual Exchange Transfusion (M-Ex)) in Reducing Hb-S and in Recovery of Acute Chest Syndrome and Other Acute Presentations of Sickle Cell Disease Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4928-4928
Author(s):  
Said Yousuf Ahmed ◽  
Sameh M. Saleh ◽  
Mohamed Shefan Hameed ◽  
Ahmed M. Ragheb ◽  
Telal M. Abbas ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Hemoglobin S ◽  
Artery Thrombosis ◽  
Hb S

Abstract Background: Sickle Cell Disease represents a national health problem in Saudi Arabia with close to 150 thousands of the population are afflicted with the disease. Patients are frequently admitted with life threatening complications like Acute chest syndrome (ACS), Hyperhemolysis (HH), pneumonia, thromboembolism including pulmonary Artery Thrombosis (PAT) or severe protracted painful vasoocclusive crises (VOC). Rapid lowering of Hemoglobin S helps in reducing sickling and in alleviating such complications and allowing rapid recovery. Exchange transfusion is the fastest way to remove pathogenetic sickling red blood cells and reducing Hb S level to a safe level. It can be done manually (Mex) or via Automated Erythrocytopharesis machine (AECP). In this study we compared manual exchange to AECP in achieving the targeted lowering of Hb S and in accelerating clinical recovery. Patients and Methods: Patients included are sickle cell disease patients (HbSS, HbSC, Hb S/thal) admitted to the ER of a central Hospital. Indications of exchange were: acute chest syndrome, acute severe painful vaso-occlusive crises refractory to standard ER protocol of analgesia, stroke, priapism, Hyperhemolysis, and acute pulmonary embolism. P value of significance was calculated using student t-test comparing between median Hb S achieved after manual exchange vs AECP. To assess the rapidity of reversal of desaturation in acute chest syndrome patients, the cumulative incidence of reversal of desaturation and normalization of Oxygen saturation on room air were plotted against time at 0 time of the start of exchange, 2 hours,4 , 12, 24, 48 and 72 hours/discharge (D/C) Results: Table 1 shows clinic-biological characteristics of patients who underwent exchange transfusion. A total of 230 patients-admissions were registered between Dec 1. 2017 to July 27, 2018 for painful VOC to ER; 51 (32%) had clinical indications for exchange (ACS 25, Stroke / fits 1, priapism 1, pulmonary artery thrombosis 1, Hyperhemolysis with VOC (n:7) , VOC with HLH (n:1), and the remaining with "refractory" painful VOC with or without infection. One patient died immediately at the time of arrival to ER before starting any standard resuscitative measures . Exchange transfusion was indicated and done for 53 (23%); 12 (22,6%) AECP and the remaining (77.4%) had Manual Exchange. The median Hb S after manual exchange was 44 % (range 31-74%) which was unsatisfactory and way higher than the targeted level while Automated ECP reached down satisfactorily to a median of 31%(range 8%-50%) ; 67% of whom achieved it with only one session. No mortalities or major procedure related complication reported with manual or automated ECP. Procedurally, 3 patients needed 2 automated sessions and 1 patient used 2 kits for one session. Manual exchange could not achieve the target Hemoglobin S level below or around 30% due to logistic and technical difficulties and sometimes patients' refusal while Automated ECP reached to a mean Hb s level of 28%( range 8%-50%) and nearly two thirds (67%) reached to as low as 31% Hb S level with only one session of Automated ECP and was associated with rapid improvement of the oxygenation within the first 2 hours of the procedure. Conclusions: Erythrocytopharesis (Automated RBC exchange) is effective, quick and safe procedure that is life saving for many patients with ACS and is associated with less difficulties and complications if compared with the manual exchange. Because SCA is a national problem in Saudi Arabia and acute chest syndrome and other acute major complications comprehensively kill SCD patients, Automated Erythocytopharesis should be available nation-wide like dialysis machines at all large hospitals in all cities and should be distributed according to the prevalence of SCA in the area or location. Disclosures No relevant conflicts of interest to declare.

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