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

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.

Download Full-text

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

Blood ◽

10.1182/blood.v116.21.4821.4821 ◽

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.

Download Full-text

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

Blood Advances ◽

10.1182/bloodadvances.2019001143 ◽

2020 ◽

Vol 4 (2) ◽

pp. 327-355 ◽

Cited By ~ 22

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.

Download Full-text

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

Blood ◽

10.1182/blood.v118.21.4850.4850 ◽

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.

Download Full-text

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

Blood ◽

10.1182/blood.v122.21.1005.1005 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1005-1005 ◽

Cited By ~ 1

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.

Download Full-text

Impact of Alloimmunization in Patients with Sickle Cell Disease

Blood ◽

10.1182/blood-2021-152829 ◽

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.

Download Full-text

TRANSFUSION PRACTICE, POST-TRANSFUSION COMPLICATIONS AND RISK FACTORS IN SICKLE CELL DISEASE IN SENEGAL, WEST AFRICA.

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2022.004 ◽

2022 ◽

Vol 14 (1) ◽

pp. e2022004

Author(s):

Moussa Seck ◽

Alioune Badara Senghor ◽

Mossane Loum ◽

Sokhna Aissatou Touré ◽

Blaise Félix Faye ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Median Number ◽

Transfusion Practice ◽

Red Cell ◽

Cell Disease ◽

Hiv Antibodies ◽

Transfusion Complications

Context and Objectives: Blood transfusions (BT) remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. We aim to assess infectious markers, red cell alloimmunization and iron overload secondary to BT in SCD patients. Materials and Methods: This is a case-control study included 253 SCD (153 SCD-transfused and 100 SCD non-transfused). We evaluated the transfusion practice (modalities, indications), post-transfusion complications (infections, alloimmunization, iron overload) and risk factors of these complications (socio-demographic, clinical, biological). Results: Median age was 28.5 years (5 - 59). Sex ratio was 0.86. Homozygous SCD was more common (95.3%). Simple BT was performed in 92.8% and transfusion exchange in 18.9%. Transfusion indications were dominated by acute anemia (57.06%) and vaso-occlusive crisis (VOCs) (14%). Red blood cell concentrates (RBC) were administered to 93.46%. Median number of RBC received per patient was 10 (2 - 48). The prevalence of VHC in SCD-transfused was 1.33% and 2% for VHB. Anti-HIV antibodies were not found. Red cell alloimmunization frequency was 16%. The most common alloantibodies were anti-rhesus (34.19%) and anti-Kell (23.67%). Iron overload was detected in 7.84%. The number of RBC transfused was the only risk factor for alloimmunization (p = 0.03) and iron overload (p = 0.023). BT frequency was not related to infectious transmission. Conclusion: Despite advances in blood safety, BT therapy is still a risk for SCD polytransfused patients. Although infectious transmission has rare, the risk of alloimmunization and iron overload is high in these patients.

Download Full-text

Clinical Effects of Chronic Red Blood Cell Exchange and Different Types of Red Cell Concentrates in Patients with Sickle Cell Disease

Blood ◽

10.1182/blood.v112.11.4823.4823 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4823-4823

Author(s):

Sergio Cabibbo ◽

Agostino Antolino ◽

Giovanni Garozzo ◽

Carmelo Fidone ◽

Pietro Bonomo

Keyword(s):

Sickle Cell Disease ◽

Blood Cell ◽

Iron Overload ◽

Sickle Cell ◽

Red Blood Cell ◽

Whole Blood ◽

Clinical Effects ◽

Red Cell ◽

Blood Components ◽

Cell Disease

Abstract For patients with severe SCD not eligible for hydroxyurea, two major therapeutic options are currently available: blood transfusion, and bone marrow transplantation. Either urgent or chronic red blood cell transfusion therapy, is widely used in the management of SCD but determines a progressive increase of ferritin level and is also limited by the development of antibodies to red cell antigens. The introduction of chronic red blood cell exchange and prestorage filtration to remove leucocytes and the use of techniques for multicomponent donation could be a good solutions. Thus, the aims of our studies were to evaluate the clinical effects of the different blood components in terms of annual transfusion needs and the intervals between transfusion, moreover we evaluated the efficacy of chronic red blood cell exchange (manual or automatic with cell separator) in preventing SCD complications and limiting iron overload. In our center we follow 78 patients affected by Sickle Cell Disease. We selected 36 patients occasionally treated with urgent red blood cell exchange because they had less than 2 complications/Year, and 42 patients regularly treated with chronic red blood cell exchange because they had more than 2 complications/Year with Hospital Admission. Moreover among these we selected 10 patients for fulfilling the criteria of continuous treatment at the Centre for at least 48 months with no interruptions, even sporadic and absolute transfusion dependency. All 10 patients were evaluated for a period of 4 years, during which two different systems of producing RCC were used. In the second two the patients were transfused with RCC obtained from filtering whole blood prestorage or with RCC from apheresis filtered prestorage. These products differed from those used in the preceding two years, during which the leucodepletion was obtained by bed-side filtration For all the patients we performed 782 automatic red blood cell exchanges and 4421 units of RCC were transfused. The exchange procedures were extremely well-tolerated by the patients and adverse effects were limited to symptoms of hypocalcaemia during automatic red blood cell exchange with cell separator. After every red blood cell exchange we obtained HbS level < 30%. The10 patients selected received respectively a mean of 6.9 and 6.1 units of RBCs exchanged per automatic procedure, in the first two years and in the second two years. Alloantibody developed in 14 patients but only 2 clinically significant and about the observed frequency of transfusion reactions it was very low. All patients treated with chronic red blood cell exchange had an improvement of the quality of life with a reduced number of complications/year (<2/year) and good compliance and moreover patients had limited iron overload making chelating therapy easier. In conclusion this study was focused on the most suitable characteristics of blood components for use in sickle cell disease patients and the choice of systematically adopting prestorage filtration of whole blood, enabled us to have RCC with a higher Hb concentration than standard. Moreover chronic manual or automatic red blood cell exchange as an alternative approach to simple long-term RBC transfusions give many advantages by being more rapid and tolerable as well as clinically safe and effective and minimize the development of iron overload especially when procedure was carried out with an automatic apparatus. To note that the clinical advantages for patients derived from good selection of the donor and good practices in the production of the blood components

Download Full-text

Splenic and Liver Involvement in Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.4763.4763 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4763-4763

Author(s):

Giovanna Graziadei ◽

Alessia Marcon ◽

Ilaria Gandolfi ◽

Martina Soldarini ◽

Erika Poggiali ◽

...

Keyword(s):

Liver Transplantation ◽

Sickle Cell Disease ◽

Liver Failure ◽

Sickle Cell ◽

Exchange Transfusion ◽

Adult Life ◽

Liver Involvement ◽

Cell Disease ◽

The Mean

Abstract Abstract 4763 Background. Sickle Cell Disease (SCD) is one of the most common severe monogenic inherited disorder worldwide characterized by the presence of hemoglobin S (HbS). HbS causes Hb polimerization leading to hemolytic anemia and vaso-occlusion due to erythrocyte rigidity, and is responsible of clinical acute events and chronic progressive multiorgan damage, which becomes evident with increasing age. The term SCD is used to refer to all the different genotypes: Sickle Cell Anemia (SCA) referring to homozygosis for βS allele; HbS/β-thalassemia, compound of β-thal and βS allele (T-SCD); and HbSC disease, owing to the coinheritance of βS and βcalleles. In Italy T-SCD is more frequent than SCA (70% vs 30% of SCD patients). Aims. This retrospective study involved 63 adult SCD patients of the Hereditary Anemia Centre of the Foundation IRCCS “Ca' Granda” Ospedale Maggiore Policlinico, in Milan, Italy. The aim was to assess and compare splenic and liver involvement in SCA and T-SCD patients. Methods. Mutation analysis of the b globin gene was performed by direct DNA sequencing by the ABI Prism 310 genetic analyzer. Clinical and hematological parameters were evaluated by routine tests and physical examination according to guidelines for SCD follow-up. Results. Sixty-three adult SCD patients, 19 SCA and 44 T-SCD patients, were evaluated. The b mutations detected in T-SCD were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2% of patients. The mean age of SCA patients was 36±8 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years and the mean age at the presentation to our Centre was 32±8 years. Five out of 19 (26.3%) of SCA group and 17/44 (38.6%) of T-SCD group were male. HbF mean levels were 7.7±4.9% and 10.7±7.5% respectively in SCA and T-SCD; Hb total mean levels were lower in SCA (9.2±1.2 g/dl) than in T-SCD (10.3±3.2 g/dl) patients. Comparing SCA and T-SCD patients, there was not statistically significant difference in the prevalence of clinical manifestations, except for splenic features. Splenectomy was performed in 3/19 (15.8%) SCA patients vs 23/44 (52.3%) T-SCD patients (p-value < 0.001). For the remaining patients, splenomegaly was absent in SCA, while was detected in 11/21 (52.4%) T-SCD. All SCA patients (100%) had functional asplenia, which was absent in T-SCD patients. Splenic infarctions were present in 2/16 (12.5%) SCA patients and in 6/21 (28.6%) T-SCD patients, of whom 5 had splenomegaly and one normal spleen size (pvalue <0.001). Liver damage is a clinical characteristic complication of adult life and plays an important role in the outcome of adult SCD patients. In our two groups 1/19 (5.3%) SCA and 3/44 (6.8%) T-SCD patients showed a severe alteration in cholestatic liver indices, and all of them showed high values of liver stiffness (KPa) detected by transient elastography suggesting cirrhosis in the SCA patient and fibrosis in the other ones. We underline a more severe increase of cholestatic indices if compared with the alterations of necrotic and stasis liver indices. Signs of liver failure were present in the SCA patient and in one of T-SCD patients. Both patients underwent to liver trans-jugular biopsy in order to evaluate the degree of liver damage. Trans-jugular approach was chosen because of high risk of bleeding with percutaneous procedure. Liver histology of the SCA patient showed signs of necrotic-inflammatory activity with packed sickle cells in the liver sinusoids, suggestive for “sickle liver cirrhosis”, while the biopsy of the T-SCD patient showed only liver fibrosis. They underwent to exchange transfusion in order to reduce the amount of sickling and were candidate to liver transplant. Conclusions. These data suggest that T-SCD patients, particularly those with severe b mutations, have similar clinical course than SCA patients. Splenomegaly is present only in T-SCD patients and seems to induce splenic infarctions. Only SCA patients experience functional asplenia. Liver involvement, a severe complication of the adult life, is characterized in both groups by sickle cholestatic liver involvement, that can lead to liver failure and, in some cases, to liver transplantation. Exchange transfusion, if started early at the diagnosis of liver disease, can avoid liver transplantation in some selected cases. Disclosures: Cappellini: Novartis Pharmaceuticals: Honoraria, Research Funding.

Download Full-text