Severity of Iron Overload in Patients with Sickle Cell Disease Receiving Chronic Red Blood Cell Transfusion Therapy

Vox Sanguinis ◽  
2000 ◽  
Vol 79 (4) ◽  
pp. 265-265 ◽  
Author(s):  
C.P. Engelfriet ◽  
P. Harmatz ◽  
E. Butenski ◽  
K. Quirolo
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Red Blood Cell Transfusion ◽  
Cell Disease ◽  
Transfusion Therapy

Sickle crisis in the critically ill

2016 ◽  
Author(s):  
Shilpa Jain ◽  
Mark T. Gladwin
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Systemic Infection ◽  
Red Blood Cell Transfusion ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Ischaemia Reperfusion Injury ◽  
Transfusion Therapy

Sickle cell disease crises are precipitated by an acute occlusion of microvessels, which can lead to end organ ischaemia reperfusion injury and acute haemolysis. Acute fat emboli syndrome, acute lung injury (the acute chest syndrome), acute pulmonary hypertension, and cor pulmonale, haemorrhagic and occlusive stroke, and systemic infection represent the most common life-threatening complications observed in current ICU practice. General principles of management in all patients admitted to the critical care unit are hydration, antibiotics, pain control, and maintenance of oxygenation and ventilation. Red blood cell transfusion therapy is the treatment of choice for most complications of sickle cell disease requiring intensive care management. Transfusion of sickle negative, leukoreduced red blood cells, phenotypically matched for Rhesus and Kell antigens is the minimum standard of care in sickle cell disease patients as they have a high incidence of red blood cell alloimmunization.

Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 76-79 ◽  
Author(s):  
Paul Harmatz ◽  
Ellen Butensky ◽  
Keith Quirolo ◽  
Roger Williams ◽  
Linda Ferrell ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Liver Biopsy ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Liver Iron ◽  
Transfusion Therapy

Chronic transfusion therapy is being used more frequently to prevent and treat the complications of sickle cell disease. Previous studies have shown that the iron overload that results from such therapy in other patient populations is associated with significant morbidity and mortality. In this study we examined the extent of iron overload as well as the presence of liver injury and the predictive value of ferritin in estimating iron overload in children with sickle cell disease who receive chronic red blood cell transfusions. A poor correlation was observed between serum ferritin and the quantitative iron on liver biopsy (mean 13.68 ± 6.64 mg/g dry weight;R = 0.350, P = .142). Quantitative iron was highly correlated with the months of transfusion (R = 0.795, P < .001), but serum ferritin at biopsy did not correlate with months of transfusion (R = 0.308, P = .200). Sixteen patients had abnormal biopsies showing mild to moderate changes on evaluation of inflammation or fibrosis. Liver iron was correlated with fibrosis score (R = 0.50, P = .042). No complications were associated with the liver biopsy. Our data suggest that, in patients with sickle cell disease, ferritin is a poor marker for accurately assessing iron overload and should not be used to direct long-term chelation therapy. Despite high levels of liver iron, the associated liver injury was not severe.

scholarly journals Effects of Combination Hydroxyurea and Chronic Red Blood Cell Transfusion Therapy on the Immune Parameters of Patients with Sickle Cell Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4840-4840
Author(s):  
Mahogany Oldham ◽  
Gelina Sani ◽  
Stefanie Margulies ◽  
Jennifer Webb ◽  
Robert Sheppard Nickel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Combination Therapy ◽  
Blood Cell ◽  
Nk Cells ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Nk Cell ◽  
Red Blood Cell Transfusion ◽  
Cell Disease ◽  
Transfusion Therapy

Background: Sickle cell disease (SCD) is typically characterized as a red blood cell disorder but our understanding of the effects on the immune system is limited. Patients with sickle cell disease have been shown to have unique inflammatory profiles, immune phenotypes and function. Others have shown that during vaso-occlusive crises patients with SCD have elevated counts of neutrophils, monocytes, and cytokines as well as increased activity of invariant natural killer T cells (iNKT).We have previously shown that hydroxyurea use is associated with a normalization of the increased NK cell number and function. While there are studies that describe on the effects of single therapy, there is little known about combination therapy. Therefore, our study investigated immunological changes in pediatric patients on combination therapy, which was defined as hydroxyurea added to chronic red blood cell transfusion treatment. Methods: Patient data and peripheral blood samples were collected from an ongoing pilot study of combination therapy hydroxyurea and simple chronic transfusion in patients with SCD previously on chronic transfusion for stroke prevention. A total of 11 patients with hemoglobin SS were studied at two time points; baseline (on chronic RBC transfusion only) and 3 months follow up after initiation of hydroxyurea 20 mg/kg/day. Comparisons were performed using paired t-tests with a p-value <0.05 being considered significant. Results: T, B and NK cell percentage was similar between baseline and after 3 months of combination therapy 62.5% (44.3-71.9) vs 67% (17.6-82.7), 16.29%(8.15-30.2) vs. 13.26% (1.07-32.8) and 7.79% (4.16-14.7) vs. 6.88 (1.54-21) (p>0.05). There were no significant differences between markers of NK cell activation between baseline and 3 months as follows: NKG2D 4.89% (0.47-28.4) vs. 24.38% (0.88-63), and NKp30 8.40% (0.81-58.7) vs. 32.42% (0.45-86.9). However there was a significant decrease in the percentage of mature (CD57+) NK cells 33.8% (10.7-67.6) vs. 23.07%(4.23-37), p =0.005. Similar results were also seen when using absolute values of the different lymphocyte subsets. Conclusion: Combination therapy appears to not affect overall percentages of B, T and NK cells but does appear to decrease the percentage of mature CD57+ NK cells that are known to have increased cytolytic activity. We plan to investigate the implications of these findings using NK functional studies such as cytotoxicity assays and cytotoxic granule release to further elucidate if combination therapy can lead to a decrease in NK cell function to normal levels. Additionally we plan to assess the effect on the immune parameters at 1 year as the hydroxyurea effect is likely time-dependent. These findings may have implications for patients on chronic transfusion therapy who plan to undergo bone marrow transplantation where a reduction in the potential for graft rejection by NK cells is desired. Disclosures No relevant conflicts of interest to declare.

Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 76-79 ◽  
Author(s):  
Paul Harmatz ◽  
Ellen Butensky ◽  
Keith Quirolo ◽  
Roger Williams ◽  
Linda Ferrell ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Liver Biopsy ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Liver Iron ◽  
Transfusion Therapy

Abstract Chronic transfusion therapy is being used more frequently to prevent and treat the complications of sickle cell disease. Previous studies have shown that the iron overload that results from such therapy in other patient populations is associated with significant morbidity and mortality. In this study we examined the extent of iron overload as well as the presence of liver injury and the predictive value of ferritin in estimating iron overload in children with sickle cell disease who receive chronic red blood cell transfusions. A poor correlation was observed between serum ferritin and the quantitative iron on liver biopsy (mean 13.68 ± 6.64 mg/g dry weight;R = 0.350, P = .142). Quantitative iron was highly correlated with the months of transfusion (R = 0.795, P &lt; .001), but serum ferritin at biopsy did not correlate with months of transfusion (R = 0.308, P = .200). Sixteen patients had abnormal biopsies showing mild to moderate changes on evaluation of inflammation or fibrosis. Liver iron was correlated with fibrosis score (R = 0.50, P = .042). No complications were associated with the liver biopsy. Our data suggest that, in patients with sickle cell disease, ferritin is a poor marker for accurately assessing iron overload and should not be used to direct long-term chelation therapy. Despite high levels of liver iron, the associated liver injury was not severe.

Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy

2021 ◽  
pp. 103304
Author(s):  
Susanna A. Curtis ◽  
Balbuena-Merle Raisa ◽  
John D. Roberts ◽  
Jeanne E. Hendrickson ◽  
Joanna Starrels ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Exchange Transfusion ◽  
Adult Patients ◽  
Cell Disease ◽  
Transfusion Therapy

scholarly journals Designated Donor Program Enrollment Does Not Affect Red Blood Cell Alloimmunization Rates in Children with Sickle Cell Disease on Chronic Transfusion Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4291-4291
Author(s):  
Ronald Jackups ◽  
Debbie Woods ◽  
Robert J. Hayashi ◽  
Monica L. Hulbert
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Categorical Variables ◽  
Patient Specific ◽  
Cell Transplant ◽  
Blood Group Antigens ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Background: Chronic red blood cell (RBC) transfusion therapy is the predominant treatment modality in children with sickle cell disease (SCD) at high risk of first or recurrent strokes. RBC alloimmunization develops in some patients receiving chronic transfusion therapy, due in part to genetic differences in the prevalence of blood group antigens between the patient population and the blood donor pool. Many children’s hospitals have developed designated donor or “buddy” programs to recruit African-American blood donors and assign them to specific SCD patients with matched phenotypes, particularly in the Rh and Kell antigen groups, to reduce the likelihood of RBC alloimmunization. However, the practical constraints of such programs may make it difficult to ensure that patients’ transfusions always come from designated donors. Moreover, it is unclear whether such programs result in a lower risk of RBC alloimmunization when compared to the use of non-designated-donor but phenotype-matched RBC units. We aimed to determine the proportion of transfusions from designated donors at our institution, hypothesizing that the development of new RBC alloantibodies is associated with a lower proportion of transfused units from designated donors. Methods: This is a single-institution retrospective cohort study of 38 patients with SCD who received chronic transfusion therapy (manual exchange or erythrocytapheresis) for primary or secondary stroke prevention from 1/1/2008 through 12/31/2012. Patients on transfusion therapy for 6 or more months were included. Subjects were censored at last date of follow-up or date of hematopoietic stem cell transplant. The local designated donor program was started in 1999. Designated donors are selected to be ABO/RhD compatible and phenotype-matched to patients for the C, E, and K antigens. When units from designated donors are not available, compatible units phenotype-matched for C, E, and K are issued from general inventory. The number and percentage of units transfused from either designated or non-designated donors, and the identification of new RBC alloantibodies during the study period, were evaluated. The rates of alloimmunization were compared between patients who received a “high” (above the median) or “low” (below the median) proportion of designated donor units. Categorical variables were compared with Fisher’s exact test and medians with the Mann-Whitney U-test in SPSS version 21 (IBM, Armonk, NY). A p-value below 0.05 was statistically significant. Results: During the study period, 38 subjects (42% male) met all inclusion criteria. A median of 120 units (IQR 60-186) was transfused to each subject, and each subject received a median of 63% (IQR 45%-77%) of units from designated donors. Of the 38 subjects, 18 (47%) produced at least one newly identified RBC alloantibody during the study period. Among these 18 antibody producers, a total of 29 new alloantibodies were detected, with a range of 1-3 per subject. Ten of the newly identified alloantibodies were directed against C, D, E, or K. No statistically significant difference between antibody producers and non-producers was identified for total number of RBC units transfused (median 161 vs. 96, p = 0.067), number of units transfused from designated donors (median 107 vs. 49, p = 0.099), number of non-designated-donor, phenotype-matched units transfused from general inventory (median 38 vs. 26, p = 0.059), or proportion of units transfused from designated donors (median 68% vs. 49%, p = 0.28). Although there was a trend toward a higher incidence of alloimmunization in patients who received a high proportion of designated donor units (OR 2.4, CI 0.6-8.7), it was not statistically significant (p= 0.33). Conclusions: Despite receiving phenotypically matched RBC units, almost half of the children with SCD on chronic transfusion therapy in this cohort developed new RBC alloantibodies during a five-year period. The number of units transfused from a designated donor did not significantly affect alloimmunization rate. One-third of the new alloantibodies were directed against antigens specifically matched for in the designated donor program. Patient-specific factors, such as genetic variation in the Rh locus, may be responsible for the risk of alloimmunization. Alternative matching strategies, such as genotypic matching of RBC donors and recipients, should be explored in prospective studies. Disclosures Jackups: Immucor: Consultancy.

Outcomes of Chronic Automated RBC Exchange Program in Omaha, Nebraska 2015-2020

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Aleh Bobr ◽  
Scott A Koepsell ◽  
Julie Eclov ◽  
Omar Abughanimeh ◽  
Steven Ebers ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Beta Thalassemia ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Before And After ◽  
Ed Visits

Background: Red blood cell exchange (RBCX) is an effective therapy in the treatment of different hemoglobinopathies. The University of Nebraska Medical Center (UNMC) established a chronic RBCX program in November 2015, which took care of patients with multiple hemoglobinopathies. In this study, we aim to evaluate the outcomes of this program. Methods: This is a retrospective study. After an IRB approval, we reviewed the charts of patients who were enrolled in the chronic RBCX program between 11/2015-7/2020 at UNMC. Data was collected to evaluate indications of RBCX, types of hemoglobinopathies, hemoglobinopathies' complications before and after the enrollment in the program, and assessment of hospital visits before and after enrollment in the program. Results: In November 2015, the chronic RBCX program was established in Nebraska. Since the start, 24 patients came through the program and 20 patients are still actively enrolled and undergoing regular exchange transfusions. The four patients who left the program did it for the following reasons: moving out of state, stem cell transplant and change to different treatment modality. Four of 24 patients were beta thalassemia patients (two of them with combined HbE/beta thalassemia). Twenty patients had sickle cell disease with two of them having combined beta thalassemia and HbS and one with alpha thalassemia and HbS. The indications ranged from history of stroke, intracranial vascular stenosis, acute chest syndrome (ACS), iron overload, multiple vascular occlusive crises (VOC) and intolerance of medications with most of the patients having multiple indications from the list above (Figure 1). There are several positive outcomes from being on the program. In the patients who had been on the program for at least one year (n=11), nine started the program with iron overload and all of them had a significant decrease in serum ferritin (average 751 ng/mL) with three patients returning to normal range. In the patients who had been in the program at least six months (n=16), 13 patients started with iron overload with five returning to normal range and average decrease in ferritin of 585 ng/mL. Another positive outcome is the number of emergency department (ED) visits for pain crisis. We noted reduction in ED visits in all patients who were in the program for at least six months (n=14), with the exception of one patient where the visits were likely the part of drug seeking behavior. In fact 12 of 13 patients had one or no ED visits within one year after starting on the chronic exchange program having had from 2-11 visits a year prior. None of the patients in the program experienced more severe complications of sickle cell disease, like stroke and acute chest syndrome, while on the program. Due to high volumes of transfusion, there is a big concern about developing red blood cell antibodies in sickle cell disease patients who in general have higher red blood cell antibody burden. Out of 24 patients in the program, six had pre-existing antibodies. For the duration of the program, no new alloantibodies were discovered in the chronically exchanged patients despite high transfusion volumes (range 14L-30L/year). The transfused blood was matched for Rh and Kell antigens for the patients with no antibody history. The patients with previous antibody history had additional matching for the antigen to which antibody was directed. Conclusion:Automated chronic RBCX transfusion program is safe to perform. It leads to significant reduction in volume overload and ED visits. Performing high volume transfusions outside of acute sickle cell crisis and with Rh and Kell matched units prevents formation of RBC antibodies Disclosures Gundabolu: BioMarin:Consultancy;Bristol Myers Squibb pharmaceuticals:Consultancy.

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

Blood ◽  
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 &lt; 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 (&lt;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

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