Therapeutic Red Blood Cell Exchange in Sickle Cell Anaemia Using the Spectra Optia® Apheresis System

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4383-4383
Author(s):  
Sabine Sipurzynski-Budraâ ◽  
Petra Sovinz ◽  
Gerhard Lanzer ◽  
Katharina Schallmoser
Keyword(s):  
Side Effects ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Organ Damage ◽  
Blood Transfusions ◽  
Adverse Side Effects ◽  
Sickle Cells

Abstract Abstract 4383 Background: Sickle cell disease, an autosomal recessive genetic blood disorder, is caused by abnormal hemoglobin (Hb) due to a substitution of valine by glutamic acid at β6 (HbS). Typical adverse events are vaso-occlusive crises due to obstruction of capillaries causing ischemia, pain and organ damage, as well as enhanced hemolysis and frequent hemolytic crises. Further complications may include acute chest syndrome and stroke. To prevent long-term sequelae, repeated blood transfusions are necessary to decrease erythropoiesis of sickle cells. We suggest that it may be more effective to reduce sickle cells by a red blood cell (RBC) exchange, which is advantageous in avoiding iron overload by transfusions. Patient and Methods: We report on a 10 year old boy suffering from the homozygote form of sickle cell anemia. RBC exchange was performed using the Spectra Optia® Apheresis System (Caridian BCT vers.5) when the patient's hematocrit (hct) was less than 26%. Traditional RBC exchange was modified by a depletion phase to improve efficacy. During this phase (= isovolemic hemodilution) HbS-containing red cells were removed without admixture of donor red cells by using plasma as replacement fluid. To prevent adverse side effects caused by adenine, the additive solution in the RBC concentrates was replaced by saline solution or plasma. Results: The therapeutic apheresis was feasible repeatedly via peripheral venous access (flow: 30 ± 3 mL/min, anticoagulant (AC) infusion rate 0.8 – 1.1mL/min/L total blood volume, inlet: AC ratio 13: 1) and no adverse side effects were observed. The median interval between the procedures was 42 ± 2 days. The depletion time (replacement fluid: plasma) was 25 ± 5 min, the exchange time 90 ± 10 min. The hct value at the end of the procedure was between 33 and 34%, the fraction of the patient's remaining cells (FCR) was 24 ± 2% (calculated by the device). Conclusion: RBC exchange with the Optia Spectra® System is a fast and safe method for reducing sickle cells, particularly efficient in combination with a depletion phase. Compared to blood transfusions alone, the HbS concentration declines rapidly by depleting and replacing sickle cells with normal RBCs without hyperviscosity or iron overload. However, only long-term surveillance and treatment of a larger patient collective will show whether it is possible to prevent vaso-occlusive crises and organ damage over a longer time period. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Sickle Cell Disease Model Mice Lacking 2,3-Dpg Show Reduced RBC Sickling and Improvements in Markers of Hemolytic Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Kelly M. Knee ◽  
Amey Barakat ◽  
Lindsay Tomlinson ◽  
Lila Ramaiah ◽  
Zane Wenzel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Organ Damage ◽  
Complete Elimination ◽  
Cell Disease ◽  
The Impact ◽  
2,3 Dpg

Sickle cell disease (SCD) is a severe genetic disorder caused by a mutation in hemoglobin (b6Glu-Val), which allows the mutant hemoglobin to assemble into long polymers when deoxygenated. Over time, these polymers build up and deform red blood cells, leading to hemolytic anemia, vaso-occlusion, and end organ damage. A number of recent therapies for SCD have focused on modulating the mutant hemoglobin directly, however, reduction or elimination of 2,3-DPG to reduce Hb S polymerization and RBC sickling has recently been proposed as a therapeutic strategy for SCD. Current clinical studies focus on activation of pyruvate kinase to reduce 2,3-DPG, however, direct targeting of the enzyme which produces 2,3-DPG; Bisphosphoglycerate Mutase (BPGM) may also be possible. In this study we evaluate the impact of elimination of 2,3-DPG on SCD pathology by complete knockout of BPGM in Townes model mice. Animals with complete knockout of BPGM (BPGM -/-) have no detectable 2,3-DPG, while animals that are heterozygous for BPGM (BPGM -/+) have 2,3-DPG levels comparable to Townes mice. Western Blot analysis confirms that BPGM -/- animals completely lack BPGM, while BPGM -/+ animals have BPGM levels that are nearly equivalent to Townes mice. As expected from the lack of 2,3-DPG, BPGM -/- animals have increased oxygen affinity, observed as a 39% decrease in p50 relative to Townes mice. Complete elimination of 2,3-DPG has significant effects on markers of hemolytic anemia in BPGM -/- mice. Mice lacking 2,3-DPG have a 60% increase in hemoglobin (3.7 g/dL), a 53% increase in red blood cell count, and a 29% increase in hematocrit relative to Townes mice. The BPGM -/- mice also have a 57% decrease in reticulocytes, and a 61% decrease in spleen weight relative to Townes animals, consistent with decreased extramedullary hematopoiesis. Consistent with the reduction in hemolysis, BPGM -/- animals had a 59% reduction in red blood cell sickling under robust hypoxic conditions. BPGM -/+ animals had hemoglobin, RBC, and hematocrit levels that were similar to Townes animals, and a similar degree of RBC sickling to Townes mice. Liver phenotype was similar across all variants, with areas of random necrosis observed in BPGM -/-, BPGM -/+ and Townes mice. Higher percentages of microcytic and/or hyperchromic RBCs were observed in BPGM -/- animals relative to BPGM -/+ or Townes animals. These results suggest that modulation of 2,3-DPG has a positive effect on RBC sickling and hemolytic anemia, which may have therapeutic benefits for SCD patients. However, the lack of improvement in organ damage suggests that modulation of 2,3-DPG alone may not be sufficient for complete elimination of SCD phenotypes, and further investigation of this therapeutic avenue may be necessary. Disclosures No relevant conflicts of interest to declare.

scholarly journals Mechanical properties of sickle cell membranes

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1711-1717 ◽  
Author(s):  
R Messmann ◽  
S Gannon ◽  
S Sarnaik ◽  
RM Johnson
Keyword(s):  
Mechanical Properties ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Membranes ◽  
Erythrocyte Membranes ◽  
Sickle Cells ◽  
Dense Cell ◽  
Cell Fractions ◽  
Membrane Mechanical Properties

Abstract The mechanical properties of sickle erythrocyte membranes were evaluated in the ektacytometer. When ghosts from the total red blood cell population were examined, the rigidity of the resealed ghosts and their rate of fragmentation by shear stress (t1/2) were normal. However, fractionation on Stractan density gradients revealed that sickle cells were heterogenous in their membrane mechanical properties. The ghosts from dense cell fractions exhibited both increased rigidity and decreased stability. Presumably, these altered mechanical properties are a reflection of the well-documented biochemical damage found in irreversibly sickle cell membranes. Nevertheless, neither of the alterations in mechanical properties are likely to be significant elements in the hemolysis of sickle cell anemia. Earlier studies of abnormal erythrocytes suggest that increases in membrane rigidity per se do not increase hemolysis, and they are, therefore, unlikely to do so in this case. The stability of membranes from the dense cell fractions was reduced to about two thirds of the control value. Comparison with the results of studies of red blood cell membranes with genetically defective or deficient spectrin suggests that a reduction in t 1/2 of 50% is not associated with significant increases in the rate of hemolysis. Although altered ghost stability and flexibility can be demonstrated in dense sickle cells, these changes in membrane mechanical properties are not likely to be significant factors in the hemolytic process.

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 < 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

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.

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