Need For Chelation Therapy Research Articles

P-072: COST COMPARISON OF TRANSFUSION CHOICES IN OMAN FOR PATIENTS SUFFERING FROM SICKLE CELL DISEASE.

Purpose: The management of sickle cell disease (SCD) can be challenging, requiring different therapeutic approaches because SCD could induce multiple complications, precipitating multi-organ failure. Red blood cell (RBC) transfusion is well known as one of the disease-modifying therapies available for long-term management of this condition. It is supported by multiple randomised clinical trials for the prevention of disease complications such as stroke in adults and children with SCD. RBCs can be delivered via three methods: Simple transfusion(ST), manual exchange(ME) and automated red blood cell exchange(aRBCX). In a simple transfusion, patients receive additional units of blood. The purpose is to raise the haemoglobin (Hb) to a steady state and maintain the oxygen-carrying capacity of the blood. Manual exchange transfusion removes the patient’s sickle-shaped RBCs and replaces them with healthy ones — lowering the concentration of sickled cells without increasing blood viscosity. This is performed using repeated alternating isovolumetric phlebotomy and blood transfusion. Automated red blood cell exchange transfusion involves removing sickled RBCs from the patient and rapid replacement with healthy RBCs while maintaining isovolemia. An advantage of aRBCX is avoiding or minimising costly iron chelation therapy to treat iron overload. As Sickle Cell disease (SCD) management is a critical cost driver to health systems, this research intended to compare the cost-effectiveness of different transfusion modalities. We wanted to compare the following transfusion types: Automated red blood cell exchange (aRBCX), Top-up transfusion and Manual red blood cell exchange (mRBCX). More specifically, we wanted to perform this evaluation in Oman as 0.2% of the Omani population suffers from this disease, which is the most frequent genetic disorder with the highest incidence. Materials and methods: Variables that drive costs have been collected to populate a de Novo cost model. We collected data from the Royal Hospital and Sultan Qaboos University Hospital. The most significant cost drivers which we took into consideration were: disease incidence, cost blood transfusion, medical equipment, disposables, complications, chelation therapy, hospitalisation, lives lost. Results: Our results reflect a 5-year overview demonstrating the costs and benefits experienced by healthcare providers. When considering the cost of treatment, consequence, complications, lives lost, life years lost, aRBCX is dominant over the transfusion modalities. Yearly intervention cost per patient per year in Omani-Rial: [Top-up 1933.5;Manual 3101.5;aRBCX 5857.5].The yearly cost of treatment choice related cost per patient per year in Omani-Rial:[12128.88; 6233.41; 789.88].Cost of disease complications per patient per year in Omani-Rial:[12706;12864; 11346].Cost of lives lost per patient per year in Omani-Rial:[1315;1288;1102). The total yearly cost per patient per year in Omani-Rial is estimated:[28084;23487.5;19095] Conclusion: aRBCX is 47% more cost-effective when compared to Top-up transfusion. aRBCX is 23% more cost-effective when compared to mRBCX. aRBCX promotes reduction in overall resources, disease burden, bed retention and the need for chelation therapy when compared to top-up transfusion and manual exchange transfusion. Cost savings may lead to better adoption. We recommend researchers rerun these calculations on an individual hospital basis.The authors do not declare any conflict of interest

S2741 Sickling Manifestations: A Challenging Case of Sickle Cell Hepatopathy

Introduction: Sickle cell hepatopathy (SCH) is an entity describing a pattern of liver injury seen in an estimated ∼10% of patients with sickle cell disease (SCD). It is more prevalent in the Sub-Saharan African region and South-East Asia. This entity is classified according to its clinical presentation into acute and chronic which differs in clinical diagnosis and management. Case Description/Methods: A 51-year-old African American male with SCD presented to our ER with complaint of joint pain and shortness of breath. Patient-reported progressive bilateral lower extremity arthralgia, sharp, 8/10 in severity for 1 week. Reported Dyspnea on exertion. Recurrent sickle cell crises were noted. The patient recently discontinued hydroxyurea because of non-healing cutaneous ulcerations. Vitals marked hypoxia at 87%, otherwise stable. Physical examination revealed icteric sclerae with bilateral lung crackles prominent at the bases. Labs showed hemoglobin at 3.0 g/dl, HB S 28.7% with reticulocyte count at 17.41%. Chemistry panel showed alkaline phosphatase (ALP) at 209 U/L, Total bilirubin at 7.0 mg/dl with direct bilirubin at 4.7 mg/dl. Gamma-glutamyl transpeptidase (GGT) was normal. Chest Xray showed bilateral multifocal infiltrates. Abdominal ultrasound was unremarkable. Computed tomography of the chest showed interspersed ground-glass opacities. Hepatology was consulted for assessment of elevated ALP and Total bilirubin. Clinical suspicion was (SCH). Patient was given multiple blood transfusions. The need for liver transplant (LT) was investigated and deemed not necessary. Pathology was reviewed. Discussion: (SCH) is included in the differential of liver injury, therefore, identifying this entity from other causes of liver disease is important. It is more prevalent in the US now. Hence, an urgent need to find new treatment options in addition to emergent blood transfusion and LT is required. Iron quantification and determining need for chelation therapy is crucial and affects long-term outcomes. LT in SCD patients is controversial due to high risk of post-transplant complications. More studies and international registries are needed to expand our knowledge of the benefits and risks of LT in patients with SCD. We anticipate that (SCH) will become a burden on the health care system in the aging population of SCD patients as they will require more blood transfusions. With a current national shortage supply, we fear future complications will include an increase in mortality rates within this patient population.Figure 1.: a (H&E stain 400x) showing sickled RBC in the sinusoids. b (H&E stain 40x) The lobules show marked sinusoidal dilatation and congestion with elongated RBCs, more pronounced in zone 3 with extravasated RBCs. c (Trichrome stain 200x) Trichrome stain shows diffuse sinusoidal fibrosis, portal, periportal with bridging.

PRO42 Cost Comparison Analysis of Transfusion Modalities for Patients Suffering from Sickle Cell Disease for the Brazilian National Healthcare System (SUS)

The purpose of this study is to perform a Cost Effectiveness Analysis (CEA) among simple transfusion (ST), manual Red Blood Cell exchange (mRBCx) and automated Red Blood Cell exchange (aRBCx), the three different transfusion modalities that the Brazilian National Healthcare System (BNHS) currently uses to treat patients with Sickle Cell Disease (SCD). Costs, technical and clinical data have been collected from PubMed, the ISPOR Scientific Database and several online government sources such as the SUS, saude.gov, etc. The most important cost drivers assessed were blood transfusion costs, medical equipment, disposables, complications/adverse events, chelation therapy, hospitalization and lives lost. They have been used to populate a cost model created with the Microsoft Excel Software. Our results reflect the costs and benefits’ differences among the three transfusion modalities for the Brazilian NHS. When considering the cost of treatment, consequence, complications, lives lost and live years lost, aRBCx is dominant over the other options. Yearly intervention cost per patient in Brazilian Reals (BRL): [ST 5672; mRBCx 10,810; aRBCx 19,519]. Yearly cost of treatment choice related in BRL: [ST 18,846.54; mRBCx 14,141.36; aRBCx 7,536.69]. Yearly cost of disease complications in BRL: [ST 178,441; mRBCx 180,667; aRBCx 159,344]. Cost of lives lost per patient in BRL per year: [ST 7,172; mRBCx 7,072; aRBCx 6,005]. Total yearly cost per patient estimated in BRL: [ST 1,268,963; mRBCx 1,284,126; aRBCx 1,161,913]. aRBCx is the most cost-effective option among the three transfusion modalities for SCD patients for the BNHS. aRBCX promotes reduction in overall resources, disease burden, bed retention and the need for chelation therapy. We recommend the BNHS to develop strategies to facilitate the inclusion of aRBCx in guidelines (PCDT) for treating SCD and to promote the use of aRBCx as the main transfusion modality for this disease.

Proton pump inhibitors use suppresses iron absorption in congenital dyserythropoietic anemia

ABSTRACTCongenital dyserythropoietic anemia type I (CDA I) is associated, as other anemic noninflammatory states, with ineffective erythropoiesis and increased iron absorption, which may lead to complication of iron overload. The latter complication requires iron-chelating therapy, which may be associated with adverse effects and toxicity. Gastric acid production is known to be an important factor that facilitates non-heme iron absorption. The purpose of this study was to examine whether treatment with proton pump inhibitors (PPIs) can decrease iron absorption in patients with CDA I. Eight CDA I patients (4 boys) aged 12–18 years with mild iron overload (not yet requiring chelating therapy) received 20 mg/d omeprazole for 6 months. Blood samples were obtained for ferritin, C-reactive protein, hemoglobin, calcium, and magnesium at baseline, at the end of months intervention and 6 months after its cessation. The mean ferritin level decreased from 585 ± 180 ng/ml at baseline to 522 ± 172 ng/ml at the end of 6-month treatment and 660 ± 256 ng/ml 6 months after cessation of omeprazole treatment (p = 0.009). Omeprazole treatment caused a nonsignificant reduction in the mean iron level (iron 159 ± 42, 136 ± 54,167 ± 34 µg/dl, p = 0.302). However, mean hemoglobin level was mildly but significantly reduced (Hg 10.0 ± 0.8, 9.55 ± 1.0, 10.4 ± 10.7 g/dl, p = 0.002). No adverse effects were reported. Our investigation suggests that administration of PPI to patients with CDA I may reduce iron absorption and may lower iron overload and the need for chelation therapy.

Assessment of Labile Plasma Iron in Patients Who Undergo Hematopoietic Stem Cell Transplantation

Body iron disorders have been reported after myeloablative conditioning in patients undergoing hematopoietic stem cell transplantation (HSCT). There is a concern that labile plasma iron (LPI), the redox-active form of iron, can be involved in the occurrence of toxicity and other complications commonly observed in the early post-HSCT period. In order to better understand the LPI kinetics and its determinants and implications, we undertook sequential LPI determinations before and after conditioning until engraftment in 25 auto-HSCT patients. Increased LPI was present in only 5 patients before starting conditioning. Shortly after conditioning, LPI levels were increased in 23 patients, with peak at day 0, returning to normal range upon engraftment in 21 patients. Overall, LPI levels correlated weakly with serum ferritin and more strongly with transferrin saturation; however, both parameters were apparently not applicable as surrogate markers for increased LPI. Although this was a small cohort, logistic regression suggested that baseline LPI levels could predict occurrence of grade III or IV toxicity. In conclusion, LPI kinetics is influenced by aplasia following conditioning and engraftment. Measuring LPI before starting conditioning can offer an opportunity to predict toxicity and, perhaps, the need for chelation therapy.

Commentary on the abuse of metal chelation therapy in patients with autism spectrum disorders.

Approximately half a million patients with autism spectrum disorders are subjected to chelation therapy in the US annually. The overwhelming majority of such cases are chelated for non-accepted medical indications. These patients may seek evaluation when a urine sample is assayed after the administration of a chelating agent and the values obtained have been improperly compared to references ranges for non-chelated urines, causing falsely elevated results. Legitimate practitioners confronted with such data must decide, preferably in consultation with the patient or their guardian(s), whether to do further testing using legitimate methodology or to simply dismiss the results of the improper testing. Bayesian principles tell us that further testing is likely to yield results within normal reference ranges. However, under some circumstances, it is useful to do such testing in order to demonstrate that there is no need for chelation therapy. Unnecessary chelation therapy is expensive, can cause significant acute adverse effects, and may be associated with long-term consequences.

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

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.

Manual erythroexchange for chronic transfusion therapy in patients with sickle cell syndromes unresponsive to hydroxyurea: A long‐term follow‐up

Between 1981 and 2010, we have treated 40 patients requiring chronic transfusion with periodic manual erythrocyte exchange and autologous plasma rescue (MEEX). Here, we present retrospective, long-term (median 22, range 14–29 years) follow-up data for a subset of seven patients with sickle cell syndromes who did not respond to hydroxyurea (HU). Patient characteristics are listed in Supporting Information, Tables I and II. MEEX was accomplished by using a single venous access and infusing 500 ml of isotonic solution (for adults) and removing 500 ml blood (range 400–600 ml according to the patient's weight and the physician's discretion). The rescue process involves centrifugation of the collected blood product and reinfusion of autologous plasma. This is followed by another 500 ml phlebotomy and the infusion of 2–3 units of packed Rh-matched, leuko-filtered, plasma-depleted red cells, with the aim of lowering HbS levels to around 40%. For pediatric patients, the bleeding volume is smaller (5–10 cc/Kg) and the volumes of infused saline and packed Rh-matched, leuko-filtered, plasma-depleted red cells are equal to the phlebotomy volumes, without plasma rescue. The interval between each MEEX procedure for these seven patients ranged from 45 to 90 days to maintain at all times HbS concentrations below 60–70% and the median number of procedures was 133 (range 85–204). None of the seven patients experienced acute complications of sickle cell disease (SCD), such as acute chest syndrome, splenic sequestration, stroke, bone necrosis, or priapism, or long-term complications such as renal failure, cerebrovascular or retinal damage, or pseudoxanthoma-like manifestations. None of the seven patients experienced alloimmunization and all but one patient had normal liver iron concentrations [assessed by superconducting quantum interference device, magnetic iron detector, magnetic resonance imaging (MRI), or biopsy]. This patient, who started the program at the age of 26 years with iron overload due to previous transfusions, required regular iron chelation therapy. Cardiac function tests indicated that all subjects had a left ventricular ejection fraction of >60% and cardiac T > 20 mms (measured by MRI). There was no evidence of pulmonary arterial hypertension on echocardiography. During the observation period, five patients required hospitalization (four with acute cholecystitis and one due to venous occlusive crisis). Only one patient requires chronic analgesia (to relieve pain caused by pre-existing femur head necrosis). Automated EEX (AEEX) ensures lower postprocedural HbS levels (30% HbS vs. 40% with our MEEX protocol) because it makes use of two distal ports to increase the volume of red cells removed. However, the larger number of transfused units in AEEX exposes the patient to a higher transfusional risk. In addition, the automated procedure is significantly more expensive than the manual one, as indicated in Table I. Previous studies have indicated that EEX is a safe and efficacious alternative to both HU and simple transfusions for preventing complications of SCD and improving patients' quality of life [1, 2]. Our results with MEEX confirm previous findings including that if MEEX is started before significant iron overload occurs, the need for chelation therapy may be obviated [3]. Given the relative simplicity and the lower cost, MEEX should be considered for chronic transfusion therapy in developing countries [4]. The authors thank Jane Tricker and Dr. Silvia Caviglia for editorial assistance in the preparation of this article. Additional Supporting Information may be found in the online version of this article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Serum Ferritin Elevation and Use of Iron Chelation In Chronically Versus Sporadically Transfused Sickle Cell Patients

AbstractAbstract 2671 Background:Red cell transfusions play an integral role in the treatment and prevention of serious complications related to sickle cell disease. It has been shown that in other hemoglobinopathies, such as β-Thalassemia, patients (pts) suffer from iron overload which can result in end organ damage. There is concern that heavily transfused sickle cell pts may also develop iron overload with consequent morbidity and mortality. While pediatric pts routinely receive blood transfusions and iron chelation therapy, adult pts often discontinue chronic transfusion programs and are transfused sporadically. These pts may not receive routine iron chelation therapy. Methods:A retrospective review of our sickle cell database from 1988–2010 which also included those pts who were not routinely followed at the comprehensive sickle cell clinic. Adult pts (>18 yrs of age) with serum ferritin (SF) levels >1000 ng/ml (criteria for iron overload in our institution) were identified and use of iron chelation was reviewed in this population. Clinical characteristics evaluated were age, type of sickle cell disease, frequency of transfusions (chronic vs. sporadic), total units transfused, use and type of chelation, as well as reasons for non-use of chelation therapy. Results:65/170(38%) pts were identified with SF >1000. The mean age is 33 years (range 19–70). 38/65 (59%) have the SS phenotype, 25/65 (38%) have the Sβ phenotype and 2/65 (3%) have the SC phenotype. The mean SF is 3697 ng/ml (range 1012–14312). Of those pts considered to have iron overload, 28/65 (43%) were treated with iron chelation: 27/65 (42%) received deferasirox and 1/65 (2%) received deferoxamine. Of the untreated pts, 24/37 (65%) had no identifiable reason for lack of chelation therapy, 10/37 (27%) had renal dysfunction, 1/37(3%) had hepatic impairment. 16/65 (25%) were transfused chronically, while 49/65 (75 %) were transfused sporadically. Chronically transfused pts received a mean of 81 units throughout their lifetime, while sporadically transfused pts received 30 units (p=0.01). The mean SF for chronically transfused pts was 5891, while the mean SF for pts transfused sporadically was 2981 (p=0.01). Of pts transfused chronically, 11/16 (69%) were on chelation therapy. Of the pts receiving sporadic transfusions, only 16/49 (33%) were on iron chelation (p= 0.01). In all pts chronically transfused, the reason for non-use of chelation therapy was renal dysfunction. In sporadically transfused pts, 33/49 (51%) had no identifiable reason for lack of chelation therapy. Conclusion:SF levels are significantly lower in pts who are sporadically transfused, though levels are high. Adult pts receiving sporadic transfusions are not routinely receiving iron chelation therapy despite elevated SF. The need for chelation therapy in both sporadically and chronically transfused pts remains to be determined. Disclosures:No relevant conflicts of interest to declare.

Erythrocytapheresis for chronically transfused children with sickle cell disease: an effective method for maintaining a low hemoglobin S level and reducing iron overload.

Cerebrovascular accident (CVA) is a major complication of sickle cell disease during childhood. Long-term transfusion reduces the hemoglobin S level and generally prevents recurrent stroke, but it also results in progressive iron overload that requires regular chelation therapy. Erythrocytapheresis offers an alternative approach aimed at reducing the iron accumulation. We reviewed the results of erythrocytapheresis in eight sickle cell patients (mean age of 12.1 years) at high risk for a first or recurrent stroke. They were maintained at the standard pre-transfusion hemoglobin S (Hb S) level of 30%. Over an average of 9 months of erythrocytapheresis, none of the patients developed complications related to the procedure or to the increased blood use. Ferritin levels decreased by a mean of 26.5% in all patients. When evaluating the ferritin level in five patients, who remained on chelation therapy with deferoxamine (DFO), the level dropped by a mean of 32%. The levels remained stable in the three patients who were not on DFO. The procedure is safe and effective in reducing iron overload and can obviate the need for chelation therapy, even when the target Hb S is maintained at the standard 30% range.

Erythrocytapheresis for chronically transfused children with sickle cell disease: An effective method for maintaining a low hemoglobin S level and reducing iron overload

Cerebrovascular accident (CVA) is a major complication of sickle cell disease during childhood. Long-term transfusion reduces the hemoglobin S level and generally prevents recurrent stroke, but it also results in progressive iron overload that requires regular chelation therapy. Erythrocytapheresis offers an alternative approach aimed at reducing the iron accumulation. We reviewed the results of erythrocytapheresis in eight sickle cell patients (mean age of 12.1 years) at high risk for a first or recurrent stroke. They were maintained at the standard pre-transfusion hemoglobin S (Hb S) level of 30%. Over an average of 9 months of erythrocytapheresis, none of the patients developed complications related to the procedure or to the increased blood use. Ferritin levels decreased by a mean of 26.5% in all patients. When evaluating the ferritin level in five patients, who remained on chelation therapy with deferoxamine (DFO), the level dropped by a mean of 32%. The levels remained stable in the three patients who were not on DFO. The procedure is safe and effective in reducing iron overload and can obviate the need for chelation therapy, even when the target Hb S is maintained at the standard 30% range. J. Clin. Apheresis 14:122–125, 1999. © 1999 Wiley-Liss, Inc.

Combined zinc/copper sulfate ingestion: Systemic manifestations and need for chelation therapy?

Combined zinc/copper sulfate ingestion: Systemic manifestations and need for chelation therapy?

Combined zinc/copper sulfate ingestion: systemic manifestations and need for chelation therapy?

Combined zinc/copper sulfate ingestion: systemic manifestations and need for chelation therapy?

Erythrocytapheresis Can Reduce Iron Overload and Prevent the Need for Chelation Therapy in Chronically Transfused Pediatric Patients

This research was undertaken to determine the advantages, complications, costs, and efficacy of erythrocytapheresis in young pediatric patients who receive chronic erythrocyte transfusion therapy. We retrospectively analyzed data for 10 children who received erythrocytapheresis for an average of 16 months. Erythrocytapheresis was compared to simple transfusion therapy with respect to annual blood unit exposure, occurrence of alloimmunization, and costs. Serum ferritin levels were compared before and after the period of erythrocytapheresis. Erythrocytapheresis was well tolerated, even in children as young as 5 years or as small as 20 kg. It required a greater annual unit exposure than simple transfusions, but did not increase alloimmunization. Ferritin levels decreased significantly in children receiving concurrent deferoxamine, and decreased or stabilized in those not on chelation therapy. Children started on erythrocytapheresis soon after stroke have not developed iron overload. Although the costs of erythrocytapheresis exceed that of simple transfusion, the substantial costs of deferoxamine therapy should be considered; one child on erythrocytapheresis has been able to discontinue chelation therapy following normalization of his ferritin level. Erythrocytapheresis is a safe and effective method for young patients receiving chronic erythrocyte transfusions. Erythrocytapheresis can reduce total iron burden and may obviate the need for expensive chelation therapy.

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

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.

Erythrocytapheresis Therapy to Reduce Iron Overload in Chronically Transfused Patients With Sickle Cell Disease

AbstractChelation 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 long-term 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 pre-transfusion 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-erythro-cytapheresis Hb levels ≥8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels ≤ 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.