Gaps in the diagnosis and management of iron overload in sickle cell disease: a ‘real‐world’ report from the GRNDaD registry

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.

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Iron Depletion: An Ameliorating Factor for Sickle Cell Disease?

ISRN Hematology ◽

10.5402/2011/473152 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 5

Author(s):

P. C. Giordano ◽

W. Huisman ◽

C. L. Harteveld

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Beneficial Effect ◽

Sickle Cell ◽

Chelation Therapy ◽

Cell Disease ◽

Laboratory Practice ◽

Iron Depletion ◽

Severity Of The Disease

We report some observations from our laboratory practice that might be important for the treatment of sickle cell disease (SCD). We describe data from two cases indicating that iron depletion might have a beneficial effect diminishing the formation of HbS in favor of HbF, possibly reducing the severity of the disease. We believe that it would be worthwhile to monitor the course of the disease comparing cases with identical genotypes with and without iron depletion, and we advise to consider chelation therapy to reduce iron overload in patients with SCD.

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Increased levels of soluble P-selectin correlate with iron overload in sickle cell disease

British Journal of Biomedical Science ◽

10.1080/09674845.2007.11732771 ◽

2007 ◽

Vol 64 (3) ◽

pp. 124-126 ◽

Cited By ~ 1

Author(s):

A.D. Blann ◽

S.S. Marwah ◽

A.J. Cobley ◽

D Bareford

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Cell Disease ◽

Soluble P

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Consequences and management of iron overload in sickle cell disease

Hematology ◽

10.1182/asheducation-2013.1.447 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 447-456 ◽

Cited By ~ 57

Author(s):

John Porter ◽

Maciej Garbowski

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Iron Overload ◽

Sickle Cell ◽

Iron Concentration ◽

Thalassemia Major ◽

Iron Loading ◽

Cell Disease ◽

Liver Iron Concentration ◽

Liver Iron

Abstract The aims of this review are to highlight the mechanisms and consequences of iron distribution that are most relevant to transfused sickle cell disease (SCD) patients and to address the particular challenges in the monitoring and treatment of iron overload. In contrast to many inherited anemias, in SCD, iron overload does not occur without blood transfusion. The rate of iron loading in SCD depends on the blood transfusion regime: with simple hypertransfusion regimes, rates approximate to thalassemia major, but iron loading can be minimal with automated erythrocyte apheresis. The consequences of transfusional iron overload largely reflect the distribution of storage iron. In SCD, a lower proportion of transfused iron distributes extrahepatically and occurs later than in thalassemia major, so complications of iron overload to the heart and endocrine system are less common. We discuss the mechanisms by which these differences may be mediated. Treatment with iron chelation and monitoring of transfusional iron overload in SCD aim principally at controlling liver iron, thereby reducing the risk of cirrhosis and hepatocellular carcinoma. Monitoring of liver iron concentration pretreatment and in response to chelation can be estimated using serum ferritin, but noninvasive measurement of liver iron concentration using validated and widely available MRI techniques reduces the risk of under- or overtreatment. The optimal use of chelation regimes to achieve these goals is described.

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Deferasirox for managing transfusional iron overload in people with sickle cell disease

Cochrane Database of Systematic Reviews ◽

10.1002/14651858.cd007477.pub3 ◽

2014 ◽

Cited By ~ 3

Author(s):

Joerg J Meerpohl ◽

Lisa K Schell ◽

Gerta Rücker ◽

Edith Motschall ◽

Nigel Fleeman ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Cell Disease

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Hydroxyurea as an Alternative to Blood Transfusions for the Prevention of Recurrent Stroke in Children With Sickle Cell Disease

Blood ◽

10.1182/blood.v94.9.3022 ◽

1999 ◽

Vol 94 (9) ◽

pp. 3022-3026 ◽

Cited By ~ 111

Author(s):

Russell E. Ware ◽

Sherri A. Zimmerman ◽

William H. Schultz

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Recurrent Stroke ◽

Fetal Hemoglobin ◽

Hemoglobin Concentration ◽

Stroke Recurrence ◽

Hematologic Toxicity ◽

Cell Disease ◽

F Cells

Abstract Children with sickle cell disease (SCD) and stroke receive chronic transfusions to prevent stroke recurrence. Transfusion risks including infection, erythrocyte allosensitization, and iron overload suggest a need for alternative therapies. We previously used hydroxyurea (HU) and phlebotomy in two young adults with SCD and stroke as an alternative to transfusions. We have now prospectively discontinued transfusions in 16 pediatric patients with SCD and stroke. Reasons to discontinue transfusions included erythrocyte alloantibodies or autoantibodies, recurrent stroke on transfusions, iron overload, noncompliance, and deferoxamine allergy. HU was started at 15 mg/kg/d and escalated to 30 mg/kg/d based on hematologic toxicity. Patients with iron overload underwent phlebotomy. The children have been off transfusions 22 months, (range, 3 to 52 months). Their average HU dose is 24.9 ± 4.2 mg/kg/d, hemoglobin concentration is 9.4 ± 1.3 g/dL, and mean corpuscular volume (MCV) is 112 ± 9 fL. Maximum percentage fetal hemoglobin (%HbF) is 20.6% ± 8.0% and percentage HbF-containing erythrocytes (%F cells) is 79.3% ± 14.7%. Fourteen patients underwent phlebotomy with an average of 8,993 mL (267 mL/kg) removed. Serum ferritin has decreased from 2,630 to 424 ng/mL, and 4 children have normal ferritin values. Three patients (19%) had neurological events considered recurrent stroke, each 3 to 4 months after discontinuing transfusions, but before maximal HU effects. These preliminary data suggest some children with SCD and stroke may discontinue chronic transfusions and use HU therapy to prevent stroke recurrence. Phlebotomy is well-tolerated and significantly reduces iron overload. Modifications in HU therapy to raise HbF more rapidly might increase protection against stroke recurrence.

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