Faculty Opinions recommendation of American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support.

Abstract To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

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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.

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2019 sickle cell disease guidelines by the American Society of Hematology: methodology, challenges, and innovations

Blood Advances ◽

10.1182/bloodadvances.2019000931 ◽

2019 ◽

Vol 3 (23) ◽

pp. 3945-3950 ◽

Cited By ~ 3

Author(s):

M. Hassan Murad ◽

Robert I. Liem ◽

Eddy S. Lang ◽

Elie A. Akl ◽

Joerg J. Meerpohl ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Guideline Development ◽

A Priori ◽

Cell Transplant ◽

Cell Disease ◽

Hematopoietic Stem ◽

Assessment Development ◽

Cerebrovascular Complications ◽

American Society

Abstract The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell transplant. Panels were multidisciplinary and consisted of patient representatives, content experts, and methodologists. The Mayo Clinic Evidence-Based Practice Center conducted systematic reviews based on a priori selected questions. In this exposition, we describe the process used by ASH, including the GRADE approach (Grades of Recommendations, Assessment, Development and Evaluation) for rating certainty of the evidence and the GRADE Evidence to Decision Framework. We also describe several unique challenges faced by the guideline panels and the specific innovations and solutions used to address them, including a curriculum to train patients to engage in guideline development, dealing with the opioid crisis, and working with indirect and noncomparative evidence.

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American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain

Blood Advances ◽

10.1182/bloodadvances.2020001851 ◽

2020 ◽

Vol 4 (12) ◽

pp. 2656-2701 ◽

Cited By ~ 5

Author(s):

Amanda M. Brandow ◽

C. Patrick Carroll ◽

Susan Creary ◽

Ronisha Edwards-Elliott ◽

Jeffrey Glassberg ◽

...

Keyword(s):

Chronic Pain ◽

Pain Management ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Practice Research ◽

Management Approach ◽

Evidence Based ◽

Cell Disease ◽

Targeted Interventions ◽

American Society

Background: The management of acute and chronic pain for individuals living with sickle cell disease (SCD) is a clinical challenge. This reflects the paucity of clinical SCD pain research and limited understanding of the complex biological differences between acute and chronic pain. These issues collectively create barriers to effective, targeted interventions. Optimal pain management requires interdisciplinary care. Objective: These evidence-based guidelines developed by the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in pain management decisions for children and adults with SCD. Methods: ASH formed a multidisciplinary panel, including 2 patient representatives, that was thoroughly vetted to minimize bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic reviews. Clinical questions and outcomes were prioritized according to importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel reached consensus on 18 recommendations specific to acute and chronic pain. The recommendations reflect a broad pain management approach, encompassing pharmacological and nonpharmacological interventions and analgesic delivery. Conclusions: Because of low-certainty evidence and closely balanced benefits and harms, most recommendations are conditional. Patient preferences should drive clinical decisions. Policymaking, including that by payers, will require substantial debate and input from stakeholders. Randomized controlled trials and comparative-effectiveness studies are needed for chronic opioid therapy, nonopioid therapies, and nonpharmacological interventions.

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Clinical Guideline Highlights for the Hospitalist: Management of Acute and Chronic Pain in Sickle Cell Disease

Journal of Hospital Medicine ◽

10.12788/jhm.3556 ◽

2021 ◽

Author(s):

Charles D Pham ◽

Duong T Hua

Keyword(s):

Chronic Pain ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pediatric Patients ◽

Clinical Guideline ◽

Target Population ◽

Cell Disease ◽

Release Date ◽

History Of ◽

American Society

GUIDELINE TITLE: American Society of Hematology 2020 Guidelines for Sickle Cell Disease: Management of Acute and Chronic Pain RELEASE DATE: June 19, 2020 PRIOR VERSION: Not applicable DEVELOPER: American Society of Hematology Guideline Panel on Sickle Cell Disease-Related Pain FUNDING SOURCE: American Society of Hematology TARGET POPULATION: Adult and pediatric patients with a history of sickle cell disease with acute and chronic pain.

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Serum Levels of Substance P Are Elevated in Patients With Sickle Cell Disease and Increase Further During Vaso-Occlusive Crisis

Blood ◽

10.1182/blood.v92.9.3148.421k12_3148_3151 ◽

1998 ◽

Vol 92 (9) ◽

pp. 3148-3151 ◽

Cited By ~ 3

Author(s):

Lisa A. Michaels ◽

Kwaku Ohene-Frempong ◽

Huaqing Zhao ◽

Steven D. Douglas

Keyword(s):

Sickle Cell Disease ◽

Substance P ◽

Sickle Cell ◽

Therapeutic Potential ◽

Serum Levels ◽

Control Group ◽

Cell Disease ◽

Neurokinin Receptor ◽

Pain Crisis ◽

American Society

As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor- (TNF-) release and a promoter of interleukin-8 (IL-8), which are reported to be increased in SCD. These cytokines enhance adhesion of leukocytes to endothelium and may play a role in vaso-occlusive events. Serum levels of IL-8, TNF, and SP were studied in three groups of children aged 2 to 18 years: 30 well children with SCD, 21 with SCD in pain crisis, and 20 healthy age-matched controls. Serum levels of SP were elevated in all SCD patients and were highest in patients in pain crisis. The percentage of sera with detectable levels of IL-8 (>5.0 pmol/L) was increased in SCD patients as compared with the control group. IL-8 levels were similar for well SCD patients and those with pain. TNF levels were not significantly different among the three groups. In three children with SCD, SP was measured at baseline and again during pain crisis. In each case, serum levels during pain crisis were higher than they were when the patient was well. We conclude that levels of SP are high in patients with SCD and increase during pain crisis. These results imply that SP plays a prominent role in the pain and inflammation of SCD and may be a measurable laboratory marker of vaso-occlusive crisis. We speculate that neurokinin receptor antagonists may have a therapeutic potential in the treatment of crisis pain. © 1998 by The American Society of Hematology.

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American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults

Blood Advances ◽

10.1182/bloodadvances.2019001142 ◽

2020 ◽

Vol 4 (8) ◽

pp. 1554-1588 ◽

Cited By ~ 8

Author(s):

M. R. DeBaun ◽

L. C. Jordan ◽

A. A. King ◽

J. Schatz ◽

E. Vichinsky ◽

...

Keyword(s):

Cognitive Function ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Care ◽

Diagnosis And Treatment ◽

Practice Research ◽

Evidence Based ◽

Ultrasound Screening ◽

Cell Disease ◽

American Society

Abstract Background: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. Objective: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. Methods: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. Results: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle– and high-income settings. Conclusions: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle–income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

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Serum Levels of Substance P Are Elevated in Patients With Sickle Cell Disease and Increase Further During Vaso-Occlusive Crisis

Blood ◽

10.1182/blood.v92.9.3148 ◽

1998 ◽

Vol 92 (9) ◽

pp. 3148-3151 ◽

Cited By ~ 55

Author(s):

Lisa A. Michaels ◽

Kwaku Ohene-Frempong ◽

Huaqing Zhao ◽

Steven D. Douglas

Keyword(s):

Sickle Cell Disease ◽

Substance P ◽

Sickle Cell ◽

Therapeutic Potential ◽

Serum Levels ◽

Control Group ◽

Cell Disease ◽

Neurokinin Receptor ◽

Pain Crisis ◽

American Society

Abstract As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor- (TNF-) release and a promoter of interleukin-8 (IL-8), which are reported to be increased in SCD. These cytokines enhance adhesion of leukocytes to endothelium and may play a role in vaso-occlusive events. Serum levels of IL-8, TNF, and SP were studied in three groups of children aged 2 to 18 years: 30 well children with SCD, 21 with SCD in pain crisis, and 20 healthy age-matched controls. Serum levels of SP were elevated in all SCD patients and were highest in patients in pain crisis. The percentage of sera with detectable levels of IL-8 (>5.0 pmol/L) was increased in SCD patients as compared with the control group. IL-8 levels were similar for well SCD patients and those with pain. TNF levels were not significantly different among the three groups. In three children with SCD, SP was measured at baseline and again during pain crisis. In each case, serum levels during pain crisis were higher than they were when the patient was well. We conclude that levels of SP are high in patients with SCD and increase during pain crisis. These results imply that SP plays a prominent role in the pain and inflammation of SCD and may be a measurable laboratory marker of vaso-occlusive crisis. We speculate that neurokinin receptor antagonists may have a therapeutic potential in the treatment of crisis pain. © 1998 by The American Society of Hematology.

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Red blood cell exchange: 2015 American Society for Apheresis consensus conference on the management of patients with sickle cell disease

Journal of Clinical Apheresis ◽

10.1002/jca.21511 ◽

2016 ◽

Vol 32 (5) ◽

pp. 342-367 ◽

Cited By ~ 16

Author(s):

Ravi Sarode ◽

Samir K. Ballas ◽

Alicia Garcia ◽

Haewon C Kim ◽

Karen King ◽

...

Keyword(s):

Sickle Cell Disease ◽

Blood Cell ◽

Sickle Cell ◽

Red Blood Cell ◽

Consensus Conference ◽

Cell Disease ◽

American Society

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Red cell exchange: special focus on sickle cell disease

Hematology ◽

10.1182/asheducation-2014.1.450 ◽

2014 ◽

Vol 2014 (1) ◽

pp. 450-456 ◽

Cited By ~ 22

Author(s):

Haewon C. Kim

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Central Venous Access ◽

Oxygen Affinity ◽

Venous Access ◽

Special Focus ◽

Red Cell ◽

Cell Disease ◽

American Society ◽

Oxygen Carrying Capacity

Abstract The primary function of red blood cells (RBCs) is to deliver oxygen from the lungs to tissues. Tissue hypoxia occurs when the oxygen-carrying capacity of RBCs is compromised due primarily to 3 causes: (1) a reduction in circulating RBC mass, (2) an increase in circulating RBC mass, or (3) abnormal hemoglobin (Hb) that either does not sufficiently release oxygen to tissues (high-oxygen-affinity hemoglobin) or occludes the microvasculature due to deformed RBCs (sickled RBCs). To improve oxygenation in patients with reduced or increased RBC mass, RBC administration (simple transfusion) or RBC removal (RBC depletion) is performed, respectively. However, for patients with abnormal Hb, RBCs containing abnormal Hb are removed and replaced by healthy volunteer donor RBCs by red cell exchange (RCE). RCE can be performed by manual exchange or by automated exchange using a blood cell separator (erythrocytapheresis). In this review, indications for RCE in sickle cell disease using the evidence-based American Society for Apheresis categories1 are presented and the rationale for RCE in each disorder are discussed. Simple transfusion versus RCE and manual RCE versus automated RCE are compared. Finally, this review briefly presents some of the challenges of performing erythrocytapheresis in small children and discusses various choices for central venous access during RCE.2

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