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

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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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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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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American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease

Blood Advances ◽

10.1182/bloodadvances.2019000916 ◽

2019 ◽

Vol 3 (23) ◽

pp. 3867-3897 ◽

Cited By ~ 18

Author(s):

Robert I. Liem ◽

Sophie Lanzkron ◽

Thomas D. Coates ◽

Laura DeCastro ◽

Ankit A. Desai ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Health Care Professionals ◽

Conflicts Of Interest ◽

Practice Research ◽

Evidence Based ◽

Cell Disease ◽

Diagnosis And Management ◽

Renal Complications ◽

American Society

Abstract Background: Prevention and management of end-organ disease represent major challenges facing providers of children and adults with sickle cell disease (SCD). Uncertainty and variability in the screening, diagnosis, and management of cardiopulmonary and renal complications in SCD lead to varying outcomes for affected individuals. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD. Methods: ASH formed a multidisciplinary guideline panel that included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews up to September 2017. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. 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, which were subject to public comment. Results: The panel agreed on 10 recommendations for screening, diagnosis, and management of cardiopulmonary and renal complications of SCD. Recommendations related to anticoagulation duration for adults with SCD and venous thromboembolism were also developed. Conclusions: Most recommendations were conditional due to a paucity of direct, high-quality evidence for outcomes of interest. Future research was identified, including the need for prospective studies to better understand the natural history of cardiopulmonary and renal disease, their relationship to patient-important outcomes, and optimal management.

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Outcome of Transitioning Pediatric Patients with Sickle Cell Disease to Adult Programs.

Blood ◽

10.1182/blood.v104.11.3743.3743 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3743-3743 ◽

Cited By ~ 3

Author(s):

Samir K. Ballas ◽

Carlton Dampier

Keyword(s):

Chronic Pain ◽

Young Adults ◽

Pain Management ◽

Sickle Cell Disease ◽

Medical Care ◽

Sickle Cell ◽

Adolescents And Young Adults ◽

Cell Disease ◽

Adult Care ◽

Female Ratio

The transition of medical care of patients with sickle cell disease (SCD) from pediatric to adult providers represents a milestone in their lives. Major concerns among adolescents and young adults about transition include taking responsibility for self, making own decisions, cost of medical care, fear of suboptimal pain management, and reluctance to leave known providers. In this study we present our experience in the process of transition to adult care and its outcome over the last ten years. Adolescents and young adults were given information about the nature of medical care provided by adult internists and hematologists. The sickle cell programs available in the city were described. Moreover, site visits to the hospitals where adult care was to be provided were arranged. During these visits, adolescents and young adults had the chance to meet the hematologist and other potential providers and ask questions, visit the emergency room, the clinic, and the sickle day unit if applicable. Patients were empowered to choose the program to which they wished to be transitioned. During the last 10 years, 90 adolescents and young adults (See Table) with SCD (Sickle Cell Anemia [SS], Hemoglobin SC Disease, and Sickle Thalassemia [ST]) were transitioned to the adult sickle cell program of Thomas Jefferson University. Age of transition varied between 18 and 25 years. Eighteen patients (20%) died. Age at death was 24.9 ± 2.95 years and the male/female ratio was 10:8. Complications of sickle cell disease after transition included leg ulcers, stroke, avascular necrosis, anxiety, depression, and priapism. Nineteen patients (10 males, 9 females) were employed. Twenty-nine (32%) patients developed chronic pain syndrome and its sequelae. Many patients failed to achieve their childhood goals. The data show that a significant number of patients die within 10 years after transition. The quality of life of survivors is suboptimal and drifts into issues of chronic pain management in the adult environment. Identifying these issues may provide predictors that identify children at risk to have undesirable outcomes after transition. Aggressive management and refining the process of transition should improve the outcome after transition. Distribution of the Transitioned Patients SS SC ST Total Male 31 8 4 43 Female 34 8 5 47 Total 65 16 9 90

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Five lessons learned about long-term pain management in adults with sickle cell disease

Hematology ◽

10.1182/asheducation-2017.1.406 ◽

2017 ◽

Vol 2017 (1) ◽

pp. 406-411 ◽

Cited By ~ 4

Author(s):

Joshua J. Field

Keyword(s):

Chronic Pain ◽

Pain Management ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Lessons Learned ◽

Cell Disease ◽

Prescribing Practices ◽

Blood Institute ◽

Pain Syndromes ◽

National Heart Lung

AbstractChronic pain affects one-half of adults with sickle cell disease (SCD). Despite the prevalence of chronic pain, few studies have been performed to determine the best practices for this patient population. Although the pathophysiology of chronic pain in SCD may be different from other chronic pain syndromes, many of the guidelines outlined in the pain literature and elsewhere are applicable; some were consensus-adopted in the 2014 National Heart, Lung, and Blood Institute SCD Guidelines. Recommended practices, such as controlled substance agreements and monitoring of urine, may seem unnecessary or counterproductive to hematologists. After all, SCD is a severe pain disorder with a clear indication for opioids, and mistrust is already a major issue. The problem, however, is not with a particular disease but with the medicines, leading many US states to pass broad legislation in attempts to curb opioid misuse. These regulations and other key tenets of chronic pain management are not meant to deprive adults with SCD of appropriate therapies, and their implementation into hematology clinics should not affect patient-provider relationships. They simply encourage prudent prescribing practices and discourage misuse, and should be seen as an opportunity to more effectively manage our patient’s pain in the safest manner possible. In line with guideline recommendations as well as newer legislation, we present five lessons learned. These lessons form the basis for our model to manage chronic pain in adults with SCD.

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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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Optimizing the care model for an uncomplicated acute pain episode in sickle cell disease

Hematology ◽

10.1182/asheducation-2017.1.525 ◽

2017 ◽

Vol 2017 (1) ◽

pp. 525-533 ◽

Cited By ~ 3

Author(s):

Paul Telfer ◽

Banu Kaya

Keyword(s):

Health Care ◽

Chronic Pain ◽

Pain Management ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Acute Pain ◽

Integrated Approach ◽

Cell Disease ◽

Care Model ◽

Strong Opioids

Abstract The pathophysiology, clinical presentation, and natural history of acute pain in sickle cell disease are unique and require a disease-centered approach that also applies general principles of acute and chronic pain management. The majority of acute pain episodes are managed at home without the need to access health care. The long-term consequences of poorly treated acute pain include chronic pain, adverse effects of chronic opioid usage, psychological maladjustment, poor quality of life, and excessive health care utilization. There is no standard protocol for management of an acute pain crisis in either the hospital or the community. The assumptions that severe acute pain must be managed in the hospital with parenteral opioids and that strong opioids are needed for home management of pain need to be questioned. Pain management in the emergency department often does not meet acceptable standards, while chronic use of strong opioids is likely to result in opioid-induced hyperalgesia, exacerbation of chronic pain symptoms, and opioid dependency. We suggest that an integrated approach is needed to control the underlying condition, modify psychological responses, optimize social support, and ensure that health care services provide safe, effective, and prompt treatment of acute pain and appropriate management of chronic pain. This integrated approach should begin at an early age and continue through the adolescent, transition, and adult phases of the care model.

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L-Glutamine Decreases Opioid Use in Individuals with Sickle Cell Disease and Chronic Pain: A Case Series

Blood ◽

10.1182/blood-2019-126179 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4849-4849

Author(s):

Samuel Wilson ◽

Frances Wright ◽

Marcus A. Carden

Keyword(s):

Chronic Pain ◽

North Carolina ◽

Pain Management ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Care Utilization ◽

Cell Disease ◽

Opioid Use ◽

Opioid Prescription ◽

Over Time

Background: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States (US), affecting approximately 100,000 individuals in the country who are primarily of African descent. One of the most prevalent complications of SCD is pain as a result of episodic vaso-occlusive crises. Over time, many individuals with SCD develop chronic pain and opioid dependence for pain management. L-glutamine (EndariTM) was approved by the US Food and Drug Administration in 2017 for patients 5 years-old and older to reduce complications from SCD after reviewing a phase-III placebo-controlled trial. In this study, L-glutamine led to a reduction in median number of pain crises and increased time to first pain crisis when compared to placebo (Niihara et al, NEJM, 2018). However, the impact of L-glutamine on opioid use over time remains unknown. In this study, we evaluated the effect on opioid use in individuals who were started on L-glutamine for worsening SCD related pain. Methods: After institutional review board approval, we retrospectively reviewed the electronic medical record (EMR) of individuals with SCD followed at the University of North Carolina Pediatric and Adult Sickle Cell clinics prescribed L-glutamine in 2018-2019 for worsening acute and chronic SCD-related pain. The North Carolina state controlled substance reporting system, an online clinical tool which collects information on dispensed controlled substance prescriptions to patients that is freely available to prescribers, was also reviewed for filled opioid prescriptions (and milligram morphine equivalents - MME) for each patient. Data, including health care utilization (e.g. hospitalizations and emergence room (ER) visits) and hemoglobin levels for each patient were also evaluated in the EMR for the four months preceding and the four months after L-glutamine was started to determine if changes were sustained. Results: We identified four female patients (ages ranging from 9 to 24 years-old) with SS genotype and chronic pain with acute exacerbations who had significant opioid prescription reduction after starting L-glutamine. Three individuals were taking the maximum tolerated dosing of hydroxyurea and experiencing escalating pain crises prior to initiation of L-glutamine. One patient was intolerant of hydroxyurea and was on a chronic transfusion program for chronic pain management when she was started on L-glutamine for worsening chronic pain. All patients, or caregivers, reported a reduction in acute on chronic pain after initiating L-glutamine. Each patient had a reduction in 4-month total opioid prescription use (in MME) after starting L-glutamine, ranging from a 21% reduction to 100% reduction (Figure 1). Heath care utilization significantly decreased in 1 patient after starting L-glutamine, with 3 ER visits and 2 hospitalizations in the pre-treatment period and no ER visits or hospitalizations in the post-treatment period. There was no difference in the average hemoglobin levels pre-and-post L-glutamine initiation among the patients (9.8g/dL vs. 9.7g/dL). Discussion: L-glutamine appears to have some benefit in reducing pain and opioid use, as well as healthcare utilization, in a subset of patients with SCD and chronic pain. Although we evaluated a small number of patients, all individuals (or caregivers) reported decreased pain very soon after starting L-glutamine. One patient stopped opioid use altogether in the time period evaluated. Future studies should investigate if effectiveness of L-glutamine may be based on unique red cell metabolic profiles, SCD genotype, or timing of drug initiation in these and similar patients. Future investigations will also determine long-term tolerability of L-glutamine and if the reduction in opioid use is sustained for longer periods among these patients and other responders. Disclosures Carden: GBT: Honoraria; NIH: Research Funding.

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Sickle Cell Disease: Challenges and Comfort in Providing Care By Family Physicians

Blood ◽

10.1182/blood.v126.23.5570.5570 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5570-5570

Author(s):

Onameyore Utuama ◽

Kitty Carter-Wicker ◽

Jennifer Herbert ◽

Robert Gibson ◽

Abdullah Kutlar ◽

...

Keyword(s):

Primary Care ◽

Pain Management ◽

Sickle Cell Disease ◽

Family Medicine ◽

Sickle Cell ◽

Family Physicians ◽

Evidence Based ◽

Cell Disease ◽

Family Medicine Residency ◽

Taking Care

Abstract Young adults with sickle cell disease (SCD) are 3 times more likely to die than their pediatric population. Transition into adulthood, limited access to specialist care, low socio-economic status, and a lack of training of family physicians (FPs), may contribute to complications leading to mortality. When compared to other chronic diseases, fewer specialized clinics and outdated evidence based guidelines exist for adults with SCD. This results in discontinuity in care, increased burden on FPs and poor clinical support. The dependence on primary care and the paucity of up-to-date evidence based management creates a situation where as-needed care is provided, but at a cost to disease management and quality of life. This study was designed to explore challenges faced by FPs in the care of patients with SCD. The survey was conducted at two family medicine residency programs: Morehouse School of Medicine (MSM, online) Atlanta and the Georgia Regents University (GRU, paper survey) Augusta, Georgia (2011-2012). Data collected included demographics, comfort with managing patients with SCD and challenges of caring for SCD patients using a 5-point Likert scale survey. Of 120 FP faculty, 75 (62%) responded. Demographics and background are listed in Table. In multivariate modeling, responds that reported seeing >=1 patients with SCD per month were more likely to report challenges (p=0.0014), and were more likely to answer correctly to 75% questions in a quiz (p=0.0131). Those that responded that pain was a challenge, were more likely to see >=1 patient per month with SCD, and reported overcoming challenges with specialist consultation (p=0.0089). Those that reported feeling mostly or completely comfortable treating patients with SCD were more likely to be male (p=0.0035), reported taking care of some patient with SCD (0.0029), residents (0.0198) and not aged 30-49 (p=0.0072). Given the current push for primary care, the role of FPs in providing continuity of care to patients with SCD, a chronic illness cannot be overemphasized. Like in previous recent studies, we report that pain management in patients with SCD was the greatest challenge reported by FPs. Sense of challenge and competency increased with exposure to patients with SCD. Perception of comfort was related to general exposure to patients with SCD, but was also influenced by other factors, including gender. To improve the competence and reduce the challenges faced by FPs in the management of SCD patients, we recommend: 1) development of primary care focused SCD guidelines, with an emphasis on transition of care. 2) Incorporation of SCD care and pain management into family medicine residency curriculum and Continuing Medical Education (CME) activities. Table. n % Female 41 55 Age 18-29 years 10 13 Age 30-49 years 42 56 Age 50-69 years 23 31 MD/DO 70 93 Other 5 7 Faculty 44 59 Resident 31 41 Training in SCD, residency 42 56 Training in SCD, peer review journals 36 48 Reported taking care of patients with SCD 51 68 >= 1 patient with SCD per month 16 21 Mostly/completely comfortable treating SCD 17 23 Reported challenges in care of patients with SCD, any 32 43 Reported challenges in care of patients with SCD, pain 22 29 Disclosures No relevant conflicts of interest to declare.

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American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation

Blood Advances ◽

10.1182/bloodadvances.2021004394c ◽

2021 ◽

Vol 5 (18) ◽

pp. 3668-3689

Author(s):

Julie Kanter ◽

Robert I. Liem ◽

Françoise Bernaudin ◽

Javier Bolaños-Meade ◽

Courtney D. Fitzhugh ◽

...

Keyword(s):

Stem Cell ◽

Sickle Cell Disease ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Sickle Cell ◽

Acute Chest Syndrome ◽

Evidence Based ◽

Cell Disease ◽

Hematopoietic Stem ◽

American Society

Abstract Background: Sickle cell disease (SCD) is a life-limiting inherited hemoglobinopathy that results in significant complications and affects quality of life. Hematopoietic stem cell transplantation (HSCT) is currently the only curative intervention for SCD; however, guidelines are needed to inform how to apply HSCT in clinical practice. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and health professionals in their decisions about HSCT for SCD. Methods: The multidisciplinary guideline panel formed by ASH included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews (through 2019). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. 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, which were subject to public comment. Results: The panel agreed on 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT. Conclusions: The evidence review yielded no randomized controlled clinical trials for HSCT in SCD; therefore, all recommendations are based on very low certainty in the evidence. Key recommendations include considering HSCT for those with neurologic injury or recurrent acute chest syndrome at an early age and to improve nonmyeloablative regimens. Future research should include the development of a robust SCD registry to serve as a comparator for HSCT studies.

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