SCD

Pain

SCD patients have acute intermittent pain, chronic daily pain, and acute on chronic pain. Pain spans the life course and begins as early as the first year of life. 30-40% of SCD adults suffer from chronic pain.

Mechanisms of SCD pain likely include components such as hypoxia-reperfusion injury, inflammation, increased red blood cell adhesion, and nervous system sensitization (central and peripheral).

Management of SCD

Cardiopulmonary And Kidney Disease

Cerebrovascular Disease

Silent strokes and cognitive impairment are the most common sequelae of SCD in children and adults. By 40 years of age, 20% of adults have a stroke.

ASH 2020 Guidelines

Primary Stroke Prevention for children

  1. Annual TCD screening recommended for HbSS/HbSβ
  2. For HbSS/HbSβ with abnormal TCD, recommend regular blood transfusion for 1 year with a goal HbS <30% and Hb > 90 to reduce the risk of stroke.
  3. Can transition to hydroxyurea therapy after 1 year with MRI/MRA of the brain to risk stratify.
  4. In LMIC settings, hydroxyurea 20 mg/kg/d can be started if regular blood transfusions are not available, for stroke prophylaxis, if the TCD is abnormal.

Treatment of Acute Stroke or TIA

  1. Prompt blood transfusion is recommended. Exchange transfusion is recommended over simple transfusion.

Secondary Stroke Prevention

  1. For children with with a history of prior stroke, recommend goal Hb > 90 at all times, and HbS < 30% between transfusions.
  2. Suggest consideration of revascularization surgery in addition to regular blood tranfusions.

Acute and Chronic Pain

In general, the optimal treatment of both acute and chronic pain requires an individualized approach that involves interdisciplinary care. This approach encompasses pharmacological, non-pharmacological, and integrative therapeutic interventions that are tailored to individual patient needs. There is no one-size-fits-all approach to optimal pain management.

ASH 2020 Guidelines

Acute Pain

  1. Rapid assessment and administration of analgesia with frequent reassessments to optimize pain control.
  2. Tailor opioid therapies based on prior opioid therapies and effective therapies. I.e. individualised care plans.
  3. NSAIDs are suggested for a short course (5-7 days) in addition to opioids for acute pain control.
  4. Steroids are suggested against for acute pain management.
  5. Subdissociative ketamine infusion can be used as an adjunct for refractory pain. Start at 0.1-0.3 mg/kg/hr up to a maximum of 1 mg/kg/hr.
  6. Regional anesthesia is suggested for refractory pain in the abdomen, hip, leg pain. Needs to be anatomically feasible and with local expertise involved (Pain medicine, anesthesia)
  7. No recommendations are made with regards to IV fluids.
  8. Nonpharmacologic therapies for acute SCD pain:
    1. Massage, yoga, TENS, VR, AV relaxation are suggested as adjuncts (!)
    2. Acupuncture or biofeedback therapies are not commented on.

Chronic Pain

  1. Continuous basal opioid infusion - not commended on. E.g. PCA pump chronically
  2. Avascular necrosis: suggest SNRI + NSAID for adults.
  3. Leg ulcers: no recommendations made.
  4. Chronic pain otherwise: SNRI, TCA, gabapentinoids, CBT could be considered (based on fibromyalgia studies etc.)
  5. Chronic opioid therapy (COT) is recommended against unless the pain is refractory to multiple other treatment modalities.
  6. Routinely screen for depression and anxiety

Chronic Transfusion Therapy

  1. Chronic monthly transfusions are recommended against, as a first-line strategy to prevent or reduce recurrent acute pain episodes.
  2. No recommendations are made for these patients with chronic pain.

Transfusion Support

RBC transfusions are a mainstay of therapy for patients with SCD. 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.

ASH 2020 Guidelines (Pocket Guide)

RBC Antigen Profiling

  1. Extended RBC antigen profile (genotype or serology) is suggested over ABO/RhD typing alone for all patients with SCD at the earliest opportunity. Includes C/c, E/e, K, Jka/Jkb, Fya/Fyb, M/N, and S/s at a minimum. Serologic phenotype may be inaccurate if the patient has been transfused in the last 3 months. Genotype is preferred over serologic phenotyping.

Prevention of Hemolytic Transfusion Reactions in High-Risk Pts

  1. Immunosuppressive therapies are suggested in patients with SCD with an acute need for transfusion and at high risk of AHTR, or with a history of multiple or life-threatening DHTRs. Therapies to consider: IVIg, steroids, RTX.

Management of Severe Hemolytic Transfusion Reactions with Hyperhemolysis

  1. Immunosuppressive therapies (IVIg, steroids, RTX, and/or eculizumab) are suggested in patients with SCD with a DHTR and ongoing hyperhemolysis.
    1. DHTR defined here as significant drop in Hb within 21 days post-transfusion with 1+ of new red cell alloantibody, hemoglobinuria, accelerated increased in HbS% with a new fall in HbA posttransfusion, relative reticulocytopenia or reticulocytosis from baseline, significant LDH elevation from baseline, and exclusion of an alternative cause.
    2. Hyperhemolysis is defined here as a rapid hemoglobin decline below the pretransfusion level and rapid decline of posttransfusion HbA level
    3. For life-threatening hemolysis, initiate immunosuppressive therapy promptly.
    4. First-line: IVIg and high dose steroids
    5. Second-line: eculizumab
    6. Avoidance of further transfusion is recommended unless patients are experiencing life-threatening anemia with ongoing hemolysis. If transfusion is warranted, extended matched red cells (C/c, E/e, K, Jka/Jkb, Fya/Fyb, S/s) should be considered.

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Transfusions for Chronic Therapy

  1. Automated RCE (red-cell exchange apheresis) is suggested over simple transfusion or manual RCE. Automated procedures are more likely to achieve HbS% targets and required half the time of manual procedures (P < .0001), but alternative methodologies of manual exchange can achieve improved adherence with HbS% targets.

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Transfusions for Acute chest Syndrome

  1. Automated RCE or manual RCE suggested over simple transfusion for SCD + severe acute chest syndrome.
  2. Automated, manual, or simple transfusions are suggested for SD + moderate acute chest syndrome.

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Transfusions During Pregnancy

  1. Prophylactic transfusions at regular intervals OR standard care are suggested for pregnancy patients with SCD.
    1. consider prophylactic transfusions for patients with a history of severe SCD related complications before the current pregnancy, or with additional features of high-risk pregnancy

PREoperative Transfusions

  1. Preoperative transfusions are recommended for patients with SCD undergoing surgeries requiring GA and lasting more than 1 hour. Pre-operative target: Hb ≥ 90. For patients with preoperative transfusion with a high Hb level, provide RCE (manual or automated).

Screening for Iron OVerload

  1. Patients should have iron overload screening (MRI liver) every 1-2 years, as opposed to serial serum ferritin level monitoring.
  2. Cardiac screening (cardiac MRI) is suggested against over serial ferritin monitoring.

References/Clinical Practice Guidelines

  1. Clinical Practice Guidelines on Sickle Cell Disease - Hematology.org Useful reference pocket guides.
  2. Sickle Cell Disease Clinical Guidelines | CDC
  3. Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Advances. 2020;4(12):2656-2701. doi:10.1182/bloodadvances.2020001851
  4. Howard J. Sickle cell disease: when and how to transfuse. Hematology Am Soc Hematol Educ Program. 2016;2016(1):625-631.