Stuck on sickle cell disease? We hammer out the basics of diagnosis, common sickle cell variants and their manifestations, preventive medicine, acute and chronic pain management, opioid use, and how to recognize and treat common complications like anemia, fever and acute chest syndrome. Sickle cell expert, Sophie Lanzkron MD, Associate Professor of Medicine and Oncology and Director of the Sickle Cell Center for Adults at Johns Hopkins joins!
Written (including CME questions) and produced by: Justin Berk MD, Martha Brucato MD PhD, Beth Garbitelli MS1
Hosts: Paul Williams MD, Justin Berk MD, Matthew Watto MD
Edited by: Matthew Watto MD
Guest: Sophie Lanzkron MD MHS
|Sickle Cell Type||Hemoglobin Composition|
|HbAS – Sickle Cell |
|60% Hemoglobin A (“normal”), |
40% Hemoglobin S (“sickle”)
|HbS𝝱+ Thalassemia||40% Hemoglobin A, 60% Hemoglobin S|
|HbSC Disease||50% Hemoglobin C (other variant), |
50% Hemoglobin S
|HbSS Disease ||80-90% Hemoglobin S |
10% other hemoglobin types e.g. F, A2
|HbS𝝱0 (Sickle – Beta |
|Mostly Hemoglobin S, |
Small amount of hemoglobin F
Typically, HbSS and HBS𝝱0 have a more severe phenotype (i.e. more severe clinical symptoms). However, some HbSC patients can present with very severe symptoms and some patients with HbSS that have few symptoms. Other complex variants also exist.
Sickle Cell trait will often not have significant clinical manifestations. [See a recent review of clinical outcomes in Naik et al. Ann Intern Med. 2018]
A hemoglobin HPLC (i.e. High Performance Liquid Chromatography, hemoglobin fracture, or hemoglobin electrophoresis) can quantify the percentage of each hemoglobin variant.
The most recent 2014 NHLBI Guidelines for Management of Sickle Cell Disease can be found here. Of note, our guest Dr. Lanzkron is a contributing author.
Given functional asplenia, patients with SCD should get extra immunization against encapsulated organisms (namely pneumococcal and meningococcal vaccines). (Yawn et al. JAMA 2014)
Patients should also get the flu shot given an increased risk for flu complications. (Bundy et al. Pediatrics 2010).
Routine CBC, reticulocyte count and kidney/liver function tests are performed annually to monitor baseline hemoglobin and look for end-organ damage. Yawn et al. JAMA 2014). Of note, serum creatinine is a poor measure of renal function in sickle cell disease.
The renal medulla is the most hypoxic part of the body and the kidney is one of the earliest affected organs in Sickle Cell Disease. When creatinine begins to rise, a significant amount of function is already lost. As such, annual screening for proteinuria and/or microalbuminuria is recommended to gauge renal function.
Patients with SCD are at high risk for visual complications and so should get annual eye exams to check for retinal disease. (Yawn et al. JAMA 2014)
Producer’s Note: Other recommendations included but not discussed: folate supplementation, ACE-inhibitors for microalbuminuria, and specific pediatric screening and prophylaxis (cf. Table 3 in Yawn et al. JAMA 2014)
Important questions to ask when taking the history of a patient with Sickle Cell Disease include:
Hydroxyurea reduces reduces crisis frequency, ACS events, need for transfusions, and hospitalizations (Charache et al. NEJM 1995) and has been shown to improve survival (Voskaridou et al. Blood. 2010).
Hydroxyurea is indicated in use for people with HbSS. There is less evidence for those who have other variants of Sickle Cell Disease.
Hydroxyurea works by increasing fetal hemoglobin (therefore decreasing the proportion of HbS) and decreasing expression of adhesion molecules. Thus, it reduces vascular occlusion (Ware. Blood 2010).
Originally a chemotherapy medication, hydroxyurea can cause bone marrow suppression. CBCs should be monitored and the dose of hydroxyurea is titrated to an a Absolute Neutrophil Count of 2,000 to 4,000 while maintaining platelets above 90K and an absolute reticulocyte count above 90K (Yawn et al. JAMA 2014).
NOTE: Decreasing Hemoglobin S to below 30% reduces risk of stroke (STOP Trial – Lee et al. Blood. 2006). Chronic transfusion therapy seems to improve health related quality of life (Beverung et al. Am J Hematol. 2015).
Acute transfusion is indicated for symptomatic anemia with low reticulocytes (Yawn et al. JAMA 2014).
Silent cerebral infarcts and resulting cognitive problems are common in this patient population. MRI imaging has demonstrated silent infarcts occurs in ~30% of patients with SCD before age 6 and ~40% before age 14 (DeBaun et al. Blood. 2012).
Pediatrics Pearl: Transcranial Dopplers are recommended to be performed annually from ages 2-16. Look for increased velocity, which is associated with cerebral infarcts (Yawn et al. JAMA 2014).
NOTE: These cognitive deficits can make patient care more challenging. Therefore, Dr. Lanzkron recommends sending patients for neurocognitive testing. Identifying deficits can provide insight for both patients and the treating clinician.
Types of activity including swimming in cold water or exposure to cold environments can cause a crisis.
There is no lab finding or specific tool that definitively indicates an acute crisis. You may not see a drop in hemoglobin. During a crisis, Absolute Reticulocyte Count should be monitored to detect an aplastic crisis early. –Dr Lanzkron’s expert opinion
Short-acting opioids or NSAIDs (if renal function allows) can be useful for managing an acute crisis.
Per Dr. Lanzkron: Patient-controlled analgesia (PCA) pumps are preferred over bolus therapy for narcotics. Check the PCA frequently (every 3 – 4 hours). Adjust dosing as needed for patient comfort. A typical crisis will require higher doses in the first 24 hours. Afterwards, doses can be weaned. Each day, it is important to calculate total opioid use in 24 hours.
NOTE: Blood transfusion may not be required for an acute crisis! The American Society of Hematology’s Choosing Wisely campaign includes this: “Don’t routinely transfuse patients with sickle cell disease (SCD) for chronic anemia or uncomplicated pain crisis without an appropriate clinical indication.”
Ideally, each patient should have a pain plan for crises at home, in the ED, and in the hospital. During a crisis, it is important to remember to consider other causes of pain. In other words, don’t anchor on SCD and forget that another diagnosis may be the cause of pain.
Chronic opioid therapy has many harms. And, it may not cause benefits in pain management (for example, see Karafin et al. Hematology 2018). There are some patients (e.g. older patients with avascular necrosis without surgical options) where long acting opioids many be useful, but this should be a discussion with a pain management team.
If patients are on chronic pain management, it should be continued while treating an acute crisis (Yawn et al. JAMA 2014).
Having a non-functional spleen puts patients with sickle cell disease at risk for life-threatening complications from severe bacterial infections, particularly due to encapsulated bacteria (Booth et al. Int J Inf Disease. 2010). SCD patients are also at risk of serious complications from flu and other infections. Therefore, cultures and antibiotics are required if a patient appears toxic.
Acute Chest Syndrome is a clinical diagnosis. Patients will have: new infiltrate on chest X-ray, along with chest pain/respiratory symptoms and/or fever. There is a spectrum of causes, including infection (i.e. community-acquired pneumonia) or fat embolism from bone marrow infarcts.
NOTE: Not everyone with Acute Chest Syndrome, particularly those with mild symptoms, requires transfusion. Remember. It is a spectrum.
People who are hypoxic require transfusion (Vichinsky et al. Blood. 1997). Use of an incentive spirometer in the hospital can help prevent acute chest syndrome (Niss et al. Blood. 2017; Bellet et al. NEJM 1995).
Listeners will develop a systematic and evidence based approach to common acute complications and routine health maintenance of Sickle Cell Disease.
After listening to this episode listeners will:
Dr. Lanzkron reports research grants or contracts from Pfizer, Ironwood, Global Blood, and Prolong. The Curbsiders are sponsored by the ACP Internal Medicine Meeting 2019 for this episode.
Links are included in the show notes above.
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