A Review of Treatment Options for the Management of Sickle Cell Disease - Episode 1

NHLBI Recommendations: Anemia-Related Disease Manifestations

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Michael R. DeBaun, MD, MPH, reviews the NHLBI (National Heart, Lung & Blood Institute) recommendations for screening and monitoring of anemia-related disease manifestations and the goals of therapy for patients with sickle cell disease (SCD).

Michael R. DeBaun, MD, MPH: One of the questions that comes up in sickle cell disease is what is the NHLBI [National Heart, Lung, and Blood Institute] recommendation for screening and monitoring of anemia-related disease manifestation? As I’m sure the audience is aware, sickle cell disease is manifested by chronic anemia. By definition, individuals with the disease have low hemoglobin. Within the hemoglobin range of typically 6 through approximately 11 g/dL, you have individuals with hemoglobin SS, S beta-zero thalassemia and S beta-plus thalassemia, hemoglobin SC. Typically children and adults with hemoglobin SS and S beta-zero thalassemia have hemoglobin levels between approximately 6 and about 9 g/dL. Individuals with S beta-plus thalassemia may have hemoglobin up to 11.5 even 12 g/dL, and individuals with hemoglobin SC will have hemoglobin between 8.5 and 12 g/dL.

The major clinical manifestation of chronic anemia is the presence of overt and silent strokes. Typically, overt and silent strokes occur in children and adults with hemoglobin SS and hemoglobin S beta-zero thalassemia, although individuals with hemoglobin S beta-plus thalassemia and hemoglobin SC disease can have silent and avert strokes as well. The biggest risk factor we can identify in children and adults with sickle cell disease who’ve had a stroke is a prior stroke that occurs anywhere from 6 months to a year after the initial ischemic injury. In addition, there is a biomarker for ischemic stroke that can be used in children between 2 and 16 years of age with hemoglobin SS and hemoglobin S beta-zero. And that biomarker is…transcranial Doppler [TCD] velocity. Using a nonimaging technique a transcranial Doppler velocity of greater than 200 cm per second is associated with about a 10% risk of stroke within a year of obtaining the imaging of the brain. This is referred to as transcranial Doppler nonimaging technique. 

As a result, screening for abnormal TCD measurements have become standard care in children with sickle cell anemia between 2 and 16 years of age. Once the child has been identified as having an abnormal TCD, then we would recommend that they be started on at least an initial transfusion for approximately 12 months and then consideration to be switched over to receive hydroxyurea at maximum tolerated dose. The major risk factor for increased transcranial Doppler velocity associated with the increased risk of stroke is a low hemoglobin. That’s the major complication of low hemoglobin in a population, neurological injury to the brain, although it also has been associated with cognitive impairment. 

What are the goals of therapy for children and adults with sickle cell disease? The main goal is to allow individuals with this disease to live a normal life, for children to go through the rites of passage you’d expect every child to go through, their first steps, their prekindergarten first day, graduation from high school, and moving along with the rest of their life. We expect the women with sickle cell disease to have children. We expect them to have a full family life. We expect the men to be fathers. Thus, our goal as providers in this population is to use every resource available to improve the quality of their lives so they can make informed decisions about the things that they want to pursue. 

What do guidelines recommend? There are multiple sets of guidelines now by national authorities. NHLBI guidelines were published in 2014. American Thoracic Society guidelines were published shortly thereafter, focused on cardiopulmonary disease. Then, ASH [the American Society of Hematology] in the last 2 years has set up several guidelines for heart, lung, and kidney disease, blood transfusion, management of pain, and preventive treatment of CNS [central nervous system] manifestation of sickle cell disease.

Transcript Edited for Clarity