What would your next line of treatment be for a patient with Hb SC with history of recurrent VOC and new bone infarct who is already on hydroxyurea and phlebotomy?

HbSC disease is the stepchild of sickle hemoglobinopathies with almost no studies of its treatment, so that any recommendation is not data based. One might consider adding crizanlizumab that blocks red cell-endothelial cell adherence. Each treatment group of the crizanlizumab study that led to its FDA approval had some patients with HbSC disease. (Ataga et al., PMID 27959701) They were part of the “other genotypes” group that also included patients with HbS-beta thalassemia. The “other genotypes” group, also responded with a reduction in painful episodes but the number of patients treated was very small. The voxelotor study also had HbSC patients but they were not analyzed separately. (Vichinsky et al., PMID 31199090) The primary endpoint o...

First, it would be important to assess whether there may be non-medical reasons for the frequent VOC. As you know, psychosocial factors are important determinants of health in sickle cell disease and I would want to make sure those are addressed. You may also want to explore whether the patient is experiencing flares of chronic pain rather than true acute VOC. This is very difficult to assess but if there is a history of avascular necrosis, leg ulcers, neuropathy, or other causes of chronic pain those may be drivers of hospitalizations and may not respond to any disease modifying treatment (DMT). If you are reasonably confident that you are dealing with recurrent VOCs you have several options. First, you should assess adherence to hydroxyur...