One of the biggest concerns is not specific to any individual agent and its toxicity profile, but rather relates to the overall treatment of patients with SCD once they are hospitalized. Hospital-acquired complications contribute substantially to morbidity in adult patients with SCD. For instance, adults with SCD and vascular disease who are hospitalized for vaso-occlusive crisis may inadvertently receive too much intravenous fluid, which may precipitate acute chest syndrome. Children with SCD who are admitted to their usual hospital are often cared for by a hematologist or an SCD specialist; hospitalized adults might not have that focused care available to them, depending on where they present.

Red blood cell transfusions are very beneficial for stroke prevention and for patients with recurrent acute chest syndrome, but we need to transfuse our patients judiciously. There are risks associated with transfusions, such as alloimmunization and iron overload, and we need to save their lifetime transfusions for when they really need them and monitor patients closely for these risks. It is not uncommon for adults with SCD in the community to have both iron overload and multiple antibodies.

As relates to hydroxyurea, it can be a great option, but you have to monitor the patient’s blood counts intermittently and you must ensure that they are taking the medication. Some of the more common side effects that my patients with SCD have concerns about with hydroxyurea use include alopecia, nail discoloration, nausea, and fatigue. Alopecia is relatively rare, but it is a significant concern for patients. With nail discoloration, patients may feel stigmatized by this outward sign of their disease. Some patients are uneasy with the fact that hydroxyurea was not developed specifically for SCD. Many individuals are also worried about the theoretical risk of a secondary malignancy, although this is not something that I have seen in clinical practice.

In addition to hydroxyurea, L-glutamine, voxelotor, and crizanlizumab are now available for the treatment of SCD. My patients who are apprehensive about taking hydroxyurea find it reassuring that the newer disease-modifying agents were specifically designed for SCD and are generally well tolerated. Side effects are possible with all medications, and it is important for people to feel that they can discuss concerns with their physician. Having an open dialogue with patients is crucial in that it allows them to express their treatment concerns without feeling penalized for inquiring about alternative treatment options. And it is wonderful to now have multiple options.