While sickle cell anemia was first reported by Dr. James Herrick more than 100 years ago1, there remains only one U.S. Food and Drug Administration (FDA)-approved drug for patients with sickle cell anemia, hydroxyurea. Sickle cell anemia is caused by an inherited mutation where the red blood cells are transformed from a flexible donut-shaped cell to a rigid banana-shaped cell. These cells get clogged in small blood vessels and can cause problems such as severe pain crises and organ damage. Fetal hemoglobin is the type of hemoglobin that we all make when we are in our mother’s wombs. Fetal hemoglobin is not affected by the sickle cell mutation and is protective against changes in the hemoglobin. Fetal hemoglobin decreases the chance that the red blood cells will transform into the banana shape and become clogged in the blood vessels. Months after we are born, our fetal hemoglobin levels usually decrease to very low levels. That is why people with sickle cell anemia typically don’t experience symptoms until they are more than 6 months old.

Hydroxyurea has many potential benefits. First, hydroxyurea significantly increases fetal hemoglobin levels in most patients. In fact, if you look at a patient’s red blood cells under the microscope, you can see that unlike before taking hydroxyurea, many of the cells will look normal. Hydroxyurea decreases the stickiness of the red blood cells to the blood vessels. And hydroxyurea helps the red blood cells to live longer; it also decreases the numbers of white blood cells that also contribute to the clogging of blood vessels. Hydroxyurea use was first reported in adults with sickle cell anemia, and it was found to decrease the number of hospitalizations for pain crises, decrease the frequency of acute chest syndrome, and decrease transfusion requirements2. Based on this study, hydroxyurea was FDA-approved for the treatment of adults with sickle cell anemia in 1998. Subsequently, studies were reported in children and infants with sickle cell anemia with similar findings, showing that hydroxyurea was safe for use in even very young children3,4. Hydroxyurea has not been tested in children to determine whether it is as effective as taking no medication, this would be unethical knowing that hydroxyurea is beneficial and safe in children; because of this, hydroxyurea has never been officially approved for use in children. There have also been multiple studies that show that patients with sickle cell anemia who take hydroxyurea live longer than those who do not take hydroxyurea5-7. Therefore, the recommendation has now been made that most adults with sickle cell anemia should take hydroxyurea and that hydroxyurea should be offered to children as young as 9 months of age, including those who don’t have symptoms8.

The main side effects associated with hydroxyurea are that white blood cells (the cells that help to fight infection) and platelets (the cells that help prevent excessive bleeding) can decrease too much. Therefore, patients who take hydroxyurea must have their blood counts monitored, initially every 2-4 weeks when the medicine is first started and then every 2-3 months when the dose is stable. Some patients are more sensitive than others, so a lower dose is initially started, and the dose can be slowly increased every 8 weeks until the ideal dose is reached. Occasionally patients who take hydroxyurea for long periods of time will notice darkening of their fingernails. Rarely, patients may experience nausea and vomiting and very rarely rash and diarrhea. Also, because of the theoretical risk that hydroxyurea can have a negative impact on the fetus, appropriate contraception should be used and patients should talk to their physicians if they are interested in either getting pregnant or getting their partner pregnant.

While we have been treating patients with sickle cell anemia for now more than 20 years, there is no evidence that hydroxyurea increases the risk of leukemia. In fact, we feel that the benefits of hydroxyurea greatly outweigh the risks in most patients with sickle cell anemia. Therefore, anyone with sickle cell anemia (HbSS or HbSb0-thalassemia disease) should talk to their hematologist about hydroxyurea management. Although hydroxyurea has been show to be potentially effective in hemoglobin SC9, the data are not as clear in patients with other types of sickle cell disease and patients should talk to their doctors about whether hydroxyurea is the right choice for them.

1. Herrick JB. Peculiar Elongated and Sickle-Shaped Red Blood Corpuscles in a Case of Severe Anemia. Arch. Intern. Med. 1910;6(5):517-521.
2. Charache S, Terrin ML, Moore RD, et al. Effect of Hydroxyurea on the Frequency of Painful Crises in Sickle Cell Anemia. The New England journal of medicine. 1995;332(20):1317-1322.
3. Wang WC, Ware RE, Miller ST, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011;377(9778):1663-1672.
4. Ferster A, Vermylen C, Cornu G, et al. Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Blood. 1996;88(6):1960-1964.
5. Steinberg MH, McCarthy WF, Castro O, et al. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. Am. J. Hematol. 2010;85(6):403-408.
6. Voskaridou E, Christoulas D, Bilalis A, et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS). Blood. 2010;115(12):2354-2363.
7. Lobo CL, Pinto JF, Nascimento EM, Moura PG, Cardoso GP, Hankins JS. The effect of hydroxcarbamide therapy on survival of children with sickle cell disease. Br. J. Haematol. 2013;161(6):852-860.
8. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033-1048.
9. Luchtman-Jones L, Pressel S, Hilliard L, et al. Effects of hydroxyurea treatment for patients with hemoglobin SC disease. Am J Hematol. 2016;91(2):238-242.