Impact of Hydroxyurea on Sickle Cell Patients Managed in a Community Medical Center
Authors: Shah Shailja , Nwosu-Iheme Adaeze , Cohen Alice J. 
Published: October 2019

Abstract
Background: Sickle Cell Disease (SCD), including the subtypes of HbSS(SS) or Hb S beta zero thalassemia(SB0) are characterized by frequent vasoocclusive pain crises (VOC) requiring numerous visits to emergency departments and admissions to the hospital. A NHLBI expert panel recommends that patients(pts) with SCD receive hydroxyurea(H) therapy to improve clinical outcomes. H, approved by the FDA in 1998 for treatment of clinically severe SCA is the only disease modifying agent for sickle cell disease. Its primary mechanism of action is induction of fetal hemoglobin (HbF) which in turn causes inhibition of sickling. As a part of our adult sickle cell comprehensive care program, aggressive education and counseling has been utilized to ensure that eligible adults with SCD are treated with H. The clinical benefits of this program were tracked for its impact on blood parameters and utilization of health care services.
Methods: Pts with SS/SB0 over the age of 18 years attending a comprehensive SCD program were tracked for use of H, clinic and ED visits, hospitalizations and transfusions over a period of 12 months. Lab parameters monitored included WBC, Hemoglobin(Hb), MCV , platelets(plts), Hb F level. Dose of H in the steady state is reported in mg/kg . Education about the benefits and side effects was provided utilizing a newly created video, one on one counselling and educational group programs. As part of the yearly visits, H education and compliance were reinforced. Pts were excluded if attempting pregnancy, currently pregnant or breast feeding.
Results: We identified 169 pts of which 135 were evaluable with complete data. 89/135 (66%) were on H and 46/135 (34%) not on H. The major barrier to not taking H was patient refusal. Pts on H were divided into two groups, Hb F < 15%(n=54) and Hb F >15% (n=35); 66/89 (75%) were SS , 22/89(25%) SB0. As expected, MCV and HB were higher in pts on H and WBC and plts were lower in pts on H and correlated with higher HbF levels (See Table 1).
Table 1. Not on H(n=46) Pts on H with HbF<15% ( n=54) Pts on H with HbF >15%( n=35) WBC(K/uL) 11.3 9.6 8.8 HB(g/dl) 8.4 8.4 9.1 MCV(fL) 90.7 102 113.3 Platelets(K/uL) 367 320 308 HbF (%) 5.5 7.6 18.8 H dose (mg/kg) N/A 22.6 18.6
The number of ED visits was significantly lower on H. Admissions trended lower on H but were not statistically different (see Table 2).
Table 2. Pts on H Pts not on H P value ER visits (mean) 1.36 3.15 0.0206 Hospital Admissions (mean) 3.05 3.41 0.6261 Clinic Visits (mean) 6.10 5.89 0.7382
Pts on H had similar ED, clinic visits and admissions with HbF levels of <15% and >15%.
The number of pts transfused were as follows: pts not on H 25/46(54%); on H 40/89(45%); and pts with HbF<15% -28/54(52%), while HbF>15%- 12/35(34%).
Conclusion: Aggressive education in a community comprehensive care clinic has allowed for a majority of eligible patients with SS/SB0 to utilize H. Use of H has significantly reduced ED visits suggesting uncomplicated VOC can be reduced utilizing H in a community setting .Transfusions were reduced in patients on H especially those with HbF >15%. Mean H dosing did not correlate with higher HbF levels, which raises the question of compliance in some pts. Continued education, monitoring of prescriptions filled and possible higher doses of H may be beneficial in reducing hospitalizations.

Disclosures
No relevant conflicts of interest to declare.