Abstract

Introduction: Sickle cell disease (SCD) is one of the most common inherited hemoglobinopathies in Middle East and specifically Saudi Arabia which leads to vaso-occlusive, hematological and infectious crises, including stroke as one of the common complications (1,2). Primary prevention of the first stroke is carried out by risk assessment using transcranial Doppler (TCD) ultrasound and providing blood transfusions to SCD patients with higher than 199 cm/sec TCD velocities (3). Furthermore, althoughhigher HbF expression is also associated with less severity of the SCD, no studies are available about association of HbF with TCD flow velocities and hence risk of stroke in SCD (4). This study has been carried out to identify SCD patients at high risk of stroke based on TCD results, and to determine the association between Hb-F levels and blood velocity using TCD results.

Patients and Methods: Cross-sectional study included 56 pediatric SCD patients. TCD ultrasounds were performed at diagnosis for assessment of first stroke risk and then after every 6 months for follow-up studies. Patients with elevated TCD velocities given monthly packed RBCs transfusions to have HbS level around 40% (5,6). Data analysis was performed by "Statistical Package for the Social Sciences (SPSS, Version 17.0)".

Results:

In our patient population, male to female ratio was 1.33:1 (32 males, 24 females) and mean age was 7.5 ± 3.42 years (range: 2-14 years). Seven (12.5%) patients had TCD velocities higher than or equal to 200 cm/second, with mean age of 4.7±1.4 years and mean HbF 7.5±3.8, which were significantly different from patient group with normal flow velocities (mean age of 7.8±3.4 years; mean HbF 20±15.9). Patients with higher TCD velocities receiving blood transfusion got velocities in normal range within 6-12 months. Most importantly, normal TCD flow velocities were significantly associated with higher HbF expression and vice versa. As protective role of HbF in sickle cell patients is well established (11;13) and inducing the HbF expression in such patients using medications like hydroxyurea (20) or by genetically modifying the silencing of fetal γ-globin gene have been long standing goal in treatment of sickle cell disease (21), our findings about correlation of higher TCD flow velocities with lower HbF expression (and vice versa) and hence higher risk of first stroke in sickle cell patients provides a new direction for assessing the risk for vasculopathy in SCD patients.

Discussion/Conclusions:

Low prevalence of SCD patients with higher TCD velocities in our study population is in accordance with previous studies (5). Risk of first stroke was clinically manageable by 6-12 months of regular PRBCs transfusions, per established clinical practice (6). Moreover, normal TCD flow velocities and hence lower risk of stroke was significantly associated with the higher hemoglobin F expression and vice versa. As protective role of HbF in sickle cell patients is well established (4) and inducing the HbF expression in such patients have been long standing goal in treatment of sickle cell disease (7), our findings about correlation of higher TCD flow velocities with lower HbF expression (and vice versa) and hence higher risk of first stroke in sickle cell patients provides a new direction for assessing the risk for vasculopathy in SCD patients.

References: 1. Kato GJ. Curr Opin Hematol. 2016 May;23(3):224-32. 2. Ahmed AE, et al. Health Qual Life Outcomes. 2015 Nov 16;13:183. 3. Lawrence C, Webb J. Curr Neurol Neurosci Rep. 2016 Mar;16(3):27. 4. Liu L, et al. Exp Biol Med (Maywood). 2016 Apr;241(7):706-18. 5. Adams R, McKie V, Hsu L, et al. N Engl J Med. 1998;339: 5-11. 6. Bernaudin F, et al. Blood. 2016 Apr7;127(14):1814-22. 7. Pule GD, et al. Clin Transl Med. 2016 Mar;5(1):15. doi: 10.1186/s40169-016-0092-7.

Disclosures

Saglio:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria.

Author notes

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Asterisk with author names denotes non-ASH members.