Page 271 - 2021_06-Haematologica-web

Letters to the Editor
effect (<76 g/L vs. >86 g/L).3 However, there may also be an additional rheological benefit in the form of improved red blood cell deformability and reduced hemolysis reducing microinfarcts. Unfortunately, we did not have sufficient data on baseline Hb levels in this cohort to assess the interaction of AT and Hb on SCI.
Our study had some important negative findings. Some studies have found low HbF levels to be a risk factor4-6 for SCI, whereas others have not.3,15 In our cohort, we did not see any association of HbF% with SCI outcomes. We also did not see an association with the genetic modula- tors of HbF, nor the composite g(HbF) prediction score,10 suggesting genetic variation of HbF levels in our popula- tion of predominantly west African and Caribbean patients does not determine the risk of SCI. However, we did not consider the possible confounding influence of concurrent large vessel vasculopathy on SCI, which has been suggested to represent an alternative pathogenic mechanism of SCI.4 Additionally, although we confirmed the increased risk with male sex previously reported,3 we did not find any association of the X-linked condition G6PD deficiency. We also did not find a correlation with candidate variants previously identified. Finally, our own genome wide analysis also did not generate novel candi- dates, although it is possible that genetic associations might be found by larger studies.
In summary, our key findings are that co-inheritance of AT and female sex, but not elevated HbF%, provide pro- tection against development of SCI in patients with HbSS. SCI are common and under recognised in patients with HbSC, and further studies are needed to better understand the prevalence rates and risk factors in this condition.
John N. Brewin,1,2 Helen Rooks,1 Kate Gardner,1,3 Harry Senior,1 Mrinmayi Morje,1 Hamel Patel,1 David Calvet,4 Pablo Bartolucci,4 Swee-Lay Thein,5 Stephan Menzel1# and David C. Rees1,2#
1Kings College London, UK; 2Kings College Hospital, London, UK; 3Guys and St Thomas Hospital, London, UK; 4Henri Mondor Hopital, Paris, France and 5NIH, Bethesda, USA
#SM and DCR contributed equally as co-senior authors. Correspondence:
JOHN BREWIN - john.brewin@kcl.ac.uk doi:10.3324/haematol.2020.265827
Received: July 3, 2020.
Accepted: December 11, 2020. Pre-published: December 23, 2020.
Disclosures: no conflicts of interest to disclose.
Contributions: JB, SM and DR designed the study; JB, HR,HS, MM, KG, SLT PB and DC recruited patients and performed research; JB analyzed the data and wrote the manuscript. All authors reviewed and approved the manuscript prior to submission
References
1. Kassim AA, Pruthi S, Day M, Rodeghier M, et al. Silent cerebral infarcts and cerebral aneurysms are prevalent in adults with sickle cell anemia. Blood. 2016;127(16):2038-2040.
2. DeBaun MR, Kirkham FJ. Central nervous system complications and management in sickle cell disease. Blood. 2016;127(7):829-838.
3. DeBaun MR, Sarnaik SA, Rodeghier MJ, et al. Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemo- globin, sex, and relative high systolic blood pressure. Blood. 2012;119(16):3684-3690.
4. Calvet D, Tuilier T, Mele N, et al. Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease. Blood Adv. 2017;1(26):2503-2509.
5. Tewari S, Renney G, Brewin J, et al. Proteomic analysis of plasma from children with sickle cell anemia and silent cerebral infarction. Haematologica. 2018;103(7):1136-1142.
6. van der Land V, Mutsaerts HJ, Engelen M, et al. Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease. Br J Haematol. 2016;172(2):274-284.
7. Guilliams P, Fields E, Hulbert L. Higher-than-expected prevalence of silent cerebral infarcts in children with hemoglobin SC disease. Blood. 2015;125(2):416.
8. Pegelow H, Macklin A, Moser G, et al. Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell dis- ease. Blood. 2002;99(8):3014.
9. Brewin JN, Smith A, Cook R, et al. Genetic analysis of patients with sickle cell anemia and stroke before 4 years of age suggest an impor- tant role for APOE. Circ Genom Precis Med. 2020;13(5):531-540.
10. Gardner K, Fulford T, Silver N, et al. g(HbF): a genetic model of fetal hemoglobin in sickle cell disease. Blood Adv. 2018;2(3):235-239.
11. Bhatnagar P, Arking DE, Casella EB, Casella JF. Genome-wide associ-
ation for silent cerebral infarction (SCI) in sickle cell disease: The
silent infarct transfusion trial (SIT) cohort. Blood. 2009;114(22)3563. 12. Bhatnagar P, Barron-Casella E, Bean CJ, et al. Genome-wide meta- analysis of systolic blood pressure in children with sickle cell disease.
PLoS One. 2013;8(9):e74193.
13. Hoppe C, Klitz W, Cheng S, et al. Gene interactions and stroke risk
in children with sickle cell anemia. Blood. 2004;103(6):2391. 14.Thein SL, Menzel S. Discovering the genetics underlying foetal haemoglobin production in adults. Br J Haematol. 2009;145(4):455-
467.
15. Kinney TR, Sleeper LA, Wang WC, et al. Silent cerebral infarcts in
sickle cell anemia: a risk factor analysis. The Cooperative Study of Sickle Cell Disease. Pediatrics. 1999;103(3):640.
haematologica | 2021; 106(6)
1773