Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease

Vandana Sachdev, Stanislav Sidenko, Melinda D. Wu, Caterina P. Minniti, Hwaida Hannoush, Cynthia L. Brenneman, Myron A. Waclawiw, Andrew E. Arai, Alan N. Schechter, Gregory J. Kato, Jonathan R. Lindner

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In sickle cell disease (SCD), abnormal microvascular function combined with chronic anaemia predisposes patients to perfusion-demand mismatch. We hypothesized that skeletal muscle and myocardial perfusion, normalized to the degree of anaemia, is reduced at basal-state compared to controls, and that this defect is ameliorated by hydroxycarbamide (HC; also termed hydroxyurea) therapy. Twenty-one SCD patients, of whom 15 were treated with HC, and 27 controls underwent contrast-enhanced ultrasound (CEU) perfusion imaging of the forearm as well as the myocardium. HC treatment was associated with lower white cell and reticulocyte counts, and higher fetal haemoglobin and total haemoglobin levels. When corrected for the degree of anaemia in SCD patients, skeletal flow in HC-treated patients was significantly higher than in untreated SCD patients (217·7 ± 125·4 vs. 85·9 ± 40·2, P = 0·018). Similarly, when normalized for both anaemia and increased myocardial work, resting myocardial perfusion was also significantly higher in HC-treated patients compared with untreated SCD patients (0·53 ± 0·47 vs. 0·13 ± 0·07, P = 0·028). Haemoglobin F (HbF) levels correlated with skeletal muscle microvascular flow (r = 0·55, P = 0·01). In conclusion, patients with SCD not on HC therapy have resting flow deficits in both skeletal muscle and myocardial flow. HC therapy normalizes flow and there is a direct correlation with HbF levels. Clinical trial registration ClinicalTrials.gov Identifier: NCT01602809; https://clinicaltrials.gov/ct2/show/NCT01602809?term=sACHDEV&rank=9.

Original languageEnglish (US)
Pages (from-to)648-656
Number of pages9
JournalBritish Journal of Haematology
Volume179
Issue number4
DOIs
StatePublished - Nov 1 2017

Fingerprint

Sickle Cell Anemia
Fetal Hemoglobin
Anemia
Skeletal Muscle
Perfusion
Reticulocyte Count
Perfusion Imaging
Hydroxyurea
Therapeutics
Forearm
Ultrasonography
Myocardium
Hemoglobins
Cell Count
Clinical Trials

Keywords

  • contrast ultrasound
  • hydroxycarbamide
  • microvasculature
  • perfusion imaging
  • sickle cell disease

ASJC Scopus subject areas

  • Hematology

Cite this

Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease. / Sachdev, Vandana; Sidenko, Stanislav; Wu, Melinda D.; Minniti, Caterina P.; Hannoush, Hwaida; Brenneman, Cynthia L.; Waclawiw, Myron A.; Arai, Andrew E.; Schechter, Alan N.; Kato, Gregory J.; Lindner, Jonathan R.

In: British Journal of Haematology, Vol. 179, No. 4, 01.11.2017, p. 648-656.

Research output: Contribution to journalArticle

Sachdev, V, Sidenko, S, Wu, MD, Minniti, CP, Hannoush, H, Brenneman, CL, Waclawiw, MA, Arai, AE, Schechter, AN, Kato, GJ & Lindner, JR 2017, 'Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease', British Journal of Haematology, vol. 179, no. 4, pp. 648-656. https://doi.org/10.1111/bjh.14918
Sachdev, Vandana ; Sidenko, Stanislav ; Wu, Melinda D. ; Minniti, Caterina P. ; Hannoush, Hwaida ; Brenneman, Cynthia L. ; Waclawiw, Myron A. ; Arai, Andrew E. ; Schechter, Alan N. ; Kato, Gregory J. ; Lindner, Jonathan R. / Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease. In: British Journal of Haematology. 2017 ; Vol. 179, No. 4. pp. 648-656.
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