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 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)
    JournalBritish Journal of Haematology
    DOIs
    StateAccepted/In press - 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.

    In: British Journal of Haematology, 2017.

    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, J 2017, 'Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease', British Journal of Haematology. 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. / Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease. In: British Journal of Haematology. 2017.
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    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.",
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    AU - Minniti, Caterina P.

    AU - Hannoush, Hwaida

    AU - Brenneman, Cynthia L.

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    AU - Kato, Gregory J.

    AU - Lindner, Jonathan

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