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Endothelium-dependent and endothelium-independent vasodilatation of the cutaneous circulation in sickle cell disease


Professor Janice M. Marshall, Centre for Cardiovascular Sciences, University of Birmingham, Birmingham, UK. Tel.: 0121-414-6911; fax: 0121-414-6919; e-mail: or Professor Gregory Y. H. Lip, Haemostasis, Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK. Tel.: 0121-507-5080; fax: 0121-554-4083; e-mail:


Eur J Clin Invest 2011; 41 (5): 546–551


Background  Whilst there is evidence of endothelial dysfunction in sickle cell disease (SCD), whether this affects regulation in the microcirculation is not known.

Methods  We studied 19 patients with SCD, eight with sickle cell-haemoglobin C (HbSC), 11 with homozygous sickle cell (HbSS) disease and 11 matched control subjects with normal haemoglobin genotype (HbAA). Vasodilator responses were evoked by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) in finger and forearm, cutaneous red cell flux (RCF) being measured by laser Doppler fluximetry.

Results  Increases in RCF evoked in the finger by ACh were not different between SCD and HbAA subjects (P = 0·789), but were smaller in patients with HbSS than HbSC (P < 0·05). By contrast, increases in RCF evoked in forearm by ACh were greater in SCD than HbAA subjects (P < 0·05) and similar in patients with HbSC and HbSS. Increases in RCF evoked by SNP did not differ between patients with SCD and HbAA subjects in finger or forearm.

Conclusions  Our results indicate that endothelium-dependent cutaneous vasodilatation is augmented in forearm of patients with SCD relative to HbAA subjects, but impaired in the finger of SCD patients with the more severe HbSS genotype. Thus, endothelial dysfunction associated with SCD is not accompanied by generalised impairment in endothelium-dependent dilatation, but with more localised impairment that includes the fingers of patients with HbSS.