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Ferrata Storti Foundation
Haematologica 2019 Volume 104(4):690-699
Red Cell Biology & its Disorders
Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
Lena Václavů,1 Benoit N. Meynart,1 Henri J.M.M. Mutsaerts,1
Esben Thade Petersen,2 Charles B.L.M. Majoie,1 Ed T. VanBavel,3
John C. Wood,4 Aart J. Nederveen1 and Bart J. Biemond5
1
Netherlands; 2Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; 3Amsterdam UMC, Biomedical Engineering and Physics, University of Amsterdam, the Netherlands; 4Cardiology and Radiology, Children's Hospital of Los Angeles, CA, USA; 5Amsterdam UMC, Hematology, Internal Medicine, University of Amsterdam, the Netherlands
ABSTRACT
Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capac- ity of the small resistance arteries, making them less adept at regu- lating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used mag- netic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9±11.3 years) and 11 healthy controls (mean age, 37.4±15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imag- ing to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cere- bral blood flow after a hemodynamic challenge with acetazolamide. Co- registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs. 51.3 [4.8] mL/100g/min, P<0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cere- bral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half com- pared to controls (34.1 [33.4] vs. 69.5 [32.4] %, P<0.001) and was associ- ated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 con- trols (45%) had silent cerebral infarcts (median volume of 0.34 vs. 0.02 mL, P=0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cere- brovascular reserve as determined by arterial spin labeling with acetazo- lamide and reflects anemia–induced impaired vascular function in sickle cell disease. This study was registered at clinicaltrials.gov identifier 02824406.
Introduction
Sickle Cell Disease (SCD) is associated with chronic hemolytic anemia and vas- cular inflammation,1 with progressive multiorgan damage including nephropathy, pulmonary hypertension, priapism, leg ulcers, and stroke.2 Manifestations of pro- gressive cerebral injury in SCD include overt stroke as well as silent cerebral
Amsterdam UMC, Radiology and Nuclear Medicine, University of Amsterdam, the
Correspondence:
LENA VACLAVU
l.vaclavu@amc.uva.nl
Received: September 5, 2018. Accepted: November 23, 2018. Pre-published: December 6, 2018.
doi:10.3324/haematol.2018.206094
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/4/690
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