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Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease.

ABSTRACT: Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell disease are reported to have pathophysiologic relevance in pain crisis. This is the first study to strictly control for LDF variability in determining the value of serial, basal (unprovoked) skin LDF as a practical method to assess resolution of acute pain crisis in sickle cell patients. Daily LDF measurements were repeated on the exact same skin areas of the calf and forehead throughout each of 12 hospital admissions for uncomplicated acute pain crisis. A progressive increase in perfusion was observed in the calf throughout hospitalization as pain crisis resolved, but measurement reproducibility in the calf was poor. Reproducibility in the forehead was better, but no significant trend over time in perfusion was seen. There was no significant correlation between perfusion and pain scores over time. There was also no significant pattern of LDF oscillations over time. In conclusion, only perfusion units and not oscillatory patterns of LDF have probable pathophysiological significance in sickle cell disease vaso-occlusion. The reproducibility of basal skin LDF specifically in sickle cell disease needs to be confirmed.

SUBMITTER: Shi PA

PROVIDER: S-EPMC4198432 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease.

Shi Patricia Ann PA Manwani Deepa D Olowokure Olugbenga O Nandi Vijay V

Blood cells, molecules & diseases 20140521 4

Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell disease are reported to have pathophysiologic relevance in pain crisis. This is the first study to strictly control for LDF variability in determining the value of serial, basal (unprovoked) skin LDF as a practical method to assess resolution of acute pain crisis in sickle cell patients. Daily LDF measurements were repeated on the exact same skin areas of the calf and forehead throughout each of 12 hospital admissio ...[more]

PMID: 24857171

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Project description:BackgroundThe up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease.MethodsIn this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed.ResultsA total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain.ConclusionsIn patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).

Dataset Information

Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease.

Publications

Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease.

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