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Hemoglobin. 2019 Mar;43(2):88-94. doi: 10.1080/03630269.2019.1623248. Epub 2019 Jul 10.

Erythrocyte cAMP in Determining Frequency of Acute Pain Episodes in Sickle Cell Disease Patients from Odisha State, India.

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a School of Life Sciences , AIPH University , Bhubaneswar , Odisha State , India.
b Sickle Cell Clinic and Molecular Biology Laboratory , Veer Surendra Sai Institute of Medical Sciences and Research , Burla, Sambalpur , Odisha State , India.
c School of Life Sciences , Sambalpur University , Jyoti Vihar, Burla , Sambalpur , Odisha State , India.
d Department of Medicine , Veer Surendra Sai Institute of Medical Sciences and Research , Burla, Sambalpur , Odisha State , India.
e Central Institute of Freshwater Aquaculture , Bhubaneswar , Odisha State , India.
f Multidisciplinary Research Unit , Maharaja Krishna Chandra Gajapati Medical College , Berhampur , Odisha State , India.


Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (p < 0.001) and epinephrine treated RBCs (p < 0.001) by Wilcoxon Rank Sum test. However, significant association of cAMP values was observed both on univariate [odds ratio (OR): 4.8, 95% confidence interval (95% CI): 1.51-15.19, p < 0.008) and multivariate logistic regression analyses only in epinephrine treated (OR: 5.07, 95% CI: 1.53-16.82, p < 0.008) but not in sham-treated RBCs. In the covariates, Hb F consistently showed protective effects in univariate as well as in multivariate analyses. Frequent acute pain episodes are associated with higher cAMP levels than those with less frequent pain episodes, only after stimulation with epinephrine but not with baseline level.


Acute pain episodes; cyclic adenosine monophosphate (cAMP); epinephrine; sickle cell disease; vaso-occlusive crisis (VOC)

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