Session Type: Abstract Submissions (ACR)
Background/Purpose: Increased platelet activation, endothelial dysfunction and oxidative stress are all thought to contribute to the pathogenesis of Raynaud’s phenomenon (RP), particularly in the context of systemic sclerosis (SSc). We report the findings of a cross-sectional study evaluating platelet function, endothelial production of prostacyclin and a novel biomarker of oxidative stress in patients with primary RP and SSc.
Methods: Patients with primary RP and SSc who were not taking anti-platelet or non-steroidal anti-inflammatory drugs were included in the study. All patients had their disease characteristics and medication use documented. Platelet number and structure (mean platelet volume, platelet distribution width and plateletcrit) were assessed using automated haematology analysis. Platelet function was assessed using light transmission aggregometry (maximum % aggregation over 5 minutes and maximum gradient of aggregation) to adenosine diphosphate (ADP, 1.25-10μl/L) and arachidonic acid (AA, 0.82-1.64mmol/L). Fasting levels of the major urinary metabolite of thromboxane (11-dehydro-TxB2), prostacyclin (2,3-dinor-6-keto-PGF1α) and non-enzymatic markers of lipid peroxidation and oxidative stress (F2-isoprostanes) were assessed using Gas Chromatography/Mass Spectrometry (GC/MS) analysis.
Results: Seventeen patients with primary RP and 17 with systemic sclerosis were recruited to the study. Age, gender, smoking status and use of vasodilator therapy were similar in each group (p>0.05). Platelet number and structure did not differ between groups. Maximum % aggregation to low concentration ADP (0.125-0.5μl/L) was significantly greater in SSc compared to primary RP (p<0.05 for all comparisons). Percent aggregation to high concentration ADP (10μl/L) and AA (1.64 and 0.82mmol/L) did not differ between groups, possibly representing a ceiling effect. The maximum gradient of aggregation was significantly greater for 1.64mmol/L AA in SSc compared with primary RP. Urinary metabolites of thromboxane (medians 425 vs. 382 pg/mg creatinine [Cr]), prostacyclin (160 vs. 122 pg/mg Cr) and F2-isoprostanes (1.00 vs. 1.12 ng/ml Cr) did not differ between SSc and primary RP (p>0.05 for all comparisons). There were moderate correlations between urinary 11-dehydro-TxB2 and both 2,3-dinor-6-keto-PGF1α and F2-isoprostanes (Spearman’s Rho 0.537 and 0.612 respectively, p≤0.001). A history of digital ulceration was associated with increased aggregation to 5μl/L ADP in SSc. There were no associations between disease characteristics and eicosanoid biosynthesis in SSc.
Conclusion: This pilot study has identified increased ex vivo platelet reactivity in SSc compared with primary RP. In vivo lipid biomarkers of platelet activation, endothelial function and oxidative stress did not differ between groups. Biosynthesis of thromboxane (a potent vasoconstrictor) is associated with increased oxidative stress and increased synthesis of prostacyclin (a potent vasodilator) in RP. Additional work evaluating the clinical associations of platelet function and eicosanoid biosynthesis in a larger cohort of patients with primary RP and SSc may help guide the use of anti-platelet therapy in these patient groups.
J. D. Pauling,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/platelet-aggregability-eicosanoid-biosynthesis-and-oxidative-stress-in-primary-raynauds-phenomenon-and-systemic-sclerosis/