Abstract 5067: Responsiveness to Low Dose Aspirin Influences Levels of Inflammatory Biomarkers

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rehan Qayyum ◽  
Nauder Faraday ◽  
Lisa R Yanek ◽  
Dhananjay Vaidya ◽  
Lewis C Becker ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Low Dose ◽  
Thromboxane B2 ◽  
Inflammatory Biomarkers ◽  
Premature Coronary Artery Disease ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Healthy Family ◽  
Hs Crp

Platelets participate in cellular and humoral immunity; however the effect of low dose aspirin (ASA) therapy on platelet-mediated inflammation is unknown. Healthy family members (N=1934) of patients with premature coronary artery disease (CAD) participated in a 14-day trial of ASA 81 mg/day. Urinary 11-dehydro thromboxane B2 (uTxM), which reflects in vivo platelet activation, was measured at baseline and after ASA. Subjects were dichotomized by post-ASA uTxM levels into ASA responsive (lower quartile) and ASA resistant (upper quartile) groups based on previous studies showing an association between the upper quartile and incident CAD events. Levels of the inflammatory biomarkers, plasma hs-CRP and IL-6, were measured at both time points and compared between the two quartile extremes using multivariable-adjusted models. The study sample had 967 participants (females, 59%; blacks, 43%, age, 43.9±13 years). At baseline, plasma hs-CRP levels were similar between the upper and the lower uTxM quartiles, but IL-6 levels were significantly higher in the upper quartile (Table ). After ASA therapy, hs-CRP and IL-6 decreased in the lowest quartile, but increased in the upper (resistant) quartile, and the between-quartile difference (post-adjusted for pre) became significant for both inflammatory markers. Compared to ASA responsive subjects, those who are ASA “resistant” have higher levels of plasma inflammatory markers after ASA therapy and demonstrate lesser reductions in inflammatory markers from baseline. These extreme quartile differences in hs-CRP and IL-6 may reflect differences in ASA’s ability to suppress platelet-mediated inflammation, and may contribute to the increased CAD risk observed in aspirin resistant persons. Table. Comparison of hs-CRP and IL-6 in the Extreme Quartiles of 11-dehydro thromboxane B2 (uTxM)

Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

1987 ◽  
Vol 57 (01) ◽  
pp. 062-066 ◽  
Author(s):  
P A Kyrle ◽  
J Westwick ◽  
M F Scully ◽  
V V Kakkar ◽  
G P Lewis
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Low Dose ◽  
Bleeding Time ◽  
Blood Platelets ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Plug Formation ◽  
Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Thrombotic Risk ◽  
Dose Aspirin ◽  
Gender And Age ◽  
Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Maternal serum thromboxane B2 concentrations do not predict improved outcomes in high-risk pregnancies in a low-dose aspirin trial

1998 ◽  
Vol 179 (5) ◽  
pp. 1193-1199 ◽  
Author(s):  
John Hauth ◽  
Baha Sibai ◽  
Steve Caritis ◽  
Peter VanDorsten ◽  
Marshall Lindheimer ◽  
...  
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Maternal Serum ◽  
Thromboxane B2 ◽  
Dose Aspirin ◽  
Improved Outcomes ◽  
Low Dose Aspirin ◽  
Serum Thromboxane

scholarly journals Low-dose aspirin does not lower in vivo platelet activation in healthy smokers

1998 ◽  
Vol 102 (5) ◽  
pp. 1229-1231 ◽  
Author(s):  
Pernerstorfer ◽  
Stohlawetz ◽  
Stummvoll ◽  
Kapiotis ◽  
Szekeres ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Low Dose ◽  
Dose Aspirin ◽  
Low Dose Aspirin

In vitro and in vivo assessment of platelet function in healthy dogs during administration of a low-dose aspirin regimen

2016 ◽  
Vol 77 (2) ◽  
pp. 174-185 ◽  
Author(s):  
Jillian M. Haines ◽  
John M. Thomason ◽  
Eileen C. Seage ◽  
Robert W. Wills ◽  
Camilo Bulla ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Healthy Dogs ◽  
In Vivo Assessment

Thromboxane A2 Signaling Regulates Heterogeneous Platelet Activation Following Laser-Induced Injury In Mouse Cremaster Arterioles

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1055-1055
Author(s):  
Jian Shen ◽  
Fei Yang ◽  
Yujun Shen ◽  
Ying Yu ◽  
Timothy J. Stalker ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Vascular Injury ◽  
Low Dose ◽  
Thromboxane A2 ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Platelet Accumulation ◽  
Cox 1 ◽  
Platelet Mass

Abstract Background A recent study demonstrated that platelet accumulation following vascular injury in vivo is hierarchically organized resulting in a structure comprised of a core of fully-activated platelets that is overlaid with an unstable shell of less activated platelets (Stalker et al, Blood, 2013). This structure results from different elements of the platelet signaling network giving rise to regions that differ in platelet activation state, packing density, and stability. It was thus proposed that regional differences in platelet activation reflect regional differences in the distribution of platelet agonists. This provides new insights into heterogeneous platelet activation during platelet accumulation in vivo. Thromboxane A2 (TxA2), a dominant prostanoid product of cyclooxygenase 1 (COX-1) generated in platelets, plays an important role in the maintenance of vascular hemostasis and is a major therapeutic target of anti-platelet therapy. But its contribution to the regional architecture of a platelet mass is unknown. Approach To determine the contribution of TxA2 activity to the hierarchical organization of a thrombus, multicolor intravital microscopy was used to observe platelet accumulation and activation in thromboxane A2 receptor knockout (TP-/-) and low dose aspirin treated WT mice following laser-induced injury in mouse cremaster arterioles. Results TP-/- mice showed reduced total platelet (CD41) accumulation following vascular injury, consistent with a previous report (Yu et al, Sci Transl Med, 2012). The peak CD41 area in TP-/- mice was significantly reduced relative to WT mice (p=0.004). Interestingly, the core area of the thrombus in which the platelets are fully activated (P-selectin+), was not significantly different in TP-/- compared to WT during thrombus formation. This suggests that TxA2 signaling via the TP receptor primarily influences platelet recruitment and retention in the outer shell region of a platelet mass, but not full platelet activation in the core region. Aspirin inhibits TxA2 production through acetylation of COX-1, and is widely used as both primary and secondary prevention of cardiovascular diseases. We treated WT mice with aspirin in their drinking water (30 mg/L) for more than 1 week to mimic the effect of low dose aspirin treatment in humans (Yu et al, J Clin Invest, 2005). Similar to our findings in TP-/- mice, we found that aspirin treatment reduced total platelet accumulation following laser-induced injury in vivo (p<0.05). The decrease in peak platelet accumulation caused by aspirin was observed in the shell region at early time points (up to 2 min post-injury). In contrast to our findings in the TP-/- mice, low dose aspirin also resulted in reduced platelet activation and core region formation at later timepoints (p<0.05), suggesting that COX-1 may contribute to full platelet activation independent of TP receptor signaling. Conclusion Our studies show for the first time the role of TxA2 signaling in producing the hierarchical structure of a platelet mass formed in response to vascular injury. Our data indicate that TxA2signaling is critical for recruitment and/or retention of platelets prior to robust platelet activation including alpha granule secretion. These findings further highlight the importance of discrete spatial localization of platelet agonists within an evolving platelet plug in order to achieve the optimal hemostatic response. (This study was supported by National Natural Science Foundation of China 81170132 to Li Zhu) Disclosures: No relevant conflicts of interest to declare.

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