High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation.

Ratnatunga, Chandana; Edmondson, S F; Rees, Gareth; Kovács, Iren B.

doi:10.1161/01.cir.85.3.1077

Cited by 138 publications

(69 citation statements)

References 32 publications

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“…Oral-Administration of Samples To evaluate the antithrombotic effect on rat blood, the MeOH extract, EtOAc sol- [28][29][30] On the basis of their published data, a three-channel haemostatometer was constructed by Yamamoto, et al, at the Faculty of Nutrition of Kobe Gakuin University for research purposes.…”

Section: Plant Materialsmentioning

confidence: 99%

The Anti-thrombotic Active Constituents from Centella asiatica

Satake

Kamiya

Yin

et al. 2007

Biological & Pharmaceutical Bulletin

104

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Section: Plant Materialsmentioning

confidence: 99%

The Anti-thrombotic Active Constituents from Centella asiatica

Satake

Kamiya

Yin

et al. 2007

Biological & Pharmaceutical Bulletin

104

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“…21,22 In various experimental settings aspirin has been shown to reduce thrombin generation. 12,23,24 Using the model of microvascular injury, it has been demonstrated that aspirin at a dose from 30 to 500 mg down-regulates thrombin formation in healthy subjects 15,25 and patients with CAD. 19,26 The purpose of the present study is to describe major coagulant events during blood clotting at the site of microvascular injury and to evaluate the effect of low-dose aspirin on the activation of prothrombin, FV, FXIII, and Fbg, and inactivation of FVa by APC.…”

Section: Introductionmentioning

confidence: 99%

“…This finding is in keeping with most, 15,23,25,26 though not all previous studies. 24 In contact pathway-inhibited whole-blood coagulation studied in vitro, high-dose aspirin administered in vivo had no effect on exclusively TF-induced coagulation. 45 This suggests that the aspirin effect in the present model may be tissueor shear-dependent.…”

mentioning

confidence: 96%

Blood coagulation at the site of microvascular injury: effects of low-dose aspirin

Undas

Brummel

Musiał

et al. 2001

Blood

108

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The sequence of coagulant reactions in vivo following vascular injury is poorly characterized. Using quantitative immunoassays, the time courses were evaluated for activation of prothrombin, factor (F)V, FXIII, fibrinogen (Fbg) cleavage, and FVa inactivation in bleeding-time blood collected at 30-second intervals from 12 healthy subjects both before and after aspirin ingestion. Prothrombin decreased at a maximum rate of 14.2 ؎ 0.6 nM per second to 10% of initial values at the end of bleeding. Significant amounts of ␣-thrombin B chain appeared rapidly at 90 seconds of bleeding and increased at a maximum rate of 0.224 ؎ 0.03 nM per second to a peak value of 38 nM. Kinetics of prethrombin 2 generation was almost identical. Prothrombinase concentration reached a peak value of 22 pM at 150 seconds and then decreased to 9 pM at the end of bleeding. Prothrombin fragment 1.2 (F1.2) was produced explosively (0.673 ؎ 0.05 nM per second), whereas thrombin-antithrombin III (TAT) complexes were generated at a much slower rate (0.11 ؎ 0.008 nM per second; P ‫؍‬ .002). FVa light chain was detectable 30 seconds later than the heavy chain (150 seconds) and was produced at a slightly slower rate (0.027 ؎ 0.001 nM per second) when compared with the heavy chain (0.032 ؎ 0.002 nM per second; P ‫؍‬ .041). The 30 000 fragment (residues 307-506) of FVa heavy chain produced by activated protein C appeared as early as at 90 seconds and increased with time. Fbg was removed from the blood shed with a high rate of 0.047 ؎ 0.02 M/s and became undetectable at approximately 180 seconds of bleeding. The velocity of FXIII activation correlated with thrombin Bchain formation. A 7-day aspirin administration (75 mg/d) resulted in significant reductions in maximum rates of (1) prothrombin removal (by 29%; P ‫؍‬ .008); generation of ␣-thrombin B-chain (by 27.2%; P ‫؍‬ .022), and prethrombin 2 (by 26%; P ‫؍‬ .014); formation of F1.2 (by 31.4%; P ‫؍‬ .009) and TAT (by 30.3%; P ‫؍‬ 0.013); (2) release of FVa heavy chain (by 25%; P ‫؍‬ .003) and FVa light chain (by 29.6%; P ‫؍‬ .007); (3) Fbg depletion from solution (by 30.5%; P ‫؍‬ .002); and (4) FXIII activation (by 28.6%; P ‫؍‬ .003). Total amounts of the proteins studied, collected at every interval, also significantly decreased following aspirin ingestion. These results indicate that low-dose aspirin impairs thrombin generation and reactions catalyzed by this enzyme at the site of the injury. IntroductionHemostasis is triggered in vivo when vascular damage exposes membrane-bound tissue factor (TF) constitutively present in the subendothelium. 1 The proteolytically active complex of TF and circulating 2-chain factor (F)VIIa, the extrinsic tenase, activates FX and FIX. FIXa and FXa, complexed with FVIIIa and FVa, respectively, form 2 enzyme-cofactor complexes-the intrinsic tenase and prothrombinase, which converts prothrombin to thrombin. The former complex activates FX at a 50-fold higher rate than the FVIIa-TF complex, whereas prothrombinase is 10 5 times more efficient in generating thrombin than ...

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“…This test induces platelet-rich thrombus formation in non-anticoagulated (native) blood solely by shear forces, as opposed to conventional tests that use chemical agonists. Further, this test detects the spontaneous lysis of formed autologous thrombi in the same blood sample (15)(16)(17)(18)(19)(20).…”

Section: Effects Of Exercise On the Thrombotic State Assessed Using Nmentioning

confidence: 99%

“…Anticoagulants interfere with the mechanism of hemostasis and render the obtained results unphysiological. To overcome this limitation, some tests (shear-induced plateletrich thrombosis and thrombolysis tests) use nonanticoagulated whole blood (15)(16)(17)(18)(19)(20). The aim of the present review was to compare the effects of short-term and long-term exercise on the thrombotic state.…”

Section: Introductionmentioning

confidence: 99%

The exercise paradox may be solved by measuring the overall thrombotic state using native blood

Ikarugi

Yamamoto

2017

DD&T

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High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation.

Abstract: It is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (greater than 300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.

Cited by 138 publications

References 32 publications

The Anti-thrombotic Active Constituents from Centella asiatica

The Anti-thrombotic Active Constituents from Centella asiatica

Blood coagulation at the site of microvascular injury: effects of low-dose aspirin

The exercise paradox may be solved by measuring the overall thrombotic state using native blood

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