Combined therapy with clopidogrel and aspirin significantly increases the bleeding time through a synergistic antiplatelet action

Payne, David A.; Hayes, Paul D.; Jones, Chris I.; Belham, P.; Naylor, A.R.; Goodall, Alison H.

doi:10.1067/mva.2002.122027

Cited by 110 publications

(67 citation statements)

References 29 publications

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“…The dosing regimen used in the study was selected from previous evidence, which compared the effects of administering 2 different doses of clopidogrel in combination with aspirin on bleeding time and platelet function. 25 Although higher doses of clopidogrel (300 mg) and aspirin conferred maximal platelet inhibition, it came at a cost of a significant increase in bleeding time. In the present study, although the lower, single dose of clopidogrel (75 mg) given Ͼ12 hours before surgery resulted in a modest reduction in platelet ADP response in vitro, it did not lead to a significant increase in markers of blood loss or the need for blood product transfusion (Table 2).…”

Section: Discussionmentioning

confidence: 99%

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Beneficial Effects of Clopidogrel Combined With Aspirin in Reducing Cerebral Emboli in Patients Undergoing Carotid Endarterectomy

et al. 2004

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Background-Postoperative thromboembolic stroke affects 2% to 3% of patients undergoing carotid endarterectomy (CEA) and is preceded by 1 to 2 hours of increasing cerebral embolization. Previous work has demonstrated that high rates of postoperative embolization are associated with increased platelet reactivity to adenosine 5Ј-diphosphate (ADP). Our hypothesis was that preoperative administration of the platelet ADP antagonist clopidogrel could reduce postoperative embolization. Methods and Results-One hundred CEA patients on routine aspirin therapy (150 mg) were randomized to 75 mg clopidogrel (nϭ46) or placebo (nϭ54) the night before surgery. Platelet response to ADP was assessed by whole-blood flow cytometry. The number of emboli detected by transcranial Doppler within 3 hours of CEA was independently quantified. Time taken from flow restoration to skin closure was used as an indirect measure of the time to secure hemostasis. In comparison with placebo, clopidogrel produced a small (8.8%) but significant reduction in the platelet response to ADP (PϽ0.05) while conferring a 10-fold reduction in the relative risk of those patients having Ͼ20 emboli in the postoperative period (odds ratio, 10.23; 95% CI, 1.3 to 83.3; Pϭ0.01, Fisher's exact test). However, in the clopidogrel-treated patients, the time from flow restoration to skin closure (an indirect marker of hemostasis) was significantly increased (Pϭ0.04, Fisher's exact test), although there was no increase in bleeding complications or blood transfusions. Conclusions-This is the first study to show that a CEA patient's postoperative thromboembolic potential can be significantly reduced by targeted preoperative antiplatelet therapy without increasing the risk of bleeding complications.

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Section: Discussionmentioning

confidence: 99%

“…25,26 Whether surrogate in vitro markers of platelet response to ADP could be incorporated into a therapeutic dosing strategy needs careful evaluation.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Clopidogrel Combined With Aspirin in Reducing Cerebral Emboli in Patients Undergoing Carotid Endarterectomy

et al. 2004

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“…Patients given a single 75-mg tablet of clopidogrel the night before surgery showed a significant 10-fold reduction in postoperative embolization compared with placebo with no increased risk of bleeding. 15 This low dose of clopidogrel was selected from previous studies in healthy volunteers 16 and in preliminary studies in patients as a dose with minimal risk of causing significant surgical bleeding.…”

mentioning

confidence: 99%

Therapeutic Benefit of Low-Dose Clopidogrel in Patients Undergoing Carotid Surgery Is Linked to Variability in the Platelet Adenosine Diphosphate Response and Patients’ Weight

Payne

Jones

Hayes

et al. 2007

Stroke

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Background and Purpose-We have previously shown that a single 75-mg tablet of clopidogrel, taken before carotid endarterectomy, significantly reduces postoperative embolization, a marker of thromboembolic stroke. This study explores the antiplatelet effect of this submaximal dose. Methods-Fifty-six patients on long-term aspirin (150 mg) were randomized to 75 mg clopidogrel or placebo before carotid endarterectomy. Blood samples were taken pre-and postdrug administration and at the end of surgery to measure platelet activation and adenosine diphosphate (ADP) response by flow cytometry and aggregometry. Results-Surgery produced a significant rise in platelet activation in vivo as evidenced by a rise in the percentage of monocyte-platelet aggregates in patients given placebo, but this was not seen in patients receiving clopidogrel. Before surgery, clopidogrel produced a significant reduction in the platelet response to ADP; for example, with 10 Ϫ6 M ADP, 77.32Ϯ2.3% bound fibrinogen in placebo group compared with 67.16Ϯ3.1% after clopidogrel (Pϭ0.01). This was accentuated after surgery when the percentage of platelets binding fibrinogen in response to ADP was 76.53Ϯ2.2% in patients given placebo and 62.84Ϯ3.3% in the clopidogrel group (Pϭ0.002). Similar differences were seen over a range of ADP concentrations and by aggregometry. Platelet responsiveness before treatment was highly variable and was positively correlated with the inhibitory effect of clopidogrel; patients with the highest baseline response to ADP showed the greatest response to clopidogrel. A negative correlation was seen between the effect of clopidogrel and patients' weight (rϭ0.57; Pϭ0.002). Conclusions-These results explain how a single 75-mg dose of clopidogrel produces a significant clinical impact on embolization.

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“…Même si de nombreuses études [24,49,240] ont mis en évidence un allongement du TS chez les patients traités par AAP, des études systématiques datant de 1990 avaient montré que le TS avait une valeur prédictive du risque hémorragique très faible [198,250]. Depuis 1998, en France, la prescription d'un TS en pré-opéra-toire n'est plus recommandée [161].…”

Section: Quel Test Biologique Peut-on Utilisé Pour éValuer Le Risquunclassified

Gestion péri-opératoire des patients traités par antithrombotiques en chirurgie orale. Argumentaire

2015

Med Buccale Chir Buccale

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Combined therapy with clopidogrel and aspirin significantly increases the bleeding time through a synergistic antiplatelet action

Abstract: The increases in bleeding times should be considered in combination antiplatelet therapy in patients who undergo open vascular surgery.

Cited by 110 publications

References 29 publications

Beneficial Effects of Clopidogrel Combined With Aspirin in Reducing Cerebral Emboli in Patients Undergoing Carotid Endarterectomy

Beneficial Effects of Clopidogrel Combined With Aspirin in Reducing Cerebral Emboli in Patients Undergoing Carotid Endarterectomy

Therapeutic Benefit of Low-Dose Clopidogrel in Patients Undergoing Carotid Surgery Is Linked to Variability in the Platelet Adenosine Diphosphate Response and Patients’ Weight

Gestion péri-opératoire des patients traités par antithrombotiques en chirurgie orale. Argumentaire

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