Normalization of platelet reactivity in clopidogrel-treated subjects

G. Vilahur, B. G. Choi, M. U. Zafar, Juan Viles Gonzalez, D. A. Vorchheimer, V. Fuster, Juan J. Badimon

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Background: Aspirin (ASA) + clopidogrel are commonly used in acute coronary syndrome (ACS), but persistent antiplatelet effects may complicate surgery. Methods and Results: To study the possibility of normalizing platelet reactivity after ASA + clopidogrel treatment, 11 healthy subjects received a 325-mg ASA + clopidogrel loading dose (300 or 600 mg dependent on study arm), followed by 81 mg of ASA + 75 mg of clopidogrel daily for 2 days. Platelet reactivity was assessed by light transmittance aggregometry (LTA) [challenged by adenosine diphosphate (ADP), arachidonic acid (AA), collagen, and thrombin receptor activating peptide (TRAP)] and flow cytometry for platelet activation by GPIIb/IIIa receptor exposure pretreatment, 4 and 72 h postload. To normalize platelet reactivity, increasing amounts of pooled platelets from five untreated volunteers [volunteers (V)-platelet-rich plasma (PRP)] were added ex vivo to the subject's PRP (S-PRP). At both 4 and 72 h, 40% and 50% V-PRP were needed to overcome platelet disaggregation in the 300 or 600 mg arms, respectively, after ADP challenge; an additional 10% V-PRP fully normalized aggregation. Recovery of function was linear with each incremental increase of V-PRP. ADP-induced GPIIb/IIIa activation showed the same pattern as LTA (r = 0.74). Forty percent V-PRP was required to normalize platelet function to AA, collagen, and TRAP. Conclusion: Our results suggest that the pre-operative transfusion of 10 platelet concentrate units (the equivalent of 40% V-PRP) after a 300-mg clopidogrel loading or 12.5 units (50% V-PRP) after a 600 mg loading may adequately reverse clopidogrel-induced platelet disaggregation to facilitate postoperative hemostasis. An additional 2.5 units fully normalized platelet function. The potential clinical implications of our observations could include shorter hospitalizations and reduced bleeding complications. But these observations should be fully explored in an in vivo clinical setting with clopidogrel-treated patients before and after surgery.

Original languageEnglish
Pages (from-to)82-90
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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clopidogrel
Platelet-Rich Plasma
Blood Platelets
thrombin receptor peptide SFLLRNP
Adenosine Diphosphate
Arachidonic Acid
Volunteers
Collagen
Light
Platelet Transfusion
Platelet Glycoprotein GPIIb-IIIa Complex
Recovery of Function
Platelet Activation
Acute Coronary Syndrome
Hemostasis
Aspirin

Keywords

  • Clopidogrel
  • Platelets
  • Subjects

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vilahur, G., Choi, B. G., Zafar, M. U., Viles Gonzalez, J., Vorchheimer, D. A., Fuster, V., & Badimon, J. J. (2007). Normalization of platelet reactivity in clopidogrel-treated subjects. Journal of Thrombosis and Haemostasis, 5(1), 82-90. https://doi.org/10.1111/j.1538-7836.2006.02245.x

Normalization of platelet reactivity in clopidogrel-treated subjects. / Vilahur, G.; Choi, B. G.; Zafar, M. U.; Viles Gonzalez, Juan; Vorchheimer, D. A.; Fuster, V.; Badimon, Juan J.

In: Journal of Thrombosis and Haemostasis, Vol. 5, No. 1, 01.01.2007, p. 82-90.

Research output: Contribution to journalArticle

Vilahur, G, Choi, BG, Zafar, MU, Viles Gonzalez, J, Vorchheimer, DA, Fuster, V & Badimon, JJ 2007, 'Normalization of platelet reactivity in clopidogrel-treated subjects', Journal of Thrombosis and Haemostasis, vol. 5, no. 1, pp. 82-90. https://doi.org/10.1111/j.1538-7836.2006.02245.x
Vilahur G, Choi BG, Zafar MU, Viles Gonzalez J, Vorchheimer DA, Fuster V et al. Normalization of platelet reactivity in clopidogrel-treated subjects. Journal of Thrombosis and Haemostasis. 2007 Jan 1;5(1):82-90. https://doi.org/10.1111/j.1538-7836.2006.02245.x
Vilahur, G. ; Choi, B. G. ; Zafar, M. U. ; Viles Gonzalez, Juan ; Vorchheimer, D. A. ; Fuster, V. ; Badimon, Juan J. / Normalization of platelet reactivity in clopidogrel-treated subjects. In: Journal of Thrombosis and Haemostasis. 2007 ; Vol. 5, No. 1. pp. 82-90.
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N2 - Background: Aspirin (ASA) + clopidogrel are commonly used in acute coronary syndrome (ACS), but persistent antiplatelet effects may complicate surgery. Methods and Results: To study the possibility of normalizing platelet reactivity after ASA + clopidogrel treatment, 11 healthy subjects received a 325-mg ASA + clopidogrel loading dose (300 or 600 mg dependent on study arm), followed by 81 mg of ASA + 75 mg of clopidogrel daily for 2 days. Platelet reactivity was assessed by light transmittance aggregometry (LTA) [challenged by adenosine diphosphate (ADP), arachidonic acid (AA), collagen, and thrombin receptor activating peptide (TRAP)] and flow cytometry for platelet activation by GPIIb/IIIa receptor exposure pretreatment, 4 and 72 h postload. To normalize platelet reactivity, increasing amounts of pooled platelets from five untreated volunteers [volunteers (V)-platelet-rich plasma (PRP)] were added ex vivo to the subject's PRP (S-PRP). At both 4 and 72 h, 40% and 50% V-PRP were needed to overcome platelet disaggregation in the 300 or 600 mg arms, respectively, after ADP challenge; an additional 10% V-PRP fully normalized aggregation. Recovery of function was linear with each incremental increase of V-PRP. ADP-induced GPIIb/IIIa activation showed the same pattern as LTA (r = 0.74). Forty percent V-PRP was required to normalize platelet function to AA, collagen, and TRAP. Conclusion: Our results suggest that the pre-operative transfusion of 10 platelet concentrate units (the equivalent of 40% V-PRP) after a 300-mg clopidogrel loading or 12.5 units (50% V-PRP) after a 600 mg loading may adequately reverse clopidogrel-induced platelet disaggregation to facilitate postoperative hemostasis. An additional 2.5 units fully normalized platelet function. The potential clinical implications of our observations could include shorter hospitalizations and reduced bleeding complications. But these observations should be fully explored in an in vivo clinical setting with clopidogrel-treated patients before and after surgery.

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