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Platelet Inhibition and Bleeding in Coronary Artery Bypass Surgery
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A substantial number of patients undergoing cardiac surgery are on dual anti-platelet treatment with clopidogrel and aspirin. A disadvantage with this treatment is increased risk of bleeding. Bleeding is a complication of major concern associated with adverse outcome for the patient and increased hospital resource utilization. Great variability in individual response to clopidogrel has been reported. If in vitro measurements of platelet reactivity would correlate with clinical bleeding parameters, potential bleeders could be identified preoperatively.

The aims of this thesis were: (1) to describe the degree of pre-operative platelet inhibition in patients scheduled for primary isolated coronary artery bypass graft surgery; (2) to prospectively investigate whether the pre-operative platelet inhibition correlated with intra- and postoperative bleeding and transfusion requirements; and (3) to test the ability of clinically relevant risk factors to predict re-exploration for bleeding. (4) In addition, a cost analysis was performed on patients re-explored for bleeding, to analyse the magnitude of added resource utilization and costs. Based on this, a cost model of prophylactic treatment with haemostatic drugs was calculated.

Platelet function tests investigated were: (1) flow cytometry, (2) VASP, (3) VerifyNowSystem, (4) PlateletMapping (a modified TEG), and (5) PFA-100.

Clinical risk factors for re-exploration and the influence of antiplatelet and antifibrinolytic therapy were evaluated in a retrospective analysis. Cost analysis at three cardiothoracic centres was performed in a case-control study.

In conclusion, there was no clinically useful correlation between preoperative assessment of platelet inhibition and blood loss or transfusion requirements during coronary artery bypass surgery. Furthermore, there was only modest agreement between the methods evaluating ADP-receptor blockade.

Pre-operative treatment with the P2Y12-receptor inhibitor clopidogrel was an essential risk factor for re-exploration due to bleeding. Except for clopidogrel, no strong clinical factor to predict the risk of re-exploration was identified.

The resource utilisation costs were 47% higher in patients requiring re-exploration due to bleeding than in those not requiring re-exploration. Prolonged stay in the ICU and recovery ward accounted for half of the added cost, a third was due to the costs of surgery, one fifth due to increased cost of transfusions, and <2% was due to haemostatic drug treatment.

 

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 80 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 648
Keyword [en]
bleeding, cardiac surgery, platelet inhibition, re-exploration, cost analysis
National Category
Anesthesiology and Intensive Care
Research subject
Thorax Surgery; Anaesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-146458ISBN: 978-91-554-8013-4OAI: oai:DiVA.org:uu-146458DiVA: diva2:399368
Public defence
2011-03-31, Robergssalen, Ingång 40, Uppsala University Hospital, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2011-03-09 Created: 2011-02-16 Last updated: 2011-05-04Bibliographically approved
List of papers
1. The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
Open this publication in new window or tab >>The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
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2007 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 120, no 3, 353-359 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy. MATERIALS AND METHODS: The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75-100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) -100 (26 patients). RESULTS: With flow cytometry, the percentage of platelets expressing P-selectin (p=0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly (p=0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel. CONCLUSION: A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.

Keyword
Clopidogrel, Flow cytometry, Thrombelastograph, Platelets, PFA-100
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-24441 (URN)10.1016/j.thromres.2006.10.009 (DOI)000247762600005 ()17137616 (PubMedID)
Available from: 2007-02-15 Created: 2007-02-15 Last updated: 2011-05-04Bibliographically approved
2. Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
Open this publication in new window or tab >>Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
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2009 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, no 5, 572-577 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements. MATERIAL AND METHODS: Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay. RESULTS: There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y(12) (r = -0.29, p<0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p<0.05) as measured by flow cytometry when platelets were stimulated with 5 microM ADP. VerifyNowP2Y(12) was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p=0.03) and red blood cell transfusion (Spearman r = 0.43, p<0.01) requirements, although this might be confounded by aprotinin treatment. CONCLUSION: We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MA(ADP). There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y(12) and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y(12) as an instrument to decide bleeding and transfusion risk does not seem helpful.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-120242 (URN)10.1016/j.thromres.2009.06.024 (DOI)000271712800012 ()19631364 (PubMedID)
Available from: 2010-03-10 Created: 2010-03-10 Last updated: 2012-07-11Bibliographically approved
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