Document Detail

Avoidance of bleeding during surgery in patients receiving anticoagulant and/or antiplatelet therapy: pharmacokinetic and pharmacodynamic considerations.
MedLine Citation:
PMID:  15530128     Owner:  NLM     Status:  MEDLINE    
Perioperative management of chronically anticoagulated patients and/or patients treated with antiplatelet therapy is a complex medical problem. This review considers the pharmacokinetic and pharmacodynamic properties of commonly used antiplatelet and anticoagulant drugs with special emphasis on loss of effects after discontinuation and possible counteracting (or antidote) strategies. These drugs are aspirin (acetylsalicylic acid), ticlopidine/clopidogrel, abciximab, tirofiban and eptifibatide, heparin (unfractionated and low-molecular-weight), warfarin and direct thrombin inhibitors. Since the pharmacological mechanisms of some of these drugs are based on irreversible or slowly reversible effects, their pharmacokinetic profiles are not necessarily predictive for their pharmacodynamic profiles. A close and direct relationship between plasma concentrations and effects is seen only for the glycoprotein (GP) IIb/IIIa inhibitors tirofiban and eptifibatide with a fast off-rate for dissociation from the GPIIb/IIIa receptor, and for direct thrombin inhibitors (hirudin and argatroban). For other compounds, drug concentrations in plasma and pharmacodynamic effects are not closely correlated because of, for example, irreversible binding to their target (aspirin, clopidogrel and abciximab), inhibition of the generation of a subset of clotting factors with differing regeneration and degradation rates (coumarins) or sustained binding to the vascular wall (heparins). Surgery in patients on anticoagulant and/or antiplatelet therapy may be categorised as: (i) elective versus urgent; and (ii) cardiopulmonary bypass (CPB) versus non-CPB. Monotherapy with clopidogrel or aspirin need not be discontinued in elective non-CPB surgery, and temporary discontinuation of warfarin should be accompanied by preoperative intravenous heparin only in selected high-risk patients. Vitamin K as an antidote for warfarin should only be used subcutaneously and solely in urgent/emergency surgery. In elective surgery requiring CPB (coronary artery bypass grafting), it is recommended to discontinue aspirin 7 days preoperatively in patients with a low risk profile. Patients requiring urgent CPB surgery (e.g. after failure of a percutaneous coronary angioplasty with or without coronary stent deployment) are usually pretreated with several antiplatelet agents (e.g. aspirin and clopidogrel, together with a GPIIb/IIIa inhibitor) together with unfractionated or low-molecular-weight heparin. With judicious planning, urgent/emergency cardiac surgery can be safely performed on these patients. Delaying surgery (e.g. for 12 hours in patients treated with abciximab) should be considered if possible. Standard heparin doses should be given to achieve optimal anticoagulation for CPB. Prophylactic use of aprotinin (intra- and/or postoperatively), aminocaproic acid or tranexamic acid should be considered. Early (in the operating theatre prior to chest closure) and judicious use of replacement blood products (platelets) should be commenced when clinically indicated.
Sebastian Harder; Ute Klinkhardt; John M Alvarez
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Clinical pharmacokinetics     Volume:  43     ISSN:  0312-5963     ISO Abbreviation:  Clin Pharmacokinet     Publication Date:  2004  
Date Detail:
Created Date:  2004-11-08     Completed Date:  2005-02-22     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  7606849     Medline TA:  Clin Pharmacokinet     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  963-81     Citation Subset:  IM    
Institute for Clinical Pharmacology, Pharmazentrum Frankfurt, University Hospital, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
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MeSH Terms
Anticoagulants / adverse effects,  pharmacokinetics*,  pharmacology
Blood Loss, Surgical / prevention & control*
Cardiac Surgical Procedures
Cardiopulmonary Bypass
Platelet Aggregation Inhibitors / adverse effects,  pharmacokinetics*,  pharmacology
Reg. No./Substance:
0/Anticoagulants; 0/Platelet Aggregation Inhibitors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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