P&T News: February/March 2002
Julie A. Volkman, Pharm.D., Janelle L. Moore, Pharm.D., Kelly
N. Schupp, Pharm.D., Mary B. Ross, RPh, MBA
Internally Peer Reviewed by: Tyrone B. Whitter,
M.D., Ph.D., Director, Presurgical Evaluation Clinic and Assistant
Professor, Department of Anesthesia
MECHANISMS OF ACTION
Antiplatelet drugs prevent the formation of the initial hemostatic plug at the sites of vascular injury. Additionally, these drugs prevent the formation of thromboses that may lead to myocardial infarction, stroke, and peripheral vascular thromboses.2 An understanding of the affect of blood thinners on platelet function is essential in evaluating the risk versus benefit of discontinuing these agents in the perioperative setting. Figure 1 outlines the sites where common antiplatelet drugs work and highlights specific aspects of the platelet function that are affected by drug therapy.
Figure 1. Sites where common antiplatelet drug therapies work.
Adapted from Wintrobe's Clinical Hematology. 10th ed. Baltimore: Williams and Wilkin. 19993
Aspirin irreversibly inhibits the enzyme cyclooxygenase (COX), which is present in at least two isoforms, COX-1 and COX-2, in vitro. Enzyme inhibition prevents the formation of thromboxane A2 from arachidonic acid.5 Thromboxane A2 is responsible for enhancing platelet activation and the secretion of platelet products, thus, reducing the formation of platelet plugs at injury sites.1 NSAIDs alter platelet aggregation by inhibiting the formation of prostaglandins produced by COX-1.5 Cilostazol blocks the activity of the enzyme phosphodiesterase which induces platelet aggregation and prevents the degradation of cyclic adenosine monophosphate (cAMP). This leads to an increase in cAMP in the platelets and blood vessels, and subsequently, platelet aggregation that is induced by adenosine diphosphate, collagen, arachidonic acid, epinephrine, thromboxane A2, platelet activating factor, or shear stress is inhibited. Clopidogrel works by selectively blocking adenosine diphosphate (ADP)-induced platelet aggregation without significantly affecting the activity of thromboxane A2, prostacyclin or phospholipase A.2 The mechanism of action of dipyridamole is not completely understood. Research indicates that it may block erythrocyte uptake and the metabolism of adenosine, inhibit platelet phosphodiesterase activity, stimulate the release of eicosanoids, and/or prevent thromboxane A2 formation. The sulfide metabolite of sulfinpyrazone affects platelet aggregation by inhibiting thromboxane production.5 The anti-platelet effect of ticlopidine is unique when compared to aspirin-containing products and NSAIDs. Ticlopidine works by blocking both the primary and secondary phase of ADP-induced aggregation and possibly interferes with platelet adhesions which may lead to the prolongation of bleeding times.2
HERBAL MEDICATIONS
Herbal medications represent an underappreciated source of blood thinners. Two surveys have illustrated the widespread use of herbal medicines in the presurgical patient population.6,7 Tsen et al concluded that 22% of patients who were being evaluated for surgery reported herbal medication use.6 Likewise, Kaye et al found that in an ambulatory surgery setting, 32% of patients indicated that they took herbal medications. Additionally, this study found that greater than 70% of the patients did not tell their physician about their use of herbal products.7
A recent study by Ang-Lee et al reviewed the literature on commonly used herbal medicines in the perioperative setting and developed guidelines for presurgical discontinuation of these products.8 Of the eight herbal medications studied, three herbs, garlic, ginkgo and ginseng, may have pharmacological effects on platelet function. Garlic may potentially irreversibly block platelet function and should be discontinued at least 7 days prior to surgery. Ginkgo has multiple potential mechanisms of action, such as altering vasoregulation, serving as an antioxidant, modulating the activities of neurotransmitters and receptors, and inhibiting platelet aggregation. In the perioperative setting, patients should be instructed to stop taking gingko a minimum of 36 hours before surgery based on pharmacokinetic data and the possibility for bleeding. Ginseng is composed of different ginsenosides that might block platelet aggregation in vitro. A study in laboratory rats showed that ginsenosides increased coagulation time of thrombin and activated partial thromboplastin (aPTT). Since the inhibition of platelet aggregation by ginsenosides is potentially irreversible, it is recommended that patients discontinue ginseng at least 7 days prior to surgery.
The relevant pharmacological effects of St. John's Wort may not be directly related to platelet aggregation. However, the guidelines suggest that St. John's Wort should be stopped 5 days before surgery in patients who might need oral anticoagulation postoperatively because St. John's Wort may induce cytochrome isoform, P4502C9, which is responsible for warfarin metabolism.8
In addition, the exact content of herbal or other alternative medications may be unknown. The pharmacologic properties of many of these preparations have not been systematically studied, and thus, their effect on bleeding is unknown. Therefore, as a general guideline, the use of herbal medications should be avoided prior to surgery.
RECOMMENDATIONS
Table 1 provides general guidelines on which prescription, non-prescription, and herbal "blood thinners" should be held prior to surgery and when the medicines should be discontinued in relationship to the date of surgery. Aspirin inhibits platelets for their lifespan. Therefore, aspirin-containing products should be stopped at least 14 days before surgery. NSAIDs only inhibit platelet aggregation while the drug is present in the body. So, the discontinuation of these drugs is based on the half-life of the specific NSAID. It is essential to note that this is not an all-inclusive list. Also, every patient should be individually evaluated to determine the indication for the particular blood thinner and the necessity of holding the drug based on the type of elective surgery.
For patients who are taking these medications for the treatment of chronic disease and/or for pain relief, for example arthritis, alternative drug therapy should be considered.1 Table 2 contains a partial list of medications that do not affect platelet aggregation and may be used for pain relief prior to surgery. These drugs can be considered as alternatives for the management of chronic disease and/or to provide pain control.
The management of bleeding in the intraoperative and postoperative settings cannot be overlooked. Thus, during perioperative evaluations, practitioners should routinely question their patients about use of prescription, non-prescription, and herbal medications. The medication histories should then thoroughly be evaluated for products that may alter platelet aggregation. Patients need to be counseled if their medications need to be held, advised when to hold them in relation to the date of their surgery, and if necessary, informed about other medications they can take as alternatives.
REFERENCES
COMPUTERIZED INCIDENT REPORT SYSTEM
Patient safety is of the utmost importance at UIHC. Staff strive to give all patients the kind of care they would want if they were hospitalized. However, healthcare is complex and try as we might to be perfect, occasionally a process fails and an adverse event may occur. Such events--including medication errors--are critical learning opportunities for improving the safety and the effectiveness of patient care. But healthcare providers can improve care only if they actively report information about adverse events and errors so that risk managers and other personnel can evaluate these incidents and institute needed operational changes.
To improve the hospital's program for capturing data about adverse events, UIHC implemented a new Computerized Incident Report (CIR) System on January 2, 2002. This system replaced the hospital's paper "Unusual Incident, Medication Error & Accident Report" (Form 260). Staff now document the facts surrounding adverse incidents electronically so that trends over time can be followed and needed safety enhancements can be implemented.
The goals of the new system are to:
This organization-wide change will affect all patient care staff from all departments. The paper forms have become obsolete, replaced by a creative new system housed in the INFORMM Patient Record (IPR). The Computerized Incident Report is available as a tab on the IPR. Staff education and training on the new system is key to successful implementation. If you have not received information about or training for the Computerized Incident Report, please contact your area manager or Sheri Swartzendruber, RN, Risk Project Manager, Clinical Outcomes and Resource Management, at 356-8127, or e-mail CIR@uihc.uiowa.edu.
ACCESSING THE ONLINE FORMULARY AND HANDBOOK VIA IPR BROWSER
Access to the online Formulary and Handbook (F&H) on multi-user computers throughout UIHC is available through the IPR Browser. The IPR Browser provides clinicians a fast way to access the F&H, as well as several other helpful resources, without having to sign on to the IPR system or open a web page.
To access the online F&H from any computer in UIHC, simply open the Informm Patient Record (IPR) program from the main menu or programs file and then select the IPR Browser button to the right of the sign-in. The online F&H is listed on the IPR Browser under the heading UIHC Clinical Practice Reference.