Blood Clotting

Cardiovascular disease, including ischemic coronary heart disease, stroke, and peripheral vascular disease, is the leading cause of death in the United States.1 Stroke is the third leading cause of death, and is the primary cause of adult disability.2 Yearly, over 1 million Americans experience new or recurrent myocardial infarction (MI) or fatal coronary heart disease. Most of these events occur in the elderly or in those with known risk factors for cardiovascular disease.3 The age-adjusted mortality rate due to coronary heart disease, cerebrovascular disease and atherosclerotic disease is 194 per 100 000 cases, which translates to more than 500 000 deaths per year. 1 These leading causes of death correspond directly to chronic conditions experienced by many patients, especially the elderly, who may live for decades with illnesses that are typically controlled with medication use. 2,4

Given these disease trends, dental professionals are seeing more patients taking anticoagulant and/or antiplatelet medications to prevent arterial or venous thrombosis and stroke.5 Controversy and confusion persist as to whether these medications actually pose a risk for significant postoperative bleeding following invasive dental procedures. However, excessive or life-threatening bleeding caused by medication use in the dental office is an extremely rare event, even among patients at risk.6,7

Determining the proper management strategy to safely treat patients taking anticoagulant and antiplatelet medications must take into account the risk of thrombus formation in the patient. The clinician must weigh the risks of potential bleeding complications against the potential risks associated with altering the medications used to reduce significant cardiovascular risk.6 According to Little and associates (2002), risk of “thrombosis is of greater overall clinical importance in terms of morbidity and mortality than all of the hemorrhagic disorders combined.”5

The decision to alter the patient’s medication regimen, by either lowering the dosage of or discontinuing the medication prior to dental treatment, is not supported by clinical studies in the literature.6,8,9 Yet, many dental clinicians continue to recommend medication alteration as a management strategy, with the belief that they are promoting patient safety. Proposed regimens are based on case reports, opinions published in the literature, and habit, and are not supported by clinical data.6,9

The justification for reducing or withdrawing anticoagulant medication prior to dental treatment can be dated back to a time when less than a dozen case reports in the literature reported excessive bleeding following dental treatment in patients taking warfarin. However, it is important to note that during the timeframe when those case studies were published, the prothrombin time test (PTT) was used to evaluate the effectiveness of warfarin; but, testing was not yet standardized, and variations in clinical efficacy were bound to occur.6,10,11 Today, standardized measures, such as the International Normalized Ratio (INR), are used to assess coagulation time in patients taking warfarin, and guidelines for therapeutic ranges of anticoagulation have been established.12 These guidelines make it easier for the clinician to predict the risks for bleeding in medicated dental patients.

A variety of other medications can contribute to bleeding complications in dental patients, including nonsteroidal anti-inflammatory analgesics, hormones, herbs, and dietary supplements. It is critical that dental professionals conduct a pharmacologic history review as a component of a comprehensive review of systems for all patients who present for oral health care. Assessing the patient’s prescription and over-the-counter (OTC) medication use provides important information about the patient’s current medical status, disease severity, compliance with drug and treatment recommendations, and orientation to health and wellness.13

Understanding medication use helps dental professionals anticipate and prevent oral and systemic complications associated with adverse drug events.14 Drug-induced adverse bleeding events can happen outside of the dental office, as well as during treatment. Assessing potential bleeding complications associated with medication and supplement use is a vital service that dental professionals provide to their patients.14 Most dental patients taking prescription medications are aware of the bleeding risks associated with their drugs, and in fact, are monitored routinely to detect alterations in coagulation before complications arise. However, these same patients may not fully understand how their lifestyle, including diet, alcohol use, and the use of OTC medications, can alter the bleeding effects of their prescription medications.

In addition, dental professionals must remember to ask their patients about the use of herbs, vitamins, and dietary supplements when assessing medication use. Surveys estimate dietary supplement usage by 12% to 24% of the general population.15 In addition, usage doubled for individuals aged 65 years and older from 1999 to 2002.16 Recent estimates suggest that over 15 million Americans take herbs, vitamins, or both, along with their prescription medications.17 Since these supplements are available OTC, many patients do not include these products when listing medications on health history forms. For example, over 51% of patients scheduled to undergo surgical procedures in a Colorado hospital were taking herbal medications, some of which may alter blood coagulation.18 Further, in a preanesthesia interview at a university medical center, nearly 70% of patients taking herbal medications did not report their usage.19

Several herbs contain substances that have coumarin, salicylate, or antiplatelet properties, such as garlic, gingko, and ginseng.20 Although no definitive studies have been performed to show a direct cause and effect of herbal use and bleeding complications, the literature suggests that this is a phenomenon of increasing concern due to the extreme popularity and increasing use of these products.

During January 2005, the National Institutes of Health (NIH) conducted a joint conference with the National Heart, Lung and Blood Institute (NHLBI), the Office of Dietary Supplements (ODS), the NIH Clinical Center (CC), the National Center of Complementary and Alternative Medicine (NCCAM), the National Institute of Neurological Disorders (NINDS), the NIH Foundation, and the Office of Rare Diseases (ORD) at the NIH that specifically addressed this issue as a public health concern. The conference goal was to “increase our understanding of the potential for dietary supplements to interfere with hemostasis and antithrombotic therapies.”15

According to the Natural Medicines Comprehensive Database, approximately 180 dietary supplements have the potential to interact with warfarin, and more than 120 may interact with aspirin, clopidogrel (Plavix®), or dipyridamole (Aggrenox®). The 2005 NIH conference specifically identified the following supplements as having this interaction potential:

• Anise
• Dong Quai
• Omega-3 fatty acids in fish oil
• Ajoene in Garlic
• Ginger
• Ginkgo
• Vitamin E
• Fucus
• Danshen
• St. John’s Wort
• American Ginseng

In addition, the following herbs may affect blood clotting, which is dependent on vitamin K:

• High dose vitamin E (specific dosage not indicated), a vitamin K antagonist
• Alfalfa –high vitamin K content
• Coenzyme Q10 – dependent on vitamin K

Several of these listed herbs are consistently among the top sellers. Data from the Centers for Disease Control and Prevention (CDC) in 2002 included ginseng, ginkgo biloba, and garlic as the dietary supplements with the 2nd, 3rd, and 4th highest sales, respectively. St John’s wort was 6th and ginger was 9th.21 The popularity of herbs with anti-coagulation potential was further validated by HerbalGram’s report of dietary supplement sales in mainstream retail stores in 2004. Garlic was the top seller with ginkgo at 4th, ginseng at 7th, St John’s wort at 9th, and ginger at 20th.22 Clearly, the popularity of these herbs has not waned.

Of the 11 herbs highlighted during the NIH conference, this article will only focus on garlic, gingko, ginseng, ginger, and St John’s wort for several reasons. First, as indicated above, these herbs consistently rank high in sales, indicating predominant usage. Second, the amount and quality of scientific evidence is more prevalent on these botanicals as compared to other herbs.

Health care professionals have an increasing responsibility to understand the rationale for use of these herbal medications and their reported effects on the body, given the large percentage of patients who take them. Unfortunately, it is challenging to locate accurate, consistent, and comprehensive information pertaining to herbal medications and their supposed mechanisms of action. While the knowledge base pertaining to herbs and other dietary supplements continues to grow, there are few studies that have determined conclusively how these products alter bleeding or interact with other herbals and prescription anti-thrombotic medications.23 Speculation and case reports from the literature have provided clues as to the purported mechanisms of action; however, relatively few clinical trials have been conducted to formally examine these issues. Further, case reports in the literature sometimes fail to take into account other herbals or drugs that the patient may have been taking. Therefore, it is difficult to credit the results of a case study to one definitive herbal action.

Clinicians encounter this same phenomenon with their own patients. When asked, a patient may know a product’s brand name, but cannot identify the multiple herbs that are contained within that same product. Further, it is not unusual for a patient to take upwards of 7 individual dietary supplements at the same time, but often on an inconsistent basis. When the CDC last reported on dietary supplement usage (1988-94), 14.4% of respondents reported usage of 3 or more supplements.24 The highest segment of users (22%) was among those aged 40 years and older. More recently, the Hartman Group, a research firm, surveyed 43 000 U.S. households, and found that 31% reported using 7 or more supplements.25 These statistics may not reflect, and in fact may underestimate, the growing use of combination products, or supplements that contain multiple herbs as well as vitamins. Given these trends, it is highly likely that an individual is unknowingly taking several herbs that have either anticoagulant or antiplatelet activity. Therefore, use of dietary supplements has the potential to a) cause a bleeding condition, b) exacerbate an existing bleeding condition, or c) alter the effectiveness of other OTC and prescription medications being taken concurrently. Obviously, the resulting complications may be potentially serious.

The purpose of this article is to assist dental professionals with understanding the mechanisms of action of popular prescription and herbal medications that alter bleeding. Drug and herbal interactions will also be discussed. Finally, practice management considerations for medicated patients and strategies for risk reduction will be presented to increase the dental professional’s confidence in making treatment decisions for patients taking these medications.