Thanks for your replies. I recall how Al explained the aPTT test is for heparin whereas the INR is for warfarin - and now perhaps the Template Bleeding Time (TBT) may be sometimes useful for platelet issues. The reason I asked about it was I was reading an article about Platelet Aggregation Inhibitors and Anticoagulants. I think I understand now what the article was saying about the TBT test - that if one is taking platelet aggregation inhibitors with coumadin perhaps one should get a TBT test to make sure they aren't taking too much platelet inhibitors. They say things like aspirin, garlic, fish oil, some anti-cholesterol supplements, vitamin E, EFA's (DHA and EPA) etc. can increase TBT bleeding time potentially. I take it that perhaps the INR test does not necessarily measure the degree of platelet aggregation inhibitors in one's blood???
Another question I have is there any possible benefit of combining platelet aggregation inhibitors with coumadin as far as preventing clots on metal valves goes?
Here's some excerpts from that article on Thrombosis prevention that mentioned the TBT test -
From:
http://www.lef.org/protocols/prtcl-155a.shtml
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Coumarin Derivatives
Derivatives of Coumarin (e.g., generics warfarin and dicumarol) interfere with the rate of synthesis of blood clotting factors II (prothrombin), VII, IX, and X. As a result, prothrombin and partial thromboplastin times are significantly altered by anticoagulants, but are not altered by antiplatelet agents such as aspirin. Patients taking Coumarin derivatives are monitored for PT and PTT times to optimize dosing and avoid excessive bleeding.
Coumadin (warfarin) is the most freqently prescribed drug for thrombosis prophylaxis (prevention). It is an anticoagulant drug that was originally isolated in 1939 from sweet clover. Interestingly, Coumadin is the active ingredient found in many commercial rat poisons and insecticides. It works by interfering with the synthesis of vitamin K-dependent coagulation factors. Coumadin is used as a prophylaxis for myocardial infarction, stroke, arterial thromboembolism, and deep venous thrombosis. It is also used in patients with prosthetic heart valves.
Coumadin prolongs both PT and APTT, but PT is the one used to guide treatment. However, the new standard is the International Normalization Ratio (INR) which is described below. Bleeding is the primary adverse effect of Coumadin therapy. Bleeding is related to the intensity of anticoagulation, length of therapy, the patient's underlying clinical state, and the use of other drugs that can affect blood coagulation or interfere with Coumadin metabolism.
Minor bleeding from Coumadin therapy usually begins with ecchymoses (purple patches on the skin). Then the mucous membranes are affected, causing epistaxis (nosebleed) and subconjunctival hemorrhage (bleeding under the mucous membranes covering the eyes and inner eyelids). Purple toe syndrome is also associated with Coumadin therapy. Hematuria (blood in the urine) may also occur. Major bleeding complications usually involve gastrointestinal (GI) and intracranial bleeding.
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Combining Coumadin with Antiplatelet Agents
As has been previously described, Coumadin interferes with specific coagulation factors that can induce a thrombotic event. Coumadin is classified as an "anticoagulant" agent.
Aspirin, fish oil, vitamin E, and garlic inhibit platelet adhesion and platelet aggregation and are classified as "antiplatelet" agents. The inhibition of blood platelets' ability to adhere and/or aggregate also decreases the likelihood of thrombosis.
In a perfect world, an individualized program would be designed to deliver the optimal combination of anticoagulation and antiplatelet agents to provide the broadest protection against thrombosis without inducing hemorrhage.
There is much debate and confusion about the interactions between dietary nutrients and prescription antithrombotic medications regarding clot formation. The concern expressed in some studies involves potential interactions between Coumadin and antiplatelet agents such as ginkgo biloba, green tea, vitamin E, garlic, and fish oil (Heck et al. 2000). There has been apprehension that certain supplements put the patient at risk for bleeding problems by adding to the overall effects of Coumadin.
As a result of this concern, some doctors advise patients who are taking Coumadin to avoid any dietary supplement that could possibly cause increased bleeding. A problem with this ultracautious approach is that it deprives the patient of nutrients they may need to sustain life.
It also prevents the use of antiplatelet agents that act on hemostatic mechanisms, separate from those of Coumadin, to reduce more effectively the risk of thrombosis. There are major medical publications that confirm the importance of lowering the incidence of cerebrovascular stroke and heart attack by such a two-pronged approach using an agent with antiplatelet activity, for example, Coumadin (Fasey et al. 2002; Hurlen et al. 2002).
A patient taking Coumadin has to be concerned that any food, drug, nutrient, or other substance they put into their body may not only increase the bleeding time, but also affect Coumadin metabolism, which may either increase or decrease the effect of Coumadin on the INR. The inherent variability that occurs in each individual taking Coumadin makes it difficult to provide general guidance. For instance, the underlying medical condition determines the degree of desired anticoagulation. No studies have correlated optimal anticoagulant doses of Coumadin, as measured by the INR reference range,
with optimal doses of multiple antiplatelet agents, as measured by the template bleeding time (TBT). The template bleeding time is done in a physician's office where a template device nicks the skin and the number of minutes it takes for blood flow to stop is assessed by a nurse or lab technician. The "normal" template bleeding time is up to 9 minutes. A bleeding time (BT) of 4-5 minutes might indicate increased thrombotic risk, although a BT over 9 minutes may indicate an increased hemorrhagic risk. However, what is really important in this setting is the patient context, as discussed below.
As it relates to antiplatelet agents like fish oil and garlic, a BT of 4-5 minutes could suggest a benefit of taking higher amounts of these agents, whereas a BT over 9 minutes in a patient already on an antiplatelet agent might indicate that antiplatelet agent doses are having a biological effect and further dose increases should be avoided.
The problem patients face today is that there are no standards that document the ideal balance between Coumadin and antiplatelet agents such as fish oil, garlic, vitamin E, etc. Too much Coumadin and/or antiplatelet agents can cause hemorrhage, whereas too little Coumadin and/or antiplatelet agent(s) can cause thrombosis. In this setting or context, as with many medical issues, balance is the key concept. ....
Thrombosis Prevention
http://www.lef.org/protocols/prtcl-155b.shtml
In an ideal setting, a physician would carefully monitor the INR and the TBT to measure precisely the optimal level of anticoagulant and antiplatelet agents, respectively, in an individual patient. For instance, a patient with a heart valve replacement may have a desired INR range of 2.5-3.0, while an optimal template bleeding time may be between 7-9 minutes. If these tests were routinely conducted, a more scientific determination of the ideal intake of Coumadin, fish oil, garlic, vitamin E, etc. could be made.
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http://www.lef.org/protocols/prtcl-155c.shtml
The nutritional supplements listed below have been scientifically studied specifically for their ability to reduce the risk of thrombosis. The bulk of the research focuses on inhibiting platelet aggregation. The supplements are divided into several broad categories based on their primary actions:
Cholesterol-lowering supplements
Natural platelet aggregation inhibitors
Homocysteine-lowering supplements
Anti-inflammatories
Antioxidants
Sulfur-containing compounds
Note: The supplements in the natural blood thinners category could easily have been put into other categories. Ginkgo and vitamin E, for instance, are very powerful antioxidants. Essential fatty acids are also known for their anti-inflammatory actions. However, their blood-thinning effects are much more important in the prevention of thrombosis.
Other protocols contain further information on specific topics. (For research on supplements that increase fibrinolysis, see the Fibrinogen section of the Cardiovascular Disease protocol.)
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Policosanol inhibits the formation of clots and may work synergistically with aspirin in this respect. In a comparison of aspirin and policosanol, aspirin was better at reducing one type of platelet aggregation (clumping together of blood cells) and policosanol was better at inhibiting another type. Together, policosanol and aspirin worked better than either one alone (Arruzazabala et al. 1997; Stusser et al. 1998).
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Aged Garlic
Aged garlic has become a well-known, popular supplement for the cardiovascular system. Garlic has been found to increase the synthesis of nitric oxide, a chemical messenger that inhibits platelet aggregation and vasodilates blood vessels (Das et al. 1995; Dirsch et al. 1998; Kim-Park et al. 2000; Kim et al. 2001).
An article in the journal Nutrition described a randomized, double-blind study of aged garlic on normal, healthy individuals. The researchers found that aged garlic inhibited platelet adherence and aggregation. Higher doses (7.2 grams daily) had a more profound effect than lower doses (2.4 grams daily) (Steiner et al. 2001).
The specific effects of aged garlic have been the subject of several studies. Aged garlic has been shown to inhibit platelet aggregation by ADP, epinephrine, and collagen, although one study found that it did not affect ADP-induced aggregation (Steiner et al. 1998; Rahman et al. 2000).
Another study examined the effects of consuming one fresh clove of garlic every day on men. After 26 weeks of garlic consumption, there was an approximate 20% reduction of serum cholesterol and about 80% reduction in serum thromboxane B2, a stable metabolite of thromboxane A2. Recall that thromboxane A2 is a platelet aggregator and vasoconstrictor secreted by platelets (Ali et al. 1990, 1995).
Natural Platelet Aggregation Inhibitors
Ginkgo Biloba
Essential Fatty Acids
Vitamin E
Vitamin K
Ginkgo Biloba
Ginkgo biloba extract is made from the leaves of the oldest living tree. Ginkgo biloba has a long history of medicinal use. It has become a very popular herb to help improve memory, particularly in the elderly.
Ginkgo biloba has been shown to inhibit platelet aggregation induced by platelet-activating factor (PAF), but not by oxidative stress (Akiba et al. 1998).
An article in the journal Thrombosis Research described a study of the effects of ginkgo biloba in combination with ticlopidine when used to treat rats with experimentally induced thrombosis. The combination of ginkgo biloba (40 mg/kg daily) and a small dose of ticlopidine (50 mg/kg daily) was shown to be comparable to a large dose of only ticlopidine (200 mg/kg daily). The combination also prolonged bleeding time by 150% and consistently decreased the thrombus weight (Kim et al. 1998).
Essential Fatty Acids
Essential fatty acids are found in healthy oils, such as flax, borage, perilla, and fish oils. Essential fatty acids are termed "essential" because they are necessary for life. Essential fatty acids, including DHA (docosahexaeonic acid) and EPA (eicosapentaeonic acid), are known to inhibit platelet aggregation and are included as potential contraindications for use with anticoagulant (warfarin) therapy. The contraindication is actually more of a strong caution to avoid thinning the blood too much.
What this means is that if a patient on Coumadin does take fish oil supplements, the TBT test should be done in addition to checking the INR reference range.
Several studies examined the antiplatelet mechanisms of essential fatty acids like EPA and DHA and showed they inhibited collagen- and arachidonic acid-induced platelet aggregation. No effects were seen in thrombin-induced aggregation. The mechanism was related to the ability of these fatty acids to suppress thromboxane A2 formation by inhibiting cyclooxygenase-1 (Ikeda et al. 1998; Akiba et al. 2000).
An Australian study found that omega-3 fatty acids (those rich in alpha-linolenic acid, such as flaxseed and perilla oils) were more effective than omega-6 fatty acids (those rich in linoleic acid, such as sunflower oil) (Allman et al. 1995). This same result was also reported in a German study which found that an omega-3 to Omega-6 ratio of 15:1 caused a significant decrease of collagen-induced platelet aggregation (Stroh et al. 1991).
Vitamin E
Vitamin E (tocopherol) is a potent antioxidant that has been shown to increase prostaglandin I2 synthesis, one of the platelet aggregation inhibitors and vasodilators. Vitamin E is depleted by estrogen, birth control pills, and chlorine.
A study found that vitamin E was able to inhibit collagen-induced platelet aggregation at concentrations achievable in blood after supplementation. The researchers also isolated a mechanism by which vitamin E blunts hydrogen peroxide formation, which then mediates arachidonic acid metabolism and phospholipase C activation in platelet aggregation induced by collagen (Pignatelli et al. 1999).
If vitamin E is used with Coumadin, the template bleeding time test should be done by the physician to guard against risk of hemorrhage.
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