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Coagulation Corner


Friday, August 5, 2011

COAGULATION CORNER: AUGUST 2011

PLATELET FUNCTION AND DRUGS, VITAMINS AND SUPPLEMENTS – OH MY!

We know that drugs like aspirin irreversibly inhibits cyclo-oxygenase-1 (COX-1), inhibiting platelet aggregation for 7-10 days, while conventional NSAIDs reversibly inhibit COX-1. The drug half-life determines the duration of the antiplatelet effect.  Clopidogrel and ticlopidine block ADP receptors, and inhibit platelet aggregation for 4–7 days.

Medications:

What about the action of other drugs on platelet function?  Some antibiotics such as penicillins and some cephalosporins bind to platelet membranes impairing platelet aggregation. Theophylline and caffeine affect platelet function in vitro via their effects on phosphodiesterase and adenosine receptors2, however there is no clinical evidence that significant antiplatelet effects or bleeding problems occur.

Antidepressants with high affinity for the serotonin transporter deplete platelet serotonin thus decreasing one of the signals for intracellular calcium release. Calcium antagonists, β-blockers and nitrates have antiplatelet effects in vitro, but information on their in vivo effect is limited. Verapamil and diltiazem have the most consistent evidence supporting an antiplatelet effect. They inhibit platelet aggregation in whole blood.  It is important to understand these effects and their impact on patients, in particular elderly patients.

Supplements: 

There have been many studies that have looked at the effect of fish oil or the n-3 fatty acids on platelet function.  Doses ranged from 1-4 g/d and as a result higher does demonstrated inhibition of platelet function. Such changes have been attributed to a reduced decrease of thromboxane A2 and an increase of the nonaggregating thromboxane A3. 

Bleeding tendencies can increase when some herbal medicines are taken in conjunction with non‐steroidal anti‐inflammatory drugs (NSAIDs) or acetaminophen. Implicated herbs include ginkgo (Ginkgo biloba), garlic (Allium sativum), ginger (Zingiber officinale), and ginseng (Panax ginseng); known as the “4 G’s”. Others include meadowsweet (Filipendula ulmaria), willow bark (Salix alba), dong guai (Angelica sinensis), turmeric (Curcuma longa), bilberry (Vaccinium myrtillus), and feverfew (Tanacetum parthenium) These are thought to impair platelet aggregation through reducing available intracellular calcium.

It has been demonstrated in patients with vitamin E deficiency, marked platelet hyperaggregability have been observed.  The action of vitamin E appears to be at the step of phospholipase A activation, or the conversion of arachidonic acid into the cyclic endoperoxides.  Administration of vitamin E appears to normalize this hyperaggregability.

Other:

Studies have been done to asses whether olive oil or its principal component, oleic acid, is capable of affecting platelet function. As far as olive oil is concerned, a daily dosage of 30 to 45 g/d has been assessed in 3 studies and the trials do not support an antiplatelet effect of either olive oil or oleic acid .

Moderate daily wine drinkers (3 to 5 glasses daily) had a lower risk of cardiovascular death compared with nondrinkers. This finding was confirmed by a meta-analysis. Globally considered, the studies inconsistently showed that short- or long-term wine intake is associated with an inhibition of platelet function in humans.  Experimental studies suggested a role for the nonalcoholic components of wine in inhibiting platelet function raised the hypothesis that polyphenols, which are abundantly present in wine, possess an antiplatelet property.

Several sources of polyphenols have been investigated to test their antiplatelet effect in human. Grape juice, berries, pomegranate, apples, garlic, onion, tea, cocoa, tomato, and garlic have been tested to asses whether they possess antiplatelet activity. Data obtained with grape juice and cocoa  seem to show an antiplatelet effect more consistently than other sources of polyphenols. An in vitro study showing that 5 to 10 μmol/L polyphenols inhibits platelet recruitment via increase of nitric oxide production. Its mechanism is unknown. Grapes and grape products, especially those made from the skins, seeds, and stems of Concord grapes, are good sources of flavonoids. Compared with white wine, red wine contains a 10-fold increase in flavonoid compounds. Flavonoids may contribute to the cardioprotective effects of grape products, as suggested by several studies associating increased flavonoid intake with reduced risk of coronary events

Tomato extracts can influence platelet activity in vitro and ex vivo.  The tomato’s bioactive components inhibit platelet aggregation in response to a range of agonists in vitro and reduce the platelet expression of activation-dependent antigens. The tomato extract is known to contain a wide variety of different types of compounds that have antiplatelet activity in vitro and that affect different mechanisms of activation and aggregation.

Substances that can affect platelet function:

aspartame (NutraSweet, can also reduce the number of platelets)
beer (including non-alcoholic beer)
blueberries
chocolate (dark)
coffee
feverfew
garlic
onions
gingko biloba
ginger
ginseng
green tea
guarana (a dietary supplement)
kiwi fruit
omega 3 fatty acids (hemp seed, fish oil)
pycnogenol (pine bark extract)
quercetin, rutin, and related bioflavonoids
red/purple grape products (grape juice, red wine, raisins, grape seeds)
red wine
tomatoes
vitamin E
wood ear or cloud ear mushroom (Auricularia auricula-judae, used in Chinese cuisine)

So, the list is quite extensive, but if you have ever done aggregation testing, you know how frustrating it can be with that abnormal result and no explanation.  The most important take away message is the impact of these products may have on bleeding when used concurrently with known medications that have anti-platelet effects.

So we know, coffee, dark chocolate, green tea and red wine, no sticky platelets, more reasons to enjoy!.

Donna Castellone

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About the Author

Donna Castellone,  MS, MT(ASCP)SH

Donna Castellone,
MS, MT(ASCP)SH

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