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Does Plavix actually CAUSE bleeding?
February 25, 2012 3:22 PM   Subscribe

Calling all knowledgeable medical persons! I need help with this medical hypothetical.

In advance: Again, this is a hypothetical; it does not involve any real-life persons (as far as I know).

Let's say you knew someone with both a history of ulcers and CHF (congestive heart failure). This person took Plavix (not sure for how long) and another heart medication that has been linked to gastrointestinal bleeding.

Then this person dies after fainting while shopping. Their autopsy shows they had been bleeding internally for some time before dying (again, not sure how long). The person bled approximately 100ml (found in the stomach/upper intestine), and had an "aggravated duodenal lesion/varicosil" (I can't find a definition for "varicosil", but I'm guessing this is an ulcer. Please correct me if I'm wrong).

Is it possible the Plavix caused the bleeding, or is it more likely that the other medicine caused the bleeding? I mean, if the Plavix were the cause, wouldn't this person have bled more?

Any help on this would be MUCH appreciated.
posted by Sakura3210 to Health & Fitness (11 answers total)
Don't know anything about Plavix but here is the definition of varices, which I think is the word you need.
posted by tamitang at 4:28 PM on February 25, 2012

Is it possible the Plavix caused the bleeding, or is it more likely that the other medicine caused the bleeding?

I don't think this is the right question. It especially can't be answered without the other drug name, and would be better served by a more complete medical history, social history, and/or autopsy report. I can think of several other questions I'd ask about organs, genetics, and social history if I was given this much information to start with.

The way Plavix works is to try to prevent platelet aggregation, aka clotting. As with any antiplatelet or anticoagulant drug, a small bleed can turn into a big one because the body can't repair it well. Plavix is contraindicated in patients with active ulcers and I suspect the other one would be as well, if it's known to cause bleeding. That being said, if no one knew about the ulcers or varices, they wouldn't know to not prescribe those meds.
posted by cobaltnine at 5:05 PM on February 25, 2012 [1 favorite]

Regardless of which medication caused the bleed, plavix would make the person bleed more due to its blood thinning properties.
posted by brevator at 5:29 PM on February 25, 2012

The other drug doesn't exist in the real world. In the hypo, it was originally meant to help glaucoma suffers by lowering eye pressure, but ended up having a positive effect on CHF.

Medical history - He had a slightly elevated blood pressure (just the systolic), but his pulse was good. The CHF caused fatigue and shortness of breath. He was aware of the ulcer, and had been receiving treatment for it for years from his doctor. Apparently it would sometimes cause him pain (though not serious).

Autopsy - The only other thing mentioned on the autopsy is an "elastic aortic wall" (outside normal limits). Apparently the hospital felt that indicated "advanced CHF".

Other notes: The guy was a smoker for about two decades but quit 5 years before he died, and he was` also a drinker, but not much (2-3 oz. a day). He was in his late sixties.

That's all the information I have. Hopefully it helps. This turns on what actually caused the bleeding to start in the first place, which is why I'm trying to pinpoint the most likely candidate.
posted by Sakura3210 at 8:25 PM on February 25, 2012

Oh, one more thing - apparently the guy wasn't showing any symptoms of the internal bleeding prior to his death. I figure this means he must have been bleeding very little for a very long time. I figured maybe that meant the Plavix wasn't having any bleeding side effects (since otherwise there would have been a lot more bleeding in total).
posted by Sakura3210 at 8:31 PM on February 25, 2012

Out of curiosity (and assuming you have enough info to answer):

What was the treatment for the ulcers, specifically? (antibiotics + antacids?)

Was an EGD (or any variation of an upper endo) ever performed?
-any polypectomies during the EGD? If so, Biopsy results?

When was he last tested for H. Pylori?

Were epithelial samples of the stomach taken postmortem? If so, what did the pathologist's report have to say?

Any significant findings in the pathologist's report, not related to my previous question or what was already given from the autopsy? I'm sure you put everything out there, but if you're focused on the drug(s), you might not have thought to bring up something we might see as a pertinent positive/negative.
posted by MansRiot at 9:31 PM on February 25, 2012

Unfortunately, I do not have the information to answer any of those questions. The autopsy info is only an excerpt of what is presumably a longer report (that I have no knowledge of). There's only one medical record, and it doesn't even mention his ulcer (it just shows BP, Pulse, CHF, his fatigue/shortness of breath and his medications). The only reason I even know about the ulcer is because the fact summary mentions it, and that a doctor had been caring for it for five years.
posted by Sakura3210 at 10:20 PM on February 25, 2012

Well, I had to ask : )

Good Luck!
posted by MansRiot at 12:10 AM on February 26, 2012

Proton pump inhibitors, a common treatment for ulcers, reduce the antiplatelet effect of clopidogrel.

Don't forget over-the-counter medications. Gastric ulcers are less common as a side effect of clopidogrel, but they are much more common as a side effect of other NSAIDs (like ibuprofen). So if they'd taken OTC ibuprofen that's a more likely candidate.

UK perpective: this is a very odd combination of medications, even taking that one is hypothetical. Standard treatment for CHF is an ACE-I plus beta blocker, plus diuretic if indicated. Since mild diuresis is an effect of some current drugs that reduce intra-ocular pressure, I'd probably put your hypothetical drug down as a diuretic, possibly plus other effects. Anti-platelets are used for other cardiac problems, such as acute coronary syndrome or atrial fibrilation. With your incomplete history it's possible that these were issues too. But otherwise, why is a patient with a history of ulcers and no apparent indication for it put on an anti-platelet?
posted by Coobeastie at 2:31 AM on February 26, 2012

also, slow bleeding into the stomach would usually have caused some vomiting of "coffee grounds" which would be looked at so I don't see that as plausible.
Also, the only other thing I can think off is the ulcer/s eroding into a major blood vessle and internal massive belld but there would be more than 100mls in that case....hmm...
posted by Wilder at 5:21 AM on February 27, 2012

Interesting. The "other drug" I guess would be acetazolamide (trade name is Diamox), a carbonic anhydrase inhibitor-type weak diuretic that is used to treat glaucoma but also occasionally by mountaineers to combat altitude sickness, for epilepsy specifically associated with menstruation, and in combination with other antiepileptics for refractory tonic-clonic, absence, and focal seizures. I don't believe it would have had any relevant effect on GI bleeding, and the BNF (British National Formulary) certainly doesn't mention any notable drug interaction with antiplatelet agents such as Aspirin (acetylsalicylic acid) and Plavix (clopidogrel). Long-term systemic (i.e. tablet) - as opposed to topical (eye drop) use of acetazolamide (a sulfonamide derivative and as such a noted cause allergic reactions) is not generally recommended as it tends to cause electrolyte imbalances and metabolic acidosis. The "common" side effects listed in the BNF are nausea, vomiting, diarrhoea, taste disturbance, loss of appetite, paraesthesia, flushing, headache, dizziness, fatigue, irritability, excitement, ataxia, depression, thirst, polyuria, and reduced libido. While Coobeastie has already noted that UK family practitioners would not generally prescribe acetazolamide as a diuretic for the treatment of hypertension and congestive cardiac failure, it may well be that this is a common prescription in the US, and it would make sense in someone who has both hypertension/CHF and glaucoma. His question of why no gastroprotection seems to have been offered is also very much to the point.

I agree that the amount of bleeding found at autopsy suggests that the bleed itself was not the primary cause of death, although there may well have been chronic blood loss from the ulceration and/or bleeding varices (bulging veins in at the oesophago-gastric junction most commonly caused by liver engorgement/fibrosis), likely causing chronic anaemia which may well have gone unnoticed. The subjective symptoms of minor gastro-oesophageal bleeding (indigestion, nausea, lack of appetite) may well have been dismissed if the patient had been made aware that Diamox can cause these as side effects ...

The aortic wall changes sound like a tissue change simply noted in passing by the pathologist that is not immediately relevant to the death but indicates a degree of arteriosclerosis and heart failure.

It would be instructive to know the time frames involved - how long had the drug(s) been taken, how sudden and quick was the demise, and also was there any suggestion of an allergic reaction (e.g. visible rash or flushing). Was it a hot day? How long after a meal/drink was the fatal event? It is worth bearing in mind that anaphylaxis and anaphylactoid reactions often present with hypotension rather than rash! Was the man known to be allergic to sulfonamide drugs?

My guess would be that the mechanism of death was acute hypotension/cardiac insufficiency caused by a combination of chronic anaemia, minor acute blood loss, acute-on-chronic dehydration from both the diuretic as well as too long a period in the day without food and drink, plus possibly an anaphylactoid reaction element. The latter could only be proven by a mast cell degranulation (histamine release) test which is unlikely to have been performed routinely, and as far as I know cannot be performed retrospectively.

Plavix would likely have made a small contribution to this, but would by no means have been a leading cause. Intermittent/occasional taking of NSAIDs such as Aspirin or Ibuprofen - e.g. for age-related aches and pains/arthritis, and insufficient attention to the adequate investigation of stomach symptoms, are probably more to blame. Also, if the patient took antidepressants (despite you not mentioning this he may well have been on serotonin or noradrenaline reuptake inhibitors, as people often hesitate admitting to being medicated for anxiety/depression) then this would also have contributed to some extent to the acute and chronic bleeding as most SSRIs and NSRIs roughly double to platelet clotting time.

So all in all I would say this man's time was simply up, given that he doesn't seem to have been too bothered having his stomach investigated to any great extent or in a short timeframe. And as someone who spends a lot of time trying to resuscitate dying people in critical care, I have to say from the description it wasn't a bad way to go?
posted by kairab at 6:24 AM on February 27, 2012

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