From: sbharris@ix.netcom.com (Steven B. Harris )
Subject: Re: Vitamin K question
Date: 09 Oct 1995
Newsgroups: sci.med,sci.med.nutrition

In <45c0sn$ckr@sundog.tiac.net> Jonathan Tward <jtward@tiac.net>
writes:

>I've been asked to report on the following question about Vitamin K from
>a patient ....
>
>
>"I'm taking Coumadin (the trade name for the drug Warfarin). Should I eat
>less green vegetables because they interfere with the action of the drug?
>
>any comments?




  Comment: No, vegetables are good for you.  The only important thing
is that you eat about the same amount each day, and not change a great
deal up or down.  Your coumadin dose is individualized to you while you
are on a specific diet.  It really doesn't matter how many vegetables
with their attendent vitamin K content you eat, it's big CHANGES in
this intake *after* your coumadin dose is individualized to you and
your diet, that get you into trouble.   If you want to change your
diet, or change your vitamin regimen, notify your doc, and he/she will
have you come in for more frequent blood testing until you get
individualized once again.

                                        Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Subject: Re: Cause of clotting
Date: 04 May 1997
Newsgroups: sci.med

In <aneumanE9MML0.9nz@netcom.com> aneuman@netcom.com (Alan Seideman)
writes:

>Had a TIA in late decmber.  Sonagram showed severe blockage left carotid.
>Followup MIA showed complete occlusion. Right carotid about 60%. 2nd TIA
>in mid jan.  Blood tests reveal nothing out of synch with exception of
>slight elevation homosystiene.  Started taking folic acid 1000 mg.
>vitamin b, vitamin e and aspirin.  two months later, another sonagram
>shows additional clot material piling up on left carotid artery.  My
>physician suggests a hematologist might have more suggestions than he.
>Blood pressure excellent. cholesteral level below 180.  I don't smoke
>(pipe and cigars were abandoned completely about 5 years back) Alchohol
>stopped about 6 years ago.  Generally good health for 68 yrs. At any
>rate, visit with hematologist last week His directive is to start
>warfarin treatment after aspirin out of my system.  Visit set to begin
>treatment on 15th May.  From what I read, warfarin requires some diligent
>monitoring to avoid bleeding form organs, et al.  None of my research
>has given me answers to what concerns me.
>
>1. how long does one have to take this medication?
>2. What could be causing the clotting?
>3. What are my chances of living another 5-10 years without some fatal or
>crippling stroke?
>4. Could diet affect the condition I have and are there alternative
>remedies being used with any benefit.
>5, What excercise could aggravate the condition.  How should one's habits
>change.
>
>Alan N




   I'd see a couple of neurologists, if I were you-- they're the
experts here.  Hematologists don't know what the hell they're doing
treating carotid disease and TIAs.  Gimme a break!

    There's NOT any good evidence that Warfarin is any better at
treating carotid embolic TIAs than aspirin.  A neurologist would
probably switch you instead to Ticlid, another platelet inhibitor.
Assuming, of course, that your TIAs are clearly on the side of your
partly blocked carotid.  If this is true, you might also be a candidate
for surgery, though not otherwise.

    Ultrasounds are tricky, and it's very difficult sometimes to say
that one is worse than the other (depends on angle of scan, etc, etc).
You might end up treating nothing but a phantom created by two
different looks at the same thing, one different than the other.  It's
worth repeating this again, if it's being used to make a very iffy
decision like putting you on Warfarin.  If you think there are any good
studies that suggest that you should put people with "more clot"
(maybe) in one carotid on Warfarin, think again!   You're in unknown
territory here, and the best thing to do in unknown territory is
generally to avoid treatments of known danger.  Warfarin and carotid
endarterectomy certainly qualify.  Ticlid and aspirin (as well as those
vitamins, which I agree with), are more conservitive.


                               Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Subject: Re: Blood Thinning
Date: Sat, 06 Dec 1997
Newsgroups: sci.med

In <3488F409.36FA@erols.com> physical@erols.com writes:

>I am hoping someone can explain how/if blood is thinned by vit E, or
>coumadin, for that matter.  I maintain that unless there is an actual
>insult that triggers either the intrinsic or extrinsic clotting
>pathways, these agents should have no effect on normal circulating
>blood.  I am told, however, that they nevertheless do thin blood by
>interfering with Ca, vit K, etc.  How can this be correct if the
>pathways are not activated?
>	Thanks in advance, email appreciated (to dilute out the junk, if
>nothing else!)



   Thinning, is, of course, a misnomer.  The blood is no more thin than
usual.  The amounts of the 4 vitamin-K dependent clotting enzymes are
reduced (or, rather, the modified proteins-- the precursors are there
in normal amounts).  That's the "effect" on circulating blood.  In the
normal body a vitamin K dependent enzyme modifies these clotting
enzymes to be able to chelate and use calcium.  Coumadin interfers with
the body's use of vit K to do this, and thus the enzymes aren't
modified, can't chelate Ca2+, and don't work.   True, this is not
apparent until you're in a situation where they are *supposed* to work
(ie, a bleeding event which is supposed to trigger the clotting
cascade).  A person poisoned with an overdose of coumadin may be
perfectly fine if he or she lies quietly in bed!  Of course, you can't
count on that, since apparently many people have a little bit of
leakage all the time from small tears in small arteries, such as in the
brain.  If these don't clot they go on to become a major hemorrage and
stroke.

                                   Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Rat Poison
Date: 13 Dec 1998 02:59:17 GMT

In <19981211190728.02242.00004296@ng19.aol.com>
wwwcdotcom@aol.com12nospam (Wwwcdotcom) writes:

>>Does anyone here know the symptoms caused by ingestion of rat poison?
>
>Well, Rat poisons commonly use the substance "WARFARIN" which inhibits
>the formation of blood components/factors which are produced by the liver
>(also are Vitamin K dependent) that serve to promote COAGULATION of the
>blood...Without the coagulation cascade functional...a "rat" (or whatever
>has ingested it, simply bleeds to death....
>JR



   But most importantly, does so slowly.  And this causes a lot of
thirst.  Which causes said rodent to journey outside to find fresh
water, so he doesn't die inside your walls or behind something in your
basement.

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med
Subject: Re: Risk of anticoagultion with history of subdural hematomas
Date: Mon, 07 Feb 2000 15:02:31 -0500

David Wright wrote:
>
> In article <389E654A.7C7E852D@ucdavis.edu>,
> Greg Rogalski  <grogalski@ucdavis.edu> wrote:
> >Hi there, I'm a 3rd year medical student.  I have an 87 y/o male patient
> >with a history of recurrent subdural hematomas in 1995 secondary to
> >trauma which were eventually treated with craniotomy and removal of the
> >clot.
> >
> >The patient now has a pulmonary embolism, and we're contemplating
> >placing him on chronic coumadin.  Is he at increased risk of recurrent
> >subdural on coumadin because of his history (disregarding his fall risk
> >for a moment)?  Is the risk high enough that we would need to
> >re-consider long-term coumadin, or at least do serial head CT's?  Is
> >there another way to evaluate for chronic subdurals other than CT?
>
> Is it just me, or do others think those questions have "homework
> assignment" written all over them?

Actually, although we certainly get lots of questions here that
sound like homework assignments, this question sounds to me more
like a real question about a real patient.

Personally, I would be fairly hesitant to treat this patient with
warfarin.  If the PE is secondary to a clot in the lower extremities,
I'd strongly consider placing a vena caval filter.

--
David Rind
drind@caregroup.harvard.edu

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med
Subject: Re: Risk of anticoagultion with history of subdural hematomas
Date: Tue, 08 Feb 2000 12:51:59 -0500

Greg Rogalski wrote:
> Interestingly, we did a Doppler of both upper and lower extremities and
> no clots were found.  I'm thinking of pelvic clots or occult
> malignancy.  Is there a non-invasive way to evaluate for pelvic clots?
> (other than angiography?)

MRV can look for pelvic clots, probably, but other possibilities
are important and perhaps more likely:

1) The clot is no longer in the extremities because it is in the lung.
2) The diagnosis of PE is wrong.  (How was the diagnosis made?)
3) The U/S is wrong and there really is clot in the legs.

--
David Rind
drind@caregroup.harvard.edu

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Risk of anticoagultion with history of subdural hematomas
Date: 9 Feb 2000 03:42:52 GMT

In <38A0C3ED.727E2704@ucdavis.edu> Greg Rogalski
<grogalski@ucdavis.edu> writes:

>Thanks!
>-g
>
>David Rind wrote:
>>
>> Greg Rogalski wrote:
>> > Interestingly, we did a Doppler of both upper and lower extremities
>> > and no clots were found.  I'm thinking of pelvic clots or occult
>> > malignancy.  Is there a non-invasive way to evaluate for pelvic
>> > clots? (other than angiography?)
>>
>> MRV can look for pelvic clots, probably, but other possibilities
>> are important and perhaps more likely:
>>
>> 1) The clot is no longer in the extremities because it is in the lung.
>> 2) The diagnosis of PE is wrong.  (How was the diagnosis made?)
>> 3) The U/S is wrong and there really is clot in the legs.
>>
>> --
>> David Rind
>> drind@caregroup.harvard.edu



   You can also run a thrombin D-dimer level, which is sensitive but
not specific.  If it's positive it means nothing, but if negative you
can guess there is probably no clot anywhere.

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: aspirin safer than warfarin
Date: 1 Apr 2005 13:38:54 -0800
Message-ID: <1112391534.644295.157840@l41g2000cwc.googlegroups.com>

So that the following generalizations can be made:


>(1) Antiplatelet agents like aspirin and clopidogrel are effective in
>situations with high flow and pressure such as exposed thrombogenic
>surfaces (type IV collagen in rupture plaques or bare surgical steel of
>stented occlusive lesions) in arteries.
>
>
>(2) Warfarin is effective in situations with low flow and pressure such
>as the case in veins with DVTs and in the left atrial appendage with
>atrial fibrillation.

====================================
COMMENT:

No, sorry, you CANNOT make such a generalization, and I already
mentioned one reason why. Warfarin works, as noted, to prevent emboli
from mechanical aortic valves, a high flow high pressure situation with
exposed thromogenic surfaces, if ever there was one. Aspirin is not
adequate or indicated for this use, nor are any other antiplatelet
agents.

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: aspirin safer than warfarin
Date: 1 Apr 2005 16:01:36 -0800
Message-ID: <1112400096.296281.138400@z14g2000cwz.googlegroups.com>

>>Given that warfarin (Coumadin) started out as rat poison, and so far I
have never heard of using aspirin for that purpose, this headline is
somewhat intuitively true. <<

Indeed. The surprise was the Warfarin could be used in medicine at all.
In the 1950's some depressed sailor tried to commit suicide with it,
and failed. They saved him with vitamin K. There was no saving people
who killed themselves with the old white phosphorus rat poisons!  So
they took a second look at Warfarin and gave it a shot as a human drug.

There was some precident for Warfarin. It's a synthetic version of
dicoumarin, a fungus product which causes sweet clover bleeding disease
in calves. That's not always fatal, and indeed dicoumarol was used
breifly in medicine in the role what Warfarin is now, before they
decided Warfarin was cheaper, and tractable enough to work with.
(Though it's still nasty and scary stuff).

The sweet clover disease work was done as pure science by the Wisconsin
Alumni Research Foundation (WARF).  Hence the rat poison name.

The stuff is a great rat poison because it doesn't kill immediately,
but causes hemorrage and thus, thirst. Rats go outside to seek water,
and die out there, instead of in your walls.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: aspirin safer than warfarin
Date: 1 Apr 2005 20:07:54 -0800
Message-ID: <1112414874.767115.222020@l41g2000cwc.googlegroups.com>

>WARF! You're kidding right?<<


Sounds like April fools, but isn't.  The Warfian hypothesis is true.
Language influences worldview. The debate on naming Warfarin wasn't
even, ah, acronymious.


>> You're wasted here. <<

Nah. Academia won't pay for trivial pursuit. Unless it's in Women's
Studies or Art History, of course.

BTW, I wrote dicoumarin, but of course it's dicoumarol (as I first
said). There is no dicoumarin that I know of. Coumarin is a completely
separate plant product, and one that is neither a blood thinner or even
toxic. The generic name of the drug Warfarin is coumaDin (note the D),
which causes no end of confusion. I've even seen warnings on red clover
herbs that they might interact with anticoagulants. Reason: they
contain coumarin. Unless you're a fungus, you can't convert that to
anything that's going to bother clotting.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: aspirin safer than warfarin
Date: 2 Apr 2005 16:10:31 -0800
Message-ID: <1112487031.579571.107240@f14g2000cwb.googlegroups.com>

>>Coumarin is responsible for the pleasant vanilla or sweet hay scent of
sweet clover, and is used commercially in perfumes, flavourings, soaps,
etc.  It used to be extracted from tonka beans (the coumarou tree, in
French), but is now mostly made synthetically.  But yeah, it's not
physiologically active in humans, and AFAIK is GRAS. <<


COMMENT:

It is indeed both GRAS and GRASS. :)   May may even have anticancer and
antiischemic properites. But it's a natural product like vitamins, so
developmental uses for it will be slow in coming. Fascinating stuff. I
have a bottle here in the lab. It's crystals and it does indeed smell
like grass freshcut with the lawnmower. Or newmown hay if you have
enough rural background to know that that smells like. Quite lovely.

SBH

From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med.nutrition
Subject: Re: Warfarin and Ginseng
Date: Tue, 9 Apr 2002 12:38:59 -0600
Message-ID: <a8vcg6$nd$1@slb2.atl.mindspring.net>

"Jean P Nance" <jpnan@bluestem.prairienet.org> wrote in message
news:a8v305$524$1@wildfire.prairienet.org...
>     I habe a related a related question. What about taking Warfarin
> (Coumadin) and ginkgo biloba together? I seem to have read that both
> ginkgo and ginseng have a blood thinning effect. Maybe a doctor who is not
> intolerant of herbals would be willing to adjust the level of blood
> thinner if one  wanted to take one or the other of these herhal
> supplements?


Not likely. A doctor can adjust for the vitamin E supplement effect, since
it affects the same PT test (serum clotting) that the Warfarin does. The
herbals (including ginkgo) that affect clotting are somewhat like aspirin--
they affect *platelet* function, and the test for "blood thinning" your
doctor uses to adjust Warfarin dose doesn't see this effect. Still, it's
additive to the Warfarin effect. It's bad in medicine to have an effect that
the tests don't "see."


SBH

From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med,misc.health.alternative,sci.med.pharmacy,sci.med.cardiology,
	sci.med.laboratory
Subject: Re: coumadin ?
Date: Sun, 11 May 2003 13:31:29 -0700
Message-ID: <b9mbv1$dvs$1@slb0.atl.mindspring.net>

"Beverly Erlebacher" <bae@cs.toronto.edu> wrote in message
news:2003May10.162530.12623@jarvis.cs.toronto.edu...

> Tools is being particularly stupid here because coumadin is a coumarin,
> and coumarins are vitamin K antagonist anticoagulants found naturally in
> stressed sweet clover.  They were discovered when dairy farmers asked
> the Wisconsin Alumni Research Foundation (WARF) to fund research into
> why their cattle died from internal bleeding after grazing on
> frost-burned or drought-stressed forage.  The first use for this was the
> rat poison warfarin (note the name) which takes long enouhg to kill the
> rat that it doesn't make the connection between its illness and the
> bait.  Later, the medical use was developed.  So just like digitalis,
> it's a botanical drug too dangerous to be used without the kind of
> carefully managed dosing that can only be achieved with a purified form,
> since the content of the plants varies much too widely.

COMMENT:

Like all good stories the really correct version is not
quite as perfect as you relate, but almost. Here's my chance
to take erudite revenge over your Canadian quibble.

The Wisconsin Alumni Research Foundation WARF did fund the
original sweet clover research. But clover don't make the
active bishydroxycoumarin due to stress-- it's a fungal
product formed from plant coumarin in wet clover cut in the
fields, perhaps made by fungi as a poison, not wanting to be
eaten. Coumarin from the plant itself (and what you get in
normal herbal red clover) is a lovely compound, non-toxic,
and with odor of newly cut grass. It may yet some clinical
uses, but isn't an anticoagulant.

Bishydroxycoumarin, the same stuff from spoiled sweet
clover, was used under the tradename Dicoumarol in medicine
as an anticoagulalant in the 1940's. There is great
confusion between Dicoumarol and Coumadin, the drug which
eventually replaced it, starting 1954.  (I don't even think
you can get medical Dicoumarol in the US anymore, though
probably you can in Europe.)

Coumadin is indeed Warfarin, the old rat poison of the
1950's, and named for WARF and Coumarin. It's a synthetic
easier to make and longer-acting derivative of
bishydroxycoumarin, in which one coumarin moiety is replaced
by a phenyl group. It may work partly because rats don't
associate it with immediate illness, as you say, but
probably the more important thing is that bleeding rats get
thirsty and go outside to drink, where they die instead of
in your walls or attic.

A famous attempted suicide case in the early 1950's in which
a sailor attempted to kill himself with Warfarin containing
rat poison (duh, a sort of poison that wouldn't work as well
on ships, but tell that to the Navy) was saved with vitamin
K and transfusions. This brought Warfarin to the attention
of the medical community as a more powerful and easier to
dose Dicoumarol replacement that could be reversed if
necessary, and Coumadin was born.

Sweet clover herbal products are certainly not made from
extract of fungally spoiled sweet clover. They have plant
coumarins, but no significant Dicoumarol/bishydroxycoumarin,
and are not anticoagulants. The presence of plant coumarins
has led to many boobs on both sides of the herb issue either
warning about clover interacting with anticoagulants (they
don't) or advocating (as the boob on this forum) clover
being used as anticoagulants (they don't do that either).
Plant coumarins are at worst harmless, and at best might
have beneficial effects on certain inflammatory processes in
the body. But that's another topic.

SBH

From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med,misc.health.alternative,sci.med.pharmacy,sci.med.cardiology,
	sci.med.laboratory
Subject: Re: coumadin ?
Date: Mon, 12 May 2003 10:37:22 -0700
Message-ID: <b9om4f$aat$1@slb6.atl.mindspring.net>

"Beverly Erlebacher" <bae@cs.toronto.edu> wrote in message
news:2003May11.233353.27442@jarvis.cs.toronto.edu...
> In article <b9mbv1$dvs$1@slb0.atl.mindspring.net>,
> Steve Harris <sbharris@ix.RETICULATEDOBJECTcom.com> wrote:
> >
> >Like all good stories the really correct version is not
> >quite as perfect as you relate, but almost. Here's my chance
> >to take erudite revenge over your Canadian quibble.
>
> Okay, Dr. Harris, I bow to your greater erudition (or better memory)!
>
> Thanks for the correct, full story.


Yr welcome.  It doesn't help that coumarin and Coumadin look
like the same word, and people forget to capitalize drug
names. Or that Dicoumarol is very similar but not the same
as either of the other two. Even stuff on the net at
pharmacy info sites screws these up.

I find it fascinating that Dicoumarol of the spoiled sweet
clover disease is a fungal product, much like the red rice
yeast statins. And it performs the same function that
antibiotics and statins and ergot alkaloids do (if you know
the fascinating history of ergotism and rye): it's aimed at
poisoning fungus-eaters. But the dose makes the poison, and
like digitalis and atropine, a lot of things meant as
toxins, at lower doses turn out to have physiological
modifying effects that are very useful.

There's a REASON that all those medicines come from the rain
forest. Plants there don't have winter to give them a yearly
start on the hatching insect hordes. So they've developed a
LOT more insect poisons.  And those are the starting points
for meds.

SBH