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Re: INR value

From: MALAZ ABUTARIF <mabutarif>
Date: Tue, 21 Oct 2008 12:03:31 -0400

Dear All,
I can't send emails from my work email address to the NONMEM user group, fo=
r
some reason. Below is my response.

On 10/21/08, Abutarif, Malaz <malaz.abutarif



> Several papers exist (mostly in the "outcomes research" area).
> What I generally used in the past is to calculate the % of time a patient
> remains between 1.5x to 3x. The % of time the patient stays above 3x INR =
is
> usually correlated with increased risk of bleeding complications (use tha=
t
> as a risk indicator). Below 1.5 (some Physicians use 2x) is considered
> sub-therapeutic. Obviously, INR or aPTT are only useful for bleeding
> complications correlation and not for other toxicities.
>
> Look at it this way, it's similar to driving at a speed higher than the
> speed limit. It doesn't mean that if you drive higher than the speed limi=
t
> you will get into a car accident, it just means:
> 1. You are at a higher probability of getting into an accident
> and
> 2. If you get into an accident, the consequences are greater than if you
> stay within the speed limit.
>
> I look at 3x INR as the "speed limit" of anticoagulants.
> Below 1.5x is just going too slow on a highway. OR, below 1.5x the patien=
t
> is not protected and is at a probability of getting a stroke similar to t=
hat
> of placebo
>
> :-)
>
> Several old references exist that use the 2-3 or 1.5 to 3x, a more recent
> one is below
>
> J Thromb Thrombolysis. 2008 Apr 5. [Epub ahead of print] Links
> Warfarin: what are the clinical implications of an out-of-range-therapeut=
ic
> international normalized ratio?Merli GJ, Tzanis G.
>
>
>
> ___________________________
> Malaz A. AbuTarif,
> B.Sc. (Pharmacy), Ph.D., G.C.P.M., M.B.A.
> Principal Scientist,
> Pharmacokinetics, Pharmacodynamics and Pharmacometrics
> Early Clinical Research and Experimental Medicine
> Schering- Plough Research Institute
> 2015 Galloping Hill Rd, K-15-2-2650
> Kenilworth, NJ 07033
> Tel: (908) 740-3835, Fax: (908) 740-2916
> malaz.abutarif
>
>
> -----Original Message-----
> From: owner-nmusers
> On Behalf Of Dominik Uehlinger
> Sent: Tuesday, October 21, 2008 10:23 AM
> To: nmusers
> Subject: Re: [NMusers] INR value
>
>
> Khaled Nm schrieb:
> > Dear nmusers,
> >
> > I am looking for a reference for a maximum value for INR, byeond this
> > value the drug toxicity of anticoagulatnt may occur.
> > thanks for any response
> > Abduljalil
> >
> > __________________________________________________
> > Do You Yahoo!?
> > Tired of spam? Yahoo! Mail has the best spam protection around
> > http://mail.yahoo.com
> Dear Abduljalil,
>
> If only it were as simple as that!
>
> The major toxicity of anticoagulation is bleeding. However bleeding
> episodes may even occur at normal INR levels (much more factors are
> involved). There is no "secure" level, below which no bleeding occurs,
> but the risk of bleeding gradually increases when the INR increases.
>
> The risk of bleeding we are willing to accept (i.e. the maximum INR
> value) is given by the probability and seriousness of expected
> thromboembolic events (risk benefit ratio). Therefore target INR values
> are fixed dependent on the underlying disease: E.g. venous
> thromboembolic disease: 2.5, artificial heart valves: 2.5-3,
> thrombophilia: 3.
>
> With respect to non-bleeding toxicity of coumarins: these are largely
> dose independent.
>
> Regards Dominik
>
> --
> =========================
==========================
===
> Prof. Dr. med. Dominik Uehlinger
> Klinik und Poliklinik für Nephrologie und Hypertonie Universität Bern=
, 3010
> Bern - Inselspital Tel. +41 31 632 31 44, Fax +41 31 632 97 34
> uehlinger
==========================
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Received on Tue Oct 21 2008 - 12:03:31 EDT

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