Mini Stroke - OnX valve - on warfarin INR range 2-3

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vivekd

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I went for Aortic Valve Replacement surgery in June 2016 to get On-X aortic valve. I've been on warfarin maintaining INR range of 2-3. My Last MRI-Brain showed that I've had a mini stroke.
MRI-Brain result "Small, 4 mm focus of subacute infarction involving the cortical/subcortical inferior left parietal lobe."

I would not have known about the stroke, if MRI was not performed, and fortunately there was no damage.

My INR has been in the range 2-3 most of the time except my INR went to 1.5, 3 weeks before MRI because of medicine mix up between warfarin and crestor. I was taking 10 mg of warfarin + 5 mg of crestor instead of 15 mg of warfarin.

On-X valve has FDA approval for INR range of 1.5-2.0

My cardiologist thinks that 7-10 days of sub-therapeutic INR should not cause blood clot. Now I'm scheduled to get a TEE to see if blood clot still exists and my INR range has been changed from 2-3 to 2.5-3.5 with baby aspirin.

My cardiologist may end up changing warfarin to other blood thinners if they see blood clot during my TEE, even though other blood thinners have not been approved for mechanical valve assuming that I've warfarin resistance.

Questions for the fellow members:

1) Could one have blood clot with INR sub therapeutic range for 7-10 days?
2) Should I've gone for bridging (lovenox or heprin) when my INR results showed 1.5
3) Do patients with low resting heart rate have high risk for blood clot during subtherapeutic INR range. My resting heart rate is around 45.
4) What should i do, if my INR ever goes low (i usually drink beer for next day or two to increase my INR, till increased warfarin dosage becomes effective in 48-72 hours)


Thanks,
--- Vivek
 

pellicle

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Hi

sorry to hear this ... Also, thanks for posting this because it should help the "brave fools" who unquestioningly wish to hover at 1.7 on their On-X valves

vivekd;n886321 said:
... My Last MRI-Brain showed that I've had a mini stroke.
MRI-Brain result "Small, 4 mm focus of subacute infarction involving the cortical/subcortical inferior left parietal lobe."

I would not have known about the stroke, if MRI was not performed, and fortunately there was no damage.
I'm glad to read that.

My INR has been in the range 2-3 most of the time except my INR went to 1.5, 3 weeks before MRI because of medicine mix up between warfarin and crestor. I was taking 10 mg of warfarin + 5 mg of crestor instead of 15 mg of warfarin.
its hard for me to be sure that this is the cause or if the infarc was from an earlier time / event ... how long did your INR go low for? I assume you are still measuring INR weekly.

On-X valve has FDA approval for INR range of 1.5-2.0
if one reads the study carefully it was:
  • selected patients for the study
  • weekly monitoring
My cardiologist thinks that 7-10 days of sub-therapeutic INR should not cause blood clot.
I'm inclined to agree ...

Now I'm scheduled to get a TEE to see if blood clot still exists
I'm a bit lost, was there clear evidence of the existence of a blood clot somewhere or is this an investigation to see if one exists.


My cardiologist may end up changing warfarin to other blood thinners if they see blood clot during my TEE, even though other blood thinners have not been approved for mechanical valve assuming that I've warfarin resistance.
  1. what other anticoagulant would they pick?
  2. what is "warfarin resitance" or is this something just being made up?

1) Could one have blood clot with INR sub therapeutic range for 7-10 days?
its unlikely

2) Should I've gone for bridging (lovenox or heprin) when my INR results showed 1.5
depending on the duration yes, but if the duration was just days why would it not be a simple matter to just correct the dose

3) Do patients with low resting heart rate have high risk for blood clot during subtherapeutic INR range. My resting heart rate is around 45.
I have no answer for that

4) What should i do, if my INR ever goes low (i usually drink beer for next day or two to increase my INR, till increased warfarin dosage becomes effective in 48-72 hours)
I always take a small increase in dose and test again in 3 days (although it depends on how low it goes and what my previous observations have been.

I caution that "having a beer" is not anything which will help raise your INR ... while it might be the case that it creates the situation of an elevated INR this is because it interferes with the disposal of warfarin (by P450 pathway) and will not create more warfarin in your system if its low ... you should always increase your dose to raise your INR, but do the increase in no more than a 50% increase in dose as a one off.

Hope to hear back from you soon.
 

vivekd

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Thanks pellicle,

Here are some additional details:


>> its hard for me to be sure that this is the cause or if the infarc was from an earlier time / event ... how long did your INR go low for? I assume you are still >> measuring INR weekly.

I test my INR @ home every Thursday.

We don't know the actual timing of the infarction, since i did not have any symptoms. My MRI-Brain report shows 4mm subactute infarction. MRI was done on 12/20 and my INR went to 1.5 on 12/7. Here are the INR details:

11/29/2018 -- 3.1 (Warfarin 15 mg)
12/6/2018 -- 1.5 (Warfarin 10 mg -- accidental less dosage)
12/9/2018 -- 3.2 (Warfarin 25 mg, 20 mg, 20 mg to bring it up and then go back to 15 mg)

>> I'm a bit lost, was there clear evidence of the existence of a blood clot somewhere or is this an investigation to see if one exists.
>> 1. what other anticoagulant would they pick?
>> 2.what is "warfarin resistance" or is this something just being made up?

My cardiologist's notes " I recommend a goal INR of 2.5-3.5 and continuation of low-dose aspirin. I will also arrange for TEE to ensure no evidence of thrombus for the rare possibility of Coumadin failure."

We don't know if he will recommend other blood thinners, and which one.

Since warfarin changes my INR, and therefore IMHO it should not be treated as Coumadin failure.

>> depending on the duration yes, but if the duration was just days why would it not be a simple matter to just correct the dose
We increased the dosage on the day low INR was reported but it took 2-3 days to bring INR back to therapeutic range.


My dosage has been increased from 2-3 to 2.5-3.5 and also added baby aspirin. I plan to stay around 3.0
 

pellicle

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Hi

vivekd;n886323 said:
Thanks pellicle,
welcome ... I know its always good to just talk sometimes ... thrash ideas around.



>> its hard for me to be sure that this is the cause or if the infarc was from an earlier time / event ... how long did your INR go low for? I assume you are still >> measuring INR weekly.

I test my INR @ home every Thursday.
ok, so it wasn't sub-therapeutic for long

We don't know the actual timing of the infarction, since i did not have any symptoms. My MRI-Brain report shows 4mm subactute infarction. MRI was done on 12/20 and my INR went to 1.5 on 12/7. Here are the INR details:
seems like too short a time between the two, do you have a previous baseline MRI to compare? There is no certainty that there is even correlation (let alone causation) between these two (espeically without any symptomatic indicators). It could be even a "thrown clot" (meaning one which was created by the closing jets of the valve triggering embolism).


11/29/2018 -- 3.1 (Warfarin 15 mg)
12/6/2018 -- 1.5 (Warfarin 10 mg -- accidental less dosage)
12/9/2018 -- 3.2 (Warfarin 25 mg, 20 mg, 20 mg to bring it up and then go back to 15 mg)
I've been sub-therapeutic longer than that when I had my colonoscopy ... if you haven't already read that I I suggest you have a glance at it and take particular notice of the sections of the journal article I used for guidance.

http://cjeastwd.blogspot.com/2017/12/perioperative-management-of-inr.html



>> I'm a bit lost, was there clear evidence of the existence of a blood clot somewhere or is this an investigation to see if one exists.
>> 1. what other anticoagulant would they pick?
>> 2.what is "warfarin resistance" or is this something just being made up?

My cardiologist's notes " I recommend a goal INR of 2.5-3.5 and continuation of low-dose aspirin. I will also arrange for TEE to ensure no evidence of thrombus for the rare possibility of Coumadin failure."

We don't know if he will recommend other blood thinners, and which one.
noted ... his choices are limited, and perhaps its a good idea to consider con-current aspirin (which IIRC is a mandate for the ongoing On-X 1.7 protocol).


Since warfarin changes my INR, and therefore IMHO it should not be treated as Coumadin failure.
agreed ... never even heard of that ... can't find anything on it either

My dosage has been increased from 2-3 to 2.5-3.5 and also added baby aspirin. I plan to stay around 3.0
I'd call that prudent ... was / has there ever been a d-dimer test?
https://en.wikipedia.org/wiki/D-dimer
 

vivekd

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>> seems like too short a time between the two, do you have a previous baseline MRI to compare? There is no certainty that there is even correlation (let alone causation) between these two (especially without any symptomatic indicators). It could be even a "thrown clot" (meaning one which was created by the closing jets of the valve triggering embolism).

I started having loss of balance symptoms in 2017, where for few seconds i will involuntarily move to the right and then i have to force myself to the left. Because of that we've started doing MRI every year. My last MRI was in Oct 2017 and last MRI was in Dec 2018. They compared both the MRIs, since there were no infarction in 2017 MRI.

I've not had any loss of balance symptoms in last 8-9 months, but plan to do MRI next year.

>> I've been sub-therapeutic longer than that when I had my colonoscopy ... if you haven't already read that I I suggest you have a glance at it and take
>> particular notice of the sections of the journal article I used for guidance.

>> http://cjeastwd.blogspot.com/2017/12...nt-of-inr.html
I was not comfortable bridging, and therefore went for virtual colonoscopy on 12/4/2018.

>>I'd call that prudent ... was / has there ever been a d-dimer test?
Nope, never heard of it, before today.
 

vivekd

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In order for me to bridge (in future), I would have to find a home nurse to administer Lovenox injection. I'm scared of needles and cant inject myself. I've tried talking to pharmacies, and urgent care places but none of them administer lovenox / heprin. I've been trying to have a backup for any possible future need for bridging.
 

vivekd

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my MRI report details and comparing the results from 2017 MRI:

Small, 4 mm focus of subacute infarction involving the cortical/subcortical inferior left parietal lobe.

Multiple small, 2-7 mm foci of T2 hyperintensity in the cerebral white matter and cerebellar vermis slightly progressed from prior study but likely related to mild chronic microvascular ischemic changes/small old infarctions and small old lacunar type
infarction in the superior left cerebellum.

Several small foci of susceptibility artifact involving the cerebral and cerebellar hemispheres consistent with hemosiderin deposition and old "microhemorrhages" as can be seen in setting of chronic hypertension or even old trauma.
 

pellicle

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well I'm not a radiologist, I'm a little clear if the above is the result of the 2018 MRI but did the 2018 radiologist have access to the actual 2017 MRI or was it just a summary report?

Its hard to know exactly when the "Small, 4 mm focus of subacute infarction involving the cortical/subcortical inferior left parietal lobe" occured, it could be any time between the two MRI (or maybe it just wasn't clear on the 2017 MRI?

Anyway ... I'm glad that youi've moved higher in INR and I'd also suggest commencing small dose aspirin (given this incident)

Best Wishes
 

vivekd

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my MRI was done at the same hospital and they compared the results from last year's MRI, and report says that infarction was not there in Oct 2017, but was present in the MRI performed on Dec 2018. My neurologist had access to both MRIs, since he ordered MRI in both 2017 and 2018.

Since MRI says 'subacute infarction', it means that it happened few weeks before MRI date (Dec 20th 2018), but no way to know, exact date when it happened, since I did not have any symptom.

I agree that increased INR (2.5 - 3.5) with baby aspirin is safer than INR range of 2-3 (at least in my current situation)
 

pellicle

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vivekd;n886329 said:
...
Since MRI says 'subacute infarction', it means that it happened few weeks before MRI date (Dec 20th 2018),
this is not my understanding of the meaning of sub-acute. My understanding is that the sub-acute means of lower intensity (unless the word period is also used; subacute period of treatment). To my understanding there is no way an MRI can identify if that infarcation is as old as a week after your last MRI.

So to me all you know is that it occured between 2017 and 2018.
 

vivekd

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Then this is even more confusing, because outside of the one week, my INR for last 1 year has always been therapeutic mostly around 2.5 and if my INR goes closer to 2, i usually check mid-week and readjust the dosage.
 

pellicle

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Hi

vivekd;n886331 said:
Then this is even more confusing, because outside of the one week, my INR for last 1 year has always been therapeutic mostly around 2.5 and if my INR goes closer to 2, i usually check mid-week and readjust the dosage.
indeed (its seemed that way to me from the beginning.

You must keep in mind that you don't actually know much yet and so its hard to make a clear determination of the cause and thus what changes are needed.

Remember there are two types of thombosis
  • ones which are triggered and grow as they flow though the blood stream (gathering size as they travel in a manner of a snowball),
  • the other type forms on a surface and grows.
The former cause strokes and can only be found when they have jammed into some bit of plumbing which is too small for them to pass. Assuming they are not broken down by the white blood cells then they form obstructions to the flow of blood (and the nutrients and oxygen it carries) causing problems. These are noticed in a profound way in a sensitive area like the brain. As it happens the brain gets the blood first and so is sensitive to these type (emboli). Evidence of these can be found by a d-dimer test (which I suggested) as long as they are still being produced.

The latter will be what can be found with a TEE which is inspecting the surface of the valve leafelets and the surrounding entrance and exit. These can on occasion break off and then cause an obstruction somewhere else.

To my reading of the data presented you're more than likely going to see a clean TEE because I believe you've suffered something from an emboli. The small area effected is consistent with that too.

I have experienced a case with a fit and active person that the valve was causing micro strokes and to allow them to continue their "high level training" they needed to have INR > 2.5 and also take antiplatelets.

They never did a d-dimer test because in the earlier stages of investigation their Dr hadn't heard of it either (its not uncommon for Dr's to be a decade or more behind the times of investigative tools)

Remember to keep an open mind during investigation and not just have a lynching for public satisfaction. Also keep in mind that the body is an immensly complex set of chemistry which is only understood in part and few practitioners are across even most of the sub-systems in detail.
 

pellicle

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a worth read:
https://www.ncbi.nlm.nih.gov/pubmed/12445606

(keep in mind the date of 2003, so this is early work, but the principles it outlines are of course still true ... later work on developing 3D computer models of pressure and shear stress have sprung from this area of research

The important points are bolded by me


The high incidence of thromboembolic complications of mechanical heart valves (MHV), primarily due to platelet activation by contact with foreign surfaces and by non-physiological flow patterns past the valve, still limits their success as permanent implants. The latter include elevated shear and turbulent stresses and shed vortices formed in the wake of the valve's leaflets during the deceleration phase, potentially entrapping activated and aggregated platelets. It is hypothesized that these flow patterns induce the formation of free emboli which are the source of cerebrovascular microemboli associated with MHV. Implicit to this hypothesis is that free emboli formation will be affected by the implantation technique employed and the valve orientation, as those will alter the flow characteristics past the valve and the interaction of the platelets with the flow. In this study, numerical simulations of turbulent pulsatile flow past a St. Jude Medical bi-leaflet MHV were conducted. Platelet shear histories were calculated along pertinent turbulent platelet trajectories, and the effect of a misaligned valve on platelet activation was quantified and compared to that of an aligned valve. It demonstrated that the combination of a tilted valve and subannularly sutured pledgets had an explicit detrimental effect on platelet activation, with the following entrapment of the platelets within the shed vortices of the wake leading to a significant increase of the thromboembolic potential of the valve. This numerical model depicted a viable course for free emboli formation, and indicated how the implantation technique may enhance the risk of cardioembolism.

Essentially at this early stage they were concerned about the issue being caused by "sloppy fittment" of the valve



however it has come to light that the opening and closing of the valve also causes high pressure gradients (put your thumb over a slow running garden hose to see that at work in the small spurt just on your thumb closing off the hose...

For a good background of the problem that was being investigated see also an earlier work:

https://www.ncbi.nlm.nih.gov/pubmed/9731602

This suggests to me microemboli is at work in your case and that probably paltelet activation is the agent (not thrombosis thus not INR related)

Best Wishes
 

vivekd

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Thanks, it was interesting reading.
I'm scheduled to go for TEE 2 weeks from now, but I plan to work with my nurse to see if i can get it lil bit earlier.

We don't know the time when I experienced infarction, but it was obviously before my MRI date 12/20/2018. So It has already been close to a month. Would TEE even be helpful if it is performed 6-7 weeks after MRI.

Are there tests for aspirin sensitivity?

I did take baby aspirin for the first 3 months after the aortic valve replacement, but was told by my cardiologist to stop using it and just stay with warfarin to maintain INR range of 2-3.

I've already moved to INR 2.5-3.5 + Baby Aspirin, so hopefully that will be safer
 

pellicle

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vivekd;n886335 said:
Are there tests for aspirin sensitivity?

I did take baby aspirin for the first 3 months after the aortic valve replacement, but was told by my cardiologist to stop using it and just stay with warfarin to maintain INR range of 2-3.
Sorry for the sparse /terse response (mobile) but yes and some further interesting reading

https://thrombosisjournal.biomedcent.../1477-9560-2-1

As to the benefits of a TEE, it would at least rule out thrombosis forming on the valve. I think it's unlikely, but WTF, it's only money and discomfort :)
 
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jwinter

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At the risk of being called a brave fool I will post a bit of my story also so you have some more to think about.

I DO have another medical that is autoimmune disease so take it for what I post it for.

A year ago I had an ongoing bleeding issue. I was transfused blood about every third day and very anemic. When I finally went to a hematologist he did a bone marrow on me and said I had no iron in my marrow. Fast forward and they found I needed a shunt in liver (caused by autoimmune disease, PBC) and after that I still was losing iron and blood.

Finally, the GI found I was bleeding out throughout my stomach area so they banded the bleeders and waited. Meanwhile a call was made on my ON-X valve and they determined mine was from a line of valves made to be maintained at INR of 1.5 to 2. They checked serial number of mine with passing of FDA rules. They all felt my INR was causing some major bleeds for me and I also picked up a good case of sepsis in the midst of this all. My family was told I almost met my maker through this ordeal.

I asked a LOT of questions and this change was very gradual but I have been around 1.7 since last May. I cannot take beta blockers as my blood pressure runs low. It seems I have some pressure issues inside my body and they feel thinning my blood too much makes me bleed internally. If you have ever laid in a pool of blood or watched someone it is not a pretty scene and death can be very close at hand.

So there you have it from my view. Do I take a chance of a stroke when my valve was made for a lower INR or do I keep adding warfarin until I bleed out? Sorry it seems a little morbid but these are questions you have to ask doctors and decide on.

If the serial number and lot number is on your card from valve surgery look it up or ask cardio to explain this to you. As for me? I am going with the newest in technology and relying on the cardiac community of surgeons and cardiologists to guide me.

Good advice on this board but just take it for what it is. We are NOT a community of doctors but we ARE a community of people with various experiences.
 

vivekd

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Thanks jwinter.

It has been close to 2.5+ yrs since my surgery and I've maintained INR between 2-3 (I've to take 15-17 mg of warfarin to achieve that INR) and never had bleeding issue of any kind. I've done 2 MRIs in last 2 years and they also did not show any hemorrhage.

My cardiologist has referred me to 2 hematologist in last 2 yrs to check increased warfarin dosage and both of times they came back as me being quick metabolizer.

I've serial number of my onX valve, so I can obviously call them after my TEE is done.
 

vivekd

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pellicle: one more question:

so do I've to rush to get TEE scheduled quickly?

I'm currently scheduled for TEE on Feb 7, which is still 2 1/2 weeks away.
 

pellicle

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vivekd;n886339 said:
so do I've to rush to get TEE scheduled quickly?
Not as I see it. If there is thrombosis present in the valve it's not going anywhere soon.

jwinter

I would describe you as brave, but not a fool.

It's correct what you say, however it's important to remember all you ever get from a medical professional is an opinion, just the same. You may even find examples here of crappy opinions being delivered. I do not myself pretend to be a surgeon nor a cardiologist, but I do actually explain my opinions and where I formed them.

Many medical professionals don't do as much. "Trust me, I'm a doctor"

It's up to the patient to also do due diligence on the opinions they choose to accept.
 
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