hypercoaguable state on withdrawal of Eliquis?

this is my biggest fear
ncbi.nlm.nih.gov/pubmed/306...

This showed that for a few weeks after stopping NOACs there was an increased risk of severe stroke due to the NOACs inducing a hypercoaguable state on withdrawal.

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anneh
this is my biggest fear
ncbi.nlm.nih.gov/pubmed/306...

The link you posted has been truncated. Can you please post the full link?

Perhaps you could taper Eliquis by going from the 5mg BID to the 2.5mg BID for a week or so before stopping. I doubt there’s any clinical data on that but I’ll bet no one would see a problem with it.

I stopped Pradaxa once after a year of use and Xarelto after using many months. Both were maximum dosage and I had no withdrawals at all. Now, I am currently on 2.5 mg of Eliquis 2x a day after LAA was isolated in 2016 Cather Ablation.

[www.ncbi.nlm.nih.gov]

This has some points on the stoppage of AOC.

Smackman:

That is good that you had no problems, perhaps most people don't but there are many that do have problems. In fact, we have had several posts from people who have had a stroke after stopping AOCs. I myself coughed up some blood clots after stopping Coumadin, this happened a couple of weeks after the stoppage, I was very lucky, so it can happen. I don't know what you do about it, seems like you are dammed if you do and dammed if you don't. I wonder if those that do have the stroke after stoppage what other meds are they on.

Here's another link.

[www.ncbi.nlm.nih.gov]

One question I have is does it matter if you're not still in AFib? Or is this not a problem if you're in nsr? Whether the hypercoagulate state causes stasis of the blood on the laa faster and thus when you go back into nsr you get the stroke, or something else that's nothing to do with that?



Edited 1 time(s). Last edit at 04/15/2019 04:38AM by Brian_og.

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Brian_og
Here's another link.

[www.ncbi.nlm.nih.gov]

One question I have is does it matter if you're not still in AFib? Or is this not a problem if you're in nsr? Whether the hypercoagulate state causes stasis of the blood on the laa faster and thus when you go back into nsr you get the stroke, or something else that's nothing to do with that?

Did I read the data correctly that 16 of the 719 stroke patients studied were "NOAC withdrawal"? Fifty-seven (57) WERE on NOACS.

Other factors seemed to be more significant (almost 1/3 had high blood pressure).

I don't see how this study concludes that Eliquis produces a state of hypercoagulation?

Edited to add: Read further and see that study concludes the strokes suffered by those withdrawing from NOAC was more severe.



Edited 1 time(s). Last edit at 04/15/2019 10:27AM by katesshadow.

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katesshadow
I don't see how this study concludes that Eliquis produces a state of hypercoagulation?

Edited to add: Read further and see that study concludes the strokes suffered by those withdrawing from NOAC was more severe.

It doesn't conclude that, and the association with stroke severity is weak. Nothing can be concluded from this study. There is no cause and effect shown, the sample size is tiny, the confidence interval is ridiculously wide, the p value is unimpressive, and the possible confounding factors and selection biases are numerous.

I think people should be careful about drawing conclusions from studies showing that strokes happen to people who discontinue anticoagulants. That finding is not a surprise.

I was on 10mg Xarelto per day for 6 months following my Watchman procedure, then switched to baby aspirin. At the six-month follow up visit, I asked Dr. Natale's N.P. what the procedure was for stopping Xarelto, and did it have to be done gradually. The answer: "No. Just stop it."

--Lance

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Carey

I don't see how this study concludes that Eliquis produces a state of hypercoagulation?

Edited to add: Read further and see that study concludes the strokes suffered by those withdrawing from NOAC was more severe.

It doesn't conclude that, and the association with stroke severity is weak. Nothing can be concluded from this study. There is no cause and effect shown, the sample size is tiny, the confidence interval is ridiculously wide, the p value is unimpressive, and the possible confounding factors and selection biases are numerous.

I think people should be careful about drawing conclusions from studies showing that strokes happen to people who discontinue anticoagulants. That finding is not a surprise.

From the link provided:

"Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes."

Not saying I agree with it, but that was the wording used. I did not draw that conclusion myself. In fact, I guess I wasn't clear in my post, but I was actually questioning their methods.



Edited 1 time(s). Last edit at 04/15/2019 01:19PM by katesshadow.

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katesshadow
From the link provided:

"Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes."

Not saying I agree with it, but that was the wording used. I did not draw that conclusion myself. In fact, I guess I wasn't clear in my post, but I was actually questioning their methods.

I understood you weren't drawing conclusions and were in fact questioning the study. I think for them to reach that conclusion based on 16 patients is a real overreach. About the only conclusion warranted is the usual "more study is needed."

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Brian_og
Here's another link.

[www.ncbi.nlm.nih.gov]

One question I have is does it matter if you're not still in AFib? Or is this not a problem if you're in nsr? Whether the hypercoagulate state causes stasis of the blood on the laa faster and thus when you go back into nsr you get the stroke, or something else that's nothing to do with that?

Brian, when I coughed up blood clots a couple of weeks after stopping Coumadin I was not in AF, in fact I had very few episodes of AF during that time which was about 15 years ago.

Liz

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Elizabeth
Brian, when I coughed up blood clots a couple of weeks after stopping Coumadin I was not in AF, in fact I had very few episodes of AF during that time which was about 15 years ago.

Coughing up blood isn't going to be relate to afib. More likely a respiratory infection.

sorry could not find my original info but it def stated that strokes can happen when you stop taking NOACs, a sort of rebound effect. I am wondering if, in that case, one would be safer to add Nattomax or similar product while stopping NOAC

anneh - Here are links to past posts on nattokinase so you know about the reliable form, NSK-SD. Nattokinase would be my choice for when you stop using an Rx anticoag because the NK is well-known to help prevent the clot formation. (unless you are soy sensitive)...then you can consider Lumbrokinase which is also highly effective.

It's also important to routinely do the labs that help identify predictors of what can contribute to clot formation... ie, inflammation - CRP, fibrinogen, etc...... there are several posts on "clot risk" etc that list the labs and details.

I have first-hand experience with clot formation after going off warfarin after my first ablation in 2003. As directed, at 90 days post ablation, I stopped the warfarin and resumed my former regimen of nattokinase. Then at 103 days, I went into Afib... and was cardioverted the following day. All was fine. Right after that, and back then, it was required to have a spiral CT scan of the heart. While I received a good report on the CT scan, when I received a copy of the results for my files about 6 weeks later, I saw there was a notation about a clot formation in the LAA. I called the EP nurse to verify and learned that - yes... at that time there was a clot in the LAA.... but apparently going back on the nattokinase dosing that I had done for years prior to the ablation had 'saved the day' for me as I was alive and well.

That experience reinforced the confidence I had gained from learning about the efficacy of nattokinase from Ralph Holsworth, DO (nattokinase expert) who had helped me understand the properties NK and why it was important for anyone with a clot risk, such as an afibber, to keep the viscosity markers in a safe range. Dr. Holsworth's medical practice is in Woodland Park, Colorado. [www.topnpi.com]

I should also mention that in the Section called Conference Room Sessions, back in I offered two very detailed reports on nattokinase in 2005 since I had such a positive experience with NK - Sessions 39 and 40.

[www.afibbers.org] - 39
[www.afibbers.org] - 40


Jackie


Clot Risk
[www.afibbers.org]

Lumbrokinase for Clot Risk Prevention
[www.afibbers.org]

Alternative to Cardiokinase
[www.afibbers.org]

Sticky, thick blood - risk of stroke or MI
[www.afibbers.org]

Silent Inflammation – Risk Marker for Stroke, Heart Attack & Much More
[www.afibbers.org]



Edited 1 time(s). Last edit at 04/20/2019 12:05PM by Jackie.

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Jackie
While I received a good report on the CT scan, when I received a copy of the results for my files about 6 weeks later, I saw there was a notation about a clot formation in the LAA. I called the EP nurse to verify and learned that - yes... at that time there was a clot in the LAA.... but apparently going back on the nattokinase dosing that I had done for years prior to the ablation had 'saved the day' for me as I was alive and well.

I don't think you can attribute being alive to the natto. I mean, after all, if the clot was there it was there, natto or not. Your day was saved solely by the fact that the clot didn't break free and get pumped out.

I'm also absolutely appalled that they detected a clot in your LAA and did nothing about it. That's mind boggling. The minute they saw it they should have been calling you in and putting you right back on warfarin, and then monitoring the clot until it was fully resolved.

Carey:

. The anticoagulants.stop new clots from forming, but doesn't your own body dissolve a clot once it is formed? I will have to say that Shannon had a stroke after his Watchman and he said he was on a natural anticoagulant, I think he said it was Nattonkinase. Of course as Jackie says you need to have the necessary tests of your blood to know how clots can affect you.

Liz


.

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Elizabeth
The anticoagulants.stop new clots from forming, but doesn't your own body dissolve a clot once it is formed? I will have to say that Shannon had a stroke after his Watchman and he said he was on a natural anticoagulant, I think he said it was Nattonkinase. Of course as Jackie says you need to have the necessary tests of your blood to know how clots can affect you.

Yes, anticoagulants only stop clots from forming or enlarging. They don't dissolve anything, and I'm pretty sure that includes natto.

Shannon's stroke was due to an entirely unrelated issue. He had an undetected leak in his LAA closure device.

Liz - Carey - At the time when I reported my news here, Hans thought that more likely, it was the effect of the electrocardioversion that promoted the clot formation. Especially, since prior to the ablation, for several years, I had endured very lengthy bouts of AF... often lasting 24 hours or more and the NK had kept me clot free... probably aided by my low platelet count as well.

In my later discussions on the topic with Dr. Holsworth, he related the efficacy of NK on lung clots of a former patient who was on long-term warfarin and who was able to transition off safely and successfully to NK. The NK studies do indicate the successes in lysing clot formation... and I always made sure the other relative lab markers were always in the safe range as well.

Nattokinase does lyse clots by degradation of the fibrin component in the clot. Following is one of the newer studies... lots in the archives on this topic. CR Session 39 on Nattokinase goes into detail about the efficacy of NK for this purpose... [www.afibbers.org]

It's worth reading there to understand the actions and benefits of NK

Jackie

Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease
Int J Mol Sci. 2017 Mar; 18(3): 523.
Published online 2017 Feb 28. doi: 10.3390/ijms18030523
PMCID: PMC5372539 PMID: 28264497
Yunqi Weng,1 Jian Yao,1 Sawyer Sparks,2 and Kevin Yueju Wang2


NK can break down blood clots by directly hydrolyzing fibrin and plasmin substrate, converts endogenous prourokinase to urokinase (uPA), degrades PAI-1 (plasminogen activator inhibitor-1), and increases tissue plasminogen activator (t-PA) which supports fibrinolytic activity (Figure 3: Mechanism of action) [2]. Unlike common fibrinolytic proteases, such as t-PA and uPA, which can produce various side effects such as bleeding, NK exhibits little to no side effects. Studies also indicate that an oral administration of NK can be absorbed by the intestinal tract [3,4]. NK exhibits strong fibrinolytic activity after intraduodenal absorption. These characteristics make NK a versatile and potent fibrinolytic enzyme that can be used to combat blood clots.
[www.ncbi.nlm.nih.gov]

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Jackie
Liz - Carey - At the time when I reported my news here, Hans thought that more likely, it was the effect of the electrocardioversion that promoted the clot formation.

Possibly. Cardioversions have a stunning effect on the heart that can reduce blood flow in the LAA. That's why the standard advice is to continue anticoagulants for a month following a cardioversion.

G'day Jackie,
Those Conference links you put up on Nattokinase in April 2005 brought the memories flooding back! Great research times for all of us back then. Thanks to you and that Conference post that's when I started eating natto food every second day. Have now been afib free ever since.

As you know I tried to get other afibbers to seriously try natto food but after all this time only one other afibber has taken it seriously....”Colindo” (Colin).

I believe Colin is now a year afib free after coming from an afib burden of several attacks a month and eats natto food every second day like me.

Colin and I regularly swap research notes on natto food. I'm in Australia and he is in New Zealand across “the ditch”. We both have a suspicion it is the large dose of the phytoestrogen Genistein in the natto food that is behind out success. From PubMed Genistein reduces arterial stiffness and down regulates and alters many ion channels in the heart. Genistein is a tryosine kinase inhibitor.

We are both about to experiment with roasted soy beans too as they have greater amount of Genistein than natto food.

I will do a separate post with all the research on natto food in the near future.

Here is some of the research on Natto food and Genistein for those interested:

[www.ncbi.nlm.nih.gov]

[www.ncbi.nlm.nih.gov]

[www.ncbi.nlm.nih.gov]


Many thanks again Jackie.

Dean

Quote
Dean
G'day Jackie,
Those Conference links you put up on Nattokinase in April 2005 brought the memories flooding back! Great research times for all of us back then. Thanks to you and that Conference post that's when I started eating natto food every second day. Have now been afib free ever since.

As you know I tried to get other afibbers to seriously try natto food but after all this time only one other afibber has taken it seriously....”Colindo” (Colin).

I believe Colin is now a year afib free after coming from an afib burden of several attacks a month and eats natto food every second day like me.

Colin and I regularly swap research notes on natto food. I'm in Australia and he is in New Zealand across “the ditch”. We both have a suspicion it is the large dose of the phytoestrogen Genistein in the natto food that is behind out success. From PubMed Genistein reduces arterial stiffness and down regulates and alters many ion channels in the heart. Genistein is a tryosine kinase inhibitor.

We are both about to experiment with roasted soy beans too as they have greater amount of Genistein than natto food.

I will do a separate post with all the research on natto food in the near future.

Here is some of the research on Natto food and Genistein for those interested:

[www.ncbi.nlm.nih.gov]

[www.ncbi.nlm.nih.gov]

[www.ncbi.nlm.nih.gov]


Many thanks again Jackie.

Dean

I would like to try the Nattokinase (I don't think I could eat the Natto , but I am currently taking blood pressure medication (a calcium channel blocker and a beta blocker) . Is is safe to take Nattokinase with these medications?

Hi Liz,

As Carey noted above my stroke was from a very different mechanism 11 months after my LARIAT LAA Ligation procedure, back before Watchman was FDA approved ( and thus I do not have Watchman device) but I did have both a LARIAT procedure, plus I had an Amplatzer Duct Occluder-2 vascular plug installed to plug the central ‘pucker’ very late leak in my LARIAT procedure, even though my three initial 2D B&W TEE scans had seemingly confirmed that my LAA was entirely sealed with no sign of any leaks over the first 2.5 months post LARIAT.

Then ... a big unexpected surprise at nearly the 11 month mark after LARIAT ... when I suddenly started talking gibberish one Saturday morning while I was writing a new issue of The AFIB Report newsletter at home!

I had the very dubious honor of being the first American to have a documented embolic event from a very late re-opening LARIAT leak. Dr Natale, who had me fly straight to Austin from Sedona (via Phoenix) the very next day after my stroke, had heard of a women in eastern Europe (think it was Romania if I recall correctly?) who had had a very similar late reopening leak at approximately 10months after her LARIAT ligation, and just three weeks before my stroke.

So when I called Andrea from the ER in Cottonwood AZ telling him about the very surprising stroke, he was sure I was having the same rare event that the Romanian lady had recently suffered as well, as she was the very first report in the world of an embolic event from a late re-opening LARIAT leak that was large enough to be dangerous (my leak was 5mm in diameter, and since my case plus the Romanian lady and a handful of others back then in early 2014, we learned that any leak from 3mm diameter, or larger, must be plugged ASAP we learned from mind, and the other handful of rare late re-opening leaks that had occurred before Dr Natale confirmed that we need to do more frequent TEE tests during the first year post LARIAT, and that all such post LARIAT TEEs should be the then new 3-D Color Doppler TEE and not just the regular and less clear 2-D B&W TEEs in order to successfully detect the smaller central pucker type leaks that can happen from a LARIAT install.

Note; that the Watchman/Amulet LAA Occulsion device can have leaks too, but anything from 5mm and smaller are typically not considered a problem as no embolic events have ever been reported from these type of ‘edge leaks’ around the perimeter of the Watchman/Amulet device. Thus such Watchman/Amulet leaks would have to be much larger, and fortunately are quite rare, in order to pose a real risk that requires plugging.

Prior to my stroke, I had been taking 300 mg /day in three 100mg divided doses every 8 hours of the Allergy Research Groups respected NSK-SD form of Nattokinase the prior 6 weeks before my stroke, as I had run out of Cardiokinase that I had taken daily at the exact same dosing for years after getting green light to stop my coumadin after my index ablation.

In any event, in my case the Nattokinase failed to prevent me from having a stroke. But I recovered so well that I truly had dodged a bullet for sure!

The two areas in my frontal lobe where the two clots wound up were right where one would expect debris from the LAA to wind up. Alas, the central ‘gunny-sack’ type LARIAT leak was big enough in my case, at 5mm diameter, to re-establish communicative blood flow between my left atria and my, by then, only small remnant pouch left over from my LARIAT’s now partially-ligated LAA.

But the good news, in addition to my essentially total and rapid post-stroke recovery, was that we all learned from my experience that all future LARIAT procedures should require at least three or four evenly spaced TEEs during the first full year after LARIAT ligation to be able to detect such later developing leaks in the ligated LAA soon enough to be able to be able to avoid an embolic consequence by plugging any leaks equal to, and greater than, 3mm in diameter.

Plus, we learned that all future LARIAT procedures should use the more resolving 3-D Color Doppler TEE test, rather than use the less resolving B&W 2-dimensional TEE that had been standard of care for all earlier LARIAT procedures before my experience caused a revamp in these two key steps that were added universally after Dr Natale got the word out.

So, at least some greater good for the field as a whole occurred too, beyond just my own experience. And from all the improvements made to what is now a third generation LARIAT device itself, plus the major improvements from those early days when I had my LAA ligation in our understanding of how to perform the procedure, it is significantly safer, and there really hasn't been any appreciable strokes that have been reported in the last few years from modern LARIAT procedures. Making it a very viable alternative for LAA-Closure too. Especially for those who may have both active LAA source AFIB/Flutter triggering that the ligation approach can eliminate, as well as minimizing future stroke risk.

Cheers!
Shannon



Edited 4 time(s). Last edit at 04/25/2019 03:53PM by Shannon.

Hello Dean - good to see you posting. Glad you and Colin are benefiting from the soy intake... esp. from the genistein benefits aspect. Even if I could get a quality natto food here, I was told to avoid soy because of a thyroid problem which has since resolved with supplemental iodine. There is a huge number of benefits from genistein so you both should remain very healthy.

I'll be interested in what your continuing research indicates.

Best to you,
Jackie

Shannon:

Thank you for the clarification, I had thought it was the Watchman that you had, sorry. I had remembered that you were on nattokinanse and it didn't protect you, I have doubts that in some situations nothing can protect against a clot.

Liz

Quote
Carey

Possibly. Cardioversions have a stunning effect on the heart that can reduce blood flow in the LAA. That's why the standard advice is to continue anticoagulants for a month following a cardioversion.

Back then, it was warfarin... and I was not told to go back on it... probably because I had resumed the NK.

.....but when, years later, the AFib revved up again as flutter, I wasn't on any Rx anticoag and had numerous ECV's... but was never told to resume taking an anticoagulant and I just continued on with my daily NK routine. The Eliquis Rx began as I prepared for ablation #2 and subsequently, #3

Jackie

Quote
Jackie
Back then, it was warfarin... and I was not told to go back on it... probably because I had resumed the NK.

.....but when, years later, the AFib revved up again as flutter, I wasn't on any Rx anticoag and had numerous ECV's... but was never told to resume taking an anticoagulant and I just continued on with my daily NK routine. The Eliquis Rx began as I prepared for ablation #2 and subsequently, #3

It's probably because it's only fairly recently that they've recognized that cardioversions have a stunning effect and they've started recommending ACs for a few weeks following. I know I was cardioverted a couple of times back in the 2010 timeframe and nobody mentioned it then either. I think very few EPs would skip such a recommendation because of NK.