Migraine, ITP, Sticky Platelets, Aspirin. SUCCESS!

Ellen started taking aspirin and stopped having frequent migraines!

Ellen has had frequent migraines since childhood, which have increased in frequency since her ITP was diagnosed ten months ago. Her headache frequency has been at least 90% over the last 300 days, at least 95% over the last 100 days, and exactly 100% over the last 60 days..... until five days ago.

On a previous thread, Sandi mentioned the possibility of antiphospholipid syndrome causing migraine headaches and suggested testing for antiphospholipid antibodies (which Ellen has not yet done). I began doing my own Google research, and found that platelet aggregability - sticky platelets - is believed by some to be a central factor in migraines. This hypothesis has been around since 1979! It is even hypothesized that migraine triggers act by making platelets more sticky.

On a hunch, I suggested that Ellen start taking aspirin to make her platelets less sticky. Her headaches occur mostly during the wee hours of the morning, so she began taking one adult aspirin each night at bedtime.

The first night went by without a migraine, and we were surprised, as Ellen has woken with a headache each of the previous 60 mornings.

The second night... no migraine. Could it be true?

The third night... no migraine.
The fourth night the same.
OMGosh!!!

Now the fifth night has passed without a migraine. I can say with almost certainty that this is not a random occurrence. Even using the lower 90% headache frequency, the probability of five nights headache-free randomly occurring is .00001, or one thousandth of one percent!

Has anyone else tried this approach?

Next steps:
Check prothrombin to make sure clotting okay
Get APAs tested.
Keep counting the days!

That's amazing, Rob. I don't get migraines, but at one point I was getting frequent stabbing head pains. Those also stopped when I started taking aspirin. I think there is a lot more to platelet aggregation and headaches than we realize.

This was the very first article I read that made me look further years ago.

www.ncbi.nlm.nih.gov/pubmed/12565721

You should talk to her doctor about this and maybe try the usual therapeutic dose aspirin (89 mg's) to see if a lower dose will work.

Sandi, I cannot believe how often you are right! Ellen has started bruising again - four new bruises today - so she probably needs to drop the aspirin for a few days, then try baby aspirin, like you suggested. She will go for a platelet count today, of course.

My understanding is that aspirin does not normally influence platelet count, only platelet stickiness. The effect of aspirin on individual platelets is permanent, so new platelets have to replace old ones before the effect will fully wear off, which takes about a week.

Time to slow down and find the right balance between bleeding and migraines. I remain very optimistic we are on the right track.

Thanks for the link. My mother has vascular dementia (and a history of migraines!) but not ITP. I doubt that anyone tested her for APAs. I could not get to the full text version of the article. Do you have it, and if so, does it mention APS anywhere? It seems strange there was no mention of APS in the Abstract. Interesting to note that splenectomy increases the rate of progression of vascular dementia... one more reason to keep it as a last resort at most.

Rob:

I don't have the full version of the article. That article was about how platelet microparticles can cause TIA's and dementia...not about APS. Separate thing. There are a lot of articles about PMP's and ITP. Most people with ITP have elevated PMP's. If you add APS into the mix and/or splenectomy, I'd imagine the risks would be greater.

I have a normal platelet count and bruise with the 89 mg's, so that in itself is not alarming. However, since your wife is fairly new to this and not technically in remission for very long, you'll want to be careful messing with aspirin. I'm supposed to keep my counts above 50k in order to continue to use aspirin.

It would be a heck of a coincidence if your Mom had APS, so I doubt that. But, anything is possible!

I just came across this one. I had it bookmarked.

www.medpagetoday.com/MeetingCoverage/ASHHematology/12103

The only OTC remedy that ever works for me to stop a migraine in progress is a caffeinated beverage with a headache powder (acetaminophen, aspirin, and caffeine). The problem with that for me is that I then have stomach pain for days, and I bleed like crazy with every little nick. (And I don't even have ITP.) I am thankful that I rarely have migraines nowadays, and they rarely progress to headache. (They ruin my vision, however, and I can't read or drive during one. If I had them every day, I couldn't work.) Nurse husband tells me those powders, and aspirin abuse, kill people through GI bleeds. In my line of work, I, too, have seen a really bad case of that. If she's going to be on an aspirin regimen, she should take the coated type and take it with food to protect her GI tract. It would be terrible to find the magic bullet for the migraines only to develop stomach ulcers. Hope this ultimately works for her.
Norma

Thanks Norma. She will definitely switch to enteric coated baby aspirin. For her I think the key is taking it as a preventative rather than using it to try to stop a migraine in progress. Hopefully, this will work at the lower dosage.

It is remarkable how different individual reactions can be. My grandfather took one headache powder every day from his late twenties until he died at 96, without any adverse effects except living to be very old.

I know that aspirin will not prevent migraines for everyone, but maybe for some.

Meanwhile, six days and counting!

Sandi, thanks for the link.

Prevention's always better than reaction. If she sticks with the baby aspirin dose, and it works, let us know. I'd certainly take one a day of it would keep the migraines at bay.
Norma

It has been a month since Ellen began taking aspirin, so time for a report.

The good news is that the aspirin strategy has really worked. Migraines are 85% less frequent, and much less severe.

We have had to refine the strategy a bit. Since the headaches would begin in the early morning hours, we found that if Ellen took aspirin too early it didn't work. She now sets an alarm for 2:00 am to take an aspirin, and this gives optimum results. She did not try baby aspirin, since regular strength did not work while it was wearing off.

The bad news is increased bruising, and Ellen developed a subconjunctival hemorrhage (bleeding in the white of her eye) today, but it is not too serious. Will watch closely, and also do platelet counts today. No other bleeding problems, though. She will not give up the aspirin unless she really has to... it has been life-changing for her.

Just my guess but I'd say that if the taking of the aspirin is time dependent then it doesn't sound like she has APS. The aspirin will work on the platelets for the whole of their ten day life so it shouldn't matter whether it's taken in the morning or the evening.

Has Ellen been tested for APS? That should be done before treating with aspirin.

Ann, I like the way your mind works regarding the time-dependence. I wonder, though, how short platelet life becomes during full-blown ITP; no, probably not hours, but certainly shorter than 10 days.

Ellen has not been tested for APS. She has no symptoms, but she should probably be tested anyway.

I found an old article that supports what we found. This study was originally presented in 1978 and published in 1980! The authors' interest lay primarily elsewhere, and they apparently dropped it; it does not look like anyone ever picked it up.

onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.1980.hed2001013.x/abstract

Platelet Antagonists in Migraine Prophylaxis A Clinical Trial Using Aspirin and Dipyridamole [Persantine]

Brent E. Masel M.D.,
Andrew L. Chesson M.D.,
Bruce H. Peters M.D.,
Harvey S. Levin Ph.D.,
Jack B. Alperin M.D.

Article first published online: 22 JUN 2005

DOI: 10.1111/j.1526-4610.1980.hed2001013.x

SYNOPSIS

The platelet hyperaggregability of the migraine population has lead us to postulate that platelet antagonists might be effective in migraine prophylaxis.

A double-blind cross-over study of aspirin, 325 mg BID, combined with dipyridamole, 25 mg TID, compared to placebo and pretreatment conditions was undertaken. Platelet aggregation studies were done during the three month active medication and placebo periods.

In patients with platelet hyperaggregability significant improvement occurred in headache frequency, intensity, and limitation of activity with no change in headache duration. Regardless of platelet aggregability, the 25 patients comprising the total sample significantly improved as compared to placebo. Sixty-eight percent of the patients tested reported subjective improvement while taking the active medication. No side effects related to the medication were reported and no patients, including those who withdrew from the study for other reasons, reported worsening of headache while on the active medication.

Although the significance of platelet hyperaggregability in migraine patients, and the pharmacological effect of aspirin and dipyridamole on this, is unclear, these medications may have potential as a method of migraine prophylaxis.

I had no APS symptoms (other than ITP) but still had the antibodies. I'm using aspirin prophylactically per my doctor although there is no evidence that it does anything. No harm in having her tested, in fact, I'd insist on it.

I've been tested for APS three times so far. Always negative but I ask to be tested every now and then. I shall ask again when I next see Dr Provan in May.

Hi rob

I just thought I'd add this thought on platelet lifespan - in November last year I had an indium platelet scan. My count was hovering at around 100 and the scan results showed that my platelets "lived" for about 26 hours. Just thought you might be interested to know it can be as short as that

Thanks Kat, that's really interesting!!

Ellen's counts are low 30s now, compared to your 100k, so her platelet life might be as low as 9 hours with a half-life of maybe 5 hours. Lots of assumptions, of course, but this at least makes it plausible for the aspirin effect to be a sticky platelet issue after all, even though it is timing dependent. In fact, if the platelet half-life is short enough it might actually explain the aspirin timing being an issue.

Have you spoken to her doctor about this yet? Please do!

She has a regular appointment with her neurologist for her headaches nest week, and will bring him up to date and also discuss the possibility of APS as it may be associated with headache. If he doesn't test for APS then she will ask her hematologist.

If she does have APS, how would it change her treatment, since she already is taking aspirin daily? Heparin instead?

Meanwhile, no missed time from work at all. Previously, she was having to use up her vacation time (PTO) to make up for missed work, and was still coming up short on her paychecks. We are looking forward to some beach time this summer, and she may even get to visit her daughter in Spain. I dare anyone to try to talk her out of taking aspirin without offering a better alternative!

Rob:

If a person has the APS antibodies, they are not usually treated with blood thinners until they experience a clot. The only mode of prevention is aspirin and according to research, there is no proof that it prevents anything. In Ellen's case it seems to prevent migraines and that is fantastic. But! With her counts so unstable, you need to be careful. I was told to take the 89 mg aspirin tablets and am not supposed to take them with counts below 50k.

Low platelets and blood thinners are difficult to balance and it should be done with a doctor's approval and careful monitoring.

Rob, just wanted to say that I am so so happy for your wife. great story and good information!
I've had migraines and they are miserable, debilitating. Mine were occasional then started getting worse in 2012, more frequent and with flashing auras- bad. No way could I drive or work. Plus they were not completely going away between attacks- a constant dull headache.

At the time I was on prednisone and taking Zantac daily for the acid reflux/heartburn that comes with pred. The active ingredient is ranitidine. I read online that a rare side effect is migraines. Of course if its rare I'll get it! I stopped taking that stuff and the worst migraines went away. I still have an occasional headache and morning headache but no more flashing auras.

Katsim wrote: I just thought I'd add this thought on platelet lifespan - in November last year I had an indium platelet scan. My count was hovering at around 100 and the scan results showed that my platelets "lived" for about 26 hours. Just thought you might be interested to know it can be as short as that

That's weird. My count was 66 when I had the test and my platelets life was 2.5 days.

The test is actually a good way of being sure that you do have ITP. When they have done studies with the test they have found a few people whose platelets life span is the normal 9 or 10 days and then had to look for a new diagnosis as they did not therefore have ITP. I found the test to be reassuring on that front.

I would think that the platelet life span would be different for everyone with ITP. Due to the volume of antibodies, the production and destruction rates would vary for each individual.

It wouldn't be normal though. Normal life means not ITP.

Sandi wrote: Rob:

If a person has the APS antibodies, they are not usually treated with blood thinners until they experience a clot. The only mode of prevention is aspirin and according to research, there is no proof that it prevents anything. In Ellen's case it seems to prevent migraines and that is fantastic. But! With her counts so unstable, you need to be careful. I was told to take the 89 mg aspirin tablets and am not supposed to take them with counts below 50k.

Low platelets and blood thinners are difficult to balance and it should be done with a doctor's approval and careful monitoring.

Ellen’s counts are gradually but steadily declining. She has never gotten low enough for any bleeding, so we don’t have any idea whether she will level out at a reasonably safe level or if she will need to have another dexamethasone pulse. She responds very well to that treatment, and afterward her platelets decline slowly from their peak.

The conventional wisdom around here is not to focus on the counts, but pay close attention to the symptoms, and we are watching VERY carefully for symptoms. So far there is some mild bruising and nothing more. Obviously, she will show symptoms at a higher count than if she were not taking aspirin, but I think the principle still holds true.

As far as doctors’ approval and careful monitoring are concerned, I will be surprised if the doctors don’t go ballistic. It is too much to expect (though hope springs eternal!) that a doctor will think this far outside the box and agree to an ITP patient with platelets in the low thirties preventing migraines with aspirin. [Isn’t it ironic that treating headaches with aspirin could be controversial!]

It is also conventional wisdom around here that sometimes the patient is in a better position than the doctor to decide what is best for herself… and sometimes it is best not to follow medical advice. That is for Ellen to decide. But remember, the alternative is waking up nearly EVERY MORNING with a migraine, some days requiring multiple self-injections which don’t always work.

I do hope we can get the doctors to work with us on this. It would be safer if a warfarin-type blood thinner could be used (if it would do the job), as it would be reversible in the ER using vitamin K. The neurologist is her best bet, and she sees him on Wednesday.

Sandi, I know that you are uncomfortable with this, and I think I understand your perspective. I respect your opinion greatly. Please, if I am missing something here let me know. The same is true for the rest of you platelet gurus out there. Please jump in if you have something to add.

Ann wrote: It wouldn't be normal though. Normal life means not ITP.

No, I wouldn't think it would be normal, just different.

Rob:

Being one of those people who also does what I think is best even though I go AMA, I do understand. I also completely understand your reasoning. However, watching symptoms of low counts vs watching symptoms of low counts + aspirin are two different things. There are now two clotting mechanisms involved. A hematologist who was familiar with clotting disorders would probably work with you on this, but you're right, most would not. Maybe Ellen's neurologist will be able to guide you but if not, try to find a hematologist who can.

Watchful waiting has worked like a charm, with platelets steady at 32-34k for a long time now, but this level is really too low if Ellen is going to take aspirin for her migraines.

Ellen saw her neurologist this morning and told him that aspirin was preventing her migraines. He was very happy. Then we told him that her platelets were now at 32k. He was not so happy. Basically, he said he would have to defer to the hematologist.

Ellen saw her hematologist this afternoon. Between Ellen’s appointments the two doctors had met to discuss Ellen’s case! The hema was, as expected, against the idea of taking aspirin with such low platelets, but begrudgingly allowed for baby aspirin with platelets above 30k. Unfortunately, baby aspirin does not get the job done. Would need platelets at 50k to agree to full strength aspirin.

Then we discussed strategies to keep her platelets at least above 50k so that Ellen can take one full strength aspirin: splenectomy (no way!), dexamethasone pulse (unpleasant; might get 60-90 days, then re-treat), long term steroids (bad side effects) and rituximab (immune-compromising, and lost time from work).

Hema stated that Rituxan is less immune-compromising than steroids. She is in oncology and is used to using rituximab frequently, and feels the risk is minimal as long as the patient has normal T-cells. She also has used Rituxan successfully to get another patient’s platelets high enough to allow aspirin use, to prevent clotting after a stent.

Lots of options, all with problems, but at least there are options. Tough decision.

Separate topic: we also discussed antiphospholipid antibody testing, and the hema said she could see no point in it, as it would not change Ellen’s treatment as long as there was no history of thrombosis. Hard to argue with that.

Rob16 wrote: Separate topic: we also discussed antiphospholipid antibody testing, and the hema said she could see no point in it, as it would not change Ellen’s treatment as long as there was no history of thrombosis. Hard to argue with that.

I agree, and this was one reason why my Hemo would never test me when I asked. However, knowing now that I have had the antibodies, if I needed to treat ITP, I would not consider TPO's or splenectomy as those raise the risk. I also would not be happy with counts that are too high. My Rheumatologist tested me prior to my Lupus diagnosis just to pacify me and when it came back with elevated Anticardiolipin Antibodies, that ended up clinching my diagnosis. Honestly, they don't like to test for that, but what is the harm? It just helps you to be more aware when making treatment choices. You don't treat APS unless you have a clot, but you may treat the ITP differently.

I'm so glad you discussed the aspirin with her doctors and they are trying to work toward a solution. Getting her counts up is a good idea. Rituxan is a decent choice at this point. I never got sick after I'd had it. You still have plenty of immune system left to tackle illnesses. As long as you don't mix it with steroids and splenectomy, it's not so bad. As you well know, every treatment has its pitfalls.

Sandi wrote: Rituxan is a decent choice at this point. I never got sick after I'd had it. You still have plenty of immune system left to tackle illnesses. As long as you don't mix it with steroids and splenectomy, it's not so bad.

Ellen's hema wants to combine Rituxan with high-dose dexamethasone. That seems to be the original protocol; she claims the combination is more effective, but I find nothing nothing that shows it is more effective than Rituxan alone (only that it is more effective than dexamethasone alone).

I also find nothing about adding dexamethasone increasing the risk or not. I understand that steroids suppress nearly all aspects of the immune system. Remember, Ellen works with AIDS patients at an infectious disease clinic.

Is there any evidence that adding dexamethasone increases the effectiveness of Rituxan without increasing the risk?

Hi Rob,

I'm not certain that there is any evidence that adding dexamethasone increases the effectiveness of Rituxan. Back in October when I had Rituxan, I stayed on 20 mg. Prednisone only because my counts were still quite low and my Hema did not want them to crash while we waited for the Rituxan to *hopefully* work.

Prior to having Rituxan, I did research on the drug and found that the typical protocol seems to be that patients are treated with steroids and Rituxan simultaneously. As you said, I found nothing to suggest that the combination is more effective than Rituxan alone.

I, too, was concerned about the immune system suppression primarily since I have a preschooler who brings home every bug going around. Both my Hema and Rheumatologist both reassured me that my immune system would be just fine. Both said that Rituxan only targets B cells, which leaves plenty of cells left to fight off the infections/viruses. My Rheumatologist also mentioned that he has treated many patients who are nurses, teachers, hospital technicians with Rituxan - and none of them have reported more frequent illnesses or infections.

Since October, I've had one bout with bronchitis that cleared up quickly after a course of antibiotics. I certainly can't say that I've had more illness than usual.

I know this decision is tough - I agonized over it for quite a while. In the end, it does appear Rituxan worked for me as my platelets are now holding steady at 120. It certainly seems like a good next step for Ellen. Good luck with your decision.

~Lauren

Rob:

It would be scary to be working with AIDS patients. Does Ellen work with needles? I don't know how far her risks go. You know as well as I do though that if contamination occurs, HIV can, and does, affect people with a healthy immune system. You'd need to discuss those risks with her doctor because yes, she would be somewhat immuno-compromised.

You're right, there isn't any data re: adding Dex to Rituxan to make Rituxan more effective. I think it would help the counts to respond faster, but don't think Dex would necessarily cause Rituxan to last longer unless Dex was the one responsible for remission. You'd have no way of knowing which caused it though. Due to the nature of her job, I'd hope that her doctor would be open to treating without Dex if that's what you decide.