Various Paths thrombocytopenia (not idiopathic)

After my diagnosis in September I have been pondering on why I got this disease. I always thought idiopathic was lazy way of getting out of the problem. I have been Reading up on the literature on platelet creation and platelet destruction

Whatever Iam writing here is from a novice and take it with a grain of salt

First we will have to understand Megakaryocytopoiesis. Basically megakaryocyte get formed by bone marrow, they have receptors on these cells. Thrompoetin(TPO) harmone which is produced in the liver combine with the receptors and finally produce the platlets.


In the process described above let us figure out various ways of getting ITP-

1. You dont have enough necessary Thrombopoetin harmone secreted. You have a typical production problem. People with cirrhosis, liver issues dont TPO secreted, so this results in Thrombocytopenia. IF you dont have enough TPO secreted any auto immune treatments wont work, nplate\promacta might be the best altaernative here. Sometime people with liver issues do have enlarged splenes so spelenectomy might work since platlets produced are trapped by spleen.

Various ways of increasing TPO naturally are increased exercise since IL-6 helps produce TPO. Also TPO is secreted by the skeletal muscular system.
Stop drinking alcohol.



2. megakaryocyte are malformed or are not formed properly. You have a bone marrow suppression issue, this could also be a production problem. This situation is more serious because you could have other problems in this case like cLL\Cancer etc.

3. No production issues pure Auto immune situation were the platlets generated are tagged as foreign bodies and are destroyed by spleen. The question is why are the platlets tagged as foreign bodies.
One theory is Th17 cells and Treg cells are imbalanced and thus platlets are tagged for destruction. Natural ways to increase Treg cells is - Probitics, butyraid, Vitamin d3, vitamin a, Dha, b12, green tea extract. This is still pure theory experimentally TH17 or Tregs donot show abnormal levels in experiments with itp patients.


Various treatments on the lines of preference in this situation-
Predisone, Rituaxin, spelenectomy, promacta, nplate.

So the conclusion is people directly jump to point 3 when it comes to thrombocytopenia but it is not always the case. My take point1 is also very highly likely.

jay, seems like if one didn't respond to either steroids or IVIG then number 1 seems plausible. But if one does respond then 1 is not. Yes?

Well, the word 'idiopathic' isn't used any more. 'Immune' is. We've all wondered why. Why do people develop antibodies against thyroid? Why do people develop antibodies that destroy tissue? We're all in the same boat.

This is the best description I've seen. It's pretty old and outdated, but the mechanisms of action are pretty good explanations.

www.samizdat.com/itp.html

Hal - it's difficult to know for sure because no one really knows if they have destruction or production problems, or both. That's we all get to try the 'down the line' treatments until we find one that works. Antibodies can be responsible for both production and destruction, so idealistically, steroids would always work.

Hello Hal,

We cannot answer the question unless someone measures TPO levels on patients with low response to IVIG. Based on the discussion with my hema she said IVIG tries to trick the immune system into ignoring the platelets. So if IVIG cannot bring up platlet count then point 1 is plausible.

The best discussion on this was an article I found recently-

www.ncbi.nlm.nih.gov/pmc/articles/PMC2789970/

Some salient points-

- "absence of TPO or its receptor, the platelet count was reduced by 90-95%"

- "In the aplastic anemia patient, platelet production is reduced far below normal, fewer platelets and megakaryocytes are available to bind and clear TPO, and levels rise."

- "TPO levels are not significantly elevated in patients with ITP"

-"Platelet turnover rates are not appreciably elevated in ITP "

jayinchicago wrote: ... So if IVIG cannot bring up platlet count then point 1 is plausible.

Jay, yes that was my point. Also, the same is true for steroids.

Now that I've read your other thread, the situation more clear.

Some folks take IVIG and it does nothing for them. Likewise, some folks take steroids and it does nothing for them - which is my case. If both of those hold true then 1 is possible, perhaps even likely.

As I understand, your case is different. You respond to both but neither (alone) gives you a normal count. You have a 'partial response' with both.

Hope this helps...

That's why some doctors say IVIG and steroids are a treatment that also has a diagnostic role. The response may be short lived, but if there is a response, there is an autoimmunity issue.
Norma

Hello Hal,

Here is something to think about-
www.hog.org/handbook/section/1/understanding-how-blood-works


"About 70% of your body’s platelets float around in your bloodstream. The other 30% are stored in an organ behind the stomach called the spleen. Each platelet travels in the bloodstream for seven to ten days. Then, if it has not been used to make a blood clot, cells in the spleen and liver destroy it. Every day 200 billion new platelets enter the bloodstream to take the place of those that are used or destroyed."




My take is we could be barking the wrong tree after reading the above. Spleen is always destroying platlets anyway so what is all this Auto immune issue anyway?


www.ncbi.nlm.nih.gov/pmc/articles/PMC2789970/#R37

If you read the above link it is always a production problem. Even predisone increases the platlets according to the NIH file.
When you destroy the spleen for people with production issues platlets will survive.

This is why after Promacta and NPlate started increasing the platlet counts everyone started signing a new song that it is production and destruction.

Jay:

ITP is considered to be an autoimmune issue because many times, there are antibodies involved that target destruction and inhibit production.

Autoantibodies against platelet antigens are considered the diagnostic hallmark of ITP. In some patients, antibodies recognize antigens derived from a single glycoprotein; whereas in others, antibodies recognize multiple glycoproteins. Opsonization by antibody accelerates platelet clearance but can also alter platelet function and interfere with platelet production. Curiously, platelet antibodies are only detected in approximately 60% of patients. Failure to detect antibodies might reflect limited test sensitivity, undetected antigens, or additional mechanisms of platelet loss.

www.bloodjournal.org/content/113/26/6511.full?sid=8c7ef2e2-6124-4b2b-9ab8-2eb9dd71d8ef&sso-checked=true

The spleen does usually destroy platelets, but in people with ITP, that destruction is much faster. They don't get to live and circulate the full 7 to 10 days. As soon as they are produced, the antibodies attach and, thinking they are a foreign cell such as bacteria, they are marked to be destroyed in the spleen.

When I first began researching ITP in 1998, it was generally known that ITP only caused destruction of platelets. We were all surprised when new research proved that production was also a factor. That was only 8 to 10 years ago, I think.

Jay, not following your point. That article (second link) mentions the 'Harrington' experiment which demonstrates clinically that it is a destruction issue.

See also (especially about immuno-globulins)
en.wikipedia.org/wiki/Harrington%E2%80%93Hollingsworth_experiment

Also, consider the case when one's count goes into the normal range when treated with IVIG (or steroids alone). As I see it, that is a strong indicator that person does not have a production problem.

For example, my count went to 314 (one week) on IVIG. How could I have a production problem? I don't think that sort of response is uncommon. Some have a full response to steroids.

Perhaps it is all the negative logic that is confusing you. LOL, there is nothing simple about ITP !

Hello Hal,

What makes you think Predisone, IVIG, Rituximab and all others do not help in production.

Spleen destroys platlets that we know for sure.

We also know that tests Sandi mentioned are highly unreliable, why dont you get tested for platlet antibodies.

I would like myself tested for platlet antibodies?

What is the test?

Iam a novice and Iam just asking simple questions.

I was tested for anti-platelet antibodies. The result was that the antibodies were critically high. Having that information did not change the course of treatment in any way, so it was basically useless. I still had to go through with the treatment line-up and find what worked. As far as I know, they do not routinely test for the antibodies that affect production. That is only done in a lab for research purposes.

It is generally assumed that most people have both problems.

The way my Hemo described ITP to me there is not a production issue. My body is destroying my platelets, since high doses of steroids and IVIG while in the hospital caused a count spike (sadly temporary). Interestingly in the no so distant past I would routinely donate platelets. I was always able to give a double or triple donation due to high platelet counts. Wish I could get some of those back now.
The search is now on to find the treatment for me that will stop my immune system from destroying the platelets that I am making.
Currently doing Rituxan infusions.

D Mann - There really isn't any way to know if production is a problem or not. Many hemo's rely on the bone marrow biopsy results for that, but it doesn't give that information (they only think it does).