The Killing of Platelets

My doctor is sure I have ITP. So, what does that mean? It means he's sure my immune system is killing my platelets. I'd like to take a step back.

Let's say my low count is due to killed platelets.
Is there anything other than immune system cells that can kill platelets?
I'm thinking the answer is yes.
If so, then how do we know it's the immune system? It seems that treatment successes (splenectomy and others that go after the immune system problem) indicate it could be the immune system. But the stats don't support that always being the case. For me, prednisone makes it worse, IV/IG had no impact, other IV treatments are ineffective, etc. So, now I'm thinking about what else could be destroying my platelets... or is my immune system so powerful that nothing holds it back?

I'd like to engage in a discussion of logic. To build a fault tree, so something. To figure out what else could be getting after my platelets or to better understand why they are signalling immune cells to come get them. Are my platelets mutated for some reason? I sure noticed they know how to count them, but can we take a look at them and compare them with normal platelets? Do mine even look normal? I don't know.

Let's talk. Let's explore.

You could get an Indium study that would tell you where in your body the platelets were being killed - spleen or liver. That would give you more clues about the mechanism that is killing them.
Erica

Erica,

I'll check into that. I had not heard of that being possible, so thank you.

Edward:

Okay. It's late, but let's go.

First of all, if your doctor suspects that it's ITP, then most likely it's ITP. If that is the case, then it is autoimmune and the platelets are affected. However, they can be affected in several ways. There are antibodies that affect destruction and antibodies that affect production. As of now, there is no way to determine which way your platelets are affected; there just isn't an accurate, practical test for that. They can test for antibodies that affect destruciton, but the test doesn't really tell you much as far as how to treat or how your particular case will go. I'd be willing to bet that most people have trouble with both destruction and production, but the percentages of each could vary from person to person. Most treatments are geared toward stopping destruction, but the only ones that aid production are the TPO's (N-Plate and Promacta).

If you are really interested in the theories, this is a great article:

www.samizdat.com/itp.html

Here's another point to consider: platelet size. If your platelets are of a greater than normal size, most docs say that means they are young and fresh (and, if it's any consolation, stickier than the older ones), and that you are adequately producing, or maybe even producing more than most folks to meet the demand, which is heightened by the killing off of the older mature platelets.

Also, I can't remember the specifics, but seems I read somewhere that lots of immature platelet particles means you are producing adequately. (Of course, I sometimes remember wrong. Sandi, can you help here?)

My understanding is that it is always your immune system that is killing the platelets, but the age old questions are why are they being killed, and are you making as many as you should? On destruction: the indicum study (not available in the US to my knowledge, but available in Europe/UK) just indicates whether they are destroyed in liver or spleen, which may predict the success/failure of a splenectomy. (I always figured my daughter may need her spleen if/when she was done with ITP, so we never considered the test or the splenectomy. She's in remission now, and I'm glad she has a spleen.) On production: there is some published concern that the TPOs may overstimulate marrow to the point of harm. (We never had to deal with TPOs, some I am grateful for one less bit of confusion and worry for this mom.)

During the worst of my daughter's ITP, I tried to help her avoid anything that would rev up her system. We did our best to manage allergies, and stayed out of crowded areas (except school) during cold and flu season. She wasn't due for any required immunizations except the hpv vaccine, which was new and a bit worrisome to me, so we put that one off for a couple years until she was in remission. She still had her flu shot every year, as her hematologist thought it better to get the shot than the flu. I still don't understand why her immune system turned on her, and I guess I never will. I've read everything I could find on the subject, and most of it was over my head. All the treatment for autoimmune stuff is geared toward symptoms, but it would really be great if there were a treatment that corrected autoimmunity instead of just suppressing the immune system altogether.

Norma

Norma - as far as I know, there isn't any real way to tell if a person is adequately producing platelets. There is a lot of misconception that the bone marow biopsy can determine that, but it isn't true. It would make sense to think that if a person responds to drugs that hinder destruction (such as Prednisone), they would have adequate production, but it probably isn't as simple as that.

I would also much rather treat the cause of ITP than just the symptoms. I have hope that eventually there will be a treatment that deals with the cause rather than the effects. I think patients in remission are the ones who should be studied the most to see what they have in common and what changes biologically when they relapse. I would like to be a research subject in a study where they track my diet, stress, immune system, and blood chemestry to try to figure out how to make remissions permanent.

On the topic of platelet production, one way to know for sure you are producing enough platelets is a rapid platelet increase. Mine went from 6 to 172 in 3 days last October. At least at that point in time, production was good. The question is, was production down when my count was down? I have no reason to believe my production was impaired because even after 2 bags of platelets the day I was diagnosed, my count rose from 1 to 3, then fell back to 1. 5 days later the recovery began.

For most, the cause of ITP is the antibodies. What caused those doesn't matter because once they are there, it's too late. They may have been triggered by a virus or a vaccination or something else but once the virus or whatever has gone there's nothing to treat except to attempt to correct the resulting platelet problem. For those in remission, the body has just stopped producing the antibodies against the platelets and that is the aim of most of the treatments... steroids, CellCept, azathioprine, rituxan and so on.

I don't think you can know if platelet production is impaired by looking at counts after treatment. It doesn't tell us anything much as the treatment that dampens down the antibodies that kill off the platelet also dampens down the antibodies that damage or kill off the megakaryocytes that produce platelets.

They also now know that production is impaired because the TPO level of ITP patients is unusually low. If the platelet count falls, there ought to be more TPO to stimulate production but there isn't. Hence the TPO drugs which give us a production boost. Nplate works for 85% or more of patients indicating that a production problem exists for the majority.

I don't know how, but our hematologist said the bone marrow testing showed adequate production. Perhaps he simply meant there was not evident condition that wound hinder production. The marrow also had some sort of dna testing and was tested for "pre-leukemia" and other "pre-cancers." Maybe he simply meant there wasn't some sort of myelopdysplasia (sp?).
Norma

Norma - it's a common misconception....older thinking.

www.pdsa.org/forum/6-general-itp-discussion/11698-bone-marrow-biopsy-and-production-answers.html

I appreciate all the responses. Got knocked out for a day due to a bad reaction to WinRho treatment but I'm back in action.

So... I'm sort of rolling with the idea that the immune system is going after my platelets and taking it from there. I want to know why those. Why would an infection that stimulates antibodies against that infectious substance lead to an attack on platelets? Do the platelets look like that infectious substance? Do they have some feature that confuses antibodies? This is where I'm at in my head. Platelets aren't cells. Viruses aren't cells. So we deal with proteins. What protein is like a platelet? What virus is? Can you make a platelet stop looking like that protein? Can you confuse the platelet-focused antibodies? Etc.

There are a lot of diseases where the body targets healthy tissue with bad results - lupus, rheumatoid arthritis, basically that's the auto immune disease concept. Read up on the research in these diseases and I suspect you'll learn a lot about these mechanisms. Also reading up on the medications that help these diseases might be relevant.

I've said it before here, I think it's more amazing when things AREN'T going wrong in our bodies - the system is so complex.
Erica

That is the essence of auto-immune for sure. I certainly accept that aspect. I don't accept that we can't figure out more about why it's happening for specific things. I've read a lot and continue to read and appreciate the links for sure.

The logic still brings it to the anti-body / platelet relationship. I'd love to see comparative analyses of platelets across a sample of people... maybe ITP afflicted and non-ITP people. And then into subdivisions within each. Is there something special about the platelets or something about the anti-bodies? Or both? And again... how closely do platelets map to other infectious elements like viruses that may have entered at some time in the past (or still be there)?

The PDSA site here describes the theories behind it all.. see here.

www.pdsa.org/about-itp/causes.html

There are papers out there about this if you search.

What Erica said. I've said this before so I apologize to those who have heard me sound like a broken record. There are about 88 autoimmune disorders. No one knows why anyone happens to acquire any of them at any particular time. Mostly it's due to a genetic predisposition and all it takes is a trigger or succession of events that cause the disorder. Many people find that autoimmune disorders run in the family, although family members usually don't have the same ones as other members, Sometimes, not always. My daughter has Graves Disease - her body produces antibodies that attack her thyroid (sometimes it also attacks the eyes.) I have Lupus and ITP - my body produces antibodies against tissues and platelets. Some Lupus patients have antibodies that attack the kidneys, heart, lungs, etc. With all of the autoimmune disorders, all they can do is treat the symptoms or try to get the disorder to remit with whatever treatments are available. Most are immunosuppressant drugs. There are no cures. As awful as ITP seems to be, it is one of the least debilitating autoimmune disorders and is usually manageable.

Yes, you can confuse the platelet-focused antibodies to a degree - Win-Rho does that. It causes the body to destroy red cells instead of platelets for a short time. That's the best they can do at this point. Some of your other questions were answered in the link I gave you in my first post to you (same one Ann just provided).

As Erica said, your best bet is to research the immune system for a better understanding of the overall process. The premise is the same for ITP.

Thanks, Ann. These are the theories I've read as well and am always encouraged seeing some research to prove them in platelet-related areas. I'll continue digging around for platelet-specific comparative analyses.

edwardmaui is asking good research questions about platelet disorders and immune disease. Now he just needs funding to open a lab and start applying the scientific method to these questions.

My point being that sure, yes, I agree those are the types of questions that need answers - and there are researchers out there but we don't get to know what exactly they are investigating until they get some results and publish. And ITP isn't exactly getting the most funding (partly because it isn't killing or even disabling that many people, also it isn't a trendy popular disease with a popular ad campaign.) And we can't really pursue those questions on our own in our basement with flasks and test tubes.

I think that research on other auto immune disorders may be helpful to ITP also - just like Rituxan came out of a blood cancer chemotherapy - all these systems are inter-related.

So edwardmaui, I'm not sure what we can do in this discussion - I endorse the questions you are asking, but I sure can't answer them. We can point you to research we've uncovered previously. And I don't have a lab or a zillion dollars.
(don't mean to sound harsh but I think I did... sorry!)
Erica

Agreed. I always appreciate these discussions though because they make us think. We don't have people asking specific questions very often...mostly just get "why can't they cure this"? If it were that simple, they would.

Edward - I have been researching ITP since I was diagnosed in 1998. Believe it or not, they have made great strides in discovering new aspects since then. When I was diagnosed, ITP was believed to be caused by destruction only. We now know that production is also affected. We have also learned a lot more about platelet microparticles and a connection between ITP and clotting disorders. We have learned that there are more problems associated with splenectomy than just infection. We have learned so much more about megakaryocytes and their role in ITP. TPO drugs have been created and are now used successfully as treatments. Rituxan is now used and it's been about 9 years since it's been an ITP treatment - the data on success rates and side effects is becoming solid.

They are researching, they are learning. They just can not fix it. Yet.

Here is an article to start with - have you searched Bloodjournal.org?

bloodjournal.hematologylibrary.org/content/117/17/4405.full?sid=e1da6a9a-a621-4450-9b9c-951345ef6847