Drug-Dependent Platelet Reactive Antibody

This was in the recent ENEWS from PDSA. The research can be found at www.ouhsc.edu/platelets/ditp.html (click on the link that says: Database from Drug-Dependent Platelet-Reactive Antibody Testing at the BloodCenter of Wisconsin, 1995-2009) . I don't really know what drug-dependent platelet reactive antibody is though. Can anyone help me out? I have chronic ITP (dx in January). They found antibodies. So they took me off Lamotrigine to rule it out as a cause for thrombocytopenia. My platelets did not go up and so they let me resume taking it.

My Hema did research and said that thrombocytopenia occurs in less than .01% of people who take lamotrigine. (I don't know where he found that out) but this report has lamotrigine on the list! My psychiatric nurse and Hematologist don't really know how I got ITP, and they couldn't find a correlation between my medicine and ITP. Is this something I should share with them? If the medicine caused the ITP but the ITP didn't go away when I stopped, is it safe to assume that I should not have to ever go off this medication? I would take ITP for the rest of my life if it meant I didn't have to stop this medication, it's the only thing that has helped me to function.

So again, does anyone know how to interpret this article?

Lorna:

I don't have time to read it now, but I can tell you that even if a drug does trigger ITP, stopping it may not resolve the ITP. I've read articles that state that once the antibody cascade begins, things change in the body that may not reverse when the drug is stopped.

Nearly every single drug there is has the potential to trigger ITP. Never be surprised when a drug is on the list.

Functioning is important. I take many drugs that are ITP no-no's because I have to in order to function. If it causes my counts to drop, so be it. We all have to do what we have to do. I'd say it's your call.

Lorna,

We were able to determine that to some extent my son's platelets would not go up (from zero mind you) because we had used LOTS of benadryl with him in his early years for hives, etc. Although we had stopped using it a long time ago, we had to homeopathically antidote it out of his body before we were able to get a platelet rise. That gave us some bump. But his body was still holding back. He had only had 4 days of prednisone but because it has ITP as a possible side effect we decided to also homeopathically antidote it as well. Sure enough, doing so sent his platelets on the upward swing to normal. This shows me two things:

1) If someone has ITP - taking a drug that can cause it is not wise.
2) Just because you stop a drug that is effecting your platelets (presumably), drug effects remain in the body for a VERY long time. The idea that when their half life is up, they're gone from the body is not necessarily so. Drug chemicals will take a very long time to detox out of a person's body. They sit in a person's tissues, cells, etc.

We were only able to detox out my son's homeopathically (because none of the doctors thought it was an issue). And yet, when we did, we got platelets.

So don't discount that the drug you were/are on can be causing an issue. I do not know how else to detox out drugs. We did it homeopathically because that's the route we took.

patti

So in theory if a drug caused ITP and you stopped taking it, it could take a while for it to completely leave your system?

Also in theory if you did not stop taking that drug and it did cause the ITP, even with treatment might never be cured?

Yes.

Lorna:

First, there is no cure for ITP. There are remissions which can be drug induced or spontaneous. The auto-antibodies are the reason for platelet destruction and inhibited production in most people. But first, you need to understand the theory behind it all. These were the best explanations that I could find for the "reasons" behind autoimmune disorders.

Microbial Trigger Theory
This theory was explored in Science News in the article "Microbial Trigger for Autoimmunity?" Lymphocytes exist in the body that are autoreactive, yet remain inactive. Researchers found that in mice, these dormant cells can become activated if the cells are near a bacterial infection. When the body fights the bacterial infection and interleukin-12 is created, the interleukin-12 creates an array of additional compounds specific to the pathogen. These anti-microbial compounds released near the infection site could accidentally activate a dormant, self-reactive lymphocyte. If the dormant lymphocyte targets platelets, then the microbial invasion may have triggered autoimmunity against platelets.

DNA Damage Theory
According to this theory, autoimmune diseases are developed due to a genetic defect that arises in a key part of the immune system.

There are many complex processes involved with avoiding autoimmunity. According to clonal deletion, T cells that react to self-molecules in the thymus are eliminated. If the presentation of self-antigen and subsequent elimination of autoreactive T cells does not proceed perfectly, a self-reactive T cell could mature, and an autoimmune disease could develop. Autoreactive T cells that are not eliminated in the thymus can be suppressed through other mechanisms. However, when those suppression mechanisms break down, an autoimmune disease can develop.

If a process becomes altered because of a genetic defect, then there is increased risk of the development of an autoimmune disease. The genetic defect could be due to free radical damage or through other causes of somatic genetic mutation. The defect could also be genetic, as a small nucleotide polymorphism in one or both alleles could make an individual more susceptible to acquiring an autoimmune disease.


Indeed, there is evidence that some individuals are genetically more prone to autoimmune diseases than others. A twins study was conducted for several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and IDDM. Monozygotic twins were compared with dizygotic twins. For each disease, the monozygotic twins showed disease concordance 20% of the time, compared with only 5% for dizygotic twins. In particular, it is thought that the MHC genotype is particularly important.

Molecular Mimicry Theory
According to this theory, autoimmune diseases are caused when pathogens are detected in the body that are similar to self-molecules. Lymphocytes are activated to target the intended antigen, but as they attack the pathogen, they also attack the similar self-molecules. By itself, it is unlikely that this theory explains the onset of an autoimmune disease. However, molecular mimicry may be an important factor when combined with either the Microbial Trigger Theory or DNA Damage Theory.

Autoimmunity often occurs spontaneously in patients, and science does not know what events trigger the onset of the disease. It is likely that autoimmune diseases arise from a confluence of factors. For example, in one experiment, it was shown that it is possible to induce an autoimmune disease through a combination of the three theories above. Genetically susceptible strains of animals (DNA damage) were injected with “self” tissues (Molecular Mimicry) mixed with strong adjuvants containing bacteria (Microbial Trigger). The combination of those events provoked autoimmunity.

Yes, it could take a long time for a drug to leave your system. Data suggests that true, confirmed drug-induced ITP resolves fairly quickly after stopping the drug....we're talking days or a few weeks. However, antibodies can remain in the body for a while. I just read today about quinine-induced ITP (which generally resolves quickly) and they found antibodies up to ten years later.

Looking at the theories above though, you can see that dormant cells can become activated, altered or damaged, causing autoimmunity. It's very possible that a drug could cause that activation or damage and it could be permanent.