Inherited Platelet Disorder

So I've had low platelets for about six years now. They've bounced around a bit but thankfully they've hovered around 65K without going much lower.

I recently found out that for as long as I've had this platelet disorder I have also had Lyme disease. This finally explained the many many other symptoms I have been having for so long. Initially my platelets went up a little with treatment for Lyme but after a month they went back to where they were.

To learn more about my health in general I recently paid the company 23andme.com $99 to sequence my DNA. They take a sample of your saliva and create a data file listing all of your DNA info including various genetic mutations. They used to prepare a health report to make sense of your results but for some reason the FDA shut that leg of their business down. I'm guessing it's because they don't officially have a license to practice medicine or something. Whatever the law is it seems shaky at best because now instead of getting your info from 23andme you can take the data file that they provide you and upload it to a number of different sites that will generate a health report for you. Some for free some for like $20.

I just ordered a health report from the site called Livewello. The different snips of DNA are called SNP's and the report lists them in categories. Everyone has gene mutations so they color code your genetic info to make it obvious which ones are fine and which ones are not the ideal version. We typically have two of each SNP so Green = both versions are good, yellow = one bad one good, and red = both versions are bad.

They have a whole section on clotting factors and obviously that's an area of interest to me. I have 3 mutations out of the 15 that this particular report pulled up. That's probably typical. 40% of the population can have a different set of genes and it will be called a mutation so that info isn't a big deal but you can click on the different genes and it pulls up whatever the current health research is based on that gene.

I was surprised to read about the following mutation:

SNP - GP6
rsID - rs1613662

From NCBI Gene : This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011] From UniProt : Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely Fyn/Lyn), the adapter protein LAT and leads to the activation of phospholipase C gamma2.


I asked my hematologist when I was first diagnosed if it was possible that I had a genetic platelet disorder. My estranged father had a brief instance of thrombocytopenia while he had a random fungal infection on his arm. She said that it was not likely because I would have had to have had thrombocytopenia from birth.

In retrospect I don't think she put much thought into my case at all because frequent coinfections associated with Lyme disease can cause thrombocytopenia but she never tested me for anything. Except AIDS at the suggestion of one of her interns.

Sorry for being so long winded but this makes me wonder if anyone knows anything more about the various genetic info out there relating to platelet disorders. I saw on the pdsa sight that they list some inherited disorders as alternative causes for thrombocytopenia. It can be really hard to find info relating specifically to various dna SNP's because the information can be so medically jargony it's hard to understand.

I'm also curious to find out if this is typical for people with ITP to have this gene. I only just learned about it so I don't know anything about it's frequency in the general public but I'm interested in learning more.

I'll keep ya updated if I find any helpful info.

Hrmm… I'm not finding info on reduced platelets though…

They mention a reduced functionality of the platelets but I haven't come across low count info. It could still be a factor. I'll keep looking. Seems like an odd coincidence.

ghr.nlm.nih.gov/gene/GP6

en.wikipedia.org/wiki/GPVI

Sem:

I don't know a whole heck of a lot about genetics and what most of that means. Two things strike me as I read your post.

1. Inherited thrombocytopenias are not always diagnosed at birth. I have read about cases that were not diagnosed until adulthood and in fact, just posted an article about that today to someone else. I'll post it for you too. I just spoke to the Phlebotomist in my doctor's office yesterday. She was diagnosed with von Wildebrands in her 40's, after her two sons were diagnosed in their teens. I wouldn't place too much importance in your Dad's brief episode; temporary thrombocytopenia is pretty common during or after an illness and most people just never know about it because they don't have a CBC. Counts just go back up on their own. My sister and I have both had ITP and we consider it a coincidence. Most doctors won't even look at a familial connection unless there are at least 3 family members involved.

2 This sentence: "This procoagulant function may contribute to arterial and venous thrombus formation." This leads me to believe that clotting is also associated with whatever you have going on. I think that would be a good avenue to search as well. Clotting and ITP often go together (as odd as that may sound).

www.bloodjournal.org/content/103/2/390?sso-checked=true

This is something I've just started looking into because of a family medical issue that arose recently. I'll be undergoing a battery of gene tests later this month or next month, and that data along with similar results for other family members will be put to good use, I hope. Maybe I'll learn something new about my platelets in the process.