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Causes

While no one knows the precise cause of ITP at this time, researchers continue to make progress in understanding it and the similarities to other autoimmune diseases.  Since ITP can vary greatly between individuals, causes of ITP may also vary. Note that the theories on this page are listed separately (in alphabetical order), however they most likely overlap.  For example, someone may have a defect in immune regulation which makes them more susceptible to developing ITP after an immunization or contracting H. pylori.

Bacteria and Virus Byproducts

This theory suggests that ITP (and other autoimmune diseases) may be caused by a person’s immune response being confused between its own cells and invading virus and bacteria.

When a virus or bacteria invades our body, special cells chop it up into thousands of fragments and put some of these fragments in a type of pocket for the immune system to disable.  T-cells (a type of white blood cell) latch on to the fragments in the pocket and send signals to destroy all of the tissues that have the same or similar makeup.  The problem comes when the fragment to be destroyed looks like part of a platelet.  In that case, antibodies attach to platelets as well as the fragments on other cells resulting in both the invaders and the platelets being destroyed.

In a similar theory, when our body is fighting a reaction, it produces a compound called interleukin-12 during its normal immune response. Interleukin-12 then creates many other immune compounds specific to a particular microbe. Researchers think this flurry of activity may activate any dormant self-reactive cells near the infection. (If the self-reactive cell is for platelets, you get ITP)


Free Radical Damage (Oxidative Stress)

In this theory, the DNA in our cells can be altered by reactive substances in our bodies. When the changed DNA is a part of the immune control function, it can result in a specific autoimmune disease.

Free radicals are particles with an unstable molecular structure that act as scavengers in the body and rob electrons from other molecules.  Their production is hastened by stress, pollution, fertilizers, pesticides, prescription drugs, alcohol, electromagnetic radiation, etc.

Our bodies have built-in methods to control free radicals and change them into neutral substances. These detoxification mechanisms require specific enzymes to make them function well.  If our bodies do not have the vitamins and minerals to make up the enzymes, or if the detoxification mechanism is damaged, the result is a surplus of free radicals and other toxic substances.

The excess free radicals and other noxious byproducts of a failed detox process roam our bodies and attack our weakest links. Depending on the DNA attacked, the electron grabbing can cause an autoimmune disease, including ITP.


Immune System Defects

Both developing and mature T-cells and B-cells (types of white blood cells) have been implicated in the development of ITP. 

The immune system has a way of determining the difference between foreign invaders and normal tissues.  It is a complicated process with various checkpoints.  When one or more of these checkpoints is faulty, antibodies can target important tissues like platelets.

T-regulatory cells (a type of white blood cell) suppress the immune response of other cells.  They keep the immune system in check by halting the immune reaction after clearing a virus or bacteria and by preventing the immune system from over-reacting and attacking normal cells, like platelets. In a study of mice with ITP, researchers found that the T-regulatory cells were retained in the thymus instead of being released into the blood where they could do their job of balancing the immune system.

People with ITP also have fewer B-regulatory cells.  These cells are important in regulating the T-regulatory cells and also play a role in deciding which cells are normal and which are not and need to be eliminated.


Intestinal Changes

Our bodies contain about 100 trillion microbes, most of them bacteria, and most of them living in the digestive tract. These microbes play a role in our adaptive immune system, the part of the immune system that disables harmful viruses and bacteria. When the beneficial bacteria living in the gut are modified by diet, antibiotics, or invading pathogens, the immune system can shift and particles can escape from the digestive tract. These disturbances of the intestinal immune system can lead to various intestinal diseases and have been increasingly linked to immune-mediated diseases outside of the intestine such as rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases.


Other Causes

People diagnosed with ITP sometimes have other diseases that contribute to their low platelets.   See the ‘Other Platelet Disorders’ page for a list.

Some cases of ITP can be drug-induced or the result of eating particular foods.  See the ‘Warnings’ page for more information on these causes.


References

Bacteria and Virus Byproducts

Aster R. “Molecular mimicry and immune thrombocytopenia,” Blood. 23 April 2009, v. 113, no. 17, p. 3887 http://bloodjournal.hematologylibrary.org/content/113/17/3887.full

Blakeslee S. "Virus’s Similarity to Body’s Proteins May Explain Autoimmune Diseases.” New York Times.  December 31, 1996. http://www.nytimes.com/1996/12/31/science/virus-s-similarity-to-body-s-proteins-may-explain-autoimmune-diseases.html

Takahashi T et al. “Helicobacter pylori and chronic ITP: the discrepancy in the clinical responses to eradication therapy might be due to differences in the bacterial strains.” Blood 2004 104:594. http://bloodjournal.hematologylibrary.org/content/104/2/594.full

Travis J. Microbial Trigger for Autoimmunity? Science News. June 21, 1997. http://www.sciencenews.org/pages/sn_arc97/6_21_97/fob1.htm

Zhang W et al. “Role of molecular mimicry of Hepatitis C virus protein with platelet GPIIIa in Hepatitis C-related immunologic thrombocytopenia” Blood 23 April 2009, Vol. 113, no. 17, pp. 4086-4093. http://www.ncbi.nlm.nih.gov/pubmed/19023115

Free Radical Damage

Imbach P. “Oxidative stress may cause ITP.” Blood. 2011 Apr 28;117(17):4405-6. http://bloodjournal.hematologylibrary.org/content/117/17/4405.long

Rogers, Sherry A, M.D., Tired or Toxic? A Blueprint for Health. Syracuse, NY: Prestige Publishing, 1990.

Sharma, Hari, M.D. Freedom from Disease, Toronto, Ontario:Veda Publishing, 1993.

Immune System Defects

Aslam R et al. "Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia (ITP)." Blood. 2012 Jul 3.
http://www.ncbi.nlm.nih.gov/pubmed/22760780

Fogarty PF. “ITP:Tolerance Lost.” Blood. 2011 Dec 8;118(24):6232-4 http://bloodjournal.hematologylibrary.org/content/118/24/6232.long

Semple JW. “Bregging rights in ITP.” Blood. 2012 Oct 18;120(16):3169.  http://bloodjournal.hematologylibrary.org/content/120/16/3169.full

"Research Sheds New Light on Common Bleeding Disorder." Insciences OrganisationPress Release. July 24, 2012.
http://insciences.org/article.php?article_id=10892

Intestinal Changes

Baydoun A et al. “Hematological manifestations of celiac disease.” Scand J Gastroenterol. 2012 Aug 6. http://www.ncbi.nlm.nih.gov/pubmed/22861356

Fasano A. “Leaky gut and autoimmune diseases.” Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8. doi: 10.1007/s12016-011-8291-x.. http://www.ncbi.nlm.nih.gov/pubmed/22109896

Maynard CL et al. "Reciprocal interactions of the intestinal microbiota and immune system." Nature 489, 231–241, 13 September 2012.
http://www.nature.com/nature/journal/v489/n7415/full/nature11551.html  

Visser J et al. “Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms.”Ann N Y Acad Sci. 2009 May;1165:195-205. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886850/