It was once thought that ITP was a simple disease... antibody coated platelets are removed by the spleen, leaving a reduced platelet count. However, as researchers study each step, from platelet production to platelet elimination, they continue to find subtleties to this process that have made a difference in how the disease is viewed and treated.
Platelets are released from cells in the bone marrow called megakaryocytes. Bits of the megakaryocyte bud and elongate, creating a long chain of proplatelets. Next, the proplatelet chain splits apart, releasing the platelets singly or in groups. These released platelets are still considered cells by some, although they lack a nucleus.
Normal production of platelets is 35,000 per microliter per day and may increase much beyond that in ITP patients. However, in people with ITP, antibodies may interfere with megakaryocyte function and reduce the ability of megakaryocytes to increase the rate of platelet production.
Thrombopoietin (TPO), a protein made in the liver, travels through the bloodstream and signals the bone marrow to make more platelets. In other diseases of low platelets the amount of TPO in the blood rises; for many reasons, the TPO level is usually not increased in people with ITP. See the treatment information on how increasing TPO can help increase the platelet count.
The foremost job of platelets is to form clots and stop bleeding. Because they have fewer platelets, people with ITP are more prone to prolonged bleeding. Platelets are also responsible for assuring the integrity of the blood vessel walls.They plug up small holes and form clots when vessel walls are injured. Without sufficient platelets to maintain the blood vessel walls, people develop spontaneous bruises or pinpoint hemorrhages called petechiae.
Platelets transport serotonin, a mood elevating neurotransmitter. Platelets also carry serotonin’s 'parent' or precursory chemical, L-tryptophan.1 These substances are involved in such processes as sleep/wake cycles, biological rhythms, appetite, mood regulation, etc.
Platelets may also play a role in the immune system. They can promote inflammation, may help regulate your innate immune system2 (the one you were born with), and can interact directly with microorganisms such as bacteria. Because they are the first to reach the scene of a wound, they are well-positioned to direct the body’s response to bacterial infections. Platelets can interact with bacteria directly or through various proteins circulating in the blood.3
Researchers continue to learn more about platelets. So far they know that platelets contain more than 5,000 different proteins, enter into more than 13,500 different reactions, and contain nearly 1,000 drug targets.5
Antibodies may attach to platelets because parts of the platelet may look like a virus or bacteria the body is fighting, because of a defect in the immune system, or for other reasons.
In most people with ITP, antibodies attach to their platelets on a surface protein called glycoprotein IIB/IIIA. However, the antibodies can attach to other parts of their platelets as well. While researchers have tried very hard to create a laboratory test to diagnose ITP by measuring the anti-platelet antibodies, this has not been successful. Some people with ITP have no detectable antibodies and some people with a normal platelet count have anti-platelet antibodies, according to these diagnostic tests.
For people with ITP, platelets stay in the blood stream from a few days to a few hours depending on the severity of the disease, much shorter than the normal lifespan of eight to ten days. The antibody-coated platelets are engulfed and eliminated by macrophages (cells designed to remove debris) in the spleen and sometimes, the liver. Platelets can also be removed by T-cells4,6 (a type of white blood cell).
Video of the platelet destruction process:
1. Gronier B et al. “Evidence for a defective platelet L-tryptophan transport in depressed patients.” Int Clin Psychopharmacol. 1993 Summer;8(2):87-93. http://www.ncbi.nlm.nih.gov/pubmed/8345162
2. Semple JW et al. “Platelets and innate immunity.” Cell Mol Life Sci. 2010 Feb;67 (4):499-511.
3. Cox D et al. “Platelets and the innate immune system: Mechanisms of bacterial-induced platelet activation.” J Thromb Haemost. 2011 Mar 21. doi: 10.1111/j.1538-7836.2011.04264.x.
4. Catani L et al. “Dendritic cells of immune thrombocytopenic purpura (ITP) show increased capacity to present apoptotic platelets to T lymphocytes.” Experimental Hematology. Vol.34, Issue 7, July 2006, Pages 879-887.(http://www.sciencedirect.com/science/article/pii/S0301472X06001962)
5. The Platelet Web http://plateletweb.bioapps.biozentrum.uni-wuerzburg.de/plateletweb.php
6. Sarpatwari A et al. “Autologous 111 In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry.” Br J Haematol. 2010 Dec;151(5):477-87. http://www.ncbi.nlm.nih.gov/pubmed/20950403