Are Platelets a Window Into the Brain?

Platelets, the second most common type of blood cell, are tiny disc-shaped cells. The main role that platelets play in the body is that of damage control. When platelets sense injured blood vessels, they become activated and release chemical signals that trigger the formation of blood clots at the site of injury so that blood does not leak.

Researchers have also found that platelets play a role in inflammation, cardiovascular disease and cancer, and they appear to help control infections.

Exactly how platelets do all of these functions is not yet clear but it may have something to do with their ability to display molecules that interact with the immune system as well as germs. Platelets can also serve as mini-warehouses storing chemical signals and proteins that are released when platelets become activated.

There are about one trillion platelets in the blood of an adult. The laboratory range for platelets will vary from one lab to another, but normal levels are usually above 150 billion. When the number of platelets falls below this level, people become at risk for uncontrolled bleeding.

In the time before potent ART became available, less-than-normal platelet levels were a relatively common complication of HIV infection. However, in the present era this complication is not common among HIV-positive people who are taking ART.

Platelets and the Brain

In 2007 a team of researchers announced that it had found a link between declining platelet levels and an increased risk for the subsequent development of extreme HIV-related neurocognitive decline -- dementia.

As assessments of neurocognitive function are complex, it would be helpful if there were a simple blood test that could be used to accurately foretell neurological complications among HIV-positive people.

Confirming unusual results is an essential part of the scientific process. Another team of neurologists across the U.S. conducted a long-term study of neurocognitive function and platelet levels in the blood. They did not find any conclusive link between declining platelet levels and HIV-related dementia. However, they did unexpectedly find that among some older people with HIV declining platelet levels might be linked to atrophy of parts of the brain.

Study Details

Since 1984, researchers in the U.S. have enrolled nearly 7,000 gay and bisexual men from these cities:

• Baltimore

• Chicago

• Los Angeles

• Pittsburg

Participants were seen twice a year by study staff; at each visit they were interviewed, examined and had blood samples drawn for analysis. From time to time, specialized neurocognitive assessments and MRI scans of the brains of some participants were also done.

For the present analysis, researchers used data from 2,125 HIV-positive men, 250 of whom subsequently developed dementia.

Results -- Platelets

Taking many factors into account -- including CD4+ cell count, viral load, red blood cell counts, age, education, alcohol and tobacco use, and so on -- falling platelet levels were not linked to an increased risk for HIV-related dementia.

This difference between the present and past studies is interesting and may have arisen because of these factors:

• In the present study, participants had been monitored for up to 25 years. In the previous study, which reported its results in 2007, participants had been monitored for only a few years.

• The present study was larger and used only men with a broad range of CD4+ cell counts. The previous study had both men and women, and many participants had less than 300 CD4+ cells.

Results -- MRI scans

In a subset of 83 HIV-positive men in the present study who were more than 51 years of age, there was a link between declining platelet levels and shrinkage of part of the brain, specifically gray matter. This term describes parts of the brain involved in thinking and memory.

Keep in mind that in the present study, only one MRI scan was done. Had multiple MRIs been done over several years, then a more robust link between brain atrophy and platelet counts might have been made.

Why Platelets?

It may seem unusual that a cell not obviously connected with the brain, such as a platelet, might have an impact on this organ. However, as explained previously, platelets perform many roles in the body. Also, researchers have found that platelets release chemical signals that aid in the development and survival of immature brain cells. Researchers have found that in monkeys infected with SIV, which causes an AIDS-like disease, declining platelets have been linked to severe SIV-related brain infection. Still other researchers have found that a decline in the health of the bone marrow is somehow linked to the presence of dementia in HIV-positive people. So the connection between platelets, which are made in the bone marrow, and brain health is not as far-fetched as it may seem.

For now, the evidence to support a relationship between low levels of platelets in the blood and subsequent severe HIV-related neurocognitive impairment in people remains contested. Until researchers can refine their studies to find a clear and consistent relationship between platelet count and HIV-related neurocognitive impairment, platelet counts by themselves are not likely to be reliable indicators of future decline in cognitive functioning.

References

1. Wachtman LM, Skolasky RL, Tarwater PM, et al. Platelet decline: an avenue for investigation into the pathogenesis of human immunodeficiency virus -associated dementia. Archives of Neurology. 2007 Sep;64(9):1264-72.

2. Peng F, Dhillon N, Callen S, et al. Platelet-derived growth factor protects neurons against gp120-mediated toxicity. Journal of Neurovirology. 2008 Jan;14(1):62-72.

3. Wachtman LM, Tarwater PM, Queen SE, et al. Platelet decline: an early predictive hematologic marker of simian immunodeficiency virus central nervous system disease. Journal of Neurovirology. 2006 Feb;12(1):25-33.

4. Potula R, Dhillion N, Sui Y, et al. Association of platelet-derived growth factor-B chain with simian human immunodeficiency virus encephalitis. American Journal of Pathology. 2004 Sep;165(3):815-24.

5. Ragin AB, Wu Y, Storey P, et al. Bone marrow diffusion measures correlate with dementia severity in HIV patients. AJNR American Journal of Neuroradiology. 2006 Mar;27(3):589-92.

6. Ragin AB, D'Souza G, Reynolds S, et al. Platelet decline as a predictor of brain injury in HIV infection. Journal of Neurovirology. 2011 Oct;17(5):487-95.