Platelet decline as a predictor of brain injury in HIV infection

Abstract

An association between platelet decline and increased risk of progression to dementia has been observed in an advanced HIV infection cohort study. This investigation evaluated the prognostic significance of platelet decline for dementia, for psychomotor slowing and for brain injury, as quantified in vivo, in a much larger population of HIV+ men. Platelet counts and neurocognitive data were available from biannual visits of 2,125 HIV+ men participating in the prospective, Multicenter AIDS Cohort Study (MACS) from 1984 to 2009. Brain volumetric data were also available from an imaging substudy of 83 seropositive participants aged 50 and older. The association of platelet counts with neurocognitive outcome was assessed using Cox proportional hazard models where change in platelet count from baseline was a time-updated variable. Marked platelet decline was associated with increased risk of dementia in univariate analysis (HR=2.5, 95%CI=1.8 – 3.5), but not after adjustment for CD4 cell count, HIV viral load, age, study site, hemoglobin, race, education, smoking and alcohol use (HR=1.4, 95%CI=0.78-2.5). Platelet decline did not predict psychomotor slowing in either univariate (HR=0.79, 95%CI=0.58-1.08) or multivariate (HR=1.10, 95%CI=0.73-1.67) analyses. Analysis of brain volumetric data, however, indicated a relationship between platelet decline and reduced gray matter volume fraction in univariate (p=0.06) and in multivariate (p<0.05) analyses. Platelet decline was not an independent predictor of dementia or psychomotor slowing, after adjusting for stage of disease. Findings from a structural brain imaging substudy of older participants, however, support a possible relationship between platelet decline and reduced gray matter.

Detection of circulating platelet–monocyte complexes in persons infected with human immunodeficiency virus type-1

“…sCD40L increases the permeability of the blood brain barrier to virus thereby potentially allowing more monocytes to enter the central nervous system (CNS; Davidson et al, unpublished data). On a related subject, a study by Ragin et al, on older patients from the MACS cohort (an advanced HIV infection cohort), has shown that platelet decline was found to be associated with reduced gray matter volume and increased risk of dementia (Ragin et al, 2011). In addition to this, there is growing evidence that the cross-talk between monocytes and activated platelets promotes the activation and modulation of monocyte behavior, and that these interactions at sites of injury and infection may function to further promote the inflammatory response [(Bournazos et al, 2008) and reviewed by Stephen et al (Stephen and Dransfield, 2010)].…”

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

“…Poorer neurocognitive performance has been associated with smaller brain volumes [22,37,39–46] and greater viral burden. In addition, impaired immune response (nadir CD4+ T lymphocyte counts) has been associated with greater atrophy [20,38,40,41,46–49]*. Cortical brain atrophy and expansion of the third ventricle has been observed soon after seroconversion [50].…”

Platelets should be at the Frontline: HIV Researchers and Care Providers Needs a lot of Sticky Notes

“…Unfortunately, the mechanisms mediating such observations remain highly speculative and highlight the urgency of additional studies. Yet, these findings further confirm that the brain is not free from the action of platelets, and emphasizes the need to revise old platelet paradigms [23].…”

“…We further demonstrated that altered platelets have a remarkable ability to damage and cross the blood brain barrier [20]. This is not unexpected, since platelets are the source of multiple pro-inflammatory substances, including TNF, IL-6 and CD40, which are known for altering the BBB [18][19][20][21][22][23]. Besides their role in pathogenesis, platelets might also play a key role in the regulation of brain function.…”

“…Yet the mechanisms of such a dysfunction are still under investigation [18][19][20][21][22][23]. Our group started by documenting the close relationship between thrombocytopenia, a condition characterized by low platelets, and cognitive alterations [19].…”