Platelet Procoagulant Potential Declines with Age in Healthy Controls – A Link to Hemorrhagic Complications in Elderly?
Philion Gatchoff1, Angelia Kirkpatrick2, Chao Xu1, Andrea Vincent5, Eleanor Mathews1, Leslie Guthery1, Fabiola Donna-Ferreira4, George Dale1, Calin Prodan3
1University of Oklahoma Health Sciences Center, 2Medicine, 3Neurology, University of Oklahoma Health Sciences Center/Oklahoma City VA Medical Center, 4University of Oklahoma Health Sciences Center/Oklahoma City VA Medical Center, 5University of Oklahoma
Objective:
To examine the relationship between platelet procoagulant potential and age in healthy controls.
Background:
Coated-platelets, a subset of highly procoagulant platelets, are observed upon dual-agonist stimulation with collagen and thrombin; they represent ~32% of all platelets in healthy controls. Coated-platelet levels are elevated in patients with ischemic stroke/TIA, with higher levels associated with increased risk for recurrence. In contrast, lower levels of coated-platelets are present in patients with hemorrhagic complications after stroke and in humans/animals with bleeding diatheses. While smoking is associated with increased levels, chronic use of statins, SSRIs or antiplatelets is associated with decreased levels.
Design/Methods:
Coated-platelet levels (expressed as percentage of platelets) were assayed as previously described. Subjects with prior stroke/TIA, intracerebral/subarachnoid hemorrhage, myocardial infarction, dementia, traumatic brain injury, bleeding diatheses or recent blood transfusions were excluded. Demographics, medications, and comorbidities were recorded for each participant. Individuals performing the coated-platelet assays were not aware of clinical data. Regression analysis was conducted to assess the relationship between coated-platelet levels and age.
Results:
We enrolled 200 control subjects, with a mean age of 57 years (range 21-94 years), and mean coated-platelet levels of 34.3% (SD 13.6%). Logistic regression identified age and smoking as independently associated with coated-platelet levels (p=0.03). Every decade of increased age was associated with a mean 1.6% decrease in the coated-platelet levels (p=0.02), with a steeper decline noted after age 75. Smokers had higher coated-platelet levels than non-smokers (38±13.4%, N=60 vs 32.8±13.4%, N=140, p=0.007). None of the remaining variables confounded the association between age and coated-platelet levels.
Conclusions:
Aging is associated with a decline in platelet procoagulant potential in controls, most noticeable after age 75. These results suggest a link to previously reported increased risk of major hemorrhagic complications with antithrombotic therapy in the elderly and deserve further examination of mechanisms involved.
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