Measurement of Platelet Dense Granule Release in Healthy Volunteers
| Status: | Withdrawn |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | July 2009 |
| End Date: | June 2012 |
Aspirin has been shown to reduce cardiovascular events in at risk individuals. Elucidation
of mechanisms of aspirin resistance and a possible loss of effect of aspirin over time with
chronic aspirin treatment necessitate a more precise method of measuring the "release phase"
of platelet activation, including the release of dense granules from platelets.
of mechanisms of aspirin resistance and a possible loss of effect of aspirin over time with
chronic aspirin treatment necessitate a more precise method of measuring the "release phase"
of platelet activation, including the release of dense granules from platelets.
This is a proposal for a pilot study to evaluate the feasibility of measuring
5-hydroxytryptamine (5-HT) release from platelets as an indicator of dense granule release
during platelet activation in volunteers taking aspirin.
One phase of platelet response to activating agonists involves release of dense granules,
which are known to contain 5HT (serotonin) and ATP. There are various methods of measuring
the degranulation of platelets: ATP release can be measured using a lumiaggregometer, and
release of 14C radiolabeled 5-HT from platelets. Using the aggregometer and a 14C labeled
5-HT assay can be used to measure 5-HT release from platelets.
Our experience suggests that ADP-induced ATP release is insensitive to detect very low
levels of platelet dense granule release, which occurs in aspirin-treated subjects. The
pilot study will permit optimizing the method for reliably detecting low levels of 5HT
release in patients who achieve submaximal inhibition of the cyclooxygenase during aspirin
treatment.
5-hydroxytryptamine (5-HT) release from platelets as an indicator of dense granule release
during platelet activation in volunteers taking aspirin.
One phase of platelet response to activating agonists involves release of dense granules,
which are known to contain 5HT (serotonin) and ATP. There are various methods of measuring
the degranulation of platelets: ATP release can be measured using a lumiaggregometer, and
release of 14C radiolabeled 5-HT from platelets. Using the aggregometer and a 14C labeled
5-HT assay can be used to measure 5-HT release from platelets.
Our experience suggests that ADP-induced ATP release is insensitive to detect very low
levels of platelet dense granule release, which occurs in aspirin-treated subjects. The
pilot study will permit optimizing the method for reliably detecting low levels of 5HT
release in patients who achieve submaximal inhibition of the cyclooxygenase during aspirin
treatment.
Inclusion Criteria:
- Males over age 18
- Non-smokers
- No chronic medical illness
- No chronic medications
Exclusion Criteria:
- ASA/NSAID use previous 14 days.
- History of chronic NSAID use.
- Currently taking NSAIDs, opioid analgesics, corticosteroids, or anticoagulants.
- History of coronary artery disease, myocardial infarction, coronary artery bypass
grafting, percutaneous angioplasty, diabetes mellitus or stroke.
- History of hypertension
- BMI >35
- Smokers
- History of gastric, duodenal, or esophageal ulcers or serious gastrointestinal bleed.
- History of frequent headaches, pain syndrome, or other condition requiring frequent
use of analgesics.
- History of adverse reaction to ASA.
- Initial platelet count <100K/µl or >500K/µl.
- Initial hematocrit <35% or >50%.
- Weight less than 110 pounds.
Female subjects will be excluded to avoid possible confounding uterine smooth muscle
production of prostaglandins which various throughout the menstrual cycle.
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