Platelet aggregation is not initiated by platelet shape change

Area of Science:

• Hematology
• Biophysics
• Cell Biology

Background:

• Platelet aggregometry commonly measures light transmission to assess platelet function.
• The initial decrease in light transmission is traditionally attributed to platelet shape change.
• It is widely believed that platelet shape change is a prerequisite for platelet aggregation.

Purpose of the Study:

• To investigate the underlying cause of the initial decrease in light transmission during platelet aggregometry.
• To determine if platelet shape change is essential for platelet aggregation.

Main Methods:

• Platelets were activated using ADP, thrombin, or thrombin receptor agonist peptide (TRAP).
• Experiments included using pre-activated platelets and shape-change inhibitors (cytochalasin D, vincristine).
• Microscopy was used to analyze platelet morphology at minimum light transmission; fibrinogen-coated latex spheres were also used to model aggregation.

Main Results:

• The initial decrease in light transmission consistently correlated with the formation of platelet microaggregates.
• Microaggregate formation occurred even with pre-activated platelets or in the presence of shape-change inhibitors.
• Microaggregation was observed in a model using non-shape-changing latex spheres, indicating it is independent of shape change.

Conclusions:

• Platelet shape change is not a prerequisite for aggregation.
• The optical signal in aggregometry attributed to shape change actually represents platelet microaggregation.
• Platelet aggregation can occur independently of shape change, and shape change does not always lead to aggregation.