Fig. 7: Force cytometry reveals single platelet contraction force as a potential clinical biophysical biomarker for bleeding severity modulated by autoantibodies targeted to the αIIbβ3 platelet integrin.

Our micropatterned hydrogel-laden microscope coverslip-based cellular contraction cytometry technology demonstrates a direct link between platelet biophysics and a patient’s bleeding phenotype. In the case of ITP, we found that a patient’s bleeding score directly correlates with a decrease in single platelet contraction. Mechanistically, we discovered that a patient’s autoantibodies targeted against the αIIbβ3 integrin “immuno-mechanically” modulate platelet contractile forces (increasing or decreasing) in a conformation- and epitope-dependent manner. Antibodies that bind to the bent or extended-closed integrin conformation decrease platelet contractile force whereas antibodies that bind to the extended-open integrin conformation increase force. Therefore, platelet contractility is associated inversely with bleeding severity in that patient platelets with low contraction forces are associated with an increased risk of a bleeding phenotype, whereas patients with highly contractile platelets will likely be asymptomatic.