Abstract Number: PB1639
Meeting: ISTH 2020 Congress
Background: Re-organization of the actin cytoskeleton accompanies platelet activation and is a pre-requisite for the development of platelet contractility, which is important in thrombus compaction and wound contraction. Defective platelet contractility can give rise to bleeding diathesis and increases the likelihood of thrombus embolization. However, how platelet contractility affects other aspects of platelet function is poorly understood. Moreover, reports suggest that current platelet function tests may be unaffected by changes in contractility.
Aims: To determine the consequences of compromised contractility on platelet adhesion under flow or static conditions, on platelet secretion, and on aggregation measurements in solution.
Methods: Blood was obtained from healthy consenting volunteers as approved by the RCSI Research Ethics Committee (REC1405). Different aspects of platelet function were assessed:
(i) translocation dynamics of single platelets on von Willebrand Factor (vWF) at arterial shear;
(ii) actin cytoskeletal morphology in spread platelets on fibrinogen;
(iii) P-selectin exposure in response to collagen-reactive peptide, and
(iv) aggregation in response to arachidonic acid or ADP.
In all cases, myosin IIa activity was dose-dependently inhibited by pre-incubation with para-amino blebbistatin (paBBT). The effect of paBBT on platelet contractility was directly measured by single platelet traction forces on micropost arrays.
Results: Platelet traction forces were significantly inhibited by doses as low as 1 µM paBBT. Myosin inhibition caused longer and faster platelet rolling on vWF. Actin filament bundling in spread platelets was reduced sensitively by paBBT whereas cytoskeletal rearrangements were inhibited only above 16 µM. Platelet alpha granule secretion in solution and aggregometry were unaffected by paBBT up to 40 µM.
Conclusions: Our preliminary results suggest that contractility critically affects several functions in adherent platelets and thus plays an important role beyond mere clot retraction. Current clinical tests insufficiently reflect this important aspect.
To cite this abstract in AMA style:Kenny M, Lickert S, Vogel V, Kenny D, Schoen I. Importance of Platelet Contractility at Different Stages of Thrombus Formation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/importance-of-platelet-contractility-at-different-stages-of-thrombus-formation/. Accessed February 21, 2024.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/importance-of-platelet-contractility-at-different-stages-of-thrombus-formation/