Research Interest

Platelet storage involves complex interactions with plasma proteins from the complement and coagulation enzyme cascades. The extent to which these enzymes are responsible for loss of platelet function, known as platelet storage lesions, is of particular interest. Not only do the platelets interact with these proteins, but they also modulate the degree of activation of the cascades.

The cascades are likely initiated by the chemical nature of the bag surface causing a chain reaction to propagate and cross-activate further enzymes. The platelets may down-regulate the activity until they are overwhelmed. As platelets fall victim to the complement effects of C1INH depletion, lysis, and/or metabolic losses, the cascade accelerates. This could give rise to the storage lesion as manifest by activated, exhausted platelets. If complement activation during storage can be reduced or totally inhibited, platelets may be able to exhibit prolonged function. The effect of complement inhibitors sCR1 (soluble complement receptor 1) and NAAGA (a peptide C3 convertase inhibitor) included in the storage container should produce an improvement of stored platelet function. There was some indication that leukocyte enzymes may also contribute to platelet storage lesions; however, with the advent of leukoreduction the contribution of leukocytes to the problem has been reduced.

Ultimately, it would be ideal to be able to provide an ‘add water and stir’ platelet substitute – one that can be dried and does not involve a human donor, but functions as an adjunct or filler to the body’s own platelets when activated. To this end, this laboratory is developing a liposome-based platelet substitute. Canadian Centre for Blood Research