Protein-platelet interactions

Static Adsorption of Plasma Proteins on Glass. Initial studies of the interaction of proteins with artificial surfaces concerned the highly simplified situation of static adsorption on glass from solutions of purified radiolabeled human plasma proteins. Albumin was chosen as a major plasma protein known for its non thrombogenic properties (5>6). Fibrinogen and fibronectin, on the contrary, are major proteins of plasma which enhance platelet and cellular adhesion (4.5.7.23-25). 

The adsorption of proteins is the first interaction which occurs when a foreign surface comes in contact with blood. The processes which then lead to hemostasis are attachment of cellular elements to the surface, platelet adhesion and release, and triggering of the blood coagulation cascade. Investigations of interactions of proteins at the interface, which are the primary steps in blood clotting and determine whether it will occur, are hence of fundamental importance. 

Li D, Chen H, Gleim McClung W, Brash JL. Lysine-PEG-modified polyurethane as a fibrinolytic surface effect of PEG chain length on protein interactions, platelet interactions and clot lysis. Acta Biomater 2009 5 1864-71. 

This review of the biocompatibility of polymeric surfaces concentrates on the observed differences of hydrophilic, hydrophobic, and heterogenic materials as measured by their interactions with proteins and platelets. Emphasis is placed on materials for use in injection molding applications. 

The effects of foreign surfaces on platelets has been intensively studied because of the place of platelets in thrombotic processes and because the visible deposition of platelets is evidence of some surface-platelet interaction. This latter is not strictly true because protein adsorption precedes platelet adsorption so that in reality it is a platelet-protein adsorbate reaction in which the nature of the adsorbate reflects the nature of the underlying surface. In vitro studies, primarily using platelet-rich plasma, have involved measurement of the adsorption rate, number adsorbed, morphological changes, and more recently, the release reaction. 

British investigators (Haddow and Timmis 1951) synthesized and studied esters of the methanesulfonic acid. The most active derivative was the dimethylsulfonic ester of 1,4-butanedione, known as busulfan. Busulfan interacts with the thiol groups of proteins and amino acids some of its metabolites can alkylate the thiols of cysteine, peptides and proteins. Busulfan exerts selective cytotoxic activity in hematopoietic bone marrow cells and inhibits the formation of granulocytes and platelets. It slightly affects the lymphoid tissue. 

The mechanisms involved in platelet activation are discussed in Chapter 51 (see Figure 51-8). The process involves interaction of the stimulus (eg, thrombin) with a receptor, activation of G proteins, stimulation of phospholipase C, and hberation from phosphatidylinositol... 

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