Contact between a polymer and whole blood: sequence of events leading to thrombin generation.
The mechanism by which thrombin is generated on a polymer surface in an extracorporeal circuit is not yet fully understood. To address this question we have developed an in vitro chamber model in which whole blood containing heparin (1 IU/mL) comes in contact with a commonly used biomaterial, polyvinyl chloride (PVC). Incubation of blood in the chamber for 60 minutes at 37 degrees C resulted in the binding of platelets to the material surface and the generation of thrombin-antithrombin complexes. Corn trypsin inhibitor, a specific inhibitor of factor XIIa, inhibited this thrombin-antithrombin complex generation in blood in contact with PVC, which is not considered an efficient activator of factor XII. The addition of the glycoprotein IIb/IIIa inhibitor Ro44-9883 abrogated platelet binding and aggregation and resulted in decreased generation of thrombin-antithrombin complexes. Thrombin-antithrombin generation was also negligible in platelet-rich plasma but could be partially restored in the presence of erythrocytes. Taken together, these data are compatible with a model in which thrombin generation is triggered by factor XII. The response to contact with PVC appears to begin with a low-grade generation of thrombin that involves both erythrocytes and leukocytes and that activates platelets, followed by the activation of a platelet-dependent amplification loop that produces most of the thrombin.
Hong
J
J
Department of Oncology, Radiology, and Clinical Immunology, Clinical Immunology, University Hospital, Uppsala, Sweden.
Larsson
A
A
Ekdahl
K N
KN
Elgue
G
G
Larsson
R
R
Nilsson
B
B
D000085:Acetates / Q000494:pharmacology; D000990:Antithrombin III / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005112:Extracorporeal Circulation; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011143:Polyvinyl Chloride / Q000494:pharmacology*; D013917:Thrombin / Q000096:biosynthesis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000085:Acetates; D010975:Platelet Aggregation Inhibitors; C046193:antithrombin III-protease complex; D014443:Tyrosine; D000990:Antithrombin III; D011143:Polyvinyl Chloride; C084062:lamifiban; D010447:Peptide Hydrolases; D013917:Thrombin