The mechanism of cold-induced platelet aggregation in the presence of heparin.
Low temperature induces platelet aggregation, but this phenomenon is slight and poorly reproduced. However, heparin potentiated the reaction in a dose dependent manner. The degree of aggregation increased as the temperature at which the platelet-rich plasma was chilled was lowered, and as the time of chilling lengthened. Acetylsalicylic acid, a cyclooxygenase inhibitor, and staurosporin, an inhibitor of protein kinase C, partially inhibited cold-induced platelet aggregation (CIPA), suggesting that at least part of the reaction mechanism involves production of thromboxane A2 and activation of protein kinase C. Prostaglandin E1 (PGE1), which inhibits platelet responses through elevating platelet cyclic AMP, completely blocked CIPA, suggesting that PGE1 dependent pathway in platelets plays an important role for CIPA. The inhibition of CIPA by these inhibitors suggests that CIPA is aggregation with platelet activation but not platelet agglutination. Extracellular Ca2+ is essential for CIPA because ethylene glycol-bis (beta-aminoethylether) N, N, N', N'-tetraacetic acid (EGTA), extracellular Ca2+ chelating agent, completely inhibited CIPA. Monoclonal antibodies against glycoprotein (GP) IIb/IIIa (10E5, P2) and Ang-Gly-Asp-Ser-peptide (RGDS-peptide) which inhibit fibrinogen binding to GPIIb/IIIa completely blocked CIPA but monoclonal antibodies against GPIb (6D1, SZ2) partially. In addition, CIPA occurred only when fibrinogen was added to washed platelets suspension. These results indicate that CIPA is dependent on binding of fibrinogen to GPIIb/IIIa and GPIb is partly related with the reaction.
Akiyama
M
M
First Department of Internal Medicine, Hirosaki University School of Medicine, Japan.
Takami
H
H
Yoshida
Y
Y
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology; D003080:Cold Temperature; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D001798:Blood Proteins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D006493:Heparin