The state of platelets preserved in extracorporeal circulation with a glycoprotein IIb/IIIa inhibitor.
BACKGROUND
Temporary inhibition of platelet function during extracorporeal circulation (platelet anesthesia) can preserve platelet count. We hypothesized that platelet anesthesia with a glycoprotein IIb/IIIa inhibitor could preserve activated platelets.


METHODS
Fresh human blood from donors was recirculated for 120 min in a simulated extracorporeal circuit. Heparin and FK633, a short-acting platelet glycoprotein IIb/IIIa inhibitor, were added to recirculated blood in one group (group F, n=5) whereas only heparin was used in controls (group C, n=5). Blood samples were obtained from the donors, and at 0, 5, 15, 30, 60, and 120 min of recirculation. Platelet counts, beta-thromboglobulin, thrombin-antithrombin complex, and aggregation to adenosine diphosphate were measured. Flow cytometry was performed for measurement of fibrinogen binding, platelet surface expression of P-selectin, and microparticles.


CONCLUSIONS
In the FK633 group, platelet counts were preserved and beta-thromboglobulin levels remained unchanged, whereas in group C, platelet counts decreased significantly and beta-thromboglobulin increased significantly from 30 and 60 min, respectively. FK633 inhibited platelet aggregation and fibrinogen binding to platelets throughout recirculation. A significant difference between groups with respect to microparticle parameters and thrombin-antithrombin complex levels was evident by 120 min. P-selectin expression increased at 0 min in both groups, and was preserved significantly at 5 min and reduced at 120 min in group F. Platelet counts were preserved by platelet anesthesia during recirculation without platelet activation. These results suggest that FK633 inhibits the amplification loop by reducing the binding of fibrinogen to glycoprotein IIb/IIIa and platelet aggregation.
Kondo
Norihiro
N
First Department of Surgery, Hirosaki University, School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. kondo18@rbb.7-dj.com
Wakayama
Fuminori
F
Suzuki
Yasuyuki
Y
Fukui
Kozo
K
Takaya
Shunichi
S
Fukuda
Ikuo
I
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D001793:Blood Preservation; D004151:Dipeptides / Q000008:administration & dosage; D005112:Extracorporeal Circulation; D005434:Flow Cytometry; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D010447:Peptide Hydrolases / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D001620:beta-Thromboglobulin / Q000378:metabolism
D015415:Biomarkers; D004151:Dipeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C046193:antithrombin III-protease complex; D001620:beta-Thromboglobulin; C103087:((4-(4-amidinophenoxy)butanoyl)aspartyl)valine; D000244:Adenosine Diphosphate; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases