Görög Thrombosis Test: a global in-vitro test of platelet function and thrombolysis.
This is the first laboratory evaluation of a new instrument, designed to test both platelet function and thrombolytic activity from a native blood sample, in vitro. The inventor assumed that the reduction and arrest of blood flow was due to activation, aggregation and stabilized thrombus formation by shear-activated platelets, and that re-establishment of flow was due to thrombolysis. Morphologic and functional studies presented here confirm these mechanisms. In vitro tests provided incontestable evidence for the principal role of platelets in the obstruction of flow (occlusion time) and for thrombolysis as the principal mechanism underlying the restoration of blood flow (lysis time). In addition to aggregation, it is the explosive generation of thrombin by shear-activated platelets that results in the formation of an occlusive haemostatic thrombus. Anticoagulation of blood completely prevented occlusion. Platelet-rich thrombus formation (occlusion time) was dose-dependently inhibited by monoclonal antibody against platelet glycoprotein (GP) Ib (6B4 and 12E4), aurin tricarboxylic acid, monoclonal antibody against platelet GPIIb/IIIa (MA-16N7C2 and abciximab), a synthetic GPIIb/IIIa antagonist (TAK-029), thrombin inhibitor (argatroban), and anti-von Willebrand factor, but not by anti-fibrinogen. Plasminogen activator streptokinase (Varidase) and tissue-type plasminogen activator (Monteplase) dose-dependently enhanced thrombolysis (lysis time) without affecting platelet function (occlusion time). The test is specific for thrombolysis. The plasmin inhibitor tranexamic acid prevented plasminogen activator-induced thrombolysis, while inhibition of clot retraction by cytochalasin B did not affect the lysis time. This rapid and sensitive global test of platelet function and thrombolytic activity could be of great value both in research and in clinical practice.
Yamamoto
Junichiro
J
Laboratory of Physiology, Faculty of Nutrition, and High Technology Research Centre, Kobe Gakuin University, Kobe, Japan. yamamoto@nutr.kobegakuin.ac.jp
Yamashita
Tsutomu
T
Ikarugi
Hideo
H
Taka
Tomomi
T
Hashimoto
Masaru
M
Ishii
Hiromitsu
H
Watanabe
Sadahiro
S
Kovacs
Iren B
IB
D000328:Adult; D000933:Antifibrinolytic Agents; D003018:Clot Retraction; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000295:instrumentation* / Q000379:methods; D013927:Thrombosis / Q000175:diagnosis* / Q000188:drug therapy; D014148:Tranexamic Acid / Q000494:pharmacology
D000933:Antifibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D003571:Cytochalasin B; D014148:Tranexamic Acid; D010960:Plasminogen Activators