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Anti‐thrombotic effects and bleeding risk of AJvW‐2, a monoclonal antibody against human von Willebrand factor
Author(s) -
Kageyama Shunsuke,
Yamamoto Hiroshi,
Nagano Mitsuyo,
Arisaka Harumi,
Kayahara Takashi,
Yoshimoto Ryota
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701354
Subject(s) - platelet , von willebrand factor , ristocetin , chemistry , platelet membrane glycoprotein , pharmacology , platelet adhesiveness , monoclonal antibody , glycoprotein ib , thrombus , guinea pig , microbiology and biotechnology , antibody , endocrinology , medicine , immunology , platelet aggregation , biology
1 A murine anti‐human vWF monoclonal antibody, AJvW‐2, was developed that inhibited the interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (vWF) during the ristocetin‐ (IC 50 =0.7±0.1 μg ml −1 ) and botrocetin‐ (IC 50 =1.8±0.3 μg ml −1 ) induced aggregation of human platelets. 2 AJvW‐2 inhibited the high shear stress (10.8 N m −2 ) induced aggregation of human platelets dose‐dependently with an IC 50 =2.4±0.3 μg ml −1 , but had no effect on low shear stress induced platelet aggregation (1.2 N m −2 ) up to 100 μg ml −1 . 3 AJvW‐2 also inhibited the high shear stress (5.0 N m −2 ) induced adhesion of human platelets to collagen I with the same efficacy (IC 50 =2.4±0.3 μg ml −1 ), but had no effect at low shear conditions (1.5 N m −2 ). 4 AJvW‐2 inhibited the botrocetin‐induced aggregation of platelets from guinea‐pig, rat, rabbit, dog and pig at the same concentration range as human platelets; it likewise also inhibited the high shear stress induced aggregation and adhesion to collagen I of guinea‐pig platelets. 5 AJvW‐2 prevented arterial thrombus formation in guinea‐pigs at a dose of 100 μg kg −1 without prolonging the template bleeding time, whereas the GPIIb/IIIa antagonist lamifiban mediated inhibition of thrombosis at 1000 μg kg −1 was accompanied by a significant prolongation of the bleeding time. 6 These results suggest that AJvW‐2 is a potent inhibitor of the GPIb‐vWF interaction and a potential novel antithrombotic agent with lower bleeding risk than GPIIb/IIIa antagonists.British Journal of Pharmacology (1997) 122 , 165–171; doi: 10.1038/sj.bjp.0701354