Monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa and Ibalpha inhibit platelet dependent thrombin generation by different mechanisms.
The antithrombotic effect of antiplatelet agents is principally due to their anti-aggregatory action, but these agents may also interfere with coagulation. We have investigated the effect of monoclonal antibodies (MAb) to platelet membrane glycoproteins (GP) IIb/IIIa and Ibalpha on thrombin generation. Antibodies to platelet membrane glycoprotein IIb/IIIa (RFGP56 and c7E3) were shown to inhibit platelet-mediated thrombin generation stimulated by both intrinsic and extrinsic methods. An antibody to GP Ibalpha (RFGP37) also inhibited thrombin generation in these systems. FITC-annexin V was used to determine the effect of these antibodies on the exposure of procoagulant phospholipids on the platelet membrane, and it was found that the anti-IIb/IIIa antibodies reduced this, whereas the anti-Ibalpha antibody caused an increase. We conclude that our monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa and Ibalpha inhibit platelet dependent thrombin generation by different mechanisms.
Division of Haematology, National Institute for Biological Standards and Control, Hertfordshire, UK. sthomas@nibsc.ac.uk
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Thomas
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Metcalfe
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Goodall
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Gray
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry; D003864:Depression, Chemical; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005343:Fibrinolytic Agents / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007616:Kaolin / Q000494:pharmacology; D008563:Membrane Lipids / Q000032:analysis; D051379:Mice; D010743:Phospholipids / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology*; D013917:Thrombin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D008563:Membrane Lipids; D010743:Phospholipids; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D007616:Kaolin; D013925:Thromboplastin; D013917:Thrombin; D002122:Calcium Chloride