title: Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons.
abstract: The pathophysiology of thrombotic thrombocytopenic purpura (TTP) can be explained by the absence of active ADAMTS13, leading to ultra-large von Willebrand factor (UL-VWF) multimers spontaneously interacting with platelets. Preventing the formation of UL-VWF-platelet aggregates therefore is an attractive new treatment strategy. Here, we demonstrate that simultaneous administration of the inhibitory anti-VWF monoclonal antibody GBR600 and the inhibitory anti-ADAMTS13 antibody 3H9 to baboons (prevention group) precluded TTP onset as severe thrombocytopenia and hemolytic anemia were absent in these animals. In addition, partial VWF inhibition was not enough to prevent thrombocytopenia, demonstrating the specificity of this therapeutic strategy. GBR600 treatment of baboons during acute TTP (treatment group) resulted in a rapid recovery of severe thrombocytopenia similar to the platelet count increases observed in TTP patients treated by plasma exchange. Baboons in the control group only injected with 3H9 developed early stages of TTP as previously described. Hence, inhibiting VWF-GPIb interactions is an effective way to prevent and treat the early symptoms of acquired TTP in baboons.
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven afdeling Kortrijk, Belgium.
authors.forename: Hendrik B
authors.initials: HB
authors.lastname: Feys
authors.forename: Jan
authors.initials: J
authors.lastname: Roodt
authors.forename: Nele
authors.initials: N
authors.lastname: Vandeputte
authors.forename: Inge
authors.initials: I
authors.lastname: Pareyn
authors.forename: Harald
authors.initials: H
authors.lastname: Mottl
authors.forename: Sam
authors.initials: S
authors.lastname: Hou
authors.forename: Seb
authors.initials: S
authors.lastname: Lamprecht
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Van Rensburg
authors.forename: Hans
authors.initials: H
authors.lastname: Deckmyn
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000743:Anemia, Hemolytic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010215:Papio; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D011697:Purpura, Thrombotic Thrombocytopenic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D051722:ADAM Proteins