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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons
Blood, Volume 120, No. 17, Year 2012
Notification
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Description
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. © 2012 by The American Society of Hematology.
Authors & Co-Authors
Feys, Hendrik B.
Belgium, Leuven
Ku Leuven
Roodt, Jan P.
South Africa, Bloemfontein
University of the Free State, School of Medicine
South Africa, Bloemfontein
Universitas Private Hospital
Belgium, Mechelen
Rode Kruis-vlaanderen
Vandeputte, Nele
Belgium, Leuven
Ku Leuven
Pareyn, Inge
Belgium, Leuven
Ku Leuven
Mottl, Harald
Switzerland, Chaux-de-fonds
Glenmark Pharmaceuticals sa
Hou, Sam
Switzerland, Chaux-de-fonds
Glenmark Pharmaceuticals sa
Lamprecht, Seb
South Africa, Bloemfontein
University of the Free State, School of Medicine
Janse van Rensburg, Walter James
South Africa, Bloemfontein
University of the Free State, School of Medicine
Deckmyn, Hans
Belgium, Leuven
Ku Leuven
Vanhoorelbeke, Karen
Belgium, Leuven
Ku Leuven
Statistics
Citations: 48
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1182/blood-2012-04-421248
ISSN:
00064971
Study Design
Randomised Control Trial