Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus)
Blood, Volume 116, No. 12, Year 2010
Notification
URL copied to clipboard!
Description
Thrombotic thrombocytopenic purpura (TTP) is the prototypical microangiopathy characterized by disseminated microthromboses, hemolytic anemia, and ultimately organ dysfunction. A link with deficiency of the von Willebrand factor - cleaving protease (ADAMTS13) has been demonstrated, but additional genetic and/or environmental triggers are thought to be required to incite acute illness. Here we report that 4 days of ADAMTS13 functional inhibition is sufficient to induce TTP in the baboon (Papio ursinus), in the absence of inciting triggers because injections with an inhibitory monoclonal antibody (mAb) consistently (n = 6) induced severe thrombocytopenia (< 12 × 109/L), microangiopathic hemolytic anemia, and a rapid rise in serum lactate dehydrogenase. Immunohistochemical staining revealed the characteristic disseminated platelet- and von Willebrand factor - rich thrombi in kidney, heart, brain, and spleen but not lungs. Prolonged inhibition (14 days, n = 1) caused myocardial ischemic damage and asplenia but not death. Control animals (n = 5) receiving equal doses of a noninhibitory anti-ADAMTS13 mAb remained unaffected. Our results provide evidence for a direct link between TTP and ADAMTS13 inhibition and for a mild disease onset. Furthermore, we present a reliable animal model of this disease as an opportunity for the development and validation of novel treatment strategies. © 2010 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
South Africa, Bloemfontein
Universitas Private Hospital
Vandeputte, Nele
Belgium, Leuven
Ku Leuven
Pareyn, Inge
Belgium, Leuven
Ku Leuven
Lamprecht, Seb
South Africa, Bloemfontein
University of the Free State
Janse van Rensburg, Walter James
South Africa, Bloemfontein
University of the Free State
Anderson, Patricia J.
United States, St. Louis
Washington University School of Medicine in St. Louis
Budde, Ulrich
Germany, Hamburg
Coagulation Laboratory
Louw, Vernon Johan
South Africa, Bloemfontein
University of the Free State
Badenhorst, Philip Nel
South Africa, Bloemfontein
University of the Free State
South Africa, Bloemfontein
Universitas Private Hospital
Deckmyn, Hans
Belgium, Leuven
Ku Leuven
Vanhoorelbeke, Karen
Belgium, Leuven
Ku Leuven
Statistics
Citations: 112
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1182/blood-2010-04-280479
ISSN:
00064971
Research Areas
Genetics And Genomics