Blood Journal
Leading the way in experimental and clinical research in hematology

Plenary Paper
Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus)

  1. Hendrik B. Feys1,
  2. Jan Roodt2,3,
  3. Nele Vandeputte1,
  4. Inge Pareyn1,
  5. Seb Lamprecht4,
  6. Walter J. van Rensburg2,
  7. Patricia J. Anderson5,
  8. Ulrich Budde6,
  9. Vernon J. Louw7,
  10. Philip N. Badenhorst2,3,
  11. Hans Deckmyn1, and
  12. Karen Vanhoorelbeke1
  1. 1Laboratory for Thrombosis Research, Katholieke Universiteit Leuven Campus Kortrijk, Kortrijk, Belgium;
  2. 2Department of Haematology and Cell Biology, University of the Free State, Bloemfontein, South Africa;
  3. 3National Health Laboratory Services Tertiary Laboratory, Universitas Hospital, Bloemfontein, South Africa;
  4. 4Experimental Animal Facility, University of the Free State, Bloemfontein, South Africa;
  5. 5Department of Hematology, Washington University School of Medicine, St Louis, MO;
  6. 6Coagulation Laboratory, Aesulabor, Hamburg, Germany; and
  7. 7Division Clinical Hematology, Department of Internal Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa

Abstract

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.

  • Submitted April 16, 2010.
  • Accepted June 1, 2010.
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