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Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons

(2012) BLOOD. 120(17). p.3611-3614
Author
Organization
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.
Keywords
APTAMER ARC1779, DRUGS

Citation

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MLA
Feys, Hendrik, Jan Roodt, Nele Vandeputte, et al. “Inhibition of Von Willebrand Factor-platelet Glycoprotein Ib Interaction Prevents and Reverses Symptoms of Acute Acquired Thrombotic Thrombocytopenic Purpura in Baboons.” BLOOD 120.17 (2012): 3611–3614. Print.
APA
Feys, Hendrik, Roodt, J., Vandeputte, N., Pareyn, I., Mottl, H., Hou, S., Lamprecht, S., et al. (2012). Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons. BLOOD, 120(17), 3611–3614.
Chicago author-date
Feys, Hendrik, Jan Roodt, Nele Vandeputte, Inge Pareyn, Harald Mottl, Sam Hou, Seb Lamprecht, Walter J Van Rensburg, Hans Deckmyn, and Karen Vanhoorelbeke. 2012. “Inhibition of Von Willebrand Factor-platelet Glycoprotein Ib Interaction Prevents and Reverses Symptoms of Acute Acquired Thrombotic Thrombocytopenic Purpura in Baboons.” Blood 120 (17): 3611–3614.
Chicago author-date (all authors)
Feys, Hendrik, Jan Roodt, Nele Vandeputte, Inge Pareyn, Harald Mottl, Sam Hou, Seb Lamprecht, Walter J Van Rensburg, Hans Deckmyn, and Karen Vanhoorelbeke. 2012. “Inhibition of Von Willebrand Factor-platelet Glycoprotein Ib Interaction Prevents and Reverses Symptoms of Acute Acquired Thrombotic Thrombocytopenic Purpura in Baboons.” Blood 120 (17): 3611–3614.
Vancouver
1.
Feys H, Roodt J, Vandeputte N, Pareyn I, Mottl H, Hou S, et al. Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons. BLOOD. 2012;120(17):3611–4.
IEEE
[1]
H. Feys et al., “Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons,” BLOOD, vol. 120, no. 17, pp. 3611–3614, 2012.
@article{8549095,
  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.},
  author       = {Feys, Hendrik and Roodt, Jan and Vandeputte, Nele and Pareyn, Inge and Mottl, Harald and Hou, Sam and Lamprecht, Seb and Van Rensburg, Walter J and Deckmyn, Hans and Vanhoorelbeke, Karen},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keywords     = {APTAMER ARC1779,DRUGS},
  language     = {eng},
  number       = {17},
  pages        = {3611--3614},
  title        = {Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons},
  url          = {http://dx.doi.org/10.1182/blood-2012-04-421248},
  volume       = {120},
  year         = {2012},
}

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