Abstract | BACKGROUND: STUDY DESIGN AND METHODS: We studied the ex vivo concentration response curves for ARC1779 on PLT function analyzer (PFA-100, Dade Behring) and cone-and-plate analyzer (CPA, Impact-R) PLT function tests, agonist-induced PLT aggregation, and VWF activity of TTP patients (n = 11, three in acute phase and eight in remission) and healthy controls (n = 44). RESULTS: VWF activity and VWF-dependent PLT plug formation were increased in TTP patients relative to healthy controls, but agonist-induced PLT aggregation was not. ARC1779 blocked collagen/ adenosine 5'-diphosphate ( ADP)-induced PLT plug formation as measured by PFA-100 with an inhibitory concentration (IC)(100) of approximately 1 microg/mL in citrate-anticoagulated samples and approximately 3 to 4 microg/mL in hirudin-anticoagulated samples. A similar concentration of ARC1779 was necessary to block shear-dependent PLT adhesion in both TTP patients and healthy controls using the CPA assay (IC(100) of approx. 1 microg/mL for both). ARC1779 blocked VWF activity with an IC(90) of approximately 3 to 4 microg/mL in all subjects, but did not inhibit PLT aggregation by ADP, collagen, or arachidonic acid even at concentrations much greater than those that fully inhibited VWF-dependent PLT function. CONCLUSIONS:
ARC1779 potently and specifically inhibits VWF activity and VWF-dependent PLT function. ARC1779 may be a promising novel therapeutic for the treatment of TTP.
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Authors | Florian B Mayr, Paul Knöbl, Bernd Jilma, Jolanta M Siller-Matula, Patricia G Wagner, Robert G Schaub, James C Gilbert, Petra Jilma-Stohlawetz |
Journal | Transfusion
(Transfusion)
Vol. 50
Issue 5
Pg. 1079-87
(May 2010)
ISSN: 1537-2995 [Electronic] United States |
PMID | 20070617
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ARC 1779
- Aptamers, Nucleotide
- von Willebrand Factor
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Topics |
- Adult
- Aptamers, Nucleotide
- Blood Platelets
(drug effects, physiology)
- Cross-Sectional Studies
- Female
- Humans
- Male
- Middle Aged
- Platelet Aggregation
(drug effects)
- Purpura, Thrombotic Thrombocytopenic
(blood, drug therapy)
- von Willebrand Factor
(antagonists & inhibitors)
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