Background: The investigational anti von Willebrand Factor (vWF) aptamer ARC1779 effectively inhibits vWF activity in blood samples of controls and of patients suffering from thrombotic thrombocytopenic purpura (TTP) (

Jilma et al, Blood 2007;110:279a
,
Gilbert et al. Circulation 2007;116:2678–2686
).

Methods: A 39 year old comatose male patient with acute (TTP) was treated with daily plasma exchange. Further, the patient received rituximab (375mg/m2 first treatment on day 8, and weekly thereafter for 8 weeks) and was splenectomized on day 18. Due to the refractory nature of his TTP, the patient received a concomitant intravenous infusion of ARC1779 at a rate of 2 μg/kg/min beginning on day 30.

Results: ARC1779 increased the platelet count slightly from 7 to a maximum of 30/nL; during this period septicaemia and DIC may have blunted the rise in platelet counts. However, platelet counts dropped to 5/nL by 16h after cessation of infusion (day 34). The infusion of ARC1779 was re-started on day 37, and platelet counts increased from 9 to 45/nL. (Figure) Due to a temporary lack of drug, the dose of ARC1779 was stopped at 78h, and platelet counts fell to 12/nL by 12 h after interruption of the infusion. (circle in the Figure) When ARC1779 was re-started, platelet counts increased to a maximum of 97/nL and the patient’s neurologic status improved to near normal under therapy with ARC1779 over the next week.

Conclusions: ARC1779 was well-tolerated, and caused a reproducible rise in platelet counts, which alleviated severe thrombocytopenia, in an otherwise refractory TTP case. This effect was reproducible under serial “re-challenge”. Together with the observed improvement in neurologic function, the data provide clinical proof-of-concept and suggest that ARC1779 treatment might improve the organ dysfunction which typically occurs in acute TTP. These data provide a rational basis for ongoing and planned phase II trials of ARC1779.

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Figure

Topics:
thrombotic thrombocytopenic purpura, von willebrand factor, infusion procedures, intravenous infusion procedures, organ failure, plasma exchange, rituximab, septicemia, thrombocytopenia, platelet count measurement

Disclosures: Jilma:Archemix Corp.: Research Funding. Wagner:Archemix Corp.: Employment. Hutabarat:Archemix Corp.: Employment. Schaub:Archemix Corp.: Employment. Gilbert:Archemix Corp.: Employment.

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2008, The American Society of Hematology
2008
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