Abstract Number: OC 01.1
Meeting: ISTH 2020 Congress
Background: von Willebrand Factor (VWF) is crucial for arterial thrombosis and its plasma levels are increased in acute coronary syndromes (ACS). Effects of conventional platelet inhibitors are compromised by elevated VWF under high shear rates. BT200 is a third generation aptamer that binds and inhibits the A1 domain of human VWF.
i) To study whether VWF is a predictor of mortality in ACS patients under potent P2Y12 blocker therapy and
ii) To examine the effects of a VWF inhibiting aptamer BT200 and its concentrations required to inhibit VWF in plasma samples of patients with ACS.
Methods: VWF activity was measured in 321 patients with ACS, and concentration- effect curves of BT200 were established in plasma pools containing different VWF concentrations.
Results: Median VWF activity in our population was 170% (IQR%CI: 85-255) and 44% of patients had high (>180%) VWF activity. Plasma levels of VWF activity predicted short (HR= 2.50; 95%CI= 1.11-5.59) and long-term (HR= 2.65; 95%CI= 1.14-6.15) mortality despite treatment with potent platelet inhibitors (dual antiplatelet therapy with aspirin and prasugrel or ticagrelor). Consistent with previous findings, age was an independent discriminator of VWF activity. Concentrations of BT200 ranging from 0.42 to 2.13 mcg/ml inhibited VWF activity to < 20% of normal in the different plasma pools (p< 0.0001) and higher concentrations of BT200 were needed in the presence of increasing VWF activity.
Conclusions: VWF is a predictor of all-cause mortality in ACS patients under contemporary potent antiplatelet therapy. BT200 potently inhibited VWF activity in a target concentrations dependent manner.
To cite this abstract in AMA style:Kovacevic K, Jilma B, Zhu S, Gilbert JC, Winter M-, Toma A, Lang I, Hengstenberg C, Siller-Matula J. von Willebrand Factor as a Predictor of Mortality and its Target Concentration Dependent Inhibition by BT200 Aptamer in Patients Treated with Potent ADP Receptor Blockers [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/von-willebrand-factor-as-a-predictor-of-mortality-and-its-target-concentration-dependent-inhibition-by-bt200-aptamer-in-patients-treated-with-potent-adp-receptor-blockers/. Accessed May 20, 2022.
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