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. 2021 Dec 23;138(25):2733-2740.
doi: 10.1182/blood.2021012277.

Antiplatelet drugs block platelet activation by VITT patient serum

Christopher W Smith  1 , Samantha J Montague  1 , Caroline Kardeby  1 , Ying Di  1 , Gillian C Lowe  2 , William A Lester  2 , Steve P Watson  1 , Phillip L R Nicolson  1   2
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Antiplatelet drugs block platelet activation by VITT patient serum

Christopher W Smith et al. Blood. .
No abstract available

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Figures

Figure 1.
Figure 1.
Serum from patients with VITT induces platelet aggregation via the FcγRIIA, and can be blocked by inhibition of COX, P2Y12, Src, and Btk. Washed platelets (2 × 108/mL) were stimulated with serum (15:1, v/v), and aggregation was measured by light transmission aggregometry. (Ai) Representative aggregation traces for AZD1222-vaccinated healthy donors (HD) or patients with VITT (P) serum before and after IVIg treatment in the presence of Tyrode’s buffer, 10 μg/mL IV.3 F(ab), low concentration heparin (0.2 U/mL), or after heat inactivation of complement (56°C, 45 minutes) and plasma exchange. Quantification of area under the curve (AUC) for 10 minutes for P2, P3, P4, P7 pre- and post-IVIg samples (Aii) and P1, P5, and P6 post-IVIg (Aiii) and plasma exchange samples. Mean ± standard error of the mean (SEM; n = 3). Statistical analysis was by 2-way analysis of variance (ANOVA) with Dunnett’s multiple comparisons (vs serum [Ai]); vs post-IVIg serum [Aiii]), *P < .05. ns, non-significant. (B) The effect of the complement inhibitors compstatin (28 μM), FUT-175 (10 μM), or vehicle on aggregation in response to serum from VITT-affected patients. Inhibitors were incubated for 10 minutes before stimulation. Representative aggregation traces and quantification of AUC for 10 minutes. Mean ± SEM (n = 9; 3 repeats P4, P5, and P7, respectively). Statistical analysis was by 1-way ANOVA with Dunnett’s multiple comparisons. ns, non-significant. (C) The effect of antiplatelet drugs and tyrosine kinase inhibitors. The effect of indomethacin (10 μM), ticagrelor (1 μM), dasatinib (1 μM), R406 (1 μM), entospletinib (1 μM), ibrutinib (0.5 μM), rilzabrutinib (0.5 μM) or vehicle (0.02% DMSO) on aggregation in response to VITT-affected patient serum. Inhibitors were incubated for 10 minutes prior to stimulation. Representative aggregation traces and quantification of AUC for 10 minutes. Mean ± SEM (n = 9; 3 repeats P3, 4 repeats P4, and 1 repeat P5 and P7). Statistical analysis was by 1-way ANOVA with Dunnett’s multiple comparisons. *P < .05. ns, non-significant.
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