PP response induced by VITT plasma is suppressed by heparin, is antibody mediated, and corresponded with clinical response to therapy. Healthy donor whole blood was treated with platelet agonist 5 µM SFLLRN and plasma from patients with VITT (n = 23) (A) or HIT (n = 8) (B) in the presence of low-dose (0.5 U/mL) or high-dose (100 U/mL) unfractionated heparin and assessed for PP formation by using flow cytometry. Blue lines represent patients with VITT who generated a heparin-enhancing PP response at low-dose heparin. Friedman test with Dunn’s correction for multiple comparisons was performed. Donor blood was pretreated with the FcγRIIa-blocking antibody IV.3 (10 µg/mL) (C) or IVIg (10 mg/mL) (D) for 15 minutes before exposure to VITT plasma and 5 µM SFLLRN. Wilcoxon matched-pairs signed rank test was performed. (E) PP response induced by VITT plasma (n = 4) collected pre-IVIg treatment was compared with the procoagulant response within 5 days’ post-IVIg therapy. The reduction in the PP response corresponded to the suppressive effect of exogenous IVIg (10 mg/mL) on the pre-IVIg sample. Results are presented as fold-change in PP proportion relative to no plasma control. Each line represents a unique patient. (F) Plasma samples from 6 patients with VITT collected before initiation of fondaparinux treatment was tested in the presence of fondaparinux (1.2 µg/mL) in vitro. PP response is normalized to no fondaparinux control. Four patients were subsequently found to be clinically responsive to fondaparinux, and 2 patients were fondaparinux resistant. Healthy donor whole blood was treated with platelet agonist 5 µM SFLLRN and VITT plasma in the presence of the ChAdOx1 nCoV-19 vaccine (AZD1222, 1:2000 [vol/vol], n = 23) (G) or recombinant SARS-CoV-2 spike protein (HexaPro 20 µg/mL, n = 10) (H) before flow cytometric assessment for PP formation. Wilcoxon matched-pairs signed rank test was performed. *P < .05, **P < .01, ***P < .001,****P <.0001. ns, not significant.