Activation of circulating platelets in vaccine‐induced thrombotic thrombocytopenia and its reversal by intravenous immunoglobulin

Anti‐severe acute respiratory syndrome coronavirus‐2 adenoviral‐vector vaccines trigger subclinical antiplatelet autoimmunity and increase of soluble platelet activation markers

“…A more recent prospective large cohort study on the clinical features of VITT found no sex preponderance among 294 patients with VITT 5 . The underlying mechanism is still not yet fully understood; however, in almost all patients anti‐platelet factor 4 (PF4)/polyanion immunoglobulin G (IgG) were found to be associated with elevated levels of pro‐inflammatory cytokines and platelet and neutrophil activation markers 6–12 . Only a few investigations to date have assessed the impact of adenoviral‐vector and mRNA anti‐SARS‐CoV‐2 vaccines on platelets and the blood clotting system in apparently healthy individuals.…”

Understanding vaccine‐induced thrombotic thrombocytopenia (VITT)

“…This is particularly important in patients with a high risk of deterioration, such as those with severe thrombocytopenia (platelet count <30 ×10 9 /L), severe thrombosis or presence of hypofibrinogenaemia (fibrinogen <1.5 g/L) 12 . Markers of platelet activation have been shown to reduce to levels comparable with a healthy donor following IVIg administration 23 . In addition, IVIg is critical in patients with profound thrombocytopenia, as raising the platelet count along with anticoagulation should reduce bleeding risk 22 .…”

“…IVIg is the only known treatment that modifies both hypercoagulability and thrombocytopenia, by preventing FcγRIIa‐mediated platelet activation. 23 , 24 IVIg should be given at a dose of 1–2 g/kg a day for two consecutive days to all cases of VITT. 12 This is particularly important in patients with a high risk of deterioration, such as those with severe thrombocytopenia (platelet count <30 ×10 9 /L), severe thrombosis or presence of hypofibrinogenaemia (fibrinogen <1.5 g/L).…”

“… 12 Markers of platelet activation have been shown to reduce to levels comparable with a healthy donor following IVIg administration. 23 In addition, IVIg is critical in patients with profound thrombocytopenia, as raising the platelet count along with anticoagulation should reduce bleeding risk. 22 Although IVIg administration has been associated with an increased incidence of thrombotic complications in other clinical contexts, the risk is thought to be negligible in the setting of VITT, particularly when given in conjunction with therapeutic anticoagulation.…”

“…IVIg is the only known treatment that modifies both hypercoagulability and thrombocytopenia, by preventing FcγRIIa‐mediated platelet activation 23,24 . IVIg should be given at a dose of 1–2 g/kg a day for two consecutive days to all cases of VITT 12 .…”