Vaccine-induced (immune) thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which are aimed to prevent and minimize coronavirus disease 2019 and related pathophysiology. 1,2 Alternatively called thrombocytopenia with thrombosis syndrome (TTS) by government reporting agencies, such as the Therapeutic Goods Administration (TGA) in Australia, VITT affects 1 in 50 000 to 100 000 individuals vaccinated with adenovirus-based vaccines. 1 VITT mimics heparin-induced thrombocytopenia with thrombosis (HIT or HITT), and reflects generation of platelet activating antibodies directed to complexed platelet factor 4 (PF4). [1][2][3][4] In HIT, the antibodies are directed against PF4 complexed to heparin, whereas different PF4 complexes form in VITT. [1][2][3][4][5] Early case series of VITT formed the basis upon which other laboratories began to investigate this immune-mediated disorder. [6][7][8] Although many diagnostic guidelines have been published, 9,10 VITT is clinically suspected when a patient develops thrombosis with associated suggestive laboratory findings, following recent exposure to an adenovirus vaccine. Two of the well-established early laboratory signs of potential VITT are thrombocytopenia (or a sharp drop in platelet count; similar to HIT), and highly elevated D-dimer. 3,[9][10][11] However, as VITT is mostly identified in the community (versus HIT being identified in the hospital setting), a sharp

| INTRODUC TI ONPlatelets are critical for haemostasis, yet they also have a central role in thrombosis and cardiovascular events, which account for approximately 30% of deaths worldwide. 1 Current antiplatelet agents reduce serious vascular events by up to 25% in high-risk groups at the cost of increased bleeding complications 2 ; however, the burden of cardiovascular diseases remains compelling. A better understanding of platelet heterogeneity through specific laboratory assays can form the foundation for improvement upon current therapeutics.Platelets circulate predominantly in a quiescent state and need to undergo transformation to an activated form to perform their haemostatic duties. This transformation requires stimulus, the source of which is mostly initiated by exposure of collagen after subendothelial injury and exposure to circulating agonists including thrombin, among other platelet-activating factors. When injury occurs, platelets must undertake a range of processes to form the haemostatic plug: adhesion to site of injury, recruitment and aggregation of more platelets, and facilitating the activation of the coagulation factor cascade to generate fibrin, which stabilizes the aggregating platelets to form an effective platelet plug and stop bleeding. While it was initially thought that platelets were homogeneous and could play any of the haemostatic roles described, it is now evident that not all platelets have the same response to strong agonist stimulation, AbstractPlatelets play a critical role in both haemostasis and thrombosis, and it is now evident that not all platelets behave the same when they are called to action. A functionally distinct subpopulation of platelets forms in response to maximal agonist stimulation: the procoagulant platelet. This platelet subpopulation is defined by its ability to expose phosphatidylserine on its surface, allowing for coagulation factor complexes to form and generate bursts of thrombin and fibrin to stabilize platelet clots. Reduced