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Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but severe complication following COVID-19 vaccination, marked by thrombocytopenia and thrombosis. Analogous to heparin-induced thrombocytopenia (HIT), VITT shares similarities in anti-platelet factor 4 (PF4) IgG-mediated platelet activation via the FcγRIIa. To investigate the involvement of platelet-antibodies in VITT, we analyzed the presence of platelet-antibodies directed against glycoproteins (GP)IIb/IIIa, GPV and GPIb/IX in the serum of 232 clinically suspected VITT patients determined based on (suspicion of) occurrence of thrombocytopenia and/or thrombosis in relation to COVID-19 vaccination. We found that 19% of clinically suspected VITT patients tested positive for anti-platelet GPs: 39%, 32% and 86% patients tested positive for GPIIb/IIIa, GPV and GPIb/IX, respectively. No HIT-like VITT patients (with thrombocytopenia and thrombosis) tested positive for platelet-antibodies. Therefore, it seems unlikely that platelet-antibodies play a role in HIT-like anti-PF4-mediated VITT. Platelet-antibodies were predominantly associated with the occurrence of thrombocytopenia. We found no association between the type of vaccination (adenoviral vector vaccine versus mRNA vaccine) or different vaccines (ChAdOx1 nCoV-19, Ad26.COV2.S, mRNA-1273, BTN162b2) and the development of platelet-antibodies. It is essential to conduct more research on the pathophysiology of VITT, to improve diagnostic approaches and identify preventive and therapeutic strategies.

Background: Routine monitoring direct oral anticoagulants (DOAC) is not recommended, yet DOAC levels are frequently measured in clinical practice. Interpretation of levels, especially those outside expected ranges, is challenging. Until now it's unclear which patients are at risk for these levels. Aim: Identify clinical characteristics of patients with DOAC levels outside expected ranges. Methods: Patients of 2 Dutch academic medical centers with a DOAC concentration measured between 2012 and 2019 were included. DOAC levels above upper limit peak and below lower limit trough ranges, based on DOAC registration trials, were assigned outside expected range. Differences between patients were evaluated using Chi-square, independent sample-T tests and multivariable logistic regression analysis. Results: Of 597 patients with DOAC measurement, 108 (18.1%) had levels outside expected ranges. Compared to patients with levels within range, patients with levels above range (n = 64) were older (71.1 vs. 60.6 years), more often had creatinine clearance