No recurrent thromboembolic events, other signs of VITT relapse, or bleeding complications occurred after discharge. patients with recurrent thromboembolic events after IVIG. Direct oral anticoagulants were given after hospital discharge. Median follow-up duration was 300 days (range 153 to 380). All patients survived the acute phase of the disease and were discharged from hospital. One patient died from long-term neurological sequelae of cerebral venous sinus thrombosis 335 days after diagnosis. Eight out of nine patients were alive at last follow-up, and seven had fully recovered. Anti-PF4 antibodies remained detectable for at least 12 weeks after diagnosis, and D-Dimer Rabbit Polyclonal to VAV1 remained elevated in some patients despite oral anticoagulation. No recurrent thromboembolic events, other signs of VITT relapse, or bleeding complications occurred after discharge. In conclusion, VITT appears to be a highly prothrombotic condition. IVIG is not always successful, and eculizumab may be considered a rescue agent. Long-term management with direct oral anticoagulants appears to be safe and effective. Oridonin (Isodonol) Keywords: AZD1222, ChAdOx1 nCoV-19, COVID-19, SARS-CoV-2, vaccination, platelet activation, thrombosis, cerebral venous sinus thrombosis, cohort studies 1. Introduction Vaccines against coronavirus disease (COVID-19) were developed, licensed, and rolled out for use in the general population with unprecedented speed and success [1]. Since the beginning of 2021, about five billion people have received about 13 billion inoculations [2]. Never has a newly licensed medicine been used by more people in such a short period of time. This may have contributed to the early discovery of a new syndrome, called vaccine-induced thrombotic thrombocytopenia (VITT) or thrombosis with Oridonin (Isodonol) thrombocytopenia syndrome (TTS) [3,4]. VITT/TTS occurs 4 to 30 days after vaccination with recombinant adenoviral vectors encoding the SARS-CoV-2 spike protein, i.e., Vaxzevria (AZD1222) or Jcovden (Ad26.COV2-S) [5,6]. The pathology of the syndrome involves formation of autoantibodies against platelet factor 4 (PF4) that activate platelets, leading to thrombocytopenia and thromboembolic events of varying severity and location [7]. Sharing striking similarities with heparin-induced thrombocytopenia (HIT), TTS/VITT was soon recommended to be managed similarly: avoiding heparins and using alternative anticoagulation (e.g., with argatroban) [8,9]. High-dose intravenous immunoglobulin (IVIG) has also been recommended in analogy to treatment-refractory HIT cases and the rare autoimmune form of HIT that occurs without prior exposure to heparin [10]. Here, we report one-year outcomes of consecutive patients with VITT/TTS diagnosed at Hannover Medical School. Together with similar Oridonin (Isodonol) reports from other institutions, our data confirm that this syndrome is a highly thrombogenic disorder. Our data also shed light on the risk of failure of IVIG and on using eculizumab as an alternative mode of treatment. 2. Materials and Methods We report results of a retrospective, consecutive cohort study of patients diagnosed with VITT/TTS based on the presence of all of the following criteria: Vaccination 4 to 21 days Oridonin (Isodonol) before symptom onset. Signs or symptoms of venous or arterial thrombosis. Thrombocytopenia < 150/nL. Positive anti-platelet factor 4 (PF4) antibody. Elevated D-Dimer > 4 times upper limit of normal. The initial course of 5 of these patients has been reported previously [7]. There was no prespecified treatment protocol at the time. However, the German, Austrian and Swiss Society on Thrombosis and Haemostasis (GTH) ad hoc recommendations on diagnosis and management of VITT were used to guide treatment as soon as published (end of March 2021) [9]. After discharge from our hospital, most patients were followed in our outpatient clinic except for patient 5, for whom data were obtained by consulting the rehabilitation clinic. We collected baseline clinical and demographic data; details on thromboembolic events and bleeding; treatment information with regards to anticoagulation, immunosuppression, use of intravenous immunoglobulin (IVIG), and eculizumab; and mortality and status of neurological and general health recovery at study end. Anti-PF4 autoantibodies were assessed as previously reported [7]. In brief, anti-PF4 IgG was detected with enzyme-linked immunosorbent assay (ELISA, Hyphen BioMed, CoaChrom, Maria Enzersdorf, Austria). Flow cytometry of patient immunoglobulin (Ig) binding to healthy donor platelets was performed using platelets from type 0 donors, freshly isolated and pre-incubated with saline or AZD1222 in the absence or existence of heparin (100 IU/mL) for 30 min. Serum Oridonin (Isodonol) samples were added. After 30 min, fluorescein isothiocyanate-labelled anti-human immunoglobulin G was put into detect antibody binding. The drug-to-saline mean fluorescence strength (MFI) percentage was determined. Ratios above 2.0 were considered.