Long-Term Outcomes after Vaccine-Induced Thrombotic Thrombocytopenia.

Vaccine-induced thrombotic thrombocytopenia (VITT), or thrombosis with thrombocytopenia syndrome (TTS), is a rare but serious complication of adenovirus-based vaccines against severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Observation of long-term outcomes is important to guide treatment of affected patients. This single-center consecutive cohort study included all patients diagnosed based on (1) vaccination 4 to 21 days before symptom onset, (2) signs or symptoms of venous or arterial thrombosis, (3) thrombocytopenia < 150/nL, (4) positive anti-platelet factor 4 (PF4) antibody, and (5) elevated D-Dimer > 4 times the upper limit of normal. Nine patients were enrolled. Acute management consisted of parenteral anticoagulants, corticosteroids, intravenous immunoglobulin (IVIG), and/or eculizumab. Eculizumab was successfully used in two 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 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.

Evaluating the Usefulness and Acceptability of a Revision-Purposed 'Specialties' Webinar for Educating UK-Based Fifth and Final Year Medical Students During the COVID-19 Pandemic: Is This the Future of Medical Education?

BACKGROUND: To assess whether an online course is a useful method of learning for medical students revising for specialty examinations in the context of social distancing restrictions during the COVID-19 pandemic. METHODS: A free, one-day webinar was offered to fifth and final year medical students with an examination-based approach. Teaching was delivered by trainees in Psychiatry, Obstetrics and Gynaecology and Paediatrics (the 'specialties'). An online, questionnaire-based cross-sectional study was conducted to assess usefulness and acceptability of the webinar by enrolled students, who were invited to complete the research questionnaire. Student responses pertaining to knowledge, confidence and interest, pre- and post-webinar, were collected and analysed. RESULTS: A total of 247 students attended the webinar, with a 98.4% response rate to the questionnaire. Ninety-one percent of students agreed that webinars offer flexibility and convenience. About 55.1% felt that the pandemic had impacted their ability to learn new information. About 92.7% felt that the webinar was useful. Matched data showed an increase in participants' knowledge (p = <0.001) and confidence (p < 0.001). CONCLUSION: Online learning provides a useful, accessible and safe method of providing medical education in the context of the global pandemic. Webinars adopting a lecture-based, examination-style approach improved students' perceived confidence and knowledge.

PF4-Dependent Immunoassays in Patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia: Results of an Interlaboratory Comparison.

BACKGROUND: Coronavirus disease 2019 vaccine ChAdOx1 nCov-19 may rarely lead to vaccine-induced thrombotic thrombocytopenia (VITT). Antibody-mediated, platelet factor 4 (PF4)-dependent platelet activation appears to resemble a key mechanism in VITT, partially comparable to heparin-induced thrombocytopenia. The use of PF4/heparin immunoassays has been proposed as part of a diagnostic approach, but their sensitivity has not been established. METHODS: Sera from 12 well-defined VITT patients were first studied by two different laboratories in functional assays. Sera where then used for an interlaboratory comparison, in which five different PF4/heparin immunoassays were used by four laboratories. RESULTS: Results for functional testing were highly concordant. VITT antibodies were also reliably detected by PF4/heparin enzyme-linked immunosorbent assays (ELISAs) (92-100%). In contrast, only 25% of VITT antibodies were reactive in a particle gel immunoassay (PaGIA), and 8% in a lateral flow assay (LFA). An automated chemiluminescence immunoassay (CLIA) was negative for all sera tested (0%). CONCLUSION: It seems feasible to establish functional antibody testing for the confirmation of VITT. For the initial screening of suspected VITT cases, PaGIA, LFA, and CLIA are useless when applied as single tests. Only ELISA-based PF4/heparin immunoassays are sensitive enough to be incorporated in the diagnostic workup. However, a combination of a positive ELISA and a negative CLIA may be useful to identify VITT antibodies in the absence of confirmatory functional assays.