ABSTRACT
Introduction.Vaccine induced immune thrombocytopenia and thrombosis (VITT) following ChAdOx1 nCOV-19 vaccine has been described, associated with unusual site thrombosis, thrombocytopenia, raised D-dimer and high titre immunoglobulin-G (IgG) class anti-Platelet Factor 4 (PF4) antibodies. Laboratory management of suspected cases begins with a sensitive anti PF4 antibodies binding assay (PF4-ELISA). If the PF4 binding assay is negative, this patient does not have Heparin induced Thrombocytopenia (HIT) or VITT. If the PF4 binding assay is positive, the positivity should be confirmed with one or multiple HIT functional assays as available, such as the serotonin release assay (SRA), heparin-induced platelet activation assay, platelet aggregation (PAT) test, flow cytometry test.Methods.We summarized clinical and laboratory findings of 7 patients in Piedmont who developed thrombosis and thrombocytopenia following AZD1222 vaccination. Plasma from all patients was used to test for anti PF4 antibodies by 2 different ELISA assays (Immucor and Stago) and by 2 different HIT functional assays, PAT and flow cytometry (HIT alert test) both performed in the presence of heparin, PF4 or both.Results.The 7 patients [6 males and 1 female, median age: 38 (range:31-76)] presented with thrombosis 2 to 17 days post vaccination: 5 males had deep vein thrombosis not in unusual sites, 1 male had stroke and the female had cerebral venous thrombosis (CVT). None had received heparin prior symptoms onset. Only 2 out of 7 patients tested positive for anti PF4 ELISA antibodies with both assays: the men with stroke showed low positivity (OD = 0,56 and 0,41) and the female with CVT strong positivity (OD = 3,2 and 3,87). Only the female patient with CVT tested positive with both HIT functional assays, PAT and HIT alert cytometry test in the presence of PF4 independently of heparin. Both assays were inhibited by high concentrations of heparin.Conclusions. In our limited experience VITT demonstrated to be an extremely rare event in the context of AZD1222 COVID-19 vaccination even in the subset of patients with thrombosis and thrombocytopenia.
ABSTRACT
Objective: CREST began in 2005 as a partnership between the ASRM, the National Institute for Child Health and Human Development, and the Duke University Clinical Research Training Program to train REI subspecialists in the conduct of clinical research. The program evolved to include urologists and other Ob-Gyn subspecialists seeking to develop their clinical research skills. Program support transitioned to an R25 grant after intramural NICHD support was terminated. CREST has trained over 100 Scholars to date. Evaluation of its first 6 years in 2012 indicated a desire for more mentoring and career advancement opportunities for Scholars. The current project sought to evaluate the recent experience of CREST Scholars to assess programmatic progress and further opportunities for improvement. Materials and Methods: Invitations to 41 Scholars from the 2013-2019 cohorts were sent by an independent evaluation entity. Scholars were invited to complete an on-line survey as well as participate in interviews. Survey questions asked about satisfaction with program components and the extent to which Scholars felt supported throughout the program. Scholar interviews centered on their experiences engaging with the program, perceptions of how CREST may have affected their careers, and the extent to which CREST contributed to Scholars’ ability to conduct ongoing research. Results: 22/41 invited Scholars completed the online survey (54%). 18/22 Scholars found the clinical research online training to be an ‘overwhelmingly positive’ experience, enabling them to acquire new and practical knowledge and skills to further their own research and/or better critique others;research. 12/22 Scholars felt very supported by program faculty and positive about mentorship throughout the program. Collaborativeness and response time of mentors were specifically cited. 6 Scholars felt specifically that CREST had motivated them to take a more research-oriented focus in their careers. A majority of Scholars interviewed believed that CREST participation helped them acquire a new leadership position or promotion. Specific barriers to research career development cited included inadequate protected time, COVID-19, and being in a subspecialty that did not quite ‘fit’ within the purview of CREST. The single biggest benefit of the program among Scholars interviewed were the networking and mentorship aspects. The proportion of Scholars who reported feeling 'very satisfied' or 'satisfied' with the program components were: 90% for the formal educational training program, 90% for the supporting faculty, 80% for the biostatistical support provided by CREST, and 68% for the manuscript publication process. Conclusions: The CREST Program continues to evolve as a premiere educational opportunity for physicians who practice reproductive medicine. CREST appears to influence physician scientists towards pursuing more research. Ongoing support through networking and career development are desired attributes of the program that can be further expanded. Impact Statement: The CREST Program has positive impact on careers beyond publications.