ABSTRACT
Background: Several studies have been published on a rare side effect of severe venous thrombosis at unusual sites and thrombocytopenia after vaccination against SARS-CoV- 2, referred to as vaccine-induced immune thrombocytopenia and thrombosis (VITT). Aim(s): To identify new cases of acute splanchnic vein thrombosis (SVT) or Budd-Chiari Syndrome (BCS) who presented following SARS-CoV- 2 vaccination in the Vascular Liver Disease Group (VALDIG) network, and to evaluate the incidence of VITT. Method(s): We conducted a prospective international cohort study between May 1st, 2021 and January 10th, 2022, on consecutive patients with acute SVT or BCS who presented within 6 weeks following any type or dose of SARS-CoV- 2 vaccination. Anonymous data were collected including baseline characteristics, risk factors, treatment and survival. Cases were identified as definite VITT, probable VITT or possible VITT or unlikely VITT as defined by Pavord et al (NEJM 2021). Result(s): 25 patients with acute (N = 24) or recurrent (N = 1) SVT or BCS were collected from 14 centers in 4 countries (after ChAdOx1 nCoV-19 N = 11, BNT162b2 N = 9, Ad26.COV2.S N = 1, mRNA-1273 N = 1). Median time after vaccination to symptoms was 10 days (2-40). Median age was 52.5 years (21-66), 52% were female. Three patients (12%) fulfilled criteria for definite VITT, 6 (24%) for probable VITT, 2 (8%) for possible VITT, 14 (56%) for unlikely VITT. Thrombosis was located in the portal vein (N = 20), hepatic vein(s) (N = 9), mesenteric vein (N = 18) or splenic vein (N = 9). Concomitant extra-abdominal thrombosis was seen in 5 patients (20%). Patients were treated with LMWH (60%), DOACs (24%) or VKA (40%). Six (2/3 with definite VITT) received IVIG. Thrombophilia was found in 5 patients and 3 had a myeloproliferative neoplasm. Conclusion(s): 25 cases of acute SVT or BCS following SARS-CoV- 2 vaccination were identified. Although definite VITT was rare (12%), no underlying disorder was identified in the majority of patients, contrary to 'typical' cases of SVT and BCS.
ABSTRACT
Background : Adeno-associated virus (AAV)-mediated gene therapy is being investigated as a treatment for people with hemophilia A (PwHA). Commonly studied AAV serotypes include AAV5, AAV6, and AAV8. Pre-existing immunity against these AAVs restricts patient eligibility yet, published data on AAV seroprevalence and seroconversion rate in PwHA are limited. Aims : To describe design and recruitment methods used for the SAVVY study. This study is designed to characterize AAV antibody prevalence and titers, evaluate changes in antibody titer over time, and examine factors that may influence antibody positivity, titer, and seroconversion. Study design and recruitment methods seek to minimize the need for in-person study interactions during the COVID-19 pandemic. Methods : SAVVY is a patient-centered, decentralized, prospective, observational study involving blood draws at 2 time points. The target sample size of 1,000 PwHA represents approximately 5% of PwHA in the US. SAVVY employs a user-friendly mobile application, provides remote recruitment through e-consent, and uses a network of 1,800+ laboratories throughout the US for biospecimen sample collection. This approach minimizes patient travel, reduces potential exposure to COVID-19, and removes burden from HTC staff to perform study assessments. Recruitment has leveraged various forms of virtual outreach to physicians, HTC staff, and patient advocacy groups;direct-to-patients are being used to create awareness of the study and its scientific aims. See Table 1. Results : First patient enrollment occurred within four months of final protocol;41 patients were enrolled within 2 weeks of activation. At the time of abstract submission, 105 patients had consented to participate. Conclusions : The COVID-19 pandemic disrupted the progress of clinical studies necessary for the advancement of treatments. Adaptability to existing conditions is critical. Careful study design and multi-modal engagement with the hemophilia community can facilitate the conduct of studies, minimize risks associated with COVID-19, and may enhance patient experience and clinical trial recruitment.