Background The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity. Methods We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications. Results In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d -dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms. Conclusions Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.

Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study (NCT04858568) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.

Despite over 20 million unrelated donors being listed worldwide, donor attrition at the confirmatory typing (CT) stage of donor acquisition is a key source of delay. Anthony Nolan undertook a study of CT requests from 2010 to 2011 to identify factors associated with attrition. Of 7541 CT requests, 38.2% were cancelled for donor reasons. Of these, 19.4% were personal, 34.1% medical, 36% no contact, 7.9% emigrated and 2.6% others. African (odds ratio (OR) 2.78, P<0.001), African-Caribbean (OR 3.07, P<0.001), Asian (OR 2.65, P<0.001), Jewish (OR 1.54, P=0.009) and Mediterranean (OR=2.38, P<0.001) donors were more likely not to be available compared to Caucasian donors. Female donors were also more likely not to be available (OR=1.32, P<0.001): primarily due to pregnancy. Older donors were less likely to be available in univariate analysis, but this association was not significant after controlling for other factors. Blood donors and those recruited within the past five years had lower rates of attrition. Accumulation of additional attrition-associated characteristics for a given donor was associated with progressively greater odds of attrition (OR 1.99, 2.52, 3.4 and 5.53, respectively, for 1, 2, 3 and 4 risk factors, P<0.001). Donor registries must develop evidence-driven strategies to recruit and retain the most reliable donors.