Background The COVID‐19 Vaccine from AstraZeneca (AZD1222) is one of several vaccines introduced to provide immunity against SARS‐CoV‐2. Recently, more than 50 cases have been reported presenting a combination of thrombosis, thrombocytopenia and remarkably high levels of anti‐PF4/polyanion antibodies post‐AZD1222 vaccination. Now linked to the vaccine, the condition is referred to as vaccine‐induced thrombotic thrombocytopenia (VITT). The European Medicines Agency still recommends vaccination with AZD1222, but several European countries have temporally paused and/or restricted its use because of the perceived risk of this severe side effect. As there is no description of PF4/polyanion antibody testing in the clinical trials, knowledge about the prevalence of such antibodies in a vaccinated cohort is needed. Objectives To investigate prevalence of thrombocytopenia and anti‐PF4/polyanion antibodies in a population recently vaccinated with AZD1222. Patients/Methods 492 health care workers recently vaccinated with the first dose of AZD1222 were recruited from two hospitals in Norway. Study individuals were screened for thrombocytopenia and the presence of anti‐PF4/polyanion antibodies with a PF4/PVS IgG ELISA immunoassay. Side effects after vaccination were registered. Results The majority of study participants had normal platelet counts and negative immunoassay. Anti‐PF4/polyanion antibodies without platelet activating properties were only detected in 6 individuals (OD ≥ 0.4, range 0.58‐1.16), all with normal platelet counts. No subjects had severe thrombocytopenia. Conclusions We found low prevalence of both thrombocytopenia and antibodies to PF4/polyanion‐complexes among Norwegian health care workers after vaccination with AZD1222.

T-cell responses have been implicated in the development of HPA-1a–induced neonatal alloimmune thrombocytopenia (NAIT). However, HPA-1a–specific T cells have neither been isolated nor characterized. Here, we aimed to determine whether HPA-1a–specific T cells could be isolated from HPA-1a–immunized women. In the present study, peripheral blood mononuclear cells (PBMCs) from an HPA-1a–alloimmunized woman were cultured for weeks in the presence of HPA-1a peptide, labeled with CFSE, and assayed for antigen-specific proliferation. Individual proliferating cells were isolated by fluorescence-activated cell sorting and expanded in culture. Antigen specificity and HLA restriction were determined by cytokine secretion (enzyme-linked immunospot [ELISPOT]) and proliferation assays. Several CD3⁺CD4⁺ T-cell clones were isolated that proliferated and secreted cytokines in response to HPA-1a peptide. Two of these clones have been established in long-term culture in our laboratory. Both of these recognize synthetic as well as naturally processed HPA-1a antigen, and the recognition is restricted by the MHC molecule HLA-DRB3*0101 that is strongly associated with NAIT. These HPA-1a–specific T-cell clones represent unambiguous evidence for the association of T-cell responses with NAIT, and they will serve as unique tools to elucidate the cellular immune response that may result in NAIT.

Vaccine‐induced immune thrombotic thrombocytopenia (VITT) has so far only been reported after adenovirus vector severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines. We report findings in a 25‐year‐old woman who presented with thrombocytopenia, venous thrombosis, elevated D‐dimer levels, and high levels of platelet‐activating antibodies to platelet factor 4‐polyanion complexes 10 days after Gardasil 9 vaccination for human papillomavirus (HPV). The patient exhibited clinical and laboratory features in line with the recently defined VITT syndrome, described after adenoviral vector vaccination to prevent coronavirus disease 2019. We report a case of VITT following HPV vaccination. This should raise awareness of the possibility of VITT also occurring after other vaccines, not exclusively adenoviral vector‐based SARS‐CoV‐2 vaccines.

Uncertainty regarding the pathophysiology of fetal and neonatal alloimmune thrombocytopenia (FNAIT) has hampered the decision regarding how to identify, follow-up and treat the women and children with this potentially serious condition. Since knowledge of the condition is derived mainly from retrospective studies, understanding of the natural history of this condition remains incomplete. General screening programs for FNAIT have still not been introduced, mainly because of a lack of reliable risk factors and effective treatment. Now, several prospective screening studies involving up to 100,000 pregnant women have been published and the results have changed the understanding of the pathophysiology of FNAIT and, thereby, the approach toward diagnostics, prevention and treatment in a more appropriate way.

Maternal alloantibodies to human platelet antigen-1a can cause severe intracranial hemorrhage in a fetus or newborn. Although never evaluated in placebo-controlled clinical trials, most Western countries use off-label weekly administration of high-dosage intravenous immunoglobulin in all pregnant women with an obstetrical history of fetal and neonatal alloimmune thrombocytopenia. In Norway, antenatal intravenous immunoglobulin is only recommended in pregnancies wherein a previous child had intracranial hemorrhage (high-risk) and is generally not given in other human platelet antigen-1a alloimmunized pregnancies (low-risk). To compare the frequency of anti-human platelet antigen-1a-induced intracranial hemorrhage in pregnancies at risk treated with intravenous immunoglobulin vs pregnancies not receiving this treatment as a part of a different management program. This was a retrospective comparative study where the neonatal outcomes of 71 untreated human platelet antigen-1a-alloimmunized pregnancies in Norway during a 20-year period was compared with 403 intravenous-immunoglobulin-treated pregnancies identified through a recent systematic review. We stratified analyses on the basis of whether the mothers belonged to high- or low-risk pregnancies. Therefore, only women who previously had a child with fetal and neonatal alloimmune thrombocytopenia were included. Two neonates with brain bleeds were identified from 313 treated low-risk pregnancies (0.6%; 95% confidence interval, 0.2-2.3). There were no neonates born with intracranial hemorrhage of 64 nontreated, low-risk mothers (0.0%; 95% confidence interval, 0.0-5.7). Thus, no significant difference was observed in the neonatal outcome between immunoglobulin-treated and untreated low-risk pregnancies. Among high-risk mothers, 5 of 90 neonates from treated pregnancies were diagnosed with intracranial hemorrhage (5.6%; 95% confidence interval, 2.4-12.4) compared with 2 of 7 neonates from nontreated pregnancies (29%; 95% confidence interval, 8.2-64.1; P=.08). The most reliable data hitherto for the evaluation of intravenous immunoglobulins treatment in low-risk pregnancies is shown herein. We did not find evidence that omitting antenatal intravenous immunoglobulin treatment in low-risk pregnancies increases the risk of neonatal intracranial hemorrhage.