Re-evaluation of the risk of venous thromboembolism after COVID-19 vaccination using haematological criteria

An elevated risk of venous thromboembolism (VTE) following a first dose of the ChAdOx1 adenovirus-vectored vaccine was found in a national epidemiological study in England using routine discharge diagnosis codes. Separately, the syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) was identified using haematological criteria based on presence of thrombocytopenia, significantly elevated D-dimers and development of anti-PF4 antibodies. To re-evaluate risk estimates using haematological criteria, we obtained the haematology results for hospital admitted patients aged 18-64 years in 43 National Health Service trusts in England who were included in the national epidemiological study. Diagnoses were confirmed and haematological parameters obtained from local records without knowledge of vaccination status. The haematological parameters in patients admitted for a confirmed VTE following ChAdOx1 or BNT162b2 mRNA vaccination were then compared with those in a randomly selected 40% sample of unvaccinated patients with VTE. Overall, 12 (14%) of the 84 vaccinated cases had a diagnosis compatible with VITT, 11 after a first dose of ChAdOx1 and one after a first dose of BNT162b2. Thrombocytopenia (platelet count <150x109/L) occurred in 17 vaccinated (20%) and 4 (4%) of 108 unvaccinated patients, with all 6 cases of severe thrombocytopenia (<50x109/L) occurring within 42 days of a first dose of ChAdOx1. The attributable risk estimates for a cerebral venous thrombosis (CVT) or other VTE with thrombocytopenia after a first dose of ChAdOx1 vaccine were 2.82 and 9.62 per million doses respectively. However, elevated risks were also found after a first dose of ChAdOx1 for VTE without thrombocytopenia with relative incidences for CVT and other VTE of 2.67 (1.77-3.77) and 1.93 (1.57-2.35) respectively. While we identified a distinct population with features of VITT within 42 days of receiving ChAdOx1 vaccination, confirming current diagnostic criteria, we also found evidence of an increased risk of a VTE without thrombocytopenia after ChAdOx1 vaccine.

The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura.

Rituximab, an anti-CD20 monoclonal antibody, can be used to treat immune thrombotic thrombocytopenic purpura (iTTP) during acute presentation or disease relapse. Undesirable side-effects include severe hypersensitivity reactions, particularly anaphylaxis and rituximab-induced serum sickness, with a minority not maintaining a response to treatment. Alternative humanised anti-CD20 treatments, obinutuzumab and ofatumumab, have been used. A review of the UK TTP Registry showed 15 patients received these drugs over 26 treatment episodes (eight obinutuzumab and 18 ofatumumab). Indications for alternative anti-CD20 treatment were severe infusion-related reactions, acute rituximab-induced serum sickness and a short duration of disease remission. All patients achieved disease remission (ADAMTS13 [A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13] activity ≥30 iu/dl) after a median 15 days and 92% of episodes achieved complete remission (≥60 iu/dl). Seven patients required further treatment for disease relapse with a median relapse-free survival of 17.4 months. All patients continued to respond to re-treatment with the preceding drug when relapse occurred. There were four adverse events in 26 treatment episodes (15%) - two infections and two infusion reactions. These results suggest that obinutuzumab and ofatumumab may be considered as an alternative option to rituximab in the treatment of iTTP with a comparable safety profile, absence of significant hypersensitivity reactions and sustained normalisation of ADAMTS13.

A Comparison of Thrombosis and Hemorrhage Rates in Patients With Severe Respiratory Failure Due to Coronavirus Disease 2019 and Influenza Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: Extracorporeal membrane oxygenation is a lifesaving therapy for patients with severe acute respiratory distress syndrome refractory to conventional mechanical ventilation. It is frequently complicated by both thrombosis and hemorrhage. A markedly prothrombotic state associated with high rates of venous thromboembolism has been described in patients with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) infection. These rates have currently not been described during extracorporeal membrane oxygenation in comparison to other viral pneumonias. DESIGN: Retrospective observational study. SETTING: Single high-volume tertiary critical care department at a university hospital. PATIENTS: Patients 16 years old or greater receiving venovenous extracorporeal membrane oxygenation between March 1, 2020, and May 31, 2020, with coronavirus disease 2019 were compared with a cohort of patients with influenza pneumonia between June 1, 2012, and May 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The rates of venous thromboembolism and hemorrhage were compared in patients with coronavirus disease 2019 against a historic population of patients with influenza pneumonia who required extracorporeal membrane oxygenation. There were 51 patients who received extracorporeal membrane oxygenation due to coronavirus disease 2019 and 80 patients with influenza. At cannulation for extracorporeal membrane oxygenation, 37% of patients with coronavirus disease 2019 compared with 8% of patients with influenza had filling defects on CT pulmonary angiography (p = 0.0001). Catheter-associated deep vein thrombosis shown on ultrasound Doppler after decannulation was present in 53% with coronavirus disease 2019 versus 25% with influenza (p = 0.01). The rates of intracranial hemorrhage at the time of cannulation were 16% with coronavirus disease 2019 and 14% with influenza (p = 0.8). Elevated d-dimer levels were seen in both conditions and were significantly higher in those with pulmonary thromboembolism than those without in coronavirus disease 2019 (p = 0.02). Fibrinogen and C-reactive protein levels were significantly higher in those with coronavirus disease 2019 than influenza (p < 0.01). CONCLUSIONS: Significant rates of pulmonary thromboembolism and of catheter-associated deep vein thrombosis were seen in both viral infections but were greater in those requiring the use of extracorporeal membrane oxygenation in coronavirus disease 2019 than for influenza.

Blood component use in critical care in patients with COVID-19 infection: a single-centre experience.

There has been a significant surge in admissions to critical care during the coronavirus disease 2019 (COVID-19) pandemic. At present, the demands on blood components have not been described. We reviewed their use during the first 6 weeks of the outbreak from 3 March 2020 in a tertiary-level critical care department providing venovenous extracorporeal membrane oxygenation (vv-ECMO). A total of 265 patients were reviewed, with 235 not requiring ECMO and 30 requiring vv-ECMO. In total, 50 patients required blood components during their critical care admission. Red cell concentrates were the most frequently transfused component in COVID-19-infected patients with higher rates of use during vv-ECMO. The use of fresh frozen plasma, cryoprecipitate and platelet transfusions was low in a period prior to the use of convalescent plasma.