Long-term persistence of anti-PF4- antibodies following vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination

Background: Vaccine-induced Thrombotic Thrombocytopenia (VITT) is a rare but potentially life-threatening complication of the ChAdOx1 COVID-vaccine, which involves binding of IgG antibodies against platelet factor 4 (PF4) to the platelet Fc-gamma receptor. This causes platelet activation with thrombosis and thrombocytopenia. Because of the similarity with heparin-induced thrombocytopenia (HIT), heparin is avoided in the acute treatment of VITT. There is limited information about the long-term persistence of anti-PF4- antibodies and their clinical relevance. Aim(s): To describe long-term clinical and serological outcomes after VITT. Method(s): A case series of patients from Leuven University Hospitals with confirmed VITT and at least 6 months of follow-up. All patients provided informed consent. Anti-PF4 antibodies were measured via chemiluminescence (HemosIL AcuStar HIT-IgG( PF4-H), Werfen) and enzyme-linked immunosorbent assay (ELISA) with immobilised polyvinylsulfonate/PF4 complexes (PF4-IgG Immucor, GTI Diagnostics);with an optical density (OD) cut-off of 0.4. Aggregation of platelets after exposure to patient plasma with 0, 1 or 200 IU/ml of heparin was measured by whole-blood impedance aggregometry (HIMEA) (Roche multiplate analyser). Result(s): Three middle-aged women presented with thrombosis with thrombocytopenia and a positive anti-PF4 ELISA 9 to 16 days after first ChAdOx1 vaccination. Their clinical presentation, lab results and treatment are summarised in Table 1. All patients recovered rapidly after non-heparin anticoagulation with (case 2-3) or without (case 1) intravenous immunoglobulins. All patients received subsequent COVID-vaccination with an mRNA-based vaccine without thrombocytopenia or symptoms. Anti-PF4- antibodies remained elevated in two patients after 3 months and in one out of three after more than 6 months, but HIMEA results for all follow-up tests became negative (Figure 1). Conclusion(s): We report good short-and long-term outcomes of three cases of VITT, including successful subsequent vaccination with an mRNA vaccine. Anti-PF4- antibodies can persist for at least several months. In contrast with the initial presentation, these persistent anti-PF4- antibodies did not trigger platelet activation in our patients. (Table Presented).

Weight adjusted prophylactic to intermediate dosed thromboprophylaxis in COVID-19

Background : COVID-19 is frequently associated with venous thromboembolism (VTE), and the use of thromboprophylaxis has been suggested to improve hospitalized patients ' outcomes. We, therefore, intensified our thromboprophylactic protocol starting March 31st. Aims : We aimed to validate the implementation of an intensified thromboprophylactic protocol by reporting VTE incidence and safety while awaiting randomized controlled trials. Methods : On March 31st, 2020, we implemented an intensified thromboprophylactic protocol based on weight and disease severity (50 IU anti-Xa LMWH/kg, once daily at the ward, twice daily at the intensive care unit (ICU)). ICU patients were monitored daily with anti-Xa serum levels. Full therapeutic doses were restricted to patients with a prior indication for therapeutic anticoagulation or confirmed VTE. As early reports demonstrated high VTE incidence, screening with duplex ultrasound became standard of care in our center as soon as logistically possible. We excluded patients with a prior indication for therapeutic anticoagulation and incidental findings of COVID-19 for analysis. The ethical committee has approved this observational study. Results : We analyzed 412 symptomatic and confirmed Covid-19 cases, of which 116 were admitted to the ICU. All symptomatic VTE cases were reported, and 20% of all patients (38% of ICU patients) received screening with venous ultrasound. In 219 patients who received the standard dose of LMWH, 16 patients (7.3%) had VTE, 10 of which were symptomatic (4.6%) (Figure 1). In 193 patients who received intensified thromboprophylaxis, there were no symptomatic VTE cases, three incidental DVT cases (1.6%), and one incidental pulmonary embolism (0.5%). Interestingly, rates of major bleeding were low (Figure 2). Conclusions : In a large cohort of hospitalized patients with COVID-19, we report no symptomatic VTE after implementing systematic thromboprophylaxis with weight-adjusted prophylactic (ward) to intermediate (ICU), but not therapeutic doses of LMWH. This strategy was associated with a low risk of major bleeding.

Anticoagulant therapy in COVID-19 critically ill: Should we go for more?

Critically ill COVID-19 patients often develop a severe pro-thrombotic milieu, as reflected by the markedly increased d-dimer levels. Several cohort studies have reported high rates of thrombotic complications, including deep venous thrombosis (DVT) and pulmonary embolism (PE), myocardial infarction, stroke and microvascular thrombosis. Accordingly, COVID-19 patients who are hospitalized either at a normal, non-intensive care unit (ICU) or at the ICU need to receive appropriate dosages of anticoagulant therapy to prevent or treat these thrombotic complications. This manuscript summarizes the institutional guidance for the antithrombotic prophylaxis and treatment of VTE as outlined by a multidisciplinary team of experts during the first weeks of the COVID-19 pandemic in Europe. Controlled studies are needed to verify the optimal anticoagulation for both prophylaxis and treatment.