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.

Aims: To describe long-term clinical and serological outcomes after VITT.

Methods: A case series of patients from Leuven University Hospitals with confirmed VITT and at least six 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 200IU/ml of heparin was measured by whole-blood impedance aggregometry (HIMEA) (Roche® multiplate analyser).

Results: 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 three months and in one out of three after more than six 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 1 – clinical characteristics, presenting symptoms and lab parameters, and treatment of three cases of vaccine-induced thrombotic thrombocytopenia.

HIT: heparin-induced thrombocytopenia; PF4: platelet factor 4; ELISA: enzyme-linked immunosorbent assay; OD: optical density; HIMEA: heparin-induced multi-electrode aggregometry; AUC: area under the curve

Figure 1 – Evolution of anti-PF4 IgG ELISA optical density and anti-PF4 induced platelet aggregation

Persistent presence of anti-PF4 antibodies for several months was noted in case 1 and 2, but not case 3. Patient plasma induced typical platelet aggregation at presentation in case 2 and 3, but persistent anti-PF4 antibodies during follow-up did not trigger platelet aggregation. PF4: platelet factor 4, ELISA: enzyme-linked immunosorbent assay; OD: optical density; HIMEA: heparin-induced multi-electrode aggregometry

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