platelet factor 4 antibody thrombotic and thrombocytopenia syndromes

Introduction

antibodies against platelet factor 4 can cause life threatening thrombosis and [thrombocytopenia]]

immune heparin-induced thrombocytopenia (HITS)
adenovirus-induced antibodies against PF4
- thrombosis with thrombocytopenia syndrome (TTS / VITT / VIPIT)
- adenoviral infections may rarely cause this syndrome
  - in 2023, 5-year-old boy who had been diagnosed as an outpatient with adenovirus infection developed cerebral sinus vein thrombosis and severe thrombocytopenia

Anti-PF4/heparin antibodies are detected by ELISA in ~10% of all patients receiving unfractionated heparin in therapeutic settings for at least a week. The incidence is higher after orthopedic surgery [3] and reaches 50% in patients undergoing cardiopulmonary bypass surgery, an incidence 20-fold higher than clinical HIT. ¹⁾
PF4 is capable of forming stable complexes with clinically relevant adenoviruses ²⁾
group 1 antibodies: most antibodies with binding forces to PF4/H complexes <60 pN do not activate platelets, even in the presence of polyanions
group 2 antibodies with binding forces between 60 and ∼100 pN activate platelets in the presence of polyanions
group 3 antibodies with binding forces >100 pN activate platelets even in the absence of polyanions and these bind not only to PF4/Heparin complexes but also to PF4 alone - to be able to activate platelets, group-3 ABS and PF4 have to be in close proximity to the platelet surface ³⁾

¹⁾

GOWTHAMI AREPALLY, … DOUGLAS B. CINES, in Autoantibodies (Second Edition), 2007

²⁾

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