Platelet factor 4 (PF4), a
protein stored in the alpha-granules of platelets and released upon activation, forms cationic tetramers that bind with various polymeric
anions, including
heparin. Some individuals develop
antibodies against PF4 in complex with
heparin (PF4/H), which potentially lead to the onset of
heparin induced
thrombocytopenia (HIT). In some patients, this may cause activation and aggregation of platelets, promoting pathological
thrombosis, in a process called
heparin induced
thrombocytopenia with
thrombosis ('HITT'). Laboratories can assess for the presence of these
antibodies using many PF4 antibody tests, including by
enzyme linked
immunosorbent assay (ELISA),
latex immunoassay (LIA), chemiluminescence immunoassay (CLIA) and even rapid nanoparticle based lateral flow immunoassays. All these assays can identify such
antibodies with high sensitivity, but methods may have variable specificity. For example, several studies have shown CLIA assays to have higher specificity to HITT than ELISA assays. Very recently, a new 'HITT-like' syndrome has been described in some individuals receiving adenovirus based
COVID-19 (
coronavirus disease 2019) vaccines. This condition has been given several names, including
vaccine induced thrombotic
thrombocytopenia (VITT) and
thrombosis with
thrombocytopenia syndrome (TTS), and also involves a mechanism mediated by
antibodies formed against PF4. These
antibodies can also be detected by PF4 antibody tests, but detection sensitivity appears to favour ELISA assays, with most other tests (including CLIA and LIA) not generally capable of detecting such
antibodies. Additional functional assays assessing for PF4 mediated platelet activation may also be performed. The current review is focussed on laboratory testing for PF4
antibodies, in particular to distinguishing patterns in HITT versus VITT.