How to assess hypercoagulability in heparin-induced thrombocytopenia? Biomarkers of potential value to support therapeutic intensity of non-heparin anticoagulation

BACKGROUND: In case of heparin-induced thrombocytopenia (HIT), the switch to a non-heparin anticoagulant is mandatory, at a therapeutic dose. Such a treatment has limitations though, especially for patients with renal and/or hepatic failure. Candidate laboratory tests could detect the more coagulable HIT patients, for whom therapeutic anticoagulation would be the more justified. PATIENTS AND METHODS: This was a monocentre observational prospective study in which 111 patients with suspected HIT were included. Nineteen were diagnosed with HIT (ELISA and platelet activation assay), among whom 10 were classified as HITT + when a thrombotic event was present at diagnosis or during the first following week. Two plasma prethrombotic biomarkers of in vivo activation of the haemostasis system, procoagulant phospholipids (ProcoagPPL) associated with extracellular vesicles and fibrin monomers (FM test), as well as in vitro thrombin potential (ST Genesia; low picomolar tissue factor) after heparin neutralization (heparinase), were studied. The results were primarily compared between HITT + and HITT- patients. RESULTS: Those HIT + patients with thrombotic events in acute phase or shortly after (referred as HITT+) had a more coagulable phenotype than HIT + patients without thrombotic events since: (i) clotting times related to plasma procoagulant phospholipids tended to be shorter; (ii) fibrin monomers levels were statistically significantly higher (p = 0.0483); (iii) thrombin potential values were statistically significantly higher (p = 0.0404). Of note, among all patients suspected of suffering from HIT, we did not evidence a hypercoagulable phenotype in patients diagnosed with HIT compared to patients for whom the diagnosis of HIT was ruled out. CONCLUSION: The three tests could help identify those HIT patients the most prone to thrombosis.