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Activated Platelet‐Derived and Leukocyte‐Derived Circulating Microparticles and the Risk of Thrombosis in Heparin‐Induced Thrombocytopenia: A Role for PF4‐Bearing Microparticles?
Author(s) -
Campello Elena,
Radu Claudia M.,
Duner Elena,
Lombardi Anna M.,
Spiezia Luca,
Bendo Raffaele,
Ferrari Silvia,
Simioni Paolo,
Fabris Fabrizio
Publication year - 2018
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.21507
Subject(s) - platelet , platelet activation , thrombosis , medicine , tissue factor , heparin , p selectin , platelet factor 4 , heparin induced thrombocytopenia , annexin , annexin a5 , flow cytometry , odds ratio , gastroenterology , immunology , coagulation
Background Though the presence of platelets‐derived microparticles (MPs) have previously been described in heparin‐induced thrombocytopenia (HIT), the mechanism of thrombosis in HIT remains poorly understood. We aimed to assess the presence and origin of MPs in patients with HIT and their possible contribution to HIT with thrombosis (HITT). Methods Forty‐five patients with HIT and 45 matched hospitalized patients with not confirmed HIT (HIT‐negative) were enrolled. Twelve HIT patients (27%) developed HITT. MPs expressing phosphatidylserine (Annexin V‐MP), activated platelet‐derived (P‐Selectin+), activated leukocyte‐derived (L‐Selectin+), PF4‐bearing and tissue factor‐bearing (TF+) MPs were measured by flow‐cytometry. Results HIT patients showed significantly higher median levels of P‐Selectin+, L‐Selectin+, PF4‐bearing, L‐Selectin+/TF + MPs than HIT‐negative; PF4‐bearing MP showed the highest statistical difference. As compared to HIT patients, HITT patients showed a trend of higher median levels of all MP subtypes considered but the differences were not statistically significant. Only levels of activated‐leukocyte/TF + MPs (L‐Selectin + CD142+) were significantly higher ( P = 0.015). Sensitive analyses showed that HIT patients with activated‐leukocyte/TF + MPs above the cut‐off (52 MP/µL) had an odds ratio (OR) for thrombosis of 3.78 (95%CI, 0.98–14.5, P = 0.045). The combination of activated‐leukocyte/TF + MPs and PF4‐bearing‐MPs above the cut‐off (1416 MP/uL) resulted in a higher risk of HITT (OR 4.49 (95% CI, 1.17–8.05, P = 0.014). Conclusions We showed for the first time the presence of circulating PF4‐bearing MPs derived from activated platelets in patients with HIT; activated leukocyte/TF + MPs are associated with an increased thrombotic risk. Our findings confirm that HIT antibodies complexes may determine a TF‐driven prothrombotic state through the activation of platelets and leukocytes. © 2017 International Clinical Cytometry Society