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.
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 HITpatients (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:HITpatients 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 HITpatients, 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 HITpatients 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.
Authors: Che Mohd Nasril Che Mohd Nassir; Mazira Mohamad Ghazali; Sabarisah Hashim; Nur Suhaila Idris; Lee Si Yuen; Wong Jia Hui; Haziq Hazman Norman; Chuang Huei Gau; Nanthini Jayabalan; Yuri Na; Linqing Feng; Lin Kooi Ong; Hafizah Abdul Hamid; Haja Nazeer Ahamed; Muzaimi Mustapha Journal: Front Cardiovasc Med Date: 2021-02-24
Authors: Stephen R Thom; Veena M Bhopale; Kevin Yu; Weiliang Huang; Maureen A Kane; David J Margolis Journal: J Biol Chem Date: 2017-09-25 Impact factor: 5.157