Platelets versus monocytes as cellular sources of blood-borne tissue factor: a quantitative and functional comparison in healthy subjects and in patients with STEMI
TL;DR
Accounting for cellular abundance identifies platelets as quantitatively predominant over monocytes, with greater thrombin-generating capacity in HS and STEMI, with greater thrombin-generating capacity in HS and STEMI.
Abstract
Monocytes are an established source of blood-borne tissue factor (TF), while platelet has emerged over 2 decades as a functionally and clinically relevant circulating source of TF. Their relative quantitative and functional contributions remain undefined. Surface TF was quantified by whole-blood flow cytometry in platelets and monocytes from 20 healthy subjects (HS) and 20 patients with ST-segment elevation myocardial infarction (STEMI). Calibrated automated thrombography (CAT) compared platelet and monocyte preparations at cell numbers reflecting their relative abundance in a reference blood volume. TF and Tissue Factor Pathway Inhibitor (TFPI) were neutralized with mAbs; platelet TF exposure was assessed under CAT-like conditions. TFpos fractions were similar, but TF-positive platelets per microliter were more than 400-fold more abundant in both groups. Platelets showed shorter lag times and higher thrombin peaks than monocytes in HS and STEMI; endogenous thrombin potential was greater in STEMI and numerically higher in HS. Anti-TF delayed and anti-TFPI accelerated thrombin generation. Platelet-associated TF increased under CAT-like conditions to 21±1.5% at 8 minutes. Accounting for cellular abundance identifies platelets as quantitatively predominant over monocytes, with greater thrombin-generating capacity in HS and STEMI.