Plasminogen activator inhibitor (PAI‐1) in plasma and platelets

TLDR

The study quantified PAI‑1 in plasma and platelets of healthy subjects and patients with platelet disorders using a sensitive ELISA (1.5 ng/ml) and a t‑PA inhibition assay on platelet‑free plasma, platelet‑rich plasma (after lysis), and serum. Normal platelet‑free plasma contained ~21 ng/ml PAI‑1, whereas platelet‑rich plasma and serum had ~280 ng/ml, with platelet‑derived PAI‑1 proportional to platelet count and independent of plasma levels; platelet PAI‑1 showed ~5‑fold lower specific activity, indicating distinct plasma and platelet PAI‑1 pools relevant to thrombotic disease.

Abstract

The distribution of PAI‐1 in the plasma and platelets of normal individuals and of patients with platelet abnormalities was studied. An ELISA, capable of measuring PAI‐1 in plasma at 1.5 ng/ml, and a functional assay of t‐PA inhibition were used to assay platelet‐free plasma (PFP), platelet‐rich plasma in which the platelets were lysed (PRP) and serum. The PAI‐1 concentration of normal PFP was 21.0 ± 7.2 ng/ml (mean ± SD) and those of PRP and serum were 282.6 ± 68.0 and 270.3 ± 71.9 ng/ml. The concentration of PAI‐1 in PRP was proportional to the platelet count with 0.67 ± 0.18 ng/10 6 platelets. Patients with thrombocy‐topenia had approximately normal PAI‐1 concentrations in PFP; the extremely low concentrations in serum or PRP reflected the platelet count. A patient with grey platelet syndrome showed a comparable pattern, confirming that PAI‐1 occurs in the platelet α‐granules and indicating that the plasma concentration of PAI‐1 is independent of the platelet pool of PAI‐1. The median inhibitory activities towards t‐PA were 1.6, 8.7 and 8.3 units/ml in normal PFP. PRP and serum respectively. PAI‐1 in PFP had a median specific activity (units/mg PAI‐1) about 5‐fold higher than platelet PAI‐1. Plasma and platelets represent two distinct pools of PAI‐1, both of which should be considered in studies on the relationship between circulating PAI‐1 and thrombotic disease.