Thrombin generation abnormalities in Quebec platelet disorder

Abstract

Introduction: Calibrated automated thrombograms (CAT) with platelet-poor (PPP) and platelet-rich plasma (PRP) have provided useful insights on bleeding disorders. We used CAT to assess thrombin generation (TG) in Quebec platelet disorder (QPD)—a bleeding disorder caused by a PLAU duplication mutation that increases platelet (but not plasma) urokinase plasminogen activator (uPA), leading to intraplatelet (but not systemic) plasmin generation that degrades α-granule proteins and causes platelet (but not plasma) factor V (FV) deficiency. Methods: Calibrated automated thrombograms was used to test QPD (n = 7) and control (n = 22) PPP and PRP, with or without added tranexamic acid (TXA). TG endpoints were evaluated for relationships to platelet FV and uPA, plasma FV and tissue factor pathway inhibitor (TFPI) levels, and bleeding scores. Results: Quebec platelet disorder PPP TG was normal whereas QPD PRP had reduced endogenous thrombin potential and peak thrombin concentrations (P values