Systemic thrombin generation by glucose

Abstract

Background: Systemic thrombin activity (F2a), i.e. thrombin protected and transported by a2- macroglobulin, is a new biomarker for the activation state of coagulation in vivo. F2a > 120% of normal diagnoses a pathologic disseminated intravascular coagulation (PIC) in humans, either acute or chronic. Since glucose triggers intrinsic coagulation, the present work aimed to quantify systemic thrombin generation induced by glucose in vivo in mice. Material and Methods: Balb/c mice were i.p. injected with different concentrations of glucose (0 - 0.3 mmoles). After 0 - 3 h EDTA-blood was withdrawn, centrifuged, and the plasma was stabilized 1 + 1 with 2.5 M arginine, pH 8.6, and analyzed for systemically circulating F2a (that is F2a.α2M). The F2a.α2M activity in mice without glucose injection was defined as 100% of murine norm. Results: 1 h after i.p. injection 0.1 - 0.3 mmoles glucose resulted in about 1.4 fold increase of plasmatic glucose and in about 2.5 fold increase of systemic F2a activity. At the 45 min time interval between i.p. injection of 0.038 mmoles glucose and blood withdrawing an approximately 1.5fold increase of plasma glucose caused a 4fold increase in systemic F2a. Discussion: When systemic F2a reaches 120% of the normal, the normal human intravascular coagulation (NIC) turns to the pre-phase of pathologic plasmatic intravascular coagulation (PIC-0 also defined as pre-PIC). At 150% systemic F2a, the PIC-0 changes to PIC-1 which is the common pathologic plasmatic intravascular coagulation (typical PIC). At 200% systemic F2a, PIC-1 changes to PIC-2 (consumption PIC). The present assay technique seems to be suitable in judging the coagulation activation state of any mammalian blood. Diabetic patients should be monitored for the new biomarker systemic F2a similarly as for the old biomarker glycated hemoglobin (HbA1c). The target systemic F2a range should be NIC, preferably around 100% of normal.