INTRODUCTION The therapeutic potential of a hemostatic agent can be assessed by investigating its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa)--a promising hemostasis-inducing biologic--experimental studies addressing its effects on thrombin generation yielded disparate results. To elucidate the inherent ability of rFVIIa to modula...

Objectives—Thrombin interacts with platelets via the protease-activated receptors (PARs) 1 and 4, and via glycoprotein Ib (GPIb ). Recently, it was shown that platelets are able to adhere to immobilized thrombin under static conditions via GPIb . Methods and Results—Here, we show that platelets are also able to adhere to and form stable aggregates on immobilized thrombin under conditions of flo...

BACKGROUND AND PURPOSE Cerebral ischemia initiates cascades of pathological events such as edema, blood-brain barrier breakdown, and tissue degeneration. Thrombin activation is a key step in coagulation, and thrombin has recently been shown to mediate endothelial permeability and cellular toxicity in vitro. We examined the effect of thrombin on vasculature during ischemia in vivo. METHODS Foc...

BACKGROUND AND PURPOSE Thrombin and lipocalin-2 (LCN2) contribute to intracerebral hemorrhage-induced brain injury. Thrombin-induced brain damage is partially through a thrombin receptor, protease-activated receptor-1. LCN2 is involved in cellular iron transport and neuroinflammation. This study investigated the role of LCN2 in thrombin-induced brain injury. METHODS There were 3 parts in this...

The serine proteinase inhibitor tissue factor pathway inhibitor-2 (TFPI-2) inhibits the tissue factor-factor VIIa complex and thereby impairs factor Xa and subsequently thrombin generation. Here we show that thrombin itself up-regulates TFPI-2 mRNA and protein expression in human liver myofibroblasts, a cell type shown to express high levels of TFPI-2 (Neaud, V., Hisaka, T., Monvoisin, A., Bedi...

Thrombin has been implicated in the stimulation of smooth muscle cell (SMC) proliferation that contributes to post angioplasty restenosis. The present studies demonstrated that human a-thrombin was a potent and efficacious mitogen for cultured rat aortic SMC, stimulating an increase in 3H-thymidine incorporation, as well as an increase in cell number at 1 to 10 nM concentration. -Thrombin, whic...

In determining heparin one has the choice to test a specific activity, such as the decay constant of thrombin or factor Xa on a global test such as the aPTT. The best test would be a global test that directly reflects the only important global effect, to wit antithrombotic efficiency. Such a test does not yet exist. We propose that the thrombin potential, i.e. the time concentration integral of...

The distribution of heparin between thrombin and antithrombin III in solutions containing both proteins has been calculated using a heparin-thrombin dissociation constant value, KgssMT, of 1.5 X lo-’ M and a heparin-antithrombin III dissociation constant value, KEgsMAT, of 2.0 x lo-’ M. The enhancing effect of heparin on the antithrombin III/thrombin reaction rate appeared to correlate with the...

OBJECTIVE The factors involved in restenosis after balloon angioplasty are poorly characterized but the local concentration of the potent mitogens angiotensin II (AII) and thrombin is known to be increased at sites of vascular injury. We investigated the possibility of a synergistic interaction between AII and thrombin by studying the effects of AII on the expression of the thrombin receptor in...

Cultured human umbilical vein endothelial cells release tissue plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) in response to alpha thrombin stimulation. In order to study the mechanisms of thrombin stimulation, we measured changes in levels of mRNA for t-PA and PAI-1 following exposure of endothelial cells to 3 U/mL alpha thrombin. Alpha thrombin causes a signif...