Prothrombin complex concentrates (PCCs) have been associated with a possible risk of thromboembolic complications, potentially attributable to an increased ratio of the plasma concentration of factor II (FII) to antithrombin (AT). We developed a mathematical model to examine the relationship between amounts of PCC or therapeutic plasma administered, and plasma levels of FII and AT. The model sh...

Accelerated antithrombin inhibition of procoagulant enzymes has been exclusively achieved with polysulfated polysaccharides. We reasoned that antithrombin activation should be possible with nonsulfated activators based only on carboxylic acid groups. As a proof of the principle, linear poly(acrylic acid)s were found to bind to antithrombin and accelerate inhibition of factor Xa and thrombin. Ou...

The medication we know as heparin is actually a heterogeneous mixture of polysaccharides derived from beef or pork livers. Although the exact mechanism for heparin’s antithrombotic properties is not known, it is believed to act by binding to antithrombin III. The heparinantithrombin III complex inhibits the activity of numerous enzymes in the clotting cascade, including factors IIa (thrombin), ...

Three different heparin-catalyzed inhibitor/protease reactions were studied: antithrombin III/thrombin, heparin cofactor II/thrombin, antithrombin III/factor Xa. The three reactions were saturable with respect to both inhibitor and protease. The initial reaction velocity, for each reaction, could be described by the general rate equation for a random-order bireactant enzyme-catalyzed reaction. ...

The ecarin clotting time (ECT) is a meizothrombin generation test that allows for precise quantification of direct thrombin inhibitors. The ECT has demonstrated its usefulness for more than 10 years in biochemical-pharmacological investigations as well as in clinical research and in the clinical routine. It has proved valuable especially as a drug-monitoring method in r-hirudin therapy. This te...

Clotting blood contains fibrin-bound thrombin, which is a major source of procoagulant activity leading to clot extension and further activation of coagulation. When bound to fibrin, thrombin is protected from inhibition by antithrombin (AT) + heparin but is neutralized when AT and heparin are covalently linked (ATH). Here, we report the surprising observation that, rather than yielding an iner...

A chromogenic assay for use as a screening test for the identification of antithrombin deficiency is described. The heparin concentration and the incubation time in the assay were optimised specifically to permit the detection of heparin binding defects of antithrombin. The sensitivity of antithrombin assays for the detection of this type of variant was significantly impaired when an incubation...

Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melag...

The N-terminal region residues, Lys11, Arg13, and Arg24, of the plasma coagulation inhibitor, antithrombin, have been implicated in binding of the anticoagulant polysaccharide, heparin, from the identification of natural mutants with impaired heparin binding or by the X-ray structure of a complex of the inhibitor with a high-affinity heparin pentasaccharide. Mutations of Lys11 or Arg24 to Ala i...

ObjectiveAlthough thromboprophylaxis is recommended to reduce death and disability from venous thromboembolism (VTE), it remains underused due a perceived risk of bleeding, especially in major abdominopelvic surgical patients.MethodsWe conducted systematic literature review identify all eligible randomized controlled trials (RCTs), searching MEDLINE Scopus databases through November 25, 2020. R...