Novel anticoagulant activity of polybrene: inhibition of monocytic tissue factor hypercoagulation following bacterial endotoxin induction

Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis
A J ChuSalwa Beydoun

Abstract

The enhanced extrinsic coagulation in response to inflammation could contribute to disseminated intravascular coagulation, often manifesting cardiovascular complications. The complex mechanism remains unclear. Nor is the effective anticoagulation well established. The search for arresting hypercoagulation is of antithrombotic relevance. The ability of polybrene (PB) to inhibit tissue factor (TF)-initiated extrinsic blood coagulation was demonstrated at the protein and cellular levels as well as in human plasma samples. In a single-stage clotting assay, PB dose-dependently offset bacterial endotoxin (lipopolysaccharide)-induced monocytic TF (mTF) hypercoagulation and inhibited rabbit brain thromboplastin (rbTF) procoagulation. Consistent with these findings, the significantly prolonged prothrombin time indicated the depressed extrinsic coagulation by PB. However, PB showed no effect on thrombin time. We dissected the extrinsic pathway to further determine the inhibitory site(s) of PB. A two-stage chromogenic assay monitoring S-2288 hydrolysis showed that PB readily blocked mTF-dependent or rbTF-dependent FVII activation, which was verified by the diminished activated factor VII (FVIIa) formation derived from the proteolytic clea...Continue Reading

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Citations

Jun 13, 2003·Archives of Biochemistry and Biophysics·Arthur J ChuJulie Hoang
Jul 26, 2002·British Journal of Haematology·Arthur J ChuEvano Piasentin
Sep 29, 2021·International Journal of Laboratory Hematology·Michael HardyFrançois Mullier

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