PMID- 7831680 OWN - NLM STAT- MEDLINE DCOM- 19950217 LR - 20190727 IS - 0049-3848 (Print) IS - 0049-3848 (Linking) VI - 75 IP - 6 DP - 1994 Sep 15 TI - Inhibitory effects of TFPI on thrombin and factor Xa generation in vitro--modulatory action of glycosaminoglycans. PG - 609-16 AB - The effect of tissue factor pathway inhibitor (TFPI) on thrombin and factor Xa generation was studied in an in vitro system using a prothrombin complex concentrate. It was found that TFPI, via the direct inhibition of factor Xa and the tissue factor/factor VIIa complex, inhibited both the further generation of factor Xa and the generation of thrombin in a concentration-dependent manner. The generation of thrombin (IC50 255 ng/ml) was more pronounced than that of factor Xa (IC50 684 ng/ml). The inhibitory activity of TFPI was significantly enhanced when unfractionated heparin was present in the assay system at a concentration of 10 micrograms/ml which did not show any inhibitory effects on protease generation in the same system. Furthermore, the influence of TFPI at subthreshold concentrations (100 ng/ml and 200 ng/ml, resp.) on the inhibitory action of unfractionated heparin (UFH), a low molecular weight heparin (LMWH), heparan sulfate (HS) and the synthetic heparin pentasaccharide (PS) was investigated. Whereas in the concentration range used (0.3-40 micrograms/ml) these glycosaminoglycans did not inhibit thrombin and factor Xa generation, after supplementation of the system with TFPI a concentration-dependent inhibition of the generation of the proteases up to 40-50% was seen for UFH, LMWH and HS. TFPI did not increase the activity of PS. FAU - Kaiser, B AU - Kaiser B AD - Loyola University Medical Center, Department of Pathology, Maywood, IL. FAU - Hoppensteadt, D A AU - Hoppensteadt DA FAU - Jeske, W AU - Jeske W FAU - Wun, T C AU - Wun TC FAU - Fareed, J AU - Fareed J LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 RN - 0 (Factor Xa Inhibitors) RN - 0 (Heparin, Low-Molecular-Weight) RN - 0 (Lipoproteins) RN - 0 (Oligosaccharides) RN - 0 (lipoprotein-associated coagulation inhibitor) RN - 88096-19-9 (IC 831423) RN - 9005-49-6 (Heparin) RN - 9035-58-9 (Thromboplastin) RN - 9050-30-0 (Heparitin Sulfate) RN - EC 3.4.21.21 (Factor VIIa) RN - EC 3.4.21.5 (Thrombin) RN - EC 3.4.21.6 (Factor Xa) SB - IM MH - Animals MH - Factor VIIa/antagonists & inhibitors MH - Factor Xa/biosynthesis MH - *Factor Xa Inhibitors MH - Heparin/*pharmacology MH - Heparin, Low-Molecular-Weight/*pharmacology MH - Heparitin Sulfate/*pharmacology MH - Lipoproteins/*pharmacology MH - Oligosaccharides/*pharmacology MH - Swine MH - Thrombin/*antagonists & inhibitors/biosynthesis MH - Thromboplastin/antagonists & inhibitors EDAT- 1994/09/15 00:00 MHDA- 1994/09/15 00:01 CRDT- 1994/09/15 00:00 PHST- 1994/09/15 00:00 [pubmed] PHST- 1994/09/15 00:01 [medline] PHST- 1994/09/15 00:00 [entrez] AID - 0049-3848(94)90173-2 [pii] AID - 10.1016/0049-3848(94)90173-2 [doi] PST - ppublish SO - Thromb Res. 1994 Sep 15;75(6):609-16. doi: 10.1016/0049-3848(94)90173-2.