Extrinsic pathway inhibitor (EPI) released to the blood by heparin is a more powerful coagulation inhibitor than is recombinant EPI
Autor: | Rita Staalesen, Anne Kari Gangnæs Hammer, Anne Karin Lindahl, Mette Lie Larsen, Thomas Christian Beck, Ulrich Abildgaard, Ole Nordfang, Per Morten Sandset |
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Rok vydání: | 1991 |
Předmět: |
medicine.medical_specialty
medicine.drug_class Lipoproteins Factor VIIa Pharmacology law.invention Thromboplastin Tissue factor law hemic and lymphatic diseases Internal medicine parasitic diseases Blood plasma medicine medicine.diagnostic_test Chemistry Heparin Anticoagulant Hematology Factor VII Recombinant Proteins Endocrinology Coagulation Clotting time Recombinant DNA Partial Thromboplastin Time Blood Coagulation Tests circulatory and respiratory physiology medicine.drug Partial thromboplastin time Factor Xa Inhibitors |
Zdroj: | Thrombosis research. 62(6) |
ISSN: | 0049-3848 |
Popis: | EPI released to the blood after injection of heparin, as well as recombinant EPI (r-EPI) added to normal plasma prolonged both the dilute Tissue Thromboplastin (TTP) time and the Activated Partial Thromboplastin Time (APTT). It is known that EPI inhibits both factor Xa and the factor VIIa-TTP complex. The prolongation of the APTT by EPI reflects only its inhibition of factor Xa. Addition of anti-EPI immunoglobulins (IgG) to normal plasma shortened the dilute TTP time 7.3 seconds (p less than 0.001) and the APTT by 0.7 seconds (p less than 0.001). In postheparin plasma, with polybrene added to neutralize the direct effect of heparin, the TTP was about 26 seconds longer and the APTT about 9 seconds longer than baseline values. These effects were completely abolished by anti-EPI IgG, as were the effects of r-EPI. The EPI activity (chromogenic substrate-assay) of this postheparin plasma was 1.7 U/ml. The EPI activity of the plasma spiked with r-EPI to obtain comparable effects on clotting were much higher; about 22 U/ml for the TTP effect and about 5 U/ml for the APTT effect. The findings indicate that r-EPI is considerably less potent than postheparin EPI as inhibitor of plasma coagulation. This is most striking when coagulation is initiated through the extrinsic pathway. Possibly, the anticoagulant effect of r-EPI mainly depends on its Xa inhibitory effect. |
Databáze: | OpenAIRE |
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