Comparative inhibition of LPS-activated human monocyte-induced thrombin generation by unfractionated heparin and low molecular weight heparins

Monocyte tissue factor may play a role in the physiological or pathological triggering of blood coagulation. It is well known that unfractionated hepa rin and low molecular weight heparins inhibit extrinsic thrombin generation . However, this notion has never been confirmed in a physiological model us ing tissue factor obtained from stimulated human monocytes. This is the pur pose of this study. It was important to obtain a pure preparation of monocy tes with no platelet contamination. This was possible by leukapheresis and elutriation. Under sterile and endotoxin-free conditions, the process does not activate tissue factor expression by monocytes. We adapted the techniqu e of thrombin generation on an automatic analyzer and used human monocyte t issue factor to trigger thrombin generation. Our results show that unfracti onated and low molecular weight heparins potently inhibit monocytic tissue factor induced thrombin generation. The comparison of low molecular weight heparins suggests that molecules with higher anti-IIa/anti-Xa ratios exert a stronger inhibitory effect. These data may be relevant to explain the the rapeutic effects of unfractionated and low molecular weight heparins in car diovascular disorders such as unstable angina. Copyright (C) 2000 S. Karger AG, Basel.