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Thromb Haemost 1994; 72(06): 862-868
DOI: 10.1055/s-0038-1648975
Original Article
Schattauer GmbH Stuttgart

Heparin and Low Molecular Weight Heparins Inhibit Prothrombinase Formation but not its Activity in Plasma

Frederick A Ofosu
1   The Canadian Red Cross Society, Blood Services, Hamilton Centre, Ontario, Canada
2   Department of Pathology, McMaster University, Hamilton, Ontario, Canada
,
J C Lormeau
3   Sanofi Recherche Centre, Gentilly, France
,
Sharon Craven
1   The Canadian Red Cross Society, Blood Services, Hamilton Centre, Ontario, Canada
,
Lori Dewar
1   The Canadian Red Cross Society, Blood Services, Hamilton Centre, Ontario, Canada
,
Noorildan Anvari
2   Department of Pathology, McMaster University, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Received 24 May 1994

Accepted after revision 08 August 1994

Publication Date:
06 July 2018 (online)

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Summary

Factor V activation is a critical step preceding prothrombinase formation. This study determined the contributions of factor Xa and thrombin, which activate purified factor V with similar catalytic efficiency, to plasma factor V activation during coagulation. Prothrombin activation began without a lag phase after a suspension of coagulant phospholipids, CaCl2, and factor Xa was added to factor X-depleted plasma. Hirudin, a potent thrombin inhibitor, abrogated prothrombin activation initiated with 0.5 and 1.0 nM factor Xa, but not with 5 nM factor Xa. In contrast, hirudin did not abrogate prothrombin activation in plasmas pre-incubated with 0.5,1.0 or 5 nM α-thrombin for 10 s followed by the coagulant suspension containing 0.5 nM factor Xa. Thus, thrombin activates plasma factor V more efficiently than factor Xa. At concentrations which doubled the clotting time of contact-activated normal plasma, heparin and three low Mr heparins also abrogated prothrombin activation initiated with 0.5 nM factor Xa, but not with 5 nM factor Xa. If factor V in the factor X-depleted plasma was activated (by pre-incubation with 10 nM a-thrombin for 60 s) before adding 0.5,1.0, or 5 nM factor Xa, neither hirudin nor the heparins altered the rates of prothrombin activation. Thus, none of the five anticoagulants inactivates prothrombinase. When 5 or 10 pM relipidated r-human tissue factor and CaCl2 were added to normal plasma, heparin and the three low Mr heparins delayed the onset of prothrombin activation until the concentration of factor Xa generated exceeded 1 nM, and they subsequently inhibited prothrombin activation to the same extent. Thus, hirudin, heparin and low Mr heparins suppress prothrombin activation solely by inhibiting prothrombinase formation.

 

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