Comparative effects of synthetic pentasaccharide, low-molecular-weight heparin, unfractionated heparin and recombinant hirudin on the generation of factor VIIa and prothrombin activation after coagulation of human plasma

被引:21
作者
Gerotziafas, GT
Bara, L
Bloch, MF
Makris, PE
Samama, MM
机构
[1] Hop Hotel Dieu, Serv Hematol Biol, F-75181 Paris 04, France
[2] Univ Paris 06, Broussais Hotel Dieu, Fac Med, Lab Thrombose Expt, Paris, France
[3] AHEPA Univ Hosp, Med Propedeut Clin 1, Thrombosis & Haemostasis Unit, Salonika, Greece
关键词
factor VII; factor VII activation; factor VIIa; UFH; LMWH; pentasaccharide; hirudin; prothrombin activation;
D O I
10.1097/00001721-199810000-00002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We studied the effect of synthetic pentasaccharide, a low-molecular-weight heparin (enoxaparin), unfractionated heparin and recombinant hirudin on the generation of factor VIIa (FVIIa) and prothrombin activation after in-vitro clotting of human platelet-poor plasma. FVIIa was measured with a new clotting assay that uses recombinant tissue factor truncated to interact only with FVIIa. Residual prothrombin was measured using the conventional clotting assay. FVIIa and residual FII were measured in the liquid - called pseudo-serum (Psi-serum) - obtained Ih after clotting of normal platelet-poor plasma. A kinetic study of the generation of FVIIa was also performed. Coagulation was initiated by triggering the extrinsic, the intrinsic and both associated clotting pathways. Levels of FVIIa in the Psi-sera (55 +/- 15, 258 +/- 18, and 164 +/- 18 ng/ml, in the extrinsic, intrinsic and intrinsic + thromboplastin Psi-serum respectively; values are means +/- SEM) were significantly increased compared with those in the platelet-poor plasma (3 ng/ml). Pentasaccharide, low-molecular-weight heparin and unfractionated heparin inhibited the generation of factor VIIa or its activity, or both, in a dose-dependent manner in all the experimental systems (60-90% inhibition). A kinetic study revealed that the inhibition of the generation of FVIIa by pentasaccharide and heparins starts 1 min after triggering either the extrinsic or the intrinsic clotting pathway. The downregulation of FVIIa by heparins was effected mainly by their anti-Xa activity, but also by their inhibitory effect on the generation of prothrombinase. Pentasaccharide, enoxaparin and unfractionated heparin significantly inhibited prothrombin activation in both extrinsic and intrinsic experimental system. Hirudin had no inhibitory effect either on the generation of FVIIa or on prothrombin activation in any experimental system. (C) 1998 Lippincott Williams & Wilkins.
引用
收藏
页码:571 / 580
页数:10
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