Gerotziafas Grigoris T, Elalamy Ismail, Depasse François, Chakroun Tahar, Bara Lucienne, Arzoglou Pantelis, Samama Meyer M
Service d'Hématologie Biologique, Hôpital Hôtel-Dieu de Paris, France.
Blood Coagul Fibrinolysis. 2003 Oct;14(7):633-8. doi: 10.1097/00001721-200310000-00003.
The tissue factor (TF) pathway is preponderant in the initiation of blood coagulation in normal haemostasis and in thrombotic states. In the present study we investigated the mechanisms by which the synthetic pentasaccharide may influence the regulation of the TF pathway during clotting of human platelet poor plasma (PPP). Clotting of normal PPP or plasmas immuno-depleted of a single clotting factor (factor VII, factor XII, factor XI, factor IX, factor VIII, factor X, factor V, factor II) was initiated by triggering the TF pathway in the presence of fondaparinux (0.5 microg/ml). Activated factor VII (FVIIa) levels were measured in serum obtained at several time intervals after re-calcification of PPP. A clotting assay highly specific for FVIIa was used. The synthetic pentasaccharide inhibited the generation of FVIIa by 66%. The inhibitory effect of fondaparinux on FVIIa was completely abolished when antithrombin activity of plasma was inhibited by a specific antibody. Following the activation of TF pathway in plasmas depleted of factor X or factor IX, the inhibitory effect of fondaparinux on FVIIa generation was completely abolished, whereas it was not significantly modified when the other clotting factor-depleted plasmas were clotted. When fondaparinux was added in the serum, after the maximal generation of FVIIa, it inhibited by 20-30% the activity of the FVIIa-TF complex. These data suggest that fondaparinux enhances the antithrombin-dependent downregulation of the TF pathway by decreasing the generation of FVIIa via the inhibition of the generation and the activity of activated factor IX and activated factor X, and by inhibiting the activity of the FVIIa-TF complex.
组织因子（TF）途径在正常止血和血栓形成状态下的血液凝固起始过程中占主导地位。在本研究中，我们调查了合成五糖在人少血小板血浆（PPP）凝血过程中影响TF途径调节的机制。通过在磺达肝癸钠（0.5微克/毫升）存在的情况下触发TF途径，启动正常PPP或单一凝血因子（因子VII、因子 XII、因子 XI、因子 IX、因子 VIII、因子 X、因子 V、因子 II）免疫耗竭的血浆的凝血。在PPP重新钙化后的几个时间间隔采集的血清中测量活化因子VII（FVIIa）水平。使用了一种对FVIIa高度特异的凝血测定法。合成五糖抑制FVIIa的生成达66%。当血浆的抗凝血酶活性被特异性抗体抑制时，磺达肝癸钠对FVIIa的抑制作用完全消除。在因子X或因子IX耗竭的血浆中激活TF途径后，磺达肝癸钠对FVIIa生成的抑制作用完全消除，而当其他凝血因子耗竭的血浆凝血时，该抑制作用没有明显改变。当在FVIIa最大生成后将磺达肝癸钠添加到血清中时，它抑制FVIIa - TF复合物的活性达20 - 30%。这些数据表明，磺达肝癸钠通过抑制活化因子IX和活化因子X的生成及活性来减少FVIIa的生成，并通过抑制FVIIa - TF复合物的活性，增强了抗凝血酶依赖性的TF途径下调作用。
