Hemker H C, Béguin S, Bendetowicz A V, Wielders S
Department of Biochemistry, Rijksuniversiteit Limburg, Maastricht, The Netherlands.
Haemostasis. 1991;21(4):258-72. doi: 10.1159/000216235.
We define a standard independent unit (SIU) of heparin as that amount that, in plasma containing 1 mumol of ATIII, raises the (pseudo-)first-order breakdown constant of factor Xa by 1 min-1. These units measure all material with a high affinity for ATIII (HAM); only material above the critical chain length of 17 monosaccharide units (above critical chain length material; ACLM) catalyzes the inactivation of thrombin. An SIU of ACLM is therefore analogously defined as the amount that, in plasma containing 1 mumol of ATIII, will raise the (pseudo-)first-order breakdown constant of thrombin by 1 min-1. Of any given heparin preparation one can determine the specific HAM and ACLM activities in terms of SIU/mg. On the basis of the factor Xa and thrombin breakdown constants found in a plasma sample one can then determine the levels of HAM and ACLM. Preliminary experiments were carried out in plasma samples obtained after subcutaneous injection of unfractionated heparin (UFH) and of two types of low-molecular-weight heparin (LMWH). About three times more of UFH activity than of LMWH activity has to be injected to obtain the same levels of ACLM in the plasma. Only with the LMWHs significant amounts of BCLM are found, which rises higher and persists longer than the ACLM. We determined the course of thrombin generation in platelet-rich plasma (PRP) and in platelet-poor plasma (PPP), as well as in the PPP factor Xa generation curve and the course of prothrombin conversion. The observed inhibitions correlated much better with the levels of ACLM than with those of below critical chain length material. The difference between UFH and LMWHs can therefore not be explained in terms of antithrombin and anti-factor-Xa activity. The essential difference between UFH and LMWH appears in the feedback effect of thrombin in PRP, where thrombin generation is both inhibited and retarded by LMWH, while it is only retarded but hardly inhibited by UFH.
我们将肝素的标准独立单位（SIU）定义为：在含有1 μmol抗凝血酶III（ATIII）的血浆中，能使因子Xa的（假）一级分解常数提高1 min⁻¹的肝素量。这些单位用于衡量所有对ATIII具有高亲和力的物质（HAM）；只有链长超过17个单糖单位的物质（临界链长以上物质；ACLM）才能催化凝血酶的失活。因此，ACLM的一个SIU类似地定义为：在含有1 μmol ATIII的血浆中，能使凝血酶的（假）一级分解常数提高1 min⁻¹的量。对于任何给定的肝素制剂，可以根据SIU/mg来确定其特定的HAM和ACLM活性。根据在血浆样本中发现的因子Xa和凝血酶分解常数，就可以确定HAM和ACLM的水平。在皮下注射普通肝素（UFH）和两种低分子量肝素（LMWH）后获得的血浆样本中进行了初步实验。为了在血浆中获得相同水平的ACLM，需要注射的UFH活性大约是LMWH活性的三倍。仅在LMWH中发现了大量的BCLM，其升高幅度比ACLM更高且持续时间更长。我们测定了富血小板血浆（PRP）和贫血小板血浆（PPP）中凝血酶生成的过程，以及PPP中因子Xa生成曲线和凝血酶原转化过程。观察到的抑制作用与ACLM水平的相关性比与临界链长以下物质水平的相关性要好得多。因此，UFH和LMWH之间的差异不能用抗凝血酶和抗因子Xa活性来解释。UFH和LMWH之间的本质区别出现在PRP中凝血酶的反馈作用上，在PRP中，LMWH既能抑制又能延迟凝血酶的生成，而UFH只能延迟凝血酶的生成但几乎不能抑制它。
