Andrew M, Mitchell L, Berry L, Paes B, Delorme M, Ofosu F, Burrows R, Khambalia B
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
J Clin Invest. 1992 Jan;89(1):321-6. doi: 10.1172/JCI115579.
Investigation of the in vitro ability of plasma from pregnant women to inhibit exogenous thrombin (25 nM) demonstrated that heparin cofactor II inhibited more thrombin (3.0 +/- 0.7 nM, mean +/- SD) than plasma from women 3-5 d postpartum (1.9 +/- 0.5 nM) or plasma from nonpregnant adults (1.5 +/- 0.4 nM). Levels of heparin cofactor II were only slightly increased over normal in both pregnant and postpartum women and did not account for the observed increase in thrombin bound to heparin cofactor II. Assay of pregnancy plasma for dermatan sulfate anticoagulant activity demonstrated the presence of activity equivalent to 0.23 +/- 0.02 micrograms/ml of porcine mucosal dermatan sulfate. This activity could not be demonstrated in normal adult plasma or plasma from women on the contraceptive pill. The mass of dermatan sulfate in pregnancy and umbilical cord plasmas was increased over adult control plasma by 0.20 micrograms/ml (53%) and 0.29 micrograms/ml (76%), respectively. The glycosaminoglycan-containing fraction of plasma was isolated and an assay for anticoagulant dermatan sulfate confirmed its presence in both pregnancy and cord plasmas but minimal activity in adult plasma. Gel chromatography of isolated fractions from both pregnancy and cord plasmas revealed a polydisperse, active species with apparent Mr 150,000 D. Reductive elimination decreased the apparent Mr of the active species on gel chromatography to 31,000 D for cord and 21,000 D for pregnancy products. This confirmed the presence of an anticoagulant active dermatan sulfate proteoglycan circulating in the plasmas of pregnant women at term and fetuses at delivery.
对孕妇血浆抑制外源性凝血酶(25 nM)的体外能力进行研究发现,肝素辅因子II抑制的凝血酶(3.0±0.7 nM,平均值±标准差)比产后3 - 5天女性的血浆(1.9±0.5 nM)或非妊娠成年女性的血浆(1.5±0.4 nM)更多。在孕妇和产后女性中,肝素辅因子II的水平仅比正常水平略有升高,且无法解释与肝素辅因子II结合的凝血酶的观察到的增加。对妊娠血浆进行硫酸皮肤素抗凝活性测定,结果显示存在相当于0.23±0.02微克/毫升猪黏膜硫酸皮肤素的活性。在正常成年血浆或服用避孕药女性的血浆中未发现这种活性。妊娠血浆和脐带血浆中硫酸皮肤素的含量分别比成年对照血浆增加了0.20微克/毫升(53%)和0.29微克/毫升(76%)。分离出血浆中含糖胺聚糖的部分,对抗凝硫酸皮肤素的测定证实其在妊娠血浆和脐带血浆中均存在,但在成年血浆中活性极小。对妊娠血浆和脐带血浆分离出的部分进行凝胶色谱分析,发现有一个多分散的活性物种,其表观分子量为150,000 D。还原消除使凝胶色谱上活性物种的表观分子量在脐带血浆中降至31,000 D,在妊娠产物中降至21,000 D。这证实了足月孕妇血浆和分娩时胎儿血浆中存在一种具有抗凝活性的硫酸皮肤素蛋白聚糖。