Deguchi H, Bouma B N, Middeldorp S, Lee Y M, Griffin J H
The Scripps Research Institute, La Jolla, CA 92037, USA.
J Thromb Haemost. 2005 May;3(5):935-8. doi: 10.1111/j.1538-7836.2005.01335.x.
Oral contraceptive (OC) use increases venous thrombosis (VTE) risk and causes activated protein C (APC) resistance. Plasma glucosylceramide (GlcCer) deficiency is associated with VTE and GlcCer functions as an APC anticoagulant cofactor. Because estradiol decreases GlcCer in cultured cells, we hypothesized OC use would decrease plasma GlcCer and contribute to APC resistance. In a pilot study, seven female adults alternatively took second and third generation OCs and plasma samples were analyzed for GlcCer using high performance liquid chromatography and for APC sensitivity using modified prothrombin time assays. Second and third generation OC usage decreased the APC sensitivity ratio by 8.1% +/- 4.7% (P = 0.004) and 11.7% +/- 8.2% (P = 0.013) and plasma GlcCer levels by 10.1% +/- 6.8% (P = 0.008) and 11.0% +/- 5.1% (P = 0.002), respectively. The plasma GlcCer level correlated with the sensitivity of plasma to APC (P = 0.017, r = 0.51, n = 21 plasma samples). Thus, both second and third generation OC usage decreased plasma GlcCer which could cause a reduction in the plasma sensitivity to APC/protein S, thereby potentially increasing VTE risk.
口服避孕药（OC）的使用会增加静脉血栓形成（VTE）风险并导致活化蛋白C（APC）抵抗。血浆葡萄糖神经酰胺（GlcCer）缺乏与VTE有关，且GlcCer作为APC抗凝辅助因子发挥作用。由于雌二醇会降低培养细胞中的GlcCer，我们推测使用OC会降低血浆GlcCer并导致APC抵抗。在一项初步研究中，7名成年女性交替服用第二代和第三代OC，使用高效液相色谱法分析血浆样本中的GlcCer，并使用改良的凝血酶原时间测定法分析APC敏感性。第二代和第三代OC的使用分别使APC敏感性比率降低了8.1%±4.7%（P = 0.004）和11.7%±8.2%（P = 0.013），血浆GlcCer水平分别降低了10.1%±6.8%（P = 0.008）和11.0%±5.1%（P = 0.002）。血浆GlcCer水平与血浆对APC的敏感性相关（P = 0.017，r = 0.51，n = 21个血浆样本）。因此，第二代和第三代OC的使用均降低了血浆GlcCer，这可能会导致血浆对APC/蛋白S的敏感性降低，从而潜在地增加VTE风险。
