Conard J, Bauer K A, Gruber A, Griffin J H, Schwarz H P, Horellou M H, Samama M M, Rosenberg R D
Service d'Hematologie-Immunologie, Hotel Dieu, Paris, France.
Blood. 1993 Aug 15;82(4):1159-64.
Homozygous or double heterozygous protein-C deficiency can present at birth with purpura fulminans or later in life with venous thrombosis. Two homozygous patients who had previously sustained thrombotic episodes were investigated at a time when they were asymptomatic and not receiving antithrombotic therapy. The plasma levels of protein-C antigen and activity in both individuals were approximately 20% of normal. We administered a highly purified plasma-derived protein C concentrate to these individuals and monitored levels of several markers of in vivo coagulation activation. Assays for protein-C activation (activated protein C and protein C activation peptide) showed a sustained increase from reduced baseline levels, whereas thrombin generation (as measured by prothrombin fragment F1 + 2) gradually decreased over about 24 hours into the normal range. These investigations provide direct evidence that protein C is converted to activated protein C in vivo, and that the protein-C anticoagulant pathway is a tonically active mechanism in the regulation of hemostatic system activation in humans.
纯合子或双杂合子蛋白C缺乏症在出生时可表现为暴发性紫癜，或在生命后期表现为静脉血栓形成。两名曾有血栓形成发作的纯合子患者在无症状且未接受抗血栓治疗时接受了研究。这两名患者的血浆蛋白C抗原水平和活性均约为正常水平的20%。我们给这些患者输注了高度纯化的血浆源性蛋白C浓缩物，并监测了体内凝血激活的几种标志物水平。蛋白C激活检测（活化蛋白C和蛋白C激活肽）显示，从降低的基线水平持续升高，而凝血酶生成（通过凝血酶原片段F1 + 2测量）在约24小时内逐渐降至正常范围。这些研究提供了直接证据，证明蛋白C在体内转化为活化蛋白C，并且蛋白C抗凝途径是调节人类止血系统激活的一种持续活跃的机制。
