Nuijens J H, Huijbregts C C, Eerenberg-Belmer A J, Abbink J J, Strack van Schijndel R J, Felt-Bersma R J, Thijs L G, Hack C E
Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Blood. 1988 Dec;72(6):1841-8.
Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(-)-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(-4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.
大量证据表明，内源性凝血接触系统的激活在脓毒性休克的发病机制中起作用。为监测脓毒症患者的接触激活情况，我们使用一种单克隆抗体（MoAb Kok 12）开发了针对因子XIIa-Cl(-)-抑制剂（Cl(-)-Inh）和激肽释放酶-Cl(-)-Inh复合物的高灵敏度放射免疫分析（RIA），该抗体可结合在复合和裂解的Cl(-)-Inh上暴露的新抗原决定簇。对48名因严重脓毒症入住重症监护病房的患者连续采集血浆样本。至少有一次，40%的患者血浆因子XIIa-Cl(-)-Inh（大于5×10(-4) U/mL）和激肽释放酶-Cl(-)-Inh（大于25×10(-4) U/mL）水平升高，二者摩尔比约为1:3。23名脓毒性休克患者的血浆因子XII抗原水平以及血浆因子XIIa-Cl(-)-Inh的最高水平和入院时水平均低于25名血压正常患者（P = 0.015：入院时因子XII；P = 0.04：最高因子XIIa-Cl(-)-Inh；P = 0.01：入院时因子XIIa-Cl(-)-Inh）。这些患者组之间血浆激肽释放酶-Cl(-)-Inh或前激肽释放酶抗原无显著差异。与无休克患者相比，脓毒性休克患者连续样本中Cl(-)-Inh复合物水平升高的检测频率较低（P小于0.0001）。基于这些结果，我们得出结论，脓毒症期间血浆Cl(-)-Inh复合物水平可能无法准确反映接触激活的程度。
