Department of Paediatrics, Faculty of Medicine, Cairo University, Egypt.
Pediatr Crit Care Med. 2010 Jan;11(1):52-9. doi: 10.1097/PCC.0b013e3181c59032.
The aim of this study is to clarify the effect of sepsis on the physiologic inhibition system of coagulation including protein S, protein C, and antithrombin III, and to study their further effect on thromboembolic accidents of septic newborns.
Clinical study including 30 septic neonates and 30 normal neonates served as control group.
MEDLINE, pediatric textbooks, Neonatal Intensive Care Unit, Department of Pediatrics, Faculty of Medicine, Cairo University.
The results of this study showed marked decrease in the level of the physiologic inhibition system of coagulation including antithrombin III, protein C, and protein S in 100% of cases, compared to the control group (p < .001). Disseminated intravascular coagulation developed and death occurred in 33.3% of cases, necrotizing enterocolitis developed in 40% of cases, rectal bleeding developed in 33.3%, hematuria developed in 20% of cases, hematemesis developed in 26.7% of cases, intracranial hemorrhage developed in 23.3% of cases, and convulsions developed in 23.3% of cases.
In this study we have tried to evaluate the effect of sepsis on the physiologic inhibition system of coagulation in neonates. We should expect the effect of sepsis and its severity and perform the necessary laboratory investigations for coagulation including antithrombin III, protein C and protein S levels to help prevent thromboembolic accidents in neonates with sepsis, including disseminated intravascular coagulation, necrotizing enterocolitis and intracranial hemorrhage. Based on the findings of our study and the results of the other studies, we are in agreement that protein C is a very useful biomarker in severe sepsis, and it is a possible tool for monitoring treatment with activated protein C. We also encourage further placebo-controlled clinical trials to investigate the role of activated protein C and antithrombin III in severe neonatal sepsis and especially in the states before disseminated intravascular coagulation and the disseminated intravascular coagulation states, on the condition that they are guided by the experience and recommendations gained from the PROWESS, ENHANCE, and RESOLVE clinical trials. Protein C might be more effective if dosed according to protein C levels rather according to weight. Furthermore, we encourage future research on activated protein C mutants, which are anticipated to appear very soon because they can reduce some side effects associated with the use of recombinant human activated protein C, such as intracranial hemorrhage and bleeding tendencies, because they have reduced anticoagulant activity while retaining the cytoprotective effects.
本研究旨在阐明脓毒症对包括蛋白 S、蛋白 C 和抗凝血酶 III 在内的凝血生理抑制系统的影响，并研究其对脓毒症新生儿血栓栓塞事件的进一步影响。
包括 30 例脓毒症新生儿和 30 例正常新生儿的临床研究作为对照组。
MEDLINE、儿科学教科书、开罗大学医学院儿科新生儿重症监护室。
本研究结果显示，脓毒症患儿凝血生理抑制系统中抗凝血酶 III、蛋白 C 和蛋白 S 的水平均显著降低（100%），与对照组相比（p<0.001）。弥漫性血管内凝血发生，死亡率为 33.3%，坏死性小肠结肠炎发生率为 40%，直肠出血发生率为 33.3%，血尿发生率为 20%，呕血发生率为 26.7%，颅内出血发生率为 23.3%，惊厥发生率为 23.3%。
本研究试图评估脓毒症对新生儿凝血生理抑制系统的影响。我们应该预计到脓毒症的影响及其严重程度，并进行必要的凝血实验室检查，包括抗凝血酶 III、蛋白 C 和蛋白 S 水平，以帮助预防脓毒症新生儿的血栓栓塞事件，包括弥漫性血管内凝血、坏死性小肠结肠炎和颅内出血。基于我们的研究结果和其他研究的结果，我们同意蛋白 C 是严重脓毒症非常有用的生物标志物，它可能是监测活化蛋白 C 治疗的工具。我们还鼓励进一步进行安慰剂对照临床试验，以研究活化蛋白 C 和抗凝血酶 III 在严重新生儿脓毒症中的作用，特别是在弥漫性血管内凝血和弥漫性血管内凝血状态之前的状态，同时根据 PROWESS、ENHANCE 和 RESOLVE 临床试验获得的经验和建议进行指导。如果根据蛋白 C 水平而不是体重给药，蛋白 C 可能更有效。此外，我们鼓励未来对抗凝酶 C 突变体的研究，因为它们有望很快出现，因为它们可以降低与使用重组人活化蛋白 C 相关的一些副作用，如颅内出血和出血倾向，因为它们的抗凝活性降低，同时保留了细胞保护作用。
