切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2023, Vol. 19 ›› Issue (04) : 379 -386. doi: 10.3877/cma.j.issn.1673-5250.2023.04.002

专题论坛

新生儿脓毒症相关性凝血病的监测和治疗
魏徐, 张鸽, 伍金林()   
  1. 四川大学华西第二医院儿科、出生缺陷与相关妇儿疾病教育部重点实验室,成都 610041
    四川大学华西第二医院医学检验科,成都 610041
  • 收稿日期:2023-02-05 修回日期:2023-07-05 出版日期:2023-08-01
  • 通信作者: 伍金林

Monitoring and treatment of neonatal sepsis-induced coagulopathy

Xu Wei, Ge Zhang, Jinlin Wu()   

  1. Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2023-02-05 Revised:2023-07-05 Published:2023-08-01
  • Corresponding author: Jinlin Wu
  • Supported by:
    Applied Basic Project of Science and Technology Department of Sichuan Province(2021YJ0211); Horizontal Project of Sichuan University(21H0865)
引用本文:

魏徐, 张鸽, 伍金林. 新生儿脓毒症相关性凝血病的监测和治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 379-386.

Xu Wei, Ge Zhang, Jinlin Wu. Monitoring and treatment of neonatal sepsis-induced coagulopathy[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 379-386.

脓毒症相关性凝血病(SIC)是新生儿常见疾病,亦是导致新生儿死亡的重要原因。目前认为,SIC新生儿中,机体炎症和凝血功能紊乱具有密切关系,但是二者相互作用机制则迄今尚未阐明,对于预防脓毒症新生儿发生SIC的治疗方案,目前亦尚无统一标准。笔者拟就新生儿SIC的发病机制、血清监测指标和治疗的最新研究进展进行阐述,旨在为新生儿SIC的进一步临床与基础研究提供参考依据,改善SIC新生儿预后。

Sepsis-induced coagulopathy (SIC) is a common disease in newborns and an important cause of neonatal death. At present, it is believed that there is a close relationship between inflammation and coagulation dysfunction in SIC newborns, but the mechanism of their interaction is still unclear, and it is lack of uniform standard treatment plan to prevent SIC in newborns with sepsis. The author intends to elaborate on the latest research progress in pathogenesis, serum monitoring indicators, and treatment of neonatal SIC, with the aim of providing reference for further clinical and basic research on SIC and improving the prognosis of newborns with SIC.

[1]
Fleischmann C, Reichert F, Cassini A, et al. Global incidence and mortality of neonatal sepsis: a systematic review and Meta-analysis[J]. Arch Dis Child, 2021, 106(8): 745-752. DOI: 10.1136/archdischild-2020-320217.
[2]
Iba T, Levy JH. Sepsis-induced coagulopathy and disseminated intravascular coagulation[J]. Anesthesiology, 2020, 132(5): 1238-1245. DOI: 10.1097/aln.0000000000003122.
[3]
Gialamprinou D, Mitsiakos G, Katsaras GN, et al. Neonatal sepsis and hemostasis[J]. Diagnostics (Basel), 2022, 12(2): 261. DOI: 10.3390/diagnostics12020261.
[4]
Go H, Ohto H, Nollet KE, et al. Risk factors and treatments for disseminated intravascular coagulation in neonates[J]. Ital J Pediatr, 2020, 46(1): 54. DOI: 10.1186/s13052-020-0815-7.
[5]
Haidl H, Zöhrer E, Pohl S, et al. New insights into neonatal coagulation: normal clot formation despite lower intra-clot thrombin levels[J]. Pediatr Res, 2019, 86(6): 719-724. DOI: 10.1038/s41390-019-0531-4.
[6]
Iba T, Connors JM, Nagaoka I, et al. Recent advances in the research and management of sepsis-associated DIC[J]. Int J Hematol, 2021, 113(1): 24-33. DOI: 10.1007/s12185-020-03053-y.
[7]
Gando S, Fujishima S, Saitoh D, et al. The significance of disseminated intravascular coagulation on multiple organ dysfunction during the early stage of acute respiratory distress syndrome[J]. Thromb Res, 2020, 191: 15-21. DOI: 10.1016/j.thromres.2020.03.023.
[8]
O′reilly D, Murphy CA, Drew R, et al. Platelets in pediatric and neonatal sepsis: novel mediators of the inflammatory cascade[J]. Pediatr Res, 2022, 91(2): 359-367. DOI: 10.1038/s41390-021-01715-z.
[9]
Sudhakar B, Kusuma S, Karunakar G, et al. Role of platelet count and indices in the diagnosis of neonatal sepsis[J]. J Dr NTR Univ Health Sci, 2022, 11(3): 233-236. DOI: 10.4103/jdrntruhs.jdrntruhs_112_22.
[10]
Yang YC, Mao J. Value of platelet count in the early diagnosis of nosocomial invasive fungal infections in premature infants[J]. Platelets, 2018, 29(1): 65-70. DOI: 10.1080/09537104.2017.1293810.
[11]
Levi M, Vincent JL, Tanaka K, et al. Effect of a recombinant human soluble thrombomodulin on baseline coagulation biomarker levels and mortality outcome in patients with sepsis-associated coagulopathy[J]. Crit Care Med, 2020, 48(8): 1140-1147. DOI: 10.1097/ccm.0000000000004426.
[12]
Iba T, Levy JH. Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis[J]. J Thromb Haemost, 2018, 16(2): 231-241. DOI: 10.1111/jth.13911.
[13]
Hsieh LT, Santos SJD, Hall BS, et al. Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1β,are linked to fibrin formation in Buruli ulcer lesions[J]. PLoS Pathog, 2022, 18(1): e1010280. DOI: 10.1371/journal.ppat.1010280.
[14]
Zelaya H, Rothmeier AS, Ruf W. Tissue factor at the crossroad of coagulation and cell signaling[J]. J Thromb Haemost, 2018, 16(10): 1941-1952. DOI: 10.1111/jth.14246.
[15]
岳少杰,钟乐,何晓凡,等. 新生儿感染性黄疸血浆组织因子和组织因子途径抑制物含量的变化[J]. 中华儿科杂志2003, 41(2): 104-106. DOI: 10.3760/cma.j.issn.0578-1310.2003.02.107.
[16]
Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis[J]. Arterioscler Thromb Vasc Biol, 2018, 38(4): 709-725. DOI: 10.1161/ATVBAHA.117.309846.
[17]
Takashi I, Midori K, Ikuro M. Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation[J]. Crit Care, 2021, 25(1): 95. DOI: 10.1186/s13054-021-03524-6.
[18]
郝玲,王娜. 败血症新生儿血栓调节蛋白和D-二聚体的变化及意义[J]. 中国当代儿科杂志2013, 15(10): 841-844. DOI: 10.7499/j.issn.1008-8830.2013.10.008.
[19]
赵瑶,王琳. 新生儿抗凝系统及血栓性疾病的研究进展[J]. 国际儿科学杂志201946(5): 323-326. DOI: 10.3760/cma.j.issn.1673-4408.2019.05.004.
[20]
Formoso VRY, Mota RB, Soares H, et al. Developmental hemostasis in the neonatal period[J]. World J Pediatr, 2022, 18(1): 7-15. DOI: 10.1007/s12519-021-00492-3.
[21]
Schupp T, Weidner K, Rusnak J, et al. Diagnostic and prognostic significance of the prothrombin time/international normalized ratio in sepsis and septic shock[J]. Clin Appl Thromb Hemost, 2022, 28. DOI: 10.1177/10760296221137893.
[22]
白丹,石境懿,张勇,等. 降钙素原联合凝血功能检测对新生儿感染性疾病危重程度及预后的预测价值[J]. 四川医学2020, 41(9): 969-973. DOI: 10.16252/j.cnki.issn1004-0501-2020.09.017.
[23]
Zhang J, Xue M, Chen Y, et al. Identification of soluble thrombomodulin and tissue plasminogen activator-inhibitor complex as biomarkers for prognosis and early evaluation of septic shock and sepsis-induced disseminated intravascular coagulation[J]. Ann Palliat Med, 2021, 10(10): 10170-10184. DOI: 10.21037/apm-21-2222.
[24]
Levi M, Scully M. How I treat disseminated intravascular coagulation[J]. Blood, 2018, 131(8): 845-854. DOI: 10.1182/blood-2017-10-804096.
[25]
Piliponsky AM, Shubin NJ, Lahiri AK, et al. Basophil-derived tumor necrosis factor can enhance survival in a sepsis model in mice[J]. Nat Immunol, 2019, 20(2): 129-140. DOI: 10.1038/s41590-018-0288-7.
[26]
钟林翠,宋景春,邓星平,等. 血栓调节蛋白联合凝血酶-抗凝血酶复合物判断脓毒症预后的临床价值[J]. 解放军医学杂志2020, 45(7): 746-750. DOI: 10.11855/j.issn.0577-7402.2020.07.12.
[27]
Sullivan BA, Fairchild KD. Vital signs as physiomarkers of neonatal sepsis[J]. Pediatr Res, 2022, 91(2): 273-282. DOI: 10.1038/s41390-021-01709-x.
[28]
Giri SHN, Aman AK, Hanafie A. Hemostasis changes and its relationship with SOFA score in sepsis patients[J]. Bali Med J, 2019, 8(2): 587. DOI: 10.15562/bmj.v8i2.1409.
[29]
Li J, Zhou J, Ren H, et al. Clinical efficacy of soluble thrombomodulin, tissue plasminogen activator inhibitor complex, thrombin-antithrombin complex, α2-plasmininhibitor-plasmin complex in pediatric sepsis[J]. Clin Appl Thromb Hemost, 2022, 28: 10760296221102929. DOI: 10.1177/10760296221102929.
[30]
Hasuike Y, Kakita N, Aichi M, et al. Imbalance of coagulation and fibrinolysis can predict vascular access failure in patients on hemodialysis after vascular access intervention[J]. J Vasc Surg, 2019, 69(1): 174.e2-180.e2. DOI: 10.1016/j.jvs.2018.04.029.
[31]
Martin-Fernandez M, Vaquero-Roncero LM, Almansa R, et al. Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients[J]. BJS Open, 2020, 4(3): 524-534. DOI: 10.1002/bjs5.50265.
[32]
魏捷,张东梅,吕菁君,等. 119例脓毒症凝血、抗凝和纤溶功能的临床研究[J]. 中华急诊医学杂志2018, 27(8): 905-911. DOI: 10.3760/cma.j.issn.1671-0282.2018.08.017.
[33]
Zhong L, Dou J, Lin Q, et al. Tissue-type plasminogen activator-inhibitor complex as an early predictor of septic shock: a retrospective, single-center study[J]. Dis Markers, 2022, 2022: 9364037. DOI: 10.1155/2022/9364037.
[34]
Leong R, Patel J, Samji N, et al. Use of thrombolytic agents to treat neonatal thrombosis in clinical practice[J]. Blood Coagul Fibrinolysis, 2022, 33(4): 193-200. DOI: 10.1097/mbc.0000000000001134.
[35]
Kurimoto T, Shimoji Y, Shimabukuro A, et al. Recombinant tissue-type plasminogen activator treatment in an extremely low birth weight infant[J]. Clin Case Rep, 2021, 9(5): e04236. DOI: 10.1002/ccr3.4236.
[36]
Cabrera-Garcia D, Miltiades A, Parsons SM, et al. High levels of plasminogen activator inhibitor-1, tissue plasminogen activator and fibrinogen in patients with severe COVID-19[J]. Cold Spring Harbor Lab Press, 2021. DOI: 10.1101/2020.12.29.20248869.
[37]
Dastgheib SA, Najafi F, Shajari A, et al. Association of plasminogen activator inhibitor-1 4G5G polymorphism with risk of diabetic nephropathy and retinopathy:?a systematic review and Meta-analysis[J]. J Diabetes Metab Disord, 2020, 19(2): 2005-2016. DOI: 10.1007/s40200-020-00675-1.
[38]
Denorme F, Rustad JL, Portier I, et al. Neutrophil extracellular trap inhibition improves survival in neonatal mouse infectious peritonitis[J]. Pediatr Res, 2023, 93(4): 862-869. DOI: 10.1038/s41390-022-02219-0.
[39]
刘雪姮,俞生林,高沙沙,等. 中性粒细胞胞外诱捕网在新生儿败血症中的表达和临床意义[J]. 中华新生儿科杂志2022, 37(3): 219-224. DOI: 10.3760/cma.j.issn.2096-2932.2022.03.006.
[40]
Uchimido R, Schmidt EP, Shapiro NI. The glycocalyx: a novel diagnostic and therapeutic target in sepsis[J]. Crit Care, 2019, 23(1): 16. DOI: 10.1186/s13054-018-2292-6.
[41]
Fernández-Sarmiento J, Molina CF, Salazar-Pelaez LM, et al. Biomarkers of glycocalyx injury and endothelial activation are associated with clinical outcomes in patients with sepsis: a systematic review and Meta-analysis[J]. J Intensive Care Med, 2023, 38(1): 95-105. DOI: 10.1177/08850666221109186.
[42]
Puchwein-Schwepcke A, Genzel-Boroviczény O, Nussbaum C. The endothelial glycocalyx: physiology and pathology in neonates, infants and children[J]. Front Cell Dev Biol, 2021, 9: 733557. DOI: 10.3389/fcell.2021.733557.
[43]
Ahlam F, Wiam S, Jesús B, et al. The endothelial glycocalyx and neonatal sepsis[J]. Int J Mol Sci, 2022, 24(1): 364. DOI: 10.3390/ijms24010364.
[44]
Resch E, Hinkas O, Urlesberger B, et al. Neonatal thrombocytopenia-causes and outcomes following platelet transfusions[J]. Eur J Pediatr, 2018, 177(7): 1045-1052. DOI: 10.1007/s00431-018-3153-7.
[45]
Patel RM, Josephson C. Neonatal and pediatric platelet transfusions: current concepts and controversies[J]. Curr Opin Hematol, 2019, 26(6): 466-472. DOI: 10.1097/moh.0000000000000542.
[46]
Ferrer-Marín F, Sola-Visner M. Neonatal platelet physiology and implications for transfusion[J]. Platelets, 2022, 33(1): 14-22. DOI: 10.1080/09537104.2021.1962837.
[47]
Vanvooren DM, Bradshaw WT, Blake SM. Disseminated Intravascular coagulation in the neonate[J]. Neonatal Netw, 2018, 37(4): 205-211. DOI: 10.1891/0730-0832.37.4.205.
[48]
Mitsiakos G, Karametou M, Gkampeta A, et al. Effectiveness and safety of 4-factor prothrombin complex concentrate (4PCC) in neonates with intractable bleeding or severe coagulation disturbances: a retrospective study of 37 cases[J]. J Pediatr Hematol Oncol, 2019, 41(3): e135-e140. DOI: 10.1097/mph.0000000000001397.
[49]
Warren BB, Moyer GC, Manco-Johnson MJ. Hemostasis in the pregnant woman, the placenta, the fetus, and the newborn infant[J]. Semin Thromb Hemost, 2023, 49(4): 319-329. DOI: 10.1055/s-0042-1760332.
[50]
Hamadah HK, Kabbani MS. Local pulmonary administration of factor VIIa (rFVIIa) in massive pulmonary haemorrhage in post-operative cardiac infant[J]. Cardiol Young, 2023, 33(5): 835-837. DOI: 10.1017/s1047951122003006.
[51]
Gunel Karaburun IE, Kayki G, Aytac SS, et al. Transplacental hemophilia A and prophylactic treatment with intravenous immunoglobulin and recombinant factor Ⅶa in the newborn period: a case report[J]. Blood Coagul Fibrinolysis, 2021, 32(2): 151-154. DOI: 10.1097/mbc.0000000000000978.
[52]
Conti GO, Molinari AC, Signorelli SS, et al. Neonatal systemic thrombosis: an updated overview[J]. Curr Vasc Pharmacol, 2018, 16(5): 499-509. DOI: 10.2174/1570161116666180117101445.
[53]
Kenet G, Cohen O, Bajorat T, et al. Insights into neonatal thrombosis[J]. Thromb Res, 2019, 181(Suppl 1): S33-S36. DOI: 10.1016/s0049-3848(19)30364-0.
[54]
Ozment CP, Scott BL, Bembea MM, et al. Anticoagulation and transfusion management during neonatal and pediatric extracorporeal membrane oxygenation: a survey of medical directors in the united states[J]. Pediatr Crit Care Med, 2021, 22(6): 530-541. DOI: 10.1097/pcc.0000000000002696.
[55]
Moiseiwitsch N, Brown AC. Neonatal coagulopathies: a review of established and emerging treatments[J]. Exp Biol Med (Maywood), 2021, 246(12): 1447-1457. DOI: 10.1177/15353702211006046.
[56]
Li B, Saka R, Takama Y, et al. Recombinant human soluble thrombomodulin reduces the severity and incidence of necrotizing enterocolitis in a newborn rat model[J]. Surg Today, 2019, 49(11): 971-976. DOI: 10.1007/s00595-019-01832-7.
[57]
Ashina M, Fujioka K, Nishida K, et al. Recombinant human thrombomodulin attenuated sepsis severity in a non-surgical preterm mouse model[J]. Sci Rep, 2020, 10(1): 333. DOI: 10.1038/s41598-019-57265-2.
[1] 李越洲, 张孔玺, 李小红, 商中华. 基于生物信息学分析胃癌中PUM的预后意义[J]. 中华普通外科学文献(电子版), 2023, 17(06): 426-432.
[2] 陈安, 冯娟, 杨振宇, 杜锡林, 柏强善, 阴继凯, 臧莉, 鲁建国. 基于生物信息学分析CCN4在肝细胞癌中表达及其临床意义[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 702-707.
[3] 孙钢. 超高场磁共振成像的发展现状与展望[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 369-372.
[4] 陆萍, 邹健. 凝血和纤维蛋白溶解标志物的动态变化对急性胰腺炎患者预后的评估价值[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 427-432.
[5] 孙晗, 武侠. 成人肠易激综合征患者肠道菌群特征与不同分型患者生活质量和精神症状的相关性[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 461-465.
[6] 杨忠华, 马晓菡, 刁磊, 胡静, 陈熙. 双气囊小肠镜在小肠CT造影结果阴性患者中的诊断价值[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 475-479.
[7] 吴蓉菊, 向平超. COPD频繁急性加重表型与炎性因子相关性研究[J]. 中华临床医师杂志(电子版), 2023, 17(9): 939-947.
[8] 邱春华, 张志宏. 1108例小肠疾病的临床诊断及检查策略分析[J]. 中华临床医师杂志(电子版), 2023, 17(9): 948-954.
[9] 卓徐鹏, 刘颖, 任菁菁. 感染性疾病与老年人低蛋白血症的相关性研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 896-899.
[10] 李静静, 翟蕾, 赵海平, 郑波. 多囊肾合并囊肿的多重耐药菌感染一例并文献复习[J]. 中华临床医师杂志(电子版), 2023, 17(08): 920-923.
[11] 周婷, 孙培培, 张二明, 安欣华, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病诊断现状调查[J]. 中华临床医师杂志(电子版), 2023, 17(07): 790-797.
[12] 静脉淋巴功能不全临床专家共识编写组. 静脉淋巴功能不全临床专家共识[J]. 中华临床医师杂志(电子版), 2023, 17(06): 630-638.
[13] 李变, 王莉娜, 桑田, 李珊, 杜雪燕, 李春华, 张兴云, 管巧, 王颖, 冯琪, 蒙景雯. 亚低温技术治疗缺氧缺血性脑病新生儿的临床分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 639-643.
[14] 魏红涛, 普布仓决, 格桑央宗, 黎燕, 益西旺扎, 李鹏. 拉萨地区上消化道溃疡患者幽门螺杆菌感染及治疗分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 662-665.
[15] 孙培培, 张二明, 时延伟, 赵春燕, 宋萍萍, 张硕, 张克, 周玉娇, 赵璨, 闫维, 吴蓉菊, 宋丽萍, 郭伟安, 马石头, 安欣华, 包曹歆, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病患病情况及相关危险因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 711-719.
阅读次数
全文


摘要