The value of antithrombin <b>Ⅲ</b> in predicting in-hospital mortality and optimizing risk stratification in acute pulmonary thromboembolism_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIN Jing ¹ , CHEN Jialong ¹ , WU Dansen ^1,2 ,  SHI Songjing ^1,2

1. Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350000, P. R. China;
2. Department 2 of Intensive Care Medicine, Fujian Provincial Hospital, Fuzhou, Fujian 350000, P. R. China;

Corresponding author：

SHI Songjing, Email: serena10@126.com

Keywords：

Acute pulmonary thromboembolism; Antithrombin Ⅲ; In-hospital mortality; Risk stratification

DOI：

10.7507/1671-6205.201912025

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Objective To explore the clinical application value of antithrombin Ⅲ (ATⅢ) in pulmonary thromboembolism (PTE).Methods A retrospective study included 204 patients with confirmed PTE who were admitted to Fujian Provincial Hospital from May 2012 to June 2019. The clinical data of the study included basic conditions, morbilities, laboratory examinations and scoring system within 24 hours after admission. The relationship between ATⅢ and PTE in-hospital death was analyzed, and the value of ATⅢ to optimize risk stratification was explored.Results For ATⅢ, the area under receiver operating characteristic curve (AUC) of predicting in-hospital mortality was 0.719, with a cut-off value of 77.7% (sensitivity 64.71%, specificity 80.21%). The patients were divided into ATⅢ≤77.7% group (n=48) and ATⅢ>77.7% group (n=156) according to the cut-off value, and significant statistically differences were found in chronic heart failure, white blood cells count, platelets count, alanine aminotransferase (ALT), albumin and troponin I (P<0.05). According to the in-hospital mortality, patients were divided into a death group (n=17) and a survival group (n=187), and the differences in count of white blood cells, ATⅢ, D-dimer, ALT, albumin, estimated glomerular filtration rate and APACHEⅡ were statistically significant. Logistic regression analysis revealed that ATⅢ≤77.7% and white blood cells count were independent risk factors for in-hospital death. The risk stratification and the risk stratification combined ATⅢ to predict in-hospital death were evaluated by receiver operating characteristic curve, and the AUC was 0.705 and 0.813, respectively (P<0.05). A new scoring model of risk stratification combined with ATⅢ was showed by nomogram.Conclusions ATⅢ≤77.7% is an independent risk factor for in-hospital death, and is beneficial to optimize risk stratification. The mechanism may be related to thrombosis, right ventricular dysfunction and inflammatory response.

Citation： LIN Jing, CHEN Jialong, WU Dansen, SHI Songjing. The value of antithrombin Ⅲ in predicting in-hospital mortality and optimizing risk stratification in acute pulmonary thromboembolism. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(3): 189-194. doi: 10.7507/1671-6205.201912025 Copy

1.	中华医学会呼吸病学分会肺栓塞与肺血管病学组, 中国医师协会呼吸医师分会肺栓塞与肺血管病工作委员会, 全国肺栓塞与肺血管病防治协作组. 肺血栓栓塞症诊治与预防指南. 中华医学杂志, 2018, 98(14): 1060-1087.
2.	Klok FA, Zondag W, van Kralingen KW, et al. Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events. Am J Respir Crit Care Med, 2010, 181(5): 501-506.
3.	Maclean PS, Tait RC. Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs, 2007, 67(10): 1429-1440.
4.	Niedermayr M, Schramm W, Kamolz L, et al. Antithrombin deficiency and its relationship to severe burns. Burns, 2007, 33(2): 173-178.
5.	Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J, 2020, 41(4): 543-603.
6.	Mizuguchi T, Kawamoto M, Meguro M, et al. Serum antithrombin Ⅲ level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients. Hepatogastroenterology, 2012, 59(114): 551-557.
7.	Hofmann E, Limacher A, Méan M, et al. Echocardiography does not predict mortality in hemodynamically stable elderly patients with acute pulmonary embolism. Thromb Res, 2016, 145: 67-71.
8.	Hellenkamp K, Pruszczyk P, Jiménez D, et al. Prognostic impact of copeptin in pulmonary embolism: a multicentre validation study. Eur Respir J, 2018, 51(4): 1702037.
9.	Stehling F, Weber R, Ozcelik A, et al. Acute changes of coagulation and fibrinolysis parameters after experimental thromboembolic stroke and thrombolytic therapy. Neurosci Lett, 2008, 441(1): 39-43.
10.	Murano G, Williams L, Miller-Andersson M, et al. Some properties of antithrombin-Ⅲ and its concentration in human plasma. Thromb Res, 1980, 18(1-2): 259-262.
11.	Bucciarelli P, Passamonti SM, Biguzzi E, et al. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost, 2012, 10(9): 1783-1791.
12.	Rao LV, Nordfang O, Hoang AD, et al. Mechanism of antithrombin Ⅲ inhibition of factor VⅡa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Ⅹa-induced inhibition of factor VⅡa/tissue factor activity. Blood, 1995, 85(1): 121-129.
13.	Choi SW, Kim BB, Choi DH, et al. Stroke or left atrial thrombus prediction using antithrombin Ⅲ and mean platelet volume in patients with nonvalvular atrial fibrillation. Clin Cardiol, 2017, 40(11): 1013-1019.
14.	De Stefano V, Simioni P, Rossi E, et al. The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. Haematologica, 2006, 91(5): 695-698.
15.	吴莎, 焦琳, 胡家豪, 等. 抗凝血酶Ⅲ缺乏致肺栓塞一例. 中国呼吸与危重监护杂志, 2017, 16(2): 177-180.
16.	Chin VM, Holland ML, Parker MM, et al. Antithrombin activity and heparin response in neonates and infants undergoing congenital cardiac surgery: a retrospective cohort study. Can J Anaesth, 2016, 63(1): 38-45.
17.	Di GG, Marinelli D. Antithrombin Ⅲ as predictor of liver reserve: a new parameter to improve the results of mechanical circulatory support therapy. J Thorac Cardiovasc Surg, 2017, 153(6): 1383.
18.	Aslan S, Meral M, Akgun M, et al. Liver dysfunction in patients with acute pulmonary embolism. Hepatol Res, 2007, 37(3): 205-213.
19.	Morikawa M, Suzuki H, Obata-Yasuoka M, et al. Association of antenatal antithrombin activity with perinatal liver dysfunction: A prospective multicenter study. J Gastroenterol Hepatol, 2017, 32(7): 1378-1386.
20.	俞聪波, 叶映月, 华双益, 等. 急诊感染患者凝血障碍与脓毒血症的关系及参考评价. 中华医院感染学杂志, 2017, 27(23): 5308-5311.
21.	Oelschläger C, Römisch J, Staubitz A, et al. Antithrombin Ⅲ inhibits nuclear factor kappaB activation in human monocytes and vascular endothelial cells. Blood, 2002, 99(11): 4015-4020.
22.	Salvatierra A, Guerrero R, Rodriguez M, et al. Antithrombin Ⅲ prevents early pulmonary dysfunction after lung transplantation in the dog. Circulation, 2001, 104(24): 2975-2980.
23.	Roemisch J, Gray E, Hoffmann JN, et al. Antithrombin: a new look at the actions of a serine protease inhibitor. Blood Coagul Fibrinolysis, 2002, 13(8): 657-670.

1. 中华医学会呼吸病学分会肺栓塞与肺血管病学组, 中国医师协会呼吸医师分会肺栓塞与肺血管病工作委员会, 全国肺栓塞与肺血管病防治协作组. 肺血栓栓塞症诊治与预防指南. 中华医学杂志, 2018, 98(14): 1060-1087.
2. Klok FA, Zondag W, van Kralingen KW, et al. Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events. Am J Respir Crit Care Med, 2010, 181(5): 501-506.
3. Maclean PS, Tait RC. Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs, 2007, 67(10): 1429-1440.
4. Niedermayr M, Schramm W, Kamolz L, et al. Antithrombin deficiency and its relationship to severe burns. Burns, 2007, 33(2): 173-178.
5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J, 2020, 41(4): 543-603.
6. Mizuguchi T, Kawamoto M, Meguro M, et al. Serum antithrombin Ⅲ level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients. Hepatogastroenterology, 2012, 59(114): 551-557.
7. Hofmann E, Limacher A, Méan M, et al. Echocardiography does not predict mortality in hemodynamically stable elderly patients with acute pulmonary embolism. Thromb Res, 2016, 145: 67-71.
8. Hellenkamp K, Pruszczyk P, Jiménez D, et al. Prognostic impact of copeptin in pulmonary embolism: a multicentre validation study. Eur Respir J, 2018, 51(4): 1702037.
9. Stehling F, Weber R, Ozcelik A, et al. Acute changes of coagulation and fibrinolysis parameters after experimental thromboembolic stroke and thrombolytic therapy. Neurosci Lett, 2008, 441(1): 39-43.
10. Murano G, Williams L, Miller-Andersson M, et al. Some properties of antithrombin-Ⅲ and its concentration in human plasma. Thromb Res, 1980, 18(1-2): 259-262.
11. Bucciarelli P, Passamonti SM, Biguzzi E, et al. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost, 2012, 10(9): 1783-1791.
12. Rao LV, Nordfang O, Hoang AD, et al. Mechanism of antithrombin Ⅲ inhibition of factor VⅡa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Ⅹa-induced inhibition of factor VⅡa/tissue factor activity. Blood, 1995, 85(1): 121-129.
13. Choi SW, Kim BB, Choi DH, et al. Stroke or left atrial thrombus prediction using antithrombin Ⅲ and mean platelet volume in patients with nonvalvular atrial fibrillation. Clin Cardiol, 2017, 40(11): 1013-1019.
14. De Stefano V, Simioni P, Rossi E, et al. The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. Haematologica, 2006, 91(5): 695-698.
15. 吴莎, 焦琳, 胡家豪, 等. 抗凝血酶Ⅲ缺乏致肺栓塞一例. 中国呼吸与危重监护杂志, 2017, 16(2): 177-180.
16. Chin VM, Holland ML, Parker MM, et al. Antithrombin activity and heparin response in neonates and infants undergoing congenital cardiac surgery: a retrospective cohort study. Can J Anaesth, 2016, 63(1): 38-45.
17. Di GG, Marinelli D. Antithrombin Ⅲ as predictor of liver reserve: a new parameter to improve the results of mechanical circulatory support therapy. J Thorac Cardiovasc Surg, 2017, 153(6): 1383.
18. Aslan S, Meral M, Akgun M, et al. Liver dysfunction in patients with acute pulmonary embolism. Hepatol Res, 2007, 37(3): 205-213.
19. Morikawa M, Suzuki H, Obata-Yasuoka M, et al. Association of antenatal antithrombin activity with perinatal liver dysfunction: A prospective multicenter study. J Gastroenterol Hepatol, 2017, 32(7): 1378-1386.
20. 俞聪波, 叶映月, 华双益, 等. 急诊感染患者凝血障碍与脓毒血症的关系及参考评价. 中华医院感染学杂志, 2017, 27(23): 5308-5311.
21. Oelschläger C, Römisch J, Staubitz A, et al. Antithrombin Ⅲ inhibits nuclear factor kappaB activation in human monocytes and vascular endothelial cells. Blood, 2002, 99(11): 4015-4020.
22. Salvatierra A, Guerrero R, Rodriguez M, et al. Antithrombin Ⅲ prevents early pulmonary dysfunction after lung transplantation in the dog. Circulation, 2001, 104(24): 2975-2980.
23. Roemisch J, Gray E, Hoffmann JN, et al. Antithrombin: a new look at the actions of a serine protease inhibitor. Blood Coagul Fibrinolysis, 2002, 13(8): 657-670.

Chinese Journal of Respiratory and Critical Care Medicine

The value of antithrombin Ⅲ in predicting in-hospital mortality and optimizing risk stratification in acute pulmonary thromboembolism

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