Correlation between activated partial thromboplastin time and prognosis after ECMO treatment: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

DING Ge , YAO Yang , LI Siyu , PENG Yimeng , MA Qing ,  WANG Shengyu

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xi'an Medical University, Xi’an 710000, P. R. China;

Corresponding author：

WANG Shengyu, Email: wangshengyu@yeah.net

Keywords：

Activated partial thromboplastin time (APTT); Extracorporeal membrane oxygenation (ECMO); Bleeding; Thrombosis; Mortality; Prognosis; Meta-analysis

DOI：

10.7507/1672-2531.202205093

Video：

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Objective To systematically review the correlation of activated partial thromboplastin time (APTT) and prognosis after ECMO treatment. Methods The PubMed, EMbase, MEDLINE, CNKI, WanFang Data and VIP databases were electronically searched to collect studies on the correlation of APTT and prognosis after ECMO treatment from database inception to April 11^th, 2022. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software. Results A total of 22 studies, involving 2 913 patients were included. The level of APTT in the bleeding group was higher than that in the non-bleeding group during ECMO support treatment (MD=10.34, 95%CI 1.32 to 19.37, P=0.02). The APTT level in the thrombus group was lower than that in the non-thrombus group (MD=−3.58, 95%CI −5.89 to −1.27, P=0.002). The level of APTT in the death group was significantly higher than that in the survival group (MD=8.97, 95%CI 5.89 to 12.06, P<0.00001). Conclusion The APTT level of ECMO patients is closely related to the prognosis of bleeding, thrombosis and death. Due to the limited quantity and quality of the included studies, the above conclusion needs to be verified by more high-quality studies.

Citation： DING Ge, YAO Yang, LI Siyu, PENG Yimeng, MA Qing, WANG Shengyu. Correlation between activated partial thromboplastin time and prognosis after ECMO treatment: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2022, 22(11): 1301-1308. doi: 10.7507/1672-2531.202205093 Copy

1.	Jiritano F, Serraino GF, Ten Cate H, et al. Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis. Intensive Care Med, 2020, 46(6): 1154-1169.
2.	Tonna JE, Abrams D, Brodie D, et al. Management of adult patients supported with venovenous extracorporeal membrane oxygenation (VV ECMO): guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J, 2021, 67(6): 601-610.
3.	中国心胸血管麻醉学会, 中华医学会麻醉学分会, 中国医师协会麻醉学医师分会, 等. 不同情况下成人体外膜肺氧合临床应用专家共识(2020版). 中国循环杂志, 2020, 35(11): 1052-1063.
4.	Cartwright B, Bruce HM, Kershaw G, et al. Hemostasis, coagulation and thrombin in venoarterial and venovenous extracorporeal membrane oxygenation: the HECTIC study. Sci Rep, 2021, 11(1): 7975.
5.	Moussa MD, Soquet J, Lamer A, et al. Evaluation of anti-activated factor X activity and activated partial thromboplastin time relations and their association with bleeding and thrombosis during veno-arterial ECMO support: a retrospective study. J Clin Med, 2021, 10(10): 2158.
6.	Oude Lansink-Hartgring A, de Vries AJ, Droogh JM, et al. Hemorrhagic complications during extracorporeal membrane oxygenation - the role of anticoagulation and platelets. J Crit Care, 2019, 54: 239-243.
7.	Aubron C, DePuydt J, Belon F, et al. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care, 2016, 6(1): 97.
8.	Riley JB, Schears GJ, Nuttall GA, et al. Coagulation parameter thresholds associated with non-bleeding in the eighth hour of adult cardiac surgical post-cardiotomy extracorporeal membrane oxygenation. J Extra Corpor Technol, 2016, 48(2): 71-78.
9.	Fong KM, Au SY, Ng GWY, et al. Bleeding, thrombosis and transfusion in patients on ECMO: a retrospective study in a tertiary center in Hong Kong. Int J Artif Organs, 2021, 44(6): 420-425.
10.	Perez OA, Dempfle CE, Jung T, et al. Assessing anticoagulation in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation: does anti-factor xa or thromboelastometry provide additional benefit. Front Pediatr, 2021, 9: 685906.
11.	Doymaz S, Zinger M, Sweberg T. Risk factors associated with intracranial hemorrhage in neonates with persistent pulmonary hypertension on ECMO. J Intensive Care, 2015, 3(1): 6.
12.	Hu W, Zhang J, Wang M, et al. Clinical features and risk factors analysis for hemorrhage in adults on ECMO. Front Med (Lausanne), 2021, 8: 731106.
13.	Amata M, Martucci G, Granata A, et al. The role of endoscopy as non-invasive procedure to manage gastrointestinal complications during extracorporeal membrane oxygenation. Perfusion, 2020, 35(8): 786-794.
14.	Camporesi EM, Omar H, Sprenker C, et al. Intracranial hemorrhage concurring during ECMO support. 2016 Annual Meeting of the International Anesthesia Research Society, San Francisco, California, 2016.
15.	Nguyen TP, Phan XT, Nguyen TH, et al. Major bleeding in adults undergoing peripheral extracorporeal membrane oxygenation (ECMO): prognosis and predictors. Crit Care Res Pract, 2022, 2022: 5348835.
16.	Lüsebrink E, Zimmer S, Schrage B, et al. Intracranial haemorrhage in adult patients on venoarterial extracorporeal membrane oxygenation. Eur Heart J Acute Cardiovasc Care, 2022, 11(4): 303-311.
17.	Trudzinski FC, Minko P, Rapp D, et al. Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis. Ann Intensive Care, 2016, 6(1): 66.
18.	Fisser C, Reichenbächer C, Müller T, et al. Incidence and risk factors for cannula-related venous thrombosis after venovenous extracorporeal membrane oxygenation in adult patients with acute respiratory failure. Crit Care Med, 2019, 47(4): e332-e339.
19.	Menaker J, Tabatabai A, Rector R, et al. Incidence of cannula-associated deep vein thrombosis after veno-venous extracorporeal membrane oxygenation. ASAIO J, 2017, 63(5): 588-591.
20.	Francischetti IMB, Szymanski J, Rodriguez D, et al. Laboratory and clinical predictors of 30-day survival for patients on extracorporeal membrane oxygenation (ECMO): 8-year experience at Albert Einstein College of Medicine, Montefiore Medical Center. J Crit Care, 2017, 40: 136-144.
21.	Bailly DK, Reeder RW, Winder M, et al. Development of the pediatric extracorporeal membrane oxygenation prediction model for risk-adjusting mortality. Pediatr Crit Care Med, 2019, 20(5): 426-434.
22.	McMichael ABV, Hornik CP, Hupp SR, et al. Correlation among antifactor xa, activated partial thromboplastin time, and heparin dose and association with pediatric extracorporeal membrane oxygenation complications. ASAIO J, 2020, 66(3): 307-313.
23.	谢婷, 邓磊, 李依, 等. 急诊静脉-动脉体外膜肺氧合患者死亡危险因素分析. 中国急救医学, 2021, 41(7): 640-644.
24.	杨建旭, 邱实, 张慧峰, 等. 凝血功能对体外膜肺氧合治疗危重症患者预后的影响. 中华实用诊断与治疗杂志, 2021, 35(5): 493-496.
25.	尹小雪, 刘德林, 刘远, 等. 活化凝血时间和活化部分凝血活酶时间在成人体外膜肺氧合支持期间抗凝的作用探讨. 中国体外循环杂志, 2019, 17(1): 18-21.
26.	孙峰, 陈旭锋, 梅勇, 等. 红细胞分布宽度与血小板分布宽度对体外膜肺氧合支持的急性心肌梗死患者预后的判断. 中国急救医学, 2022, 42(3): 251-254.
27.	高国栋, 龙村, 胡强, 等. 体外膜肺氧合支持治疗期间机体凝血功能的动态变化. 实用临床医药杂志, 2015, 19(9): 9-11, 17.
28.	杨峰, 王粮山. 成人体外膜氧合循环辅助专家共识. 中华重症医学电子杂志(网络版), 2018, 4(2): 114-122.
29.	Protti A, Iapichino GE, Di Nardo M, et al. Anticoagulation management and antithrombin supplementation practice during veno-venous extracorporeal membrane oxygenation: a worldwide survey. Anesthesiology, 2020, 132(3): 562-570.
30.	赵举, 崔勇丽, 刘刚. ECMO中的抗凝管理. 中国急救医学, 2021, 41(7): 607-609.
31.	Basu D, Gallus A, Hirsh J, et al. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med, 1972, 287(7): 324-327.
32.	McMichael ABV, Ryerson LM, Ratano D, et al. 2021 ELSO adult and pediatric anticoagulation guidelines. ASAIO J, 2022, 68(3): 303-310.
33.	Whitman-Purves E, Coons JC, Miller T, et al. Performance of anti-factor xa versus activated partial thromboplastin time for heparin monitoring using multiple nomograms. Clin Appl Thromb Hemost, 2018, 24(2): 310-316.
34.	Frugé KS, Lee YR. Comparison of unfractionated heparin protocols using antifactor Xa monitoring or activated partial thrombin time monitoring. Am J Health Syst Pharm, 2015, 72(17 Suppl 2): S90-97.
35.	Schriefl C, Schoergenhofer C, Grafeneder J, et al. Prolonged activated partial thromboplastin time after successful resuscitation from cardiac arrest is associated with unfavorable neurologic outcome. Thromb Haemost, 2021, 121(4): 477-483.
36.	Van Den Helm S, Yaw HP, Letunica N, et al. Platelet phenotype and function changes with increasing duration of extracorporeal membrane oxygenation. Crit Care Med, 2022, 50(8): 1236-1245.
37.	Chen Y, Chen H, Liu X, et al. Inferior vena cava thrombosis during extracorporeal membrane oxygenation: a case report and review of the literature. J Med Case Rep, 2021, 15(1): 529.
38.	Combes A, Schmidt M, Hodgson CL, et al. Extracorporeal life support for adults with acute respiratory distress syndrome. Intensive Care Med, 2020, 46(12): 2464-2476.
39.	Mazzeffi MA, Tanaka K, Roberts A, et al. Bleeding, thrombosis, and transfusion with two heparin anticoagulation protocols in venoarterial ECMO patients. J Cardiothorac Vasc Anesth, 2019, 33(5): 1216-1220.
40.	Delmas C, Jacquemin A, Vardon-Bounes F, et al. Anticoagulation monitoring under ECMO support: a comparative study between the activated coagulation time and the anti-Xa activity assay. J Intensive Care Med, 2020, 35(7): 679-686.
41.	Northam KA, Nguyen B, Chen SL, et al. Evaluation of a multimodal heparin laboratory monitoring protocol in adult extracorporeal membrane oxygenation patients. J Pharm Pract, 2021.
42.	Baluwala I, Favaloro EJ, Pasalic L. Therapeutic monitoring of unfractionated heparin - trials and tribulations. Expert Rev Hematol, 2017, 10(7): 595-605.
43.	Moynihan K, Johnson K, Straney L, et al. Coagulation monitoring correlation with heparin dose in pediatric extracorporeal life support. Perfusion, 2017, 32(8): 675-685.

1. Jiritano F, Serraino GF, Ten Cate H, et al. Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis. Intensive Care Med, 2020, 46(6): 1154-1169.
2. Tonna JE, Abrams D, Brodie D, et al. Management of adult patients supported with venovenous extracorporeal membrane oxygenation (VV ECMO): guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J, 2021, 67(6): 601-610.
3. 中国心胸血管麻醉学会, 中华医学会麻醉学分会, 中国医师协会麻醉学医师分会, 等. 不同情况下成人体外膜肺氧合临床应用专家共识(2020版). 中国循环杂志, 2020, 35(11): 1052-1063.
4. Cartwright B, Bruce HM, Kershaw G, et al. Hemostasis, coagulation and thrombin in venoarterial and venovenous extracorporeal membrane oxygenation: the HECTIC study. Sci Rep, 2021, 11(1): 7975.
5. Moussa MD, Soquet J, Lamer A, et al. Evaluation of anti-activated factor X activity and activated partial thromboplastin time relations and their association with bleeding and thrombosis during veno-arterial ECMO support: a retrospective study. J Clin Med, 2021, 10(10): 2158.
6. Oude Lansink-Hartgring A, de Vries AJ, Droogh JM, et al. Hemorrhagic complications during extracorporeal membrane oxygenation - the role of anticoagulation and platelets. J Crit Care, 2019, 54: 239-243.
7. Aubron C, DePuydt J, Belon F, et al. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care, 2016, 6(1): 97.
8. Riley JB, Schears GJ, Nuttall GA, et al. Coagulation parameter thresholds associated with non-bleeding in the eighth hour of adult cardiac surgical post-cardiotomy extracorporeal membrane oxygenation. J Extra Corpor Technol, 2016, 48(2): 71-78.
9. Fong KM, Au SY, Ng GWY, et al. Bleeding, thrombosis and transfusion in patients on ECMO: a retrospective study in a tertiary center in Hong Kong. Int J Artif Organs, 2021, 44(6): 420-425.
10. Perez OA, Dempfle CE, Jung T, et al. Assessing anticoagulation in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation: does anti-factor xa or thromboelastometry provide additional benefit. Front Pediatr, 2021, 9: 685906.
11. Doymaz S, Zinger M, Sweberg T. Risk factors associated with intracranial hemorrhage in neonates with persistent pulmonary hypertension on ECMO. J Intensive Care, 2015, 3(1): 6.
12. Hu W, Zhang J, Wang M, et al. Clinical features and risk factors analysis for hemorrhage in adults on ECMO. Front Med (Lausanne), 2021, 8: 731106.
13. Amata M, Martucci G, Granata A, et al. The role of endoscopy as non-invasive procedure to manage gastrointestinal complications during extracorporeal membrane oxygenation. Perfusion, 2020, 35(8): 786-794.
14. Camporesi EM, Omar H, Sprenker C, et al. Intracranial hemorrhage concurring during ECMO support. 2016 Annual Meeting of the International Anesthesia Research Society, San Francisco, California, 2016.
15. Nguyen TP, Phan XT, Nguyen TH, et al. Major bleeding in adults undergoing peripheral extracorporeal membrane oxygenation (ECMO): prognosis and predictors. Crit Care Res Pract, 2022, 2022: 5348835.
16. Lüsebrink E, Zimmer S, Schrage B, et al. Intracranial haemorrhage in adult patients on venoarterial extracorporeal membrane oxygenation. Eur Heart J Acute Cardiovasc Care, 2022, 11(4): 303-311.
17. Trudzinski FC, Minko P, Rapp D, et al. Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis. Ann Intensive Care, 2016, 6(1): 66.
18. Fisser C, Reichenbächer C, Müller T, et al. Incidence and risk factors for cannula-related venous thrombosis after venovenous extracorporeal membrane oxygenation in adult patients with acute respiratory failure. Crit Care Med, 2019, 47(4): e332-e339.
19. Menaker J, Tabatabai A, Rector R, et al. Incidence of cannula-associated deep vein thrombosis after veno-venous extracorporeal membrane oxygenation. ASAIO J, 2017, 63(5): 588-591.
20. Francischetti IMB, Szymanski J, Rodriguez D, et al. Laboratory and clinical predictors of 30-day survival for patients on extracorporeal membrane oxygenation (ECMO): 8-year experience at Albert Einstein College of Medicine, Montefiore Medical Center. J Crit Care, 2017, 40: 136-144.
21. Bailly DK, Reeder RW, Winder M, et al. Development of the pediatric extracorporeal membrane oxygenation prediction model for risk-adjusting mortality. Pediatr Crit Care Med, 2019, 20(5): 426-434.
22. McMichael ABV, Hornik CP, Hupp SR, et al. Correlation among antifactor xa, activated partial thromboplastin time, and heparin dose and association with pediatric extracorporeal membrane oxygenation complications. ASAIO J, 2020, 66(3): 307-313.
23. 谢婷, 邓磊, 李依, 等. 急诊静脉-动脉体外膜肺氧合患者死亡危险因素分析. 中国急救医学, 2021, 41(7): 640-644.
24. 杨建旭, 邱实, 张慧峰, 等. 凝血功能对体外膜肺氧合治疗危重症患者预后的影响. 中华实用诊断与治疗杂志, 2021, 35(5): 493-496.
25. 尹小雪, 刘德林, 刘远, 等. 活化凝血时间和活化部分凝血活酶时间在成人体外膜肺氧合支持期间抗凝的作用探讨. 中国体外循环杂志, 2019, 17(1): 18-21.
26. 孙峰, 陈旭锋, 梅勇, 等. 红细胞分布宽度与血小板分布宽度对体外膜肺氧合支持的急性心肌梗死患者预后的判断. 中国急救医学, 2022, 42(3): 251-254.
27. 高国栋, 龙村, 胡强, 等. 体外膜肺氧合支持治疗期间机体凝血功能的动态变化. 实用临床医药杂志, 2015, 19(9): 9-11, 17.
28. 杨峰, 王粮山. 成人体外膜氧合循环辅助专家共识. 中华重症医学电子杂志(网络版), 2018, 4(2): 114-122.
29. Protti A, Iapichino GE, Di Nardo M, et al. Anticoagulation management and antithrombin supplementation practice during veno-venous extracorporeal membrane oxygenation: a worldwide survey. Anesthesiology, 2020, 132(3): 562-570.
30. 赵举, 崔勇丽, 刘刚. ECMO中的抗凝管理. 中国急救医学, 2021, 41(7): 607-609.
31. Basu D, Gallus A, Hirsh J, et al. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med, 1972, 287(7): 324-327.
32. McMichael ABV, Ryerson LM, Ratano D, et al. 2021 ELSO adult and pediatric anticoagulation guidelines. ASAIO J, 2022, 68(3): 303-310.
33. Whitman-Purves E, Coons JC, Miller T, et al. Performance of anti-factor xa versus activated partial thromboplastin time for heparin monitoring using multiple nomograms. Clin Appl Thromb Hemost, 2018, 24(2): 310-316.
34. Frugé KS, Lee YR. Comparison of unfractionated heparin protocols using antifactor Xa monitoring or activated partial thrombin time monitoring. Am J Health Syst Pharm, 2015, 72(17 Suppl 2): S90-97.
35. Schriefl C, Schoergenhofer C, Grafeneder J, et al. Prolonged activated partial thromboplastin time after successful resuscitation from cardiac arrest is associated with unfavorable neurologic outcome. Thromb Haemost, 2021, 121(4): 477-483.
36. Van Den Helm S, Yaw HP, Letunica N, et al. Platelet phenotype and function changes with increasing duration of extracorporeal membrane oxygenation. Crit Care Med, 2022, 50(8): 1236-1245.
37. Chen Y, Chen H, Liu X, et al. Inferior vena cava thrombosis during extracorporeal membrane oxygenation: a case report and review of the literature. J Med Case Rep, 2021, 15(1): 529.
38. Combes A, Schmidt M, Hodgson CL, et al. Extracorporeal life support for adults with acute respiratory distress syndrome. Intensive Care Med, 2020, 46(12): 2464-2476.
39. Mazzeffi MA, Tanaka K, Roberts A, et al. Bleeding, thrombosis, and transfusion with two heparin anticoagulation protocols in venoarterial ECMO patients. J Cardiothorac Vasc Anesth, 2019, 33(5): 1216-1220.
40. Delmas C, Jacquemin A, Vardon-Bounes F, et al. Anticoagulation monitoring under ECMO support: a comparative study between the activated coagulation time and the anti-Xa activity assay. J Intensive Care Med, 2020, 35(7): 679-686.
41. Northam KA, Nguyen B, Chen SL, et al. Evaluation of a multimodal heparin laboratory monitoring protocol in adult extracorporeal membrane oxygenation patients. J Pharm Pract, 2021.
42. Baluwala I, Favaloro EJ, Pasalic L. Therapeutic monitoring of unfractionated heparin - trials and tribulations. Expert Rev Hematol, 2017, 10(7): 595-605.
43. Moynihan K, Johnson K, Straney L, et al. Coagulation monitoring correlation with heparin dose in pediatric extracorporeal life support. Perfusion, 2017, 32(8): 675-685.

Chinese Journal of Evidence-Based Medicine

Correlation between activated partial thromboplastin time and prognosis after ECMO treatment: a meta-analysis

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