Cannula-Associated Deep Vein Thrombosis After Extracorporeal Life Support: A Prospective Diagnostic Study
Abstract
1. Introduction
2. Materials and Methods
2.1. General Methods
2.2. VTE Detection
2.3. Post-Mortem Examinations
2.4. Anticoagulation Regime
2.5. Local Management
2.6. Documentation
2.7. Statistical Analysis
3. Results
3.1. Population
3.2. DVT Prevalence
3.3. PE Prevalence
3.4. Anticoagulation and Anti-PLT Therapy
3.5. Multivariate Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AF | atrial fibrillation |
AMI | acute myocardial infarction |
Anti-Xa | anti-factor Xa activity |
aPTT | activated partial thromboplastin time |
ARDS | acute respiratory distress syndrome |
BMI | body mass index |
CI | confidence interval |
CKD | chronic kidney disease |
CPR | cardiopulmonary resuscitation |
CS | cardiogenic shock |
CT | computed tomography |
DVT | deep vein thrombosis |
ECMO | extracorporeal membrane oxygenation |
ECLS | extracorporeal life support |
ECPR | extracorporeal cardiopulmonary resuscitation |
ICU | intensive care unit |
IQR | interquartile range |
LOS | length of stay |
n.a. | not applicable |
PE | pulmonary embolism |
PLT | platelets |
PT | prothrombin time |
RVAD | right ventricular assist device |
SAPS II | simplified acute physiology score II |
SD | standard deviation |
UFH | unfractionated heparin |
VA | venoarterial |
VV | venovenous |
VTE | venous thromboembolism |
Y/N | Yes/No |
References
- Li, H.L.; Zhang, H.; Chan, Y.C.; Cheng, S.W. Prevalence and risk factors of hospital acquired venous thromboembolism. Phlebology 2024, 40, 2683555241297566. [Google Scholar] [CrossRef]
- Moller, M.H.; Skrifvars, M.B.; Azoulay, E. ICM focus on thrombosis and bleeding. Intensive Care Med. 2017, 43, 1910–1911. [Google Scholar] [CrossRef]
- Murphy, D.A.; Hockings, L.E.; Andrews, R.K.; Aubron, C.; Gardiner, E.E.; Pellegrino, V.A.; Davis, A.K. Extracorporeal membrane oxygenation-hemostatic complications. Transfus. Med. Rev. 2015, 29, 90–101. [Google Scholar] [CrossRef]
- Weingart, C.; Lubnow, M.; Philipp, A.; Bein, T.; Camboni, D.; Muller, T. Comparison of Coagulation Parameters, Anticoagulation, and Need for Transfusion in Patients on Interventional Lung Assist or Veno-Venous Extracorporeal Membrane Oxygenation. Artif. Organs 2015, 39, 765–773. [Google Scholar] [CrossRef]
- Abruzzo, A.; Gorantla, V.; Thomas, S.E. Venous thromboembolic events in the setting of extracorporeal membrane oxygenation support in adults: A systematic review. Thromb. Res. 2022, 212, 58–71. [Google Scholar] [CrossRef]
- van Minnen, O.; van den Bergh, W.M.; Droogh, J.M.; Koehorst, L.; Lagrand, W.K.; Raasveld, S.J.; Oude Lansink-Hartgring, A.; Terpstra, A.; Smit, J.M.; Tuinman, P.R.; et al. Incidence and risk factors of deep vein thrombosis after extracorporeal life support. Artif. Organs 2022, 46, 1893–1900. [Google Scholar] [CrossRef]
- Lamarche, Y.; Chow, B.; Bedard, A.; Johal, N.; Kaan, A.; Humphries, K.H.; Cheung, A. Thromboembolic events in patients on extracorporeal membrane oxygenation without anticoagulation. Innovations 2010, 5, 424–429. [Google Scholar] [CrossRef]
- Rastan, A.J.; Lachmann, N.; Walther, T.; Doll, N.; Gradistanac, T.; Gommert, J.F.; Lehmann, S.; Wittekind, C.; Mohr, F.W. Autopsy findings in patients on postcardiotomy extracorporeal membrane oxygenation (ECMO). Int. J. Artif. Organs 2006, 29, 1121–1131. [Google Scholar] [CrossRef]
- Zangrillo, A.; Landoni, G.; Biondi-Zoccai, G.; Greco, M.; Greco, T.; Frati, G.; Patroniti, N.; Antonelli, M.; Pesenti, A.; Pappalardo, F. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit. Care Resusc. 2013, 15, 172–178. [Google Scholar] [CrossRef]
- Menaker, J.; Tabatabai, A.; Rector, R.; Dolly, K.; Kufera, J.; Lee, E.; Kon, Z.; Sanchez, P.; Pham, S.; Herr, D.L.; et al. Incidence of Cannula-Associated Deep Vein Thrombosis After Veno-Venous Extracorporeal Membrane Oxygenation. ASAIO J. 2017, 63, 588–591. [Google Scholar] [CrossRef]
- Fisser, C.; Reichenbacher, C.; Muller, T.; Schneckenpointner, R.; Malfertheiner, M.V.; Philipp, A.; Foltan, M.; Lunz, D.; Zeman, F.; Lubnow, M. 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, e332–e339. [Google Scholar] [CrossRef]
- Parzy, G.; Daviet, F.; Puech, B.; Sylvestre, A.; Guervilly, C.; Porto, A.; Hraiech, S.; Chaumoitre, K.; Papazian, L.; Forel, J.M. Venous Thromboembolism Events Following Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Syndrome Coronavirus 2 Based on CT Scans. Crit. Care Med. 2020, 48, e971–e975. [Google Scholar] [CrossRef]
- Cooper, E.; Burns, J.; Retter, A.; Salt, G.; Camporota, L.; Meadows, C.I.; Langrish, C.C.; Wyncoll, D.; Glover, G.; Ioannou, N.; et al. Prevalence of Venous Thrombosis Following Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Respiratory Failure. Crit. Care Med. 2015, 43, e581–e584. [Google Scholar] [CrossRef] [PubMed]
- Trudzinski, F.C.; Minko, P.; Rapp, D.; Fahndrich, S.; Haake, H.; Haab, M.; Bohle, R.M.; Flaig, M.; Kaestner, F.; Bals, R.; et al. Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: A retrospective analysis. Ann. Intensive Care 2016, 6, 66. [Google Scholar] [CrossRef] [PubMed]
- Nunez, J.I.; Gosling, A.F.; O’Gara, B.; Kennedy, K.F.; Rycus, P.; Abrams, D.; Brodie, D.; Shaefi, S.; Garan, A.R.; Grandin, E.W. Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: An ELSO registry analysis. Intensive Care Med. 2022, 48, 213–224. [Google Scholar] [CrossRef] [PubMed]
- Chung, M.; Cabezas, F.R.; Nunez, J.I.; Kennedy, K.F.; Rick, K.; Rycus, P.; Mehra, M.R.; Garan, A.R.; Kociol, R.D.; Grandin, E.W. Hemocompatibility-Related Adverse Events and Survival on Venoarterial Extracorporeal Life Support: An ELSO Registry Analysis. JACC Heart Fail. 2020, 8, 892–902. [Google Scholar] [CrossRef]
- Robba, C.; Wong, A.; Poole, D.; Al Tayar, A.; Arntfield, R.T.; Chew, M.S.; Corradi, F.; Douflé, G.; Goffi, A.; Lamperti, M.; et al. Basic ultrasound head-to-toe skills for intensivists in the general and neuro intensive care unit population: Consensus and expert recommendations of the European Society of Intensive Care Medicine. Intensive Care Med. 2021, 47, 1347–1367. [Google Scholar] [CrossRef]
- McMichael, A.B.V.; Ryerson, L.M.; Ratano, D.; Fan, E.; Faraoni, D.; Annich, G.M. 2021 ELSO Adult and Pediatric Anticoagulation Guidelines. ASAIO J. 2022, 68, 303–310. [Google Scholar] [CrossRef]
- Gray, E.; Mulloy, B.; Barrowcliffe, T.W. Heparin and low-molecular-weight heparin. Thromb. Haemost. 2008, 99, 807–818. [Google Scholar]
- Melehy, A.; Ning, Y.; Kurlansky, P.; Kaku, Y.; Fried, J.; Hastie, J.; Ciolek, A.; Brodie, D.; Eisenberger, A.B.; Sayer, G.; et al. Bleeding and Thrombotic Events During Extracorporeal Membrane Oxygenation for Postcardiotomy Shock. Ann. Thorac. Surg. 2022, 113, 131–137. [Google Scholar] [CrossRef]
- Beurtheret, S.; Mastroianni, C.; Pozzi, M.; D’Alessandro, C.; Luyt, C.E.; Combes, A.; Pavie, A.; Leprince, P. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome: Single-centre experience with 1-year follow-up. Eur. J. Cardiothorac. Surg. 2012, 41, 691–695. [Google Scholar] [CrossRef]
- Kohs, T.C.L.; Liu, P.; Raghunathan, V.; Amirsoltani, R.; Oakes, M.; McCarty, O.J.T.; Olson, S.R.; Masha, L.; Zonies, D.; Shatzel, J.J. Severe thrombocytopenia in adults undergoing extracorporeal membrane oxygenation is predictive of thrombosis. Platelets 2022, 33, 570–576. [Google Scholar] [CrossRef] [PubMed]
- Bidar, F.; Lancelot, A.; Lebreton, G.; Pineton de Chambrun, M.; Schmidt, M.; Hekimian, G.; Uvin, C.; Bréchot, N.; Schoell, T.; Leprince, P.; et al. Venous or arterial thromboses after venoarterial extracorporeal membrane oxygenation support: Frequency and risk factors. J. Heart Lung Transplant. 2021, 40, 307–315. [Google Scholar] [CrossRef]
- Shafii, A.E.; Brown, C.R.; Murthy, S.C.; Mason, D.P. High incidence of upper-extremity deep vein thrombosis with dual-lumen venovenous extracorporeal membrane oxygenation. J. Thorac. Cardiovasc. Surg. 2012, 144, 988–989. [Google Scholar] [CrossRef]
- Vazquez, Z.G.S.; Sodha, N.R.; Devers, C.; Ventetuolo, C.E.; Abbasi, A. Prevalence of Deep Vein Thrombosis in Patients Supported With Extracorporeal Membrane Oxygenation. ASAIO J. 2021, 67, e169–e171. [Google Scholar] [CrossRef]
- Zhao, L.; Wang, C.; Chen, J.Y.; Liang, C.Y.; Guo, L.J.; Li, M.; Chen, W.H. A single-center experience of venous thromboembolism after adult lung transplantation. Chinese Journal of Tuberculosis and Respiratory Diseases 2019, 42, 694–699. [Google Scholar]
- Ribeiro Neto, M.L.; Budev, M.; Culver, D.A.; Lane, C.R.; Gomes, M.; Wang, X.F.; Olman, M.A. Venous Thromboembolism After Adult Lung Transplantation: A Frequent Event Associated With Lower Survival. Transplantation 2018, 102, 681–687. [Google Scholar] [CrossRef]
- Tonna, J.E.; Boonstra, P.S.; MacLaren, G.; Paden, M.; Brodie, D.; Anders, M.; Hoskote, A.; Ramanathan, K.; Hyslop, R.; Fanning, J.J.; et al. Extracorporeal Life Support Organization Registry International Report 2022: 100,000 Survivors. ASAIO J. 2024, 70, 131–143. [Google Scholar] [CrossRef]
- Zhu, Y.; Lan, M.J.; Liang, J.S.; Cai, L.Y.; Guo, L.Y.; Gu, P.P.; Zeng, F. Assessing Venous Thrombotic Risks in Extracorporeal Membrane Oxygenation-Supported Patients: A Systematic Review and Meta-Analysis. Clin. Appl. Thromb. Hemost. 2024, 30, 10760296241279293. [Google Scholar] [CrossRef] [PubMed]
- Millar, J.E.; Fanning, J.P.; McDonald, C.I.; McAuley, D.F.; Fraser, J.F. The inflammatory response to extracorporeal membrane oxygenation (ECMO): A review of the pathophysiology. Crit. Care 2016, 20, 387. [Google Scholar] [CrossRef] [PubMed]
- Calfee, C.S.; Delucchi, K.; Parsons, P.E.; Thompson, B.T.; Ware, L.B.; Matthay, M.A. Subphenotypes in acute respiratory distress syndrome: Latent class analysis of data from two randomised controlled trials. Lancet Respir. Med. 2014, 2, 611–620. [Google Scholar] [CrossRef]
- Maddali, M.V.; Churpek, M.; Pham, T.; Rezoagli, E.; Zhuo, H.; Zhao, W.; He, J.; Delucchi, K.L.; Wang, C.; Wickersham, N.; et al. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: An observational, multicohort, retrospective analysis. Lancet Respir. Med. 2022, 10, 367–377. [Google Scholar] [CrossRef] [PubMed]
- Patel, P.; Walborn, A.; Rondina, M.; Fareed, J.; Hoppensteadt, D. Markers of Inflammation and Infection in Sepsis and Disseminated Intravascular Coagulation. Clin. Appl. Thromb. Hemost. 2019, 25, 1076029619843338. [Google Scholar] [CrossRef]
- Prandoni, P.; Noventa, F.; Milan, M. Aspirin and recurrent venous thromboembolism. Phlebology 2013, 28 (Suppl. S1), 99–104. [Google Scholar] [CrossRef] [PubMed]
- Buchtele, N.; Schorgenhofer, C.; Schwameis, M.; Jilma, B.; Schellongowski, P.; Herkner, H.; Riss, K.; Schmid, M.; Hermann, A.; Robak, O.; et al. Add-On Prostaglandin E(1) in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial. Am. J. Respir. Crit. Care Med. 2022, 206, 170–177. [Google Scholar] [CrossRef]
- Schulman, S.; Makatsariya, A.; Khizroeva, J.; Bitsadze, V.; Kapanadze, D. The Basic Principles of Pathophysiology of Venous Thrombosis. Int. J. Mol. Sci. 2024, 25, 11447. [Google Scholar] [CrossRef]
- Yeo, H.J.; Kim, D.H.; Jeon, D.; Kim, Y.S.; Cho, W.H. Low-dose heparin during extracorporeal membrane oxygenation treatment in adults. Intensive Care Med. 2015, 41, 2020–2021. [Google Scholar] [CrossRef]
- Willers, A.; Arens, J.; Mariani, S.; Pels, H.; Maessen, J.G.; Hackeng, T.M.; Lorusso, R.; Swol, J. New Trends, Advantages and Disadvantages in Anticoagulation and Coating Methods Used in Extracorporeal Life Support Devices. Membranes 2021, 11, 617. [Google Scholar] [CrossRef] [PubMed]
- Rali, P.; Gandhi, V.; Sockrider, M. Acute Treatment of Pulmonary Embolism: Part 2. Am. J. Respir. Crit. Care Med. 2019, 199, P15–P16. [Google Scholar] [CrossRef]
- Ki, K.K.; Passmore, M.R.; Chan, C.H.H.; Malfertheiner, M.V.; Fanning, J.P.; Bouquet, M.; Millar, J.E.; Fraser, J.F.; Suen, J.Y. Low flow rate alters haemostatic parameters in an ex-vivo extracorporeal membrane oxygenation circuit. Intensive Care Med. Exp. 2019, 7, 51. [Google Scholar] [CrossRef]
n | All (n = 101) | Overall DVT: No (n = 66) | Overall DVT: Yes (n = 35) | p | ||
---|---|---|---|---|---|---|
Age (yrs) | 101 | 53 (45–62) | 56 (47–64) | 49 (43–58) | 0.031 | |
Sex | male | 101 | 72 (71%) | 45 (68%) | 27 (77%) | 0.368 |
female | 29 (29%) | 21 (32%) | 8 (23%) | |||
BMI | 101 | 26 (23–30) | 26 (23–31) | 26 (23–29) | 0.923 | |
SAPS II | 101 | 42 (34–52) | 44 (34–54) | 40 (30–47) | 0.030 | |
ECLS runtime (d) | 101 | 10 (5–17) | 8 (4–13) | 13 (7–21) | 0.021 | |
Configuration | VV | 101 | 41 (41%) | 16 (24%) | 25 (71%) | <0.001 |
VA | 56 (55%) | 47 (71%) | 9 (26%) | |||
RVAD | 4 (4%) | 3 (5%) | 1 (3%) | |||
Antiplatelet therapy at screening | Y | 95 | 31 (33%) | 26 (41%) | 5 (16%) | 0.012 |
N | 64 (67%) | 37 (59%) | 27 (84%) | |||
Heparin at screening | Y | 97 | 71 (73%) | 45 (71%) | 26 (76%) | 0.639 |
N | 26 (27%) | 18 (29%) | 8 (24%) | |||
Double lumen cannula | Y | 101 | 12 (12%) | 6 (9%) | 6 (17%) | 0.332 |
N | 89 (88%) | 60 (91%) | 29 (83%) | |||
DVT at drainage cannula | Y | 89 | 15 (17%) | 0 (0%) | 16 (55%) | n.a. |
N | 74 (83%) | 60 (100%) | 13 (45%) | |||
Drainage cannula placement | Percutaneous | 71 | 36 (51%) | 19 (41%) | 17 (68%) | 0.047 |
Surgical | 35 (49%) | 27 (59%) | 8 (32%) | |||
DVT at reperfusion cannula | Y | 89 | 23 (26%) | 0 (0%) | 19 (66%) | n.a. |
N | 66 (74%) | 60 (100%) | 10 (34%) | |||
Reperfusion cannula placement | Percutaneous | 71 | 36 (51%) | 19 (41%) | 17 (68%) | 0.047 |
Surgical | 35 (49%) | 27 (59%) | 8 (32%) | |||
DVT at dual lumen cannula | Y | 12 | 6 (50%) | 0 (0%) | 6 (100%) | n.a. |
N | 6 (50%) | 6 (100%) | 0 (0%) | |||
Dual lumen cannula placement | Percutaneous | 11 | 8 (73%) | 4 (67%) | 4 (80%) | 1 |
Surgical | 3 (27%) | 2 (33%) | 1 (20%) |
n | All (n = 101) | Overall DVT: No (n = 66) | Overall DVT: Yes (n = 35) | p | ||
---|---|---|---|---|---|---|
ICU survival | Y | 69 (68%) | 44 (67%) | 25 (71%) | ||
N | 101 | 32 (32%) | 22 (33%) | 10 (29%) | 0.660 | |
Hospital survival | Y | 68 (67%) | 44 (67%) | 24 (69%) | ||
N | 101 | 33 (33%) | 22 (33%) | 11 (31%) | 1 | |
Overall PE | Y | 9 (9%) | 1 (2%) | 8 (23%) | ||
N | 101 | 92 (91%) | 65 (98%) | 27 (77%) | <0.001 | |
Postmortem examination | Y | 13 (13%) | 8 (12%) | 5 (14%) | ||
N | 101 | 88 (87%) | 58 (88%) | 30 (86%) | 0.763 | |
PE in postmortem examination | Y | 3 (23%) | 0 (0%) | 3 (60%) | ||
N | 13 | 10 (77%) | 8 (100%) | 2 (40%) | 0.035 |
n | All (n = 101) | Overall DVT: No (n = 66) | Overall DVT: Yes (n = 35) | p | ||
---|---|---|---|---|---|---|
aPTT (s) | Mean | 98 | 57.7 (50.8–64.7) | 57.8 (51.1–64.7) | 57.4 (51.1–64.4) | 0.908 |
Baseline | 93 | 47.4 (38.1–61.4) | 47.9 (40.0–64.3) | 45.2 (37.3–58.1) | 0.522 | |
Fibrinogen (mg/dL) | Mean | 98 | 399 (316–522) | 399 (314–498) | 399 (331–533) | 0.509 |
Baseline | 91 | 422 (287–564) | 359 (252–552) | 475 (398–615) | 0.035 | |
Anti-factor Xa (UFH- | Mean | 69 | 0.19 (0.12–0.27) | 0.15 (0.12–0.27) | 0.22 (0.13–0.26) | 0.802 |
assay) (IU/mL) | Baseline | 49 | 0.09 (0.09–0.23) | 0.09 (0.09–0.26) | 0.1 (0.09–0.21) | 0.754 |
D-Dimer (mcg/mL) | Mean | 98 | 8.1 (4.7–12.9) | 7.2 (4.4–10.9) | 10.3 (6.0–13.8) | 0.049 |
Baseline | 82 | 4.6 (2.5–9.7) | 4.6 (2.4–10.2) | 5.1 (2.9–8.8) | 0.930 | |
PLT (G/L) | Mean | 98 | 139 (95–175) | 135 (90–167) | 146 (103–194) | 0.250 |
Baseline | 92 | 201 (142–265) | 191 (138–255) | 219 (157–324) | 0.263 | |
TPZ (Owren) (%) | Mean | 98 | 69 (57–82) | 67 (55–81) | 71 (58–83) | 0.397 |
Baseline | 93 | 69 (57–86) | 70 (50–87) | 67 (59–83) | 0.832 |
Variable | Odds Ratio (95% CI) | p |
---|---|---|
Anti-PLT therapy | 0.75 (0.20–2.78) | 0.667 |
ECMO runtime | 0.99 (0.96–1.02) | 0.422 |
VA vs. VV configuration | 0.12 (0.04–0.39) | <0.001 |
RVAD vs. VV configuration | 0.24 (0.02–2.62) | 0.244 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Hermann, A.; Krais, J.; Tremetsberger, A.-M.; Ristl, R.; Klaeger, J.P.; Schoergenhofer, C.; Buchtele, N.; Nagler, B.; Schellongowski, P.; Robak, O.; et al. Cannula-Associated Deep Vein Thrombosis After Extracorporeal Life Support: A Prospective Diagnostic Study. J. Clin. Med. 2025, 14, 7241. https://doi.org/10.3390/jcm14207241
Hermann A, Krais J, Tremetsberger A-M, Ristl R, Klaeger JP, Schoergenhofer C, Buchtele N, Nagler B, Schellongowski P, Robak O, et al. Cannula-Associated Deep Vein Thrombosis After Extracorporeal Life Support: A Prospective Diagnostic Study. Journal of Clinical Medicine. 2025; 14(20):7241. https://doi.org/10.3390/jcm14207241
Chicago/Turabian StyleHermann, Alexander, Jannis Krais, Anna-Maria Tremetsberger, Robin Ristl, Johannes Philipp Klaeger, Christian Schoergenhofer, Nina Buchtele, Bernhard Nagler, Peter Schellongowski, Oliver Robak, and et al. 2025. "Cannula-Associated Deep Vein Thrombosis After Extracorporeal Life Support: A Prospective Diagnostic Study" Journal of Clinical Medicine 14, no. 20: 7241. https://doi.org/10.3390/jcm14207241
APA StyleHermann, A., Krais, J., Tremetsberger, A.-M., Ristl, R., Klaeger, J. P., Schoergenhofer, C., Buchtele, N., Nagler, B., Schellongowski, P., Robak, O., Stommel, A.-M., & Staudinger, T. (2025). Cannula-Associated Deep Vein Thrombosis After Extracorporeal Life Support: A Prospective Diagnostic Study. Journal of Clinical Medicine, 14(20), 7241. https://doi.org/10.3390/jcm14207241