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Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS)

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Abstract

Purpose

Extracorporeal life support (ECLS) is used for patients with refractory heart failure with or without respiratory failure. This temporary support is provided by blood pumps which are connected to large vessels. Bleeding episodes are a typical complication in patients with ECLS. Recently, several studies illustrated that acquired von Willebrand syndrome (AVWS) can contribute to bleeding tendencies in patients with long-term ventricular assist devices (VAD). AVWS is characterized by loss of the high molecular weight (HMW) multimers of von Willebrand factor (VWF) as a result of high shear stress and leads to impaired binding of VWF to platelets and to subendothelial matrix. Since ECLS and VAD share several features, we investigated patients with ECLS for AVWS.

Methods

We analyzed 32 patients with ECLS and 19 of them without support. To diagnose AVWS, ratios of ristocetin cofactor activity (VWF:RCo) and collagen binding capacity (VWF:CB) to VWF antigen (VWF:Ag) were employed in conjunction with multimeric analysis.

Results

Reduced VWF:RCo/VWF:Ag ratios were identified in 28 ECLS patients. Furthermore, VWF:CB/VWF:Ag ratios were decreased in 31 patients. HMW multimers of VWF were missing in the same 31 patients. Thus, 31 of 32 ECLS patients presented with AVWS. Twenty-two of the 32 patients suffered from bleeding complications. Without support, AVWS was not detectable in any analyzed patient.

Conclusion

Our data indicate that AVWS is a typical disorder in patients with ECLS. We hypothesize that AVWS could contribute to aggravation of bleeding tendencies in ECLS patients.

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References

  1. Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Sousa Uva M, Taggart D, Vahanian A, Auricchio A, Bax J, Ceconi C, Dean V, Filippatos G, Funck-Brentano C, Hobbs R, Kearney P, McDonagh T, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Vardas PE, Widimsky P, Kolh P, Alfieri O, Dunning J, Elia S, Kappetein P, Lockowandt U, Sarris G, Vouhe P, Kearney P, von Segesser L, Agewall S, Aladashvili A, Alexopoulos D, Antunes MJ, Atalar E, Brutel de la Riviere A, Doganov A, Eha J, Fajadet J, Ferreira R, Garot J, Halcox J, Hasin Y, Janssens S, Kervinen K, Laufer G, Legrand V, Nashef SA, Neumann FJ, Niemela K, Nihoyannopoulos P, Noc M, Piek JJ, Pirk J, Rozenman Y, Sabate M, Starc R, Thielmann M, Wheatley DJ, Windecker S, Zembala M (2010) Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 31:2501–2555

    Article  PubMed  Google Scholar 

  2. Hsu PS, Chen JL, Hong GJ, Tsai YT, Lin CY, Lee CY, Chen YG, Tsai CS (2010) Extracorporeal membrane oxygenation for refractory cardiogenic shock after cardiac surgery: predictors of early mortality and outcome from 51 adult patients. Eur J Cardiothorac Surg 37:328–333

    PubMed  Google Scholar 

  3. D’Alessandro C, Aubert S, Golmard JL, Praschker BL, Luyt CE, Pavie A, Gandjbakhch I, Leprince P (2010) Extra-corporeal membrane oxygenation temporary support for early graft failure after cardiac transplantation. Eur J Cardiothorac Surg 37:343–349

    PubMed  Google Scholar 

  4. Hsu KH, Chi NH, Yu HY, Wang CH, Huang SC, Wang SS, Ko WJ, Chen YS (2011) Extracorporeal membranous oxygenation support for acute fulminant myocarditis: analysis of a single center’s experience. Eur J Cardiothorac Surg 40(3):682–688

    PubMed  Google Scholar 

  5. Pagani FD, Aaronson KD, Swaniker F, Bartlett RH (2001) The use of extracorporeal life support in adult patients with primary cardiac failure as a bridge to implantable left ventricular assist device. Ann Thorac Surg 71:S77–S81 (discussion S82-75)

    Article  PubMed  CAS  Google Scholar 

  6. Gaffney AM, Wildhirt SM, Griffin MJ, Annich GM, Radomski MW (2010) Extracorporeal life support. BMJ 341:c5317

    Article  PubMed  Google Scholar 

  7. ELSO (2009) ELSO guidelines for cardiopulmonary extracorporeal life support, version 1:1, April 2009. Extracorporeal Life Support Organization, Ann Arbor, MI. Available via www.elso.med.umich.edu. Accessed 23 Feb 2011

  8. Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, Bauters A, Decoene C, Goudemand J, Prat A, Jude B (2003) Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 349:343–349

    Article  PubMed  Google Scholar 

  9. Shimizu M, Masai H, Miwa Y (2007) Occult gastrointestinal bleeding due to acquired von Willebrand syndrome in a patient with hypertrophic obstructive cardiomyopathy. Intern Med 46:481–485

    Article  PubMed  Google Scholar 

  10. Le Tourneau T, Susen S, Caron C, Millaire A, Marechaux S, Polge AS, Vincentelli A, Mouquet F, Ennezat PV, Lamblin N, de Groote P, Van Belle E, Deklunder G, Goudemand J, Bauters C, Jude B (2008) Functional impairment of von Willebrand factor in hypertrophic cardiomyopathy: relation to rest and exercise obstruction. Circulation 118:1550–1557

    Article  PubMed  CAS  Google Scholar 

  11. Velik-Salchner C, Eschertzhuber S, Streif W, Hangler H, Budde U, Fries D (2008) Acquired von Willebrand syndrome in cardiac patients. J Cardiothorac Vasc Anesth 22:719–724

    Article  PubMed  CAS  Google Scholar 

  12. Baldauf C, Schneppenheim R, Stacklies W, Obser T, Pieconka A, Schneppenheim S, Budde U, Zhou J, Grater F (2009) Shear-induced unfolding activates von Willebrand factor A2 domain for proteolysis. J Thromb Haemost 7:2096–2105

    Article  PubMed  CAS  Google Scholar 

  13. Feys HB, Anderson PJ, Vanhoorelbeke K, Majerus EM, Sadler JE (2009) Multi-step binding of ADAMTS-13 to von Willebrand factor. J Thromb Haemost 7:2088–2095

    Article  PubMed  CAS  Google Scholar 

  14. Federici AB, Rand JH, Bucciarelli P, Budde U, van Genderen PJ, Mohri H, Meyer D, Rodeghiero F, Sadler JE (2000) Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost 84:345–349

    PubMed  CAS  Google Scholar 

  15. Mohri H (2006) Acquired von Willebrand syndrome: features and management. Am J Hematol 81:616–623

    Article  PubMed  CAS  Google Scholar 

  16. Geisen U, Heilmann C, Beyersdorf F, Benk C, Berchtold-Herz M, Schlensak C, Budde U, Zieger B (2008) Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease. Eur J Cardiothorac Surg 33:679–684

    Article  PubMed  Google Scholar 

  17. Klovaite J, Gustafsson F, Mortensen SA, Sander K, Nielsen LB (2009) Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II). J Am Coll Cardiol 53:2162–2167

    Article  PubMed  CAS  Google Scholar 

  18. Steinlechner B, Dworschak M, Birkenberg B, Duris M, Zeidler P, Fischer H, Milosevic L, Wieselthaler G, Wolner E, Quehenberger P, Jilma B (2009) Platelet dysfunction in outpatients with left ventricular assist devices. Ann Thorac Surg 87:131–137

    Article  PubMed  Google Scholar 

  19. Rastan AJ, Dege A, Mohr M, Doll N, Falk V, Walther T, Mohr FW (2010) Early and late outcomes of 517 consecutive adult patients treated with extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. J Thorac Cardiovasc Surg 139:302–311

    Google Scholar 

  20. Wang J, Han J, Jia Y, Zeng W, Shi J, Hou X, Meng X (2009) Early and intermediate results of rescue extracorporeal membrane oxygenation in adult cardiogenic shock. Ann Thorac Surg 88:1897–1903

    Article  PubMed  Google Scholar 

  21. Brogan TV, Thiagarajan RR, Rycus PT, Bartlett RH, Bratton SL (2009) Extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database. Intensive Care Med 35:2105–2114

    Article  PubMed  CAS  Google Scholar 

  22. Malehsa D, Meyer AL, Bara C, Struber M (2009) Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II ventricular assist device. Eur J Cardiothorac Surg 35:1091–1093

    Article  PubMed  Google Scholar 

  23. Crow S, Chen D, Milano C, Thomas W, Joyce L, Piacentino V 3rd, Sharma R, Wu J, Arepally G, Bowles D, Rogers J, Villamizar-Ortiz N (2010) Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients. Ann Thorac Surg 90:1263–1269 (discussion 1269)

    Article  PubMed  Google Scholar 

  24. Heilmann C, Geisen U, Beyersdorf F, Nakamura L, Benk C, Berchtold-Herz M, Trummer G, Schlensak C, Zieger B (2010) Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart. Thromb Haemost 103:962–967

    Article  PubMed  CAS  Google Scholar 

  25. Uriel N, Pak SW, Jorde UP, Jude B, Susen S, Vincentelli A, Ennezat PV, Cappleman S, Naka Y, Mancini D (2010) Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation. J Am Coll Cardiol 56:1207–1213

    Article  PubMed  Google Scholar 

  26. Markl M, Benk C, Klausmann D, Stalder AF, Frydrychowicz A, Hennig J, Beyersdorf F (2007) Three-dimensional magnetic resonance flow analysis in a ventricular assist device. J Thorac Cardiovasc Surg 134:1471–1476

    Article  PubMed  Google Scholar 

  27. Chua LP, Su B, Lim TM, Zhou T (2007) Numerical simulation of an axial blood pump. Artif Organs 31:560–570

    Article  PubMed  Google Scholar 

  28. Wu J, Paden BE, Borovetz HS, Antaki JF (2010) Computational fluid dynamics analysis of blade tip clearances on hemodynamic performance and blood damage in a centrifugal ventricular assist device. Artif Organs 34:402–411

    Article  PubMed  Google Scholar 

  29. Song G, Chua LP, Lim TM (2010) Numerical study of a centrifugal blood pump with different impeller profiles. ASAIO J 56:24–29

    Article  PubMed  Google Scholar 

  30. Song G, Chua LP, Lim TM (2010) Numerical study of a bio-centrifugal blood pump with straight impeller blade profiles. Artif Organs 34:98–104

    Article  PubMed  Google Scholar 

  31. Mizunuma H, Nakajima R (2007) Experimental study on shear stress distributions in a centrifugal blood pump. Artif Organs 31:550–559

    Article  PubMed  Google Scholar 

  32. Heilmann C, Geisen U, Beyersdorf F, Nakamura L, Trummer G, Berchtold-Herz M, Schlensak C, Zieger B Acquired Von Willebrand syndrome is an early-onset problem in ventricular assist device patients. Eur J Cardiothorac Surg. doi:10.1016/j.ejcts.2011.03.021

  33. Ruggeri ZM (2007) The role of von Willebrand factor in thrombus formation. Thromb Res 120(Suppl 1):S5–S9

    Article  PubMed  CAS  Google Scholar 

  34. Crawley JT, de Groot R, Luken BM (2009) Circulating ADAMTS-13-von Willebrand factor complexes: an enzyme on demand. J Thromb Haemost 7:2085–2087

    Article  PubMed  CAS  Google Scholar 

  35. Schneider AG, Perez MH, Tozzi P, Voirol P, Schoettker P, Angelillo-Scherrer A, Cotting J, Von Segesser L, Eggimann P (2010) Recombinant factor VIIa for intractable life-threatening bleeding in patients with circulatory assist devices. Intensive Care Med 36:1620–1621

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Ms. Ulrike Heizmann and Mr. Bernd Koch for technical support. The indispensable expertise and dedication of our perfusionist team are highly appreciated. The study presented here is supported in part by CLS Behring, Hattersheim am Main, Germany, according to agreement with the University Freiburg Medical Center, and it is associated with the comprehensive project “Cardiac assist devices for long-term support in cardiac insufficiency” supported by the German Research Foundation, Bonn, Germany (reference no. PAK 350).

Conflict of interest

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, University Heart Center Freiburg-Bad Krozingen, Hugstetter Str. 55, 79106, Freiburg, Germany

    Claudia Heilmann, Friedhelm Beyersdorf, Christoph Benk, Georg Trummer, Michael Berchtold-Herz & Christian Schlensak

  2. Clinical Chemistry, University Freiburg Medical Center, Freiburg, Germany

    Ulrich Geisen

  3. Laboratory for Hemostaseology, Department of Pediatrics and Adolescent Medicine, University Freiburg Medical Center, Freiburg, Germany

    Lea Nakamura & Barbara Zieger

Authors
  1. Claudia Heilmann
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  2. Ulrich Geisen
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  4. Lea Nakamura
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  5. Christoph Benk
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  6. Georg Trummer
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  7. Michael Berchtold-Herz
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  8. Christian Schlensak
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  9. Barbara Zieger
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Corresponding author

Correspondence to Claudia Heilmann.

Additional information

C. Heilmann and U. Geisen contributed equally to this study.

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Heilmann, C., Geisen, U., Beyersdorf, F. et al. Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med 38, 62–68 (2012). https://doi.org/10.1007/s00134-011-2370-6

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  • DOI: https://doi.org/10.1007/s00134-011-2370-6

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