Advertisement

In Vitro Treatment of Extracorporeal Membrane Oxygenation Coagulopathy with Recombinant von Willebrand Factor or Lyophilized Platelets

Published:December 29, 2022DOI:https://doi.org/10.1053/j.jvca.2022.12.028

      Objectives

      The objective was to compare primary hemostasis between adult ECMO patients and cardiac surgical patients before heparinization and cardiopulmonary bypass. Furthermore, the authors explored whether in vitro treatment of ECMO patient blood samples with recombinant von Willebrand Factor (vWF) or lyophilized platelets improved primary hemostasis in vitro.

      Design

      Prospective cohort study.

      Setting

      Single academic medical center.

      Participants

      Ten cardiac surgical patients and 8 adult ECMO patients.

      Interventions

      Cardiac surgical patients and ECMO patients had blood samples collected, and in vitro platelet thrombus formation was assessed using the ATLAS PST device. The ECMO patients had platelet thrombus formation evaluated at baseline and after in vitro treatment with recombinant vWF or lyophilized platelets, whereas cardiac surgical patients had a single blood sample obtained before heparinization and cardiopulmonary bypass run.

      Measurements and Main Results

      Median maximum force (39.7 v 260.2 nN) and thrombus area (0.05 v 0.11) at 5 minutes were lower in untreated ECMO patient samples compared with cardiac surgical patients (p = 0.008 and p < 0.001, respectively). The ECMO patient samples treated with recombinant vWF demonstrated an increase in both platelet maximum force (median value of 222.1 v 39.7 nN) (p = 0.01) and platelet thrombus area (median value of 0.16 v 0.05; p = 0.001). The ECMO patient samples treated with lyophilized platelets demonstrated no increase in platelet maximum force (median value of 193.3 v 39.7 nN; p = 0.18); however, there was a significant increase in platelet thrombus area (median value of 0.13 v 0.05; p = 0.04).

      Conclusions

      Recombinant vWF and lyophilized platelets may help to restore primary hemostasis in ECMO patients. Future studies should further evaluate the safety and efficacy of these potential therapeutics in ECMO patients.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Cardiothoracic and Vascular Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • ELSO
        ECLS Registry Report, International Summary.
        ELSO, 2022 (Available at) (Accessed December 22, 2022)
        • Cheng R
        • Hachamovitch R
        • Kittleson M
        • et al.
        Complications of extracorporeal membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: A meta-analysis of 1,866 adult patients.
        Ann Thorac Surg. 2014; 97: 610-616
        • Mazzeffi M
        • Greenwood J
        • Tanaka K
        • et al.
        Bleeding, transfusion, and mortality on extracorporeal life support: ECLS Working Group on Thrombosis and Hemostasis.
        Ann Thorac Surg. 2016; 101: 682-689
        • Kalbhenn J
        • Schlagenhauf A
        • Rosenfelder S
        • et al.
        Acquired von Willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: Rapid onset and fast recovery.
        J Heart Lung Transplant. 2018; 37: 985-991
        • Abrams D
        • Baldwin MR
        • Champion M
        • et al.
        Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: A cohort study.
        Intensive Care Med. 2016; 42: 844-852
        • Chen Z
        • Koenig SC
        • Slaughter MS
        • et al.
        Quantitative characterization of shear-induced platelet receptor shedding: Glycoprotein ibalpha, glycoprotein VI, and glycoprotein IIb/IIIa.
        ASAIO J. 2018; 64: 773-778
        • Mazzeffi M
        • Hasan S
        • Abuelkasem E
        • et al.
        Von Willebrand Factor-GP1balpha interactions in venoarterial extracorporeal membrane oxygenation patients.
        J Cardiothorac Vasc Anesth. 2019; 33: 2125-2132
        • Mazzeffi M
        • Bathula A
        • Tabatabai A
        • et al.
        Von Willebrand Factor concentrate administration for acquired von Willebrand Syndrome- related bleeding during adult extracorporeal membrane oxygenation.
        J Cardiothorac Vasc Anesth. 2021; 35: 882-887
        • Mazzeffi M
        • Henderson R
        • Krause E
        • et al.
        In vitro comparison of recombinant and plasma-derived von Willebrand Factor concentrate for treatment of acquired von Willebrand syndrome in adult extracorporeal membrane oxygenation patients.
        Anesth Analg. 2022; 134: 312-321
        • Tauber H
        • Ott H
        • Streif W
        • et al.
        Extracorporeal membrane oxygenation induces short-term loss of high-molecular-weight von Willebrand factor multimers.
        Anesth Analg. 2015; 120: 730-736
        • Chan CH
        • Pieper IL
        • Fleming S
        • et al.
        The effect of shear stress on the size, structure, and function of human von Willebrand factor.
        Artif Organs. 2014; 38: 741-750
        • Ting LH
        • Feghhi S
        • Taparia N
        • et al.
        Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk.
        Nat Commun. 2019; 10: 1204
        • Bynum JA
        • Meledeo MA
        • Peltier GC
        • et al.
        Evaluation of a lyophilized platelet-derived hemostatic product.
        Transfusion. 2019; 59: 1490-1498
        • Ohanian M
        • Cancelas JA
        • Davenport R
        • et al.
        Freeze-dried platelets are a promising alternative in bleeding thrombocytopenic patients with hematological malignancies.
        Am J Hematol. 2022; 97: 256-266
        • Aubron C
        • Cheng AC
        • Pilcher D
        • et al.
        Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: A 5-year cohort study.
        Crit Care. 2013; 17: R73
        • Aubron C
        • DePuydt J
        • Belon F
        • et al.
        Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation.
        Ann Intensive Care. 2016; 6: 97
        • Chen FT
        • Chen SW
        • Wu VC
        • et al.
        Impact of massive blood transfusion during adult extracorporeal membrane oxygenation support on long-term outcomes: A nationwide cohort study in Taiwan.
        BMJ Open. 2020; 10e035486
        • Nair P
        • Hoechter DJ
        • Buscher H
        • et al.
        Prospective observational study of hemostatic alterations during adult extracorporeal membrane oxygenation (ECMO) using point-of-care thromboelastometry and platelet aggregometry.
        J Cardiothorac Vasc Anesth. 2015; 29: 288-296
        • 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: 7975
        • Balle CM
        • Jeppesen AN
        • Christensen S
        • et al.
        Platelet function during extracorporeal membrane oxygenation in adult patients.
        Front Cardiovasc Med. 2019; 6: 114
        • Chen Z
        • Mondal NK
        • Ding J
        • et al.
        Shear-induced platelet receptor shedding by non-physiological high shear stress with short exposure time: Glycoprotein Ibalpha and glycoprotein VI.
        Thromb Res. 2015; 135: 692-698
        • Oury C
        • Sticker E
        • Cornelissen H
        • et al.
        ATP augments von Willebrand factor-dependent shear-induced platelet aggregation through Ca2+-calmodulin and myosin light chain kinase activation.
        J Biol Chem. 2004; 279: 26266-26273