Design

Coagulation Testing

An automated blood test would have to be performed by an ACT, aPTT, or TEG test [31]

  • ACT is often unreliable, as they can be influenced by hemodilution, platelet count, and other factors [32]
  • In general, aPTT tends to be more reliable than ACT in ECMO patients [14]

Design Components

  • A combination of aPTT and TEG testing, as per protocol, rather than ACT testing
  • A cartridge-based system to easily perform testing
  • Basic software to control direction of blood to cartridges

Open-Ended Solution

  • Secondary loop for automated blood aspiration
    • Build off success of “the Loop”[33]
      • Already incorporates pressure monitoring in the secondary loop
      • Provides multiple stopcock access points for sampling
    • Automate aspiration of blood with servo motor and microcontroller
  • Use chemically-based existing test cartridges
    • Single-use cartridges introduce need for testing with multiple cartridges to reduce need of human intervention
    • Chemical test for easy of automated testing
  • Two possible solutions for multi-cartridge testing
    • Use manifold to direct aspirated blood to multiple lined-up cartridges
      • Control blood to each cartridge with servo-controlled valves
      • Store which cartridges have been used in microcontroller memory
    • Move cartridges to aspirated blood instead of moving blood to cartridges
      • Can be done with motorized rails that moves cartridges to blood
      • Less components, but more complex design
    • Evaluate advantages of blood-to-cartridge vs. cartridge-to-blood testing solutions
  • Flushing system to prevent coagulation from automated aspiration
    • Start with existing ECMO cannulae flushing protocol
      • Use 9% NaCl solution and heparin for flushing [34]

Pre-Coating

  • Blood clot formation in ECMO is mainly caused by blood in the circuit interacting with non-endothelial surfaces, so it’s important that we find the optimal pre-coating that minimizes coagulation in our device [39].
  • Our final design’s first prototype will feature a heparin pre-coating.
  • Heparin is already integrated in multiple parts of the ECMO circuit and our design
    • bioactive coatings: heparin [37]
    • decreases inflammation reactions
    • blood platelet conservation
    • long term oxygenation with decreased magnitude of heparin [38]
    • counteractive disease HIT (anticoagulation agents end up causing blood clot formation) [14]

Other possible options:

    • another bioactive: fibronectin [36]
    • decreased blood protein absorption
    • biopassive coatings: phosphorylcholine [37]
    • prevents blood clot formation
    • reduces blood loss/leakage
    • membrane option: PMP membrane [39]
    • poreless membrane (no leakage)
    • no clot formation
Figure 1: Final Design
Figure 2: Alternate Rail Design

References:

[31]: Cannon, C. P., Dingemanse, J., Kleinbloesem, C. H., Jannett, T., Curry, K. M., & Valcke, C. P. (1999). Automated heparin-delivery system to control activated partial thromboplastin time: evaluation in normal volunteers. Circulation, 99(6), 751-756. doi:10.1161/01.cir.99.6.751

[32]: Sulkowski, J. P., Preston, T. J., Cooper, J. N., Duffy, V. L., Deans, K. J., Chicoine, L. G., & Minneci, P. C. (2014). Comparison of routine laboratory measures of heparin anticoagulation for neonates on extracorporeal membrane oxygenation. J Extra Corpor Technol, 46(1), 69-76. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24779122

[14]: Chlebowski, M.M., Baltagi, S., Carlson, M. et al. Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO. Crit Care 24, 19 (2020). https://doi.org/10.1186/s13054-020-2726-9

[33] Broman, L.M., Introducing the Loop for Circuit Access during Extracorporeal Membrane Oxygenation: Feasibility and Safety. J Extra Corpor Technol, 2019: p. 175-178.

[34] McNinch, J., B. Searles, and E. Darling, Preserving ECMO Cannulae Patency. Extra Corpor Technol, 2018: p. 99-101.

[35] Murphy, D.A., et al., Extracorporeal membrane oxygenation-hemostatic complications. Transfus Med Rev, 2015. 29(2): p. 90-101.

[36] Cornelissen, C.G., et al., Fibronectin coating of oxygenator membranes enhances endothelial cell attachment. Biomedical engineering online, 2013. 12(1): p. 7-7.

[37] Silvetti, S., A. Koster, and F. Pappalardo, Do we need heparin coating for extracorporeal membrane oxygenation? New concepts and controversial positions about coating surfaces of extracorporeal circuits. Artif Organs, 2015. 39(2): p. 176-9.

[38] Pappalardo, F., et al., Bioline® heparin-coated ECMO with bivalirudin anticoagulation in a patient with acute heparin-induced thrombocytopenia: the immune reaction appeared to continue unabated. Perfusion, 2009. 24(2): p. 135-137.

[39] Yu, K., et al., Clinical Evaluation of Two Different Extracorporeal Membrane Oxygenation Systems: A Single Center Report. Artificial organs, 2011. 35(7): p. 733-737.