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Thrombocytopenia under ECMO and Shear-induced shedding of platelet receptor Glycoprotein-(GP)Ialpha

Session Poster Session 2

Speaker Hugues Spillemaeker

Event : ESC Congress 2019

  • Topic : interventional cardiology and cardiovascular surgery
  • Sub-topic : Cardiovascular Surgery - Circulatory Support
  • Session type : Poster Session

Authors : F Vincent (Lille,FR), A Rauch (Lille,FR), M Desvages (Lille,FR), H Spillemaeker (Lille,FR), N Rousse (Lille,FR), A Dupont (Lille,FR), E Jeanpierre (Lille,FR), C Delhaye (Lille,FR), M Moussa (Lille,FR), A Vincentelli (Lille,FR), B Verdier (Lille,FR), N Debry (Lille,FR), F Lassalle (Lille,FR), S Susen (Lille,FR), E Van Belle (Lille,FR)

Authors:
F. Vincent1 , A. Rauch2 , M. Desvages2 , H. Spillemaeker1 , N. Rousse3 , A. Dupont2 , E. Jeanpierre2 , C. Delhaye1 , M. Moussa4 , A. Vincentelli3 , B. Verdier1 , N. Debry1 , F. Lassalle2 , S. Susen2 , E. Van Belle1 , 1Lille University Hospital, Interventional Coronary and Structural Cardiology, Institut Coeur Poumon - Lille - France , 2Lille University Hospital, Hematology and Transfusion - Lille - France , 3Lille University Hospital, Department of Cardiac Surgery - Lille - France , 4Lille University Hospital, Intensive Care Unit and Anesthesia - Lille - France ,

Citation:
European Heart Journal ( 2019 ) 40 ( Supplement ), 1133

Background: Several mechanisms are suspected to thrombocytopenia under Extracorporeal Membrane Oxygenation (ECMO) such as platelet-consumption or sepsis. Shedding of glycoprotein-(GP)Ibα is a recently identified mechanism of platelet clearance. ECMO generates high shear stress forces that could impact GPIbα-shedding. We hypothesized that ECMO continuous-flow devices could directly induce thrombocytopenia through shear-induced GPIbα-shedding.

Aims: Determine if ECMO induce GpIb-shedding in vitro and in vivo and determinates the kinetic evolution of platelet-count and GpIb-shedding after patient's implantation.

Methods: Platelet GPIbα-shedding was first investigated in vitro using a high-shear pump loop model. Plasma with normal platelet count (plasma-NPC) was obtained by dilution of platelet-rich plasma obtained from healthy donors in fresh-frozen-plasma. Samples were collected before and after (5, 30, 60 and 180 min) perfusion at 37°C of plasma-NPC at intermediate and high speed (2.6 and 3.6 L min–1 respectively, n=4 each). Platelet count and GPIbα-shedding were next investigated in 20 ECMO patients before/after implantation (WITECMO trial) and in 20 healthy volunteers. The geometric mean-fluorescence-intensity (gMFI) of platelet GPIbα (PE-staining) and GPIX (FITC-staining) was measured with a Navios flow cytometer (Beckman Coulter, Miami, FL). Results are expressed as GPIbα/GPIX gMFI-ratio.

Results: A significant time-dependent loss of GPIbα/GPIX gMFI-ratio was already apparent after 30 min in vitro and was significantly more pronounced at high-speed compared to intermediate-speed (pANOVA<0.001 and p<0.01 at 180 min respectively). GPIbα/GPIX gMFI-ratio was significantly increased in ECMO patients compared to healthy subjects 1- and 24-hour after implantation (p<0.001). A significantly lower platelet count was observed 1 hour after ECMO implantation (−23% vs baseline, p<0.01) with a further significant decrease at 24-hours (−53% vs baseline, p<0.0001).

Figure 1. A. Significant time-dependent loss of platelet GPIb&#x03B1;/GPIX gMFI-ratio (pANOVA &#x003C;0.001) assessed by flow-cytometry after 30 min of perfusion at 3.6 L/min with a high-shear continuous-flow device in vitro. B. Representative experiment showing the apparition of a platelet sub-population with loss of GPIb&#x03B1; expression after 30 min of perfusion at 3.6 L/minwith a high-shear continuous-flow device in vitro.

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