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Changes in Fibrinolytic Factors in a Simulated Extracorporeal Membrane Oxygenator Circuit

A. Doyle1, N. Gooby2, K. Parmar1, K.A. Breen2, N.A. Barrett2, A. Retter2, B.J. Hunt1

1Guy's and St Thomas' NHS Foundation Trust, Haematology, London, United Kingdom, 2Guy's and St Thomas' NHS Foundation Trust, Critical Care, London, United Kingdom

Abstract Number: PB0749

Meeting: ISTH 2020 Congress

Theme: Fibrinolysis and Proteolysis » Fibrinolytic Factors and Inhibitors

Background: Thrombosis and haemorrhage are common complications of extracorporeal membrane oxygenation (ECMO). Haemostatic changes that occur during ECMO and their contribution to these complications have been poorly studied, especially fibrinolysis.

Aims: To assess the changes in fibrinolytic factors over a 24-hour period in an ex vivo model of ECMO.

Methods: A simulated adult ex vivo circuit with a centrifugal pump was designed for 24-hours using whole blood (donors had hereditary haemochromatosis) diluted with 3.2% sodium citrate and PlasmaLyte 148 solution. Six circuits were analysed. Samples were taken with time-matched controls at 6 time points (0, 1, 4, 8, 12 and 24 hours). Clauss fibrinogen levels and ELISA were performed for D-dimer, plasminogen activator inhibitor (PAI)-1, tissue plasminogen activator (t-PA) antigen, prothrombin fragments (PF) 1+2, thrombin-activated fibrinolysis inhibitor (TAFI) antigen and plasmin-antiplasmin (PAP) complexes. Statistical analysis was measured by Mann-Whitney U test. Haemostatic results were expressed as % of the value at initiation of the experiment.

Results: Haemodilution occurred with a haematocrit fall from a median 0.40 (range 0.37 – 0.54) to 0.19 (0.18-0.22) after addition of PlasmaLyte, but there were no further significant changes. There were no changes over time in D-dimers, PF1+2 and fibrinogen. tPA levels decreased over 24-hours with a larger decrease in samples from the circuit than control (56% vs 12%, p=0.025). PAP complexes, TAFI antigen and PAI-1 levels increased over time (91%, 20% and 48% increases from baseline respectively, non-significant). There was an increase in PAP complexes and PAI-1 levels (91% vs 32% and 48% vs 27% at 24-hours) from the circuit compared to controls although similar TAFI levels (20% vs 18% at 24-hours).

Conclusions: This ex vivo simulated circuit showed an elevation in PAP complexes during ECMO. PAI-1 increased and tPA decreased over 24-hours. Further analysis is required in patients during ECMO and correlated with haemostatic phenotype.

Fibrinolytic Factor Fibrinogen D-dimer PF1+2 PAP Complex tPA Antigen PAI-1 TAFI
Circuit after 24 hours -5.5% +4.1% +9.8% +90.7% -56.2% +48.2% +19.7
Control after 24 hours +2.6% +0.5% -5.7% +31.6% -12.4% +26.6% +17.6%

[Mean % changes in fibrinolytic factors at 24 hours compared to initiation of ex vivo circuit]

To cite this abstract in AMA style:

Doyle A, Gooby N, Parmar K, Breen KA, Barrett NA, Retter A, Hunt BJ. Changes in Fibrinolytic Factors in a Simulated Extracorporeal Membrane Oxygenator Circuit [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/changes-in-fibrinolytic-factors-in-a-simulated-extracorporeal-membrane-oxygenator-circuit/. Accessed October 2, 2023.

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