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Extracorporeal membrane oxygenation in trauma patients with hypovolaemic shock

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posted on 2024-09-03, 06:29 authored by Magnus Larsson

Lifesaving or Life-threatening? If the worst thing happens, and you get seriously injured in an accident, your body has a pronounced ability to immediately stop bleedings and start the process of healing. This unique capacity only works to a certain degree. Our body cannot by itself handle life-threatening bleedings from the heart, large blood vessels or severe injuries to highly vascularized organs. Transfusion of blood products, acute surgery and intensive care are necessary to support the body. In devastating injuries even this may not be enough and new ways of treating massive bleeding needs to be explored. Sometimes our body’s rescue system gets overloaded and starts to counteract the intended positive reaction. Excessive coagulation with a resulting occlusion of a blood vessel is one example. In that case anticoagulation is needed. Another example is if inflammation, the process necessary to start healing, derails. This may cause an overwhelming inflammation in the lungs that abolish their ability of saturating our blood. If the lungs take time off, a heart lung machine can buy time for the healing and save the life. A heart lung machine (ECMO) needs anticoagulation since the plastic tubings can cause clotting. Anticoagulation is associated with the risk of dangerous bleeding. If the system clots, and the machine shut down, a life saving procedure can suddenly change to a life-threatening situation.

This Thesis highlights both sides of the hemostatic and anticoagulative coin. We have attacked the mentioned challenges from four different angles. In Article I venoarterial ECMO’s effect on central blood pressure was investigated. The reason for this is that we had found an unexpected effect of ECMO, during trauma resuscitation. A young girl’s severe liver bleeding suddenly could be controlled when ECMO was initiated because of lung failure. Swine were used in the study and we found that VA ECMO reduced the central venous pressure while mean arterial pressure was improved.

In Article II a novel way of anticoagulation or “thromboprotection” in an ECMO system was evaluated. 3F7, an antibody that inhibits the activated form of coagulation factor XII was studied on rabbits connected to ECMO. 3F7 could prevent clotting in the ECMO system as effective as heparin but did not impair the hemostatic capacity and did not increase wound bleedings.

In Article III venoarterial ECMO’s effect on rabbits in lethal traumatic bleeding shock was evaluated. Focus was on how the ECMO treatment affects central circulation, temperature, acid-base balance and the coagulation ability. ECMO efficiently increased the temperature, stabilized the circulation, improved the pH and ameliorated the hemostatic capacity.

In Article IV Polyphosphate (PolyP), a substance that is released from activated platelets and that induces coagulation by activating FXII was investigated. Liver injuries in swine were treated with PolyP, Kaolin and a non-active substance. PolyP efficiently initiated thrombin formation and terminated bleeding as efficiently as Kaolin but with less inflammation.

List of scientific papers

I. Larsson M, Talving P, Palmér K, Frenckner B, Riddez L, Broomé M. Experimental extracorporeal membrane oxygenation reduces central venous pressure : an adjunct to control of venous hemorrhage? Perfusion 2010. 25(4) : 217–223.
https://doi.org/10.1177/0267659110375864

II. Larsson M, Rayzman V, Nolte M, Nickel K, Björkqvist J, Jämsä A, Hardy M, Fries M, Schmidbauer S, Hedenqvist P, Broomé M, Pragst I, Dickneite G, Wilson M, Nash A, Panousis C, Renné T. A Factor XIIa Inhibitory Antibody Provides Thromboprotection in Extracorporeal Circulation Without Increasing Bleeding Risk. Sci Transl Med 2014. 6(222) : 222ra17
https://doi.org/10.1126/scitranslmed.3006804

III. Larsson M, Forsman P, Hedenqvist P, Östlund A, Hultman J, Wikman A, Riddez L, Frenckner B, Wahlgren C-M Extracorporeal Membrane Oxygenation Improves Coagulopathy in an Experimental Traumatic Hemmorrhagic Model. [Submitted]

IV. Larsson M, Österholm C, Hultenby K, Frenckner B, Hultman J, Renné T. Polyphosphates are Hemostatic Agents In Vivo. [Manuscript]

History

Defence date

2015-12-04

Department

  • Department of Molecular Medicine and Surgery

Publisher/Institution

Karolinska Institutet

Main supervisor

Renne, Thomas

Publication year

2015

Thesis type

  • Doctoral thesis

ISBN

978-91-7676-156-4

Number of supporting papers

4

Language

  • eng

Original publication date

2015-11-10

Author name in thesis

Larsson, Magnus

Original department name

Department of Molecular Medicine and Surgery

Place of publication

Stockholm

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