Fibrinolysis in Cardiac Arrest Patients Treated with Hypothermia

TY - JOUR

T1 - Fibrinolysis in Cardiac Arrest Patients Treated with Hypothermia

AU - Jeppesen, Anni Nørgaard

AU - Duez, Christophe

AU - Kirkegaard, Hans

AU - Grejs, Anders Morten

AU - Hvas, Anne-Mette

PY - 2023/9/1

Y1 - 2023/9/1

N2 - Hypothermia affects coagulation, but the effect of hypothermia on fibrinolysis is not clarified. Imbalance in the fibrinolytic system may lead to increased risk of bleeding or thrombosis. Our aim was to investigate if resuscitated cardiac arrest patients treated with hypothermia had an unbalanced fibrinolysis. A prospective cohort study, including 82 patients were treated with hypothermia at 33°C ± 1°C after out-of-hospital cardiac arrest. Blood samples were collected at 24 hours (hypothermia) and at 72 hours (normothermia). Samples were analyzed for fibrin D-dimer, tissue plasminogen activator (tPA), plasminogen, plasminogen activator Inhibitor-1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and an in-house dynamic fibrin clot formation and lysis assay.Compared with normothermia, hypothermia significantly increased plasminogen activity (mean difference = 10.4%, 95% confidence interval [CI] 7.9-12.9), p  < 0.001), PAI-1 levels (mean difference = 275 ng/mL, 95% CI 203-348, p  < 0.001), and tPA levels (mean difference = 1.0 ng/mL, 95% CI 0.2-1.7, p  = 0.01). No differences between hypothermia and normothermia were found in TAFI activity ( p  = 0.59) or in the fibrin D-dimer levels ( p  = 0.08). The fibrin clot lysis curves showed three different patterns: normal-, flat-, or resistant clot lysis curve. At hypothermia 45 (55%) patients had a resistant clot lysis curve and 33 (44%) patients had a resistant clot lysis curve at normothermia ( p  = 0.047). Comatose, resuscitated, cardiac arrest patients treated with hypothermia express an inhibited fibrinolysis even after rewarming. This could potentially increase the thromboembolic risk. ClinicalTrials.gov ID: NCT02258360.

AB - Hypothermia affects coagulation, but the effect of hypothermia on fibrinolysis is not clarified. Imbalance in the fibrinolytic system may lead to increased risk of bleeding or thrombosis. Our aim was to investigate if resuscitated cardiac arrest patients treated with hypothermia had an unbalanced fibrinolysis. A prospective cohort study, including 82 patients were treated with hypothermia at 33°C ± 1°C after out-of-hospital cardiac arrest. Blood samples were collected at 24 hours (hypothermia) and at 72 hours (normothermia). Samples were analyzed for fibrin D-dimer, tissue plasminogen activator (tPA), plasminogen, plasminogen activator Inhibitor-1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and an in-house dynamic fibrin clot formation and lysis assay.Compared with normothermia, hypothermia significantly increased plasminogen activity (mean difference = 10.4%, 95% confidence interval [CI] 7.9-12.9), p  < 0.001), PAI-1 levels (mean difference = 275 ng/mL, 95% CI 203-348, p  < 0.001), and tPA levels (mean difference = 1.0 ng/mL, 95% CI 0.2-1.7, p  = 0.01). No differences between hypothermia and normothermia were found in TAFI activity ( p  = 0.59) or in the fibrin D-dimer levels ( p  = 0.08). The fibrin clot lysis curves showed three different patterns: normal-, flat-, or resistant clot lysis curve. At hypothermia 45 (55%) patients had a resistant clot lysis curve and 33 (44%) patients had a resistant clot lysis curve at normothermia ( p  = 0.047). Comatose, resuscitated, cardiac arrest patients treated with hypothermia express an inhibited fibrinolysis even after rewarming. This could potentially increase the thromboembolic risk. ClinicalTrials.gov ID: NCT02258360.

KW - fibrinolysis

KW - heart arrest

KW - hemostasis

KW - postcardiac arrest syndrome

KW - temperature

KW - Tissue Plasminogen Activator/pharmacology

KW - Prospective Studies

KW - Humans

KW - Out-of-Hospital Cardiac Arrest/therapy

KW - Fibrinolysis

KW - Plasminogen/pharmacology

KW - Fibrin/pharmacology

KW - Plasminogen Activator Inhibitor 1/pharmacology

KW - Hypothermia

KW - Hypothermia, Induced/adverse effects

UR - http://www.scopus.com/inward/record.url?scp=85163647443&partnerID=8YFLogxK

U2 - 10.1089/ther.2022.0037

DO - 10.1089/ther.2022.0037

M3 - Journal article

C2 - 36473198

SN - 2153-7658

VL - 13

SP - 112

EP - 119

JO - Therapeutic Hypothermia and Temperature Management

JF - Therapeutic Hypothermia and Temperature Management

IS - 3

ER -