Clinical paperHyperfibrinolysis is common in out-of-hospital cardiac arrest: Results from a prospective observational thromboelastometry study☆
Introduction
Hypoperfusion and stasis in the course of cardiocirculatory arrest (CCA) are associated with marked activation of procoagulant pathways and a pronounced inflammatory response.1 Enhanced tissue factor expression results in distinct thrombin generation, followed by an increase in plasminogen activator inhibitor (PAI-1) activity and subsequent inhibition of fibrinolysis.2, 3, 4 This imbalance causes intravascular fibrin deposition, microthrombosis, and insufficient fibrin removal; it is assumed to be an important contributor to multi organ dysfunction syndrome and the “no reflow” phenomenon following successful cardiopulmonary resuscitation (CPR).1, 5, 6
To characterize alterations of the coagulation system in the course of CCA, standard coagulation tests (prothrombin time PT, alternatively prothrombin time index PTI, and activated partial thromboplastin time, aPTT) and extended coagulation analyses (e.g. levels of thrombin–antithrombin complex, d-dimers, tissue plasminogen activator, plasmin–antiplasmin complexes, plasmin activator inhibitor) have been used.2, 3, 5 These tests are performed in plasma rather than whole blood, whereby blood cells such as platelets, erythrocytes and monocytes are removed by centrifugation. However, blood cells play a pivotal role in coagulation and subsequent fibrinolysis.7 In contrast to standard coagulation tests, viscoelastic coagulation tests (VETs) are performed in whole blood. This enables the contribution of blood cells to the coagulation process to be included in the evaluation.8
Viscoelastic coagulation analysers such as thromboelastometry (ROTEM®, TEM international, Munich, Germany) and thrombelastography (TEG®, Haemonetics Corp., Braintree, MA, USA) have gained increasing interest in clinical settings such as liver transplant,9 trauma,10 cardiovascular surgery,11 and postpartum hemorrhage.12 Viscoelastic coagulation analysers can be used as point-of-care devices and provide a comprehensive overview of the whole coagulation process. This includes information on the initiation of coagulation, the speed of clot formation and clot strength.13 Furthermore, VETs provide rapid information on premature dissolution of the clot (hyperfibrinolysis, HF).
Until now, no study has investigated the potential role of whole-blood VETs in patients with out-of-hospital cardiac arrest (OHCA). Therefore, we conducted a study investigating thromboelastometric findings in patients with OHCA and subsequent CPR. We compared routine coagulation tests with thromboelastometric findings. The hypothesis was that ROTEM measurements provide a more comprehensive overview of coagulation status following OHCA than standard coagulation tests.
Section snippets
Methods
After approval by the local Ethics Committee of the State of Salzburg (E 1143-09), the study took place in Salzburg, Austria between January 2010 and April 2011. The study was performed according to the ethical rules of the local Ethics Committee; the requirement for signed informed consent was waived. No previous thromboelastometric data from patients with CCA were available. Therefore, the study was considered as explorative.
Patients were enrolled into the study when emergency physicians were
Results
From 1.1.2010 until 30.4.2011, the emergency physicians of the Salzburg Emergency Care Service attended 122 patients with established non-traumatic OHCA. These patients represented 4.5% of all rescue missions (2729). Sixty patients (49.2%) were enrolled for the study.
In 3 patients, ROTEM analyses could not be performed due to technical difficulties and, in another 4 patients, ROTEM analyses were terminated before the 60-min running time was completed. These patients were excluded from further
Discussion
In the current study, we used whole-blood VETs to characterize coagulation and fibrinolysis in patients with OHCA. EXTEM CT, which assesses the initiation phase of extrinsically activated coagulation in ROTEM analysis, was significantly prolonged in non-ROSC patients compared to the ROSC group. The remaining EXTEM parameters were similar in the two groups. The most striking finding was that, in contrast to most previous reports, HF was observed in 35.8% of all patients with established OHCA.
Conclusions
The current study revealed significant differences between ROSC and non-ROSC patients with established OHCA in relation to the initiation of coagulation (EXTEM CT, PTI and aPTT). Other ROTEM coagulation parameters were similar in the two patient groups. The most prominent finding was that approximately one third of all patients demonstrated HF according to ROTEM test results. This observation is in sharp contrast to previous reports suggesting inhibition of profibrinolytic pathways.
Conflict of interest statement
The authors have no conflicts of interest to declare.
Acknowledgment
We gratefully acknowledge the emergency physicians of the Salzburg Emergency Care First Response Team for their exceptional work in collecting the blood samples. Furthermore, we thank the laboratory staff of the University Hospital Salzburg for performing the ROTEM analyses. We also thank Anna Khadem from the Ludwig Boltzmann Institute for Experimental and Clinical Traumatology for her outstanding work.
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2012.08.318.