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Ability of Fibrin Monomers to Predict Progressive Hemorrhagic Injury in Patients with Severe Traumatic Brain Injury

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Abstract

Background

Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with poor outcomes. TBI-associated coagulopathy is frequent and has been described as risk factor for PHI. This coagulopathy is a dynamic process involving hypercoagulable and hypocoagulable states either one after the other either concomitant. Fibrin monomers (FMs) are a direct marker of thrombin action and thus reflect coagulation activation. This study sought to determine the ability of FM to predict PHI after severe TBI.

Methods

We conducted a prospective, observational study including all severe TBI patients admitted in the trauma center. Between September 2011 and September 2016, we enrolled patients with severe TBI into the derivation cohort. Between October 2016 and December 2018, we recruited the validation cohort on the same basis. Study protocol included FM measurements and standard coagulation test at admission and two computed tomography (CT) scans (upon arrival and at least 6 h thereafter). A PHI was defined by an increment in size of initial lesion (25% or more) or the development of a new hemorrhage in the follow-up CT scan. Multivariate logistic regression analysis was applied to identify predictors of PHI.

Results

Overall, 106 patients were included in the derivation cohort. Fifty-four (50.9%) experienced PHI. FM values were higher in these patients (151 [136.8–151] vs. 120.5 [53.3–151], p < 0.0001). The ROC curve demonstrated that FM had a fair accuracy to predict the occurrence of PHI with an area under curve of 0.7 (95% CI [0.6–0.79]). The best threshold was determined at 131.7 μg/ml. In the validation cohort of 54 patients, this threshold had a negative predictive value of 94% (95% CI [71–100]) and a positive predictive value of 49% (95% CI [32–66]). The multivariate logistic regression analysis identified 2 parameters associated with PHI: FM ≥ 131.7 (OR 6.8; 95% CI [2.8–18.1]) and Marshall category (OR 1.7; 95% CI [1.3–2.2]). Coagulopathy was not associated with PHI (OR 1.3; 95% CI [0.5–3.0]). The proportion of patients with an unfavorable functional neurologic outcome at 6-months follow-up was higher in patients with positive FM: 59 (62.1%) versus 16 (29.1%), p < 0.0001.

Conclusions

FM levels at admission had a fair accuracy to predict PHI in patients with severe TBI. FM values ≥ 131.7 μg/ml are independently associated with the occurrence of PHI.

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Abbreviations

TBI:

Traumatic brain injury

GCS:

Glasgow Coma Scale

ICU:

Intensive care unit

ICP:

Intracranial pressure

GOS:

Glasgow Outcome Scale

AUC:

Area under curve

ROC:

Receiver operating characteristic

95% CI:

95% confidence intervals

PHI:

Progressive hemorrhagic injury

INR:

Internationalized normalized ratio

FM:

Fibrin monomer

FDP:

Fibrin/fibrinogen-degradation products

TIC:

Trauma-induced coagulopathy

PT:

Prothrombin time

aPTT:

Activated partial thromboplastin time

Se:

Sensitivity

Spe:

Specificity

PPV:

Positive predictive value

NPV:

Negative predictive value

LR+:

Positive likelihood ratio

ISS:

Injury Severity Score

ADP:

Agonists adenosine diphosphate

AA:

Arachidonic acid

TF:

Tissue factor

MVs:

Microvesicles

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Authors and Affiliations

  1. Intensive Care Unit, Sainte Anne Military Hospital, Toulon, France

    Pierre Esnault, Quentin Mathais, Erwan D’Aranda, Ambroise Montcriol, Mickaël Cardinale, Pierre-Julien Cungi, Philippe Goutorbe & Eric Meaudre

  2. Department of Neurosurgery, Sainte Anne Military Hospital, Toulon, France

    Christophe Joubert & Arnaud Dagain

  3. French Military Health Service Academy Unit, Ecole du Val-de-Grâce, Paris, France

    Arnaud Dagain & Eric Meaudre

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  1. Pierre Esnault
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Contributions

PE, QM, and EM contributed to the study concept and design. PE, QM, ED, AM, PJC, and MC contributed to the acquisition of data. PE, CD, AD, and PG contributed to the analysis and interpretation of data. PE, PG, and EM contributed to drafting the manuscript and critically revising the manuscript for important intellectual content. All authors read and approved the final manuscript.

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Conflicts of Interest

The authors have no conflicts of interest related to this study.

Ethical Approval/Informed Consent

This study was approved by the Institutional Review Board of the Sainte Anne Military Hospital, Toulon (France). The institutional review board waived the requirement for informed consent from patients or their kin, given the observational nature of the study.

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Correspondence to Pierre Esnault.

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Esnault, P., Mathais, Q., D’Aranda, E. et al. Ability of Fibrin Monomers to Predict Progressive Hemorrhagic Injury in Patients with Severe Traumatic Brain Injury. Neurocrit Care 33, 182–195 (2020). https://doi.org/10.1007/s12028-019-00882-6

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