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D-dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases

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Abstract

This study sought to describe and evaluate any relationship between D-dimer values and progressive hemorrhagic injury (PHI) after traumatic brain injury (TBI). In patients with TBI, plasma D-dimer was measured while a computed tomography (CT) scan was conducted as soon as the patient was admitted to the emergency department. A series of other clinical and laboratory parameters were also measured and recorded. A logistic multiple regression analysis was used to identify risk factors for PHI. A cohort of 194 patients with TBI was evaluated in this clinical study. Eighty-one (41.8%) patients suffered PHI as determined by a second CT scan. The plasma D-dimer level was higher in patients who demonstrated PHI compared with those who did not (P < 0.001. Using a receiver–operator characteristic curve to predict the possibility by measuring the D-dimer level, a value of 5.00 mg/L was considered the cutoff point, with a sensitivity of 72.8% and a specificity of 78.8%. Eight-four patients had D-dimer levels higher than the cut point value (5.0 mg/L); PHI was seen in 71.4% of these patients and in 19.1% of the other patients (P < 0.01). Factors with P < 0.2 on bivariate analysis were included in a stepwise logistic regression analysis to identify independent risk factors for TBI coagulopathy. Logistic regression analysis showed that the D-dimer value was a predictor of PHI, and the odds ratio (OR) was 1.341 with per milligram per liter (P = 0.020). The stepwise logistic regression also identified that time from injury to the first CT shorter than 2 h (OR = 2.118, P = 0.047), PLT counts lesser than 100 × 109/L (OR = 7.853, P = 0.018), and Fg lower than 2.0 g/L (OR = 3.001, P = 0.012) were risk factors for the development of PHI. When D-dimer values were dichotomized at 5 mg/L, time from injury to the first CT scan was no longer a risk factor statistically while the OR value of D-dimer to the occurrence of PHI elevated to 11.850(P < 0.001). The level of plasma D-dimer after TBI can be a useful prognostic factor for PHI and should be considered in the clinical management of patients in combination with neuroimaging and other data.

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Correspondence to Bing-Shan Wu.

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Jorge Humberto Tapia-Pérez, Magdeburg, Germany

In this study, the authors tried to explain the role of D-dimer as predictor for progression of hemorrhagic injury (PHI) in trauma patients. The sufficient number of patients could have been shown more detail; nevertheless, with the given data, many interesting conclusions are obtained. The patients with PHI displayed more frequent abnormalities in coagulation parameters; based on these observations, it could be expressed that a kind of coagulopathy is associated. Pathophysiologic considerations allow us, assuming that inflammation and endothelial injury are contributing. Recently, a study from Canada showed that coagulation abnormalities detected in routine laboratory tests in the first hours are predictors of hemorrhagic progression [1]. This study provides support to this observation. The causal relationship between coagulopathy and progression will require further studies.

The relevance as therapeutic target has been described by Narayan et al. [2] in their study about factor VIIa. A consideration is that the delay or limitation of PHI could not redound in a clinical improvement, despite the association of bad outcome described by Tian et al. In this way, targeting traumatic coagulopathy could be just an additional therapy, if the future studies do not demonstrate an increased risk of thrombotic events.

The first regression model presented showed the time to first CT scan as risk factor for PHI, but it should not necessarily be considered as that. An early CT scan could not detect lesions because some of them do not develop yet. It is probably an evidence of a natural PHI after trauma, which is linked to coagulation disorders; further studies are needed.

The authors' conclusion provides us an easy clinical tool. Reasonably, in patients with severe head injury, admitted early, and with abnormalities in coagulation (especially DD) can the performance of a CT scan be very useful. Evidently, the therapeutic decision must be taken in context of each case.

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2. Narayan RK, Maas AI, Marshall LF, Servadei F, Skolnick BE, Tillinger MN; rFVIIa Traumatic ICH Study Group. Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial. Neurosurgery 2008 ;62:776–778.

Ignacio J. Previgliano, Buenos Aires, Argentina

This paper by Tian et al. is very interesting in addressing the issue of bleeding disorders following head injury.

Although based on retrospective data, their finding that D-dimer at a cutoff point of 5 mg/l with a sensitivity of 72.8% and a specificity of 78.8% is an important clue for further investigation.

The authors gave substantial bibliographic support for the use of D-dimer as a prognostic toll of progressive hemorrhagic injury in patients with traumatic brain injury. Most of their findings showed that patients with D-dimer above 5 mg/l were older and had a severe head injury according to the initial GCS, so they underwent early to diagnostic studies. They also pointed out in the paper that D-dimer is augmented in many acute neurological disorders mainly to the activation of the coagulation process due to the liberation of tissue factor.

Nevertheless, some important points should be highlighted:

(a) In the logistic regression model, only patients with determinations above the cutoff point were included.

(b) It was not possible to identify the exact coagulation problem in most of the study population.

(c) Regarding this dilution, coagulopathy and disseminated intravascular coagulation (DIC) diagnosis should be ruled out for the reason that a different therapeutic approach is needed.

The International Society on Thrombosis and Haemostasis developed a simple scoring system for the diagnosis of overt DIC (see Table 1). A score of 5 or greater indicates overt DIC, whereas a score of less than 5 does not rule out DIC, but may indicate non-overt DIC. Studies have demonstrated the DIC score to be 93% sensitive and 98% specific for DIC.

figure a

Table 1. DIC scoring system. Modify from Taylor Jr FB, Thromb Haemost 2001;86:1327–1330.

I think this is a good tool for the neurosurgeon to confront acute bleeding disorders in head injury patients.

As stated above, this paper is a good starting point for further research in such important issue as the prognosis of delayed hematomas.

Susanne Mink, Zurich, Switzerland

It still remains challenging to find outcome predictors for progression of acute hemorrhagic injury (PHI) of traumatic brain-injured patients. In this comprehensive article, the authors summarize their experience with D-dimer levels in nearly 200 patients with traumatic brain injury. The results and conclusion of the study are very interesting and may be one part of the facts for clinical judgement and therapeutic decisions in the acute state of injury. A relevant limitation of the study represents the retrospective character. However, more detailed and additional information should be addressed in further prospective studies. Thereby, subgroup analysis and enhanced CT time management would be of interest in these cases. Early CT scans can miss lesions which are not developed at the time of examination. This leads to the necessity for definition of exact time intervals of D-dimer plasma levels and further coagulation parameters. Sawamura et al. (1) described the parameters of disseminated intravascular coagulation in general traumatic patients in more detail, considering, additionally, ratios to be more specific and significant in outcome prediction. Generally, contributing factors in PHI are endothelial damage and associated inflammation which seek still for causal relationship between coagulopathy and the PHI.

Reference

1. Sawamura A, Hayakawa M, Gando S, et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb Res 2009;124:608–613.

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Tian, HL., Chen, H., Wu, BS. et al. D-dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases. Neurosurg Rev 33, 359–366 (2010). https://doi.org/10.1007/s10143-010-0251-z

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