Coagulation parameters and risk of progressive hemorrhagic injury after traumatic brain injury … – europe pmc article – europe pmc anoxia refers to

1. Introduction

Traumatic brain injury (TBI) remains the leading cause of death after trauma, often leading to long term physical and neuropsychiatric deficits [ 1– 6]. Although some damage to the brain occurs in the initial of injury, secondary brain damage due to ongoing intracranial bleeding and brain swelling is an eminent and potentially avoidable cause of morbidity and mortality. Of many potential secondary processes, progressive hemorrhagic injury (PHI) is one of the most important and devastating issues [ 7].

PHI is generally defined as the appearance of new hemorrhage lesion or evident expansion of previous hematoma [ 8– 13], with an incidence ranging from 6% to 67% [ 8– 26].


Traditionally, PHI is diagnosed by repeated CT scanning before irreversible deterioration occurs.Anoxia refers to nevertheless, practices of some trauma centers turned out to be time-consuming and costly [ 20]. Therefore, addressing risk factors closely associated with PHI would be of great avail. Several factors, such as male gender, low initial level of consciousness, older age, and presence of the spot sign on CT angiography and coagulopathy, have been implicated as impact factors of intracranial hemorrhage (ICH) progression [ 8, 27– 29]. Coagulopathy, traditionally diagnosed by routine laboratory tests such as international normalized ratio (INR), activated partial thromboplastin time (APTT), and platelet count (PLT), is common in TBI and may be a potential prognostic factor.

However, data regarding the association between laboratory tests and PHI have been somewhat inconsistent.Anoxia refers to stein and associates indicated that abnormal values of INR, APTT, and PLT were independently correlated with PHI [ 27]. A study by oertel and colleagues found that only prolonged PTT was associated with PHI [ 8], whereas engström and coworkers reported that only low PLT count was related to PHI [ 15]. In view of discrepancies among literatures, the purpose of our meta-analysis is to explore the relationship between coagulation tests and PHI to improve evidence-based management of patients with TBI.

3.3.1. Coagulation parameters in PHI versus non-PHI (continuous data)

PLT and PHI. Four studies were included to investigate the association between decreased PLT counts and the incidence of PHI following TBI [ 8, 10, 12, 13].Anoxia refers to no significant effect was detected after the meta-analysis ( P = 0.06).

PT and PHI. Two studies were available for meta-analysis with heterogeneous outcomes [ 8, 10]. The overall result demonstrated no significant effect, with a mean difference of 0.25 (95% CI, −0.60–1.11; P = 0.56).

PTT and PHI. PTT was tested in four studies designed for the american and the chinese as well [ 8, 10, 12, 13]. No positive results were discovered in any study ( P = 0.92).

D-dimer and PHI. Two studies probed the potential effect of D-dimer [ 10, 12] on PHI. Significantly increased D-dimer values were found in both studies, which raised no statistically significant result after pooling together, with a mean difference of 34.48 (95% CI, −32.15–101.11; P = 0.31).Anoxia refers to

Fg and PHI. We identified three studies [ 9, 10, 12], two of which showed decreased fg in patients with PHI. The overall meta-analysis showed a tendency towards fg reduction in PHI-positive patients: MD of −0.26 (95% CI, −0.39–−0.13; P 0.001), with no heterogeneity ( I 2 = 0, P = 0.96).

INR and PHI. Two recent studies examining possible relationship between INR and PHI both detected a higher INR in PHI-positive patients [ 12, 13]. However, gathering extracted data brought out marginal statistical significance [MD: 0.50 (95% CI, −0.09–1.08; P = 0.10)].

3.3.2. Prevalence of PHI in normal coagulation versus coagulopathy (dichotomous data)

PLT and PHI. Dichotomous data for PLT were retrievable from four studies [ 8– 11].Anoxia refers to meta-analysis of included studies suggested statistically significant association between PLT reduction and subsequent PHI, with a pooled OR of 2.76 (95% CI, 1.62–4.70; P 0.001).

PT and PHI. Meta-analysis was possible for five studies examining PT values for both groups and reporting dichotomous data [ 8– 12]. Overall, there was a significant increased incidence of PHI with prolonging PT value (OR, 2.69; 95% CI, 1.55–4.66; P 0.001).

PTT and PHI. Potential link between PTT and PHI was assessed in four studies [ 8– 11]. The pooled result failed to prove such association (OR, 2.39; 95% CI 0.72–7.95; P = 0.15), with a moderate degree of heterogeneity ( I 2 = 70%; P = 0.02).

D-dimer and PHI. Three studies hit our search [ 9– 11], demonstrating a significant bound for D-dimer with PHI, with a pooled OR of 16.50 (95% CI, 4.94–55.04; P 0.001).Anoxia refers to

Fg and PHI. Three case-control studies were aggregated to unravel the possible effect of abnormal fg on the genesis of PHI [ 9– 11]. The summary result favored a strong efficacy of decreased fg to bring about PHI (OR, 3.44 95% CI, 2.37–4.99; P 0.001).

INR and PHI. Meta-analysis was conducted for two studies [ 11, 13]. General inverse variance method was adopted because of the lack of absolute data in white 2009. Positive associations between INR and PHI were found (OR, 3.70; 95% CI, 1.11–6.29; P 0.001).

4. Discussion

High prevalence and mortality highlight the importance of timely prognosis of PHI with good sensitivity and specificity. With repeated CT scanning which is time-consuming and costly, addressing the associations between the abnormal coagulation tests and PHI would be of great avail.Anoxia refers to so whether coagulopathy correlates with PHI occurrence, which laboratory test is meaningful, and which parameter carries the most weight in predicting PHI become burning questions confronting us.

Our findings showed statistically significant positive associations between PT, D-dimer level, INR, and the risk of PHI after TBI. Higher level of PLT and fg seemed to suggest a lower risk of PHI. Independent PTT seemed to be of no indicative value. As for dichotomous variables, the contributions to PHI were as follows: DD INR PT fg PLT. But when examined as continuous variables, the sequence seemed to be INR DD fg PLT. Meta-analysis of continuous data was perceived to be more meaningful compared with that of dichotomous data because of less conversion steps to correlation coefficient ( r).Anoxia refers to

Meanwhile, there were some discrepancies in association strength between dichotomous and continuous data. Contributions of DD and INR were similar, with INR being a little more influential in the analysis of continuous data, while, as a dichotomous variable, DD had the strongest relationship with PHI. The distinction was speculated to derive from different conversion steps, limited included articles, and subjects. As a dichotomous variate, the predicting value for PT was significant, but that was not the case when it was examined as a continuous variate, which might owe to different test methods of included studies. In analysis for PTT as a dichotomous variate, positive association was detected when ignoring oertel et al. [ 8] or tong et al. [ 10].Anoxia refers to when D-dimer was modeled as a dichotomous variate, a robust significance was detected, but we only found a marginally significant positive association for it as a continuous variate. Those too few studies were included and internal nonspecificity might bring the divergence. As for fg, moderate association with PHI was noticed, whether it was examined as a continuous variable or dichotomous variable. Finally, for INR, powerful association with PHI was detected in both data types.

While the quantitative association between coagulative tests and the risk of PHI has been confirmed, we have to acknowledge that four of our included studies are from china and 2 from america. But this does not significantly mean the incidence of ICH in eastern population is higher than in the counterparts, because of lacking in large prospective epidemic studies in our analysis.Anoxia refers to potential bias from population difference should be further evaluated through more large epidemic studies.

No meta-analysis about PHI was published before. There is currently 1 publication that we are aware of that has reviewed the current etiology research available to interpret the predictor and mechanism of PHI [ 33]. In this paper, relationships between PHI and measurable coagulopathy, while clinically useful, were described to be not one of simple cause and effect. Our findings are in agreement with previous articles by stein et al. [ 27], engström et al. [ 15], schnüriger et al. [ 19], and allard et al. [ 16], in which abnormal laboratory test values were independently associated with PHI.Anoxia refers to in addition, from another perspective, even though PHI was most often diagnosed by the 24-hour CT scan, it might have occurred earlier, preceding and perhaps contributing to the abnormal laboratory tests, which can be regarded as indicators.

Our findings implied that abnormal coagulation tests might indicate occurrence of PHI, which might lead to focused monitoring among TBI patients, and thus save plenty of medical resources. Our interpretation could form the basis for further studies exploring whether correcting these values would prevent PHI and moreover make for subsequent operation. However, there is no strong evidence that correcting laboratorial tests in this situation actually improves outcome.Anoxia refers to according to perel et al., there is no reliable evidence from randomized controlled trials to support the effectiveness of hemostatic drugs in reducing mortality or disability in patients with TBI [ 34], whereas, in another article, tranexamic acid can reduce all-cause mortality in bleeding trauma patients, with no apparent increase in the risk of vascular occlusive events, if given as early as possible and within three hours of injury, as treatment later than this is unlikely to be effective [ 35]. Therefore further prospective studies are needed to determine the effects of coagulation-associated therapies in patients with TBI. In any case, however, the correction of abnormal values will indisputably ensure safer operation.Anoxia refers to

As with all meta-analysis, some caveats are in order. Firstly, bias exists because of defects in study design of included studies and meta-analysis itself, such as publication bias, selection bias, confounding bias, and recall bias. Reporting bias might have also occurred, which derived from the disparities in testing method and cutoff point for each parameter in pertinent studies, which, though moderate, might serve as the confounding factors. We tried our best to minimize the bias by excluding those studies with insufficient patient characteristics [ 8, 19, 21]. Secondly, the limited literature quantity, which partly comes from inaccurate definitions of PHI, is devoted substantially to the heterogeneities between studies.Anoxia refers to thirdly, potential indicators in our meta-analysis were all single parameters, while combined parameters, routinely defined as coagulopathy, may be more powerful in predicting PHI. The criteria of coagulopathy have been changed over time. In 2001, the international society of thrombosis and haemostasis (ISTH) simplified the laboratory diagnosis of DIC [ 36]. However, only one of our included studies had used this score [ 12]. More studies on relationship between combined parameters and PHI are suggested here. Fourthly, in most studies, blood sample was tested only once upon admission, with the possibility of potential measurement errors. Therefore, dynamic monitoring of coagulation function should be adopted to ensure convincing results.Anoxia refers to finally, suggested definition of PHI in most articles only allowed for a 25% or more increase of bleeding in the subsequent CT scan but does not take the absolute bleeding volume into account. As a consequence, comparability between studies or different subjects becomes questionable.

However, our study had strengths in including relatively newer studies with reliable imaging examinations, quantitative analyses, and precise and consistent definition of PHI as we described above. Moreover, we calculated the comparable association strength in predicting PHI after TBI for each parameter for the first time, which was much more clinically meaningful than the association alone. Thus we could assess the prognostic value of these parameters, which might further guide clinical practices.Anoxia refers to

5. Conclusion

Despite the limitations, this meta-analysis has notable clinical and public health implications, which indicate significant inverse associations for PLT level, fg level, and positive associations for PT, D-dimer level, and INR value in predicting PHI, among which abnormal D-dimer level and INR value were more meaningful. Independent PTT seemed to be meaningless. This study suggests instant test and correction of coagulation parameters at admission to predict PHI and, possibly, better outcome of TBI patients. The focus of our meta-analysis is upon the capability for individual test to predict the presence of PHI after TBI. However, to demonstrate the relationship between coagulopathy and the extent of PHI seems more meaningful, which may be the interest of future studies.Anoxia refers to moreover, interrelationships between coagulation tests, which were not discussed here, remain to be unraveled. Eventually, large prospective studies are needed to investigate the underlying pathogenesis better and identify effective therapy to reap the maximum benefits.