EHS
EHS

Hyperfibrinolysis and fibrinolysis shutdown in patients with traumatic brain injury


A total of 61 consecutive TBI cases were included in the study. There were 122 missing values (5.3%) in this study’s dataset, which were complemented by the multiple imputation method. Demographic, clinical, and radiological characteristics are summarised in Table 1. ASDH was found in 49 patients (80.3%), AEDH in 10 patients (16.4%), ICH in 52 patients (85.2%), and TSAH in 58 patients (95.1%) (some patients had more than one diagnosis). The good outcome group consisted of 30 cases (49.2%) and the poor outcome group consisted of 31 cases (50.8%). Seven patients died between 1 and 3 days after injury and five patients died between 3 and 7 days after injury due to TBI. Age was significantly lower in the good outcome group than in the poor outcome group [median 48 years (IQR 32–66 years) vs. 78 years (IQR 59–82 years), p < 0.001]. There was no difference in gender between the two groups. The good outcome group had higher GCS scores at admission [median 13 (IQR 11–15) vs. 6 (IQR 4–13), p < 0.001], lower AIS-head [median 4 (IQR 3–5) vs. 5 (IQR 5–5), p < 0.001], lower incidence of ASDH (63.3% vs. 96.8%, p = 0.009), and lower volume of FFP transfusion [median 0 mL (IQR 0–0 mL) vs. 0 mL (IQR 0–1200 mL), p = 0.008] than the poor outcome group. There was no difference in the rate of TXA use between the two groups.

Table 1 Initial demographic, clinical, and radiologic characteristics of the study population.

Time course of TAT, D-dimer, PAI-1, platelet count, PT, and APTT

Figure 1 shows the time course of plasma TAT, D-dimer, and PAI-1 levels of all patients on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after TBI. Plasma TAT levels (normal range: 0.0–3.0 ng/mL) at admission were abnormally high in all patients. The median plasma level of TAT decreased rapidly and significantly from admission to 1 day after injury [1–3 h: t (60) = 4.531, p < 0.001; 3–6 h: t (60) = 7.753, p < 0.001; 6–12 h: t (60) = 4.907, p < 0.001; 12 h–1 day: t (60) = 5.665, p < 0.001], subsequently decreased insignificantly from 1 to 3 days after injury [t (53)  = 1.374, p = 0.17], and decreased significantly from 3 to 7 days after injury [t (48) = 2.657, p = 0.008].

Figure 1
figure 1

Boxplots showing plasma levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) of all patients on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after traumatic brain injury. *p < 0.05, **p < 0.01, ***p < 0.001, N.S = Not Significant.

The median plasma D-dimer level (normal range: 0.0–1.0 μg/mL) at admission was abnormally high in 60 (98.4%) of the 61 patients. It increased significantly from admission to 3 h after injury [t (60) = − 3.198, p = 0.01]. Three hours after injury, it decreased significantly up to 3 day after injury [3–6 h: t (60) = 4.709, p < 0.001; 6–12 h: t (60) = 3.629, p < 0.001; 12 h–1 day: t (60) = 4.880, p < 0.001; 1–3 days: t (53) = 4.798, p < 0.001], and subsequently increased significantly again from 3 to 7 days after injury [t (48) = − 6.444, p < 0.001].

The median plasma PAI-1 level (normal range: 0.0–50.0 ng/mL) at admission was within the normal range in 53 (86.9%) of the 61 patients. It increased significantly from admission to 3 h after injury [t (60) = − 5.302, p < 0.001]. The upward trend continued up to 6 h after injury [3–6 h: t (60) = − 1.550, p = 0.12; 1–6 h: t (60) = − 4.560, p < 0.001]. After 6 h post-injury, it decreased up to 3 days [6–12 h: t (60) = 0.640, p = 0.52; 12 h–1 day: t (60) = 2.309, p = 0.02; 6 h–1 day: t (60) = 3.193, p = 0.001; 1–3 days: t (53) = 3.868, p < 0.001], subsequently increasing insignificantly again from 3 to 7 days after injury [t (48) = − 0.400, p = 0.69].

Supplementary Fig. 1 shows the time course of platelet count, PT, and APTT of all patients on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after TBI. The median platelet count (normal range: 120–400 × 109/L) decreased significantly from admission to 1 day after injury [1–3 h: t (60) = 5.881, p < 0.001; 3–6 h: t (60) = 3.157, p = 0.002; 6–12 h: t (60) = 2.048, p = 0.04; 12 h–1 day: t (60) = 2.486, p = 0.01], subsequently increased insignificantly from 1 to 3 days after injury [t (53) = − 0.224, p = 0.82], and increased significantly from 3 to 7 days after injury [t (48) = − 9.496, p < 0.001].

The median PT [normal range: 0.8–1.2 international normalised ratio (INR)] increased significantly from admission to 3 h after injury [t (60) = − 3.210, p = 0.003], subsequently decreased insignificantly from 3 h to 1 day after injury [3–6 h: t (60) = 1.426, p = 0.16; 6–12 h: t (60) = 1.639, p = 0.12; 12 h–1 day: t (60) = 1.612, p = 0.12], decreased significantly from 1 to 3 days after injury [t (53) = 5.582, p < 0.001], and increased significantly again from 3 to 7 days after injury [t (48) = − 4.436, p < 0.001].

The median APTT (normal range: 24–36 s) increased insignificantly from admission to 1 day after injury [1–3 h: t (60) = − 0.911, p = 0.36; 3–6 h: t (60) = − 0.138, p = 0.89; 6–12 h: t (60) = − 1.165, p = 0.24; 12 h–1 day: t (60) = − 0.766, p = 0.44], subsequently decreased significantly from 1 to 3 days after injury [t (53) = 4.270, p < 0.001], and decreased insignificantly from 3 to 7 days after injury [t (48) = − 0.595, p = 0.55].

TAT, D-dimer, PAI-1, platelet count, PT, APTT and long-term outcome

The plasma levels of TAT, D-dimer, and PAI-1 were higher in the poor outcome group than in the good outcome group from the time of admission to 7 days after injury as analysed by GLMM (all p < 0.001) (Fig. 2). PT and APTT were higher in the poor outcome group than in the good outcome group (both p < 0.001), but platelet counts did not significantly differ between groups (p = 0.06) from the time of admission to 7 days after injury, as analysed by GLMM (Supplementary Fig. 2).

Figure 2
figure 2

Boxplots showing plasma levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) of cases with good outcome and poor outcome on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after traumatic brain injury.

Correlation between plasma D-dimer levels 3 h after injury and plasma PAI-1 levels 6 h after injury

Figure 1 shows that plasma D-dimer level as a biomarker of hyperfibrinolysis peaked 3 h after injury and plasma PAI-1 level as a biomarker of fibrinolysis shutdown peaked 6 h after injury. To investigate the correlation between hyperfibrinolysis and subsequent fibrinolysis shutdown, Spearman’s rank correlation coefficient between plasma D-dimer levels 3 h after injury and plasma PAI-1 levels 6 h after injury were calculated. Positive correlations were found between plasma D-dimer levels 3 h after injury and plasma PAI-1 levels 6 h after injury (p < 0.001, r = 0.68) (Fig. 3).

Figure 3
figure 3

Correlation between plasma D-dimer level 3 h after injury and plasma PAI-1 level 6 h after injury.

Coagulation and fibrinolysis parameters as independent risk factors for poor prognosis

To evaluate independent risk factors at admission related to poor prognosis, multivariate logistic regression analysis was performed (Table 2). The explanatory variables were age3,4,15,16,17, GCS score3,16,18,19,20, AIS-head3,4,18, presence of ASDH3,16,18,20 and ICH3,16,20,21, and plasma levels of TAT, D-dimer, and PAI-1. The response variable was a good outcome with GOS-E of 6–8 or poor outcome with GOS-E of 1–5 at 6 months after injury. The results showed that independent risk factors at admission for poor prognosis were older age, presence of ASDH, and elevated D-dimer.

Table 2 Multivariate logistic regression analysis of initial variables as independent risk factors for poor prognosis.

Multivariate logistic regression analysis was also performed using plasma levels of TAT, D-dimer, and PAI-1 from admission to 7 days after injury to identify reliable prognostic coagulation and fibrinolysis parameters at each time point after TBI (Table 3). Elevated D-dimer levels from admission to 3 h after injury and elevated PAI-1 levels from 6 h to 1 day after injury were significant negative prognostic indicators.

Table 3 Multivariate logistic regression analysis of coagulation/fibrinolysis parameters as independent risk factors for poor prognosis.



Source link

EHS
Back to top button