Gender-related differences in the coagulofibrinolytic responses and long-term outcomes in patients with isolated traumatic brain injury: A 2-center retrospective study

Abstract

Coagulation function differs by gender, with women being characterized as more hypercoagulable. Even in the early stages of trauma, women have been shown to be hypercoagulable. Several studies have also examined the relationship between gender and the prognosis of trauma patients, but no certain conclusions have been reached. Patients with isolated traumatic brain injury (iTBI) are known to have coagulopathy, but no previous studies have examined the gender differences in detail. This is a retrospective analysis of a prospective registry conducted at 2 centers. The study included adult patients with iTBI enrolled from April 2018 to March 2021. Coagulofibrinolytic markers were measured in each patient at 1 hour, 24 hours, 3 days, and 7 days after injury, and neurological outcomes were assessed with the Glasgow Outcome Scale Extended at 6 months. Subgroup analysis was also performed by categorizing patients into groups according to neurological prognosis or age at 50 years. Males (n = 31) and females (n = 21) were included in the analysis. In males, there was a significant difference in the levels of activated partial thromboplastin time ( P = .007), fibrin/fibrinogen degradation products ( P = .025), D-dimer ( P = .034), α2-plasmin inhibitor ( P = .030), plasmin-α2-plasmin inhibitor complex ( P = .004) at 1 hour after injury between favorable and unfavorable long-term neurological outcome groups, while in females there was no significant difference in these markers between 2 groups. In the age group under 50 years, there were significant gender differences in fibrinogen (day 3: P = .018), fibrin/fibrinogen degradation products (1 hour: P = .037, day 3: P = .009, day 7: P = .037), D-dimer (day 3: P = .005, day 7: P = .010), plasminogen (day 3: P = .032, day 7: P = .032), and plasmin-α2-plasmin inhibitor complex (day 3: P = .001, day 7: P = .001), and these differences were not evident in the age group over 50 years. There were differences in coagulofibrinolytic markers depending on gender in patients with iTBI. In male patients, aggravation of coagulofibrinolytic markers immediately after traumatic brain injury may be associated with poor neurologic outcome 6 months after injury.

The association between warfarin usage and international normalized ratio increase: systematic analysis of FDA Adverse Event Reporting System (FAERS)

“…A case-control study assessing factors that influence INR values greater than 5 in elderly patients treated with warfarin ( n = 304) found that the risk of elevated INR > 5 increased by 60% (RR = 1.60, 95%CI: 1.12–2.28) for every 10-year increase in age [ 22 ] . Women are less susceptible to elevated INR as the major sex hormone estrogen has been shown to promote the expression of procoagulatory factors including FVIII, FVII, FXII, von Willebrand Factor (VWF), and fibrinogen while simultaneously inhibiting the release of anticoagulatory factors such as protein S, antithrombin, and plasminogen activator inhibitor 1 (PAI-1) [ 23 , 24 ] . Because of this, females have higher coagulation capacity than males of comparable age and are less at risk of excessive bleeding and elevated INR while also being at greater risk for blood clots and thrombosis [ 23 , 24 ] .…”

Effect of Gender on 28-Day Survival Rates and Transfusion Volume in Severe Trauma Patients: A Multicenter Observational Study

“…This is a physiological function of the female-specific event of pregnancy and delivery, and estrogen has been hypothesized to be involved in the modulation of immune responses in trauma and hormoneinduced hypercoagulability (11). Hormone-induced hypercoagulability may affect the response to hemorrhage and critical injury in premenopausal females, and some studies have focused their analysis on the age of female patients with trauma, particularly around menopause (4,7,12,13). These sex comparative studies are also inconclusive, with mixed reports of changes in prognosis and coagulopathy by age group (7,12,13) and no change in prognosis or coagulopathy (4).…”

“…Several studies have investigated the relationship between sex and prognosis following trauma with conflicting results (1)(2)(3)(4)(5)(6)(7)(8). Mixed reports suggest females have a better (1,3,8), similar (2,4,5), or worse prognosis (6).…”

“…Mixed reports suggest females have a better (1,3,8), similar (2,4,5), or worse prognosis (6). In patients with isolated traumatic brain injury, worsening of coagulation-fibrinolysis markers immediately after injury may have been associated with unfavorable neurologic prognosis in males but not in females (7). In trauma populations not limited to head trauma, there are also reports of a relatively higher mortality rate for male patients in the older population (9).…”

“…Hormone-induced hypercoagulability may affect the response to hemorrhage and critical injury in premenopausal females, and some studies have focused their analysis on the age of female patients with trauma, particularly around menopause (4,7,12,13). These sex comparative studies are also inconclusive, with mixed reports of changes in prognosis and coagulopathy by age group (7,12,13) and no change in prognosis or coagulopathy (4).…”