Abstract
Anti-thrombotic drugs may increase the risk for chronic subdural hematoma (CSDH). However, whether to continue or discontinue/counteract these drugs has not been investigated in patients with mild head trauma. CSDH incidence after mild head trauma, as well as the risk for CSDH in patients with anti-thrombotic drugs, were investigated in this study. The study included 765 consecutive elderly (>65 y.o.) patients with mild head trauma and an initial Glasgow Coma Scale (GCS) score of 14 or 15. All patients received initial CT within 24 hours after trauma and were re-examined 30 days after trauma to detect CSDH formation, repeating for every 30 days to examine symptomatic CSDH progression. Patients were divided into two groups, with anti-thrombotic drugs (n = 195) or without them (n = 263), to investigate the influence of pre-traumatic conditioning with anti-thrombotic drugs on CSDH. The whole sample was 458 out of 765 cases. The incidence of CSDH formation was 91 out of 458 cases (19.9%) after mild head trauma, with no significant difference between with and without anti-thrombotic drugs. CSDH progressed as symptomatic in 21 out of 458 cases (4.6%), with no significant difference between with and without anti-thrombotic drugs. Pre-traumatic conditioning with anti-thrombotic drugs and its continuation after trauma did not affect the incidence of formation or symptomatic progression of CSDH. This finding suggests that discontinuing and/or counteracting anti-thrombotic drugs may be unnecessary in patients with mild head trauma.
Keywords: chronic subdural hematoma, mild head trauma, anticoagulant, antiplatelet, anti-thrombotic drug
Introduction
Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases, especially in elderly patients. In developed countries, including Japan, the population has been aging, affecting the epidemiology, which frequently occurs in the elderly. The incidence of CSDH was reportedly 1.7/100,000/year in the general population.1) It increased to 10.9/100,000/year in 2000 and to 19.0/100,000/year in 2015 in Denmark.2) In Japan, the incidence of CSDH also increased to 13.1/100,000/year in 19923) and 20.6/100,000/year in 2011.4)
The most frequent cause of CSDH has been supposed to be mild head trauma, although the causative history of trauma is not obvious in approximately 25%-40% of patients.4,5) CSDHs appear to originate from a small oligo- or asymptomatic traumatic acute subdural hematoma (ASDH),6,7) which develops into CSDH in approximately 10%-20% of them.8,9) Another possible origin of CSDH is subdural hygroma arising from traumatic tearing of the arachnoid membrane to allow cerebrospinal fluid passage into the subdural space.6,10-14) Subdural hygroma reportedly develops into CSDH in approximately 10%-25% of cases.10,12) However, the frequency of CSDH arising from mild head trauma is not fully clarified,15) mainly because no studies have investigated using the cohort fashion.
The aging population explains most of the recent increase in the incidence of CSDH.4,16) Pre-traumatic conditioning with anti-thrombotic drugs might be another risk factor for CSDH.2,5,17-20) De Bonis et al. demonstrated that CSDH risk increased to 2.45 in odds ratio (OR) for patients receiving anticoagulants or to 1.42 in OR for patients receiving antiplatelets in a case-control study.5) Recently, Gaist et al. also demonstrated a similar risk for CSDH in patients receiving anti-thrombotic drugs, maximally 7.93 in OR for patients receiving both clopidogrel and vitamin K antagonist.2) These results suggest that patients who suffer mild head trauma under pre-traumatic conditioning with anti-thrombotic drugs require some countermeasures to avoid the development of CSDH. However, it remains unclear whether or not to discontinue and/or counteract anti-thrombotic drugs in such situations.
In this retrospective observational study, the frequency of CSDH originating from mild head trauma, either arising through ASDH or not, is investigated to clarify its natural history, especially its frequencies of formation, development, or spontaneous resolution. This study also investigated the natural radiological course after mild head trauma in elderly patients with or without anti-thrombotic drugs to clarify whether or not to discontinue anti-thrombotic drugs to avoid CSDH after mild head trauma.
Clinical Materials and Methods
The Ethical Committee of the Sendai City Hospital approved the present study (#20220103). The study protocol, including purpose, subject of the study, methods of data collection, the confidentiality of personal information, and publication of results, was published on the homepage of Sendai City Hospital on the internet with the opportunity to opt-out. This study complied with the principles outlined in the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects.
This study involved 765 consecutive elderly (>65 y.o.) patients with mild head trauma, who visited as outpatients of our hospital's emergency or neurosurgery department within 24 hours after trauma, between January 1, 2018, and December 31, 2021. Our institute, the Sendai City Hospital, carries a role mainly as a tertiary emergency and critical care center. Initial CT was examined in all patients, based on the Japan Guideline for the Management of Severe Traumatic Brain Injury 3rd edition.21) An initial Glasgow Coma Scale (GCS) score of 14 or 15 was considered mild head trauma. Patients with a traumatic intracranial abnormality (t-IA) on initial CT were admitted for one or a few days until stabilization of t-IA on daily repeated CT. Patients without t-IA, as well as those with t-IA after discharge, were followed up at the outpatient of the neurosurgery department by examining CT 30 days after trauma to evaluate CSDH formation. Patients who demonstrated CSDH formation on CT at 30 days after trauma underwent repeat CTs every 30 days until becoming symptomatic or spontaneous resolution, up to 12 months. Patients who presented with symptomatic CSDH underwent surgical treatment. According to the pre-traumatic conditioning with anti-thrombotic drug (ATD), patients were divided into two groups, with or without ATD. In all ATD cases, the patients took all drugs continuously after head trauma, with neither discontinuation nor counteraction.
Statistical analysis
A descriptive statistical analysis was carried out by means of frequencies and mean ± standard deviation for qualitative and quantitative variables, respectively. As a comparative statistical analysis, χ2-test with Bonferroni correction was used to examine the difference in the incidence of one month CSDH formation or of delayed symptomatic CSDH progression between groups. Statistical difference was considered significant at p < 0.05.
Results
Among the initially involved 765 patients, 307 dropped out from the study protocol since they did not appear outpatient to examine CT one month after head trauma, resulting in a sample of 458 cases. The mean age of the sample was 82 ± 7.5 years old, and the majority were female (M:F = 207:251). One month after head trauma, 91 patients (19.9%) revealed asymptomatic CSDH formation on CT. Progression to symptomatic CSDH occurred in 21 patients (4.6%).
Among 458 total patients, initial CT revealed t-IA in 136 patients (29.7%), including 86 cases (18.8%) with ASDH, 67 cases (14.6%) with traumatic subarachnoid hemorrhage, 18 cases (3.9%) with cerebral contusions, and three cases (0.7%) with acute epidural hematoma.
Among the 458 total patients, 195 (42.6%) cases were pre-traumatically conditioned with ATD, and 263 (57.4%) cases were without it. In cases with ATD, 124 (27.1%) were taking antiplatelets: 103 (22.5%) were taking single antiplatelets, and 11 (2.4%) were taking double antiplatelets. As an antiplatelet, 100 patients took aspirin, 20 took clopidogrel, 7 took cilostazol, 6 took prasugrel, 5 took ticlopidine, and so on. Seventy-five (16.4%) were on anticoagulants: 64 (14.0%) were taking single anticoagulants, and one (0.2%) was taking double anticoagulants. As an anticoagulant, 24 patients took warfarin, 19 took apixaban, 13 took rivaroxaban, 12 took edoxaban, 2 took dabigatran, and so on. Ten cases (2.2%) were taking both antiplatelet and anticoagulant. Three cases (0.7%) received heparin for hemodialysis every other day, and three received unknown ATDs (0.7%) (Table 1).
Table 1.
Background of patients at the time of trauma
| Number of Patients | 458 | |
| Age | 82 ± 7.5 | |
| Gender | 207:251 | |
| Radiological features | ||
| traumatic intracranial abnormalities (t-IA) on CT within 24 hrs after trauma | 136 | |
| ASDH | 86 | |
| t-SAH | 67 | |
| contusion | 18 | |
| AEDH | 3 | |
| Pre-traumatic conditioning with antithrombotic drugs | 195 | |
| oral antiplatelet | 124 | |
| single | 103 | |
| double | 11 | |
| oral anticoagulant | 75 | |
| single | 64 | |
| double | 1 | |
| (both oral antiplatelet and anticoagulant | 10) | |
| heparin (hemodialysis) | 3 | |
| unknown | 3 | |
abbreviations used: t-IA = traumatic intracranial abnormalities, ASDH = acute subdural hematoma, t-SAH = traumatic subarachnoid hemorrhage, AEDH = acute epidural hematoma
Relationship between t-IA on initial CT and development to CSDH
In 136 patients with t-IA on initial CT, 50 (36.8%) showed CSDH formation on CT one month after head trauma. In 86 patients with ASDH on initial CT, 37 (43.0%) showed asymptomatic CSDH formation on CT one month after head trauma, and five cases (5.8%) presented with symptomatic CSDH progression more than one month after head trauma. In 50 patients with t-IA other than ASDH on initial CT, 13 patients (26.0%) presented with asymptomatic CSDH formation on CT one month after head trauma, and two cases (4.0%) presented with symptomatic CSDH progression at more than one month after head trauma. In 322 patients without any t-IA on initial CT, 41 patients (12.7%) presented with asymptomatic CSDH formation on CT one month after head trauma, and 14 cases (4.3%) presented with symptomatic CSDH progression more than one month after head trauma. The incidence of asymptomatic CSDH formation was significantly higher in patients with t-IA on initial CT than in patients without it (p < 0.0001, chi-square test). There was no significant difference in the incidence of symptomatic CSDH progression between 2 groups, as 7 of 136 cases (5.1%) in patients with t-IA and as 14 out of 322 cases (4.3%) in patients without it (p = 0.66, chi-square test) (Table 2).
Table 2.
Relationship between traumatic intracranial abnormality (t-IA) on initial CT and development of CSDH
| ASDH
(n = 86) |
t-IA other than ASDH
(n = 50) |
t-IA total
(n = 136) |
control
(n = 322) |
|
|---|---|---|---|---|
| CSDH formation at one month after trauma | 37 (43.0%) * | 13 (26.0%) | 50 (36.8%) | 41 (12.7%) |
| CSDH evolution at more than one month after trauma | 5 (5.8%) | 2 (4.0%) | 7 (5.1%) | 14 (4.3%) |
abbreviations used: ASDH = acute subdural hematoma, t-IA = traumatic intracranial abonormality, CSDH = chronic subdural hematoma, *p < 0.05 compared to control.
Development of CSDH in patients with/without anti-thrombotic drugs
In this study, 195 patients with pre-traumatic conditioning by ATD presented with ASDH in 39 cases (20.0%), t-IA other than ASDH in 21 cases (10.8%), and without t-IA 135 cases (69.2%). There were 263 patients without ATD who presented with ASDH in 47 cases (17.8%), t-IA other than ASDH in 29 cases (11.0%), and without t-IA in 187 cases (71.1%). The configuration of t-IAs was not statistically different between those with and without ATD.
In 195 patients with pre-traumatic conditioning by anti-thrombotic drugs, 34 (17.4%) showed asymptomatic CSDH formation on CT one month after head trauma. In 263 patients without pre-traumatic conditioning of anti-thrombotic drugs, 57 patients (21.7%) showed asymptomatic CSDH formation on CT at 1 month after head trauma. There was no significant difference in the incidence of CSDH formation between 2 groups at 1 month after mild head trauma (p = 0.36, chi-square test). The incidences of asymptomatic CSDH formation were not statistically examined among drugs since the number of cases was not large enough in each drug.
In 195 patients with pre-traumatic conditioning by anti-thrombotic drugs, seven patients (3.6%) showed symptomatic CSDH progression. In 263 patients without pre-traumatic conditioning by anti-thrombotic drugs, 14 (5.3%) showed symptomatic CSDH progression. There was no significant difference in the incidence of symptomatic CSDH progression between 2 groups I (p=0.40, chi-square test) (Table 3).
Table 3.
Relationship between pre-traumatic conditioning with antithrombotic drugs and development of CSDH
| pre-traumatic conditioning with antithrmobotic drugs
(n = 195) |
control
(n = 263) |
||
|---|---|---|---|
| t-IA on initial CT | |||
| ASDH | 39 (20.0%) | 47 (17.8%) | |
| t-IA other than ASDH | 21 (10.8%) | 29 (11.0%) | |
| no t-IA | 135 (69.2%) | 187 (71.1%) | |
| CSDH formation at one month after trauma | 34 (17.4%) | 57 (21.7%) | |
| CSDH evolution at more than one month after trauma | 7 (3.6%) | 14 (5.3%) | |
abbreviations used: t-IA = traumatic intracranial abnormalities, ASDH = acute subdural hematoma, CSDH = chronic subdural hematoma
Discussion
This study demonstrated that 29.7% of elderly patients who suffered mild head trauma presented with t-IAs, including 18.8% with ASDH, on the initial CT performed within 24 hours after head trauma. In Japan, any studies have not been investigated concerning the incidence of t-IA in patients with head trauma. However, it depends on the patient's age, the severity of the trauma, CT criteria, and the local socio-medical circumstance. Although acute CT criteria in patients with head trauma have been mentioned in the 3rd edition of the Japan Guidelines for the Management of Traumatic Brain Injury,21) it has been cited from guidelines of western countries.22) Since this is the first study to demonstrate the incidence of t-IA on initial CT after mild head trauma in Japan, the present results may have a certain value in providing useful local information concerning this issue. The incidence of t-IA on acute CT in patients with mild head trauma has ranged between 4.7% and 38.9%.23-25) A relatively high incidence of t-IA may be mainly explained by the aged subjects in this study, supporting the guideline that all elderly (≥65 y.o.) patients with mild head trauma should undergo acute CT.
One of the most important findings of the present study is that the incidence of CSDH formation occurred as 91 out of 458 cases (20.1%) in elderly patients with mild head trauma. CSDH is the most common neurosurgical disease, and the most frequent cause of it has been supposed to be mild head trauma. However, the incidence of CSDH was unknown in patients with mild head trauma because there was no prospective or retrospective cohort study. This is the first retrospective cohort study to reveal that the incidence of CSDH formation is 20.1% in patients with mild head trauma. In addition, the incidence of symptomatic CSDH progression is also revealed as 21 out of 458 cases (4.6%) in elderly patients with mild head trauma. These results may be quite useful in clinical practice, such as informing of CSDH risk to elderly patients with mild head trauma.
Relationship between ASDH and CSDH development
The possible transformation of ASDH into CSDH has been documented in previous case series studies,8,9) but not clarified in any studies of cohort fashion. This retrospective cohort study demonstrated that 37 out of 86 patients (43.0%) with ASDH transformed into asymptomatic CSDH formation, and five patients (5.8%) developed into symptomatic CSDH more than one month after head trauma. The incidence of CSDH formation one month after head trauma was significantly higher in patients with ASDH than without it. However, the incidence of symptomatic CSDH progression in patients with ASDH was not significantly different compared to those without ASDH more than one month after head trauma. These results suggest that the existence of ASDH itself is not necessary for developing CSDH. As Kristof et al.15) suggested, arachnoid tearing which allows CSF influx to the subdural space and subsequent mechanisms such as repetitive microbleeding from the neomembranes,6,26) inflammatory reactions,27-31) local hyperfibrinolysis,32,33) and osmotic pressure gradients28) may be necessary for the development to symptomatic CSDH. The transition of ASDH to the chronic stage might explain the higher incidence of CSDH formation in patients with ASDH than in those without it.
Formation and progression into symptomatic CSDH in patients with/without anti-thrombotic drugs
This study demonstrated that pre-traumatic conditioning with anti-thrombotic agents increase the incidence of neither CSDH formation at one month nor symptomatic CSDH progression at more than one month after head trauma. In this study, patients with pre-traumatic conditions with anti-thrombotic drugs received neither discontinuation nor counteraction of anti-thrombotic drugs. This suggests that neither discontinuation nor counteraction of anti-thrombotic drugs is unnecessary after mild head trauma in the clinical setting of the outpatient tertiary emergency medical facility from a CSDH development perspective.
However, antiplatelet or anticoagulant therapy are possible CSDH risk factors, mostly based on case series studies.18,34) Recently, it has been verified by case-control studies.2,5) These results contradict the present study's results since the incidence of symptomatic CSDH progression does not increase in patients with pre-traumatic conditioning with anti-thrombotic drugs. Several limitations of this study may explain this apparent contradiction. First, the configuration of the patients with mild head trauma in this study may not effectively cover the patient at risk of CSDH. As generally known, although the majority of patients with CSDH have a history of minor head trauma, they do not visit the hospital at the time of trauma. In addition, this study is conducted in a single institute, carrying a role mainly as a tertiary emergency and critical care center. Thus, only relatively severer patients were included despite minor head trauma in this study. Second, some risk factors for CSDH (alcohol intake, epilepsy, coagulopathy, etc.) are not considered in this study. It has been suggested that a history of trauma is less frequent in the elderly than in younger CSDH patients.16) Brain weight declines as age increases, which increases the volume of extracerebral space, resulting in an arachnoid tear in milder head trauma.16) Actually, the number of patients without a causative history of trauma is not negligible. Anti-thrombotic drugs may affect patients with less minor head trauma or with risk factors other than minor head trauma. The results of this study may be applied only in a certain clinical setting, such as minor head trauma patients who visit a tertiary emergency and critical care center.
Conflicts of Interest Disclosure
The authors report no conflict of interest for the study.
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