This study investigated the outcomes of head trauma patients that were taking antithrombotic drugs. The results showed that the patients that were taking antithrombotic drugs had poor outcomes despite exhibiting lower frequencies of ICH and extracranial injuries than the patients that were not taking antithrombotic drugs. This suggests that antithrombotic drugs can cause poor outcomes even in cases of lower-energy trauma. A previous retrospective cohort study suggested that antiplatelet therapy could be a risk factor for hematoma enlargement and poor outcomes after mild head trauma4. Among the patients using antiplatelet drugs, the risk of hematoma enlargement was two-fold higher and the risk of a poor outcome was 50% higher (relative risk: 1.58, 95%CI: 1.28-1.95). Anticoagulant drug use was also reported to be related to poor outcomes5. The adjusted OR for 30-day mortality of VKA users was 8.3 (95%CI: 2.0-34.8).
In this study, being aged ≥70, the absence of antiplatelet drug treatment, and the intracranial hematoma enlargement occurring within 72 hours were identified as predictors of poor outcomes in the patients being treated with antithrombotic drugs. Subanalyses revealed that hematoma enlargement was related to anticoagulant drug use, but not antiplatelet drug use. Some studies of spontaneous ICH have shown that hematoma enlargement was associated with poor outcomes6-13. In addition, it was also reported that in cases of ICH hematoma volume was related to anticoagulant drug use, but was not related to antiplatelet drug use14. A retrospective study of head trauma also revealed that that VKA use alone, but not antiplatelet drug use alone or direct oral anticoagulant use, was a significant predictor of the progression of ICH compared with non-use of these drugs (OR: 5.30, 95%CI: 2.48-11.31)15. Therefore, head trauma patients that are taking anticoagulant drugs, especially VKA, could have a poor prognosis.
Almost all cases of hematoma enlargement occurred within 24 hours of the initial injury, regardless of whether the patients were using antithrombotic drugs. A retrospective review of 419 spontaneous ICH reported that hematoma enlargement often occurred within 6 hours of onset10. In a retrospective review of spontaneous ICH, two thirds of cases of hematoma enlargement occurred within 24 hours of onset16. Moreover, a case study of mild head trauma reported that 87% of cases of delayed neurological deterioration occurred within 24 hours17. On the other hand, achieving hemostasis takes longer than normal in patients taking antithrombotic drugs 18. In a prospective cohort study of ICH patients that were taking VKA, 3 of 7 patients exhibited hematoma enlargement within 24 hours19. The time from the injury to hemostasis being achieved could not be examined in this study, but close follow-up, involving neurological examinations and CT, for at least within 24 hours are considered important for ensuring that treatment is timed appropriately.
The appropriate use of reversal agents seems to be important for preventing the expansion of hematomas and improving outcomes. Two randomized controlled trials of 4F-PCC vs. vitamin K or plasma for cases of spontaneous ICH involving patients that were taking VKA showed that 4F-PCC had a superior ability to rapidly reduce the international normalized ratio20, 21. In addition, 4F-PCC reduced the frequencies of hematoma enlargement and hematoma-related early death22. As the number of patients treated with reversal agents has increased, however, the frequency of thromboembolic events has also risen. In this study, ischemic strokes occurred in 2 of the 9 cases in which 4F-PCC was used. One of these patients suffered a cerebral infarction within 24 hours. In a previous case report, an ischemic stroke occurred on the day after warfarin reversal with 4F-PCC for surgery23. To prevent thromboembolic events, the early resumption of antithrombotic drug treatment is necessary. In a retrospective study of chronic subdural hematomas, the early resumption of antithrombotic drug treatment was recommended because many thromboembolic events occurred within one month of drug withdrawal24. In a meta-analysis of spontaneous ICH, the resumption of anticoagulant treatment between days 10 and 39 after onset produced good results2. In the present study, there were 2 cases of rebleeding after antithrombotic drug therapy was restarted within 2 days of admission. Therefore, the early resumption of antithrombotic drug treatment is considered beneficial when hemostasis has been confirmed on CT after more than 48 hours.
Limitations of This Study
This study was retrospective, and hence, background factor variability was its greatest limitation. Low-energy trauma is probably more common among patients taking antithrombotic drugs, which may explain why no correlation was detected between antithrombotic drug use and hematoma enlargement. A prospective cohort study is needed to provide more accurate data about the outcomes of head trauma among patients taking antithrombotic drugs.
In conclusion, patients that are taking antithrombotic drugs are at high risk of a poor prognosis after head trauma, even after low-energy head trauma. Among such patients, the prognosis of those that exhibit acute hematoma enlargement is poor, and active hemostasis, such as using neutralizers, is important. In order to prevent thromboembolic events, the active resumption of antithrombotic drugs is desirable in cases in which hemostasis has been confirmed after more than 48 hours.