Discharging Anticoagulated Patients After Head Injury
In the four studies reviewed, the incidence of delayed ICH after normal CT scan ranged from 0.6% to 6%. However, if a diagnosed ICH has no effect on the patient's outcome or treatment, then it would be considered a surrogate outcome, which is often used as a substitute for a clinically meaningful end point that measures directly how a patient feels, functions, or survives. As such outcomes are often found to be clinically insignificant, their use has been questioned in the literature, and the incidence of patient important outcomes should be considered instead (Table 2). In these studies, the majority of patients found to have delayed ICH required no neurosurgical intervention and had no adverse outcome documented. The incidence of death or neurosurgical intervention ranged from 0 to 1.1%.
The authors of one of the articles suggest that "our data support the general effectiveness of the European Federation of Neurological Societies' recommendations for 24-hour observation followed by a repeated head CT scan for anticoagulated patients with a minor head injury". However, this conclusion is based on the incidence of delayed ICH (6%) rather than the incidence of clinically important outcomes (1.1%). In this study, only one patient out of 87 suffered clinically significant delayed ICH. It is mentioned in the study that one patient showed signs of neurologic deterioration, however, they do not say if this was the same patient who required neurosurgical intervention. If so, this would suggest that observation alone would suffice to detect any clinically significant delayed ICH.
Additionally, the authors do not perform a cost-effectiveness analysis to support their conclusion. In a subsequent editorial appearing in the same journal, it is suggested that a protocol of 24-h observation and routine repeat CT scanning would cost an average of just over $1 million per patient saved. The author of the editorial suggests that home observation and telephone call follow-up would be more cost-effective, and likely as safe, though this has not been studied.
One difficulty in studies of prognosis involves homogeneity. It would be unfair to say that all head injury patients on warfarin carry the same risk for delayed ICH. There are many risk factors that need to be considered, and a one-size-fits-all approach may not be warranted. A prior study on warfarin use in head trauma showed that the degree of anticoagulation was predictive of risk of ICH, rather than the use of warfarin alone, with an odds ratio of 2.59 in patients with an INR ≥ 2.0. Another retrospective study of 1493 patients admitted for traumatic brain injury with preinjury warfarin use showed that both the risk of ICH and mortality were increased with higher INR. Whether this association can be applied to the risk of delayed ICH remains to be shown, however, one of the articles reviewed here suggests an increased risk in patients with an INR ≥ 3 (relative risk = 14; 95% CI 4–49).
An additional prognostic factor to consider is concomitant antiplatelet therapy. The risk of major bleeding is known to increase for those on combined anticoagulant–antiplatelet therapy, with hazard ratios of 1.83 (95% CI 1.72–1.96) and 3.08 (95% CI 2.32–3.91) for combined warfarin–aspirin and warfarin–clopidogrel use, respectively, compared to warfarin therapy alone. It seems reasonable to assume that combined therapy would lead to increased rates of both initial and delayed ICH in head injury patients, and in one of the studies that identified 2 patients with delayed ICH, both were taking aspirin in addition to warfarin. Concomitant antiplatelet therapy in three of the studies ranged from 0 to 5.9%, and the fourth paper specifically excluded such patients. Studies in the US have demonstrated much higher rates of concomitant antiplatelet therapy in patients taking warfarin, ranging from 19.4% to 38.5%.
It is important to recognize the populations to whom the evidence applies. The current studies were predominantly (>80%) geriatric patients who had suffered a standing-level fall. These were not young adults who were the victims of violence or motor vehicle accidents, so the evidence should not be applied to younger populations. Elderly adults are not a homogenous population. Numerous occult geriatric syndromes exist that differentiate biological age from physiological age, most of which are unrecognized in today's ED. Geriatric syndromes include frailty, dementia, delirium, falls, functional status, and social isolation. As with any predictor variable, if one cannot measure a phenomenon, then one cannot study or understand that phenomenon. In anticoagulated head injury patients, the decision to obtain a repeat CT scan or observe for a prolonged period of time incorporates clinicians' gestalt for many of these geriatric syndromes, and future elderly patient head injury research will need to adjust prognostic models for these confounding variables.
Although the current literature does not support routine hospital observation for 24 h or repeat cranial CT scans in all anticoagulated patients with head injury, this may be warranted in those at increased risk of delayed bleeding, such as those with supratherapeutic INR levels or concomitant antiplatelet therapy. Further studies are needed to identify these higher-risk patients for delayed bleeding to determine appropriate management. Furthermore, as a result of the inherent difficulties in warfarin administration, including the need for strict dietary compliance and routine INR monitoring, attempts have been made to find alternative anticoagulants. As newer agents enter the market and begin to replace warfarin, such as the anti-Xa agents dabigatran and rivaroxaban, further studies on the risk of delayed hemorrhage may be necessary to determine the best management strategy for patients on these medications.
Conclusion
In the four studies reviewed, the incidence of delayed ICH after normal CT scan ranged from 0.6% to 6%. However, if a diagnosed ICH has no effect on the patient's outcome or treatment, then it would be considered a surrogate outcome, which is often used as a substitute for a clinically meaningful end point that measures directly how a patient feels, functions, or survives. As such outcomes are often found to be clinically insignificant, their use has been questioned in the literature, and the incidence of patient important outcomes should be considered instead (Table 2). In these studies, the majority of patients found to have delayed ICH required no neurosurgical intervention and had no adverse outcome documented. The incidence of death or neurosurgical intervention ranged from 0 to 1.1%.
The authors of one of the articles suggest that "our data support the general effectiveness of the European Federation of Neurological Societies' recommendations for 24-hour observation followed by a repeated head CT scan for anticoagulated patients with a minor head injury". However, this conclusion is based on the incidence of delayed ICH (6%) rather than the incidence of clinically important outcomes (1.1%). In this study, only one patient out of 87 suffered clinically significant delayed ICH. It is mentioned in the study that one patient showed signs of neurologic deterioration, however, they do not say if this was the same patient who required neurosurgical intervention. If so, this would suggest that observation alone would suffice to detect any clinically significant delayed ICH.
Additionally, the authors do not perform a cost-effectiveness analysis to support their conclusion. In a subsequent editorial appearing in the same journal, it is suggested that a protocol of 24-h observation and routine repeat CT scanning would cost an average of just over $1 million per patient saved. The author of the editorial suggests that home observation and telephone call follow-up would be more cost-effective, and likely as safe, though this has not been studied.
One difficulty in studies of prognosis involves homogeneity. It would be unfair to say that all head injury patients on warfarin carry the same risk for delayed ICH. There are many risk factors that need to be considered, and a one-size-fits-all approach may not be warranted. A prior study on warfarin use in head trauma showed that the degree of anticoagulation was predictive of risk of ICH, rather than the use of warfarin alone, with an odds ratio of 2.59 in patients with an INR ≥ 2.0. Another retrospective study of 1493 patients admitted for traumatic brain injury with preinjury warfarin use showed that both the risk of ICH and mortality were increased with higher INR. Whether this association can be applied to the risk of delayed ICH remains to be shown, however, one of the articles reviewed here suggests an increased risk in patients with an INR ≥ 3 (relative risk = 14; 95% CI 4–49).
An additional prognostic factor to consider is concomitant antiplatelet therapy. The risk of major bleeding is known to increase for those on combined anticoagulant–antiplatelet therapy, with hazard ratios of 1.83 (95% CI 1.72–1.96) and 3.08 (95% CI 2.32–3.91) for combined warfarin–aspirin and warfarin–clopidogrel use, respectively, compared to warfarin therapy alone. It seems reasonable to assume that combined therapy would lead to increased rates of both initial and delayed ICH in head injury patients, and in one of the studies that identified 2 patients with delayed ICH, both were taking aspirin in addition to warfarin. Concomitant antiplatelet therapy in three of the studies ranged from 0 to 5.9%, and the fourth paper specifically excluded such patients. Studies in the US have demonstrated much higher rates of concomitant antiplatelet therapy in patients taking warfarin, ranging from 19.4% to 38.5%.
It is important to recognize the populations to whom the evidence applies. The current studies were predominantly (>80%) geriatric patients who had suffered a standing-level fall. These were not young adults who were the victims of violence or motor vehicle accidents, so the evidence should not be applied to younger populations. Elderly adults are not a homogenous population. Numerous occult geriatric syndromes exist that differentiate biological age from physiological age, most of which are unrecognized in today's ED. Geriatric syndromes include frailty, dementia, delirium, falls, functional status, and social isolation. As with any predictor variable, if one cannot measure a phenomenon, then one cannot study or understand that phenomenon. In anticoagulated head injury patients, the decision to obtain a repeat CT scan or observe for a prolonged period of time incorporates clinicians' gestalt for many of these geriatric syndromes, and future elderly patient head injury research will need to adjust prognostic models for these confounding variables.
Although the current literature does not support routine hospital observation for 24 h or repeat cranial CT scans in all anticoagulated patients with head injury, this may be warranted in those at increased risk of delayed bleeding, such as those with supratherapeutic INR levels or concomitant antiplatelet therapy. Further studies are needed to identify these higher-risk patients for delayed bleeding to determine appropriate management. Furthermore, as a result of the inherent difficulties in warfarin administration, including the need for strict dietary compliance and routine INR monitoring, attempts have been made to find alternative anticoagulants. As newer agents enter the market and begin to replace warfarin, such as the anti-Xa agents dabigatran and rivaroxaban, further studies on the risk of delayed hemorrhage may be necessary to determine the best management strategy for patients on these medications.
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