DÄ internationalArchive12/2022Chronic Subdural Hematoma

Review article

Chronic Subdural Hematoma

Antithrombotics and thrombotic complications

Dtsch Arztebl Int 2022; 119: 208-13. DOI: 10.3238/arztebl.m2022.0144

Hamou, H A; Clusmann, H; Schulz, J B; Wiesmann, M; Altiok, E; Höllig, A

Background: Chronic subdural hematoma (cSDH) is typically a disease that affects the elderly. Neurosurgical evacuation is generally indicated for hematomas that are wider than the thickness of the skull. The available guidelines do not address the common clinical issue of the proper management of antithrombotic drugs that the patient has been taking up to the time of diagnosis of the cSDH. Whether antithrombotic treatment should be stopped or continued depends on whether the concern about spontaneous or postoperative intracranial bleeding, and a presumably higher rate of progression or recurrence, with continued medication outweighs the concern about a possibly higher rate of thrombotic complications if it is stopped.

Methods: In this article, we review publications from January 2015 to October 2020 addressing the issue of the management of antithrombotics in patients with cSDH that were retrieved by a selective search in the Pubmed and EMBASE databases, and we present the findings of a cohort study of 395 patients who underwent surgery for cSDH consecutively between October 2014 and December 2019.

Results: The findings published in the literature are difficult to summarize concisely because of the heterogeneity of study designs. Among the seven studies in which a group of patients on antithrombotics was compared with a control group, four revealed significant differences with respect to the risk of thromboembolic complications depending on previous antithrombotic use and the duration of discontinuation, while three others did not. In our own cohort, discontinuation of antithrombotics (including both plasmatic and antiplatelet drugs) was associated with thrombotic complications in 9.1% of patients.

Conclusion: These findings imply that the management of antithrombotics should be dealt with critically on an individual basis. In patients with cSDH who are at elevated risk, an early restart of antithrombotic treatment or even an operation under continued antithrombotic therapy should be considered.

LNSLNS

Chronic subdural hematoma (cSDH) is a spontaneous or post-traumatic serous fluid collection containing blood that is located between the dura mater and arachnoid and develops over a period of three or more weeks.

cSDH is most common in the elderly. Its incidence seems to be rising as the population ages (1), but it varies (1.72 to 20.6 per 100 000 persons/year [2, 3]) as a function of multiple factors, including sex (male predominance) and age distribution. For example, a Finnish study (1) revealed a marked effect of age on incidence (1), with an increase from 18.2/100 000 in the seventh decade to 52.1/100 000 in the eighth, 130.3/100 000 in the ninth, and 125/100 000 in persons aged 90 and older (study period: 2011–2015). The rising use of antithrombotics also seems to favor the development of cSDH (4, 5); according to a case-control study, both anticoagulants and platelet inhibitors increase the risk of cSDH (6). There is often a history of minimal head trauma, but this alone does not explain the chronic, progressive accumulation of fluid in the subdural space (7). Angiogenic stimuli may promote the generation of fragile vessels, which in turn give rise to microhemorrhages that make the hematoma larger (7). Inflammation also seems to play a role in the pathophysiology of cSDH (3, 7, 8).

Symptoms and diagnostic evaluation

Because it enlarges slowly, the hematoma is often well tolerated at first, with mild symptoms or none. Yet experience shows that cSDH is only rarely an incidental finding. Patients often present with nonspecific symptoms such as headache, unsteady gait, or cognitive impairment (9). There may also be focal neurological deficits such as hemiparesis or aphasia (9). Along with normal pressure hydrocephalus, cSDH is considered one of the few treatable causes of dementia (10). A clinical challenge of cSDH is to suspect the diagnosis and order the appropriate imaging studies of the head on the basis of nonspecific symptoms alone. cSDH is reliably demonstrated by non-contrast computed tomography (CT, the most common study) and by magnetic resonance imaging (MRI) (11, 12) (Figure 1, eFigure 1).

An 89-year-old woman who fell at home.
Figure 1
An 89-year-old woman who fell at home.
An 83-year-old woman was found lying on the floor with a right hemiparesis. There was no history of trauma in the weeks prior to the event.
eFigure 1
An 83-year-old woman was found lying on the floor with a right hemiparesis. There was no history of trauma in the weeks prior to the event.

Treatment and problems of antithrombotics

An asymptomatic, incidentally discovered hematoma that is no thicker than the width of the skull can usually be observed at first, but cSDH that is symptomatic when diagnosed usually requires surgical treatment (3, 12). Operative techniques range from bedside puncture procedures to extended burr hole trephination with or without the insertion of a drain (3, 12). cSDH is usually of liquid consistency and thus easily treated through a small operative approach, yet it tends to recur, with reported recurrence rates ranging from 10% to 20% (3). Embolization of the middle meningeal artery is a newer treatment option that can be performed in addition to, or instead of, evacuation of the hematoma; initial data on this method are promising, but the published case numbers are low (13). Although cSDH carries a better prognosis than other types of intracranial bleeding, patients with cSDH suffer a higher mortality for up to one year after diagnosis than persons in an age-adjusted cohort (14, 15, 16). For example, the average survival time in a group of patients with cSDH whose average age was 80.6 years (range, 65–89) was 4.4 years, while the expected average survival time among persons of that age is 6 years (hazard ratio: 1.94) (16).

The optimal management of antithrombotic medication remains an unresolved issue (12): medications are often discontinued for fear of acute bleeding and an increased risk of recurrence. There is still no generally accepted scheme for managing antithrombotic drugs in patients with cSDH, who often suffer from multiple comorbidities; uncertainty arises from the trade-off of opposing risks (thrombotic complications versus cSDH recurrence or acute bleeding into a cSDH) (12,17). In particular, there are hardly any robust data on the management of the direct oral anticoagulant (DOAC) drugs that have been introduced from 2010 onward. Thus, the question of antithrombotic medication in patients with cSDH still needs to be scientifically addressed.

Literature review

A selective search for relevant publications (January 1, 2015, to October 1, 2020) was carried out in the PubMed and EMBASE databases (for details, see eMethods, eFigure 2). The aim was to identify clinical studies (randomized controlled trials, cohort studies, case-control studies, and case reports with >10 patients) of patients with cSDH focusing on the management of antithrombotic medication, specifically including documentation of thromboembolic events during follow-up. The time period mentioned was chosen to be as up-to-date as possible in order to reflect current issues, including the use of DOACs. All DOACs that are now available were approved by the European Medicines Agency by 2015 (most recently edoxaban, in 2015). The primary endpoint was defined as the number of thromboembolic complications depending on the management of antithrombotics. Because of heterogeneity in the management of antithrombotic drugs across studies, no quantitative analysis was possible. The literature search was registered in the PROSPERO database (CRD42021215982) and carried out as specified in the PRISMA statement (18).

Flow chart of the literature review. 11 publications were included in the analysis. TC, thrombotic complications.
eFigure 2
Flow chart of the literature review. 11 publications were included in the analysis. TC, thrombotic complications.

Literature analysis

A total of 856 abstracts (search on January 18, 2021: EMBASE: 692; PubMed: 164) that were published in the specified time period were examined. In 49 of these articles, antithrombotic medication and/or thrombotic complications were mentioned in the abstract; the full text of these 49 articles was analyzed, and 11 articles (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29) ultimately met the predefined inclusion criteria (eFigure 2).

The average number of patients per study was 448 (range, 150–817), and three studies with 140, 198, and 211 patients were restricted to patients taking antithrombotic drugs (24, 25, 27). All studies showed the well-known male predominance of 62–75%. The duration of follow-up ranged from 36 days to six months. All studies included surgically treated patients. Overall, the percentage of patients taking antithrombotic drugs (excluding data from the three studies [24, 25, 27] that were restricted to such patients) was 39.4 ± 17.3% (1636 patients on antithrombotics out of a total of 3824).

The management of antithrombotic drugs was highly heterogeneous. These drugs were temporarily discontinued in all studies (exception: only a few patients taking acetylsalicylic acid [ASA]), and they were restarted after a widely varying interval ranging from 2 to 90 days. When antithrombotic medication was restarted early, pausing the drug for an interval of 3 to 10 days was recommended (19, 20, 21, 23, 24). Early restarting of antithrombotic drugs was not associated with complications. Surgery under ASA was also associated with a low risk profile (25). Longer interruptions of anticoagulation (30 days postoperatively) have also been advocated (27).

The overall rate of thrombotic events was 81 in 3824 cases (2.1% in all studies combined; range, 0–3.3%). The three studies that included only patients on antithrombotics (24, 25, 27) were excluded from this analysis as well. A total of 34 thrombotic events were detected in 549 patients, corresponding to a cumulative risk of 6.2%; the management of antithrombotics varied widely across studies.

An association between the occurrence of thrombotic events and the discontinuation of antithrombotic medication was significant in five studies and insignificant in six. After the analysis was restricted to studies comparing patients on antithrombotics to a control group, there were four studies that found significant differences in the risk of thrombotic complications depending on prior antithrombotic drug use or the duration of discontinuation (20, 22, 26, 28), and three that did not find any such significant differences (19, 23, 29). In one study, the number of thrombotic complications was zero (n = 178); thus, no increased risk was found in this study from temporarily discontinuing antithrombotics, although the study involved only 40 patients on antithrombotics (21). Prior use of antithrombotics was not found to increase the risk of recurrent cSDH in five studies (20, 21, 22, 23, 26); in one study, prior anticoagulation (but not antiplatelet agents) (29) was associated with an increased recurrence rate, as was antithrombotic therapy with multiple drugs in another study (19).

In two studies of ASA use (24, 25), the duration of interruption of ASA had no effect on the rate of thromboembolic complications. An early restart of ASA was not associated with a higher cSDH recurrence rate. The case numbers were low in these two studies (140 and 198 patients, respectively), particularly in view of the study of more than one treatment regimens (short versus long ASA interruption). In another study that included only patients on antithrombotics (n = 211) (27), longer pauses in antithrombotic medication were indeed associated with increases in thromboembolic complications. Moreover, in this study, the risk of recurrence was increased here if antithrombotic medication was restarted earlier than 30 days after surgery.

It should be pointed out that these studies were heterogeneous with respect to methodology, antithrombotic drugs (some studies dealt only with ASA monotherapy), only monotherapies with ASA were investigated), anticoagulant management (a pause after surgery of anywhere from 0 to 90 days’ duration), and methods of data analysis.

Adding up the case numbers of the six studies with data on anticoagulated as well as non-anticoagulated patients (19, 20, 21, 23, 26, 29), we find a 3.7% rate of thromboembolic complications in the former (33 of 883 patients) versus a 1.1% rate in the latter (18 of 1578 patients). This observed increased risk of thrombotic complications among patients on antithrombotics was statistically significant (Chi-square; p = 0.000014; odds ratio: 3.36; 95% confidence interval: [1,88; 6,01]), though the interpretability of this finding, derived from a simple addition of case numbers, is limited by the heterogeneity of the underlying studies. The findings of the individual studies are summarized in eTable 4. The authors of 9 of these 11 studies recommended restarting antithrombotic medication as early as possible (Box, Table, Figure 2).

Clinical data
Box
Clinical data
The temporal course of thrombotic complications (TC) as a function of the use of antithrombotic drugs (AT).
Figure 2
The temporal course of thrombotic complications (TC) as a function of the use of antithrombotic drugs (AT).
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without thromboembolic complications (TC)
Table
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without thromboembolic complications (TC)
Markwalder classification (<a class=e2)" width="250" src="https://cfcdn.aerzteblatt.de/bilder/144057-250-0" data-bigsrc="https://cfcdn.aerzteblatt.de/bilder/144057-1400-0" data-fullurl="https://cfcdn.aerzteblatt.de/bilder/2022/07/img268616862.gif" />
eTable 1
Markwalder classification (e2)
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without antithrombotic medication (AT)
eTable 2
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without antithrombotic medication (AT)
Analysis of predictors in the multivariable model: statistical significance, odds ratios, and 95% confidence intervals
eTable 3
Analysis of predictors in the multivariable model: statistical significance, odds ratios, and 95% confidence intervals
Overview of studies
eTable 4
Overview of studies

Evaluation and perspectives

Chronic subdural hematoma is a common disease with relevance in everyday life. Its incidence has risen in recent years, possibly because multimorbidity has become more common, along with the rising use of antithrombotic drugs and the increased availability of neuroimaging (1). Most patients have a positive past medical history. There are not yet any guidelines for the optimal management of anticoagulation. Current data suggest that interrupting antithrombotic medication for longer times leads to a clinically significant rise in thrombotic events (9.1% among our own patients who were taking anticoagulants preoperatively), and that the early restarting of antithrombotics (depending on the indication) most likely does not lead to additional complications (literature review). The management of antithrombotics in cSDH patients must therefore be reevaluated, as current knowledge suggests that the early restarting of antithrombotic medication ought to be considered.

For a subset of these patients, especially those with an absolute medical indication for antithrombotic therapy with multiple drugs, embolization of the middle meningeal artery (MMA) may be a therapeutic alternative (30,31).

The high rate of thrombotic events in our own cohort is most likely attributable to our restrictive use of antithrombotic drugs, with temporary discontinuation as our internal hospital standard. These drugs were managed more liberally, with a shorter interruption of antithrombotic medication, in the studies that were included in our literature review.

A large study based on the Medicare database (32) confirmed the clinical importance of cSDH and of the management of antithrombotic drugs in patients with this disease. Out of 1.7 million cases analyzed, there were 2939 with an atraumatic subdural hematoma. The affected patients were more likely to have pre-existing illnesses than the age-matched population without subdural hematoma, and they had a significantly increased risk of arterial ischemic complications (hazard ratio [HR]: 3.6; [1.9; 5.5]), and stroke in particular (HR: 4.2; [2.1; 7.3]), in the first 4 weeks after treatment for SDH, but not at later times. Subgroup analysis revealed a higher risk of arterial ischemic events among patients who had an indication for antithrombotic treatment, and the authors inferred that this may have been caused by intentional interruption of antithrombotic therapy for four weeks (in analogy to the American Heart Association recommendations for intracerebral hemorrhage [33]). In Germany, there are not yet any specific guidelines for antithrombotic management in patients with cSDH. AWMF guidelines on intracerebral hemorrhage are now in preparation.

Among the studies we analyzed, the one with the largest number of cases (a subsidiary analysis of patients included in a randomized controlled trial; n = 817 [26]), displayed a problem that was also prominent in the literature analysis as a whole: the management of anticoagulation in patients with chronic subdural hematoma is highly heterogeneous. It is based not only on individual, patient-specific factors, but also by historical circumstances (“local hospital tradition”).

In a systematic literature review and meta-analysis concerning anticoagulation in chronic subdural hematoma dating from 2014, only three studies were found suitable for inclusion, with a total of 64 patients (34). The authors concluded that there was little empirical evidence to support any particular mode of managing antithrombotics. A recent paper on the resumption of antithrombotic therapy after surgery for cSDH, summarizing data from eight primary publications, revealed no difference in the rate of hemorrhagic complications after the restarting vs. continued pausing of antithrombotic drugs (35); patients whose anticoagulants were restarted had significantly fewer thromboembolic complications (2.9% vs. 6.8%, p < 0.001).

A survey revealed uncertainty among physicians about whether they should restart anticoagulant drugs; widely varying approaches were found, with different estimations of the risk of thromboembolic complications on the one hand, and hemorrhagic complications on the other (36). The interpretation of the findings reported in this review is limited by the fact that all antithrombotic drugs were grouped together, and that thrombotic complications were defined to include as both arterial and venous vaso-occlusive events. For more detailed analyses, studies with higher case numbers will be needed. Any conclusions drawn from this literature review are tentative in view of the heterogeneity of the underlying studies in their methods and in the questions asked.

Overview

The incidence of chronic subdural hematoma is rising, in parallel with the demographic trend. There are, as yet, no guidelines for the use of antithrombotics in the treatment of this disease.

Conclusion

The data presented here tend to support the early restarting of antithrombotic drugs after the surgical treatment of cSDH, or even, in some cases, treatment under uninterrupted antithrombotic therapy in patients at particular risk. This represents a paradigm shift in the management of cSDH for quite a few patients. Early restarting of antithrombotic drugs seems to carry little risk, particularly as concerns recurrent cSDH. Continuing antiplatelet therapy with ASA is justifiable in view of the available data.

Conflict of interest statement
Prof. Clusmann is a member of the extended board of directors of the German Society of Neurosurgery (Deutsche Gesellschaft für Neurochirurgie) and the Professional Association of German Neurosurgeons (Berufsverband Deutscher Neurochirurgen), the executive director and spokesman of the Neurosurgical Academy, a member of the scientific advisory board of the German Medical Association, and a member of the editorial board of this journal (Deutsches Ärzteblatt).

PD Altiok has received lecturing fees and course honoraria from Bayer, Daiichi Sankyo, Novartis, and Servier, and reimbursement of travel expenses from Pfizer/Bristol-Myers Squibb and Bayer.

The remaining authors state that they have no conflict of interest.

Manuscript received on 30 June 2021; revised version accepted on 7 February 2022.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
PD Dr. med. Anke Höllig
Klinik für Neurochirurgie, Universitätsklinik RWTH Aachen
Pauwelsstr. 30, 52074 Aachen, Germany
ahoellig@ukaachen.de

Cite this as:
Hamou HA, Clusmann H, Schulz JB, Wiesmann M, Altiok E, Höllig A: Chronic subdural hematoma—antithrombotics and thrombotic complications.
Dtsch Arztebl Int 2022; 119: 208–13. DOI: 10.3238/arztebl.m2022.0144

Supplementary material

eReferences, eMethods, eTables, eFigures:
www.aerzteblatt-international.de/m2022.0144

cme plus

This article has been certified by the North Rhine Academy for Continuing Medical Education. Participation in the CME certification program is possible only over the internet at cme.aerztebatt.de. The deadline for submission is 24 March 2023.

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Department of Neurosurgery, University Hospital RWTH Aachen: Dr. med. Hussam A. Hamou, Prof. Dr. med. Hans Clusmann, PD Dr. med. Anke Höllig
Department of Neurology, University Hospital RWTH Aachen: Prof. Dr. med. Jörg B. Schulz
JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen: Prof. Dr. med. Jörg B. Schulz
Department of Diagnostic and Interventional Neuroradiology, University Hospital RWTH Aachen:
Prof. Dr. med. Martin Wiesmann
Department of Cardiology, Angiology and Intensive Care Medicine (Department of Internal Medicine I), University Hospital RWTH Aachen: PD Dr. med. Ertunc Altiok
Clinical data
Box
Clinical data
An 89-year-old woman who fell at home.
Figure 1
An 89-year-old woman who fell at home.
The temporal course of thrombotic complications (TC) as a function of the use of antithrombotic drugs (AT).
Figure 2
The temporal course of thrombotic complications (TC) as a function of the use of antithrombotic drugs (AT).
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without thromboembolic complications (TC)
Table
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without thromboembolic complications (TC)
An 83-year-old woman was found lying on the floor with a right hemiparesis. There was no history of trauma in the weeks prior to the event.
eFigure 1
An 83-year-old woman was found lying on the floor with a right hemiparesis. There was no history of trauma in the weeks prior to the event.
Flow chart of the literature review. 11 publications were included in the analysis. TC, thrombotic complications.
eFigure 2
Flow chart of the literature review. 11 publications were included in the analysis. TC, thrombotic complications.
Markwalder classification (e2)
eTable 1
Markwalder classification (e2)
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without antithrombotic medication (AT)
eTable 2
Distribution of variables (stated as total numbers and percentages, with means and standard deviations) for the overall patient collective, with and without antithrombotic medication (AT)
Analysis of predictors in the multivariable model: statistical significance, odds ratios, and 95% confidence intervals
eTable 3
Analysis of predictors in the multivariable model: statistical significance, odds ratios, and 95% confidence intervals
Overview of studies
eTable 4
Overview of studies
1.Rauhala M, Helén P, Huhtala H, et al.: Chronic subdural hematoma—incidence, complications, and financial impact. Acta Neurochir (Wien) 2020; 162: 2033–43 CrossRef MEDLINE PubMed Central
2.Yang W, Huang J: Chronic subdural hematoma: epidemiology and natural history. Neurosurg Clin N Am 2017; 28: 205–10 CrossRef MEDLINE
3.Feghali J, Yang W, Huang J: Updates in chronic subdural hematoma: epidemiology, etiology, pathogenesis, treatment, and outcome. World Neurosurg 2020; 141: 339–45 CrossRef MEDLINE
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