Original Article

Subdural Hematoma and Oral Anticoagulation:

A Therapeutic Dilemma from the Neurosurgical
Point of View
M. Javad Mirzayan1 Karoline Calvelli1 Hans-Holger Capelle1 Jessica Weigand1 Joachim K. Krauss1

1 Department of Neurosurgery, Medical University Hannover, Address for correspondence M. Javad Mirzayan, MD, Department of
Hannover, Germany Neurosurgery, Medical School Hannover, Carl-Neuberg-Str. 1,
Hannover 30625, Germany (e-mail: mirzayan@hotmail.com).
J Neurol Surg A

Abstract Background Oral anticoagulation is a common prophylactic therapy for several

diseases with a high thromboembolic risk. Such medication harbors a possible hemor-
rhage risk, with a special risk for subdural hematoma (SDH). The safety and efficacy of

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resumption of oral anticoagulation versus long-term discontinuation has not been fully
clarified in patients who experienced SDH while under treatment with oral
anticoagulation.
Material and Methods We investigated the outcome of 49 patients who were
identified retrospectively to have a SDH while receiving oral anticoagulation.
Results Most bleeding occurred while patients were within the recommended
therapeutic window for oral anticoagulation. Mortality was 15%. The event-free survival
probability was higher in the group of patients with reinstitution of phenprocoumon
therapy than in the group without. Over a median follow-up of 32 months, thrombo-
embolic events occurred in 4 of 23 patients without oral anticoagulation versus in none
Keywords of 15 patients with phenprocoumon; hemorrhagic complications occurred in 1 in 23
► oral anticoagulation versus 3 in 15 patients.
► phenprocoumon Conclusions Reinstitution of oral anticoagulation with phenprocoumon after previous
► subdural hematoma SDH appears to have an acceptable risk for hemorrhagic complications. Decision making
► thrombosis might consider case-by-case differences. To establish specific guidelines, prospective
► warfarin large cohort studies are needed.

Introduction anticoagulant treatment ranges between 23% and 58%.6,7

Currently,
300,000 to 500,000 patients in Germany are
being treated with oral anticoagulation because of various
internal diseases.1 This treatment is applied to avoid throm-
boembolic events with the acceptance of the increased risk of
hemorrhage.
Intracranial hemorrhage constitutes a severe and fre-
quently life-threatening side effect of oral anticoagulant
treatment.2 The risk for hemorrhage is increased by the factor
8 to 11 and ranges between 0.1% and 0.9% yearly.3–5 The 6-
month mortality rate of intracranial hemorrhage after oral
Subdural hematoma (SDH) accounts for 35 to 50% of all
intracranial hemorrhages under oral anticoagulant treat-
ment.3,8 The risk to develop a subdural hematoma is 42.5
times higher under oral anticoagulation.9
From a neurosurgical point of view, there is concern about
recurrent hemorrhage following the resumption of oral anti-
coagulant treatment in those patients who experienced SDH
during anticoagulation therapy.
Based on a retrospective analysis of 49 patients, we
investigated whether there is an increased risk of recurrent
hemorrhage when anticoagulant treatment is restarted or if

received © Georg Thieme Verlag KG DOI http://dx.doi.org/

December 2, 2014 Stuttgart · New York 10.1055/s-0035-1558407.
accepted after revision ISSN 2193-6315.
March 31, 2015
Subdural Hematoma and Oral Anticoagulation Mirzayan et al.
the risk of an ischemic event at withdrawal of phenprocou-
mon therapy outweighs that risk.
Material and Methods
Forty-nine patients were identified retrospectively to have
experienced an SDH while under oral anticoagulant treat-
ment and were referred to the Department of Neurosurgery
of Medical School Hannover within a 9-year period
(1995–2003).
There were 21 women (43%) and 28 men (57%). In 22
patients SDH was located on the left side, in 19 on the right
side, and in 8 bilaterally. Average age was 71 years (range:
55–87; median: 71) at the occurrence of SDH. Nineteen SDHs
were classified as acute, 5 as subacute, and 25 as chronic. Nine
of the patients with a chronic SDH suffered a secondary acute
hemorrhage.
Indications for oral anticoagulation were atrial fibrillation
(n ¼ 19), valvular transplant (n ¼ 12), deep vein thrombosis
(n ¼ 9), vascular bypass (n ¼ 4), aneurysm of the heart cavity
(n ¼ 1), stroke (n ¼ 1), pulmonary embolism (n ¼ 1), dilative
cardiomyopathy (n ¼ 1), and cardiac insufficiency (n ¼ 1).
Patients were under phenprocoumon therapy for an average
of 7 years (range: 1–13 years). Other disorders implicating
additional possible risk factors for a hemorrhagic complica-
tion were arterial hypertension in 31 patients, diabetes
mellitus in 4, alcohol abuse in 6, and pathologic thrombocyte
function in 1, respectively. In 28 cases, a history of trauma was
reported prior to the occurrence of SDH. Twenty-one of those
cases were classified as having suffered from mild to moder-
ate head injury. A history of severe cranial trauma was evident
in seven patients. In addition to medical treatment for
correction of impaired coagulation, 39 patients underwent
a neurosurgical operation. Twenty-nine of them had a burr
hole craniotomy, and 10 had a craniotomy with subsequent
drainage of the SDH. Ten patients received medical treatment
(PPSB, vitamin K) without surgery.
In the postacute phase, patients were referred to rehabili-
tation departments. No specific instructions for reinstitution
of oral anticoagulation were given at that time.
For evaluation of outcome following initial treatment, data
were analyzed from admission protocols, surgical reports,
discharge letters, medical records of the rehabilitation clinics
and a follow-up questionnaire sent to the general physicians
and to the patients.
The chi-square test was used to compare the two groups.
Kaplan-Meier test was applied to investigate the survival of
the patients. Log-rank test was used for investigation of the
survival distribution of the two groups.
Primary outcome was defined as occurrence of a hemor-
rhagic or ischemic event. Secondary outcome was defined as
survival time.
Results
The Quick test was obtained prior to correction of impaired
hemostasis in 48 patients. In 30 patients therapeutic values
ranged between 15 and 45, eight patients had a value > 45,
Journal of Neurological Surgery—Part A
and 10 patients had a value < 15. Thus most SDHs (n ¼ 30)
occurred in patients within an optimal therapeutic window.
Seven patients died during the early phase. In all of them
fatal outcome was attributed directly to SDH itself with
secondary herniation. The initial Glasgow Coma Scale (GCS)
score of these patients varied between 3 and 15. Although
two of them had a GCS score of 15, in five patients it was  8.
The median Quick value in these patients was 29 (range: 8–
74). Occurrence of the SDH was spontaneous in 21 patients
and after trauma in 28 patients. The distribution within the
two study groups did not differ significantly.
Follow-up data were available for 38 of the remaining 42
patients. The average follow-up period was 39 months (range:
1 month to 10.5 years; median: 32 months). Twenty-three
patients did not resume oral anticoagulant treatment with
phenprocoumon later on. Treatment proceeded with heparin
(n ¼ 11), acetylsalicylic acid (ASA) (n ¼ 5), heparin plus ASA
(n ¼ 1), or none of them (n ¼ 6). Heparin administration was
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low-dose antithrombotic prophylaxis except in one patient
who had full heparinization. The reason for full heparin-
ization was that the patient had a mechanical heart valve.
Four patients without oral anticoagulation developed
thromboembolic complications. One patient had a cerebello-
pontine stroke 75 days after having sustained SDH. After
1 year, one patient each had a pulmonary embolism and
deep vein thrombosis. One other patient had a thrombosis
of the greater saphenous vein 16 months later. These compli-
cations occurred at a mean of 12.5 months (range: 2.5–16
months) after discontinuation of oral anticoagulation. The
patient with therapeutic heparinization had an intracerebral
hemorrhage 4 days later. The difference in the distribution of
thromboembolic versus hemorrhagic complications was not
significant.
In 15 patients phenprocoumon was reinstalled for oral
anticoagulant treatment. Three of those patients had hemor-
rhagic complications. One patient experienced epistaxis. In
two patients SDH reoccurred, in one ipsilateral and in one
contralateral to the initial side. Recurrent SDH was observed
without any trauma and at Quick values within the desired
therapeutic window. Oral anticoagulation had been restarted
after an average of 124 days (range: 35–263 days). None of the
patients within this group had an ischemic complication
(►Table 1).
There was no significant difference between the two
groups (resumption or withdrawal of oral anticoagulation)
in terms of comorbidity profile. Risk factors like cardiovascu-
lar diseases were comparable.
The Kaplan-Meier analysis and the log-rank test revealed
that the event-free survival probability was higher in the
group with reinstitution of phenprocoumon therapy than in
the group without (p ¼ 0.02). Overall, more ischemic com-
plications occurred in the group without resumed phenpro-
coumon therapy and hemorrhagic complications were less
frequent.
Comparing the hemorrhagic and ischemic events between
the two groups yielded no significant difference. The better
survival within the group with resumption of oral antico-
agulation was significant (p ¼ 0.02) (►Fig. 1). Using the chi-
 Subdural Hematoma and Oral Anticoagulation
Table 1 Summary of the study
Total no. of patients
No. of patients who died initially
No. of patients who survived initially
No. of patients available for follow-up
Discontinuation of oral anticoagulation
Resumption of oral anticoagulation
square test no significant difference between the two groups
was evident regarding the distribution of traumatic SDH,
bleeding risk factors, and comorbidity.
Discussion
Soon after its inception, hemorrhage during dicumarol ther-
apy was described as a side effect.10 More recent studies
reported bleeding complications in 3 to 5% of all patients
taking oral anticoagulation. Often these complications are
clinically irrelevant, but in
0.3 to 0.6% per year, intracranial
bleedings with a mortality between 70% and 80% were
noted.11,12 It should also be considered how the nature of
the surgery and perioperative anticoagulation may affect
hemostasis and outcome.13,14
Subdural Hematoma and the Quick/International
Normalized Ratio Value
It is important to note that in our study SDHs occurred also
when international normalized ratio (INR) values were with-
in the therapeutic window. Although this might indicate a
relatively higher risk of oral anticoagulation therapy within
Fig. 1 Survival curves of the two study groups (blue: without oral
anticoagulation; green: with oral anticoagulation).
Mirzayan et al.
49
7
42
38
23 (4 thromboembolic events
and 1 hemorrhagic event)
15 (3 hemorrhagic events)
the therapeutic range, it should also be considered that the
INR value measured at admission differs from the INR value
when SDH had occurred.15 In our study, the initial INR value
was below the therapeutic range in only 13 patients (27%)
upon admission. Similar distributions were reported previ-
ously.8,16–18 In an earlier study, 33% of patients with SDH
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while under treatment with phenprocoumon had an INR
value below the therapeutic range, as compared with only 5%
of patients without SDH.19 Treatment of these patients starts
with emergency reversal of the INR.20
Mortality from Subdural Hematoma under Oral
Anticoagulation and Risk Factors
Moskopp et al reported that 80% of patients with coma
following intracranial hematoma under oral anticoagulation
died during the initial period.21 Another study described a
mortality rate of 45.5% at 6 months following traumatic SDH
with preexisting oral anticoagulation.22 The clinical status of
these patients must be considered when compared with our
results. We observed a lower mortality rate in our population,
that is, 15% (7 of 49). Two of them had a Glasgow Coma Scale
(GCS) score of 15, and five of them a GCS < 8. Brain atrophy,
tearing of bridging veins, and weakness of venous walls in
elderly patients favor the development of SDH.23,24 Higher
age appears to be a risk factor per se. A mean age  70 years
was found earlier.25–27 Gait disturbance with increased risk
for falls is an additional risk factor in this population. Thus
mild head injury might cause SDH even at therapeutic INR
levels.11,28 Notably, a history of mild or moderate head injury
was evident in 42% of our patients prior to the development
of SDH.
The slightly higher proportion of men in our study is in
agreement with data published previously.19 The difference
in gender might be explained by the relatively higher risk for
men to develop cardiovascular diseases, which are the most
common indications for oral anticoagulation.29
Outcome after Discontinuation or Resumption of Oral
Anticoagulation
According to the European Society of Cardiologists and the
European Stroke Initiative, it has been recommended to
withhold all oral anticoagulation therapy for 7 to 14 days
after oral anticoagulation–related intracranial hemorrhage,
even in high-risk cases with mechanic heart valves.30–33
Notably, also in our study population there was no early
thromboembolic complication after stopping the oral
Journal of Neurological Surgery—Part A
Subdural Hematoma and Oral Anticoagulation Mirzayan et al.
anticoagulation for 7 to 14 days. Restarting phenprocoumon
therapy within 3 days was only established in single high-risk
patients.
The consensus guidelines for warfarin therapy from the
Australasian Society of Thrombosis and Hemostasis recom-
mend a review of the need for warfarin after bleeding and a
closer monitoring of the INR.18 It remains unclear when to
reinstall oral anticoagulation therapy after SDH.34 A system-
atic review of the literature on the management of oral
anticoagulation therapy after cerebral hemorrhage in pa-
tients with mechanical heart valves indicated that restarting
oral anticoagulation therapy after cerebral hemorrhage is
relatively safe. However, published evidence is rather
poor.35 Mainly observational cohort studies and case reports
are available.36 Warfarin therapy does not need to be with-
held for > 3 days after burr hole drainage, particularly in
patients with a high thromboembolic risk.37 Early resump-
tion of anticoagulant therapy (within 3 days) did not cause
intracranial rebleeding in patients undergoing surgery for
intracranial hematoma associated with anticoagulant thera-
py.38 Anticoagulant therapy does not seem to influence the
rate of chronic SDH recurrence.39 Although resumption of oral
anticoagulation in our population was not that brisk, only 2 of
the 15 patients experienced a recurrent SDH.
It is often unclear who will finally decide in an individual
patient to restart anticoagulation therapy. Overall, it appears
that neurosurgeons tend to be more hesitant to do so than
internists and cardiologists.40,41 The decision to restart oral
anticoagulation therapy should balance the risk of a second
hemorrhage and the risk of a thromboembolic event. Both
Broderick et al and Appelboam et al recommend distinguish-
ing between low-risk cases (e.g., past history of deep vein
thrombosis or pulmonary embolism), in which the risk of
suffering a repeated hemorrhage might outweigh the benefit
of repeated anticoagulation, and high-risk cases (e.g., pros-
thetic heart valves and chronic atrial fibrillation with prior
ischemic events) in which resumption of oral anticoagulation
is unavoidable.42,43
Although our study has limitations such as its retrospec-
tive nature and the nonsystemic decision making to resume
anticoagulant therapy, it clearly shows that overall the risk of
withholding oral anticoagulation might be higher than the
risk for hemorrhagic complications after restarting it. Sur-
vival can be further improved by better adjustment of
hypertension, discontinuation of smoking, and alcohol
abuse.44 In a subset of patients with atrial fibrillation, left
atrial appendage closure has become an alternative to
chronic anticoagulation.45,46
Considering the demographical changes in a continuously
aging society, the impact of the subject under study becomes
increasingly relevant. Prospective multicenter studies includ-
ing stratifying larger numbers of patients in different risk
groups are needed and might be able to formulate valid
guidelines.
Twenty-three patients in our study did not received oral
anticoagulation; however, most of them had heparin and/or
ASA. This group is heterogeneous, and this in fact could
potentially affect the analysis and interpretation of data.
Journal of Neurological Surgery—Part A
Because the number of patients in our study is relatively
low and because of the nonsystematic approach to resum-
ing anticoagulation therapy, the results do not justify any
definitive conclusions. Another limitation of the study is
that final follow-up evaluation was performed only by
questionnaire but not by clinical examination and without
neuroimaging.
Although this study is far away from providing guidelines,
it seems helpful to serve as an orientation. We would like to
stress the multidisciplinary approach in these patients that
result in individualized recommendation for every single
patient.41 Future studies also need to investigate newer
anticoagulant drugs. After reassessment of the indication
for oral anticoagulation, categorizations like “absolute” or
“relative” would help identify patients who would benefit
from the resumption versus withdrawal.
Conclusion
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Reinstitution of oral anticoagulation with phenprocoumon
after previous SDH appears to have an acceptable risk for
hemorrhagic complications. To develop specific guidelines,
prospective large cohort studies are needed.
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Journal of Neurological Surgery—Part A