The Relationship of LEWIS M. WIENER, M.D.

Subdural Hematoma to AND

MORTON NATHANSON, M.D.

NEW YORK

Anticoagulant Therapy

At the present time, hypoprothrombinemia autopsy was found to have a subdural

induced by anticoagulant drugs is the most hematoma in addition to extensive bleeding
commonly encountered coagulation defect in in other parts of the body. Nathanson,
medical practice.1 The extensive use of anti- Cravioto, and Cohen11 in 1958 discussed
coagulants in the treatment of thromboem- the development of subdural hematomas in
bolic and cardiovascular disorders has been 3 patients receiving anticoagulant therapy.
accompanied by reports of neurological com- Wells and Urrea12 found subdural hema-
plications including subarachnoid bleeding, tomas in 5 patients out of a group of 23
intracerebral hemorrhage, intraspinal hemor- who developed cerebral dysfunction while
rhage, and subdural hematoma.2-9 Although being treated with anticoagulants. Eisen-
subdural hematoma has been reported least berg,13 Pan, Rogers, and Pearlman,14 and
frequently, this study suggests that it occurs Barron and Fergusson 9 have also reported
more often in relation to anticoagulant this complication in isolated cases. Since
therapy than has been realized. As early as effective treatment for subdural hematomas
1944, Shleven and Lederer10 presented a can be expected, awareness of its occurrence
patient with uncontrollable hemorrhage after in patients receiving anticoagulant drugs,
therapy with bishydroxycoumarin who at and the need to establish an early diagnosis
Received for publication Aug. 21, 1961. are of importance. The incidence of sub¬
U.S. Public Health Service Trainee (Grant No. dural hematomas in patients receiving anti¬
478) (Dr. Wiener). Present address: Department coagulant drugs is difficult to determine;
of Neurology, Jefferson Medical College, Phila-
delphia.
however, the incidence of prior anticoagulant
From the Department of Neurology, The Mount therapy
in patients with proven subdural
Sinai Hospital, New York, and the Section of collections can be readily assessed. An in¬
Neurology, Division of Medicine, Long Island vestigation of all subdural hematomas en¬
Jewish Hospital, New Hyde Park, N.Y. countered at The Mount Sinai Hospital

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 during the past 5 years revealed that 12%
the patients had received
Material
During the 5-year period from Jan. 1, 1956, to
Dec. 31, 1960, there were 50 patients with verified
subdural hematomas in The Mount Sinai Hospital.
The diagnosis was established by angiography,
surgery, or autopsy. Six patients of this series
(12%) had been on anticoagulant therapy at least
during the month preceding hospitalization. Five
other patients had various noninduced coagulation
disorders associated with severe liver disease,
leukemia, and thrombocytopenia, with an over-all
incidence of coagulation defects in patients with
subdural hematomas of 22%. A seventh patient
with subdural hematoma, who had been on anti¬
a After 2 weeks of treatment, he had a transient
coagulant therapy, was recently encountered at
the Long Island Jewish Hospital.
of Cases
Report
Case 1.—In December, 1958, this 67-year-old
man had an acute myocardial infarction and was
placed on anticoagulant therapy with bishydroxy-
coumarin. Five months later he developed a severe
persistent left frontal headache, and anticoagulant
therapy was discontinued. Over the ensuing week
he became increasingly drowsy and confused and
could be aroused only with difficulty. On ad¬
mission he was found to be drowsy, and he showed
a marked memory deficit. Bilateral Babinski signs
were elicited. The blood pressure was 135/80 mm.
Hg. Skull x-rays showed a pineal displacement
from left to right. The spinal fluid was pink
with supernatant xanthochromia. The prothrombin
time was 13 seconds (normal, 12.5 seconds). Left
carotid angiography demonstrated a subdural collec¬
tion in the temporoparietal region, and a liquid
hematoma was evacuated. The patient had a slow,
but eventually complete, postoperative recovery.
No history of trauma was elicited.
Case 2.—In early 1957, a 74-year-old woman
with a background of coronary artery disease and
recurrent pulmonary emboli was started on anti¬
coagulant therapy. Despite adequate medication,
she had an additional pulmonary infarcì, and in
October, 1958, suddenly developed a right hemi-
paresis and hemisensory defect with aphasia. She
recovered completely and was continued on therapy
with bishydroxycoumarin. In February, 1959, she
developed persistent headache, became somnolent,
confused, and incontinent of urine and feces. There
was no history of head trauma. On admission
she was found to be lethargic and confused; a
left Babinski sign was elicited. The prothrombin
time was 15 seconds (normal, 11 seconds). The
spinal fluid was xanthochromic. On the second
hospital day she developed a left homonymous
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of hemianopsia and a left hemisensory deficit for
anticoagulants. auditory, visual, and somatosensory stimuli. Carotid
angiography revealed bilateral subdural collections
which were promptly evacuated. She improved
slowly, and at the time of her discharge from
the hospital in March, 1959, had residual language
dysfunction and a minimal left brachial paresis.
Case 3.—A 72-year-old man was placed on anti¬
coagulant therapy with warfarin sodium after an
acute myocardial infarction. Two months later he
developed ecchymoses, hematemesis, and continuous
bifrontal headache. He was given vitamin
oxide, and the prothrombin time on the following
day was 28 seconds (normal, 12 seconds). Anti¬
coagulants were discontinued for one week, during
which the headaches lessened and the ecchymoses
faded. Anticoagulant therapy was then resumed.
episode of difficulty in speaking associated with
numbness of the right upper extremity. Thereafter,
he developed progressive difficulty in verbal ex¬
pression and was hospitalized one month later.
Examination revealed disorientation, dysnomia,
right hemiparesis, and right hemisensory defect.
At times there was a suggestion of a left homon¬
ymous field defect. The spinal fluid was
xanthochromic. The prothrombin time was 22.5
seconds (normal, 12 seconds), bleeding time, 5
minutes, and clotting time, 9 minutes. Carotid
angiography disclosed bilateral subdural collections.
At the time of angiography, the patient began
to show distinct improvement, and it was decided
to defer surgery and to observe the patient further.
Within 10 days the weakness, disorientation, and
language dysfunction disappeared. A history
review at this time failed to reveal any back¬
ground of head trauma. Left carotid angiography
one month later showed disappearance of the sub¬
dural collections. When last seen, 6 months after
his discharge from the hospital, he was free of
neurologic symptoms and signs.
Case 4.—In May, 1960, an 80-year-old man
developed a partial heart block while hospitalized
for congestive heart failure, hypertension, and
pulmonary edema. He was treated with warfarin
sodium, and after one month of anticoagulant
therapy developed persistent frontal headaches
and difficulty in walking. During this period, pro¬
thrombin times of 43 and 39 seconds were re¬
corded. His gait was found to be broad-based,
and there were decreased power and tone in the
lower limbs. Spinal fluid examination disclosed
no abnormalities. The electroencephalogram was
abnormal, with shifting anterior temporal -burst
activity. He subsequently complained of dizziness
and fear of falling in addition to headaches.
Several days later, he fell while getting out of
bed, striking his head but sustaining no loss of
consciousness. Nine hours later he was comatose;
his blood pressure was 215/100 mm. Hg, compared
 with 130/80 mm. Hg. on the previous day. A Case 6.—This patient has already been dis¬
repeat spinal fluid examination was normal. The cussed by Nathanson, Cravioto, and Cohenn in a
prothrombin time was 18 seconds (normal, 11 previous article on the relationship of anticoagulant
seconds). Angiography revealed a left subdural therapy to subdural hematomas. Because she was
collection, and a subdural hematoma consisting hospitalized during the period under study, a
of fresh blood clots evacuated. The hematoma
was brief summary of her illness will be included.
was approximately 1 inch thick and extended over A 71-year-old woman developed phlebitis of the
most of the superolateral surface of the cerebrum. left thigh and was treated with bishydroxycou-
He remained comatose and died 24 hours later. marin, 50 mg. daily. Prothrombin times were
Postmortem examination did not disclose an determined at irregular intervals; the last de¬
intracerebral hematoma, and there had been no termination, one month prior to hospitalization,
recurrence of the subdural bleeding. was said to be "within the usual range." Five
Case 5.—The patient was a 64-year-old man weeks after the onset of treatment she developed
who had received intermittent anticoagulant ther¬ progressively severe headache and drowsiness, but
apy, first because of a myoeardial infarction and continued to take her medication. On the day of
later because of an undiagnosed cerebral disorder hospitalization, the prothrombin time was 71 sec¬
characterized by left-sided sensory seizures and onds (normal, 13 seconds). She was stuporous,
gradual development of left facial weakness, left and a left hemiparesis was evident. Bilateral sub¬
hyperreflexia, and mental deterioration. Previous dural collections of brownish watery fluid were
pneumoencephalography had shown dilatation of evacuated. She improved during the first post¬
the lateral ventricles, and carotid angiography operative day, but then became comatose. A repeat
was normal.May, 1960, he fell on several
In craniotomy did not disclose a residual subdural
occasions, presumably as the result of "orthostatic hematoma. She died on the second postoperative
hypotension," and on June 1, I960, he sustained day. No residual clot or intracerebral hematoma
an injury to the left side of his head. Several was found at autopsy.
hours later he vomited and lapsed into a transient In addition to the 6 patients hospitalized at the
stupor. In addition to his altered state of conscious¬ Mount Sinai Hospital during the period of this
ness, an abrasion of the left temple and a left study, another patient was seen in consultation
hemiparesis were found on admission. The pro¬ by one of us (M.N.) at the Long Island Jewish
thrombin time was 19 seconds (normal, 12 seconds). Hospital.
The spinal fluid was xanthochromic. A right Case 7.—A 61-year-old man was started on
carotid angiogram revealed a subdural collection, anticoagulant therapy in July, 1960, following an
and a large chronic subdural hematoma with well- acute myocardial infarction. At the end of Novem¬
formed membranes was evacuated. The patient ber, 1960, he developed persistent headache and
never regained consciousness, and he died on the after 2 weeks discontinued the anticoagulant medi¬
14th poetoperative day. Postmortem examination cation; however, the headache continued, and on
showed no evidence of subdural bleeding, but did Jan. 19, 1961, he was hospitalized. In addition
reveal several old and recent hemorrhagic infarcts to severe persistent headaches, he showed moderate
in the right fusiform and superior parietal gyri. bradyphrenia and periods of mild disorientation.
An area of encephalomalacia also1 was encountered The spinal fluid was found to> be xanthochromic.
in the midbrain. A right carotid angiogram revealed a subdural

^ 70 iRP
CO The prothrombin
Q
times determined by
g 60
the
were
Quick one-stage
Lü method. Normal control
CO 50
values, 11-13.5 seconds.
Case 3 (DS) and Case 4
40 (VP) on whom detailed
records were available
30 had fluctuating prothrom¬
m
bin levels, which on oc¬
I 20
casions exceeded optimum
therapeutic anticoagula-
tion. Case 6 (RP) was
IO V the only patient with
_ _L J_ _L J_ _I_ _L » _ _L
known excessive hypopro-
39 34 30 26 22 18 14 IO 6 2 0 2 4 thrombinemia.
DAYS PRIOR TO DIAGNOSIS

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 collection that proved to be a chronic subdural
hematoma at operation. The patient recovered
completely. No history of head trauma was
elicited.
Comment
Prothrombin Level.—In all patients an
effort was made to determine the prothrom¬
bin level during the month prior to the
diagnosis of the subdural hematoma; how¬
ever, this was possible in only 2 patients
(Figure). Prothrombin times were available
for the others only during the period of
hospitalization. In neither of the 2 patients
on whom detailed records were available
(Cases 3 and 4) was the prothrombin time
excessively elevated, although in one (Case
4), prothrombin times of 43 and 39 seconds
were obtained during the week prior to the
diagnosis of the subdural hematoma. Three
other patients (Cases 1, 2, and 5), on whom
detailed records were not available, had only
moderately elevated or normal prothrombin
times when admitted to the hospital. One
patient (Case 6) was hospitalized and found
to have a prothrombin time of 71 seconds.
The last patient (Case 7) had received no
anticoagulant drugs for approximately one hospitalization.
month ; however, his symptoms had begun
2 weeks prior to discontinuation of anti¬ entire group of 50 patients was 63.4 years,
coagulant therapy.
with anticoagulant drugs. While the exact
role of trauma in the production of subdural
hematomas is not fully understood, it would
probably be incorrect to imply that the sub¬
dural hematomas occurred spontaneously. As
previously suggested by Nathanson, Cravi-
oto, and Cohen,11 "minor trauma to the head,
quickly forgotten by the patient, may very
well initiate oozing of blood that continues
uncontrolled" under therapeutic anticoagula-
tion. One patient (Case 4) became comatose
9 hours after a head injury which was not
associated with loss of consciousness. Al¬
though a fresh subdural hematoma was
completely evacuated, the patient died, and at
autopsy the brain appeared normal. This
rapid development of coma in the absence
of an intracerebral hematoma or cerebral
laceration suggests that hypoprothrombi¬
nemia was a contributing factor. Another
patient (Case 5) was known to have sus¬
tained head trauma on the day of admission
to the hospital ; however, at operation a
chronic subdural hematoma was found. It
should be noted that this patient had fallen
several times during the weeks preceding
Clinical Course.—The mean age of the
while the mean age of the patients who* had t

While excessive hypoprothrombinemia received anticoagulant therapy was 71.3

may increase the likelihood of hemorrhage years. This may reflect the greater use of
anywhere in the body, it does not seem to anticoagulants in older age groups. There
be a necessary prerequisite for the develop¬ was no significant difference between the
ment of a subdural hematoma ; the usual clinical pictures of those patients with sub¬
levels of therapeutic anticoagulation will dural hematomas who had received antico¬
suffice. It may be that what appears to be agulant therapy and those who* had not.
a "safe" prothrombin time for some pa¬ Treatment.—Six patients who had re¬
tients actually reflects a dangerous state of ceived anticoagulant drugs were treated
potential hemorrhage. It has been pointed surgically, while 1 patient (Case 3) im¬
out by Quick,16 Alexander,1 and others that proved so rapidly that surgical intervention
there is no single test which defines the was deferred, and it later became unneces¬
coagulability of blood or measures all of the sary, since subsequent angiography showed
various effects exerted by coumarin com¬ resolution of the subdural collection. The
pounds and similar drugs on stable factor, nonsurgical management of certain patients
plasma thromboplastin, and other factors with angiographically demonstrated subdural
necessary for the prevention of bleeding. collections has recently been reported by
Trauma.—No history of trauma was Bender.15 At operation, well-defined sub¬
elicited in 18 of the 50 patients in the series, dural membranes were found in 6 patients,
including 4 of the 6 who had been treated while in 1 patient there was little or no

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 neomembrane formation. The composition Lewis M. Wiener, M.D., Department of Neurol¬
of the subdural collection varied from fresh ogy» Jefferson Medical College, Philadelphia, Pa.
blood clots to watery fluid containing blood
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