456 Case report

A surgical case of cerebral hemorrhage in a patient with
factor XI deficiency
Yukihiro Gotoa, Ichita Taniyamab, Toshihiko Ebisua and Katsuyoshi Mineurab
A 63-year-old man suddenly presented with right
hemiplegia and was taken to our hospital. Computed
tomography (CT) scan revealed subcortical hemorrhage of
the left parietal lobe. He had no medical history except
hypertension; thus, it initially appeared to be a typical
hypertensive hemorrhage. However, blood analysis showed
an abnormally elevated activated partial thromboplastin
time. One hour after admission, his Glasgow Coma Scale
fell from 14 to 11. We performed an echo-guided stereotaxic
removal of the hematoma. He improved immediately and
was diagnosed with congenital factor XI (FXI) deficiency a
few days after surgery. FXI deficiency, described as
hemophilic syndrome C, rarely manifests as spontaneous
bleeding, but surgical intervention has been known to
manifest as bleeding. This case highlights the importance of
evaluation of coagulopathies in patients with intracerebral
hemorrhage before surgery, and, in cases wherein blood

Introduction
Factor XI (FXI) deficiency, described as hemophilic
syndrome C or plasma thromboplastin antecedent
deficiency, represents 7% of all hereditary coagulation
factor deficiencies [1]. This deficit has been reported in
many racial groups, but occurs predominantly in the
Ashkenazi Jewish population [2]. In factor VIII and IX
deficiency (hemophilia A and B), bleeding tendency is
related to its plasmatic level, and requires awareness of
the potential for spontaneous bleeding [3]. Compared
with these deficiencies, FXI deficiency rarely manifests
as spontaneous bleeding. In general, patients with FXI
deficiency are known to have unpredictable bleeding
tendencies after surgery [1,2]. To date, only seven
hemorrhagic cases related to the central neural system
have been reported in FXI deficiency [4–10]. Herein, we
report a case of cerebral hemorrhage in a FXI deficiency
patient who was first diagnosed after surgery.

Case presentation
A 63-year-old right-handed man presented with right
hemiplegia for the past hour after falling asleep and was
admitted to our emergency ward. He exhibited slight
chronic hypertension, but did not undergo medical
treatment. The Glasgow Coma Scale (GCS) upon arrival
was 14. Neurologic examination revealed restlessness and
sensory aphasia in addition to right hemiplegia. Brain
computed tomography (CT) scan showed a subcortical
hemorrhage of the left parietal lobe (Fig. 1). CT angiography showed no obvious vascular abnormalities. Routine
0957-5235 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

analysis results suggest coexisting coagulation disorders,
less invasive surgical methods would likely lead to good
outcomes. Blood Coagul Fibrinolysis 23:456–458 ß 2012
Wolters Kluwer Health | Lippincott Williams & Wilkins.

Blood Coagulation and Fibrinolysis 2012, 23:456–458
Keywords: cerebral hemorrhage, factor XI deficiency, surgery
a

Department of Neurosurgery, Nantan General Hospital, Nantan-city and
Department of Neurosurgery, Kyoto Prefectural University Graduate School of
Medicine, Kamigyo-ku, Kyoto, Japan

b

Correspondence to Yukihiro Goto, MD, Department of Neurosurgery, Nantan
General Hospital, Yagicho-Yagiueno 25, Nantan-city, Kyoto 629-0197, Japan
Tel: +81 771 42 2510; fax: +81 771 42 2096;
e-mail: yoursongmysong@hotmail.com
Received 13 December 2011 Revised 17 February 2012
Accepted 13 March 2012

blood analysis conducted just after admission indicated a
prolonged activated partial thromboplastin time (APTT)
of 101 s (normal range 25–40 s) and a normal prothrombin
time (PT) of 104% (normal range 70–140%). A repeat
blood analysis indicated the same findings. He and his
family had not previously been diagnosed as having
hereditary coagulation factor deficiencies, and we believed
he had an acquired coagulation disorder, such as circulating
anticoagulants, including antiphospholipid syndrome.
After infusion of fresh-frozen plasma (FFP), his APTT
improved to 47 s, but 1 h after admission, his neurological
examination was impaired and the GSC fell to 11. We
performed echo-guided stereotactic removal of hematoma
and silicone tube insertion, focusing on less traumatic
methods of clot evacuation. After the surgery, the clinical
status recovered immediately. In order to drain the
residual hematoma, we injected urokinase, 12 000 U in
2 ml saline, into the hematoma cavity and reopened the
space 8 h after the administration. The plasmatic FXI level
at admission was reported to us after surgery. The level was
at 3 U/dl (i.e., 3%, normal range 75–145%) and the patient
was diagnosed as having congenital FXI deficiency.
During the postoperative period, we intermittently
applied FFP infusion for 2 weeks. After the infusion of
FFP was ceased, his APTT score reverted to around 100 s,
but no rebleeding or new bleeding was observed (Fig. 1).
His aphasia and right hemiplegia improved by degrees
and he was discharged from our hospital 6 weeks
after admission. Six months after the onset, his modified
Rankin Scale grade increased to 1.
DOI:10.1097/MBC.0b013e328353a5e3

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Case of cerebral hemorrhage with factor XI deficiency Goto et al. 457

Fig. 1

Upper panel: CT images on admission demonstrated subcortical hemorrhage in the left parietal region. Lower panel: CT images obtained 6 weeks
after stereotaxic evacuation of hematoma and drainage insertion.

Discussion
FXI deficiency was first described as hemophilic syndrome C or plasma thromboplastin antecedent deficiency
by Rosenthal et al. in 1953 [11]. This deficit occurs
predominantly in the Ashkenazi Jewish population, but
has been reported in many other racial groups [1,2]. The
inheritance of this deficiency is autosomal, affecting men
and women equally. In this case, the patient and his
daughter were both diagnosed as having FXI deficiency
after his admission.
In factor VIII and IX deficiency, a certain proportion of
patients suffer spontaneous bleeding [3]. It depends to
their plasmatic level, and severe deficiency requires
replacement therapy. The incidence of intracerebral
hemorrhage in factor VIII and IX deficiency ranges from
2.2 to 7.8% [3]. In comparison, FXI deficiency rarely
manifests as spontaneous bleeding. The deficiency is
usually asymptomatic with a mild-to-moderate bleeding
tendency in few patients [1,2].
Patients with FXI deficiency are known to have an
unpredictable tendency to bleed after surgery. This
tendency is not fully understood and is not directly

related to its plasmatic level [1,2]. In this case, coagulation tests were performed, and revealed a decrease of
FXI coagulant activity of 3 U/dl. Severe FXI deficiency is
defined as levels less than 15–20 U/dl, and individuals
with severe deficiency have a high likelihood to develop
postoperative hemorrhage [2]. Patients with FXI levels of
65–80 U/dl are classified as having partial or mild
deficiency, and exhibit variable severity that does not
necessarily correlate with the plasma FXI coagulant
activity [1,2]. Studies have confirmed that 20–50% of
patients with partial deficiency experience excessive
bleeding after surgery [1].
An optimal therapeutic strategy when one suffers from
unanticipated bleeding is the administration of human
FXI concentrate (HFC) [7]. However, infusion of HFC
should be approached with caution, because fatal thrombosis events have been reported in some cases. Siao et al.
[7] reported the administration of HCF under strict
monitoring to maintain the target concentration, which
required a multidisciplinary approach. Furthermore, in
some countries, including Japan, FXI concentrate is not
commercially available or licensed for use. When FXI

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458 Blood Coagulation and Fibrinolysis 2012, Vol 23 No 5

concentrate is not available, the next best choice is FFP.
Its advantage is that their use is familiar, but has a greater
risk of virus infection compared with HFC and because
the plasma half-life of FXI is approximately 80 h [1],
considerable volume infusions are needed to maintain
the FXI level for struggling patients. Fibrin glue or
tranexamic acid has also been reported to be useful in
preventing postoperative bleeding.
The cause of intracerebral hemorrhage (ICH) is generally
classified as primary or secondary. Primary ICH, due to
spontaneous rupture of damaged small vessels or amyloid
angiopathy, accounts for 78–88% of all cases [3].
Secondary ICH, associated with vascular anomalies,
tumors, or impaired coagulation, occurs only in a minority
of patients. In this case, high blood pressure was evident
upon admission. As FXI deficiency is an uncommon
cause of ICH, hypertension would be the primary etiological factor. It is not certain whether deficit of FXI
coagulant activity together with the occurrence of a
cerebral hemorrhage leads to a potential increase in
hemorrhagic stroke or possible extension of the hematoma. However, increase in hemorrhage or bleeding
during surgery or the postoperative period could lead
to an extremely terrible neurological outcome. Therefore, at least replacement therapy should be done and in
cases in which a surgical procedure is necessary, a less
invasive method should be selected.
The management of ICH remains controversial [12]. A
surgical approach should be considered for a lobar clot
within 1 cm of the surface to prevent any progressive
neurologic deficit [13]. The three generally accepted
surgical options are conventional craniotomy, stereotactic
evacuation of the hematoma, which can be performed
under local anesthesia, and more recently, endoscopic
methods. To avoid disruption of the surrounding brain
and on the assumption that there could be a coagulation
disorder, we focused on less traumatic methods. We
carried out echo-guided stereotactic removal of the
hematoma and silicone tube insertion to allow us to inject
urokinase. This led to a good outcome, but it was unclear
whether this was the best, the mildest, and the most
effective operative method. Generally in cases of spontaneous ICH, Kim reported that stereotactic evacuation
of hematoma and drainage insertion is a simple, well
tolerated, and brief procedure with a very low rebleeding
rate, but that endoscopic methods and drainage insertion
also provided a similar outcome [14].
This case highlights the importance of evaluation of
coagulopathies in this patient who appeared to exhibit
a typical hypertensive hemorrhage. Seven hemorrhagic
cases have been reported related to the central neural
system in FXI deficiency and most cases, except one,
were diagnosed after admission. Among these seven
cases, there were two cases of subarachnoid hemorrhage
(SAH) [7,8], two cases of spinal hemorrhage [6,10], and

one case of cerebellar hemorrhage [4] who underwent
surgical treatment. Both SAHs were due to ruptured
aneurysm; one was treated using the clipping method
and another the coiling method, which reportedly led to a
second episode of SAH due to aneurysmal revascularization and rupture. Cerebellar hemorrhage requires drainage due to obstruction of the fourth ventricle and both
spinal hemorrhages require laminectomy. Among seven
cases, five cases had a good prognosis. On the contrary,
two cases had a poor prognosis. This is the first reported
case of a FXI deficiency patient who underwent evacuation of hematoma for ICH. When one encounters an ICH
patient whose blood analysis suggests a coexisting coagulation disorder, it is useful to take minor coagulation
disorders into consideration and in cases of hematoma
evacuation, the stereotaxic method and drainage insertion should be considered as one of the good procedures.

Acknowledgements
Conflicts of interest

There are no conflicts of interest.

References
1
2

3

4

5
6

7

8
9

10

11

12

13

14

Bolton-Magga PH. Factor XI deficiency and its management. Haemophilia
2000; 6:100–109.
Keeling D, Tait C, Makris M. Guideline on the selection and use of
therapeutic products to treat haemophilia and other hereditary bleeding
disorders. A United Kingdom Haemophilia Center Doctors Organisation
(UKHCDO) guideline approved by the British Committee for Standards in
Haematology. Haemophilia 2008; 14:671–684.
Quinones-Hinojosa A, Gulati M, Singh V, Lawton MT. Spontaneous
intracerebtral hemorrhage due to coagulation disorders. Neurosurg Focus
2003; 15:E3.
Brichant S, Vokaer M, Beukinga I, De San N, Blecic SA, Kentos A, et al.
Cerebellar hemorrhage due to factor XI deficiency. Cerebrovasc Dis 2005;
19:138–139.
Khealani B, Farhat Z, Mozaffar T. Factor XI deficiency-related spontaneous
primary intraventricular hemorrhage. South Med J 2000; 93:1017–1018.
Mustafa MH, Bernstein RA. Spontaneous spinal epidural hematoma.
Brown-Sequard syndrome, and factor XI deficiency. Ann Intern Med 1987;
106:477–478.
Siao D, Seetapah A, Ryman A, Guerin V, Mesli A, Maurette P. Optimal
management of aneurysmal subarachnoid hemorrhage in a patient with
known factor XI deficiency: a case report. Clin Appl Thromb Hemost 2008;
14:108–111.
Slade WR Jr, Rabiner AM. Plasma thromboplastin antecedent deficiency
and subarachnoid hemorrhage. Angiology 1973; 24:533–537.
Vasileiadis I, El-Ali M, Nanas S, Kolias S, Zacharatos P, ChristopoulouCokkinou V, et al. First diagnosis of factor XI deficiency in a patient with
subarachnoid haemorrhage. Blood Coagul Fibrinolysis 2009; 20:309–
313.
Wisoff JH, Rovit RL, Ho V, Leventhal H. Spontaneous hematomyelia
secondary to factor XI deficiency. Case report. J Neurosurg 1985;
63:293–295.
Rosenthal RL, Dreskin OH, Rosenthal N. New hemophilia-like disease
caused by deficiency of a third plasma thromboplastin factor. Proc Soc Exp
Biol Med 1953; 82:171–174.
Pantazis G, Tsitsopoulos P, Mihas C, Katsiva V, Stavrianos V, Zymaris S.
Early surgical treatment vs conservative management for spontaneous
supratentorial intracerebral hematomas: a prospective randomized study.
Surg Neurol 2006; 66:492–501.
Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP,
Connolly ES Jr, et al. American Heart Association Stroke Council and
Council on Cardiovascular Nursing. Guidelines for the management of
spontaneous intracerebral hemorrhage: a guideline for healthcare
professionals from the American Heart Association/American Stroke
Association. Stroke 2010; 4:2108–2129.
Kim MH, Kim EY, Song JH, Shin KM. Surgical options of hypertensive
intracerebral hematoma: stereotactic endoscopic removal versus
stereotactic catheter drainage. J Korean Med Sci 1998; 13:533–540.

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