Treatment SDH Chronic
Treatment SDH Chronic
Treatment SDH Chronic
AANS, 2013
1
Department of Neurosurgery, Kuki General Hospital, Kuki, Saitama; and 2Department of Neurosurgery,
Juntendo University, Tokyo, Japan
Object. Chronic subdural hematoma (CSDH) is a common condition after head trauma. It can often be successfully treated surgically by inserting a bur hole and draining the liquefied hematoma. However, to the best of
the authors knowledge, for nonemergency cases not requiring surgery, no reports have indicated the best approach
for preventing hematoma enlargement or resolving it completely. The authors hypothesized that hyperfibrinolysis
plays a major role in liquefaction of the hematoma. Therefore, they evaluated the ability of an antifibrinolytic drug,
tranexamic acid, to completely resolve CSDH compared with bur hole surgery alone.
Methods. From 2007 to 2011, a total of 21 patients with CSDH seen consecutively at Kuki General Hospital,
Japan, were given 750 mg of tranexamic acid orally every day. Patients were identified by a retrospective records
review, which collected data on the volume of the hematoma (based on radiographic measurements) and any complications. Follow-up for each patient consisted of CT or MRI every 21 days from diagnosis to resolution of the CSDH.
Results. Of the 21 patients, 3 with early stages of CSDH were treated by bur hole surgery before receiving medical therapy. The median duration of clinical and radiographic follow-up was 58 days (range 28137 days). Before
tranexamic acid therapy was initiated, the median hematoma volume for the 21 patients was 58.5 ml (range 7.5223.2
ml); for the 18 patients who had not undergone surgery, the median hematoma volume was 55.6 ml (range 7.5140.5
ml). After therapy, the median volume for all 21 patients was 3.7 ml (range 022.1 ml). No hematomas recurred or
progressed.
Conclusions. Chronic subdural hematoma can be treated with tranexamic acid without concomitant surgery.
Tranexamic acid might simultaneously inhibit the fibrinolytic and inflammatory (kinin-kallikrein) systems, which
might consequently resolve CSDH. This medical therapy could prevent the early stages of CSDH that can occur after
head trauma and the recurrence of CSDH after surgery.
(http://thejns.org/doi/abs/10.3171/2013.3.JNS122162)
332
Patient Population
Methods
Treatment
Imaging Evaluations
For all patients, CT and/or MRI without contrast enhancement (slice thickness 5 mm) were conducted at the
time of diagnosis. Each patient underwent CT scanning
every 21 days. Final imaging studies were performed 21
days after the end of tranexamic acid administration. The
volume (in milliliters) of the hematoma was calculated
from the CT or MR images before, during, and after the
therapy by using image analysis software (ImageJ, National Institutes of Health). The size of the hematoma was
computed on the basis of imaging results and slice thicknesses.
Outcomes
Therapy and therapeutic periods for CSDH were recorded for all patients, regardless of whether they received
surgical intervention. Each clinical symptom was evaluated as improved or not improved. The hematoma categories were as follows: cure (defined as sufficient decrease
of the CSDH according to imaging studies); recurrence
(defined as a new CSDH in a new location or in the same
location after confirmation of hematoma disappearance 21
days after cure); or progression (defined as expansion of
the CSDH in the same location without cure or regression).
Patient Characteristics
Results
72, M
88, F
71, M
82, F
54, F
91, F
65, M
82, M
76, M
88, M
88, F
75, M
92, M
90, M
78, F
93, F
70, M
69, M
67, F
79, F
82, M
History
parkinsonism
HT, parkinsonism
AF
HL
cilostazol
aspirin
lymphoma
lumbar fracture
ticlopidine, DM, CHF, AF, OMI
brain contusion
dementia, HT
epilepsy
AEDH
breast cancer
clavicle fracture
Symptoms
none
gait disturbance, dementia
lt hemiparesis
gait disturbance
none
none
headache
none
dementia
none
none
none
rt hemiparesis, dementia
none
none
gait disturbance, polyuria
gait disturbance, headache
headache
headache
gait disturbance, dementia
none
Hematoma Hematoma
Therapy Duration
Laterality Volume (ml) Op
(days)
rt
bilat
bilat
bilat
lt
lt
bilat
rt
rt
bilat
lt
rt
lt
lt
rt
rt
bilat
lt
bilat
bilat
rt
54.2
223.2 (61.4)
96.7 (16.9)
87.4
18.7
7.5
122.2 (20.6)
21.8
31.2
73.5
32.1
29.0
126.1
58.5
22.5
34.4
129.6
73.4
85.2
140.5
56.9
+
+
70
55
57
91
29
58
72
58
28
28
50
63
127
137
28
56
59
70
127
99
28
Result
improved
improved
improved
improved
improved
improved
improved
improved
improved
improved
improved
* AEDH = acute epidural hematoma; AF = atrial fibrillation; CHF = chronic heart failure; DM = diabetes mellitus; HL = hyperlipidemia; HT = hypertension;
OMI = old myocardial infarction; Op = operation (bur hole insertion); + = yes; = no.
Values inside parentheses indicate volume after surgery.
Medical therapy with tranexamic acid.
333
H. Kageyama et al.
tion or coronary heart disease; 2 (10%) had atrial fibrillation but were not taking any anticoagulant drugs; and 1
(5%) received a diagnosis of malignant lymphoma after
chemotherapy, but platelet counts and coagulation data
were within reference ranges.
Clinical Presentations
Treatment
Imaging Studies
Among all patients, clinical symptoms improved before the hematomas were fully reduced. For all patients
with headache who did not undergo surgery, the headache
pain rapidly disappeared by the second visit after starting
therapy. Follow-up visits were performed for each patient
for a median of 58 days (range 28137 days). After therapy, the median volume of the hematomas in all patients
was 3.7 ml (range 022.1 ml). Figure 1 shows the changes
in the volumes of the hematomas in the 18 patients who
did not undergo surgery. For all patients, hematomas were
assigned to the category of cure. None of the hematomas recurred or progressed. Among all study patients, no
adverse events, including thromboembolic events, were
observed; thus, tranexamic acid was not discontinued for
reasons of death or severe adverse event.
The patient in Case 19 represents a common case
from this study (Fig. 2). The patient was a 67-year-old
woman who had an acute epidural hematoma on her right
334
After Treatment
Case No.
Lt
Rt
Total
Lt
Rt
Total
Period (days)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
54.2
84.0
16.9
63.9
0
0
53.2
21.8
17.7
32.3
0
29.0
0
0
22.5
34.4
48.1
0
9.4
68.3
56.9
0
139.2
79.8
23.6
18.7
7.5
69
0
13.5
41.2
32.1
0
126.1
58.5
0
0
81.5
73.4
75.8
72.1
0
54.2
223.2
96.7
87.5
18.7
7.5
122.2
21.8
31.2
73.5
32.1
29.0
126.1
58.5
22.5
34.4
129.6
73.4
85.2
140.4
56.9
2.6
9.5
4.3
3.9
0
0
1.2
3.5
20.8
7.2
0
3.7
0
0
2.5
7.1
1.7
0
0
0
0
0
7.4
5.0
11.5
0
0.7
0.6
0
1.3
5.0
0.3
0
17.8
9.5
0
0
8.6
0
3.8
0
0
2.6
16.9
9.3
15.4
0
0.7
1.8
3.5
22.1
12.2
0.3
3.7
17.8
9.5
2.5
7.1
10.3
0
3.8
0
0
70
55
57
91
29
58
72
58
28
28
50
63
127
137
28
56
59
70
127
99
28
Fig. 1. Changes in the hematoma volumes in 18 patients who received tranexamic acid therapy but did not undergo surgery. Key to the
right of the graph lists patients according to their case number.
side. The hematoma was removed through a small craniotomy, and the patient was discharged from the hospital 2 months later. One month after discharge, she complained of a headache. Computed tomography scanning
showed a thin hematoma on the right side of her head and
a thick hematoma on the left side. Tranexamic acid was
then given, after which the neuroimaging course varied;
initially the density decreased, and then the hematoma
diminished. The hematoma was completely resolved 4
months later.
The patient in Case 13, a 92-year-old man who was
receiving ticlopidine for an old myocardial infarction, had
a CSDH of the maximum size on 1 side; he did not undergo surgical intervention (Fig. 3). After a fall, he suffered rib fractures, and 2 weeks later, right hemiparesis
and dementia developed. We recommended bur hole surgery, but he rejected it. The massive hematoma was treated with tranexamic acid without surgery and completely
resolved after 4 months (Fig. 4).
One patient with CSDH was not treated with tranex
amic acid. This patient was an 81-year-old man who received a bruise on his head from a fall after drinking.
Traumatic subarachnoid hemorrhage and a thin acute
subdural hematoma developed. The hemorrhage and the
hematoma did not worsen. Because he had progressing
dementia, he was transferred to a psychiatric hospital.
Follow-up 1 month later at Kuki General Hospital showed
that his neurological symptoms had not changed; however,
J Neurosurg / Volume 119 / August 2013
Discussion
H. Kageyama et al.
Fig. 6. Fibrinolytic system and kallikrein system. FDP = fibrin degradation products; HMW = high molecular weight.
Conclusions
1. CRASH-2 Collaborators, Intracranial Bleeding Study: Effect of tranexamic acid in traumatic brain injury: a nested
randomised, placebo controlled trial (CRASH-2 Intracranial
Bleeding Study). BMJ 343:d3795, 2011
2. Ducloy-Bouthors AS, Jude B, Duhamel A, Broisin F, Huissoud C, Keita-Meyer H, et al: High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care 15:
R117, 2011
3. Dunn CJ, Goa KL: Tranexamic acid: a review of its use in surgery and other indications. Drugs 57:10051032, 1999
4. Fujisawa H, Ito H, Kashiwagi S, Nomura S, Toyosawa M: Kal
likrein-kinin system in chronic subdural haematomas: its roles
in vascular permeability and regulation of fibrinolysis and coagulation. J Neurol Neurosurg Psychiatry 59:388394, 1995
5. Gksu E, Akyz M, Uar T, Kazan S: Spontaneous resolution of a large chronic subdural hematoma: a case report and
review of the literature. Ulus Travma Acil Cerrahi Derg 15:
9598, 2009
6. Harada K, Orita T, Abiko S, Aoki H: [Coagulation and fibrinolysis in chronic subdural hematoma. Measurement of fibrinopeptides.] Neurol Med Chir (Tokyo) 29:113116, 1989 (Jpn)
7. Horikoshi T, Naganuma H, Fukasawa I, Uchida M, Nukui H:
Computed tomography characteristics suggestive of spontaneous resolution of chronic subdural hematoma. Neurol Med
Chir (Tokyo) 38:527533, 1998
8. Ito H, Yamamoto S, Komai T, Mizukoshi H: Role of local hyperfibrinolysis in the etiology of chronic subdural hematoma.
J Neurosurg 45:2631, 1976
9. Kassell NF, Torner JC, Adams HP Jr: Antifibrinolytic therapy
in the acute period following aneurysmal subarachnoid hemorrhage. Preliminary observations from the Cooperative Aneurysm Study. J Neurosurg 61:225230, 1984
10. Kawakami Y, Chikama M, Tamiya T, Shimamura Y: Coagulation and fibrinolysis in chronic subdural hematoma. Neurosurgery 25:2529, 1989
11. Ker K, Edwards P, Perel P, Shakur H, Roberts I: Effect of
tranexamic acid on surgical bleeding: systematic review and
cumulative meta-analysis. BMJ 344:e3054, 2012
12. Nomura S, Kashiwagi S, Fujisawa H, Ito H, Nakamura K:
Characterization of local hyperfibrinolysis in chronic subdural hematomas by SDS-PAGE and immunoblot. J Neurosurg
81:910913, 1994
13. Oh HJ, Lee KS, Shim JJ, Yoon SM, Yun IG, Bae HG: Postoperative course and recurrence of chronic subdural hematoma.
J Korean Neurosurg Soc 48:518523, 2010
14. Saito K, Ito H, Hasegawa T, Yamamoto S: Plasmin-alpha 2plasmin inhibitor complex and alpha 2-plasmin inhibitor in
chronic subdural hematoma. J Neurosurg 70:6872, 1989
15. Suzuki M, Kudo A, Kitakami A, Doi M, Kubo N, Kuroda K, et
al: Local hypercoagulative activity precedes hyperfibrinolytic
activity in the subdural space during development of chronic
subdural haematoma from subdural effusion. Acta Neurochir (Wien) 140:261266, 1998
16. Yamashima T, Yamamoto S, Friede RL: The role of endothelial gap junctions in the enlargement of chronic subdural hematomas. J Neurosurg 59:298303, 1983
Manuscript submitted November 13, 2012.
Accepted March 29, 2013.
Please include this information when citing this paper: published online May 3, 2013; DOI: 10.3171/2013.3.JNS122162.
Address correspondence to: Hiroshi Kageyama, M.D., Kuki General Hospital, Kamihayami 418-1, Kuki, Saitama 346-0021, Japan.
email: kageyamahiroshi29@gmail.com.
337