e-ISSN 1941-5923
© Am J Case Rep, 2019; 20: 1852-1856
DOI: 10.12659/AJCR.919649
Received:
Accepted:
Published:

Primary Antiphospholipid Antibody Syndrome
Complicated with Cerebellar Hemorrhage and
Aortic Dissection: A Case Report

2019.08.25
2019.10.16
2019.12.11

Authors’ Contribution:
Study Design A
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G

ABCDEF 1
ABCDE 1
CDEF 1
ABCDEF 2

Yoshio Tatsuoka
Yui Mano
Shuichi Ishikawa
Shigeru Shinozaki

1 Department of Neurosurgery, Japanese Red Cross Ishinomaki Hospital,
Ishinomaki, Miyagi, Japan
2 Department of Critical Care Medicine, Japanese Red Cross Ishinomaki Hospital,
Ishinomaki, Miyagi, Japan

Corresponding Author:
Conflict of interest:

Yoshio Tatsuoka, e-mail: yoshiotatsuoka@gmail.com
None declared

Patient:
Final Diagnosis:
Symptoms:
Medication:
Clinical Procedure:

Female, 42-year-old
Primary antiphospholipid antibody syndrome
Coma
—
Evacuation of the intracranial hematoma • suboccipital decompression • intraventricular catheter
placement
Neurosurgery

Specialty:
Objective:
Background:

Case Report:

Conclusions:

MeSH Keywords:
Full-text PDF:

Rare co-existance of disease or pathology
Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease associated with arterial and venous thromboembolism and pregnancy complications. There have been several reports of APS with systemic
lupus erythematosus (SLE) complicated with aortic dissection. However, none of them has been primary APS,
which is APS without SLE.
A 42-year-old woman with primary APS and APS nephropathy on warfarin and aspirin therapy presented with
coma due to cerebellar hemorrhage. The effect of warfarin was immediately reversed with prothrombin complex concentrate. We performed emergent evacuation of the hematoma, and her level of consciousness improved to normal on postoperative day (POD) 1. She had acute hypertension on arrival, which was resistant to
multiple antihypertensives and was stabilized on POD 3. She also had exacerbation of chronic kidney disease
after using contrast and prothrombin concentrate complex, and was on temporary renal replacement therapy
from POD 3. Aortic dissection was found accidentally on echocardiography on POD 7, and she was subsequently
treated medically. She was transferred to the rehabilitation hospital with mild dysarthria and truncal ataxia on
POD 59.
We report the first case in the English literature of primary APS complicated with cerebellar hemorrhage and
aortic dissection. Acute hypertension following hemorrhage and exacerbation of APS nephropathy likely triggered the dissection of the aortic wall, the integrity of which might have been compromised by longstanding
antiphospholipid antibody and vasa vasorum thrombosis.
Antiphospholipid Syndrome • Aortic Diseases • Intracranial Hemorrhages
https://www.amjcaserep.com/abstract/index/idArt/919649

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Tatsuoka Y. et al.:
APS with cerebellar hemorrhage and aortic dissection
© Am J Case Rep, 2019; 20: 1852-1856

Background
Antiphospholipid antibody syndrome (APS) is characterized by
venous or arterial thromboses or pregnancy morbidity in the
presence of persistent laboratory evidence of antiphospholipid antibodies. APS is well known to be associated with systemic lupus erythematosus (SLE), although approximately half
of APS cases are diagnosed as primary APS without SLE [1].
Patients with APS continue to have significant morbidity and
mortality despite current treatment. According to a multicenter prospective study of 1000 patients, the survival probability at 10 years was 91% [2]. In this study, the vast majority of patients were under antithrombotic treatment, and the
causes of death were thrombosis, including myocardial infarction, stroke, and pulmonary embolism (37% of total deaths),
as well as hemorrhages (11%) [2]. Valvular heart disease and
coronary artery disease are the most frequent cardiac manifestations of APS [3]. However, APS complicated with aortic
dissection is extremely rare [4–6], and no such case in primary
APS has previously been reported in the English literature.

Case Report
A 42-year-old woman was diagnosed with primary APS 16
years ago following an unexplained abortion in the 24th week
of her first pregnancy combined with pulmonary embolism
and a confirmed so-called “triple-positive” antibody test result (positive test results for lupus anticoagulant, anticardiolipin antibody, and anti-beta-2 glycoprotein-I antibody test).
She was treated with prednisolone for 5 years, cyclophosphamide for 1 year, and warfarin except during pregnancy.
During her second pregnancy, which occurred 4 years after
the diagnosis, she was given aspirin, but the pregnancy resulted in intrauterine fetal death, with thrombosis confirmed
in the placenta. During her third pregnancy, which occurred
9 years after the diagnosis, she was placed on continuous intravenous heparin therapy and gave birth to her first child by
Cesarean section without any major complications. She was
then given warfarin again in addition to aspirin. She subsequently had no hemorrhagic or thrombotic events until hypermenorrhea at 15 years after the initial diagnosis. Warfarin
was suspended, but her serum creatine level then gradually
increased to 1.43 mg/dl, with an estimated glomerular filtration rate (eGFR) of 33 mL/min/1.73 m2, which was normal before the suspension. She was diagnosed with APS nephropathy and was re-administered warfarin, which resulted in slight
and gradual improvement in her eGFR.
She woke up in the morning of the day of presentation, 16 years
after the initial diagnosis of primary APS, with a severe headache, nausea, and dizziness and soon lost consciousness.
She was carried to our emergency room (ER) by ambulance,

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Figure 1. Noncontrast CT in the transverse plane on the day of
presentation. The arrow indicates the right cerebellar
hemorrhage.

with a Glasgow coma scale (GCS) score of 3 and pinpoint pupils. Her heart rate was 49 beats per minute, and her blood
pressure was 198/65 mmHg. Noncontrast computed tomography (CT) revealed right cerebellar hemorrhage with brainstem compression and intraventricular hematoma (Figure 1).
No intracranial arteriovenous malformation or arterial aneurysm was detected on contrast-enhanced CT. The prothrombin
time-international normalized ratio (PT-INR) was 2.16 with a
normal platelet count, and the eGFR was 36 mL/min/1.73 m2.
The effect of warfarin was immediately reversed with prothrombin complex concentrate. Then, an emergent evacuation of the hematoma, suboccipital decompression, and intraventricular catheter placement were performed (Figure 2).
She had severe hypertension on presentation despite no previous history of chronic hypertension. She needed high doses
of multiple antihypertensives until discharge.
On postoperative day (POD) 1, she improved to GCS 15 and
was extubated. Her blood pressure was 167/70 mmHg on
POD 1, 170/58 mmHg on POD 2, and stabilized to within normal range after POD 3. She resumed warfarin on the same day.
Additionally, pleural effusion was detected on chest X-ray and
was confirmed for the next 1 month. The eGFR decreased from
admission and was 11 mL/min/1.73 m2 on POD 3. The patient
was diagnosed with contrast-induced nephropathy based on the
contrast-enhanced CT scan performed on the first day. She was

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Tatsuoka Y. et al.:
APS with cerebellar hemorrhage and aortic dissection
© Am J Case Rep, 2019; 20: 1852-1856

Figure 2. Noncontrast CT scan in the transverse plane soon after
the operation. The arrow indicates that the hematoma
was evacuated.

on temporary renal replacement therapy from POD 3. On POD 7,
an echocardiography was performed to evaluate her cardiac
function and volume status and accidentally showed a flap in
the descending aorta. A contrast-enhanced CT scan revealed
a communicating aortic dissection (Stanford type-B, De Bakey
type-IIIb) with an entry in the lesser curvature of the aortic arch
(Figure 3). All of the major organ arteries originating from the
aorta were supplied from the true lumen with no organ damage. She was treated medically, and her systolic blood pressure
has been maintained between 100 and 120 mmHg since then.
She developed contrast-induced nephropathy again, and her
eGFR decreased to 13 mL/min/1.73 m2 on POD 11. She kept
receiving temporary renal replacement therapy until POD 21,
and her renal function then improved to the same level as that
observed at baseline on admission. No major organ complications related to the dissection or the extension of the false
lumen was confirmed until discharge. She was transferred to
the rehabilitation hospital due to mild dysarthria and truncal
ataxia on POD 59. She was able to walk short distances with
a walker at the time of discharge.

Discussion
We hypothesize that aortic dissection occurred after cerebellar
hemorrhage for the following reasons. First, serum C-reactive

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Figure 3. Contrast-enhanced CT in the sagittal plane on POD 7.
The arrow indicates a communicating aortic dissection
with an entry into the lesser curvature of the aortic
arch.

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Tatsuoka Y. et al.:
APS with cerebellar hemorrhage and aortic dissection
© Am J Case Rep, 2019; 20: 1852-1856

protein levels were normal on presentation but gradually increased from POD 1 before starting to decrease from POD 6,
as is usually observed in acute aortic dissection [7]. Second,
pleural effusion was prolonged for 1 month beginning on POD
3 but was not confirmed at admission. Pleural effusion itself
can be seen in either acute or chronic dissection [8], but its
new onset suggests acute dissection. Finally, acute hypertension after cerebellar hemorrhage could have been the triggering event. However, it remains possible that the dissection occurred before the hemorrhage because approximately 10%
of aortic dissections are painless on presentation, and this
has been reported in younger patients similar to our case [9].
This patient was relatively young to develop aortic dissection. The question remains as to whether the aortic dissection was related to the primary APS in this patient. APS complicated with aortic dissection is extremely rare [4–6], and to
our knowledge, no such case in primary APS without SLE has
been reported in the English literature. The common risk factors for aortic dissection are chronic hypertension, smoking,
dyslipidemia, connective tissue diseases, and trauma, none of
which were present in this patient. A few case reports have
described APS complicated with aortitis [10], but this did not
occur in this patient due to a lack of stenosis or hypertrophy
of the aorta or laboratory evidence of chronic inflammation.
Giant cell arteritis or malignant rheumatoid arteritis were also
ruled out based on laboratory and clinical findings.
The etiology of aortic dissection is multifactorial. In general,
a triggering event initiates the dissection of a previously damaged aortic wall, except in traumatic cases. It is commonly recognized that the triggering event in aortic dissection is a tear
in the intima that leads to the destruction of the inner part
of the wall and blood flowing into the media. The onset of
the dissection was not clear since she had no typical chest or
back pain before the dissection was accidentally found. She
had only mild chest discomfort a few days after the diagnosis.
We suspect that the triggering event was acute hypertension
during the first 3 days since there was no other suspicious
triggering event. She had no history of hypertension before
the cerebellar hemorrhage, and she presented to the ER with
Cushing reflex (increasing systolic and pulse pressure with
bradycardia due to intracranial pressure.) Her hypertension
continued postoperatively and was resistant to antihypertensives; it required 3 days to be stabilized. High doses of multiple antihypertensives were needed through hospitalization
and were not explained by the Cushing reflex alone. The new
onset of drug-resistant hypertension was probably caused by
the exacerbation of APS nephropathy. APS nephropathy is a
renal involvement of primary APS patients, is characterized
by small vessel occlusion, and most commonly presents with
hypertension [11]. Some patients present with hypertensive

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emergencies without a previous history of hypertension [11].
GFR also decreases with APS nephropathy, although it did not
necessarily reflect the exacerbation of APS nephropathy in this
case since she had contrast-induced nephropathy in the same
period. The reversal and discontinuation of antithrombotics
might have accelerated small vessel thrombus formation, leading to exacerbation of the existing APS nephropathy, which
likely contributed to postoperative hypertension in this patient.
We also propose that the APS itself caused aortic fragility in
this patient. Medial necrosis was confirmed in all 3 pathological reports that showed aortic dissection with APS, and old
thrombosis in the veins in aortic wall was also confirmed in
one of them [4–6]. The patient’s history of pulmonary embolism, thrombosis in the placenta, and APS nephropathy suggests longstanding multiple microthrombosis in this patient.
It was previously demonstrated in a dog model that the impairment of vasa vasorum blood flow leads to necrosis in the
aortic media [12]. We assume that in this case, vasa vasorum
thrombosis might have led to medial necrosis, which contributed to aortic wall fragility. Moreover, some studies have suggested that antiphospholipid antibodies accelerate atherosclerosis [13], which can impair resistance of the aortic wall
to pressure. It is widely accepted that long-term corticosteroid use induces discontinuation of the connective tissue of
the media [14], although this was not the primary cause of
wall fragility in this case considering the relatively short history of steroid therapy.
The combination of anticoagulation therapy with aspirin and
warfarin is highly likely to have contributed to the cerebellar
hemorrhage observed in this patient. Warfarin increases the
risk of intracranial bleeding, and adding aspirin to warfarin further increases this risk [15]. The target range for PT-INR was
1.6 to 2.0 before hospitalization in this patient. A target range
of 2.0 to 3.0 is recommended in some guidelines in the US
and EU [16,17]. However, the risk of intracranial hemorrhage
caused by anticoagulation is far higher in Asian individuals than
in whites [18]. There are no widely accepted guidelines suggesting the optimal target range for Asian patients with APS.

Conclusions
Here, we report the first case in the English literature of primary APS complicated with cerebellar hemorrhage and aortic dissection. Acute hypertension following hemorrhage and
exacerbation of APS nephropathy likely triggered the dissection of the aortic wall, the integrity of which might have been
compromised by longstanding antiphospholipid antibody and
vasa vasorum thrombosis.

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Tatsuoka Y. et al.:
APS with cerebellar hemorrhage and aortic dissection
© Am J Case Rep, 2019; 20: 1852-1856

Department and Institution where work was done

Conflicts of interest

Department of Neurosurgery, Japanese Red Cross Ishinomaki
Hospital, 71 Nishimichishita Hebita, Ishinomaki, Miyagi, Japan

None.

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