CASE REPORT

Autoimmune Hemolytic Anemia Following Bronchoscopic Examination

for Lung Cancer: a Case Report

Yosuke Eguchi1; Ichiro Sato1; Kohei Iwasaki1; Koichi Ogawa1; Gaku Kuwabara1;
Kohei Nishida1; Masato Shinoki1; Nobuyuki Uraoka1; Tamaki Kawamoto1;
Yuko Nakatsuji1; Yuzo Miki1; Mami Shinyama1; Kenichi Minami1

ABSTRACT ━━ Background. There is no previous report of autoimmune hemolytic anemia manifesting after bron-
choscopic examination. Case. A 73-year-old woman presented with a dry cough. Computed tomography revealed a
nodule measuring 4×2 cm in size at the base of the left lung. A bronchoscopic examination revealed malignancy in
the form of adenocarcinoma. Two days later, the patient was admitted to the emergency department with complaints
of dizziness. The direct Coombs test yielded positive findings, and the patient was diagnosed with autoimmune
hemolytic anemia. The patient received treatment with oral steroids because of the positive Coombs test results, but
no first-line chemotherapy for lung cancer was performed. However, her performance status gradually declined. The
patient died 2 months after the initial administration of oral steroids. Conclusions. This report highlights the possibil-
ity of autoimmune hemolytic anemia occurring after bronchoscopic examination in a patient with primary lung can-
cer.
(JJSRE. 2017;39:181-184)
KEY WORDS ━━ Autoimmune hemolytic anemia, Bronchoscopy, Coombs test, Paraneoplastic syndrome, Primary
adenocarcinoma of the lung cancer

choscopic examination. Here, we report a case of rap-

INTRODUCTION
Autoimmune hemolytic anemia (AIHA) is a rare para-
neoplastic syndrome (PNS) associated with malignant
solid tumors.1 It has been reported to occur in 52 per
1,050 individuals with malignant solid tumor or 9 per
219 patients with non-small cell lung cancers.1 However
both the mechanism underlying PNS-AIHA and timing
of manifestation of PNS-AIHA are not well understood.
A recent case report describing a patient with PNS-
AIHA indicated the presence of antibodies against the
tumor antigens, which cross-reacted with the erythro-
cyte antigen: band 3.2 Further study of this case may
provide clues to novel mechanisms and immunotherapy
targets for against AIHA and solid tumors. However,
the timing of the manifestation varies greatly, and there
is no previous report of AIHA manifested after bron-
idly progressing anemia manifested after broncho-
scopic examination in a patient who had primary lung
cancer.
CASE REPORT
A 73-year-old woman ( performance status : 1, never-
smoker) presented at the outpatient clinic of Ishikiri-
Seiki Hospital (Higashi-Osaka, Japan) with a history of a
dry cough. Initial computed tomography ( CT ) of the
chest demonstrated a nodule measuring 4×2 cm in size
at the base of the left lung (Figure 1). During broncho-
scopic examination, a transbronchial biopsy was taken
from the left B 10, and revealed malignancy in the form
of adenocarcinoma (epidermal growth factor receptor
( EGFR ) mutation and anaplastic lymphoma kinase
( ALK ) ; negative ) . [ 18 F ] fluorodeoxyglucose ( FDG ) -

1Department of Respiratory Medicine, Ishikiri-Seiki Hospital, Japan.

Correspondence: Yosuke Eguchi, Department of Respiratory Medicine, Ishikiri-Seiki Hospital, 18-28 Yayoi-cho, Higashi-Osaka, Osaka
579-8026, Japan (e-mail: m1293549@msic.med.osaka-cu.ac.jp)．
Received September 24, 2015; accepted November 23, 2016．
! 2017 The Japan Society for Respiratory Endoscopy

The Journal of the Japan Society for Respiratory Endoscopy―Vol 39, No 2, Mar 2017―www.jsre.org 181
 Autoimmune Hemolytic Anemia Following Bronchoscopic Examination for Lung Cancer―Eguchi et al

Figure 1. Initial computed tomography of the chest. A tumor measuring 4×2 cm can be seen at the
left lung base.

Table 1. Peripheral Blood (Before Bronchoscopic Table 2. Peripheral Blood (Two Days After Broncho-
Examination) scopic Examination)

Hematology Biochemistry Hematology Biochemistry

WBC 12,730/μl T-Bil 0.8 mg/dl WBC 22,430/μl T-Bil 1.5 mg/dl
Neu 85.0% D-Bil 0.4 mg/dl Neu 87.0% D-Bil 0.5 mg/dl
Ly 11.5% BUN 17.6 mg/dl Ly 6.0% BUN 16.6 mg/dl
RBC 349×104/μl Cr 0.69 mg/dl RBC 199×104/μl Cr 0.68 mg/dl
Hb 11.0 g/dl TP 7.6 g/dl Hb 6.2 g/dl TP 7.5 g/dl
Ht 31.2% ALB 2.6 g/dl Ht 17.8% ALB 2.5 g/dl
PLT 22.5×104/μl Na 136 mEq/l PLT 46.2×104/μl Na 133 mEq/l
K 4.3 mEq/l Ret 4.9% K 3.9 mEq/l
Serology Cl 99 mEq/l Cl 98 mEq/l
CRP 15.6 mg/dl AST 31 IU/l Serology AST 20 IU/l
CEA 4.8 ng/ml ALT 28 IU/l CRP 8.61 mg/dl ALT 49 IU/l
LDH 204 IU/l Direct Coombs test positive LDH 260 IU/l
CK 128 IU/l CK 9 IU/l
IgG 2,318 mg/dl

positron emission tomography ( PET ) examination in-

itially revealed an abnormal uptake of FDG in the medi-
astinal lymph nodes, while magnetic resonance imaging
(MRI) revealed brain metastasis (cT2aN3M1b; stage
IV ) . Despite absence of complications from broncho-
scopic examination, the patient presented at the emer-
gency department of the hospital 2 days after broncho-
scopic examination, complaining of dizziness. Labora-
tory analysis of the peripheral blood showed decreased
levels of hemoglobin and increased levels of indirect
bilirubin and lactate dehydrogenase (Table 1，2).
Upper gastrointestinal endoscopy was performed;
however, the reason for the worsened anemia remained
unclear. There was no melena, and thus colonoscopy
was not performed. The patient was concerned about
mass bleeding in the lung and requested a repeat bron-
coscopic examination ; however, there was no bloody
sputum or hemoptysis, and thus bronchoscopic exami-
nation was not repeated. In reference to the blood ex-
amination result, a hematological condition was consid-
ered, such as AIHA as PNS. The direct Coombs test
was positive; therefore, we diagnosed AIHA. The pa-
tient was treated with oral steroids; however, no first-
line chemotherapy was administered because her per-
formance status declined. Despite administration of oral

182 The Journal of the Japan Society for Respiratory Endoscopy―Vol 39, No 2, Mar 2017―www.jsre.org
 Autoimmune Hemolytic Anemia Following Bronchoscopic Examination for Lung Cancer―Eguchi et al

LDH (IU/ ) Hb (g/dl)

300 12 T-Bil (mg/dl)
Prednisolone 25 mg/day

250 10

200 8

LDH
150 6
Hb
T-Bil

Transfusion
100 4

Bronchoscopic examination

50 2

0 0
0 2 4 6 8 10 12

(Days aŌer bronchoĮberscopic examinaƟon)

Figure 2. Clinical course. Two days after bronchoscopic examination, the patient was admit-
ted to Emergency Department with complaints of dizziness, because of the rapid progress of
anemia.

steroid, and palliative care, the patient s condition con-
tinued to worsen until she died due to tumor progres-
sion.
DISCUSSION
To the best of our knowledge, this is the first report of
AIHA following bronchoscopic examination in the pa-
tient who had primary lung cancer. Most cases of AIHA
in cancer patients occur as a result of cytotoxic chemo-
therapy.3,4 The typical symptoms include dizziness, pal-
pitation, or breathlessness.5
In our case, the levels of hemoglobin had rapidly de-
creased, and those of in-direct bilirubin and lactate de-
hydrogenase had increased by 2 days after broncho-
scopic examination ( Figure 2 ) . Given that the direct
Coombs test was positive, we made a final diagnosis of
AIHA. Midazolam, lidocaine, and pre-medication drugs
used in this case, have not been reported as triggers
that induce AIHA, while infection and drugs such as an-
tibiotics have been reported as a general trigger induc-
ing AIHA.6 Anemia developed rapidly (within 2 days)
and caused dizziness. However we hesitated to perform
a transfusion, as the patients had an irregular antibody
in blood. AIHA is an acquired immunological disease in
which red blood cells are selectively attacked and de-
stroyed ( hemolyzed ) by autoantibodies. Several hy-
potheses regarding the mechanisms underlying the de-
velopment of AIHA have been proposed, but the actual
pathogenesis remains unclear. The major autoantigens
in AIHA have been shown to be Rh protein, band 3 and
glycophorin A. In a recent case report describing a pa-
tient with PNS-AIHA, antibodies had formed against tu-
mor antigens and cross-reacted with erythrocyte anti-
gen: band 3.2,7
In the present case, systemic chemotherapy and sur-
gical resection was not administered because MRI re-
vealed metastasis to the brain and performance status
became markedly poor after manifestation of AIHA. In
the present case, oral steroids administered after diag-
nosis did not improve the patient s performance status
after bronchoscopic examination.
Bronchoscopic examination is the most essential ex-
amination for diagnosis for lung cancer.8 Both before
and during the examination, we failed to fully notice
any signs of concurrence of AIHA in patients with pri-
mary lung cancer.
Fifty-two cases with PNS-AIHA with solid tumors
were identified between 1945 and 2009.1 According to
the temporal relationship between the cancer and mani-
festation of AIHA, patients were divided into 4 groups:

The Journal of the Japan Society for Respiratory Endoscopy―Vol 39, No 2, Mar 2017―www.jsre.org 183
 Autoimmune Hemolytic Anemia Following Bronchoscopic Examination for Lung Cancer―Eguchi et al
1) PNS-AIHA was manifested prior to malignancy, 2)
PNS-AIHA was manifested within 6 months before or
after malignancy, 3) PNS-AIHA was manifested with
recurrence of solid cancers, 4 ) PNS-AIHA was mani-
fested after complete remission of solid tumor following
treatment. Type 2 was subdivided according to cancer
stage (A) early stage or (B) with metastasis; our case
thus had type 2-B PNS-AIHA.
In total, there were 28 cases diagnosed with type 2-B
AIHA, with metastatic solid cancers, including 16
males and 12 females, with an age range of 17-82 years.
The cancers included 5 lung, 3 ovarian, 2 testicular, 2
colon, 2 thymic, 1 laryngeal, 1 gastric, 1 renal, 1 uterine,
1 adrenal, 1 prostate, 1 mixed parotid cancer and 1 peri-
toneal mesothelioma. Fifteen patients were treated
with steroids. Of these, 10 showed a complete or partial
response of AIHA, but remained steroid-dependent.
Five were refractory to treatment.1
In these 28 cases, there was no case in that invasive
examinations was a trigger for incidental manifestation
of PNS-AIHA. Thus, the manifestation of AIHA in prox-
imity to the performance of bronchoscopic examination
may simply be due to chance, and PNS-AIHA may have
manifested even in the absence of bronchoscopy.
Finally drugs involved in drug-induced AIHA had
been known to be antibiotics, etc.9,10 Lidocaine and mi-
dazolam have not reported as triggers, and thus it is not
likely that our patient suffered from drug-induced
AIHA.
The relationship between PNS and cancers is very
complex, particularly in terms of the temporal relation-
ship between the clinical symptoms of the PNS (as de-
fined by the presence of the paraneoplastic antibody)
and the time of clinical diagnosis of the tumor.
In conclusion, we have reported a case of AIHA mani-
184 The Journal of the Japan Society for Respiratory Endoscopy―Vol 39, No 2, Mar 2017―www.jsre.org
fested after bronchoscopic examination in a patient
who had primary lung cancer.
No potential conflicts of interest are disclosed.
Acknowledgement: We express our appreciation Shinichiro
Mori, of the Department of Hematology, Ishikiri-Seiki Hospi-
tal, Japan.
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