Isaku Yoshioka

Isaya Hashimoto

Kazuhiro Tsukada

Koshi Matsui

Makoto Moriyama

Takuya Nagata

Tomoyuki Okumura

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Moriyama et al. Surgical Case Reports  (2015) 1:57 
DOI 10.1186/s40792-015-0059-8CASE REPORT Open AccessA patient with paroxysmal nocturnal
hemoglobinuria being treated with
eculizumab who underwent laparoscopic
cholecystectomy: report of a case
Makoto Moriyama*, Takuya Nagata, Isaku Yoshioka, Isaya Hashimoto, Koshi Matsui, Tomoyuki Okumura
and Kazuhiro TsukadaAbstract
Paroxysmal nocturnal hemoglobinuria (PNH) is acquired hemolytic anemia characterized by symptoms such as
anemia and hemoglobinuria. In recent years, eculizumab as an anti-complement (C5) monoclonal antibody has
been used for PNH and shown to have marked effects. We performed laparoscopic cholecystectomy in a patient
with PNH being treated with eculizumab, and could avoid the risk of perioperative hemolysis and thrombosis.
[Patient] The patient was a 48-year-old female who had developed PNH when she was 39 years old. At the age
of 46 years, eculizumab administration was initiated once every 2 weeks. During the administration period, neither
the progression of anemia nor hemoglobinuria was observed. In March 2013, gallstones were detected, and she
was referred to our hospital for surgery. Eculizumab was administered 10 days before surgery, and laparoscopic
cholecystectomy was performed in May 2013. After the operation, for the prevention of thrombosis, elastic
stockings and a foot pump were used without anticoagulant administration. After the operation, neither the
progression of anemia nor hemoglobinuria was observed. On postoperative day 5, eculizumab was administered
as planned, and she showed a favorable general condition and was discharged. [Discussion] Perioperative care in
PNH patients was conventionally considered to involve a high risk of developing anemia, thrombosis, or infection.
However, after the advent of eculizumab, the control of the symptoms of PNH became possible in many patients.
In this patient with PNH being treated with eculizumab, safe perioperative management was possible without the
development of complications.
Keywords: Paroxysmal nocturnal hemoglobinuria; Eculizumab; Laparoscopic cholecystectomyBackground
Paroxysmal nocturnal hemoglobinuria (PNH) is character-
ized by the appearance of complement-sensitive erythro-
cytes due to an acquired mutation in hematopoietic cells
and resulting chronic intravascular hemolysis [1, 2]. PNH
affects 6.9 per million people. As perioperative care for
PNH, the prevention of hemolytic attacks and thrombosis
is important. The mechanism of hemolytic attacks is con-
sidered to be complement activation due to perioperative
invasion, acidosis, and hypoxemia. For the prevention of
thrombosis, since hemolysis increases the activity of the* Correspondence: moriyama@med.u-toyama.ac.jp
Department of Surgery & Science, University of Toyama, 2630 Sugitani,
Toyama-city, Toyama 930-0194, Japan
© 2015 Moriyama et al. This is an Open Access
(http://creativecommons.org/licenses/by/4.0), w
provided the original work is properly creditedcoagulation system, the use of drugs such as heparin
is recommended [3]. In recent years, the administration of
eculizumab as an anti-complement (C5) monoclonal
antibody for PNH has produced marked effects.
We report a patient with PNH being treated with eculizu-
mab in whom laparoscopic cholecystectomy was performed,
and the risk of perioperative hemolysis or thrombosis could
be avoided.Case presentation
Patient
A 48-year-old female.article distributed under the terms of the Creative Commons Attribution License
hich permits unrestricted use, distribution, and reproduction in any medium,
..
Fig. 2 High-density shadows were observed, suggesting stones in
the gallbladder
Moriyama et al. Surgical Case Reports  (2015) 1:57 Page 2 of 4Chief complaint
No symptoms.
Past history
She had developed PNH when she was 39 years old. At
the age of 46 years, eculizumab administration once every
2 weeks was initiated, and neither progression of anemia
nor hemoglobinuria was observed during the administra-
tion period.
Present illness
In March 2013, she visited a local hospital due to
jaundice and abdominal pain, and was diagnosed with
cholecystolithiasis and choledocholithiasis. She continued
administration of eculizumab once every 2 weeks then
for two years. She was referred to the Department of
Gastroenterology. Common bile duct stones were re-
moved using endoscopic sphinterotomy (EST), and she
was then referred to our department for surgery for
cholecystolithiasis.
Physical findings
She was 165.3 cm tall and weighed 74.7 kg, and showed
a BMI of 27.94, blood pressure of 127/94 mmHg, pulse
of 74 bpm, body temperature of 36.8°C, and no anemia
or jaundice in the conjunctiva.
Blood examination findings
The leukocyte count was 2,930, and the Hb value was
8.2, both showing decreases.Fig. 1 There were many stones accumulating in the common bile ductERCP findings
Radiolucent images in the common bile duct showing
aggregation and extension to the porta hepatis were
observed, suggesting many stones (Fig. 1).CT findings
There were many high-density shadows suggesting
gallstones (Fig. 2).MRCP findings
After EST, there were no findings suggesting stones in
the common bile duct. In the gallbladder, many stones
were observed (Fig. 3).Fig. 3 After EST, no stones were observed in the common bile duct.
There were numerous stones in the gallbladder
Fig. 4 After the operation, bilirubin and LDH slightly increased but showed rapid improvement. No progression of anemia requiring blood
transfusion was observed
Moriyama et al. Surgical Case Reports  (2015) 1:57 Page 3 of 4Surgical findings
Eculizumab was administered 10 days before surgery,
and laparoscopic cholecystectomy was performed. The
operation time was 1 hour and 59 minutes, and the
bleeding volume was small. No complications occurred
during the operation.
Postoperative course
For the prevention of thrombosis, elastic stockings
and a foot pump were used without anticoagulant
administration. After the operation, neither theFig. 5 Eculizumab acts on C5 in the complement cascade, blocking complprogression of anemia or hemoglobinuria was ob-
served. Slight increases in D-Bil and LDH with peaks
on postoperative day 3 and a slight decrease in Hb
were observed, but rapidly improved (Fig. 4). On postop-
erative day 5, after eculizumab had been administered as
planned, she showed a favorable general condition,
and was discharged.
Discussion
PNH is acquired hemolytic anemia characterized by
intravascular hemolysis caused by increased complementement activation by the C5-converting enzyme
Moriyama et al. Surgical Case Reports  (2015) 1:57 Page 4 of 4sensitivity due to the deficiency of complement regu-
latory factor on the cell membrane surface [4]. This
disease is rare, affecting 6.9 per million people, and
slightly more frequent in males (male : female ratio =
1 : 0.77) [5].
Eculizumab as a treatment for PNH is an anti-
complement (C5) monoclonal antibody, and acts on C5 in
the complement cascade, blocking complement activation
by the C5-converting enzyme and inhibiting hemolytic
attacks (Fig. 5) [6, 7]. In Japan, this drug was approved as
a treatment for PNH in 2010. As perioperative care in
PNH patients, the prevention of hemolytic attacks
due to surgical invasion and thrombosis associated
with increased activity in the coagulation system is
important. Conventionally, the pre- and postoperative
administration of heparin calcium or dalteparin sodium
was recommended as perioperative care [8, 9]. To prevent
hemolytic attacks, the use of steroids was also recom-
mended [10]. However, after the advent of eculizumab,
patients in whom PNH symptoms can be controlled
with this drug have been increasing. In our patient,
hemolytic attacks and hemolysis could be avoided during
the perioperative period without using anticoagulants
or steroids.
Eculizumab is administerd once in two weeks, but the
blood concentration two weeks after administration
eculizumab 900 mg is approximately 110 μg/ml, and
blood concentration more than 35 μg/ml is recom-
mended. Therefore, as for the timing of the operation,
it is thought that it is no problem when if during a
administeration period of eculizimab.
So far, patients who underwent cholecystectomy in PNH
patients under eculizumab administration has been re-
ported two cases, both of which are open cholecystectomy.
The patient who underwent laparoscopic-cholecystectomy
in PNH patients under eculizumab administration has
been slightly observed in the conference proceedings. In
any case, it has not happened serious complications
in the perioperative in PNH patients under eculizumab
administration [11, 12].
Surgically treated PNH patients are extremely rare. In
this patient, we had difficulty in determining the extent
of preventive measures, such as the use of coagulants or
steroids. However, since steroid administration was
previously effective against hemolytic attacks in this
patient, we prepared for rapid steroid administration
and blood transfusion against the possible development of
hemolytic attacks. However, neither hemolytic attacks
nor thrombosis developed. These results suggest that
eculizumab adequately acted on the complement system
even during the perioperative period, enabling safe
perioperative care without severe complications in this
patient who underwent laparoscopic cholecystectomy as
minimally invasive surgery.Conclusion
We encountered a patient with PNH being treated with
eculizumab in whom safe perioperative care was possible
without complications.
Consent
Written informed consent was obtained from the patient
for publication of this Case report and any accompanying
images.
Competing interests
Makoto Moriyama and his co-authors have no conflict of interest.
Authors’ contributions
Makoto Moriyama, Isaku Yoshioka and Isaya Hashimoto accomplished an
operation and post operative management. Takuya Nagata, Koshi Matsui,
Tomoyuki Okumura, and Kazuhiro Tsukada conceived of the study, and
participated in its design and coordination and helped to draft the
manuscript. All authors read and approved the final manuscript.
Received: 29 March 2015 Accepted: 25 June 2015
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A patient with paroxysmal nocturnal hemoglobinuria being treated with eculizumab who underwent laparoscopic cholecystectomy: report of a case

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A patient with paroxysmal nocturnal hemoglobinuria being treated with eculizumab who underwent laparoscopic cholecystectomy: report of a case

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