E  Case Report

Anesthetic Management of Living-Donor Renal
Transplantation in a Patient With Epstein Syndrome
Using Rotational Thromboelastometry: A Case Report
Midoriko Higashi, MD, PhD,* Keizo Kaku, MD, PhD,† Yasuhiro Okabe, MD,† and Ken Yamaura, MD*
Epstein syndrome is a myosin heavy chain 9 (MYH9)-related disorder characterized by hearing
loss and macrothrombocytopenia with renal failure, which usually requires platelet transfusion
during surgery. We report the case of a 22-year-old man who underwent living-donor renal transplantation without platelet transfusion using rotational thromboelastometry (ROTEM) monitoring.
His intraoperative laboratory coagulation findings were a platelet count of 28–31 × 109/L based
on microscopy and fibrinogen of 256 mg/dL. However, his extrinsic pathway evaluations by ROTEM
were normal. The estimated blood loss during the operation was 150 mL, and the patient showed
no bleeding complications without platelet transfusion. (A&A Practice. 2020;14:e01350.)

GLOSSARY
Downloaded from http://journals.lww.com/aacr by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60Etgtdnn9T1vLQWJq/+R2O4Kjt58 on 11/25/2020

α = α angle; A10 = clot firmness measured at 10 minutes after start of clot formation; aPTT =
activated partial thromboplastin time; CFT = clot formation time; CT = clotting time; EQUATOR =
Enhancing the Quality and Transparency of Health Research; EXTEM = evaluation of the extrinsic
pathway; FIBTEM = evaluation of the contribution of fibrinogen to clot formation; INR = international normalized ratio; INTEM = evaluation of the intrinsic pathway; MCF = maximum clot firmness; ML = maximum lysis; MYH9 = myosin heavy chain 9; P2Y12 = P2Y purinergic receptor 12;
POD = postoperative day; PT = prothrombin time; ROTEM = rotational thromboelastometry

E

pstein syndrome is a hereditary myosin heavy chain
9 (MYH9)–related disorder, characterized by hearing
loss and macrothrombocytopenia with renal failure,
which often requires renal transplantation.1–3 Perioperative
management for thrombocytop; enia is important for these
patients, with most undergoing platelet transfusion.3
Here, we report a case of a patient with Epstein syndrome undergoing living-donor renal transplantation
without platelet transfusion under coagulation monitoring using rotational thromboelastometry (ROTEM;
TEM International GmbH, Munich, Germany). Written
informed consent for publication was obtained from the
patient. This article adheres to the applicable Enhancing the
Quality and Transparency of Health Research (EQUATOR)
guideline.

From the Departments of *Anesthesiology and Critical Care Medicine and
†Surgery and Oncology, Graduate School of Medical Sciences, Kyushu
University, Fukuoka, Japan.
Accepted for publication October 2, 2020.
Funding: None.
The authors declare no conflicts of interest.
Address correspondence to Midoriko Higashi, MD, PhD, Department of
Anesthesiology and Critical Care Medicine, Graduate School of Medical
Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582,
Japan. Address e-mail to midoriko@kuaccm.med.kyushu-u.ac.jp.
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health,
Inc. on behalf of the International Anesthesia Research Society. This is an
open-access article distributed under the terms of the Creative Commons
Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND),
where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially
without permission from the journal.
DOI: 10.1213/XAA.0000000000001350

November 2020 • Volume 14 • Number 13

CASE DESCRIPTION
A 22-year-old man (height, 175 cm; weight, 65 kg) was
scheduled to undergo living-donor renal transplantation.
The patient had been diagnosed with Epstein syndrome
at the age of 9 years. He had renal failure, macrothrombocytopenia, and hearing loss due to Epstein syndrome
and had started hemodialysis when he was 19 years old.
Peripheral blood examination revealed a platelet count of
37 × 109/L with giant platelets and neutrophils containing
Döhle bodies.
Anesthesia was induced with fentanyl (2 µg/kg body
weight) and propofol (2.5 mg/kg). Rocuronium was administered. Anesthesia was maintained with isoflurane (1%–
1.5%) and remifentanil (0.2–0.3 µg/kg/min) with a 50%
oxygen-air mixture. In addition to standard intraoperative
monitoring, direct arterial and central venous pressures
were monitored. Platelet counts, prothrombin time (PT),
activated partial thromboplastin time (aPTT), and ROTEM
findings were monitored.
Preoperatively, the white blood cell count was 5080/µL;
hemoglobin concentration was 9.8 g/dL; platelet count was
17 × 109 /L based on automatic blood cell counting (MEK
Nihon Kohden, Tokyo, Japan) and 37 × 109 /L based on
microscopy; international normalized ratio (INR) was 1.06;
aPTT was 30.4 seconds; and fibrinogen concentration was
359 mg/dL.
Intraoperative and postoperative laboratory coagulation
and ROTEM findings are shown in the Table. Platelet counts
were 0.0 (uncounted) to 17 × 109/L based on automatic blood
cell counting and 28–31 × 109/L based on microscopy; INR
was 0.9–1.0; fibrinogen concentration was 256 mg/dL. The α
angle (α), clotting time, and maximum clot firmness (MCF)
cases-anesthesia-analgesia.org

1

Table. Coagulation Laboratory Data and ROTEM Findings
Laboratory test

EXTEM

INTEM

FIBTEM

Platelets, ×109/L
PT, s
Fibrinogen, mg
CT, s
CFT, s
α, °
A10, mm
MCF, mm
ML, %
CT, s
CFT, s
α, °
A10, mm
MCF, mm
ML, %
A10, mm
MCF, mm
ML, %

Before surgery
37
10.3

Pretransplant
33
11.4

42
106
79
53
64
2
146
89
52
52
64
0
19
19
0

44
138
73
48
59
2
139
105
50
50
63
0
17
18
0

Posttransplant
28
11.8
256
43
155
72
46
59
3
137
118
49
49
62
0
14
15
0

After surgery
59
11.3
261
39
117
76
51
62
1
129
80
56
56
66
0
15
16
0

POD1
48
12.3
256
45
103
78
54
64
2
146
78
55
55
66
1
19
21
0

Abbreviations: α, α angle; A10, clot firmness measured at 10 min after start of clot formation; CFT, clot formation time; CT, clotting time; EXTEM, evaluation of the
extrinsic pathway; FIBTEM, evaluation of the contribution of fibrinogen to clot formation; INTEM, evaluation of the intrinsic pathway; MCF, maximum clot firmness;
ML, maximum lysis; POD, postoperative day; ROTEM, rotational thromboelastometry.

in the evaluations of the extrinsic pathways (EXTEMs; TEM
International GmbH, Munich, Germany), and contribution
of fibrinogen to clot formation (FIBTEM; TEM International
GmbH, Munich, Germany) were normal.
Operation time was 5 hours and 16 minutes, and anesthesia time was 6 hours and 47 minutes. Estimated blood
loss was 150 mL during the operation with further bleeding on postoperative day (POD) 1. The patient received no
blood transfusions and experienced no bleeding complications. The function of the transplanted kidney was stable,
and the patient was discharged from the intensive care unit
without complications except for ureteral reanastomosis
surgery on POD 2.

DISCUSSION
Macrothrombocytopenia associated with Epstein syndrome is
related to both bleeding and thromboembolic risk.1,4 Surgical
interventions in patients with MYH9-related disorders may
be associated with bleeding complications. However, it has
been reported that a wide variety of surgeries, including
dental extraction, tonsillectomy and adenoidectomy, cesarean delivery, orthopedic joint replacement, cardiopulmonary
bypass surgery, and neurosurgical intervention, can be successfully conducted without severe hemorrhage.1 Apart from
bleeding, however, there are also concerns regarding thrombosis, especially in the postoperative period.1
The recommended platelet count is >50 × 109/L for
invasive procedures and 100 × 109/L for high-risk surgeries according to the old guidelines5; however, these values were based on minimal evidence. Currently, there is
still no consensus for platelet count in perioperative settings.6 In critical care patients, there has been no reported
benefit but increased complication and mortality rates
due to liberal platelet transfusion.7 An increased mortality
rate associated with platelet transfusion has been shown
in patients undergoing liver transplantation with platelet counts both higher and lower than 50 × 109/L.8 There
is also no consensus on what platelet count is safe for surgery
in patients with MYH9-related disorders. Several reports

2   
cases-anesthesia-analgesia.org

have suggested safe platelet counts for renal transplantation in patients with MYH9-related disorders with macrothrombocytopenia. Renal transplantation was successfully
performed when the platelet count was maintained >100
× 109/L with transfusions, but bleeding complications and
intracranial hemorrhage occurred at platelet counts higher
than 50 × 109/L.9 Intraperitoneal hemorrhage on POD
19 and POD 25 occurred at platelet counts of 27 and 36 ×
109/L, but patients recovered when platelet counts were >50
× 109/L.10 These case reports and a recent case series suggest
that a safe platelet count for living-donor renal transplantation is at least 100 × 109/L with platelet transfusion.3,10
Hemostasis coagulation monitoring, especially the
monitoring of platelet function, is limited in operating
rooms. Platelet counting, a standard coagulation test, is
difficult to perform using automated blood cell counters
and should therefore be conducted using a microscope.
In our case, platelet counts based on microscopy were
higher than those based on automated blood cell counting. Because automated blood cell counters measure pulse
height values resulting from minute voltage changes,
counts may be lower if large platelets are present. Platelet
counts therefore need to be determined by visual inspection. In our case, we used ROTEM in addition to standard
coagulation monitoring of platelet counts, fibrinogen concentration, PT, and aPTT. While ROTEM is a viscoelastic
hemostatic assay that provides point-of-care monitoring
using whole blood, it does not allow for the evaluation of
platelet aggregation ability. For example, patients on an
antiplatelet agent such as clopidogrel (P2Y12 purinergic
receptor inhibitor) will often have normal tracings. Platelet
aggregation ability can be evaluated at the point of care
with ROTEM platelet or Multiplate (Roche, Switzerland)
even in patients with a low platelet count and in the
field of organ transplantation.11 These devices have been
reported to be effective in determining platelet deficiency
in clinical practice.12 It has been shown that clot firmness
in ROTEM has a superior accuracy for predicting bleeding compared to platelet counts in thrombocytopenic

A & A PRACTICE

children as well as in those undergoing liver transplantation.13 Despite low platelet counts, 70%–80% of patients
can be managed safely without platelet transfusion, if
guided by thromboelastometry.14 In the current case,
the α, clotting time, and MCF in EXTEM and FIBTEM were
normal, which suggests that the coagulation ability and
function via activated platelets were normal. The MCF of
FIBTEM was high, which may compensate for the relatively
low platelet counts, a situation often observed in liver transplantation and reported in patients on dialysis who qualified for kidney transplantation.15 In addition, because we
observed no excess bleeding in the surgical field, we did not
transfuse platelets even when the count was 26–33 × 109/L
during the perioperative period. We measured ROTEM up
to POD 1 and observed no bleeding complications.
To summarize, we could manage the patient with Epstein
syndrome characterized by macrothrombocytopenia undergoing living-donor renal transplantation without inappropriate platelet transfusion despite low platelet counts under
careful coagulation monitoring using ROTEM. E
ACKNOWLEDGMENTS

The authors thank Editage (www.editage.com) for the careful
reading and editing of the manuscript.
DISCLOSURES

Name: Midoriko Higashi, MD, PhD.
Contribution: This author helped write the original draft and
edit the later versions.
Name: Keizo Kaku, MD, PhD.
Contribution: This author helped conduct the data collection
and review and edit the manuscript.
Name: Yasuhiro Okabe, MD.
Contribution: This author helped review and edit the manuscript for submission.
Name: Ken Yamaura, MD.
Contribution: This author helped prepare the figures, review
and edit the manuscript, and supervise other stages of the preparation for submission.
This manuscript was handled by: BobbieJean Sweitzer, MD,
FACP.

November 2020 • Volume 14 • Number 13

REFERENCES
1. Althaus K, Greinacher A. MYH9-related platelet disorders.
Semin Thromb Hemost. 2009;35:189–203.
2. Balwani MR, Engineer DP, Gumber MR, et al. An unusual cause of
renal failure; Epstein syndrome. J Nephropharmacol. 2016;5:63–65.
3. Hashimoto J, Hamasaki Y, Takahashi Y, et al. Management of
patients with severe Epstein syndrome: review of four patients
who received living-donor renal transplantation. Nephrology
(Carlton). 2019;24:450–455.
4. Balduini CL, Pecci A, Savoia A. Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Br J Haematol. 2011;154:161–174.
5. Kaufman RM, Djulbegovic B, Gernsheimer T, et al; AABB.
Platelet transfusion: a clinical practice guideline from the
AABB. Ann Intern Med. 2015;162:205–213.
6. Levy JH, Rossaint R, Zacharowski K, Spahn DR. What is the
evidence for platelet transfusion in perioperative settings? Vox
Sang. 2017;112:704–712.
7. Warner MA, Chandran A, Frank RD, Kor DJ. Prophylactic
platelet transfusions for critically ill patients with thrombocytopenia: a single-institution propensity-matched cohort study.
Anesth Analg. 2019;128:288–295.
8. Pereboom IT, de Boer MT, Haagsma EB, Hendriks HG, Lisman
T, Porte RJ. Platelet transfusion during liver transplantation is
associated with increased postoperative mortality due to acute
lung injury. Anesth Analg. 2009;108:1083–1091.
9. Min SY, Ahn HJ, Park WS, Kim JW. Successful renal transplantation in MYH9-related disorder with severe macrothrombocytopenia: first report in Korea. Transplant Proc. 2014;46:
654–656.
10. Ogura M, Kikuchi E, Kaito H, et al. ABO-incompatible
renal transplantation in Epstein syndrome. Clin Transplant.
2010;24(suppl 22):31–34.
11. Soliman M, Hartmann M. Impedance aggregometry reveals
increased platelet aggregation during liver transplantation. J
Clin Med. 2019;8:1803.
12. Solomon C, Schöchl H, Ranucci M, Schlimp CJ. Can the viscoelastic parameter α-Angle distinguish fibrinogen from platelet deficiency and guide fibrinogen supplementation? Anesth
Analg. 2015;121:289–301.
13. Fayed NA, Abdallah AR, Khalil MK, Marwan IK. Therapeutic rather
than prophylactic platelet transfusion policy for severe thrombocytopenia during liver transplantation. Platelets. 2014;25:576–586.
14. Kirchner C, Dirkmann D, Treckmann JW, et al. Coagulation
management with factor concentrates in liver transplantation:
a single-center experience. Transfusion. 2014;54:2760–2768.
15. Velik-Salchner C, Haas T, Innerhofer P, et al. The effect of fibrinogen concentrate on thrombocytopenia. J Thromb Haemost. 2007;
5:1019–1025.

cases-anesthesia-analgesia.org

3