CASE REPORT
CASE REPORTS OF IDIOPATHIC THROMBOCYTOPENIA
UNRESPONSIVE TO FIRST-LINE THERAPIES TREATED
WITH TRADITIONAL HERBAL MEDICINES BASED ON
SYNDROME DIFFERENTIATION
Juno Yang, KMD, PhD1,a Beom-Joon Lee, KMD, PhD2,a and
Jun-Hwan Lee, KMD, PhD3,4#
The objective of our study is to present two cases showing the
effects of traditional Korean herbal medicines based on tradi-
tional Korean medicine (TKM) for the treatment of immune
thrombocytopenic purpura (ITP). One patient showed no
response to treatment with steroids and an immunosuppres-
sive agent. Moreover, liver toxicity and side effects of steroids
were evident. However, after he ceased conventional treatment
and started to take an herbal medicine, his liver function
normalized and the steroid side effects resolved. Ultimately, he
achieved complete remission. Another patient with ITP had
sustained remission after steroid therapy in childhood, but
extensive uterine bleeding and thrombocytopenia recurred
when she was 16 years old. She was managed with steroids
again for 2 years, but severe side effects occurred, and
eventually she ceased taking steroids. She refused a
INTRODUCTION
Primary idiopathic thrombocytopenic purpura (ITP) or pri-
mary immune thrombocytopenia, is characterized by platelet
destruction (to o100  109/L) in the absence of other causes
or disorders that may be associated with thrombocytopenia.
The main clinical challenge of primary ITP lies in the
increased risk of bleeding, although bleeding symptoms,
including epistaxis, petechiae, bruising, and purpura, are not
always present.1
1 Kyungheeyedang Oriental Medical Clinic, Suwon-City, Kyonggi-do,
Republic of Korea
2 Division of Allergy, Immune and Respiratory System, Department
of Internal Medicine, College of Korean Medicine, Kyung Hee
University, Seoul, Republic of Korea
3 Clinical Research Division, Korea Institute of Oriental Medicine,
Daejeon, Republic of Korea
4 Korean Medicine Life Science, University of Science & Technology
(UST), Campus of Korea Institute of Oriental Medicine, Daejeon,
Republic of Korea
a
Juno Yang and Beom-Joon Lee contributed equally as first
author.
# Correspondence to: 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054,
Republic of Korea.
e-mail: omdjun@kiom.re.kr
68 & 2017 The Authors. Published by Elsevier Inc. This is an open
access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
ISSN 1550-8307/$36.00
splenectomy, and was then treated with a herbal medicine
for 7 months, ultimately leading to sustained remission
again. Many patients with resistance to first-line treatments
tend to be reluctant to undergo a splenectomy, considered a
standard second-line treatment. In conclusion, herbal med-
icines, based on TKM, may offer alternative treatments for
persistent or chronic ITP that is resistant to existing first-line
treatments.
Keywords: idiopathic thrombocytopenic purpura, traditional
Korean medicine, syndrome differentiation, herbal medicine
(Explore 2017; 13:68-74 & 2017 The Authors. Published by
Elsevier Inc. This is an open access article under the CC BY-NC-
ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)
The primary first-line treatment of ITP is corticosteroids and
intravenous immunoglobulin (IVIG) or anti-D globulin (anti-
D). Corticosteroids are usually the first choice, and IVIG or
anti-D is used as first-line treatment for patients for whom
steroids are contraindicated. If first-line therapies fail, splenec-
tomy, rituximab, immunosuppressive agents (e.g., cyclophos-
phamide and azathioprine), and thrombopoietin-receptor
agonists (e.g., romiplostim and eltrombopag) may be consid-
ered as second-line treatments.2,3
Splenectomy has also been regarded as a standard second-
line treatment in the management of patients who are
refractory to first-line treatments. Other second-line therapies
are considered after the failure of splenectomy, but they are
expensive and have various side effects.3 However, many
patients are reluctant to undergo a splenectomy because of
the unpredictability of the response,4 its invasiveness,5 and
possible complications.6,7 Thus, many patients tend to post-
pone or avoid a splenectomy when possible.8
Between adults and children with ITP, there are several
clinical differences. In the case of adult ITP treatment, the
spontaneous remission rate is lower, corticosteroids are used
more frequently, and splenectomy is more often considered.9
Syndrome differentiation is not only a typical traditional
Korean medical diagnostic system but also a key concept in
the practice of traditional Korean medicine (TKM). According
EXPLORE January/February 2017, Vol. 13, No. 1
http://dx.doi.org/10.1016/j.explore.2016.10.007
to the syndrome differentiation diagnostic system, a disease
can be categorized into any of several different patterns based
on the analysis of clinical information obtained from the
following four major traditional diagnostic procedures: obser-
vation, listening, questioning, and pulse analyses. These
patterns are also used in traditional medical treatments,
including the prescription of herbal medicine and acupunc-
ture.10–12
There have been some reports demonstrating the efficacy of
herbal medicine instead of first-line treatments for ITP,13,14
and there was one report of treatment of childhood persistent
ITP with herbal medicine.15 However, there has been no
report demonstrating the effectiveness of herbal medicine in
treating adult persistent or chronic ITP patients who were
unresponsive to standard first-line therapies, based on the
syndrome differentiation diagnostic system.
Thus, in this article, we present two ITP patients, both of
whom were unresponsive to the first-line treatment or discon-
tinued conventional treatment due to the side effects of
steroids. Nonetheless, they achieved complete or partial
remission by taking herbal medicines based on syndrome
differentiation without requiring a splenectomy. Fig. 1. Timeline of interventions and outcomes in case 1. PDN,
prednisone; AZ, azathioprine; CS, cyclosporine; TKM, traditional
Korean medicine, red arrow: TKM clinic visit day.
CASE 1
A 25-year-old male patient, a Korean student who resided in platelet count of 49  109/L and aspartate aminotransferase
the Philippines, visited a local hospital with high fever (AST)/alanine transaminase (ALT) of 211/230 UI/L. The
(4401C) and a decreased platelet count (o100  109/L) in patient was taking oral prednisone 60 mg/d, calcium carbonate
January 2011, and was treated for dengue fever. The fever 40 mg/d, furocemide 40 mg/d, and celecoxib 400 mg/d.
became stable after 1 week, but the thrombocytopenia per- The patient was administered modified jigolpieum water
sisted. A bone marrow biopsy showed moderate megakaryo- extract orally (Table 1) three times per day under a diagnosis
cytic hyperplasia, and treatment with oral prednisone 60 mg/d of persistent ITP, and furocemide was stopped. After three
was started for newly diagnosed ITP on February 4. However, weeks, his platelet count increased to 126  109/L, and the
the patient was unresponsive to the treatment, and azathio- AST/ALT ratio decreased to 130/150 UI/L. The prednisone
prine 100 mg/d and prednisone 180 mg/d were administered was tapered down to 30 mg/d. However, the platelet count
orally on February 18. Subsequently, the patient started to then fell to 49  109/L because of the reduced steroid dose.
suffer from side effects of the steroid, including weight gain Thus, the herbal medicine was changed to a modified
and swelling, and liver toxicity was detected in a biochemical seongyutang with Salviae miltiorrhizae radix and Scutellariae
analysis on March 22. The azathioprine was replaced by radix water extract (Table 2). Subsequently, the platelet
cyclosporine 200 mg/d due to the liver toxicity. On April count increased again, and the AST/ALT ratio decreased
26, because of persistent liver toxicity, the immunosuppressive gradually. After three months, the steroid was discontinued.
drug—cyclosporine was stopped, and prednisone was reduced After four months, the platelet counts and AST/ALT ratio
to 60 mg/d. However, the platelet count still did not increase. were 232  109/L and 54/62 IU/L, respectively, the cutaneous
Moreover, the patient could not walk properly due to vertebral wound had healed, and the general condition of the patient
pain, weight gain, and peripheral edema in both legs. The had improved. Thus, the dose of the herbal medicine was
patient eventually came to Korea and visited our clinic in a tapered to two-thirds the previous dose. After five months, the
wheelchair on August 5 (Fig. 1). platelet counts and AST/ALT ratio were 184  109/L and 41/
On physical examination, the patient was unable to walk 47 IU/L, respectively, indicating a complete response; how-
due to severe back pain and peripheral edema and had a ever, the platelet count was maintained at 4100  109/L3.
cutaneous wound on his ankle that was not healing well. He Given the patient's recovery, the herbal medicine was discon-
was suffering from side effects of the steroid: moon face, tinued on January 7, 2012. Even with no medication, there
edema, weight gain, muscle weakness, and pain in the back was no bleeding sign, and the platelet count was still 4150 
and knees. An erythematous facial complexion and dark red- 109/L on May 15, 2014 (Fig. 2).
colored tiny petechiae were observed around his trunk and
neck. The patient also reported fatigue, mild irritability,
insomnia, thirst, and yellow urine. A taut, rapid, and weak CASE 2
pulse was found on pulse examination. A dark red and dry This 20-year-old female patient suffered from a common cold
tongue was observed. However, he had no bleeding symp- when she was eight years old. A local pediatric doctor
toms, and no splenomegaly. Laboratory analyses showed a administered a cutaneous intermuscular injection of

ITP Treated with Traditional Herbal Medicines EXPLORE January/February 2017, Vol. 13, No. 1 69
Table 1. Ingredients and Doses of the Modified jigolpieum Water Extract Used in Case 1 and Activities of the Herbs
Pharmaceutical Name Total Daily Dose (g/d) Main Activity of Herbal Drug in This Case
Lycii radicis cortex 15 Clear deficiency in heat
Moutan cortex 15 Activate blood and resolve stasis
Ginseng radix 12 Tonify Qi and engender fluid
Zingiberis rhizoma siccus 12 Tonify Qi and warm the interior
Cinnamomi cortex spissus 12 Tonify Qi and tonify Yang
Glycyrrhizae radix 6 Tonify Qi and harmonize Qi and blood
Angelicae gigantis radix 6 Nourish Yin and harmonize the blood
Cnidii rhizoma 6 Nourish Yin and activate blood; move Qi
Paeoniae radix rubra 6 Nourish Yin and activated blood; resolve stasis
Rehmanniae radix 6 Nourish Yin; enrich Yin; and subdue Yang
Poria (Hoelen) 12 Drain dampness and invigorate spleen and stomach
Alismatis rhizoma 12 Induce diuresis to alleviate edema

antibiotics in her hip, which produced an extensive hematoma
in the injected area. The patient was transferred to the
emergency room and treated with IVIG; however, treatment
with steroids was maintained under a diagnosis of ITP. A bone
marrow biopsy revealed erythroid hyperplasia and increased
megakaryocytes. Despite the severe side effects of the steroids
(stomach irritation, swelling, weight gain, and moon face), the
patient achieved a sustained remission approximately after six
months. When the patient was 16 years old, she experienced
extensive uterine bleeding, and her platelet count decreased to
8  109/L on January 10, 2010. She was treated with two
cycles of IVIG, 1.0 g/kg/d intravenously for two days, and with
oral steroids 60 mg/d based on a diagnosis of relapsed severe
chronic ITP. She continued the oral steroid treatment for
approximately two years, and she showed a partial response
and sustained remission. However, the platelet count decreased
to 37  109/L on February 2, 2011. Furthermore, steroids side
effects such as bone pain, alopecia, weight gain, swelling, and
fibromyalgia made the patient's symptoms much more serious.
She finally stopped taking the steroids and visited our clinic
seeking an alternative treatment on April 4, 2011 (Fig. 3).
On physical examination, the patient had no bleeding or
petechiae. Her general condition was poor, and she felt
tired all the time. She was reported to have experienced
lassitude, emaciation, low voice, dry mouth and throat,
dizziness, mild insomnia, spontaneous sweating, intermit-
tent palpitations, and delayed menstruation cycles. A thin,
weak, and rapid pulse was noted on pulse examination.
A pale tongue proper without coating was observed on
tongue examination.
She was treated with oral modified seongyutang with
Salviae miltiorrhizae radix, Artemisiae apiaceae herba, Lycii
radicis cortex, Biotae cacumen, and Lonicerae flos water extract
(Table 3) three times per day. Although her platelet count
temporarily fell to 44  109/L due to hives, supposedly
caused by the summer heat, her platelet count increased
gradually for seven months. On November 11, 2011, her
platelet count was maintained at 61  109/L and we stopped
the herbal medicine and continued to observe the patient.
Since then, there has been no bleeding sign; her platelet
count was 90  109/L on July 6, 2012, and 93  109/L on
June 5, 2014 (Fig. 4).

Table 2. Ingredients and Doses of the Modified seongyutang Water Extract Used in Case 1 and Activities of the Herbs
Pharmaceutical Name Total Daily Dose (g/d) Main Activity of Herbal Drug in this Case
Astragali radix 30 Tonify Qi and secure the exterior
Ginseng radix 12 Tonify Qi and engender fluid
Zingiberis rhizoma siccus 12 Tonify Qi and warm the interior
Cinnamomi cortex spissus 12 Tonify Qi and tonify Yang
Glycyrrhizae radix 6 Tonify Qi; harmonize Qi and blood
Angelicae gigantis radix 6 Nourish Yin and harmonize the blood
Cnidii rhizoma 6 Nourish Yin, activate blood, and move Qi
Paeoniae radix rubra 6 Nourish Yin and activated blood; resolve stasis
Rehmanniae radix 6 Nourish Yin; enrich Yin; and subdue Yang
Atractylodis rhizoma 6 Resolve dampness to move Qi and fortify the spleen
Salviae miltiorrhizae radix 15 Tonify blood and activated blood to resolve stasis
Scutellariae radix 15 Purge fire, clear heat, and detoxify

70 EXPLORE January/February 2017, Vol. 13, No. 1 ITP Treated with Traditional Herbal Medicines
Fig. 2. Changes in platelet counts and AST/ALT ratio during the course of treatment in case 1. Plt, platelets; AST, aspartate aminotransferase;
ALT, alanine transaminase.
DISCUSSION
Primary ITP is an acquired autoimmune disorder characterized
by a low platelet count in the peripheral blood without any
recognized cause, mediated by platelet antibodies that accel-
erate platelet destruction, and inhibit their production.2,16
Population-based studies have estimated the incidence of ITP
to be 1.9–6.4 per 100,000 children and 3.3 per 100,000 adults
per year.17 However, although two-thirds of newly diagnosed
Fig. 3. Timeline of interventions and outcomes in case 2. PDN,
prednisone; IVIG, intravenous immunoglobulin, red arrow: TKM clinic
visit day.
ITP Treated with Traditional Herbal Medicines
children obtain complete responses with the first-line treat-
ment,  30% of children with newly diagnosed ITP progress
to persistent or chronic ITP.18 In Korea, 22.5–37% of children
with ITP develop persistent or chronic ITP,19 whereas  60%
of adults with newly diagnosed ITP maintain a response after
initial treatment with standard first-line therapies, although
most adult patients exhibit chronic relapse after one year.20,21
Second-line therapies, including splenectomy, rituximab,
immunosuppressive agents (e.g., cyclophosphamide and aza-
thioprine), and thrombopoietic-receptor agonists (e.g., romi-
plostim and eltrombopagand), are indicated for those patients
who are unresponsive to or relapse after initial first-line
therapies.3 For decades, splenectomy has been considered a
standard second-line therapy because it is highly effective and
inexpensive compared with other second-line therapies.2,22
Additionally, each of the other second-line therapies has
unique potential toxicities, such as immune suppression,
secondary malignancies, hypertension, and hepatic toxicity.
Thus, splenectomy has been recommended for patients who
fail corticosteroid therapy.3 Nevertheless, the number of
patients who opt to avoid a splenectomy has increased.5,23
Many patients are simply reluctant to remove a healthy organ
that has multiple hematological and immunological functions,
and to undergo an invasive and irreversible procedure. More-
over, the procedure itself can cause mortality and increases the
morbidity of various complications, including bacterial sep-
sis,7 vascular disease such as venous thromboembolism or
atherosclerosis,24 thrombosis,25 prolonged hospitalization,
readmission to the hospital, and the requirement of
additional interventions.6,8 In children, in particular, post-
splenectomy sepsis has risen to 3%, and an increased risk of
sepsis probably persists for life.2
In Korea, there are various norms for ITP treatment. Most
patients receive their initial diagnosis and management from a
EXPLORE January/February 2017, Vol. 13, No. 1 71
Table 3. Ingredients and Doses in the Modified seongyutang Water Extract Used in Case 2 and Activities of the Herbs
Pharmaceutical Name Total Daily Dose (g/d) Main Activity of Herbal Drug in this Case
Astragali radix 30 Tonify Qi and secure the exterior
Ginseng radix 12 Tonify Qi and engender fluid
Zingiberis rhizoma siccus 12 Tonify Qi and warm the interior
Cinnamomi cortex spissus 12 Tonify Qi and tonify Yang
Glycyrrhizae radix 6 Tonify Qi; harmonize Qi and blood
Angelicae gigantis radix 6 Nourish Yin and harmonize the blood
Cnidii rhizoma 6 Nourish Yin, activate blood, and move Qi
Paeoniae radix rubra 6 Nourish Yin and activated blood; resolve stasis
Rehmanniae radix 6 Nourish Yin; enrich Yin; and subdue Yang
Salviae miltiorrhizae radix 15 Tonify blood and activated blood; resolve stasis
Artemisiae apiaceae herba 6 Clear heat to cool the blood
Lycii radicis cortex 15 Clear deficiency heat
Biotae cacumen 30 Dissipate blood stasis and resolve phlegm
Lonicerae flos 6 Clear heat to cool the blood and detoxify

hematologist and routinely undergo a bone marrow examina-
tion. Regarding treatment, corticosteroids and anti-D are used
commonly as first-line pharmacological treatments over IVIG,
and splenectomy is generally considered for ITP patients who
show first-line treatment resistance.26,27 Nonetheless, because
of complications, many patients in Korea have also been
opting to defer a splenectomy as long as possible, and the need
for alternative therapies before splenectomy to manage ITP
unresponsive to first-line therapy has, therefore, increased.
The main treatment goal in all ITP patients must be to
maintain a safe platelet count, that is, not to normalize the
platelet count, but keep it at a level that will prevent or stop
major bleeding. However, no treatment objective in persistent
or chronic ITP has been firmly defined as yet, and it is often
driven by the desire to postpone or avoid the risks of more
extreme treatments such as a splenectomy or immunosuppres-
sion.28 Generally, most fatal bleeding has been reported to
occur in ITP patients whose platelet counts were o30  109/L.
Thus, a platelet count of 430  109/L is generally considered
safe for patients who do not perform physical labor, such as
Fig. 4. Changes in platelet counts during the course of treatment in
case 2.
carpenters or farmers.29 In this study, we defined remission as
Z26 consecutive weeks of a platelet count Z50  109/L after
discontinuing the herbal medicine with no other ITP
treatment, 30 and complete remission was defined as a
platelet count Z100  109/L.
Traditional herbal medicine has been used for thousands of
years in Korea. From the point of view of pathology, in
traditional medicine based on syndrome differentiation, ITP is
caused by blood heat expelling the blood from the vessels,
which induces bleeding, such as epistaxis, plurimenorrhea,
ulemorrhagia, and petechiae. After bleeding, the extravasated
blood stagnates in the body (blood stasis) and inhibits
circulation, so as to aggravate the bleeding.31 In the chronic
stage, the retained blood heat and extravasated blood, which
act like toxins, can exhaust Qi and Yin, resulting in their
deficiency.32 Thus, chronic ITP is treated primarily by
dissipating blood heat, removing toxins, promoting blood
circulation, and by tonifYing Qi and nourishing Yin.33,34
In Case 1, the patient was treated with prednisone as an
initial therapy. Prednisone generally shows an initial response
within two weeks,2 but the patient was unresponsive to the
steroid. Thus, an immunosuppressant was added, and the
steroid dose was increased. However, the patient failed to
show any response over three months, and he experienced side
effects, including liver toxicity. The patient ceased the ongoing
conventional therapies and visited our clinic when the disease
had progressed to a chronic stage. We diagnosed him with
persistent ITP and a blood heat–predominant pattern, based
on Yin and Qi deficiency complex syndrome, according to the
traditional syndrome differentiation diagnosis system. Thus,
we administered a modified jigolpium water extract to initially
clear the toxins including the blood heat. He responded well,
and the steroid was tapered, but his platelet count then
decreased again. Next, we changed the herbal medicine to a
modified seongyutang water extract, invigorating the Qi and
Yin to promote blood circulation. After that, he showed a
continued complete response, and we discontinued the herbal
treatment. Three years later, he exhibited sustained complete

72 EXPLORE January/February 2017, Vol. 13, No. 1 ITP Treated with Traditional Herbal Medicines
remission, defined, as above, by a platelet count 4100  109/L
without treatment.
In Case 2, the patient experienced sustained remission after
steroid therapy in childhood, but thrombocytopenia recurred
with a low platelet level, 8  109/L, in January 2011. She
started to undergo ITP treatment again and continued to take
oral steroids with a platelet count 430  109/L for two years.
However, after two years of treatment, she had to discontinue
the steroid treatment because of side effects. She visited our
clinic for an alternative therapy, and we diagnosed her with a
blood-heat subordinate pattern based on Qi and Yin defi-
ciency complex syndrome. Thus, we treated her with a
modified seongyutang water extract for seven months. She
showed a continued partial response, defined as platelet count
430  109/L.3 Given her busy schedule, the absence of
bleeding allowed us to discontinue the herbal medicine and to
apply a “watchful observation” strategy.29 At about two years
later, her remission continued.
In conclusion, herbal medicine based on TKM offers
potential alternative therapies for patients with persistent or
chronic ITP who do not respond sufficiently to the first-line
treatments: corticosteroids, IVIG, and anti-D. Still, very little
is known about the biological mechanism of traditional herbal
medicines, and only limited data were generated in this study.
Thus, further studies, including case–control studies and
randomized control trials with larger population sizes, are
needed to demonstrate the efficacy, safety, and biological
mechanism of herbal medicines in the treatment of ITP.
CONFLICTS OF INTEREST
The authors declare that they have no conflict of interest
regarding the publication of this article.
The English in this document has been checked by at least
two professional editors, both native speakers of English. For a
certificate, please see http://www.textcheck.com/certificate/
pkLssI
Acknowledgments
This research was supported by the Korea Institute of Oriental
Medicine, South Korea (K16121)
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ITP Treated with Traditional Herbal Medicines