Ef fi cacy evaluation of Buyang Huanwu Decoction and Hydroxyurea in treatment with essential thrombocytosis

康財(cái)庸，榮光，孟慶剛

（北京中醫(yī)藥大學(xué) 基礎(chǔ)醫(yī)學(xué)院，北京 100029）

Ef fi cacy evaluation of Buyang Huanwu Decoction and Hydroxyurea in treatment with essential thrombocytosis

康財(cái)庸，榮光，孟慶剛Δ

（北京中醫(yī)藥大學(xué) 基礎(chǔ)醫(yī)學(xué)院，北京 100029）

Objective To evaluate the efficacy of Buyang Huanwu Decoction and hydroxyurea in treatment with essential thrombocytosis(ET).Methods120 patients with ET were randomly divided into observation group(OG) and control group(CG). Patients in OG were treated with Buyang huanwu decoction and hydroxyurea, while those in CG were only given hydroxyurea. Therapeutic effect in two groups were observed after 6 months treatment.ResultsTotal effective rate of OG was higher than that of CG(P＜0.05). TCM symptoms remission in OG was better than that in CG(P＜0.05).After treatment, blood platelet count and megakaryocyte count were decreased in both two groups(P＜0.05), and the difference between two groups was significant(P＜0.05).ConclusionThe therapeutic effect of Chinese and western medicine in treatment with ET is better than simple western medicine.

Hydroxyurea; Buyang Huanwu Decoction; essential thrombocytosis; integrated Chinese-western medicine therapy

1 Clinical materials

1.1 General materials 120 cases，collected in Taoyuan Hospital of Chinese medicine from Jan， 2010 to Jun，2013 were included in this research. They were equally divided into observation group(OG) and control group(CG) using random number table. In OG， the ages of 60 patients(male 36， female 24) were between 42-68 years and the average was 57.72±7.41 years. Their course of disease were between 11-60 months， and the average was 2.73±0.36 years. 27 cases were with the symptom of hemorrhage and 11 with thrombosis. In CG， the ages of 60 patients(male 27， female 33)， were between 45-62 years， and the average age was 52.19±10.10 years. Their course of disease were between 10-60 months， and the average was 3.15±0.28 years. 36 cases were with the symptoms of hemorrhage and 24 with thrombosis. The differences of sex， age， the course of disease and symptoms between two groups were not statistically significant.

Diagnostic criteria Our diagnostic criteria was established by the ET diagnostic criteria 2001 proposed by WHO[12]： a. Clinical manifestations： the presence of disease history of hemorrhage and/or thrombosis， or the presence of splenomegaly； b. Hemogram shows a platelet count above 600×109/L； c. Mylogram shows the overproduction of megakaryocytes and the sizes are uncommonly large with the predominance of mature type.The diagnostic criteria in a sense of Chinese medicine includes limb numbness， lip and nail cyanosis， discomfort feeling in abdominal region； dark purple discoloration of tongue with thin and white coating and the pulse felt to be thready and choppy.

Exclusion criteria： a. Patients show symptoms inconsistent with the above-mentioned diagnostic criteria；b. The disease is compbined with severe primary disease(s) involving blood vessels， brain， liver and kidney. c. Patients in pregnancy or lactation. d. Patients with allergy； e. patients with other myeloproliferative disorders. f. Patients with secondary or reactive thrombocytosis such as acute blood loss， inflammation，tumor， post-splenectomy， autoimmune hemolytic anemia and convalescence after the medication of myeloproliferation inhibitor. g. Patients refuse to take part in the research； h. Non-compliant patients.

1.2 Treatment methods Control group was given hydroxyurea 15mg/kg， orally taken， once daily，combined with interferon of 3，000，000 U， intramuscular injected， every two days. Treatment group was given Yang-Supplementing and Five-Returning Decoction(buyang huanwu Decoction， 補(bǔ)陽還五湯) on the basis of CG. The formula of buyang huanwu is as follows：Astragalus membranaceus(黃芪) 120g； Angelica sinensis(當(dāng)歸) 6g； Radix Paeoniae Rubra(赤芍) 4.5g；Ligusticum wallichii(川芎) 3g； earthworm (地龍) 3g； Semen Persicae(桃仁) 3g； Carthamus tinctorius(紅花) 3g. The formula was decocted with water， and then divided equally into 2 dosages. A patient was given a dosage once， twice daily. Patients in both two groups were treated for 6 months， which was regarded a course. The effecicy was observed after a course has been finished，.

1.3 Indicators

1.3.1 Effectiveness indicators： a. Clinical manifestations： limb numbness， lip and nail cyanosis，abdominal discomfort， hemorrhage and thrombosis (each symptom was scored as none， mild， moderate or severe，which was scored as 0， 5， 10 or 15， respectively)； b.Major physical signs： body temperature， pulse rate，breaths， blood pressure， cardio-pulmonary function，liver-spleen function， tongue coating， pulse manifestation；c. pathological findings： peripheral hemogram (platelet counts)， myelogram (megakaryocyte counts).

1.3.2 Safety indictors： urine routine； fecal routine；electrocardiogram； liver function； possible side effects.

1.4 The determination of effectiveness

1.4.1 The criteria for determining effectiveness[13]：Responsive： the platelet counts reduce to below 600×109/L， or 50% of the counts before treatment with no relapse for at least 4 weeks； Partially responsive： the platelet counts reduce by 20%-50% of the number before treatment； Non-responsive： the platelet counts reduce by no more than 20% of the number before treatment.

1.4.2 The criteria for determining the effectiveness for solving symptoms in a sense of Chinese medicine：Clinically recovered： The symptoms and signs in a sense of Chinese medicine completely or almost completely disappear， and the reduction of syndrome scores is above 95%； Significantly responsive： The symptoms and signs in a sense of Chinese medicine are to a large extent ameliorated， and the reduction of syndrome scores is above 70%； Responsive： The symptoms and signs in a sense of Chinese medicine are moderately ameliorated， and the reduction of syndrome scores is above 30%； Nonresponsive： The symptoms and signs in a sense of Chinese medicine show no improvement， and the reduction of syndrome scores is below 30%.

1.5 Statistical methods The datas were collected and analyzed with SPSS 18.0， P＜0.05 was statistically significant. The datas were described with “±s”. Before the inter-group comparisons were drawn， the normality test was performed to find out if the data conforms to normal distribution. If it does， the pair t test will be performed； if it does not， corrected t test will be used.

2 Results

2.1 The effectiveness in OG and CG post-therapy Total effective rate of OG was higher than that of CG， the difference between two groups was statistically significant (P＜0.05). See Tab.1.

Tab.1 Comparison of treatment effectiveness between OG and CG

2.2 Treatment effectiveness in a sense of Chinese medicine between OG and CG

The total effective rate of OG was higher than that of CG， the difference between two groups was statistically significant(P＜0.05). See Tab. 2.

Tab.2 Comparison of treatment effectiveness between OG and CG in a sense of Chinese medicine

2.3 Pre-and Post-treatment platelet and megakaryocyte counts between TC and CG

After treatment， patients in both groups showed a decrease in platelet and megakaryocyte counts， and this decrease went especially significant in OG in comparison to CG with the difference being statistically significant(P＜0.05). See Tab. 3.

Tab.3 Comparison of platelet count and megakaryocyte count pre- and post-treatment between TC and CG

2.4 Adverse effects During the treatment， no adverse effect was observed in patients from OG， while 3 case of fever and 3 case of gastrointestinal reaction were found in patients from CG， the incidence rate was 10%.

3 Discussion

Although the pathogenesis of ET is unclear， it is a kind of myeloproliferative disorder. In present， most researchers believe that the mechanism of the platelets overproduction are as follows： a. the spontaneous proliferation of megakaryocytes； b. the over-release of platelets by megakaryocytes； c. extramedullary hematopoiesis； d. over-release of platelets from spleen and lung[14]. So， the treatment of ET is to inhibit the proliferation. However， there are some limits in the prevailing treatment methods， and it was reported that Busulfan and Hydroxyurea may be evolved in acute leukemia[15].

As clinical manifestations， ET can be categorized into “blood syndrome” or deficiency-consumption in the domain of Chinese medicine. Its cause and mechanism are deficiency， toxin and stasis. Deficiency means the weakening of healthy qi， which cause is too much laboring or improper diet. Toxin stands for exogenous evils combined with heat toxin， and it invades human body as it is in a deficient condition， leaving the blood and qi consumed. As for stasis， when there is emotional disorders that incurs disharmony between channels and collaterals，the qi stagnation and blood stasis can accumulate in human body and finally cause the disease. Buyang Huanwu Decoction is typically suitable for solving these problems.In this study， integrated Chinese-western medicine was adopted， patents with ET were treated with hydroxyurea，interferon and Buyang Huanwu Decoction， the efficacy of it was compared with those simply treated with hydroxyurea and interferon. Total effective rate， Chinese medicine symptom scores ， platelet and megakaryocyte counts， side effects in OG were better than that in CG. It can be concluded that the therapeutic effect of ET treated with Chinese and western medicine is better than simple western medicine， not only in ameliorated symptoms ， but reduced platelet ， megakaryocyte counts and stable disease condition.

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KANG Cai-yong,RONG Guang,MENG Qing-gangΔ
（Basic Medical College, Beijing University of Chinese Medicine, Beijing 100029, China）

補(bǔ)陽還五湯配合羥基脲治療原發(fā)性血小板增多癥的效果評估

目的評估補(bǔ)陽還五湯配合羥基脲治療原發(fā)性血小板增多癥的臨床效果。方法將120例原發(fā)性血小板增多癥患者隨機(jī)均分為2組。觀察組60例采用補(bǔ)陽還五配湯合羥基脲治療；對照組60例采用羥基脲治療。6個(gè)月后評估治療效果。結(jié)果治療后，觀察組療效好于對照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0．05）；觀察組中醫(yī)證候緩解程度優(yōu)于對照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0．05）。2組治療后血小板計(jì)數(shù)、巨核細(xì)胞計(jì)數(shù)均有所下降；與對照組比較，觀察組患者治療后血小板計(jì)數(shù)、巨核細(xì)胞計(jì)數(shù)下降更為明顯，差異均具有統(tǒng)計(jì)學(xué)意義（P＜0．05）。結(jié)論中西醫(yī)結(jié)合治療在治療原發(fā)性血小板增多癥方面優(yōu)于單純西醫(yī)療法。

羥基脲；補(bǔ)陽還五湯；原發(fā)性血小板增多癥；中西醫(yī)結(jié)合療法

R 259

A

1005-1678(2014)02-0111-03

北京中醫(yī)藥大學(xué)創(chuàng)新團(tuán)隊(duì)項(xiàng)目（2011CXTD03）；十二五科技支撐計(jì)劃項(xiàng)目（2013 BAI 102 B10）

康財(cái)庸，男，博士，研究方向：中醫(yī)基礎(chǔ)理論體系構(gòu)建,E-mail:ddoctorkangtw@yahoo.com.tw;孟慶剛，通信作者,男,博士，教授，主任醫(yī)師，博士生導(dǎo)師，研究方向：中醫(yī)理論體系研究，E-mail：mqgang@126.com。

Essential thrombocytosis(ET) is a clonal disorder which originated in a multi-potent stem cell.Approximately 1-2.5 people per 100，000 are diagnosed with ET，and the peak age of disease incidence is 50-70.years old[1-6]. The pathogenesis of ET is not yet to be understood， but it is characterized by latent and slowly disease progression and platelets overproduction significantly， and always compbined with hemorrhage and thrombosis[7-8]. In modern medicine， ET is always treated with myelo-proliferation inhibitor， interferon or therapeutic apheresis. These methods were not highly acceptable due to long-term medication， frequent relapses after drug discontinuation， serious side-effect and high cost， though these therapies can reduce the level of platelets at varying degrees[9-11]. In this study， 60cases with ET were treated in a pattern of “deficiency of qi and blood”(氣血虧虛，a specific pattern of a host of diseases with similar mechanism in the domain of Chinese medicine) therapy of integrated Chinese-western medicine， another 60 cases with ET were simply treated with western medicine， the efficacy of two methods were observed and compared.