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ORIGINAL ARTICLE
Year : 2023 | Volume
: 9
| Issue : 4 | Page : 438-446
Clinical factors affecting platelet growth in the treatment of aplastic anemia by tonifying kidney and generating blood
Jian Liu1, Chao-Chang Zhang2, Sheng-Qi Zhang1, Jin-Huan Wang3, Rui-Rong Xu4, Shu-Lian Yang5, Tao Wang6, Qi-Feng Liu7, Hai-Xia Wang8, Xu-Dong Tang2
1 Graduate School, Beijing University of Chinese Medicine, Beijing, China
2 Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
3 Department of Hematology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
4 Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
5 Department of Hematology, Langfang Hospital of Traditional Chinese Medicine, Langfang, China
6 Department of Hematology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
7 Department of Hematology, Jilin Provincial People's Hospital, Changchun, China
8 Department of Hematology, Affiliated Hospital of Weifang Medical University, Weifang, China
Correspondence Address:
Prof. Xu-Dong Tang
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100 091
China
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2311-8571.391115
Objective: To investigate the influence of kidney-tonifying and blood-generating method on platelet (PLT) growth in the treatment of aplastic anemia (AA) and analyze the characteristics of the clinical factors affecting PLT growth. We enrolled patients treated from September 2018 to March 2021 in the China Academy of Traditional Chinese Medicine (TCM) Xiyuan Hospital, China Academy of TCM hospital gate 19 sub-center. We enrolled 128 AA patients, for whom the inclusion criteria were: treatment is given priority to with kidney and heart's-blood method, on the basis of western medicine treatment for kidney fill party avoid Fried instant particles, stay for 3 months for a period of treatment, taking two consecutive period of treatment, changes in the PLT were observed, and the clinical characteristics of AA patients, such as PLT growth and recovery from baseline value, were analyzed. Materials and Methods: A total of 128 AA patients from 19 branches of Xiyuan Hospital, China Academy of Chinese Medical Sciences and Guang'anmen Hospital, China Academy of Chinese Medical Sciences treated from September 2018 to March 2021 were enrolled. The treatment was based on the kidney-tonifying and blood-generating method and lasted for 3 months as a course of treatment. The changes in the number of PLT in patients were observed, and the clinical characteristics of AA affecting PLT growth and recovery from baseline value were analyzed. Results: After 6 months of treatment following the kidney-tonifying and blood-generating method, PLT increased from the baseline values in 75 cases, including 21 cases of AA with normal PLT recovery and 54 cases of AA without normal PLT recovery. There were 53 cases of AA in whom PLT did not increase from the baseline. Analysis of the general data showed that patients with lower Karnofsky Performance Status (KPS) score were more likely to experience PLT growth or even return to normal after therapy (P < 0.05). The results of routine blood analysis showed that when hemoglobin (HGB) was ≥60 g/L and the reticulocyte (RET) proportion was ≥0.3% before treatment, PLTs were more likely to increase, even returning to normal in some patients (P < 0.05). Analysis of bone puncture results before treatment showed that when the proliferation of nucleated cells was low or extremely low in bone puncture examination, with the proportion of granulocytes <40%, and the proportion of erythroid cells <20%, the treatment method was more effective at increasing PLT count (P < 0.05). Analysis of the chromosome karyotype results before treatment showed that when the chromosome karyotype was normal, PLTs were more likely to increase or even return to normal after treatment (P < 0.05). Analysis of T-lymphocyte subsets before treatment showed that when CD3+ human leukocyte antigen (HLA)-DR+ proportion was ≥30%, PLTs were more likely to increase or even return to normal (P < 0.05). Conclusions: AA patients with a low KPS score, higher HGB ≥60 g/L, RET proportion ≥0.3%, low or extremely low proliferation of nucleated cells, granulocytes proportion <40%, erythroid proportion <20%, normal chromosome karyotype, CD3+HLA-DR+ ≥30%, should be treated with a kidney-tonifying and blood-generating method. Such patients are more likely to show PLT growth and the values may even return to normal.
Keywords: Aplastic anemia, influencing factor, integrated traditional Chinese and Western medicine treatment, method of tonifying kidney and generating blood, platelet
Aplastic anemia (AA) is a bone marrow hematopoietic disorder caused by single or multiple factors. AA manifests as hypoplasia of bone marrow nucleated cells and peripheral whole blood cytopenia, without abnormal cell infiltration or myelofibrosis.[1] The most common clinical features of AA are anemia, hemorrhage, and infection of varying degrees.[2] At present, the pathogenesis of AA has not been fully elucidated, although it is generally believed to be related to immune abnormalities, hematopoietic microenvironment defects, hematopoietic stem cell abnormalities, and genetic abnormalities. A large number of studies have proved that T-lymphocytes are closely related to hematopoietic failure.[3] In this context, the wide application and strong efficacy of immunosuppressants have confirmed the significance of immunopathology in the occurrence and development of AA.[4],[5]
AA has no name in traditional Chinese medicine (TCM). However, according to its clinical manifestations, AA is classified into the categories of “asthenia,” “blood asthenia,” and “medulla.”[6] “Pulp” represents the location of the disease, and “Lao” represents its pathogenicity.[7]Huangdi Neijing describes it as “Bone marrow is solid, qi and blood are sufficient.” The etiology of AA in TCM includes genetic factors, exogenous factors, improper diet, the disorder of the seven emotions, and drug poisoning that damage the viscera and organs, depleting the essence and leading to deficiency of qi and blood.[8] The treatment of AA in TCM includes the differentiation of qi and blood to the differentiation of zang-fu organs, and it has gradually been recognized that “kidney deficiency” is the key to the pathogenesis of AA. As such, TCM experts have begun to explore the theory and clinical practice of treating AA from the perspective of the kidney.[9] The method of tonifying kidney and generating blood is the main treatment for patients with kidney deficiency syndrome, for which the clinical effect is remarkable.
The Hematology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences, has been at the forefront of clinical practice and scientific research in treating AA with TCM for over 60 years. Our experience in the clinical treatment of AA patients in outpatient clinics and in the wards has shown that the method of tonifying kidney and generating blood has a strong therapeutic effect for AA, mainly manifesting as a gradual increase of hemoglobin (HGB). However, the growth of platelets (PLT) in some patients can be slow, which remains a difficult problem to be solved. However, there has been no relevant clinical research in China or abroad on this topic. This article introduces our clinical research on the treatment of AA by tonifying kidney and generating blood, exploring the influence and clinical characteristics of the treatment on PLT, and providing the basis and support for the selection of these treatment methods to enhance PLT growth in the clinical treatment of AA.
Materials and MethodsSubjects
This study was a multicenter, prospective, randomized, double-blind, controlled clinical trial, conducted retrospectively. A total of 128 AA patients treated from September 2018 to March 2021 in 19 separate hospitals were enrolled in the study. The relevant centers were as follows: Xiyuan Hospital, China Academy of Chinese Medical Sciences; Guang'anmen Hospital, China Academy of Chinese Medical Sciences; Dongzhimen Hospital, Beijing University of Chinese Medicine; Dongfang Hospital, Beijing University of Chinese Medicine; the First Affiliated Hospital of Tianjin Medical University; Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of TCM; Shanghai Municipal Hospital of TCM; Zhejiang Provincial Hospital of Chinese Medicine; Henan University of Chinese Medicine Cure Hospital; Affiliated Hospital of Shandong University of TCM in Langfang City; the First Affiliated Hospital of Hunan University of Medicine; Hospital of TCM; Xinjiang Uygur Autonomous Region Hospital of TCM; the Second Affiliated Hospital of Guiyang College of TCM; Cangzhou Hospital of Integrated TCM–WM, Hebei; Affiliated Hospital of Weifang Medical University Hospital; the First Affiliated Hospital of Heilongjiang University of Chinese Medicine; Gansu Provincial Hospital of TCM; Shijiazhuang Hospital of TCM. This study was registered in the Chinese Clinical Trial Registry (CHICTR-OOC-16009834) and was approved by the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences (2018XLA036-3).
Diagnostic criteria
Diagnostic criteria in western medicine
With reference to the Criteria for Diagnosis and Efficacy of Hematological Diseases (Fourth Edition),[10] patients with severe AA (SAA) and chronic AA (CAA) were included. The diagnostic criteria were as follows: (1) Clinical manifestations: anemia, infection, and bleeding; (2) blood biochemical parameters: reduced HGB, reticulocyte (RET), absolute neutrophil count (ANC), and PLT count; (3) bone marrow: (A) At least one form of dysplasia, such as active proliferation, a relative increase of lymphocytes, and significantly reduced megakaryocytes; (B) increase of nonhematopoietic cells (such as adipocytes) in bone marrow granules; (4) physical symptoms: No general hepatosplenomegaly.
Standards for traditional Chinese medicine syndrome differentiation
Patients were diagnosed according to the Reference Standard for Deficiency Syndrome Differentiation of TCM:[11] (1) Deficiency syndrome of kidney and essence: lumbar spine pain, tibial soreness, and soft knee or heel pain; tinnitus or deafness; flaking or toothing; residual urination or incontinence. (2) Deficiency syndrome of qi and blood: pale face, fatigue, less breath or lazy speech, spontaneous sweating, pale fat tongue or teeth marks, weak pulse or counting. Patients with three symptoms of deficiency of kidney and essence and one symptom of deficiency of qi and blood were diagnosed as patients with kidney deficiency AA and received treatment of tonifying kidney and generating blood.
Inclusion criteria
(1) Met the AA diagnostic criteria and TCM syndrome differentiation criteria. (2) Aged from 14 to 80 years; (3) had normal liver and kidney function.
Exclusion criteria
The exclusion criteria were as follows: (1) Other diseases causing pancytopenia, such as paroxysmal sleep hemoglobinuria, myelodysplastic syndrome, acute hematopoietic stagnation, and myelofibrosis; (2) congenital AA; (3) patients with serious heart, brain, liver, and kidney diseases, mental illness, during stages of pregnancy or lactation; (4) patients with severe infection or bleeding, which seriously threatens the safety of life and requires emergency marrow transplantation.
Off criteria
(1) Due to subjective or objective reasons, medication was not prescribed, or data required for the evaluation of curative effect was incomplete; (2) patients with myelodysplastic syndrome, or paroxysmal nocturnal hemoglobinuria AA during treatment; (3) severe organ dysfunction occurred during the treatment, and the patient could not continue to undergo observation.
Termination and exit criteria
(1) Unable to take medicine on time; (2) serious adverse reactions, such as infection lasting 1 week or more and bleeding in the head and face; (3) during the treatment, important organ functions were impaired, such as creatinine, alanine aminotransferase, or aspartate aminotransferase increased to 1.5 times the baseline value.
Treatment methods
All patients were given the nondecoction instant granules of the Tonifying Kidney Prescription (Beijing Tcmages Pharmaceutical Co., LTD.). The formula for tonifying kidney essence was as follows: 30 g Shu Di Huang (Radix Rehmanniae Preparata), 15 g Zhi He Shou Wu (Radix Polygoni Multiflori Preparata), 20 g Huang Jing (Rhizoma Polygonati), 15 g Bu Gu Zhi (Fructus Psoraleae), 20 g Tu Si Zi (Semen Cuscutae), 15 g Rou Cong Rong (Herba Cistanches), 15 g Ba Ji Tian (Radix Morindae Officinalis) and 20 g Suo Yang (Herba Cynomorii). The granules were taken with boiled water, one pack in the morning and one in the evening.
Western medicine treatment: (1) Cyclosporine A soft capsule (Hangzhou Zhongmei Huadong Pharmaceutical Co., LTD., Batch No. 20180312): 100–125 mg for each dose, 2 doses per day, oral administration, with CsA blood concentration maintained at 100–250 ng/L; (2) rabbit anti-thymocyte globulin (ATG) (Genzyme Polyclonals S. A. S, Lot No. 20180518): suitable for SAA, 2.5–3.5 mg/kg per day for 5 days; or porcine ATG (Wuhan Zhongsheng Yujin Biomedical Co., LTD., Batch No. 20180218): 20–30 mg/kg per day for 5 days; (3) stanozolol tablets (Guangxi Nanning Baihui Pharmaceutical Group Co., LTD., Batch No. 20180413): 2–4 mg for each dose, 3 doses per day, oral administration; or testosterone undecanoate capsule (Catalent France Beinheim S. A, Lot No. 20180101): 40–80 mg for each dose, 3 doses per day, oral administration.
Supportive treatment: (1) Erythrocyte suspension infusion for anemia: HGB <60 g/L, or HGB <80 g/L for elderly patients; (2) PLT suspension infusion for bleeding: PLT <10 × 109/L with bleeding or PLT >10 × 109/L with risk factors of bleeding (such as ATG or concurrent infection); (3) effective antibiotic treatment for infection: medicine was given based on the location and severity of infection.
Continuous treatment for 3 months was considered one course of treatment. Patients went through two courses of treatment and were followed up once a month.
Observation indicators
Main outcome measures
(1) Routine blood testing for white blood cells (WBC), HGB, PLT, and ANC: venous blood was collected for laboratory analysis before and 6 months after treatment. (2) Morphological examination of bone marrow cells: Bone marrow biopsy was performed before and 6 months after treatment, and the bone marrow fluid smear was tested; (3) blood transfusion frequency: the average monthly blood transfusion volume before and after treatment and the time of the last blood transfusion during treatment were recorded.
Precautionary measures
(1) Liver and kidney function indicators: glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, serum bilirubin, indirect bilirubin, creatinine, urea nitrogen, blood uric acid, etc., Patients included in the study underwent fasting venous blood extraction in the morning every month before treatment and during follow-up; (2) routine urine and stool samples were collected before and after treatment. (3) Electrocardiogram was performed on the day when patients entered and left the group.
Grouping
A total of 128 patients with AA syndrome of kidney deficiency were included in this study. The main method for treatment was tonifying kidney and invigorating blood, consisting of Western medicine treatment and the Bushen Tianjing prescription nondecoction instant granules, with two consecutive courses lasting 3 months each. Born at the end of the course, namely to accept kidney blood method is given priority to 6 months after treatment, the patients with AA PLT and into the treatment group after treatment compared with baseline values, look to whether growth. Overall, 75 AA patients showed a growth of PLT from the baseline, 53 patients with AA PLT a baseline value growth, and PLT is baseline value growth in 75 patients with AA. The PLT values of 21 AA patients returned to normal, while that of 54 AA patients did not return to normal. Therefore, the 128 AA patients were divided into three groups: The normal group comprised 21 AA patients whose PLT increased from baseline and returned to normal; the abnormal group comprised 54 AA patients whose PLT increased from baseline but did not return to normal; the nongrowth group consisted of 53 AA patients whose PLT did not increase from baseline. Based on this grouping, statistical methods were used to compare and analyze the differences in clinical characteristics before treatment among the three groups.
Note: Normal range of PLT: (100–300) × 109/L
Statistical methods
SPSS 20.0 statistical software (IBM Corporation, New York, USA) was used for data analysis. The measurement data with normal distribution and uniform variance could be described as Mean ± standard deviation (X ± S). The Chi-square test and Fisher's test were used to compare the differences among variables of categorical data. The independent factors of population grouping were determined by one-way analysis of variance. P < 0.05 indicated a statistically significant difference.
ResultsGeneral information
A total of 128 patients with kidney deficiency syndrome were included, and the general information of the patients is shown in [Table 1].
Platelet growth in aplastic anemia patients
Among the 128 patients with AA kidney deficiency syndrome, PLT increased from baseline and returned to normal in 21 cases (16.4%), PLT did increased but did not return to normal in 54 cases (42.2%), and PLT did not increase from baseline in 53 cases (41.4%). Overall, 58.6% of patients showed PLT growth, which indicated that the method of tonifying kidney and generating blood had a good effect on the PLT growth of AA patients.
Analysis of clinical characteristics of aplastic anemia patients under different platelet growth conditions
General features
A total of 128 patients were statistically analyzed, including 69 males and 59 females with an average age of 42.00 ± 10.20 years. PLT increased from baseline and returned to normal (normal group) in 21 patients, including 13 males and 8 females, with an average age of 46.14 ± 18.33 years. The increase of PLT from baseline did not return to normal (abnormal group) in 54 patients, including 24 males and 30 females, with an average age of 39.81 ± 17.14 years. Furthermore, there were 53 patients with no increase in PLT from baseline (nongrowth group), including 32 males and 21 females, with an average age of 41.77 ± 17.63 years. There were no significant differences in gender or age among the three groups (P > 0.05), indicating comparability.
As can be seen from [Table 2], the difference in the Karnofsky Performance Status (KPS) score of the 128 AA patients was statistically significant (P < 0.05). The normal group had the lowest KPS score (74.76 ± 21.36), and the nongrowth group had the highest KPS score (81.70 ± 15.07). As shown in [Table 3], when the KPS score of AA patients was <40, the PLT had more easily restored to normal after treatment involving tonifying kidney and generating blood.
Table 2: One-way ANOVA results of general data of aplastic anemia patients under different platelets growth conditions (mean±standard deviation)
Table 3: Chi-square test results of general data of aplastic anemia patients under different platelets growth conditions, case (%)Routine blood analysis before treatment
As shown in [Table 4], the difference in HGB between groups was statistically significant (P < 0.05); the normal group had the highest value at 90.86 ± 33.97 g/L. This indicates that the higher the HGB before treatment, the greater the treatment efficacy, with PLT values more likely to increase or even return to normal. The Chi-square test was performed on blood tests before treatment to further explore the blood routine characteristics of patients with effective AA treatment by tonifying kidney and generating blood, as shown in [Table 5]. When HGB ≥60 g/L accounted for a higher proportion than when HGB <60 g/L before treatment, that is, when HGB ≥60 g/L, the PLT of AA patients treated by tonifying kidney and generating blood was more likely to increase or even return to normal (P < 0.05), as shown in [Figure 1]. Similarly, the proportion of patients with AA that showed an increase in PLT baseline and returned to normal (normal group) was higher with RET% ≥0.3% before treatment than with RET% <0.3%, that is, when RET% ≥0.3%, the PLT of AA patients treated with kidney tonifying method was more likely to increase or even return to normal (P < 0.05), as shown in [Figure 2]. There was no significant difference between WBC and ANC (P = 0.201, P = 0.155).
Table 4: One-way ANOVA results of routine blood testing in aplastic anemia patients under different platelets growth conditions (mean±standard deviation)
Table 5: Chi-square test results of routine blood testing before treatment in aplastic anemia patients, case (%)Comparison of bone puncture indicators before treatment
Morphological examination of bone marrow cells before treatment, as well as the analysis of chromosome karyotype and PLT growth of AA patients after 6 months of treatment, showed that there were statistically significant differences in the degree of proliferation of nucleated cells, the proportion of grain lines, the proportion of red lines, and chromosome number (P < 0.05). Compared to patients with active hyperplasia, the PLTs of patients with low or extremely low nuclear cell proliferation were more likely to increase or even return to normal. When the proportion of granulocytes was <40% and the proportion of erythroid cells was <20%, an increase in PLTs was more likely, indicating that these patients could be targeted for treatment by tonifying kidney and generating blood. As shown in [Table 6], there was no significant difference in bone marrow granules and fat droplets between the groups (P = 0.218, P = 0.067).
Table 6: Growth of different platelet parameters on bone puncture and chromosome examination in aplastic anemia patients before treatment, case (%)Analysis of T lymphocyte subsets and fusion gene indices before treatment
The examination results of T lymphocyte subsets and fusion genes before treatment in relation to PLT growth of AA patients after 6 months of treatment were analyzed and the results are shown in [Table 7]. The difference in the proportion of CD3+ human leukocyte antigen (HLA)-DR+ was statistically significant (P < 0.05). The mean of CD3+HLA-DR+ among the three groups before treatment showed the following trend: normal group > abnormal group > nongrowth group. In other words, when the CD3+HLA-DR+ was higher before treatment, the PLT of AA was more likely to increase or even return to normal. Further Chi-square analysis of CD3 + HLA-DR+ showed that when CD3+HLA-DR+was ≥30% before treatment, the PLT of AA treated by kidney-invigorating and blood-generating method was significantly more likely to increase (P < 0.05), as shown in [Figure 3].
Table 7: Results of T lymphocyte subsets and fusion genes of aplastic anemia patients before treatment (mean±standard deviation) Discussion AA is an autoimmune disease of unknown etiology. Activated cytotoxic T lymphocytes can recognize class I or II HLA introduced by infection, drugs, or another unknown environment. HLA molecules act as self-antigens to destroy hematopoietic stem cells or the hematopoietic microenvironment,[12],[13] resulting in hematopoietic failure and peripheral hemocytopenia. Western medicine treatment for this condition primarily comprises allogeneic hematopoietic stem cell transplantation or ATG in the early stages. Other treatments include ATG combined with cyclosporine-enhanced immunosuppressive therapy with the research on the disease at home and abroad, mainly nontransplant treatment immunosuppression accompanied by androgen, eltrombopag and other hematopoietic stimulation,[14],[15] blood transfusion, anti-infection and other supportive treatments. Unfortunately, the efficacy of Western medicine treatment alone is often unsatisfying, involving long treatment duration and obvious side effects.
According to TCM, the clinical characteristics of AA are classified in the category of “medullary fatigue.” The pathogenesis involves invasion of external evil, or internal injury leading to deficiency of qi and blood, resulting in damage to the liver, kidney, and spleen, and the emptiness of medullary veins. Finally, the endogenous toxic evil consumes the medullary veins, leading to a lack of blood and the manifestation of blood deficiency syndrome. TCM proposes that the Yin and Yang of long illness kidney injury empties the kidney, resulting in kidney sperm loss, difficulty to breed blood, essence deficiency, blood deficiency, and pulp emptying.[16] Therefore, the essence of AA is kidney deficiency mainly, and then develops into qi and blood deficiency and the damage of Yin and Yang of zang-fu organs is caused by exogenous evil poison, congenital endowment and acquired hyponourishment, etc., In treatment for this condition, the dialectical method of Yin and Yang of kidney, nourishing kidney and generating blood, can often achieve good results. As shown by Professor Zhou Ai-Xiang,[17] the addition of Da Tu Zi Yin consisting of He Shou Wu (Radix Polygoni Multiflori), Tu Si Zi (Semen Cuscutae), Rou Cong Rong (Herba Cistanches), Bu Gu Zhi (Fructus Psoraleae), Euphorbia officinalis, and Cymbidium cymbidium, could promote the proliferation of granulocytes and erythroid progenitor cells, thereby improving the treatment. Modern medical research has confirmed that Da Tu Zi Yin can improve the Th1/Th2 immune imbalance, causing activation of various cell signaling pathways,[18] and can promote the recovery of the bone marrow hematopoietic system by regulating immunity. Kidney blood party with modified Da Tu Zi Yin, dodder solid acidity gathered to make up for YangYi Yin, malaytea scurfpea fruit, air temperature, the fire of kidney in yiyang Ming, c. deserticola GanWen lubrication, raising five zang-organs beneficial nutrients, medicinal indianmulberry root removing JingXie, zi yi zong jin, lock Yang, Yin solid pith of a temperature dryness, rehmannia glutinosa living flesh, zi kidney water, joint bone marrow, relatively true Yin, radix polygoni multiflori filling kidney profit JingXie, Huangjing tonifies the essence of spleen and stomach and moistens the dryness of heart and lung.
RET is defined as immature red blood cells between late juvenile red blood cells and mature red blood cells, and the proportion of RET in the blood is an important indicator of hematopoietic function. RET parameters are important factors in the clinical treatment of patients with AA, and are of great significance in the examination of the therapeutic effectiveness of patients.[19] Research has shown that several RET parameters of acute or CAA patients show obvious differences between cells in patients with two type number of RET, naive degree (RNA), cell volume, etc., also have obvious difference, comprehensive utilization of a variety of test parameters on the diagnosis, classification, treatment effect of AA and the evaluation of the bone marrow hematopoietic function has a guiding significance to the.[20] A previous study by our team showed that RET counting should be an effective indicator with potential for the early prediction of clinical efficacy and cumulative survival rate of patients before and during the treatment of SAA treated with Antithymocyte globulin/Antilymphocyte globulin (ATG/ALG), which is based on kidney toning TCM.[21] Hou Shu-Feng's study showed that Bushen Shengxue granules could effectively improve the level of peripheral blood cells and bone marrow nucleated cells in AA, and can promote the proliferation and differentiation of granulocyte progenitor cells.[22]
The results of Li Dan-Dong's study showed that HLA-DR+ is a late marker of T-cell activation, and that patients have more activated HLA-DR+ cells, which may result in the production of more hematopoietic inhibitors, leading to hematopoietic inhibition in the bone marrow and hematopoietic failure, which is one of the biological mechanisms in SAA patients. CD3+HLA-DR+T-cell subsets are not only related to the pathogenesis of SAA, but can also be used to predict treatment efficacy. A CD3+HLA-DR+T-cell proportion >7% is linked to a longer survival period in patients.[23] Domestic studies have shown that, compared with healthy controls, the expression level of CD3+HLA-DR+T-cells in the peripheral blood of AA patients is higher, suggesting that the pathogenesis of AA may be related to the expression imbalance of CD3+HLA-DR+TT cells.[24]
The results of this study showed that after 6 months of treatment with the method of tonifying kidney and generating blood, the total growth rate of PLT in patients was 58.6%, among which 16.4% of them showed a PLT level which returned to normal, showing good treatment efficacy. We investigated the relationship between the clinical indicators of AA patients before treatment and PLT growth after 6 months of treatment with the kidney tonification and blood generation method. The results showed that KPS score, HGB, RET%, degree of myelodysplasia, proportion of bone marrow granulated system, chromosome karyotype, CD3+HLA-DR+T-cells, and other clinical factors could be used to evaluate the PLT growth. Domestic studies have shown that kidney-tonifying TCM can promote the proliferation and differentiation of bone marrow hematopoietic stem/progenitor cells, improve the hematopoietic microenvironment, promote the recovery of bone marrow hematopoietic, and regulate the immune function of the body.[18],[19] Abnormal immune mechanisms are key in the pathogenesis of AA, if AA patients before treatment or greater HGB 60 g/L and the higher the value, the patient did not rely on blood transfusion, illustrating the immune mechanism of damage to a lesser degree, in patients with bone marrow hematopoietic stem cells, bone marrow hematopoietic ability well, under the treatment of kidney raw method is given priority to with blood, and are more likely to restore the bone marrow hematopoietic, to regulate the body's immune function, making the patient heal gradually. There is low proliferation of nuclear cells in bone marrow, which is the concept of “marrow blight” in TCM. “Element ask · Yin and Yang should be like a big discussion” has “kidney bone marrow,” so tonifying the kidney as the principle of treatment can consolidate the essence of marrow and promote the recovery of bone marrow hematopoiesis, so that the disease gradually subsides. Relevant studies at home and abroad have shown that kidney-invigorating and blood-generating methods can reduce the expression level of CD3+HLA-DR+T-cells in the peripheral blood of AA patients, and plays a role in regulating the immune function of the body.[24] Therefore, when CD3+HLA-DR+T-cells are highly expressed in AA patients, kidney-invigorating and blood-generating method is more effective at reducing the expression of CD3+HLA-DR+T-cells, thereby balancing body immunity, restoring bone marrow hematopoietic function, and achieving the effect of PLT growth.
In summary, the clinical characteristics associated with PLT growth in patients treated with the method of tonifying kidney and generating blood to treat AA, were lower KPS score, higher HGB ≥60 g/L, RET% ≥0.3%, low and extremely low proliferation of nucleated cells, proportion of granulocytes <40%, proportion of erythrocytes <20%, normal chromosomal karyotype, CD3+HLA-DR+ ≥30% and higher proportion. In combination with modern medicine, this study analyzed the clinical characteristics of PLT growth in the treatment of AA by tonifying kidney and generating blood. However, we did not discuss the relevant immune mechanism of AA from the level of cytokines, nor did we clarify the immune regulatory mechanism of the treatment of AA by tonifying kidney and generating blood. These factors need to be further explored.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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