| Background and objectivePrimary immune thrombocytopenia(ITP)is the most common bleeding disorder encountered in the clinic.Adult ITP may recur and can evolve into chronic ITP(cITP)that poses a therapeutic challenge.Patients suffering from ITP are commonly anxious,present with limitations in activities of daily living,and severe impairment of health-related quality of life(HRQoL),which are often overlooked during treatment.The emergence of holistic integrative medicine(HIM)has provided insights and methods to address these problems.HIM refers to the organic integration of advanced medical knowledge and clinically-effective practical experience,with adjustments being made based on social,environmental,and psychological reality to form a new system of medicine that is more beneficial for human health and treatment of diseases.The study used the concept of HIM as a guide,and focused on the organic integration of theoretical exploration,clinical trials,and clinical experience to demonstrate the superiority of the HIM approach and maximally improve the clinical efficacy for ITP(especially for cITP)and improve the HRQoL of patients.MethodsThis study divided into 4 parts based on the research direction established by HIM of Hematology:literature mining,integration of Traditional Chinese medicine(TCM)and western medicine,medical humanities,and "How-I-Treat".The first part was literature mining.(1)Analysis on Medication Rule in Prescriptions for cITP Based on Data Mining Technology.CNKI Chinese academic journal database,VIP Chinese periodical database and Wanfang Chinese academic journal database were all searched for the relevant clinical literature on TCM treatment for cITP.Then establish a medication database and conduct data mining on the properties,tastes,meridian entries,and compatibility regularity of TCMs by using frequency analysis,association rules analysis and cluster analysis.(2)Relevant publications from Medline,Embase,and the Cochrane database were searched.The purpose of this systematic review and network meta-analysis was to establish a clinically relevant ranking of the efficacy and safety of second-line medications for adults with ITP.The primary outcome was the overall response(defined as a platelet count ? 50 ×10~9/L at the end of treatment without emergency therapy),while the secondary endpoints included early response(defined as a platelet count ? 50×10~9/L at week 2 after initiation of treatment without emergency therapy)and therapy-related severe adverse events.The second part was a cross-sectional study(medical humanities).A Medical Outcome Study SF-36 form(SF-36)and the Functional Assessment of Chronic Illness Therapy-Fatigue scale(FACIT-F scale)were used to investigate the HRQoL and fatigue status of adult patients with ITP in Jiangsu province and an age-and gender-matched healthy population was used as control.The third part was a prospective study(combination of TCM and Western medicine).To evaluate the 8-week comprehensive effect of Supplementing Qi,Nourishing Yin and Hamonizing Blood Decoction and changes in the HRQoL of adult patients with cITP.92 patients from the Department of Hematology of Affiliated Hospital of Nanjing University of Chinese Medicine were enrolled.The patients were assigned to receive decoction self-developed by our research group for 8 weeks,platelet counts,bleeding,and glucocorticoid withdrawal conditions of patients were observed before and after treatment.Meanwhile,the changes in patients'HRQoL and fatigue scores were compared using SF-36 scales and FACIT-F scales.The fourth part was"How-I-treat",in which five typical cases were recorded,the pathogenesis,treatments,and medication characteristics were analysed to summarize and refine the academic thoughts and clinical experiences of Professor Shen Qun in the treatment of ITP.ResultsThe first part.(1)We screened clinical papers on TCM treated for cITP and included 87 prescriptions and 137 TCM flavours.Frequency analysis suggested that the nature of TCM and flavours for treating cITP mainly consist of sweet and cold drugs and liver channel drugs.Twenty-six flavours such as Astragalus propinquus,Rehmannia glutinosa,Angelica sinensis,Agrimonia pilosa,and tree peony bark were most frequently used.Based on association rules,13 pairs of drugs were obtained,namely Astragalus propinquus-Suberect Spatholobus stem,Angelica sinensis-Codonopsis pilosula,Astragalus propinquus-Codonopsis pilosula,and other combinations.Cluster analysis confirmed presence of four basic groups:left-restoring beverages,double supreme pills,Angelica sinensis blood supplementing soups,and rhinoceros' horn and Rehmannia glutinosa soups.(2)Systematic review and network meta-analysis showed that the best overall response rate was obtained with romiplostim,followed by avatrombopag,eltrombopag,fostamatinib,and rituximab.Avatrombopag showed the best early-response rate.The safety of the included drugs was high,and the incidences of adverse reactions of Grade 3 and above were low and controllable.The second part.The cross-sectional study showed that the HRQoL of ITP patients was significantly poorer,and the condition affected both physiological and psychological health.Compared with the normal control group,the difference of physical function,social function,and role emotional exceeded the minimum clinical significance difference.Patients with persistent ITP showed the greatest impairment in SF-36.Fatigue was widespread in all patients,out of which those with cITP had the most severe burden of the symptom.The third part.After 8 weeks of treatment,the overall response rate was 66.3%(61/92),of which six patients demonstrated Complete response,whereas 55 patients showed Response.The pre-treatment platelet count was 27(1-85)×10~9/L,and that after treatment was 60(1-258)×109/L(P<0.01).Thirty-three patients had bleeding before treatment as compared to ten patients after treatment(P<0.01).Total corticosteroid withdrawal rate was 88.2%(45/51).After treatment,the scores of the four parameters(physical function,general health,vitality,and social function)in the SF-36 scale and the FACIT-F scale were significantly higher compared to that before treatment(P<0.05).The gender and age of the patients,stage of ITP,presence of any co-morbidity,pre-treatment platelet count,bleeding score,and concomitant usage of glucocorticoids were not related to the treatment response(P>0.05).The adverse reaction that occurred was diarrhoea,with an incidence of 2.2%(2/92).The fourth part.Five typical cases,including children,adolescents and adults with ITP,were found to have failed corticosteroid therapy,difficulty in reduction or recurrence after corticosteroid withdrawal.Professor Shea believes that the pathogenesis of ITP is mainly"deficiency of both Qi and Yin".According to the unique physiological characteristics and clinical manifestations of different age groups,the principle of "supplementing Qi,nourishing Yin,and hamonizing blood",supplemented by the medicine of"tonifying spleen","softening liver",and"regulating blood"is needed to guide the clinical medication with remarkable effect.ConclusionsUnder the guidance of HIM,the study explored and summarized the advanced theoretical knowledge and clinical practical experience for management of ITP.The compatibility rule of cITP was found to be"treating qi,fire and blood",and"Supplementing Qi,nourishing Yin,and hamonizing blood"was taken as the basic therapeutic criterion;This study also prospectively validated the efficacy and safety of the Supplementing Qi,Nourishing Yin and Hamonizing Blood Decoction in the treatment of cITP,and verified for the first time that this decoction could effectively improve ITP-related fatigue;Four factors(platelet count,bleeding,HRQoL,and fatigue level)were comprehensively considered in assessment of the efficacy,such that the goal of improving physical and mental health,utilizing TCM and Western medicine,and treating both the patient and the disease were achieved simultaneously in medical services. |
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