The Effect of Costimulatory Factors in the Pathogenesis of Chronic Idiopathic Thrombocytopenic Purpura

To investigate the effect of costimulatory factors in the pathogenesis of chronic idiopathic thrombocytopenic purpura(CITP), we examined the expression of CD80 on platelets and megakaryocytes in patients with CITP and the controls by FACS. By using CD80 monoclonal antibody (McAb) to inhibit interaction among cells which is mediated by costimulatory factors, we observed the effect of CD80 McAb on the growth and maturation of megakaryocytic progenitors of patients with CITP in vitro . The results showed the expression of CD80 on platelets and megakaryocytes in CITP group was significantly higher than that in controls ( P <0.01). There was a significantly positive correlation between the expression of CD80 on platelets and serum PAIgG in CITP (r=0.86, P <0.05). The mean of various clone numbers (CFU MK, BFU MK and mCFU MK) in CITP were all lower than those in controls ( P <0.05). In megakaryocytes co cultured with CD80 McAb, there was an increasing tendency of the number of CFU MK and big CFU MK (the number of megakaryocyte with GPⅢ a positive was more than 20) and mediate CFU MK (the number of megakaryocyte with GPⅢ a positive was 11-20). When the concentration of CD80 McAb was 10 μg/L, there was a significant difference in the number of megakaryocytic colony formation (CFU MK, BFU MK and mCFU MK) between the group with CD80 McAb and that without it ( P <0.05).These showed the abnormality of costimulatory factors had important effect in the pathogenesis of CITP.

Clinical Study on the Effect of Shengxueling (生血灵) on Idiopathic Thrombocytopenic Purpura

Objective:To observe the clinical effect of Shengxueling (生血灵, SXL) on idiopathic thrombocytopenic purpura (ITP), and study the possible mechanism.Methods: Eighty-six cases of ITP were randomly divided into two groups. The SXL group, 56 patients treated with SXL, a traditinal Chinese medicine and 30 patients administered with prednisone were taken as control. Each group took drugs for 3 months and was under follow-up observation.Results: In the SXL group, the total effective rate was 85.71%, similar to prednisone 83.33%( P >0.05) for 3 months, but the total effective rate of SXL (91.07%) were obviously better than that of the control group (53.33%) ( P <0.01) for 6 months and had no obvious adverse reaction. The patients bleeding was alleviated or stopped, the general condition was improved. At the same time, blood platelet count (PLT) was increased, platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly dropped, the level of natural killers cells activity (NKa) increased, the rate of T lymphocyte subsets gradually returned to normal level. Megakaryocyte tended to maturation on bone marrow smear after treatment. All differences above were statistically significant.Conclusion: SXL is an effective and safe medicine for ITP. Its mechanism could regulate cytoimmune, inhibit platelet antibody to reduce the destruction of platelet, increase the number of platelet, promote the division and maturation of megakaryocyte, facilitate the production and release of platelet, lower the fragility of capillary, prevent and cure hemorrhagic tendency.

Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year- old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB10601 and DRB10803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.

Refractory case of ulcerative colitis with idiopathic thrombocytopenic purpura successfully treated by Janus kinase inhibitor tofacitinib:A case report

BACKGROUND Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura(ITP) is a rare phenomenon. The management of UC with ITP can be challenging,since a decreased platelet count augments UC.CASE SUMMARY A 24-year-old man with UC and steroid-resistant ITP experienced UC flare.Although continuous infusion of cyclosporine was initiated, UC did not improve.The administration of tofacitinib subsequently led to the induction of remission.The patient has maintained remission of UC and ITP for over one year ontofacitinib treatment. Whole transcriptomic sequencing was performed forinflamed rectal mucosae obtained before and after the initiation of Janus kinase(JAK) inhibitor, suggesting that distinct molecular signatures seemed to beregulated by JAK inhibitors and other conventional therapies including tumornecrosis factor lockers.CONCLUSION Tofacitinib should be considered in refractory cases of UC with ITP.

Direct Infection of Colony Forming Unit-Megakaryocyte by Human Cytomegalovirus Contributes the Pathogenesis of Idiopathic Thrombocytopenic Purpura

Human cytomegalovirus （HCMV） late mRNA expression in megakaryoblast and in turn the pathogenesis of idiopathic thrombocytopenic purpura （ITP） patients with HCMV infection, and effectiveness of ganciclovir were investigated. Colony forming unit-megakaryocytes （CFU-MK） of 46 ITP patients with HCMV infection were incubated from patients＇ bone marrow mononuclear cells （MNC）. Reverse transcriptase-polymerase chain reaction （RT-PCR） was subsequently used for CFU-MK for HCMV-late mRNA detection, Ganciclovir therapy was given to both HCMV-late mRNA positive and negative groups for comparison of therapeutic effectiveness, The results in 19 of 46 CFU-MK culture cells specimens with positive HCMV-DNA by PCR or positive CMV-IgM by enzyme linked immunosorbent assay （ELISA） in the correspondent serum of peripheral blood were positive for HCMV-late mRNA, Sixteen out of 19 patients with positive HCMV-late mRNA CFU-MK had a positive response to ganciclovir. Amongst 27 patients with negative HCMV-late mRNA CFU-MK, only 4 positive responders to ganciclovir therapy were observed. Curative effectiveness of ganciclovir in HCMV-late mRNA positive group was significantly higher than that in HCMV-late mRNA negative group （P〈0.01）, It was suggested that HCMV could directly infect CFU-MK, which might be one of the mechanisms responsible for HCMV related ITE The ganci- clovir is an effective therapy in resulting in the increases in thrombocyte in the ITP patients whose HCMV- late mRNA was positive in their CFU-MK.

原发性血小板减少紫癜(Idiopathic thrombocytopenic purpura,ITP)的治疗

治疗原则对急性、重型患者,目的是防止致命性出血;对慢性或已缓解者,是促进病情缓解或维持缓解;联合用药能提高疗效。治疗方案推荐方案1~61、肾上腺皮质激素适用血小板计数明显减少,有较严重皮肤、粘膜出血,有颅内出血倾向者;脾切除前作减少手术出血的措施。用法:强的松40~60mg/日、严重出血者60~100mg/日,疗程2~4周,缓解后渐减量维持治疗。急性出血者可用氢化考的松200mg/iv qd或氟美松10~20mg/iv qd,连用3~5日,缓解后改口服强的松维持。

Therapeutic Uses of Lycium barbarum Polysaccharides on Idiopathic Thrombocytopenic Purpura Mice via Inhibition of Oxidative Stress

The aim of the present study was to investigate the effect of Lycium barbarum polysaccharides (LBP) on the treatment of ITP mice and to explore its mechanism. Forty idiopathic thrombocytopenic purpura (ITP) mice were divided randomly into a model control group and LBP groups I, II, III and IV. ITP mice in LBP groups I, II, III, and IV were administered LBP at four different doses (50, 100, 200 and 400 mg·kg-1·d-1, respectively) for 7 days by gavage. Blood samples were collected from the tail veins of the mice after treatment. Platelet counts were determined, and the total antioxidant status (TAS), total oxidant status (TOS) were measured with ELISA kits. The platelet count was (30.28 ± 13.42) × 109/L in the model control group, and the number of platelets in all LBP groups was higher than that in the model control group. The platelet count increased, and it reached (67.09 ± 10.81) × 109/L in LBP group I;the platelet counts in the other three groups increased significantly compared to LBP group I, and they did not differ significantly. TAS concentrations in the LBP groups were significantly increased compared to the model control group, whereas TOS concentrations were significantly decreased. Taken together, these results indicate that LBP is effective at increasing the number of platelet (PLT), and LBP may treat ITP mice via suppressing oxidative stress.

Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection

We report the first case of a patient with hepatitis C virus(HCV) infection and idiopathic thrombocytopenic purpura(ITP), who later developed acquired amegakaryocytic thrombocytopenia(AAMT), with autoantibodies to the thrombopoietin(TPO) receptor(c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.

Lymphocytosis in Idiopathic Thrombocytopenic Purpura Patients Infected by <i>Helicobacter pylori</i>

Background and Objectives: Several recent reports have demonstrated a close linkage between idiopathic thrombocytopenic purpura (ITP) and Helicobacter pylori (H. pylori) infection in some patient’s populations. However, the pathogenetic mechanisms of H. pylori-induced thrombocytopenia remain obscure. Therefore, we investigated the prevalence of H. pylori infection pylori and performed a comparative analysis of a subset of H. pylori-infected patients (group A) with non-infected patients (group B) using the standard statistical methods. Design and Methods: From December 2001 to October 2002, we investigated the presence of gastric H. pylori infection in 30 adult ITP patients and 19 patients were treated with standard antibiotic therapy for H. pylori eradication (amoxicillin and clarithromycin plus lansoprazole combination). We used the standard statisticsto analyze the difference between group A and group B. Results: H. pylori eradication was achieved in 17/19 (89.4%) H.pylori-infected patients. An improvement of platelet count was observed in 14/19 patients (73.6%) who achieved the eradication. Five of these patients achieved CR (two patients were with the acute ITP) and nine patients reached PR. The difference between the mean platelet count ± S.D. before and after H. pylori therapy was statistically significant in patients with successful decontamination (65 ± 48 × 109/L vs. 200 ± 140 × 109/L;p = 0.018). Lymphocyte counts at the diagnosis of H. pylori infected cases were significant higher than those of non-infected cases (1.58 ± 0.13 ×

Current Concept for the Diagnosis and Treatment of Adult Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder manifested by immunemediated thrombocytopenia. The estimated incidence ranges from 50 ～ 100 per million each year in western countries, roughly divided between adults and children.

Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

AIM:To compare the prevalence of Helicobacter pylori (Hpylon)infection in autoimmune thrombocytopenic purpura (AITP)patients with that of nonthrombocytopenic controls, and to evaluate the efficacy of the treatment in H pylori(+) and H pylor(-)AITP patients. METHODS:The prevalence of gastric H pylori infection in 38 adult AITP patients(29 female and 9 male;median age 27 years;range 18-39 years)who consecutively admitted to our clinic was investagated. RESULTS:H pylori infection was found in 26 of 38 AITP patients(68.5%).H pylori infection was found in 15 of 23 control subjects(65.2%).The difference in H pylori infection between the 2 groups was not significant.Thrombocyte count of H pylori-positive AITP patients was significantly lower than that of H pylori-negative AITP patients(P<0.05). Thrombocyte recovery of H pylori-positive group was less than that of H pylori-negative group(P<0.05). CONCLUSION:H pylori infection should be considerecd in the treatment of AITP patients with H pylori infection.

Plasma thrombopoietin levels in patients with aplastic anemia and idiopathic thrombocytopenic purpura

OBJECTIVE: To evaluate the role of thrombopoietin (TPO) in the pathology of chronic thrombocytopenic disease. METHODS: We measured the endogenous plasma concentration of TPO in 40 patients with acquired aplastic anaemia (AA) and in 32 patients with idiopathic thrombocytopenic purpura (ITP) by a sensitive Sandwich enzyme-linked immunosorbent assay (ELISA) and compared the results. RESULTS: Plasma TPO concentrations were significantly higher in AA patients (774 +/- 393 pg/ ml) in comparison with healthy control subjects (55 +/- 34 pg/ml, P 0.05). There was also no relationship between their plasma TPO levels and platelet counts. CONCLUSIONS: TPO levels may be regulated not only by platelets but also by megakaryocytes in AA and ITP, and measurement of TPO levels is useful for diagnosing thrombocytopenia and understanding the pathophysiology of thrombocytopenia.

Polarization and Apoptosis of T Cell Subsets in Idiopathic Thrombocytopenic Purpura

It is well-known that idiopathic thrombocytopenic purpura （ITP） is an acquired organ-specific autoimmune hemorrhagic disease and dysfunctional cellular immunity is considered important in the pathophysiology of ITP. However, polarization patterns and apoptosis profiles of T lymphocytes remain unclear. In this study, we investigated the polarization of T cell subsets, the expressions of apoptotic proteins Fas/FasL on the subsets and the level of anti-apoptotic gene bcl-2 and bax mRNA. It was demonstrated that the ratios of Thl/Th2 and Tcl/Tc2 in ITP children were increased obviously and that the average percentages were increased clearly for Thl and Th2, but not for Tcl and Tc2. In ITP children, the enhancing expressions were detected for FasL on Thl and Tcl and for Fas on Th2 and Tc2. With increasing level of bcl-2 mRNA and decreasing expression of bax mRNA in ITP children, the ratio of bcl-2/bax mRNA was improved obviously, which was positive correlated with the ratio of Thl/Th2. Taken together, our findings indicate that ITP is a Thl predominant disease. This polarization pattern of T cell subsets might be related to the high ratio of bcl-2/bax mRNA and the abnormal expressions of Fas and FasL on T cell subsets.

Chronic idiopathic thrombocytopenic purpura in adult Chinese patients: a retrospective single centered analysis of 1791 cases

Background Adult chronic idiopathic thrombocytopenic purpura (ITP) is a common hematologic disease characterized by persistent thrombocytopenia. So far, there were only a few reports on adult Chinese patients with chronic ITP. This study aimed at defining the treatment outcome and prognostic factors for chronic ITP based on a large cohort of Chinese patients followed up for over 25 years at a single center Methods The medical records of 1791 patients aged 14 years or older who were diagnosed as having chronic ITP at our hospital from 1974 to 1999 were retrospectively analyzed Results The female to male ratio was 2∶1, with a median age of 34 years (ranging from 14 to 80 years), median platelet count of 38×10 9/L [range (1-99)×10 9/L], and median follow up of 36 months (range 1-220 months) Steroids were used in 689 patients, among them 209 (30.3%) achieved complete remission (CR) A splenectomy was performed in 124 patients, and response to steriod pre splenectomy was not available in 14 patients The CR rate after a splenectomy was lower in steroid nonresponders (29 of 90, 32.2%) than in those who relapsed after successful steroid treatment (12 of 20, 60.0%) ( P <0 05) In comparison with patients negative for antinuclear antibody (ANA), those who were ANA positive had similar responses to steroids, but a significantly shorter remission period after a splenectomy ( P <0 01) Conclusions Adult Chinese chronic ITP patients can have long term remission after steroid therapy and splenectomies Primary steroid refractoriness is a prognostic factor predicting poor subsequent response to a splenectomy

Treatment of 37 Patients with Refractory Idiopathic Thrombocytopenic Purpura by Shengxueling (升血灵)

Objective： To explore the clinical effect and possible mechanism of Shengxueling （升血灵, SXL）, a Chinese medical preparation mainly consisting of ginseng saponins, in treating refractory idiopathic thrombocytopenic purpura （ITP）. Methods： The selected 69 patients with ITP were randomly assigned to two groups, the 37 patients in the treated group were treated orally by SXL with the dose for adult as 60 mg twice a day for two weeks. Then when no marked rise of platelet count after that, the dose would be doubled and administered for another two weeks. Then the dose could be gradually reduced to the initiative level in patients who responded to the treatment, and if they did not, the treatment was regarded as ineffective and be terminated. The 32 patients in the control group were treated with ampeptide elemente instead of SXL, 0.4 g each time three times a day in the first two weeks, and, if that was ineffective, 0.2 g would be added each time and 1.8 g would be administered a day for two more weeks. Four weeks＇ treatment was regarded as one therapeutic course for both groups and the observation lasted for two successive courses in patients showing positive reslbonse. Results： In the 37 patients in the treated group, markedly effective was obtained in 7 （19.0%）, favorably effective in 15 （40.5%）, improved in 5 （13.5%） and ineffective in 10 （27.0%）, the total effective rate being 59.5%. The corresponding number in the 32 patients in the control group was 4 （12.5%）, 6 （18.8%）, 3 （9.4%）, 19 （59.4%） and 31.3% respectively. Comparison showed the difference in therapeutic efficacy between the two groups was significant （P〈0.05）. Conclusion： SXL is a safe and effective preparation for treatment of ITP, showing an immediate effect which is obviously superior to that of ampeptide elemente with less adverse effect.

Clinical Observation on the Treatment of Childhood Refractory Idiopathic Thrombocytopenic Purpura with Dihuang Zhixue Capsule(地黄止血胶囊)

Objective： To observe the clinical effect of Dihuang Zhixue Capsule （地黄止血胶囊, DZC, a Chinese preparation for cooling blood and dispelling toxic substances） in the treatment of childhood refractory idiopathic thrombocytopenic purpura （RITP）, with cyclosporin A （CsA） used as the control. Methods： Forty-one children of RITP were randomized into the treated group and the control group. The 21 patients in the treated group were orally given 2 to 3 DZC capsules each time, thrice a day and the 20 in the control group were given 3 mg/kg CsA per day, with 3 months as one therapeutic course. The therapeutic efficacy, platelet count and adverse reaction in the two groups were compared at the end of the course. Results： （1） In the treated group, 1 （4.8%） patient was evaluated as cured, 3 （14.3%） as markedly effective, 5 （23.8%） as effective, 5 （23.8%） as improved, 7 （33.3%） as ineffective, with the total effective rate being 66.7%; while in the control group, the corresponding numbers were 0. 2 （10.0%）, 2 （10.0%）, 3 （15.0%）, 13 （65.0%） and 35.0%, respectively, showing statistical significance in difference between the total effective rates of the two groups （ Х^2=4.11, P=0.0426）. （2） As compared with the baseline, the platelet count increased in both groups after 2 months＇ treatment （P〈0.05）. After 3 months＇ treatment, the platelet count was higher in the treated group than in the control group （P〈0.05）. （3） The improvement of hemorrhage in the treated group after 8 weeks＇ treatment was better than that in the control group （P〈0.05）. （4） No apparent adverse reaction was observed in the treated group, while in the control group, hirsutism was shown in 15 cases; gingival hyperplasia in 10; digestive reaction in 5, liver function impairment in 5, hypertension in 2 and renal impairment in 2. Conclusion： The therapeutic efficacy of DZC is better than that of CsA, and DZC shows good compliance but brings no obvious adverse reaction.

Co-infection of Pneumocystis jirovecii and Aspergillus in a patient with idiopathic thrombocytopenic purpura

PCP and IA co-infection in HIV patients has been reported.[3] However,only nine cases co-infected with PCP and IA in non-HIV patients are reported.[4-6] Herein,we report a fatal case of PCP and IA co-infection in a patient undergoing high-dose corticosteroid therapy for idiopathic thrombocytopenic purpura.

Thrombotic Thrombocytopenic Purpura in a Parturient Leading to Life-Threatening Thrombocytopenia and Neonatal Demise—A Case Report

Thrombocytopenia is common (up to 12%) in pregnancy;thrombotic thrombocytopenia is a rare cause of thrombocytopenia;however,it is immediately life-threatening to both mother and fetus and requires immediate intervention.This is compounded by the need to act on a presumptive diagnosis with high level of suspicion given the relatively long laboratory confirmation time.A 31-year-old gravida 3,para 1 parturient at 26 weeks of gestation presented to outside hospital with recent onset of easy bruising and blurry vision.A blood count was drawn and showed a platelet count of 19,000/μL.She was transferred to our institution for management where an initial diagnosis of preeclampsia with severe features was made based on thrombocytopenia and fetal growth restriction (<1%).Platelet count nadired at 14,000/μL and a blood smear showed schistocytes,suggesting microangiopathic hemolysis,prompting discussion of urgent cesarean delivery and anesthesia consult.An urgent hematology consult led to presumptively diagnosing thrombotic thrombocytopenic purpura and cesarean delivery was deferred after discussion with the patient and team.Plasma exchange and steroid therapy were started promptly,and her platelet count improved within 12 hours.Unfortunately,the patient experienced neonatal demise.Undetectable ADAMTS13 levels confirmed diagnosis of thrombotic thrombocytopenia.She was transitioned to rituximab,platelets recovered to baseline,and she continues to do well.Thrombotic thrombocytopenia is a rare,life-threatening cause of thrombocytopenia in pregnancy.Despite grim fetal prognosis,especially in early pregnancy,low threshold of suspicion,early anesthesia involvement,and multi-disciplinary approach can facilitate diagnosis and timely intervention.In our case,it was likely lifesaving.

艾曲泊帕乙醇胺片对特发性血小板减少性紫癜患儿CD40/CD40L的影响

目的探讨艾曲泊帕乙醇胺片对特发性血小板减少性紫癜(ITP)患儿CD40/CD40L轴的影响机制。方法选取80例ITP患儿作为研究对象,根据数字随机表法将其分为对照组(n=40)和研究组(n=40)。对照组给予环孢素治疗,研究组给予艾曲泊帕乙醇胺片治疗,两组均连续治疗3个月。对比两组患者的临床疗效、T淋巴细胞亚群水平(CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+))以及不良反应。检测两组患者淋巴细胞膜表面和血小板膜表面的CD40、CD40L水平,使用ELISA检测血浆sCD40和sCD40L水平。结果研究组的总有效率(92.50%)明显高于对照组的总有效率(75.00%)(P<0.05)。两组治疗后的CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、血浆s CD40表达水平均高于治疗前,CD8^(+)以及外周血CD19^(+)CD40^(+)、CD3^(+)CD40L^(+)细胞和血浆sCD40L表达水平低于治疗前;研究组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、血浆sCD40表达水平高于对照组,CD8^(+)以及外周血CD19^(+)CD40^(+)、CD3^(+)CD40L^(+)细胞和血浆sCD40L表达水平低于对照组(P<0.05)。两组治疗后的外周血血小板膜表面的CD40L^(+)细胞低于治疗前;研究组的外周血血小板膜表面的CD40^(+)高于对照组,CD40L^(+)细胞低于对照组(P<0.05)。研究组的总不良率(15.00%)低于对照组的总不良率(22.50%),但是两组比较差异无统计学意义(P>0.05)。结论艾曲泊帕乙醇胺片治疗ITP患儿具有良好的临床疗效,调节T淋巴细胞亚群水平,安全性良好。