A Case of Investigation and Diagnosis of Immune Thrombocytopenic Purpura After Vaccination of COVID-19 Inactivated Vaccine

Objective:Analyze the relationship between inoculating one case of the COVID-19 inactivated vaccine(Vero cell)and immune thrombocytopenic purpura to provide a reference for the standardized handling of adverse events following immunization.Methods:According to the"National Monitoring Program for Suspected Adverse Reactions to Vaccinations,"an on-site investigation,data collection and analysis,expert group diagnosis,and medical association assessment were conducted on a case of immune thrombocytopenic purpura in District A of Chongqing after vaccination with the inactivated COVID-19 vaccine.The assessment report was delivered to the three relevant parties,the case was reviewed,and the experience was summarized.Results:The investigation and diagnosis by the district-level vaccination abnormal reaction expert group concluded that the disease that occurred after vaccination with the COVID-19 inactivated vaccine was secondary immune thrombocytopenic purpura,an abnormal reaction to the vaccination.The medical damage was classified as Level II Grade B.The vaccine production enterprise raised objections to this conclusion.After re-assessment by the municipal-level medical association,the conclusion was consistent with that of the district-level medical association.The vaccine production enterprise did not raise any further objections.Conclusion:Through active collaboration among district and municipal-level medical associations,disease control institutions,and vaccination units,the recipients have been promptly and effectively treated,providing financial support for their subsequent treatment and safeguarding their rights.The investigation and disposal procedures for adverse events following immunization in Chongqing are clear,and the mechanism is sound.It is necessary to continue strengthening the monitoring of adverse events following immunization according to the existing plan and to ensure timely and standardized handling.Simultaneously,it is crucial to strengthen vaccine management and vaccination management.

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP).

A murine model for human immune thrombocytopenic purpura and comparative analysis of multiple gene expression in bone marrow and spleen

Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other im- munological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura （ITP） has not been fully understood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or platelet destruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into the Balb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the mini- mum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h （6 days）. Final homeostasis reached at approximately 408 h （17 days）, following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed and compared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration of mRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes be- tween bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when platelet number reached the maximum （144 h）. In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleen tissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Our results provided the supportive evidence that expression of the above seven genes are more related to negative regulation of platelet number in spleen tissue, at least in the model animals.

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura(ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack oftuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

Eltrombopag Managed Severe Immune Thrombocytopenic Purpura in Pregnancy: A Case Report, Latifa Hospital, DHA, Dubai, UAE

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder, defined by a platelet count of less than 100 × 109/L, secondary to impaired production and immune destruction of platelets. Bleeding tendency is the main presentation of this condition. Clinical symptoms and investigations will confirm the diagnosis. Steroid is the first line of treatment. Although Rituximab and Thrombopoietin receptor agonists are useful second line agents in non-pregnant adults, the data about their role in pregnancy are still limited. We present the case of a 30 year old primigravida, who was a known case of chronic ITP since childhood;the course of her disease was fluctuating, for which oral steroids were used accordingly. She presented with gum bleeding and petechial rash with very low platelets count. She was sponsored by the Patient Support Program and was given Eltrombopag during the third trimester. She responded well to Eltrombopag with no noticeable side effects, neither to the mother nor to the baby so far. Eltrombopag has been assigned Category C by the Federal Drugs Agency (FDA) nevertheless there are no well controlled data in the literature about its role in pregnancy.

Chronic Immune Thrombocytopenic Purpura in a Young Female with Rheumatoid Arthritis (Unusual Course)

We present a case of a 29-year-old female from Sudan, who was diagnosed with rheumatoid arthritis (RA) in 2005 and with immune thrombocytopenic purpura (ITP) in 2009. The ITP immediately followed using, for four weeks, a combination of medications that included rifampicin. The platelets count continued to be low thereafter. During the year following her diagnosis with ITP, she reported gradual improvement in her joints symptoms, which continued during her pregnancy in 2011. Following puerperium, her chronic ITP resolved completely;however, her joint disease flared up few months later. To our knowledge, there are no reported cases of chronic ITP, which were drug induced at first in a patient of RA except with gold therapy. Similarly, there are no reports on cases that recovered from chronic ITP after delivery. Finally, this case highlights the impact different coexisting autoimmune diseases may have on each other regarding course and prognosis.

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。

New mechanisms of the TCM spleen-based treatment of immune thrombocytopenia purpura from the perspective of blood neurotransmitters

Objective:To explore new mechanisms of the traditional Chinese medicine (TCM)spleen-based treatment of immune thrombocytopenic purpura (ITP) from the perspective of blood neurotransmitters.Methods:In this randomized controlled multi-center clinical study,271 ITP patients who met the diagnostic criteria of 'syndrome of spleen failing to manage blood' were randomized into three groups:group A administered Jianpi Yiqi Shexue (JYS) granules,1 bag per treatment,bid;group C administered prednisone as a draught at an initial dose of 1.0-1.5 mg/kg/day at 8:00 AM;and group B administered a combination of the interventions in groups A and C.Each treatment cycle lasted 21 days.Results:After treatment,scores of platelet distribution width (PDW) were significantly decreased in groups B and C,and there were significant differences among the three groups (P =.0131).Pairwise comparisons showed that PDW was significantly different between group A and group B (P =.005) and between group A and group C (P =.041) but not between group B and group C.Hemorrhage grading scores were significantly different between day 1 and day 7 in group A and group B (P <.001) but not in group C.The hemorrhage grading scores on day 14 and day 21 were significantly different from that on day 1 in all three groups (P <.001).Serum 5-hydroxytryptaminelevels did not change significantly before and after treatment in the three groups (P >.05).Serum β-endorphin and vasoactive intestinal peptide levels were significantly different between group A and group B (both P <.001).Conclusions:The JYS prescription may regulate the expression levels of blood neurotransmitters via the brain-gut axis in patients with 'spleen deficiency' ITP and thus activate hemostatic mechanisms to promote hemostasis.β-EP and VIP are key neurotransmitters of the JYS-induced functional regulation.

Effectiveness of total therapy in immune thrombocytopenia purpura:case series

Immune Thrombocytopenic purpura(ITP)is a haematologicimmune-mediated disorder in which the amount of platelet in the blood decreases abnormally.Single-agent therapies for ITP have not proven successful in achieving long-term remission,with relapse occurring in about half of the patients(p/t).Treatment options which include Rituximab with Dexamethasone as frontline therapy,have durable response rates ranging from 58%to 76%.In this study,we have used‘Total therapy’as treatment which includes low-dose Rituximab in combination with Thrombopoietin receptor agonist(TPO-RA)(Romiplostim)and high-dose Dexamethasone.In this case series study,each patient received romiplostim(250 mcg weekly s/c,4 doses)in combination with low-dose rituximab(100 mg weekly IV,4 doses)and high-dose dexamethasone(40 mgIV on days 1-4and days 15-18).This treatment combination demonstrated rapid response rates and a low rate of side effects,making it a good alternative for individuals with ITP.

Helicobacter pylori-associated immune thrombocytopenia:Clinical features and pathogenic mechanisms

Immune thrombocytopenia (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. There is growing evidence that the eradication of Helicobacter pylori (H. pylori) effectively increases platelet count in a considerable proportion of ITP patients infected with this bacterium. In the majority of ITP patients responding to H. pylori eradication therapy, the anti-platelet autoantibody response is completely resolved with no relapse for more than 7 years, indicating that the disease is cured. Therefore, adult patients with suspected ITP should be examined for H. pylori infection, and eradication therapy is recommended if the infection is present. Notably, however, the efficacy of H. pylori eradication therapy in ITP patients varies widely among countries, with a higher response rate in Japan compared with the United States and European countries other than Italy. The pathogenesis of H. pylori-associated ITP is still uncertain, although the mechanisms are known to involve multiple factors. H. pylori may modulate the Fc&#x003b3;-receptor balance of monocytes/macrophages in favor of activating Fc&#x003b3; receptors, and H. pylori components may mimic the molecular makeup of platelet antigens. Further studies of the pathogenic process of H. pylori-associated ITP may be useful for the development of new therapeutic strategies for ITP.

Eltrombopag-related renal vein thromboembolism in a patient with immune thrombocytopenia: A case report

BACKGROUND Eltrombopag is an orally administered thrombopoietin receptor agonist linked to a heightened risk of treatment-related thromboembolism.Both venous and arterial thromboses have been documented in the medical literature.CASE SUMMARY In the absence of nephropathy,a 48-year-old patient receiving eltrombopag for immune thrombocytopenia(ITP)developed renal vein thrombosis and pulmonary embolism.The renal vein thrombus spontaneously resolved during subsequent anticoagulant treatment,restoring venous circulation.CONCLUSION A rapid upsurge in platelets,rather than their absolute number,may trigger thrombotic events in this setting.For patients at high thrombotic risk,individualized eltrombopag dosing and vigilance in platelet monitoring are perhaps needed during treatment of ITP.

Mechanism study of the effect of Ningxue Shengban decoction on regulating the ratio of Treg/Th17 cells and downstream inflammatory factors in immune thrombocytopenia model mice

Background:To explore the role and mechanism of T cell imbalance in the process of immune thrombocytopenic purpura(ITP)and the efficacy of the Ningxue Shengban decoction in treating this disease.Methods:Passive immune ITP mouse model was established by injecting CD41 monoclonal antibody into BALB/c mice.The mice were divided into different groups for intervention and drug administration for 9 days.The therapeutic effects(blood cell count,bone marrow morphology)were observed.The changes in the number and proportion of regulatory T/Th17 cells in each group,as well as the expression of key transcription proteins and genes(Foxp3,RORγt)in mouse spleen,and the secretion of related inflammatory factors(interleukin-17,TGF-β,interleukin-21,interleukin-10)in serum were detected.Results:Ningxue Shengban decoction significantly increased the peripheral blood platelet count in ITP mice,improved bone marrow morphology,restored the imbalance of regulatory T/Th17 ratio,and exerted a positive regulatory effect on target proteins and downstream inflammatory factor secretion.Conclusion:Ningxue Shengban decoction may exert its therapeutic effect in treating ITP by regulating T cells and exerting immune regulatory function.

Laparoscopic splenectomy for immune thrombocytopenic purpura at a teaching institution

Background High anatomic location, fragility, and generous blood supply of the spleen makes laparoscopic splenectomy （LS） difficult to master, and few patients need splenectomy for benign disorders. The aim of this research was to assess operative outcomes and hematological results of a large series of patients treated with LS for chronic immune thrombocytopenic purpura （ITP） and to determine which clinical variables predict favorable hematological outcome.Methods LS was successfully performed for 154 patients with chronic ITP from September 1999 to April 2009 at the First Affiliated Hospital of Sun Yat-sen University. Operative outcomes were assessed retrospectively. Long-term follow-up data were obtained from outpatient medical records and phone interviews. Clinical and laboratory variables （including gender, age, disease duration before surgery, previous response to steroids, preoperative platelet count, and postoperative peak platelet count） were evaluated by univariate analysis to identify potential predictors of hematological outcome. Multivariate Logistic regression model was used to determine independent predictors of hematological outcome.Results One patient died from subphrenic abscess and postoperative sepsis. The overall major morbidity rate was 8.4%. None of the patients required a second surgery for complications. Of the 127 patients available for a mean follow-up of 43.6 months （range 9-114 months）, the overall initial response （i.e., at two months after LS） and long-term response to LS were achieved in 89.0% and 80.3%, respectively. Five patients （3.9%） developed pneumonia 3-35 months after LS. Univariate analysis showed a significant difference in mean age between responders （29.1 years） and nonresponders （38.8 years; P ＜0.05）. Patients who responded to steroid therapy had better hematological outcome than those who did not respond （P ＜0.05）. Compared to nonresponders, responders to LS had a significantly higher postoperative peak platelet count （404x109/L versus 213×109/L, P ＜0.001）. Multivariate Logistic regression analysis identified postoperative peak platelet count as the only independent predictor of favorable response to LS （P＜0.001）.Conclusiona LS is a safe and effective treatment for chronic ITP. Postoperative peak platelet count may serve as a major predictor of long-term response.

Supraclavicular lymph node tuberculosis presenting with immune thrombocytopenic purpura

Tuberculosis （TB） differs from many other infectious maladies in having particular social and geographic distributions. The disease was under control in developed nations and being brought under control in developing countries, as in China. TB has now been recognized as a public health threat and the incidence of TB is steadily rising. Though a lot of various hematological disorders have been described in TB, like anemia, leukocytosis and, the most frequently cited, pancytopenia, immune thrombocytopenic purpura （ITP） is extremely rare. When thrombocytopenia occurs in TB, it happens most commonly via non-immune pathways, as typically described in the context of pancytopenia that develops secondary to tuberculous granulomatous infiltration of the bone marrow, but a causal relationship between TB and immune thrombocvtonenia is extraordinarilv rare.

Evaluation of miR-21 and miR-150 expression in immune thrombocytopenic purpura pathogenesis： a case-control study

BACKGROUND： Immune thrombocytopenic purpnra （ITP） is a common autoimmune disorder diagnosed with thrombocytopenia and bleeding symptoms due to production of autoantibodies （Abs） against platelets. Nowadays, microRNAs are known as novel biomarkers for diagnosis of diseases. The aim of this study was to investigate the expression levels of miR-21 and miR-150 in ITP patients and determine the role of these miRNAs in ITP pathogenesis. MATERIALS and METHODS： Thirty newly diagnosed patients with acute ITP and 30 healthy subjects（ age and sex matched） as controls were enrolled in this study. The expression level ofmiR-21 and miR- 150 was investigated using Real-time-PCR. Comparison of demographic characteristics of the cases was done using independent t-test and chi-square test. Comparison of the expression level of miR-21 and miR-150 with the related parameters was done using independent t-test or Mann-Whitney and Kruskal-Wallis test, Spearman rho correlation coefficient was used to investigate the relationship between the expression of miR-21 and miR-150 with demographic characteristics. RESULTS： The expression of miR-21, 150 in the patients was not different compared with the control group in general. A significant relationship between the expression of miR-21 with hemoglobin, hematocrit and red blood cell hemoglobin concentration was observed. DISCUSSION： Expression of miR-21 and miR-150 is not associated with pathogenesis of acute ITP and can involve the synergistic role of other miRNAs. Investigation of miR-21 and miR-150 expression along with other miRNAs and cytokines can be helpful in diagnosis and pathogenesis of ITP.

CBA技术检测ITP患者Th1/Th2细胞因子平衡偏移的临床意义

目的:探讨CBA技术检测原发性免疫性血小板减少性紫癜(ITP)患者治疗前后外周血Th1/Th2细胞因子水平变化及其临床意义。方法:98例ITP患者分为激素治疗有效组和无效组;选择健康体检正常者40例为对照组,用流式细胞术微珠阵列(CBA)分别检测各组治疗前和治疗后4周、3个月、6个月外周血Th1细胞因子(IFN-γ,TNFα、IL-2)和Th2细胞因子(IL-4、IL-5、IL-10)水平,并分析指标间的变化关系。结果:治疗前,初治ITP组外周血Th1细胞因子明显高于正常对照组,Th2细胞因子明显低于正常对照组,差异均有统计学意义(P<0.05),IL-2/IL-4比值明显高于正常对照组;治疗后,激素治疗有效组Th1细胞水平均较治疗前明显下降,IL-2/IL-4比值也明显下降,与治疗前相比,治疗6个月后IL-2/IL-4比值为(1.05±0.43 vs 2.53±0.72),其差异均有统计学意义(P<0.05);而激素治疗无效组则无明显变化。结论:初治ITP患者外周血Th1/Th2细胞存在平衡偏移现象,ITP是一种Th1优势疾病,治疗前后IL-2/IL-4的比值变化与预后相关,对指导ITP个体化治疗有一定临床意义。

不同脾蒂离断法在腹腔镜脾切除治疗ITP中的成本-效果比较

目的比较腹腔镜下原位二级脾蒂离断法脾切除术(laparoscopic splenectomy by secondary pedicledivision,LSSP)和腹腔镜下直线切割闭合器脾切除术(laparoscopic splenectomy by Endo-GIA,LSED)治疗特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)的成本-效果。方法收集本院2007年5月～2009年6月因ITP行腹腔镜下脾切除术治疗的患者42例,随机分为LSSP和LSED两组,每组21例,比较两种治疗方法的疗效差异,并进行成本-效果分析。结果 LSSP组的手术时间、术中出血量、术中住院时间分别为(152.8±61.4)min、(202.5±88.4)mL和(5.9±0.7)d,与LSED组(161.5±31.8)min、(219.7±79.6)mL和(6.1±0.4)d相比均无统计学差异(P>0.05),LSSP组治疗总有效率为81.0%,与LSED组(90.5%)相比无统计学差异(P>0.05)。而在手术费用上LSSP组为(7681.7±752.1)元,与LSED组的(10138.5±631.3)元相比差异有显著性(P<0.05)。结论 LSSP治疗ITP的治疗效果与LSED相近,但更节约医疗成本。

糖皮质激素对ITP初治患者T辅助细胞相关细胞因子基因表达的影响

本研究旨在探讨免疫性血小板减少性紫癜(ITP)患者中T辅助细胞(helper T cell,Th)细胞免疫状态以及其与治疗反应的关系。应用实时荧光定量RT-PCR方法检测20例初发ITP患者(男性8例,女性12例,中位年龄41.0岁)接受糖皮质激素治疗[泼尼松1mg/(kg.d)]前后以及20例正常对照者外周血单个核细胞中Th细胞相关基因(T-bet、IFN-γ、GATA-3、TGF-β、Foxp3、IL-2、IL-4)表达水平的变化。结果表明:治疗前ITP患者外周血单个核细胞中T-bet、IFN-γ、IL-2表达较正常对照明显升高,差异有显著统计学意义(p<0.01),治疗后患者T-bet、IFN-γ、IL-2表达较治疗前降低(p<0.05);治疗前Foxp3表达较正常无明显变化,治疗后Foxp3表达较治疗前升高(p<0.05)。治疗前患者TGF-β的表达与正常对照相比无明显差别,治疗后老年患者与年轻患者中呈现不同的变化模式,年龄<60岁患者治疗后TGF-β表达水平较治疗前降低(p<0.05),而年龄≥60岁患者TGF-β较治疗前升高。结论:ITP患者存在Th细胞亚群失衡,常规糖皮质激素治疗仍是针对初治ITP患者的有效治疗手段,其作用机制可能与改善Th细胞亚群失衡有关。

IL-21在ITP中的表达及大剂量地塞米松对其调控的研究

目的:探究免疫性血小板减少症(immunologic thrombocytopenia,ITP)与IL-21表达异常的相关性,同时探究大剂量地塞米松(high-dose dexamethasone,HD-DXM)冲击治疗ITP的疗效是否与IL-21有关。方法:抽取26例初诊ITP患者及24例健康人的外周血10 ml,密度梯度离心法获得血清及单个核细胞,分别采用流式细胞术和实时荧光定量PCR法检测单个核细胞IL-21的表达,采用酶联免疫吸附实验(ELISA)检测ITP治疗前后及正常对照者血浆中IL-21,IFN-γ和IL-4的水平。结果:流式细胞术测定发现,ITP患者单个核细胞表面分子IL-21表达明显高于健康对照(13.07%vs 8.2%);ITP患者IL-21 mRNA(9.524±0.97)与健康对照组(3.701±0.60)存在显著统计学差异,经HD-DEX治疗后IL-21 mRNA的比率值(5.87±1.21)较治疗前显著降低(P<0.01);ITP患者血清中IL-21和IFN-γ水平与健康对照组和HD-DEX治疗组相比均具有显著的统计学差异(P<0.01);而IL-4在治疗后含量却上调,与治疗前相比有统计学意义。结论:IL-21的表达异常参与了ITP发病过程,地塞米松对ITP的疗效与下调IL-21表达有关。