Diagnosis Of Idiopathic Thrombocytopenic Purpura Research Articles

Immune Thrombocytopenia in Children

Immune thrombocytopenia is a hematological disorder defined by an isolated decrease in platelet numbers. We present a retrospective-descriptive study that enrolls twenty-five children (aged 0-18 years old) admitted to Brasov Children’s Hospital from the 1st of January 2020 until the 1st of September 2023 with the diagnosis of idiopathic thrombocytopenic purpura (ITP).
 We could find proof of recent viral infection in seven patients out of twenty-five; three of them also had immunological findings- positive antinuclear, positive direct Coombs test, or antiplatelet antibodies. The medical literature mentions glucocorticoids and IVIG therapy as the first line of treatment for immune thrombocytopenic purpura, while new pharmaceutical agents are still under review.

Association Between Idiopathic Thrombocytopenic Purpura and Hemorrhagic and Nonhemorrhagic Stroke.

Idiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count. This may lead to an increased risk of hemorrhagic stroke but a lower rate of nonhemorrhagic stroke. The goal of this study was to evaluate the association between ITP and both hemorrhagic and nonhemorrhagic strokes using a large database. We used the Nationwide Inpatient Sample (NIS) database to analyze the occurrence of hemorrhagic and nonhemorrhagic stroke in patients with and without a diagnosis of ITP from 2005 to 2014. Univariate analysis revealed a higher incidence of hemorrhagic stroke in patients with ITP in the year studied. (for example, in 2005: OR, 1.75; 95% CI, 1.57-1.94; P < 0.001; 2014: OR, 2.19; 95% CI, 2.03-2.36; P < 0.001). After adjusting for age, gender, race, and hypertension, hemorrhagic stroke remained significantly associated with ITP (in 2005: OR, 1.85; 95% CI, 1.49-1.89; P < 0.001; 2014: OR, 2.01; 95% CI, 1.86-2.18; P < 0.001) for all the years studied. Nonhemorrhagic stroke occurred at a lower rate in patients with ITP in most years (2006: OR, 0.91; 95% CI, 0.85-0.97; P = 0.004; 2014: OR, 0.88; 95% CI, 0.83-0.93; P < 0.001). Multivariate analysis confirmed a higher rate of nonhemorrhagic stroke in ITP patients. Our analysis showed that there was a higher rate of hemorrhagic stroke but a lower rate of ischemic stroke in ITP patients, suggesting an important role of platelets in the occurrence of stroke.

Management of patients with immune thrombocytopenia in the Moscow region

Background. Idiopathic thrombocytopenic purpura (ITp) is an autoimmune disease characterized by antibody-mediated platelets destruction and impairment of their production, which manifests itself as: isolated thrombocytopenia, risk of spontaneous hemorrhage and bleeding of varying severity. ITp is a hematological, orphan disease with an incidence of 1–4 cases per 100,000 population. In modern literature, primary and secondary immune thrombocytopenias are distinguished. primary immune thrombocytopenia is a diagnosis of exclusion. To verify it, a certain diagnostic search is required.Aim. To evaluate clinical characteristics and treatment efficacy in patients with a confirmed primary immune thrombocytopenia in the Moscow region.Materials and methods. This article presents the results of an analysis of more than 2,400 outpatient records of patients diagnosed with thrombocytopenia (for the period from 2010 to 2022). Of these, about 400 confirmed clinical cases of various ITp forms were included in the ITp registry of the Moscow Region. All patients live in the Moscow region, receive treatment and are observed at the Center for Orphan diseases of the M.f. vladimirskiy Moscow Regional Research Clinical Institute.Results. There are 415 patients with a verified diagnosis of ITp in the register of the Moscow Region Center for Orphan diseases of the M.f. vladimirskiy Moscow Regional Research Clinical Institute (71 % (n = 294) are female). In 69.8 % (n = 290) of patients at the time of disease manifestation, hemorrhagic syndrome was recorded. As a first-line therapy, 92.8 % (n = 385) of patients received corticosteroids (prednisolone, methylprednisolone, dexamethasone), in the second-line therapy, 82 % (n = 340) of patients were recommended therapy with thrombopoietin receptor agonists (romiplostim, eltrombopag). The options for third-line therapy in patients with ITp are rituximab monotherapy, splenectomy, and intravenous immunoglobulin. Splenectomy was performed in 3.37 % (n = 14) of patients.Conclusion. when evaluating this register, the highest efficiency of thrombopoietin receptor agonists (romiplostim, eltrombopag) is observed – 84.1 % of the objective response.

A Nomogram Model for Individualized Prediction of the Risk of Respiratory Tract Infection within Six Months after Diagnosis in Patients with Primary Immune Thrombocytopenia.

The risk factors of upper respiratory tract infection (URI) within 6 months after diagnosis in patients with idiopathic thrombocytopenic purpura (ITP) were analyzed, and the nomogram model was established and verified, with 242 and 50 ITP patients as the training and validation set, respectively. The patients were followed up for six months after the diagnosis of ITP. The clinical data of patients were collected, and the risk factors of URI in ITP patients within six months after diagnosis were analyzed using univariable, followed by multivariable logistic regression. Among the 242 ITP patients in the training set, 52 cases (21.49%) had URI, including 24 cases of viral infection, 11 cases of Mycoplasma pneumoniae infection, and 17 cases of bacterial infection. Logistic regression analysis showed that advanced age, use of glucocorticoid, smoking history, platelet count, serum CRP level, and lymphocyte subsets CD4+ and CD8+ were all risk factors for ITP patients to develop symptoms within six months after diagnosis (P < 0.05). Using the above five indicators, a nomogram prediction model was built for URI occurrence in patients with ITP within half a year after diagnosis, and the results showed an AUC, a sensitivity, and a specificity of 0.936 (95% CI: 0.878-0.983), 0.942, and 0.865, respectively. The nomogram model was internally verified by the bootstrap method for 500 self-sampling times, and the prediction of the calibration curve was in high consistency with the real results. External validation of the nomogram model resulted in an AUC, a sensitivity, and a specificity of 0.890 (95% CI: 0.757-0.975), 0.949, and 0.727, respectively. The nomogram model of URI in ITP patients within half a year after diagnosis based on logistic regression analysis has good discrimination and prediction accuracy. This provides important guidance value for individualized prediction of URI in ITP patients.

Acquired Amegakaryocytic Thrombocytopenic Purpura that Presented as Cyclic Thrombocytopenia Associated with Anti-Phospholipid Antibody Syndrome

A 52-year-old female, who had been taking prednisolone (PSL) for anti-phospholipid antibody syndrome (APS), was admitted to our hospital because of repeated nasal bleeding, purpura and petechiae of the extremities, and a platelet count of 7,000/μL. The PSL dose was increased due to a tentative diagnosis of idiopathic thrombocytopenic purpura (ITP), but she presented with cyclic thrombocytopenia independent of the PSL dose and repeated nasal, oral, and gastrointestinal bleeding.

Hemorrhagic plaques in the oral cavity: A clue to diagnosing thrombocytopenia

Idiopathic thrombocytopenic purpura is a disorder with a myriad of possible clinical presentations. The mechanism of thrombocytopenia involves both increased platelet destruction and impaired platelet production. The patient can manifest a wide range of symptoms: from asymptomatic or minimal gingival bleeding to profuse bleeding from any site. The disease may first present itself to the dermatologist in cutaneous findings such as petechiae, purpura, and mucosal manifestations in the form of gingival bleeding and hemorrhagic bullae. The diagnosis of idiopathic thrombocytopenic purpura is mostly done by exclusion. In this report, we present two cases with characteristic oral manifestations, who were diagnosed, on investigation, with idiopathic thrombocytopenic purpura. The patients were successfully treated with immunosuppressive therapy. The report aims to raise awareness that would help in enabling prompt referral to the appropriate specialty, especially because of the rarity of this presentation.

Bilateral simultaneous multilayered retinal hemorrhages in a young adult with Idiopathic Thrombocytopenic Purpura (ITP): A rare case report

Introduction: Idiopathic thrombocytopenic purpura is an autoimmune hematological disorder characterized by isolated low platelet count without any known clinically apparent etiology. Although usually most cases are asymptomatic, it may present with bleeding manifestations in forms of bruises, petechiae, nose bleeding etc. Very rarely, it may present with ocular manifestations in the form of subretinal, preretinal, intraretinal or vitreous haemorrhage.&#x0D; Case: A 26-year-old female presented to the ophthalmology department with chief complaint of sudden painless diminution of vision in both eyes for the last one week. Her best corrected visual acuity for distance was 20/200 in right eye and 20/600 in left eye. Dilated fundus examination showed right eye sub-internal limiting membrane (ILM) haemorrhage, left eye large subretinal and intra-retinal haemorrhages over posterior pole, with Roth’s spot in both eyes. Haematological investigations revealed moderate anaemia (Hemoglobin level of 7 gm %) and severe thrombocytopenia (25,000/ ul). Diagnosis of idiopathic thrombocytopenic purpura (ITP) was made after consultation with an internist. She was treated with systemic steroid and blood transfusion for systemic disease and kept under regular ophthalmic follow up. Over a period of six months, she showed gradual near total resolution of retinal hemorrhages in both eyes and improvement in visual acuity in both eyes.&#x0D; Conclusion: This case gives a unique outlook to simultaneous varied ocular manifestations of ITP in a single patient and stresses upon thorough systemic evaluation in the presence of such manifestations. Optimization of systemic parameters without active ocular intervention in select cases may achieve favourable outcome.

A preliminary study on the diagnostic value of infrared thermography in children with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is a common bloody disease with a high incidence in children, but its diagnostic method is exclusive diagnosis, and the existing detection techniques are mostly invasive, which may cause secondary injury to patients and also may increase the risk of disease. In order to make up for the lack of the detection method, this study made a preliminary exploration on the diagnosis of children's ITP from the perspective of infrared thermography. In this study, a total of 11 healthy children and 22 ITP children's frontal infrared thermal images were collected, and the pattern characteristic (PFD), average temperature (Troi) and maximum temperature (MAX) characteristics of 7 target areas were extracted. The weighted PFD parameters were correlated with the platelet count commonly used in clinical diagnosis, and the sensitivity and specificity of the weighted PFD parameters for children's ITP were calculated through the receiver operating characteristic curve (ROC). The final results showed that the difference of the weighted PFD parameters between healthy children and ITP children was statistically significant, and the parameters negatively correlated with platelet count. Under the ROC curve, the area under the curve (AUC) of this parameter is as high as 92.1%. Based on the research results of this paper, infrared thermography can clearly show the difference between ITP children and healthy children. It is hoped that the methods proposed in this paper can non-invasively and objectively describe the characteristics of ITP infrared thermal imaging of children, and provide a new ideas for ITP diagnosis.

Pregnancy of patients with idiopathic thrombocytopenic purpura: maternal and neonatal outcomes

Objective:Thrombocytopenia occurs in 7% of pregnant women. Along with other causes, idiopathic thrombocytopenic purpura (ITP), which is an autoimmune disease with autoantibodies causing platelet destruction, must be considered in the differential diagnosis. Antiplatelet antibodies can cross the placenta and cause thrombocytopenia in the newborn. The aim of our study was to assess the management of ITP in pregnancy, and to investigate neonatal outcomes.Material and Methods:This retrospective study was conducted in a tertiary center including 89 pregnant patients with ITP followed between October 2011 and January 2018. Patients were evaluated in two groups according to diagnoses of ITP and chronic ITP. Age, obstetric history, ITP diagnosis, and follow-up period, presence of splenectomy, platelet count during pregnancy and after birth, treatment during pregnancy, route of delivery, weight and platelet count of newborn, sign of hemorrhage, and fetal congenital anomaly were assessedResults:Considering the ITP and chronic ITP groups, no significant difference was seen with respect to parity, timing of delivery, preoperative and postoperative platelet counts, and hemoglobin values. Route of delivery, birth weight, APGAR scores, newborn platelet count, and congenital anomaly rates were also similar. The timing of treatment was different because patients whose diagnoses were established during pregnancy were mostly treated for preparation of delivery. Treatment modalities were similar.Conclusion:Probability of severe thrombocytopenia at delivery is higher in patients with ITP who are diagnosed during pregnancy when compared with patients who received prepregnancy diagnoses. ITP is an important disease for both the mother and newborn. Patients should be followed closely in cooperation with the hematology department.

Abstract P3-08-52: Systemic toxicities of trastuzumab-emtansine predict tumor response in HER2+ metastatic breast cancer

Abstract Introduction: The plant alkaloid Maytansine and its derivatives with anti-microtubule activity failed in early trials due to significant toxicity.When linked to trastuzumab as an antibody-drug conjugate (ADC), emtansine can be delivered directly into the target cell with little systemic toxicity since the emtansine is inactive before the linker of the ADC is cleaved inside the tumor cells. Systemic toxicities with trastuzumab-emtansine (T-DM1) include thrombocytopenia and transaminase elevations, unlike trastuzumab alone. We hypothesized that systemic toxicities of this ADC are in part the result of emtansine released from the lysed tumor cells, and if so, that they may predict its tumor response. To evaluate this hypothesis, the correlation between early toxicity and initial tumor response, as well as progression free survival, are examined in a retrospective multi-center study. Methods: Records of women with metastatic or locally advanced/inoperable HER2+ breast cancer who received at least one dose of T-DM1 were retrospectively abstracted from 3 centers with IRB approval. Eighty-two patients were identified. Nine were excluded—one due to a diagnosis of idiopathic thrombocytopenic purpura and eight due to lack of follow-up imaging after starting T-DM1. Platelet count, AST, and ALT results from baseline up to the 8th cycle were graded with the NCI CTCAEv5.0 toxicity scale and grades were summed as a toxicity score for the 73 evaluable patients. Sequential CT or PET/CT response to therapy were defined by RECIST criteria with the addition of a mixed response category. Results: A significant association between improved ordinal imaging response (complete, partial, stable, mixed, progression) and higher toxicity sum score was observed by the Jonckheere-Terpstra two-sided test (Z=-2.194, p=0.028). 66% of the progression free patients (29/44) had toxicity sum scores ≥2 compared to 45% with disease progression (13/29), Z=-1.89, p=0.059 by two-sided Cochran-Armitage Trend Test. Progression free survival (PFS) was significantly longer with toxicity score ≥ 2 compared to score ≤ 1, p = 0.012 by log-rank test. Further, longer PFS was significantly associated with higher toxicity sum score with HR= 0.67 (β= -0.418, SE(β) = 0.169, χ2 = 6.08, d.f.=1, p = 0.014) indicating a 33% decrease in hazard of progression for each one-point increase in toxicity score. Discussion: This small, retrospective study demonstrates a significant association between higher toxicity sum score and more favorable tumor response as well as progression free survival in women with metastatic or locally advanced/inoperable HER2+ breast cancer treated with T-DM1. Further study in large-scale trials is warranted to confirm this association and determine the clinical utility of toxicity score as a predictor of therapeutic response. Our finding does not exclude systemic toxicity from the possible ADC linker cleavage prior to endocytosis. However, when T-DM1 was studied in the metastatic setting, 48% of patients experienced a Grade 3 or higher adverse event leading to dose reductions or discontinuation of the drug in 19% and 10% of patients, respectively. In the adjuvant setting, with only residual tumor that can account for ADC-related tumor lysis, only 25% had a Grade 3 or higher adverse event leading to 18% of patients discontinuing the drug. Should our observation prove predictive in further studies, it may have ramifications for many more antibody-drug conjugates. Citation Format: Shou-Ching Tang, Carter Louis Capra, Germame H Ajebo, Simon Mairs, Judith Meza-Junco, William B. Hillegass, Barbara S. Craft, Xiaofu Zhu. Systemic toxicities of trastuzumab-emtansine predict tumor response in HER2+ metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-52.

Preoperative Virtual 3D Modeling and Planning for Splenectomy

Objectives: To explore the possibilities of preoperative 3D modelling and analysis system based on multislice computed tomography data, to evaluate its effectiveness in performing laparoscopic splenectomy for the primary immune thrombocytopenia. Methods: A patient, (61 yrs) with the diagnosis of idiopathic thrombocytopenic purpura, recurrent course. For 10 years she had been observed and underwent the numerous courses of conservative treatment; she also took daily 60 mg of prednisolone. The blood platelet levels reduced below 30×109/l. The splenectomy was indicated due to the failure of conservative treatment. Multislice computed tomography with contrast bolus was performed. For preoperative planning a color 3D model of the surgical site was created on the basis of the obtained data in the “Autoplan” system. Systems giving the ability to plan surgical intervention combines the medical equipment, PACS system (picture archiving and communication system) available onsite advanced image-viewing workstations that can guide physicians; the ability to view images from various workstations via the network including the navigation enabling physicians to create the accurate and realistic models from stereo cameras, and to use computers as well as mobile computing devices directly in the operating room. The patient was underwent laparoscopic hybrid splenectomy. Results: According to the 3D model a main type of vascularization of the spleen was revealed. The distal part of the pancreatic tail did not reach (1.5 cm) the gate of the spleen. Accessory spleens and periprotsess were absent. The data of 3D model were confirmed intraoperatively and allowed performing a laparoscopic hybrid splenectomy without technical difficulties precisely with a minimal blood loss. The postoperative period was uneventful. The patient was discharged on the 5th day in a satisfactory condition. The parameters of platelet level have reached the reference values (356×109 /l). Conclusion: Preoperative 3D modelling permits the surgeon to make pre-operative planning and provides him with important information on individual topographic and anatomic features in forthcoming operation sites. The information about the individual characteristics of the splenic vascularization and pancreatic topography in its gate lets to allocate and ligate vessels precisely, that improves the quality of hemostasis and also reduces the probability of the pancreatic injury. Preoperative visualization of accessory spleens increases the radicalism of the surgery. Keywords: Splenectomy, thrombocytopenia, computer tomography, 3D modelling, hemostasis, vascularization. Read more →

1355 Accessory Spleen: An Unusual Pancreatic Mass Posing a Diagnostic Dilemma

INTRODUCTION: There are two main causes of accessory spleen; failure of fusion of the splenic anlage during the fifth week of fetal life and following autotransplantation after a splenectomy. They are structurally identical to the spleen and are most commonly found in the splenic hilum or pancreatic tail. Although rarely noted on radiograph due to low spatial resolution, their detection is increasing with more advanced modalities. This can result in the finding of a pancreatic mass that poses a diagnostic dilemma. CASE DESCRIPTION/METHODS: The patient is a 62-year-old man with a history of hepatitis B infection. On routine surveillance he had ultrasound findings of a liver calcification with inability to determine the presence of cirrhosis and a mildly elevated alpha-fetoprotein level. He was sent for an MRI, which revealed a 2.3 × 1.9 cm mass in the pancreatic tail showing mild hyperintense T2 signal and hypointense T1 signal. A CT from 2011 showed a slight contour bulge to the pancreatic tail in the same region, without appreciation of a discrete lesion. He underwent EGD with endoscopic ultrasound (EUS). A 21.4 × 13.7 mm well-circumscribed, homogeneous lesion was found in the pancreatic tail and biopsied. The pathology shows an immunohistochemical-staining pattern consistent with splenic tissue, confirming the diagnosis of an intrapancreatic accessory spleen (IPAS). No further intervention was needed and the patient was sent home. DISCUSSION: Pancreatic cancer has a 5-year survival rate of 9%, therefore it is imperative that all pancreatic masses are investigated thoroughly and promptly. In cases of an IPAS, its differentiation from a pancreatic mass is difficult as splenic tissue can mimic pancreatic tumors, especially on MRI. It is essential to differentiate between the two as IPAS are only clinical relevant when there is torsion, rupture, hemorrhage, or the patient carries a diagnosis of idiopathic thrombocytopenic purpura requiring the removal of all splenic tissue. Imaging modalities such as ultrasound, CT, MRI, and scintigraphy can aid in the diagnosis of IPAS. However, these have limitations and have not shown to provide a definitive diagnosis. EUS with fine needle aspiration is being increasingly used to characterize pancreatic lesions. In this case, it enabled adequate tissue sampling while avoiding unnecessary procedures. This case illustrates another use for EUS in an otherwise difficult diagnostic scenario.

The Role of IL-23 in Patients with Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP)is a bleeding disorder with an unclear etiology ,The most common hemorrhagic autoimmune disease, and characterized by isolated thrombocytopenia that is not accompanied by any other disorders that may lead to thrombocytopenia. Interleukin-23 (IL-23) is a member of the IL-12 family; it is primarily secreted by activated dendritic cells, Monocytes, and macrophages and has important implication in the pathogenesis of many autoimmune diseases. The aims of this study was to evaluate the role of IL-23 in diagnosis of idiopathic thrombocytopenic purpura. A total of 5 papers were obtained using the mentioned keywords in the research of all internet-based databases. The total number of cases in all of the studies was 239 cases. The mean age was recorded in 5 papers, and the mean age of each of them was 32.8 years. There are different method of detection of IL23 in different studies such as PCR, ELISA and flow cytometry These findings suggest that levels of IL-23 are significantly higher in ITP patients.

Предоперационное 3-D моделирование спленэктомии у пациентки с первичной иммунной тромбоцитопенией

Objectives. To explore the possibilities of preoperative 3D modelling and analysis system based on multislice computed tomography data, to evaluate its effectiveness in performing laparoscopic splenectomy for the primary immune thrombocytopenia. Methods. A female patient, (55 yrs) with the diagnosis of idiopathic thrombocytopenic purpura, recurrent course. For 10 years she had been observed and underwent the numerous courses of conservative treatment; she also took daily 60 mg of prednisolone. The blood platelet levels reduced below 30×109/l. The splenectomy was indicated due to the failure of conservative treatment. Multislice computed tomography with contrast bolus was performed. For preoperative planning a color 3D model of the surgical site was created on the basis of the obtained data in the “Autoplan” system. Systems giving the ability to plan surgical intervention combines the medical equipment, PACS system (picture archiving and communication system) available onsite advanced image-viewing workstations that can guide physicians; the ability to view images from various workstations via the network including the navigation enabling physicians to create the accurate and realistic models from stereo cameras, and to use computers as well as mobile computing devices directly in the operating room. The patient was underwent laparoscopic hybrid splenectomy. Results. According to the 3D model a main type of vascularization of the spleen was revealed. The distal part of the pancreatic tail did not reach (1.5 cm) the gate of the spleen. Accessory spleens and periprotsess were absent. The data of 3D model were confirmed intraoperatively and allowed performing a laparoscopic hybrid splenectomy without technical difficulties precisely with a minimal blood loss. The postoperative period was uneventful. The patient was discharged on the 5th day in a satisfactory condition. The parameters of platelet level have reached the reference values (356×109/l). Conclusion. Preoperative 3D modelling permits the surgeon to make pre-operative planning and provides him with important information on individual topographic and anatomic features in forthcoming operation sites. The information about the individual characteristics of the splenic vascularization and pancreatic topography in its gate lets to allocate and ligate vessels precisely, that improves the quality of hemostasis and also reduces the probability of the pancreatic injury. Preoperative visualization of accessory spleens increases the radicalism of the surgery.

Pharmacoeconomic Analysis of the Use of Thrombopoietin Receptors Agonists in Idiopathic Thrombocytopenic Purpura Therapy

Background. New medications, thrombopoietin mimetics which were recently introduced into clinical practice allowed to achieve clinical response in patients with chronic glucocorticoid-resistant idiopathic thrombocytopenic purpura (ITP). However, the high cost and the need for long-term administration necessitate a pharmacoeconomic analysis of the use of thrombopoietin receptors agonists in the treatment of ITP. Aim. To assess the cost-effectiveness of the use of thrombopoietin mimetics (romiplostim and eltrombopag) and immunosuppressive therapy in the treatment of chronic glucocorticoid-resistant ITP. Materials &amp; Methods. The Markov modelling of diagnosis and treatment of ITP was conducted in accordance with the National guidelines for diagnosis and treatment of primary ITP. The cost-benefit analysis of the use of thrombopoietin receptors agonists (romiplostim and eltrombopag) and immunosuppressive therapy was performed. The time period (horizon) of the study was 5 years. Results. The therapy with thrombopoietin mimetics had higher costs but was shown to be more effective compared to immunosuppressive therapy. The cost-effectiveness for achieving 1 QALY in the treatment was 1.33 million rubles with eltrombopag, 4.2 million rubles with romiplostim, and 0.17 million rubles with immunosuppressive therapy. The lowest additional costs compared to immunosuppressive therapy had eltrombopag treatment, whereas romiplostim treatment doubled the additional costs. The threshold values of the ratio of thrombopoietin receptors agonists costs were determined for the cost-benefit analysis. The use of romiplostim is cost-effective at a price for 1 vial of 15-18 % less than for 1 package of eltrombopag. The total cumulative burden of treatment of chronic ITP for 5 years may be 7.18 billion rubles with the use of eltrombopag, 23.23 billion rubles with romiplostim, and 0.91 billion rubles with immunosuppressive therapy only. The results confirm the need for budgeting the diagnosis and treatment of ITP not as a part of general approach, but to consider ITP as an orphan disease. Conclusion. The developed pharmacoeconomic model can be used as an assessment tool of the costs of new diagnostic approaches and treatment strategies and optimizing budget expenditures.

Regulatory and Memory B Lymphocytes in Children With Newly Diagnosed Immune Thrombocytopenia.

BackgroundImmune (idiopathic) thrombocytopenic purpura (ITP) is a primary autoimmune disease. It is characterized by a diminished peripheral platelet count (< 100 × 109/L) caused by platelet destruction with an increased risk of mucocutaneous bleeding. The diagnosis of ITP depends on clinical characteristics and the laboratory examinations conducted, as well as the ability to exclude other diseases associated with thrombocytopenia. Antiplatelet autoantibodies are responsible for platelet destruction and probably for inhibition of megakaryopoiesis. B lymphocytes participate in immune responses through production of antibodies, antigen presentation to T cells, and cytokine secretion. The aims of this study were to investigate the levels of Bregs and memory B lymphocytes in newly diagnosed pediatric ITP patients and to correlate their levels with the course of the disease.MethodsThis study was a case-control study. The study included 30 patients with acute ITP. The patients were recruited from Pediatric Clinical Hematology Unit of Children Hospital, Assiut University. In addition, 20 healthy children of comparable age and sex were taken as controls. The institutional review board approved the study and informed consents were obtained.ResultsThere is a significant alteration of B-cell homeostasis in patients with ITP.ConclusionAnalysis of Bregs and memory B cells could serve as prognostic markers and might guide therapy in ITP patients in the future.

Analysis of clinical effects and mechanism of recombinant human interleukin-11 with glucocorticoids for treatment of idiopathic thrombocytopenic purpura.

The aim of the present study was to evaluate the effectiveness and safety of recombinant human interleukin-11 (IL-11) with glucocorticoids for treatment of adult idiopathic thrombocytopenic purpura (ITP) and the regulatory effect on immune mechanisms. A total of 80 patients with initial diagnosis of ITP admitted to our hospital were selected. Patients were randomly divided into the control group and observation group, with 40 cases each. The control group received glucocorticoids treatment, and the observation group received IL-11 and glucocorticoids. The treatment effects were compared. The total effective rate and effective degree of the observation group was higher than in the control group and the difference was statistically significant (P<0.05); comparing the incidence of complications of the two groups, there was no statistical difference (P>0.05). In the observation group, onset time was reduced, platelet recovery level increased and platelet antibody positive rate decreased, and the differences were statistically significant (P<0.05). The total treatment course was shorter and recurrence rate was lower in the observation group compared with the control group, and the differences were statistically significant (P<0.05). The percentage of CD4+CD25+ regulatory T cells decreased in the two groups after treatment, and was more pronounced in the observation group. The difference was statistically significant (P<0.05). In conclusion, IL-11 with glucocorticoids for the treatment of adult ITP is safe and effective, and may be associated with decreased percentage of CD4+CD25+ regulatory T cells.

ITP or Not-ITP - a Rare Case of PTLD Recurrence Presenting As Autoimmune Thrombocytopenia

Introduction:Post-transplant lymphoprolifeative disorder (PTLD) is a heterogeneous group of lymphoproliferative disorders of lymphoid and/or plasmacytic differentiation that range from hyperplasias to aggressive non-hodgkin's lymphoma. It occurs in the setting of iatrogenic immunosuppression and usually EBV infection after solid organ or hematopoietic stem cell transplantation. PTLD can assume an astonishing number of guises and can often presents with fatigue, fever, weight loss to common hematologic disorders such as anemia and thrombocytopenia. PTLDs have been known to give rise to autoimmune hematologic disorders such as AIHA but it is extremely rare to see autoimmune thrombocytopenia as the presenting clinical sign.Case:A 46 year old male who underwent OLT for history of primary sclerosing cholangitis in 2007 and received graft rejection prevention with Tacrolimus. In 2008, he developed EBV positive PTLD while on immunosuppression, which was successfully treated with reducing to half dose and administration of three doses of Rituximab. Since resolution of PTLD, he was maintained on Tacrolimus up until current presentation.Patient presented to the hospital in July 2016 with mild gingival bleeding and platelet count of 4,000 cells/ml. Presuming a diagnosis of idiopathic thrombocytopenic purpura (ITP), he was started on prednisone 1mg/kg/day, was given two doses each of IVIG and RhoGam, as well as platelet transfusions with a goal of >10K. His thrombocytopenia remained non-responsive to aforementioned therapies, prompting further evaluation for a lymphoproliferative disorder. The bone marrow biopsy showed no evidence of clonal proliferation or dysplastic cells but increased megakaryocytes. However, a CT scan showed right axillary, subpectoral, and periaortic lymphadenopathy as well as a splenic mass. An excisional biopsy of the right axillary node revealed B-cell neoplasm, EBV negative, weakly CD20+ with focal plasmacytoma-like features, consistent with PTLD. Subsequently, we held Tacrolimus immunosuppression while closely monitoring hepatic function.He was started on weekly rituximab infusions, with a plan to evaluate his response before considering chemoimmunotherapy with CHOP. We opted not to pursue adding CHOP therapy upfront due to severe thrombocytopenia and risk of further myelosuppression. The patient's platelet count remained at 5,000-7,000 cells/ml until the end of week 2 of rituximab treatment. He was then discharged home on hospital day 20 with a platelet count of 58. As an outpatient, he continued to receive weekly Rituximab for a total of 4 doses and his platelet count eventually improved to 246,000 cells/ml.Discussion:PTLD is now the most common malignancy complicating solid organ transplantation (excluding nonmelanoma skin cancer and in situ cervical cancer). The majority of PTLD cases are secondary to EBV primary infection/reactivation which present early (within 1 year of transplant) but up to 33% to 48% cases are EBV negative, which usually present late in the course. The presenting symptom is highly variable, and it is imperative to differentiate between autoimmune thrombocytopenia due to PTLD vs idiopathic origin, as this determines the appropriate treatment strategy. In our patient, the cause of thrombocytopenia is likely due to a paraneoplastic process secondary to underlying PTLD. He did not have any significant response with steroids or IVIG, which is the conventional treatment for ITP, but instead showed clinical improvement with reduction in immunosuppression (RIS) and the anti-CD20 monoclonal antibody rituximab.Successful treatment of autoimmune thrombocytopenia secondary to PTLD involves early diagnosis and prompt institution of appropriate treatment. The treatment for PTLD lacks a standardized therapeutic approach with multiple treatment modalities. Despite the pathologic diversity, RIS remains the cornerstone of the treatment. Additional treatment with immunotherapy with rituximab has shown up to 50% response rates in CD20+ PTLDs. Systemic chemoimmunotherapy with R-CHOP is also considered in patients who are highly symptomatic and can tolerate chemotherapy.As displayed in the case of our patient, PTLD presents a multifaceted challenge in diagnosis and treatment. Early recognition of autoimmune thrombocytopenia secondary to PTLD is critical in rendering appropriate therapeutic intervention. DisclosuresNo relevant conflicts of interest to declare.

Megaloblastic Erythropoiesis- An Incidental Finding in Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura(ITP) presents as a primary form characterized by isolated thrombocytopenia(platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. The diagnosis of ITP is usually a diagnosis by exclusion based on a demonstration of peripheral thrombocytopenia, with a history, physical examination, and complete blood count that do not suggest another cause for the thrombocytopenia ITP may affect individuals of all ages, with peaks during childhood and middle aged. Pallor was the most common clinical manifestation of ITP. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Thrombocytopenia is caused by antibodies that react with glycoproteins expressed on platelets and megakaryocytes (glycoprotein IIb/IIIa, Ib/IX and others), causing shortened survival of circulating platelets and impairing platelet production. Bone marrow examination done in most of the patients. Micro- normoblastic erythropoiesis found to predominate. Megaloblastic erythropoiesis found in 20.3% cases. Megaloblastic erythropoiesis- A finding which can be seen in vitamin B12 deficiency, Anti intrinsic factor or Anti gastric mural cell antibodies and may be associated with other disorders of autoimmunity, the most usual being autoimmune thyroid disorders, type I diabetes mellitus, hypoparathyroidism, Addison's disease, post-partum hypophyseal necrosis, ulcerative colitis and vitiligo. The aim of this study is to correlate Bone marrow aspiration findings and possibility of autoimmunity with Idiopathic thrombocytopenic purpura (ITP).

Cyclic thrombocytopenia associated with menorrhagia

We studied a 17-year-old female P0 + 0 who presented with menorrhagia and cyclic thrombocytopenia (CTP). Cyclic changes were observed in platelet count in phase with menstruation with a nadir of 4–30 × 109/L and a rise of above 600 × 109/L noted over the 4 months period of the observation. Thrombocytopenia was associated with menorrhagia, gum bleeding and epistaxis, followed about 14 days later by normal or elevated platelet counts. Presenting packed cell volume (PCV), platelet count, and white blood cell (WBC) count were, 0.25 L/L, 4 × 109/L, and 6.8 × 109/L respectively, WBC and PCV all remain stable all through the period of study; antinuclear antibody, direct and indirect antiglobulin test was negative while flow cytometry for Gp IIb/IIIa and Ib were not done. Bone marrow examinations performed at the time of reduced platelet counts showed increased megakaryopoiesis. The patient was monitored and observed with only hematinics prescribed over the follow-up period, and menstrual suppression with combined oral contraceptives. CTP should always be suspected when a diagnosis of idiopathic thrombocytopenic purpura is entertained especially when there is a history of menorrhagia, thrombocytopenia, and rebound thrombocytosis.