Objective: To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods: Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results: Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion: Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.
Male ; Humans ; Adult ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Purpura, Thrombocytopenic, Idiopathic/diagnosis* ; Retrospective Studies ; Treatment Outcome ; China/epidemiology* ; Benzoates/therapeutic use*

OBJECTIVE: To investigate the changes of mean platelet volume (MPV), platelet distribution width (PDW) and platelet associated antibodies (PAIg) in children with acute immune thrombocytopenic purpura (aITP), and to explore the diagnostic value of MPV, PDW, PAIg and their combination for megakaryocyte dysmaturity in aITP children. METHODS: Plt count, MPV and PDW of 36 aITP children were measured by using Sysmex XN automatic blood cell analyzer, and 33 children with acquired thrombocytopenic purpura (ATP) without megakaryocyte dysmaturity. The expression of PAIg was detected by flow cytometry, and the number and classification of megakaryocytes in the bone marrow were performed by marrow cytology. The diagnostic significances of MPV, PDW, PAIg and their combination as well as the sensitivity and specificity for megakaryocytes dysmaturity in aITP were assessed through calculating the area under ROC curve (AUC), after determining the influence of each parameters on the megakaryocyte dysmaturity by Logistic regression. RESULTS: MPV, PDW and PAIg of aITP children were significantly higher than those of the ATP children (P＜0.05), while the Plt count and number of thromocytogenic megakaryocytes per area (1.5 cm×3 cm) were less than those of the controls (P＜0.05). Count of RBC and WBC, percentages of neutrophil granulocytes and lymphocydes in aITP were similar to those in the controls（P＞0.05）. The results of Logistic regression showed that Plt count, MPV, PDW and PAIg were the factors influencing megakaryocyte dysmaturity in aITP children, and the regression model has a high statistical significance (χ=65.491，P=0.001) and r square (R=0.713). The AUC of the combined detection of Plt count, MPV, PDW and PAIg was 0.863, which was much higher than that of Plt count, MPV, PDW, PAIg individually or in pairs. The sensitivity and specificity of the combined detection were 79.167% and 89.697%, which were higher than those of Plt count, MPV, PDW, PAIg individually or in pairs. CONCLUSION The diagnostic significance of MPV and PDW for megakaryocyte dysmaturity in aITP are insufficient, but the diagnostic efficacy can be improved by combined examination with PAIg.
Antibodies ; Blood Platelets ; Child ; Humans ; Mean Platelet Volume ; Megakaryocytes ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; diagnosis

MYH9-related disorders (MYH9RD) are autosomal-dominant disorders characterized by macrothrombocytopenia with or without leukocyte inclusion bodies or extra-hematological features, such as sensorineural deafness and renal impairment. MYH9RD can be misdiagnosed as an acquired form of thrombocytopenia including immune thrombocytopenic purpura (ITP). This leads to delayed diagnosis or administration of ineffective treatment. In the present study, we investigated the clinical and molecular characteristics of five unrelated Korean patients with MYH9RD and their family members, from four institutions. We reviewed clinical and laboratory data including extra-hematological manifestations. MYH9 pathogenic variants were detected by direct sequencing in all probands and the affected family members (N=10): two probands with c.5521G>A (p.Glu1841Lys) and one proband each with c.99G>T (p.Trp33Cys), c.287C>T (p.Ser96Leu), and c.3493C>T (p.Arg1165Cys). All patients had macrothrombocytopenia. Only the proband with Ser96Leu had extra-hematological manifestations. Past history revealed that two patients had been misdiagnosed with ITP and one of them had received a splenectomy. We validated the frequency of misdiagnosis (~20%) and genotype-phenotype correlations through a comprehensive review of previously reported cases of MYH9RD in Korea. It is important to suspect MYH9RD in patients with thrombocytopenia, and timely identification of macrothrombocytopenia and MYH9 pathogenic variants is required for early and accurate diagnosis of MYH9RD.
Deafness ; Delayed Diagnosis ; Diagnosis ; Diagnostic Errors ; Genetic Association Studies ; Humans ; Inclusion Bodies ; Korea ; Leukocytes ; Purpura, Thrombocytopenic, Idiopathic ; Splenectomy ; Thrombocytopenia

BACKGROUND: Immune thrombocytopenic purpura (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school-age children. Since children of different ages may have differing clinical courses, better delineation of the natural history of ITP in infants is needed. METHODS: We retrospectively reviewed the admission records of 248 consecutive pediatric patients between 1 month and 15 years of age who were admitted and treated for acute ITP at Pusan National University Children's Hospital from 2009 through 2017. All patients less than 1 year of age were identified and enrolled in this study. We investigated their demographics, clinical features, laboratory examinations, response to treatment, and long-term outcomes and made a comparison to those of children aged 1 to 10 years of age. RESULTS: Ninety nine infants were identified. Male to female ratio was highest in infants and decreased with age. Seventy nine (79.8%) of the 99 infant were found to be under 6 months old. The median platelet counts at diagnosis was 6×10⁹/L. Minor bleeding (bleeding score 0–2) was significantly dominant in infant compared to older subjects. Eighty two (96.5%) out of 85 patients achieved complete remission after initial intravenous immunoglobulin (IVIG) treatment. The relapse rate after initial CR was significantly lower than older ages (P=0.003). The platelet count after IVIG treatment in infant showed more rapid response compared to older subjects (P=0.04). Follow up information at 12 months was available for 70 infants. Chronic ITP at 12 month was seen less frequently in infants than in children 1 to 10 years of age (1.4% vs. 20.2%, P<0.001). CONCLUSION: Infants with acute ITP respond more favorably to IVIG treatment and are less likely to develop chronic ITP compared to children 1 to 10 years of age.
Busan ; Child ; Demography ; Diagnosis ; Female ; Follow-Up Studies ; Hemorrhage ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Infant ; Male ; Natural History ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Recurrence ; Retrospective Studies

BACKGROUND: Infants with immune thrombocytopenia (ITP) are at increased risk of high risk bleeding and vaccination-associated ITP. Infants with ITP respond favorably to treatment and are less likely to develop chronic ITP compared to older children. However the characteristics of this entity in infants have rarely been analyzed. We investigated the clinical characteristics and response to treatment of newly diagnosed ITP in infants under 1 year of age. METHODS: We retrospectively reviewed the medical records of newly diagnosed ITP infants between 1 month to 11 months of age at Chonbuk National University Hospital from 2002 to 2017. The demographics, complete blood count, absolute lymphocyte count (ALC), absolute neutrophil count, vaccination history, upper respiratory infection, viral study (cytomegalovirus) and treatment of patients with ITP were reviewed. RESULTS: A total of 85 patients satisfied the criteria for newly diagnosed ITP. Of these patients, 83 were in complete remission, 6 were in persistent remission, and 2 progressed to chronic ITP. As a result of the study, 57 patients (67%) were male. 71 patients (83.5%) were secondary ITP. Among secondary ITP, vaccination related ITP was the most common cause with 60 patients (84.5%). The mean at diagnosis was 4.3±3.2 month. There was no statistically significant difference in ALC between the time of diagnosis and treatment. Hemoglobin was 10.8 g/dL at diagnosis and increased significantly to 12.3 g/dL after treatment. CONCLUSION: Ninety-seven percent of ITP patients diagnosed under 1 year of age were in remission.
Blood Cell Count ; Child ; Demography ; Diagnosis ; Hemorrhage ; Humans ; Infant* ; Jeollabuk-do ; Lymphocyte Count ; Male ; Medical Records ; Neutrophils ; Purpura, Thrombocytopenic, Idiopathic* ; Retrospective Studies ; Vaccination

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory disorder characterized by specific pathological findings and elevated serum IgG4 level. IgG4-RD in the stomach is rare, and occasionally diagnosed as gastric subepithelial tumor (SET) by endoscopy or computed tomography scan. Two female patients in the age group of 40–50 years were diagnosed with 4 cm sized gastric SET. One underwent laparoscopic gastric wedge resection. Another one had a history of subtotal gastrectomy for early gastric cancer and idiopathic thrombocytopenic purpura with oral steroids administration. She underwent a completion total gastrectomy with splenectomy for the gastric SET and ITP. The pathology showed storiform fibrosis, and IgG4 was positive in immunohistochemistry (IHC) stain. IgG4-RD is known as a medical disease that could be treated with oral steroids. The difficulty in preoperative diagnosis of the disease occasionally causes unnecessary gastric resection. Thus, preoperative diagnostic methods for IgG4-RD such as deep biopsy with IHC stain or magnetic resonance imaging are needed.
Biopsy ; Diagnosis ; Endoscopy ; Female ; Fibrosis ; Gastrectomy ; Gastrointestinal Stromal Tumors* ; Humans ; Immunoglobulin G ; Immunoglobulins ; Immunohistochemistry ; Magnetic Resonance Imaging ; Pathology ; Purpura, Thrombocytopenic, Idiopathic ; Splenectomy ; Steroids ; Stomach Neoplasms ; Stomach*

Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children and can be defined as an autoimmune disorder of isolated thrombocytopenia without other causes of thrombocytopenia. This review will focus on the diagnostic approach of ITP, especially regarding the differential diagnosis. The practice of differential diagnosis has the goal of distinguishing primary ITP from secondary ITP and nonimmune thrombocytopenia requiring different treatments and showing different prognoses.
Child ; Diagnosis ; Diagnosis, Differential ; Humans ; Prognosis ; Purpura, Thrombocytopenic, Idiopathic* ; Thrombocytopenia

BACKGROUND: Cytomegalovirus (CMV) causes severe diseases in premature infants and immunocompromised hosts, and antiviral therapy is often required for disease control. However, the clinical manifestations and treatment courses for CMV-associated thrombocytopenia in immunocompetent children are unclear. METHODS: Medical records of the children who suffered from thrombocytopenia, and showed positive CMV polymerase chain reaction and CMV-like symptoms were retrospectively analyzed at three university hospitals in Daegu from January 2000 to March 2017. Patients suffering from leukemia, immunodeficiency, and other infections were excluded. RESULTS: Among 1,065 children with thrombocytopenia, 29 (2.7%) displayed CMV-associated thrombocytopenia. The median age at diagnosis was 15 months and the median platelet count was 26,000/µL. They were classified into the CMV-induced thrombocytopenia (23/29) and CMV-related secondary immune thrombocytopenia (ITP, 6/29) groups. Fourteen subjects had hepatic dysfunction, four had Evans syndrome, two had pneumonitis, and one had gastritis. IVIG was used for 21 patients, and six patients among them showed recurrence, for whom IVIG or antiviral therapy was used. All, except one, recurrent or chronic cases belonged to the CMV-induced thrombocytopenia group. Antiviral therapy was used more frequently for the CMV-induced thrombocytopenia group (8/23, 34.8%) than for the CMV-related secondary ITP group (0/6); however, the results were not statistically significant (P=0.148). CONCLUSION: CMV is a rare but unique etiology of thrombocytopenia, and observed even in healthy children after the neonatal period. About one-third patients need antiviral therapy for disease control. Further, CMV-induced thrombocytopenia is more complex than CMV-related secondary ITP.
Child* ; Cytomegalovirus ; Daegu ; Diagnosis ; Ganciclovir ; Gastritis ; Hospitals, University ; Humans ; Immunocompromised Host ; Immunoglobulins, Intravenous ; Infant, Newborn ; Infant, Premature ; Leukemia ; Medical Records ; Platelet Count ; Pneumonia ; Polymerase Chain Reaction ; Purpura, Thrombocytopenic, Idiopathic ; Recurrence ; Retrospective Studies ; Thrombocytopenia*

BACKGROUND: Autoimmune cytopenia (AIC) is a rare complication of allogeneic hematopoietic cell transplantation (HCT). In this study, we reviewed the diagnosis, treatment and response to therapy for pediatric patients with post-HCT AIC at our institution. METHODS: Of the 292 allogeneic HCTs performed from January, 2011 to December, 2015 at the Department of Pediatrics, The Catholic University of Korea, seven were complicated by post-HCT AIC, resulting in an incidence of 2.4%. RESULTS: All seven patients with post-HCT AIC had received unrelated donor transplant. Six of seven patients had a major donor-recipient blood type mismatch. The subtypes of AIC were as follows: immune thrombocytopenia (ITP) 2, autoimmune hemolytic anemia (AIHA) 2, Evans syndrome 3. Median time from HCT to AIC diagnosis was 3.6 months. All but one patient responded to first line therapy of steroid±intravenous immunoglobulin (IVIG), but none achieved complete response (CR) with this treatment. After a median duration of treatment of 15.3 months, two patients with ITP achieved CR and five had partial response (PR) of AIC. Five patients were treated with rituximab, resulting in the following response: 2 CR, 2 PR, 1 no response (NR). Median time to response to rituximab was 26 days from first infusion. All patients are alive without event. CONCLUSION: Post-HCT AIC is a rare complication that may not resolve despite prolonged therapy. Rapid initiation of second line agents including but not limited to B cell depleting treatment should be considered for those that fail to achieve CR with first line therapy.
Anemia, Hemolytic, Autoimmune ; Cell Transplantation* ; Child* ; Diagnosis ; Humans ; Immunoglobulins ; Incidence ; Korea ; Pediatrics ; Purpura, Thrombocytopenic, Idiopathic ; Rituximab ; Transplants* ; Unrelated Donors

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an acquired bleeding disorder in which the immune system destroys platelets. There were many studies which predicted the factors associated with the prognosis of childhood ITP, but controversies remained. We analyzed the predicting factors associated with the clinical outcome and prognosis of pediatric patients with newly diagnosed ITP in a single institution.METHODS: We reviewed retrospectively the medical records of 170 patients with newly diagnosed ITP at Chungnam National University Hospital (CNUH) from January 2005 to December 2015. The demographics, complete blood count (CBC), leukocyte differential counts and treatment of patients with ITP were reviewed.RESULTS: The median age at diagnosis were 20 months old (range, 0 to 189 months) for acute ITP and 52 months old for chronic ITP. After initial diagnosis of ITP, 20 of 170 patients (11.8%) were later diagnosed as chronic ITP. Age at diagnosis and absolute lymphocyte count (ALC) at diagnosis were statistically correlated with development of chronic ITP. ALC at diagnosis and at discharge were significantly higher in acute ITP patients than chronic ITP patients. We determined that ALC >4,109/μL at diagnosis and ALC >3,825/μL at discharge were associated with platelet recovery after 12 months.CONCLUSION: This study demonstrated that that high ALC at admission and discharge predict a favorable outcome in children with newly diagnosed ITP. Further studies are warranted to validate these findings.
Blood Cell Count ; Blood Platelets ; Child ; Chungcheongnam-do ; Demography ; Diagnosis ; Hemorrhage ; Humans ; Immune System ; Leukocytes ; Lymphocyte Count ; Medical Records ; Prognosis ; Purpura, Thrombocytopenic, Idiopathic ; Retrospective Studies