ITP Cases Research Articles

BAFF as a predictive marker for treatment response in immune thrombocytopenia patients

Abstract Background Immune thrombocytopenic purpura (ITP) is a hematological autoimmune bleeding disorder that characterized by isolated thrombocytopenia (platelet count <100 × 109/L) with unclear pathophysiology due to contribution of many cytokines, one of them is B-cell activating factor (BAFF) which affect both B-cell and T-cell activation and survival. Objectives This work aimed to study serum BAFF levels in the Egyptian ITP patients, and the relation between its level and response to steroid therapy, as well its value as a predictive marker for steroid response in ITP patients. Patients and methods 90 subjects were recruited, and divided into 45 patients with primary ITP, and 45 healthy subjects. Serum BAFF was estimated using the ELISA technique. Results BAFF level was significantly higher in the ITP patients than in the control group. Serum BAFF level was significantly higher in newly diagnosed ITP cases and steroids-resistant ITP cases. BAFF was negatively correlated with platelet count, while MPV, PDW, and LDH were positively correlated, BAFF level at a cut-off 201.01 pg/ml is a good predictive for steroid resistance in ITP cases. Conclusion BAFF could be a good inexpensive helper to determine the response to steroid treatment in ITP cases.

A case–control study of single-nucleotide variants in microRNA biogenesis genes (AGO1 and GEMIN4) in people with primary immune thrombocytopenia

BackgroundThe role of microRNA (miRNA) is to regulate the translation of genes involved in a variety of diseases.Aim of the workThis study investigated the relation between the rs636832 and rs2740348 single-nucleotide polymorphisms (SNPs) of the AGO1 gene and the GEMIN4 gene of miRNA biogenesis genes and the risk for primary ITP and the response to therapy.Patients and methodsIn this case–control study, 100 patients with immune thrombocytopenic purpura from the clinical hematology department and outpatient clinic were compared to 100 control subjects. Patients' blood samples are taken, and DNA extraction and PCR amplification of rs636832 A/G of AGO1 and rs2740348 G/C of GEMIN4 were done on sera and compared to the clinical status of the patients.ResultsAccording to statistical analysis, the genotype and allele frequencies of both variants did not differ significantly between cases and controls. The GG genotype was found to be more prevalent in the chronic phase of ITP than the AA and AG genotypes, with a significance level of p 0.05. The GG genotype was found to be more prevalent in the chronic phase of ITP than the AA and AG genotypes, with a significance level of p 0.05. In addition, the GG genotype was more prevalent in ITP patients who did not respond to treatment compared to the AA and AG genotypes, although this difference was not statistically significant. Concerning rs2740348: the CC genotype was more common than the GC genotype in ITP cases that did not respond to treatment and needed a second line of therapy like splenectomy or TPO-RA, but this did not reach statistical significance.ConclusionThe rs636832 and rs2740348 SNPs did not appear to be risk factors for ITP; however, the rs636832:GG genotype was more prevalent in older patients, who tend to have the chronic phase of the disease. Although this distinction was not statistically significant, they were less responsive to therapy than the AA and AG genotypes. Concerning rs2740348: the CC genotype was more common than the GC genotype in ITP cases that did not respond to treatment and needed a second line of therapy like splenectomy or TPO-RA, but this did not reach statistical significance.

Resource stewardship and Choosing Wisely in a children's hospital.

Evidence suggests that approximately 30% of the tests and treatments currently prescribed in healthcare are potentially unnecessary, may not add value, and in some cases cause harm. We describe the evolution of our hospital's Choosing Wisely (CW) program over the first 5 years of existence, highlighting the enablers, challenges, and overall lessons learned with the goal of informing other healthcare providers about implementing resource stewardship initiatives in paediatric healthcare settings. We describe the development of de novo "top 5" CW lists of recommendations using anonymous surveys and Likert scale scoring. Composition and role of the steering committee, measurement of data and outcomes, and implementation strategies are outlined. Many projects have resulted in a successful decrease in inappropriate utilization while simultaneously monitoring for unintended consequences. Examples include respiratory viral testing in the emergency department (ED) decreased by greater than 80%; ankle radiographs for children with ankle injuries decreased from 88% to 54%; and use of IVIG for treatment of typical ITP cases decreased from 88% to 55%. Early involvement focused within General Paediatrics and the ED, but later expanded to include perioperative services and paediatric subspecialties. An internally developed CW program in a children's hospital can reduce targeted areas of potentially unnecessary tests and treatments. Enablers include credible clinician champions, organizational leadership support, reliable measurement strategies, and dedicated resource stewardship education. The lessons learned may be generalizable to other paediatric healthcare settings and providers looking to introduce a similar approach to target unnecessary care in their own organizations.

Immune thrombocytopenia and COVID-19 vaccination: Outcomes and comparisons to prepandemic patients

BackgroundImmune thrombocytopenia (ITP) has been reported following COVID-19 vaccination. After index case fatalities, there was concern among patients both with and without a prior history of ITP in Australia. ObjectivesTo describe treatment outcomes of ITP after COVID-19 vaccination and compare relapsed vs historical pre-COVID-19 ITP cohorts. MethodsWe collected ITP cases in Australia within 6 weeks of receiving any COVID-19 vaccination as part of primary vaccination (up to October 17, 2021). Second, we reviewed platelet charts in a historical ITP cohort to determine whether platelet variability was distinct from relapsed ITP after vaccination. ResultsWe report on 50 patients (37 de novo, 13 relapsed ITP) vaccinated from March 22, 2021, to October 17, 2021. Although there was 1 fatality, bleeding was otherwise mostly minor: (70% WHO bleeding grade <2). De novo ITP was more likely after AstraZeneca ChAdOx1 nCoV-19 (89%) than Pfizer BNT162b2 (11%). Most patients responded quickly (median, 4 days; complete response, 40 of 45 [89%]). In the historical cohort, only 6 of 47 patients exhibited platelet variability (>50% decrease and platelets <100 × 109/L), but median platelet nadir was significantly higher than vaccination relapse (27 vs 6 × 109/L, P =.005). ConclusionITP was more frequently reported after AstraZeneca ChAdOx1 nCoV-19 than Pfizer BNT162b2 vaccination. Standard ITP treatments remain highly effective for de novo and relapsed ITP (96%). Although thrombocytopenia can be severe after vaccination, bleeding is usually mild. Despite some sampling bias, our data do not support a change in treatment strategies for patients with ITP after vaccination.

P647 Idiopathic Thrombocytopenic Purpura associated with Inflammatory Bowel Disease: a multi-centre ECCO CONFER case series

Abstract Background Idiopathic Thrombocytopenic Purpura (ITP) is an acquired haematological disorder with an incidence of 1 to 6 per 100.000, with reported comorbidity in patients with Inflammatory Bowel Disease (IBD). The current study aimed to evaluate the clinical presentation and outcome of ITP in IBD patients. Methods This multicenter retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports (CONFER) project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardised collection form. Results This report includes 20 patients with concurrent ITP and IBD: 15 were males, median age was 34 [Interquartile range (IQR) 25–56]. 12 subjects had a diagnosis of ulcerative colitis and 8 of Crohn’s disease. The diagnosis of IBD preceded the ITP diagnosis in 17 patients (median time between diagnosis was 7 years [IQR 1–14 years]). Among those, 10 patients were in IBD clinical remission at ITP diagnosis. Nine were treated with mesalamine, one with thiopurine, 4 with tumor necrosis factor-alpha (TNF) blockers, and 3 with no treatment. The mean platelet count at the presentation of ITP was 41.7±38.6 ×109/L. 6 patients had rectal bleeding, 8 had purpura, 6 had mucosal petechia, 2 had epistaxis, and 6 patients were asymptomatic. Regarding ITP treatment, 11 were treated with corticosteroids, 1 with Anti-RhD immunoglobulin, 7 with intravenous immunoglobulins (IVIG), 2 with rituximab and 2 patients eventually required splenectomy. All patients whose first presentation of ITP was rectal bleeding were treated medically with successful control of the ITP and IBD, None of them required splenectomy. 3 patients required colectomy with long-term follow-up, indicated by the IBD and not due to massive bleeding as a complication of ITP. With long-term follow-up, all patients had thrombocytes count above 50 ×109/L, and 18 were in IBD clinical remission. Conclusion Most ITP cases in this case series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients follows a regular course, including response to medical therapy and low rates of splenectomy.

Retrospective Evaluation of the Use of Romiplostim after Hematopoietic Stem Cell Transplantation0

Background Prolonged thrombocytopenia following hematopoietic stem cell transplant (HSCT) is a common complication associated with risks of major bleeding and high platelet transfusion requirements. Although not approved in the setting of post-HSCT thrombocytopenia, few case series have investigated the use of thrombopoietin (TPO)-receptor agonist romiplostim for patients receiving HSCT. Herein, we reviewed its use in the setting of HSCT at our Institution. Methods From January 2006 to December 2017, 4642 patients received a first HSCT. Of these patients, 2152 (46%) received an autologous HSCT (auto-HSCT) while 2490 (54%) received an allogeneic HSCT (allo-HSCT). Among the patients in the allo-HSCT group, 752 (30%) received a matched related HSCT, 1125 (45%) a matched unrelated HSCT, 278 (11%) a mismatch unrelated HSCT and 335 (13%) a cord blood HSCT. A reduced intensity conditioning regimen was used in 629 (25%) patients receiving an allogeneic HSCT. An adequate clinical response was considered as a reduction of transfusion requirement and a platelet count PLT ≥ 50*103 /µL. This research was approved by the Institutional Review Board (IRB). Results Seven patients (adults n=5, children n=2) received romiplostim for thrombocytopenia. Patients' characteristics are reported in Table 1. All but one (who had CLL-related ITP) received the drug while in remission for the underlying hematologic disease. Romiplostim was used in 6 patients after an allo-HSCT and in 1 after an auto-HCT. Among the allo-HSCT recipients, all 6 reached neutrophil engraftment at a median time of 19 days (range 14-28 days). Romiplostim was administered for ITP (n=2) and poor graft function (PGF, n=4), at a median time of 7.5 months (range 2 - 34 months), with a median of 16 administrations (range 3-18) per patient. All patients received romiplostim weekly, with a median initial and maximum dose of 1 µg/kg (range 1-3 µg/kg) and 9.5 µg/kg (range 3-10 µg/kg), respectively. For the 2 ITP cases, romiplostim was given as third line of therapy, after a lack of response to both high dose steroids and intravenous immunoglobulin. One patient responded to the treatment, achieving a platelet count ≥ 50*103/µL after 2 months, while the other patient did not show any improvement and the drug was discontinued after 3 months. All the 4 PGF cases were thought to be secondary to medications, with one patient also having acute graft versus host disease (GvHD) as possible cause. Romiplostim was given as first line of treatment in all the cases; median platelet counts at the time of starting the treatment was 21*103/µL (range 13-42*103/µL). One patient did not show any response after 4 months of treatment and was subsequently switched to another TPO receptor agonist. Three patients showed a clinical benefit: one patient achieved a stable platelet count ≥50*103/µL after one month, another patient had a partial response achieving transfusion-independence after 3.5 months, but with PLT counts remaining below 50*103/µL; the third patient had a transient increase in platelet counts with decreased transfusion requirement, but the response was lost after two weeks. Overall romiplostim was well tolerated, with no major side effects related to its administration. In two cases mild increase in reticulin stain (grading 0-1) was observed. The auto-HSCT patient receiving romiplostim had Hodgkin's Lymphoma and was diagnosed with recurrent ITP 7.5 years after HSCT, while in complete remission for the underlying disease; he received romiplostim as part of the ITP treatment, and responded to a combination of romiplostim and mycophenolate mofetil without reporting adverse events. Conclusion In our analysis, the use of romiplostim was limited to very few cases of HSCT. The retrospective nature of this study along with a very small and heterogeneous cohort does not allow us to draw any efficacy conclusions. However, our data suggest that romiplostim could be considered a safe option to treat prolonged thrombocytopenia after HSCT. Prospective, randomized clinical trials using TPO-receptor agonists for thrombocytopenia in HSCT are needed to determine efficacy and potential side effects. Disclosures Lawrence: Amgen Inc.: Employment, Equity Ownership. Gernsheimer:Dova pharmaceuticals: Consultancy; Novartis: Honoraria; Amgen: Consultancy, Honoraria; Rigel: Consultancy; Shionogi: Consultancy; Cellphire: Consultancy; Fuji film: Consultancy; Bioverativ: Consultancy. Milano:Amgen: Research Funding; ExCellThera: Research Funding. OffLabel Disclosure: We investigated the use of Romiplostim for thrombocytopenia after hematopoietic cell transplant.

PF691 SPLENECTOMY IN IMMUNE THROMBOCYTOPENIA: DO CHANGING TREATMENT PATTERNS FOR ITP AFFECT OUTCOMES? DATA FROM THE UK ITP REGISTRY

Background:The advent of medical alternatives to splenectomy, particularly the thrombopoietin receptor agonists (TPO‐RA) has seen reduction in its use for ITP. It is now generally reserved in the UK for patients who fail multiple lines of therapy.Aims:We aimed to evaluate practices around splenectomy in the UK and long term response rates using data from the UK ITP registry, a large national database of primary ITP cases set up in 2007.Methods:We analysed all splenectomy cases from the UK ITP registry entered to December 2018. Data was studied on demographics, response rates, relapse rates and influence on response to medical therapies. Statistical analysis was performed using STATA. To identify the influence of medical therapies, we divided patients into treatment time brackets: 1989–1998, 1999–2008 and 2009–2018. The following response criteria were used:Complete response (CR platelets&gt;100 x 109/l),partial response (PR platelets&gt;30 but &lt;100x109/l or doubling from baseline),overall response (OR = PR+CR).Results:Of 3236 registered patients(ITP diagnosis date ranging 1951 – 2018), 321(9.92%)(62%F/38%M) had undergone splenectomy with a total of 4611patient‐years follow‐up(Median 13.2 years, IQR 6.68,23.6). Median age at splenectomy was 40 years(y)(IQR27.0, 55.5).86.2%(268 patients) were &lt;65y old and 13.8%(43 patients) 65y or older.72 patients were excluded from subsequent analysis due to incomplete data(including patients who had splenectomy &lt;1989).Number of patients undergoing splenectomy decreased over time:1989–1998 34.1%;1999–2008 14.8%;2009–2018 4.8%. Median time from ITP diagnosis to splenectomy was 1.46y(IQR 0,20.3) increasing from 1.51y(IQR0,9.23.) in 1989–1998 to 1.69y(IQR0.14,18.5) in 2009–2018. This was associated with an increase in median number of treatment modalities from 2(IQR1,3) in 1989–1998 to 3 (IQR1,7) in 2009–2018 and median number of treatment episodes from 1(IQR1,2) in 1989–1998 to 3 (IQR1,11) in 2009–2018 pre‐splenectomy. The most common treatment modalities pre‐splenectomy were prednisolone(92%),IV immunoglobulin(50%),Azathioprine(27%),Rituximab(21%),Dexamethasone(12%),Mycophenolate(10%) and Romiplostim(10%).CR/PR and OR rates post‐splenectomy were 63.1%/24.3%/87.4% at 1month and 52.2%/15.3%/67.5% at 6months.67.2% of patients who had OR to splenectomy at 1month still had OR at latest follow‐up(median follow‐up 10.5y,IQR4.37,14.4).OR in patients &lt;65y old were 86.8% at 1month and 51.8% at 6months post‐splenectomy.OR in those 65y and older were 73.9% at 1month and 46.2% at 6months post‐splenectomy.Beyond 6 months there is a trend towards reducing response in &gt;65y group, but currently further analysis is limited by missing data.Overall median duration of response(DOR) was 2.5y(IQR0.51,7.01).The median DOR fell over time from 7.35y(1989–1998) to 0.52y(2009–2018).Median DOR was 3.02y in &lt;65y old(IQR0.60,7.70) and 0.76y in 65y or older(IQR0.17,4.2.93).In patients who relapsed post‐splenectomy, median time to treatment was 2.56y(IQR0.09,35.48).59patients(18.4%) had complications post splenectomy.42patients(13.1%) had infections of which 32cases(76.2%) were attributed to splenectomy.53patients(11.2%) had an arterial or venous thrombotic event post‐splenectomy. Of 4deaths(1.25%),1 was listed as being attributed to splenectomy.Summary/Conclusion:Splenectomy rates for ITP in the UK have fallen since 1989, associated with increased medical treatment. There appears to be a trend to reduced response rates and shortened remission duration when this is used later in the treatment pathway.

Reduced 25-OH vitamin D in patients with autoimmune cytopenias, clinical correlations and literature review.

Vitamin D deficiency is widespread in Western Countries and has been found related to autoimmune and hematologic disease incidence and clinical course. We evaluated vitamin D levels, vitamin D receptor (VDR) and T helper (Th)1, Th2 and Th17 immunomodulatory cytokines in patients with immune thrombocytopenic purpura (ITP, N=44), primary autoimmune hemolytic anemia (AIHA, n=35), Evans' syndrome (n=5) and chronic idiopathic neutropenia (CIN, n=19) and also tested vitamin D effect on the in vitro production of anti-erythrocyte autoantibodies. 25-OH-vitamin D levels were significantly lower and vitamin D receptor higher in patients than in controls. Among ITP cases, those with very low vitamin D levels displayed reduced platelet counts, irrespective of the bleeding history. In AIHA patients, LDH values negatively correlated with vitamin D levels in mixed forms, and reticulocyte counts were positively related with vitamin D. Considering treatment, AIHA patients who had been treated with 2 therapy lines or more showed lower mean 25-OH-vitamin D levels than those untreated or treated with one line of therapy only. IL-6, IL-10, IL-17 and IFN-γ levels were higher in patients versus controls, whereas TNF-α was significantly reduced. Finally, vitamin D at concentrations of 10, 20, and 40ng/mL reduced the in vitro production of anti-erythrocyte autoantibodies both in pokeweed-stimulated and unstimulated cultures. In conclusion, vitamin D is reduced in autoimmune cytopenias and correlate with disease severity, supporting its possible protective role against the development of autoimmunity. Literature review showed vitamin D deficiency reports both in onco- and in non onco-hematologic diseases with a relationship with disease severity/activity in myeloid and lymphoid neoplasms, as well as in sickle cell disease. Supplementation has produced weak results in autoimmune and hematologic diseases, and further studies are needed.

Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura.

Notch signalling is involved in the development of several autoimmune diseases, one of such diseases is ITP. The aim of this study was to investigate and compare the expression levels of Notch1 receptor and its target Hes1 gene in Egyptian paediatric ITP patients. Real-time quantitative reverse transcriptase polymerase chain reaction was used to analyse the expression levels of Notch1 and Hes1 in 42 children with primary ITP (22 newly diagnosed and 20 persistent) cases. Twenty age and sex matched non-ITP controls were included. The expression levels of Notch1 were higher in newly diagnosed and persistent cases than controls with high statistical significant difference (P value <0.001, P<0.001) respectively, similarly as regards the expression levels of HES1 (P value <0.001, P<0.007) respectively. A significant positive correlation was found between Notch1 and Hes1 expression levels in newly diagnosed cases (r=0.587, P value=0.004). There was an association between levels of both genes in most of ITP patients but Hes1 was markedly elevated than Notch1 in few cases. High expression levels of Notch1/Hes1 indicated the important role of Notch signalling in both newly diagnosed and persistent ITP. High expression levels of Hes1 than Notch1 may shed light on its value as a therapeutic target for future research in ITP.

A Study of Human Killer Cell Immunoglobulin-Like Receptor and Multidrug Resistance Gene Polymorphisms in Children With Immune Thrombocytopenia.

This study was undertaken to detect characterization of the different gene polymorphisms in Human killer cell immunoglobulin-like receptor (KIR2) gene and multi-drug resistance (MDR1) gene, among childhood ITP Egyptian patients. In addition to assess the potential role of these polymorphisms in relation to types of ITP and response to different treatment modalities. A total of 48 pediatric patients with immune thrombocytopenia (ITP; 24 newly diagnosed and 24 chronic) and 35 healthy controls were investigated via polymerase chain reaction-restriction fragment length polymorphism analysis for multidrug resistance (MDR) 1 and killer cell immunoglobulin-like receptor (KIR) 2 genes. The frequency of MDR1 gene in patients and control was not significant (P = .090). The CT genotype was the highest distribution among all ITP cases (62.50%, n = 30) and control (48.60%, n = 17). There was a significant difference in age at diagnosis of MDR1 gene with the CC genotype had the eldest age and lowest initial platelets count (P = .029 and P = .004). The distribution of KIR2 gene among all patients with ITP and controls was significant (P = .026) with (KIRDL2-/KIRDS2-) genotype was the most prevalent among patients. The frequency of MDR1 polymorphisms was not associated with susceptibility to the development and clinical progression of the disease. However, KIR2 gene polymorphisms were independently associated with childhood ITP in Egyptian patients with highest prevalence among (KIRDL2-/KIRDS2-) genotypes.

Recurrent Immune Thrombocytopenic Purpura: Interesting Case of a Child with 5 Recurrences

Immune thrombocytopenic purpura [ITP], also known as idiopathic or autoimmune thrombocytopenic purpura, is a benign hematological disorder characterized by a low circulating platelet count, caused by destruction of antibodysensitized platelets in the reticuloendothelial system. It is a common cause of acquired thrombocytopenia particularly in children, which often remits in weeks to years. ITP can be classified based on duration of thrombocytopenia as acute and chronic form. Recurrent ITP is defined as recurrence of symptoms, after at least three months of remission without treatment. It is rare entity and seen in just 5% of all ITP cases. Further, its treatment is often cumbersome and warrants use of non-conventional drugs and splenectomy. We report a case of ITP in a 9 year old boy, who presented with five recurrences and all episodes were successfully treated with just oral prednisolone.

Retrospective Review of 524 Cases of Pediatric ITP at An Academic Medical Center: Changes In Treatment of Childhood ITP Between 2003–2010

AbstractAbstract 2510 Background:Childhood ITP is an immune-mediated disorder characterized by low platelet counts and increased risk of bleeding, but life-threatening bleeding is extremely rare, and 2/3 of childhood ITP cases spontaneously resolve. Thus, studies to discern “best” initial therapy have not been feasible. The choice of observation vs. pharmacologic treatment and among treatments is empirical, varying by clinician and center. Expert consensus statements recommend initial observation but how closely these suggestions are followed is unclear (Provan D, et al. Blood 2010; 115: 168). Our objective for this study was to evaluate a large cohort of ITP patients at a single center for treatment trends. Methods:After IRB approval, charts were reviewed from 524 subjects with ITP, identified from Children's Hospital Boston hematology records and from hospital wide ICD-9 billing codes. Only subjects with a first hematology clinic visit from April 2003 through June 2010 were included. Demographic, laboratory, and treatment data were collected. Treatment with “short steroid course” was defined as ≤14 days. Initial observation was defined as ≥7 days from diagnosis without treatment. Remission from ITP on observation was defined as a platelet count ≥ 100,000/uL. SAS 9.3 was utilized for Cochran-Armitage tests for trend. Results:Of the 524 subjects, 92 % had primary ITP and 8% had secondary ITP, including Evans syndrome and ALPS. 73% had acute (<3 months) or persistent ITP (<1 year), and 27% had chronic ITP (>1 year duration)(Rodeghiero F, et al. Blood 2009; 113:2386). Median age at diagnosis in those with acute or persistent ITP was 4.4 y (IQR 2–10.1) and with chronic ITP was 10.8 years (IQR 4.4–15.1), p<0.001. 39 (7.4%) subjects experienced Grade IV bleeding, and 6 (1.1%) had Grade V (life threatening) bleeding by the scoring system of Buchanan and Adix (J Pediatr 2002; 141:683). The most frequent first treatments used were: anti-D globulin (anti-D)(40.2%), short steroid course (38%), and IVIG (12%). Of 280 Rh+-subjects who received treatment, 133 (47.5%) received anti-D. Use of anti-D as first line therapy significantly decreased by year from 2003 to 2009 (p for trend<.001). Short course steroid use for initial therapy increased by year over the same time period (p for trend <.001). These changes preceded the recent U.S. FDA-mandated boxed warning regarding hemolysis with anti-D. There was no significant trend in use of IVIG and observation as initial therapy over time. 204 (39%) subjects were initially observed without medications. Of these, 60% went into remission during observation and required no further treatment. 17% of the 204 observation subjects developed chronic ITP and continued observation. 23% (47) of the 204 initially observed later received treatment; in this group, median time between diagnosis and treatment after a period of observation was 1.6 mos (IQR 0.5–9.4 mos). Of the 47 observed patients who were later treated, the most commonly cited reasons for treatment initiation included “thrombocytopenia” (25%), bruising (15%), and lifestyle considerations (i.e. desire to be more active)(14%). The most common reasons subjects received drug therapy rather than observation as a first treatment option were thrombocytopenia (27%), bruising (21%), and active bleeding (13%). Conclusions:Within one large ITP center, initial treatment choices changed over the past 7 years. Previously, anti-D was given most frequently, but its use has declined while use of short course steroids increased. IVIG use remained constant. Despite recommendations for observation and data confirming its safety, use of observation has not changed with time and only 39% of patients in our center were initially observed without pharmacologic therapy. The most common reason for taking children off of observation and treating was not bleeding. Inconsistencies in treatment of pediatric ITP exist even within academic centers. Efforts should be made to follow published treatment guidelines. Disclosures:No relevant conflicts of interest to declare.

Clinical Features and Effects of Eradication on Helicobacter Pylori Positive 207 ITP Cases in Japan.

In 1998, Gasbarrini et al reported that in ITP cases with Helicobacter pylori (H.pylori) infection, elevation of platelet counts was observed by eradication of this bacterium. Since then, several reports from Italy and Japan confirmed the elevation of platelet counts after eradication. However, the characteristic background in the H.pylori positive ITP and eradication effects on platelet counts is unclear. On the other hand, reports from Spain, North Europe and USA could not show the evidence that eradication is effective on elevating platelet counts in H.pylori positive ITP.Therefore, we designed a nationwide retrospective study in Japan to evaluate the incidence of H.pylori positive ITP cases and the effects of eradication on platelet counts and to clear above problems.Four hundred and thirty-five ITP cases were enrolled over a period of one and half years (2002. 7~2003.12) from 12 hospitals. H. pylori infection was found in 300 cases(65%), who were significantly (P<0.005) older and showed hyperplastic megakaryocyte in bone marrow (P=0.011) comparison with negative cases. Eradication to H. pylori was performed in 207 H. pylori positive ITP cases and as a whole, the platelet count response was observed in 63% of eradication succeeded group. In the successful group, CR and PR rate were 23% and 42% respectively at 12 months after eradication. The platelet count response was significant in the successfully eradicated group (P<0.005) and the increased platelet count was maintained without ITP treatment for over 12 months. In conclusion, H. pylori infection was involved in most ITP patients over 40 years old in Japan and eradication therapy proved effective for increasing platelet counts even in splenectomy non-responsive cases and the platelet count response appeared one month after eradication. This evidence suggests that eradication therapy is the first line of treatment in H. pylori positive ITP patients.

Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura

We investigated the levels of various chemokines and soluble CD40L (sCD40L) in ITP patients, in order to determine the influence of CD40-CD40L interaction on the pathogenesis of ITP. We found increases in MCP-1 and RANTES levels in ITP patients compared with those in healthy individuals. Thirty-eight of the 65 ITP patients (58.5%) had elevated levels of sCD40L. We found significant decreases in platelet counts in sCD40L-positive ITP patients. Although the sCD40L level did not differ significantly between the control and nonimmune thrombocytopenia groups, but among ITP patients. sCD40L level was significantly higher in those with untreated ITP than in those with treated ITP. In addition, significant increases in RANTES, MCP-1, sCD14, and sP-selectin levels were observed in sCD40L-positive ITP patients, although sE-selectin levels were not increased in such patients. For other factors examined, however, there were no differences in level between sCD40L-positive and -negative ITP patients. These findings suggests that there are two groups of ITP patients, one with elevated and one with normal of sCD40L. ITP cases in which sCD40L was increased appeared to involve changes in platelet counts and monocyte activation. The pathogenesis of ITP may in some patients include alterations of the CD40/CD40L pathway.

Idiopathic Thrombocytopenic Purpura (ITP)

Sir.—I read with interest the article by Movassaghi et al entitled Antiplatelet Antibodies in Childhood Idiopathic Thrombocytopenic Purpura (Journal133:257-259, 1979). However, I cannot agree with their conclusion that platelet antibody usually disappears with recovery from thrombocytopenia in childhood ITP. We have already shown in three chronic and five acute cases of childhood ITP that have been in remission for up to six years that mean platelet survival is shorter with platelet opsonization in five cases (in whom it could be determined).1.2 The study has been extended to include 14 children with ITP (six chronic and eight acute) in remission, and again, severe reduction in platelet survival (mean, 4.0 days, which is shorter than in previous reports1.2) with platelet opsonization was shown in every case. The antiplatelet antibodies shown by the Handin and Stossel method3related to acute phase and remission of 49 childhood ITP cases, and

A SURGICAL CASE OF GASTRIC CANCER ASSOCIATED WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

A 39-year-old male patient with gastric carcinoma associated with idiopathic thrombocytopenic purpura is reported. A total of 125g of complete molecular-type γ-globulin (400mg/kg/day) and 10 units of platelets were administered preoperatively. When prepoerative platelet counts increased from 7.3×104/mm3 to 18.8×104/mm3 with these treatments, total gastrectomy with regional lymph node dissection and splenectomy were safely performed without blood transfusion. Postoperative administration of 20 units of platelets resulted in maintaining of stable platelet count at approximately 80×104/mm3. Postoperative course was uneventful and the patient was discharged on 21st day after surgery. A large quantity of intact γ-globulin regimen, which can increase platelet count safely and certainly in a short time, may be most appropriate in ITP cases necessitating a transient increase in thrombocytes for surgical procedures in which other drugs are ineffective, and hemorrhagic tendency is severe.

血小板減少を主症状としたSLEの1例と,当内科で経験したいわゆるITP 10症例の自己抗体に関する検討

血小板減少を主症状としたSLEの1例と,当内科で経験したいわゆるITP 10症例の自己抗体に関する検討

Idiopathic Thrombocytopenic Purpura (ITP)

Sir.—I read with interest the article by Movassaghi et al entitled Antiplatelet Antibodies in Childhood Idiopathic Thrombocytopenic Purpura (Journal133:257-259, 1979). However, I cannot agree with their conclusion that platelet antibody usually disappears with recovery from thrombocytopenia in childhood ITP. We have already shown in three chronic and five acute cases of childhood ITP that have been in remission for up to six years that mean platelet survival is shorter with platelet opsonization in five cases (in whom it could be determined).1.2 The study has been extended to include 14 children with ITP (six chronic and eight acute) in remission, and again, severe reduction in platelet survival (mean, 4.0 days, which is shorter than in previous reports1.2) with platelet opsonization was shown in every case. The antiplatelet antibodies shown by the Handin and Stossel method3related to acute phase and remission of 49 childhood ITP cases, and

QUANTITATIVE NITROBLUE TETRAZOLIUM (NBT) IN IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

Antiplatelet antibodies acting as opsonins to promote phagocytosis of sensitized platelets by normal granulocytes in 5cacute and 4 chronic ITP cases in relapse, which did not change in remission, were shown. In spite of this finding, in vivo granulocyte stimulation was not shown in 14 cases of ITP by NBT reduction, by the method of Baehner and Nathan. These findings will be discussed.

THE ROLE OF THE HUMORAL IMMUNE SYSTEM IN CHILDHOOD IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

The pathogenesis of childhood ITP is not well understood. To explore the role of the humoral immune system in ITP, bone marrow (BM) and splenic (Sp) lymphocytes from ITP and control children were cultured and in vitro IgG production was measured; in some cases platelet specificity was assessed. Platelet-associated IgG (PAIgG) was also determined as a measure of platelet-bound antibody or complexes. BM and Sp cells were cultured in 20% fetal calf serum, Dulbecco's medium, for 10 days. The Fab-anti-Fab immunoassay was used in all IgG determinations. Platelet specificity was determined using an IgG absorption technique. PAIgG of circulating platelets from control and ITP subjects was assayed directly after washing the platelets by gel filtration. Mean BM synthesis rates (ngIgG/106 lymphocytes/day) of acute and chronic ITP cases were 219±92 and 619±216; both were significantly greater than control values of 98±62 (p<0.01 and 0.001 respectively). SpIgG synthesis rates of chronic cases and controls were 85.9±52 and 22.9±11, respectively, and differed significantly (p< 0.001). Four of 4 splenic samples showed significant binding to target platelets which averaged 1232 ngIgG/109 platelets. Blood PAIgG values (ngIgG/10 platelets) of acute cases (range 5588–56,250) and chronic cases (range 2425–16,800) were greater than control values of 1089±213 (p<0.001) and the two ITP groups appeared to reflect different statistical populations. We conclude these data support immune-mediated platelet destruction in both acute and chronic childhood ITP. Differences in PAIgG values, although preliminary, may be of diagnostic importance and suggest different mechanisms may be involved.