Diagnosis Of Immune Thrombocytopenic Purpura Research Articles

Role of Mean Platelet Volume (MPV), Platelet Distribution Width (PDW) and Platelet Large Cell Ratio (P-LCR) Value in the Diagnosis of Immune Thrombocytopenic Purpura

A cross-sectional retrospective study was carried out at the Bangabandhu Sheikh Mujib Medical University, Dhaka to determine the diagnostic significance of platelet indices in ITP. Total 60 cases were included in this study. Complete history was taken either from patient or accompanying attendants. Thorough clinical examination was done. Mean age of the study population of aplastic anaemia (AA) was 36.66(±17.04) years and immune thrombocytopenic purpura (ITP) was 29.70(±13.99) years. Mean platelet count was 38.73(±15.99) x109/L and 30.46(±14.17) x109/L in AA and ITP respectively and that was not statistically significant. In AA mean platelet volume was 9.75(±1.15) fl and in ITP mean platelet volume was 12.01(±1.23) fl. In AA mean platelet distribution width was 11.75(±2.13) fl and in ITP mean platelet distribution width was 18.07(±2.52) fl. In AA mean platelet large cell ratio was 21.07(±5.51) % and in ITP mean platelet large cell ratio was 36.68(±7.91) % and that was statistically significant. Sensitivity and specificity of platelet indices to make a diagnosis of ITP was calculated under various cut-off ranges. MPV cut of value >11fl sensitivity was 73.33% and Specificity was 80.0%, MPV cut of value >12 fl sensitivity was 53.3% and Specificity was 96.7%, MPV cut of value >13 fl sensitivity was 26.7% and Specificity was 100%. PDW cut of value >14 fl sensitivity was 86.67% and Specificity was 93.3%. PDW cut of value >15 fl sensitivity was 100% and Specificity was 83.0%. P-LCR cut of value >40% sensitivity was 100% and Specificity was 63.0%. These indices could help to distinguish hyper-destructive thrombocytopenia and hypo-productive thrombocytopenia very easily and it is also cost effective. Platelet indices, if reported, provide a lot of clinical information about the underlying conditions of thrombocytopenia.

Importance of immature platelet fraction as predictor of immune thrombocytopenic purpura.

Background and Objective:Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura) or extravasation of blood from capillaries into skin and mucous membranes (petechiae). The diagnosis of ITP can be made clinically on the basis of symptoms, we need to see if ITP can be confirmed in patients by quantification of residual RNA containing immature platelets (megakaryocytic mass) or immature platelets fraction (IPF) using automated hematology analyzers (Sysmex XE-2100).Methods:In order to check the efficacy of IPF% parameter of Sysmex XE-2100 a total of 231 patients of thrombocytopenia were included in this study. Complete blood count (CBC) was estimated. The data was statistically analyzed by SPSS version 17.Results:About 62 patients were diagnosed as ITP and 169 patients were diagnosed as non ITP on the basis of clinical history. The mean IPF % value of ITP patients was 16.39% and the IPF % value of Non ITP patients was ~7.69% respectively. There was no significant difference in IPF% values with respect to time between sampling and acquisition of complete blood count. The diagnostic sensitivity of IPF% as biomarker for ITP and non-ITP was 85.71% (95%CI: 84.04% to 85.96%) and 41.76% (95% CI: 39.87% to 43.65%).Conclusion:The mean IPF % value by Sysmex XE-2100 can be used to predict ITP.

Ovarian Torsion-A Rare Presentation in Immune Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder that is caused by antibody mediated platelet destruction with a normal bone marrow. Bleeding manifestations are mostly muco-cutaneous and mild. Intra-ovarian bleeding leading to enlargement and subsequent torsion is extremely rare and only one case has been reported so far in literature. We describe a case of a 14 year old girl who presented in Medical Emergency with abdominal pain, vomiting and low grade fever. She was clinically observed for gastroenteritis as all her investigations were normal, except for ultrasound which depicted a mildly enlarged polycystic left ovary. On further continuation of symptoms, a repeat scan showed heterogeneous complex left adnexal mass. Color Doppler and MRI confirmed ovarian infarction. She was prepared for laparotomy but had very low platelet counts on pre-anesthetic checkup. With hematology consultation and bone marrow biopsy, a diagnosis of immune thrombocytopenic purpura was made. With initiation of prednisolone her counts improved dramatically and later laparotomy was done after 7 days. Histopathology specimen of ovary confirmed stromal hemorrhage and areas of necrosis. Intra-ovarian bleeding, possibly because of very low platelet count, resulting in an enlarged ovary and subsequent torsion might be the association between these two clinical entities.

Seasonal variation of immune thrombocytopenic purpura related hospitalizations among adults in the USA: analysis of the nationwide inpatient sample database.

Prior studies in the USA and elsewhere have suggested a distinct seasonal pattern in the incidence of immune thrombocytopenic purpura (ITP) among children [Kuhne et al. 2001; Moussalem and Yassine, 2003; Watts, 2004; Zeller et al. 2005; Yong et al. 2010]. However, it remains unknown if such a seasonal trend exists among adults with ITP-related hospitalizations. We utilized the Nationwide Inpatient Sample (NIS) database to study the seasonal pattern of ITP-related hospitalizations among adults in the US. NIS is the largest inpatient database in the USA and is sponsored by the Agency for Healthcare Research and Quality. International Classification of Diseases ninth revision, Clinical Modification code 287.31 was used to identify all patients discharged with a principal diagnosis of ITP between 1 January 2005 and 31 December 2011. We stratified each hospitalization with a primary diagnosis of ITP by the month of presentation. Walter and Elwood modification of the Edwards test was used to determine the monthly variation in the frequency of hospitalizations. Statistical analysis was conducted using STATA-MP 13.0 (StataCorp LP, College Station, TX, USA). ITP accounted for a total of 69,981 hospitalizations between 2005 and 2011. No significant monthly variation in ITP-related hospitalizations was seen during the study period (Figure 1). There was a nonsignificant trend towards peak hospitalization during the month of September (peak/low ratio of 1.01, 95% confidence interval 1.0–1.03). Figure 1. Monthly frequency distribution of immune thrombocytopenic purpura (ITP)-related hospitalizations in the USA based on the Nationwide Inpatient Sample database 2005–2011. Our study shows a lack of a seasonal trend among ITP-related hospitalizations among adults in the USA. This is in contrast to childhood ITP, for which a distinct seasonal trend has been shown [Kuhne et al. 2001; Moussalem and Yassine, 2003; Zeller et al. 2005; Yong et al. 2010]. The seasonal pattern among children with ITP likely reflects the seasonality of viral infections such as influenza, which is responsible for the majority of cases of ITP in children [Yong et al. 2010]. Unlike in children, ITP in adults has an insidious onset and a chronic course with no preceding viral illness or other infection [Liu et al. 2013]. The large sample size and inclusion of different regions of the USA are the main strengths of our study. However, our study has several limitations. It was a retrospective study based on discharge-level patient data with limited clinical information. NIS is a deidentified administrative database and is prone to errors in coding of diagnoses that cannot be individually verified.

Significance of lymphocyte counts at diagnosis in the management of ITP: the relationship between lymphocyte counts and treatment success in H. pylori-infected patients.

Immune thrombocytopenic purpura (ITP) is an acquired disorder characterized by thrombocytopenia, increased platelet destruction, and the inhibition of platelet production by specific autoantibodies. Previous studies have reported improvements in ITP following the eradication of Helicobacter pylori (H. pylori) infection. We, herein, investigated the relationship between initial therapy for ITP and lymphocyte counts at diagnosis. We retrospectively examined 52 adult patients with ITP between March 1998 and March 2013. Standard H. pylori eradication therapy was performed in 31 patients, and lymphocyte counts were compared before and after this therapy. At the diagnosis of ITP, lymphocyte counts in H. pylori-infected patients were significantly higher than those in H. pylori-negative patients (1.92 ± 0.68 × 10(9)/L vs. 1.42 ± 0.67 × 10(9)/L; p = 0.010). H. pylori eradication was successful in 6/11 patients (54.5 %) and the platelet count increased in 4/11 H. pylori-positive patients (36.4 %) who received eradication therapy. On the other hand, eradication therapy was also administered to 15 patients without H. pylori infection, and responses were obtained in some H. pylori-negative patients receiving eradication therapy (9/15). Furthermore, lymphocyte counts were significantly higher in patients who achieved a complete response receiving H. pylori eradication therapy than in patients who did not achieve a complete response (2.4 ± 0.59 × 10(9)/L vs. 1.37 ± 0.60 × 10(9)/L, p = 0.0023). The response of ITP patients to the initial treatment may be predicted by measuring the lymphocyte count at diagnosis. Further studies that analyze lymphocyte subsets and the cytokine network are needed to elucidate the underlying mechanisms.

Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study.

AIM:Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy.MATERIALS AND METHODS:Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy.RESULTS:There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05).CONCLUSIONS:SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy.

Long-Term Complications after Splenectomy in Adult Chronic Immune Thrombocytopenia with a Minimum Follow up of 10 Years. First Results from a Single-Center Case-Control Study in 140 Patients with Primary ITP

Introduction:Splenectomy was historically regarded as the gold standard for treatment in chronic adult immune thrombocytopenic purpura (ITP). However, the recent emergence of new drugs has deeply modified ITP management and splenectomy is no longer viewed as an unavoidable step in adult chronic ITP in many countries. The estimation of the risk over benefit of this potential curative treatment remains challenging both for patients and physicians. A retrospective Italian study focused on long-term outcome of patients splenectomized for ITP gave reassuring data concerning safety. A recent study from a large cohort of American veterans showed an increased risk of death due to septicemia, pulmonary embolism, coronary artery disease and cancer more than 10 years after splenectomy. We reported here the results of the first single center case-control study evaluating the long-term incidence of splenectomy complications with a minimum follow-up of 10 years.Methods:We retrospectively selected in a clinical computer database all primary ITP patients splenectomized more than 10 years ago in our unit. We matched 1 by 1 to non-splenectomized ITP patients based on date and age at ITP diagnosis and sex criteria. Clinical data were then completed from medical charts. All patients were interviewed by phone and a standardized questionnaire was used. Medical records from general practitioner or from Medical care center have been systematically obtained if necessary, especially for deceased patients. Comparison between groups were made using Fisher’s test for qualitative variables, Kaplan-Meier method to estimate incidence and Rank test for comparison of cumulative incidence, with p<0.05 defining significance.Results:Seventy splenectomized ITP patients were included (19men/51women) with a median age at ITP diagnosis of 37 years (range: 3-92). Sixty one (87%) initially responded to splenectomy but only 34(48.5%) maintained a sustained response after a median follow-up of 189 months (range:120-528). Matched non-splenectomized ITP patients had a median age at diagnosis of 40 years (range: 3-93) and a median follow-up since ITP diagnosis of 197 months (range: 96-504).Cumulative incidence of thromboembolic events was higher in the splenectomized group (p=0.029) (Figure1). Four (6%) episodes of post-operative portal vein thrombosis were observed, 3 were complicated by portal cavernoma requiring long-term anticoagulation. They tended to present with more thromboembolic events on a long-term (n=7) than non-splenectomized ITP patients (n=3, p=0.113). Two splenectomized (2.8%) and 1 non-splenectomized (1.4%) patients were diagnosed with post-embolic pulmonary arterial hypertension. The incidence of cardiovascular events was significantly higher in splenectomized group (9(13%) versus 2(2.8%), p=0.005) (Figure 2) with 6 transient and/or ischemic strokes in splenectomized patients (none in non-splenectomized).Infectious events were similar in the two groups (splenectomized: 12 (17%) vs 10 (14%)) but infections were more frequent and severe in splenectomized patients. Indeed, 12 splenectomized patients presented 20 infectious events requiring hospitalization, 13 of them were pneumonia (Streptococcus Pneumoniae: n=4, Haemophilus Influenzae: n=1, undocumented: n=9). Five complicated septic-shocks leading to 3 deaths. In non-splenectomized group, 10 patients had 10 infectious events (Pneumonia n=4, Streptococcus Pneumoniae n=1), 7 were hospitalized, none had septic-hock. Incidence of cancer was similar in the 2 groups (splenectomized: 11 (16%), non-splenectomized: 10 (14%).Finally, the mortality rate was not different between two groups (splenectomized: n=14 (20%), non-splenectomized n=9, 13%). Ten (38%) of the 36 non-responders patients deceased, 7 from hemorrhage and/or septic shock. Other splenectomized and non-splenectomized patients died from malignant cancer/hemopathy (n=5), coronary artery disease (n=2),other (n=6).Conclusion:Based on this case control single center study, we observed that long-term splenectomized patients have not only an increase risk of life-threatening infections, but also an increased risk of thromboembolic, and cardiovascular events. A long-term follow-up is therefore recommended in this patient population regardless the status of ITP in order to better prevent and manage such complications. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Autoimmune Hemolysis & Immune Thrombocytopenic Purpura after Cord Blood Transplantation (CBT) May be Life-Threatening & Warrants Early Therapy with Rituximab

▪Introduction: Autoimmune hemolysis (AH) & immune thrombocytopenic purpura (ITP) are recognized complications of CBT. However, the incidence, severity, treatment response, & prognosis of these autoimmune cytopenias are not established.Methods: We evaluated AH/ITP after CBT in a landmark analysis of 152 patients who received double-unit grafts, had sustained donor engraftment, & were disease-free at 100 days post-transplant. This landmark was chosen as no patient has developed AH/ITP prior to day 100. CBT recipients (median 38 years, range 0.9-70) were transplanted for hematologic malignancies with myeloablative (MA) or non-myeloablative (NMA) conditioning and calcineurin-inhibitor (CNI)/mycophenolate mofetil immunosuppression.Results: With a median follow-up of survivors in this cohort of 50.6 months (range 7.6-105.4) post-CBT, 9 patients [median age 42 years (range 2-54), 5 MA & 4 NMA conditioning] have developed autoimmune cytopenias (7 AH, 1 ITP, 1 both). All AH patients were IgG Direct Antiglobulin Test (Coombs) positive and ITP diagnosis was made by standard criteria. The cumulative incidence of AH/ITP is 6% (95%CI:3-11) at 3-years after the day 100 landmark with a median onset of 8.6 months (range 5.8-24.5) post-CBT (Figure). Six patients presented with severe disease (Hb <6 gm/dl &/or plts <20) requiring immediate aggressive supportive care. The lowest counts (Hb 2.6-6.8 & plts 0-4) were observed a median of 1 day (range 0-94) after diagnosis. Six patients had grade II-IV acute GVHD (onset 17-175 days post-CBT, all prior to development of AH/ITP), and all 9 cases developed in the context of immunosuppression taper. No relationship was observed according to age, diagnosis (acute leukemia vs lymphoma), preparative regimen intensity (MA vs NMA), or recipient CMV serostatus. Treatment during the first week included IVIg/corticosteroids/rituximab in 3 patients or a variety of approaches (1 increased CNI dose, 2 IVIg only, 2 rituximab only, 1 corticosteroids/IVIg). Overall, all 9 patients received rituximab starting 2-18 days (4-6 doses) with initial treatment. Early rituximab at <7 days from diagnosis reduced time to complete response (CR, Hb >8 &/or plts >100): median 13 days (7-49 days) in 4 early rituximab patients vs 58 days (19-98 days) in 5 without early rituximab. Moreover, an initial IVIg/corticosteroids/rituximab combination was best (CR 7-13 days). Four patients flared after CR at 28-393 days & all patients achieved CR with further therapy. Three patients underwent splenectomy (2 with initial therapy & 1 with flare). Eight/9 AH/ITP patients are alive & disease-free (one patient died of GVHD in remission from AH). Seven/8 surviving patients are in CR from AH/ITP (median 30 months after AH/ITP diagnosis, range 9-102) & 1 has recurrent AH requiring therapy. Treatment was well tolerated although 4 patients required intermittent IVIg & 4 had transient neutropenia. Conclusions: AH/ITP occurs infrequently after CBT but is associated with sudden onset and may be life-threatening. The onset during immunosuppressant taper suggests the mechanism may be due to transient immune dysregulation at this time-point, and investigation of whether AH/ITP can be predicted from analysis of B-cell immune reconstitution is underway. IVIg/corticosteroid/rituximab combination is appropriate initial therapy in severe disease & our data suggests this is the most effective although the role of IVIg is unclear. Earlier treatment with Rituximab may reduce corticosteroid exposure & avoid early splenectomy. While the optimal treatment regimen is not established, our series suggests rituximab is essential to achieve & maintain CR & has an excellent safety profile. Finally, survival was high in AH/ITP patients with no deaths from this complication although this was likely contingent on aggressive supportive care in these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risk of venous thromboembolism occurrence among adults with selected autoimmune diseases: A study among a U.S. cohort of commercial insurance enrollees

ObjectiveThis study assessed the risk of venous thromboembolism (VTE) among privately insured adults in the U.S. with one or more of the following autoimmune diseases: autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Materials and MethodsUsing the Truven Health MarketScan® Databases, patients 18–64 years of age with a diagnosis of AIHA, ITP, RA, or SLE in 2007 and a sex and age-group matched comparison group of enrollees were followed up through 2010 to identify VTE events. Survival curve and Cox proportional hazards analyses were conducted to assess differences between groups. ResultsAmong patients with AIHA, ITP, RA, or SLE, or >1 of these diseases, the risk of at least one VTE event was 19.74, 7.72, 4.90, 9.89, and 13.35 per 1,000 person-years, respectively; among the comparison group, the risk was 1.91 per 1,000 person-years. The adjusted hazard ratios (aHRs) for VTE among patients with AIHA, ITP, RA, or SLE, or >1 of these diseases (when compared with the comparison group) tended to decline over follow-up time; at 1year, the aHRs were 6.30 (95% confidence interval [CI]: 4.44–8.94), 2.95 (95% CI: 2.18–4.00), 2.13 (95% CI: 1.89–2.40), 4.68 (95% CI: 4.10–5.33), and 5.11 (95% CI: 4.26–6.14), respectively. ConclusionHaving AIHA, ITP, RA, or SLE, or >1 of these diseases was associated with an increased likelihood of a VTE event. More research is necessary to develop better understanding of VTE occurrence among people with autoimmune diseases.

An improved flow cytometric immunobead array to detect autoantibodies in plasma from patients with immune thrombocytopenic purpura

BackgroundAutoantibodies against platelet glycoproteins (GPs) play an important role in immune thrombocytopenic purpura (ITP). This study was to develop an improved flow cytometric immunobead array (FCIA) assay to detect platelet autoantibodies in ITP patient plasma. MethodsPlasma samples were isolated from 71 ITP patients and 136 non-ITP controls and incubated with platelets from normal individuals. After washing, platelets were lysed and the platelet lysates were incubated with polystyrene microbeads coupled with monoclonal antibodies against human GPs IX (SZ1), Ib (SZ2), IIIa (SZ21), IIb (SZ22), and P-selectin (SZ51). Platelet GP–autoantibody complexes were detected by flow cytometry using a FITC-labeled secondary antibody. ResultAutoantibodies against platelet GPIb, GPIIb, GPIIIa, GPIX and P-selectin were detected in plasma from ITP patients, as indicated by high mean fluorescent intensity values when microbeads with antibodies SZ1, SZ2, SZ21, SZ22, and SZ51 were used. In ROC analysis, values of the area under the curve were 0.74, 0.83, 0.80, 0.79 and 0.87, respectively. Compared with the previously reported assays, this new FCIA eliminated the need of isolating platelets from ITP patients without compromising assay sensitivity and accuracy in predicting ITP. ConclusionThis simplified FICA assay may be more suitable for ITP diagnosis in clinical laboratory settings.

Risk of venous thromboembolism among hospitalizations of adults with selected autoimmune diseases

Previous research has suggested autoimmune diseases are risk factors for developing venous thromboembolism (VTE). We assessed whether having diagnoses of selected autoimmune diseases associated with antiphospholipid antibodies--autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE)--were associated with having a VTE diagnosis among US adult hospitalizations. A cross-sectional study was conducted using the 2010 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. VTE and autoimmune diseases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification coded diagnoses information. The percentages of hospitalizations with a VTE diagnosis among all non-maternal adult hospitalizations without any of the four autoimmune diseases of interest and among those with AIHA, ITP, RA, and SLE diagnoses were 2.28, 4.46, 3.35, 2.65 and 2.77%, respectively. The adjusted odds ratios (OR) for having a diagnosis of VTE among non-maternal adult hospitalizations with diagnoses of AIHA, ITP, RA, and SLE were 1.25 [95% confidence interval (CI) 1.05-1.49], 1.20 (95% CI 1.07-1.34), 1.17 (95% CI 1.13-1.21), and 1.23 (95% CI 1.15-1.32), respectively, when compared to those without the corresponding conditions. The adjusted OR for a diagnosis of VTE associated with a diagnosis of any of the four autoimmune diseases was 1.20 (95% CI 1.16-1.24). The presence of a diagnosis of AIHA, ITP, RA, and SLE was associated with an increased likelihood of having a VTE diagnosis among the group of all non-maternal adult hospitalizations.

As a Rare Disease Bernard–Soulier Syndrome in Differential Diagnosis of Immune Thrombocytopenic Purpura: A Case Report

Introduction: Bernard–Soulier syndrome is a rare autosomal recessive disease that causes a deficiency of glycoprotein Ib, the receptor for von Willebrand factor, which is important for clot formation. It is estimated to occur in fewer than 1 per 1 million persons. The differential diagnosis includes von Willebrand disease, immune thrombocytopenic purpura, May–Hegglin anomaly, thrombocytopenia-absent radius syndrome, grey platelet syndrome, and other inherited giant platelet disorders. Case Presentation: A 30-year-old Turkish woman was admitted to the Department of Heamatology for evaluation of thrombocytopenia. Because she had repeated epistaxis during admission, she was assessed to evaluate for haemorrhagic diathesis. She had been diagnosed with immune thrombocytopenic purpura and given steroid therapy at different times. Peripheral blood smear was characterized by neutrophils 75%, lymphocytes 20%, monocytes 5%, giant platelets and platelets forming three to four clusters, a normal red blood cell morphology. A decreased ristocetin-induced platelet aggregation was detected in low and high concentration. On the basis of these findings, Bernard–Soulier syndrome was screened with flow cytometry and genetic mutation. CD41a 86.2%, CD42a 92.9%, CD42b 92.5%, and CD61 87.8% were detected in flow cytometry. Normal platelet GPIb/IX levels by flow cytometry turned down the suspected diagnosis. genetic analysis, we have applied to our patient and her parents. We detected same mutation in patient and her mother. Laboratuar parameters and flow cytometry of mother did not support diagnosis of Bernard–Soulier syndrome. Conclusion: Bernard–Soulier syndrome should be considered before a young patient is diagnosed with immune thrombocytopenia purpura and peripheral blood smear should be examined for giant platelets.

Platelet indices: consideration in thrombocytopenia

Background There is increasing evidence that platelet indices, such as mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR), have a significant role in the discrimination between hyperdestructive thrombocytopenia and hypoproductive thrombocytopenia, and they can be of great help as they are routinely generated by automated cell counters.Objective In this study, we aimed to assess the sensitivity and specificity of these indices and set cutoff values that aid in the diagnosis of thrombocytopenia cause.Materials and methods We recruited 20 individuals as the control group and 80 thrombocytopenic patients, who were divided into two groups: group I ( n = 40) included newly diagnosed immune thrombocytopenic purpura (ITP) patients (hyperdestructive thrombocytopenia), whereas group II ( n = 40) included hypoproductive thrombocytopenia patients. The MPV and platelet distribution width were derived from automated cell counter results. The P-LCR was calculated.Results In ITP (hyperdestructive thrombocytopenia) patients, the MPV and P-LCR were significantly higher; the best cutoff value for MPV was greater than 9.7 fl and for P-LCR was greater than 33.6%, with a diagnostic accuracy of 70.1 and 99.6%, respectively.Conclusion The MPV and P-LCR provide information about the underlying conditions of thrombocytopenia. These indices should be considered in the diagnosis of thrombocytopenia. The P-LCR can be safely relied upon for a positive diagnosis of ITP.

Detection of autoantibodies against platelet glycoproteins in patients with immune thrombocytopenic purpura by flow cytometric immunobead array

BackgroundThe goal of this study is to develop a flow cytometric immunobead array (FCIA) assay to detect platelet autoantibodies commonly present in bleeding patients with immune thrombocytopenic purpura (ITP). MethodsPolystyrene microbeads coated with antibodies against human platelet glycoproteins (GPs) IX (SZ1), Ib (SZ2), IIIa (SZ21), IIb (SZ22), and P-selectin (SZ51) were incubated with platelet lysate from 50 ITP patients and 86 controls. The platelet antigen–autoantibody complexes were detected by flow cytometry using an FITC-labeled antibody. The results were compared with that of a monoclonal antibody immobilization of platelet antigen (MAIPA) assay. ResultsBy FCIA, platelet autoantibodies against GPIb, GPIIb, GPIIIa, GPIX and P-selectin were detected in ITP patients. Mean fluorescent intensity values with antibodies SZ1, SZ2, SZ21, SZ22 and SZ51 were all higher in ITP patients than controls (p values<0.01). In ROC analysis, values of the area under the curve were 0.89, 0.82, 0.93, 0.94 and 0.95, respectively. In ITP diagnosis, the FCIA assay with these five antibodies had better sensitivity and accuracy than the MAIPA assay (96% vs. 44% in sensitivity; 80.9% vs. 64.7% in accuracy, p<0.01). ConclusionFCIA assays with multiple antibodies against platelet GPs may be used to improve the diagnosis of ITP in hospitals.

Adult Primary and Secondary Immune Thrombocytopenic Purpura

This study was conducted to compare the platelet count and the presence of bleeding manifestations at initial diagnosis of immune thrombocytopenic purpura (ITP) between patients with primary and secondary ITP. Medical records for 67 consecutive adult patients with ITP were reviewed retrospectively and the relevant data were abstracted. Thirty-eight (56.7%) patients were diagnosed as having primary ITP and 29 (43.3%) were considered to have secondary ITP. At the time of diagnosis, the median initial platelet count (median: 60 × 10(9)/L) for patients with secondary ITP was significantly (P < .005) higher than that for patients with primary ITP (median: 3.5 × 10(9)/L). Ecchymosis and/or purpura was observed in 4 (13.8%) patients with secondary ITP and in 33 (86.6%) patients with primary ITP (P value <.005). In conclusion, patients with secondary ITP had higher platelet count at diagnosis and were less likely to present with bleeding manifestations than those with primary ITP.

Patterns of Inpatient Care for Acute Immune Thrombocytopenic Purpura in U.S. Children’s Hospitals, 2008–2010

Abstract 341 Background:A state of equipoise exists in the pediatric hematology community regarding the management of acute immune thrombocytopenic purpura (ITP). While studies have established that ITP treatment raises platelet counts, there is no evidence that treatment prevents serious hemorrhage. Recent guidelines from both an international expert panel and the American Society of Hematology recommend that children with no or mild bleeding be managed with observation alone, and hospitalization be reserved for those with clinically significant bleeding. There are no published data regarding current patterns of inpatient care for pediatric ITP, and the impact of guidelines on clinical practice cannot be determined unless a baseline is established. The objective of this study was to better understand current national practice patterns for acute ITP in United States children's hospitals and investigate regional differences in care. Methods:We examined data from the Pediatric Health Information System, a proprietary database containing clinical and financial data from 43 U.S. children’s hospital. Hospitals were divided into regions based on U.S. Census divisions. Data were extracted for all inpatients with ITP (ICD-9 code 287.31) aged 1–18 years discharged in 2008–2010. As our aim was to describe practice patterns for newly diagnosed acute ITP, patients were excluded if they had an ITP-related admission within six months prior to the study period. In patients with multiple ITP admissions during the study period, only the first admission was analyzed. To minimize the number of patients with thrombocytopenia due to other causes (ITP coding errors), we excluded those with other diagnoses associated with thrombocytopenia, such as cancer and lupus. We compared treatment strategies, length of stay, readmissions within 60 days, and total charges by region. Statistical analyses included χ2 tests for categorical outcomes and Kruskal-Wallis tests for ordinal outcomes. Results:Between 2008 and 2010, we identified 2,314 unique patients meeting the study diagnosis of acute ITP (Table). Only 13.1% of patients had an ICD-9 code suggestive of significant bleeding, with epistaxis the most commonly reported symptom. Even in our hospitalized population, <1% of patients had a diagnosis code of intracranial hemorrhage. We identified significant variation (p<0.05) by geographic region in all examined parameters (treatment strategies, length of stay, hospital charges, and likelihood of readmission). In all geographic regions, IVIG was the most utilized treatment strategy. The use of IVIG as a solitary therapy ranged from 66.2% of patients in Pacific states to 85.0% of patients in the West North Central region (MN, MO, KS). Mean length of stay ranged from 1.0–2.0 days among regions, with mean total charges per admission ranging from $12,460 in the New England/Mid-Atlantic region to $21,623 in the West South Central region (AR, LA, TX). Pharmacy costs accounted for 50% of charges. Rates of readmission within 60 days of initial ITP admission ranged from 5.5%-14.4% of patients. Conclusions:This analysis of the Pediatric Health Information System identified geographic variability in the use of ITP therapies and costs of care for children hospitalized with acute ITP in U.S. children's hospitals. While our data source did not allow us to determine platelet count or indication for hospitalization, our results suggest that a large number of children admitted with ITP in recent years did not have clinically significant bleeding, and potentially could have been managed with outpatient observation. Future studies will be able to identify if the number of ITP admissions, costs of care, and geographic variability in care decrease with the dissemination and implementation of recently published clinical guidelines.TableCharacteristics of 2314 pediatric inpatients with acute ITP, Pediatric Health Information System, 2008–2010(%)Males52.4Age1–3 years35.84–12 years42.113–18 years22.1ICD-9 bleeding codesEpistaxis7.9Menorrhagia2.3Gastrointestinal hemorrhage2.3Intracranial hemorrhage0.6Medication useIVIG72.2Corticosteroids alone7.8Anti-D4.8IVIG and Anti-D5.3No ITP treatment identified9.4Length of stay (days) − median, range2.0 days, 1–14Readmissions within 60 days10.1 Disclosures:No relevant conflicts of interest to declare.

Autoantibodies Directed Against Moesin C471-577/N1-297 Are Novel and Specific Biomarkers of Immune Thrombocytopenic Purpura (ITP),

Abstract 3301Moesin is a member of the protein 4.1 superfamily and shares structure homology with ezrin and radixin. The phosphorylation of moesin increases the aggregation of Fas, activation of capases, and triggers the apoptotic pathways through the Rho-ROCK pathway. The moesin protein is highly expressed in human platelets and phosphorylation of threonine558 is associated with the activation of platelets. Autoantibodies against moesin have not been evaluated in patients with ITP. Thus, we designed and expressed three polypeptides of moesin: N1-297 terminal, α 298–470 helix domain and C471-577 terminal for ELISA assays. Serum samples from patients with ITP (n=148), patients with non-immune thrombocytopenia (n=32), and other patients with hematologic diseases (n=102) as well as gender-matched healthy control subjects (n=50) were evaluated. All ITP patients clinically met an eligibility of ITP minimal standardized criteria from an international working group.1 The titers of moesin autoanitbodies were significantly elevated in the sera from patients with ITP compared with healthy subjects (Mean of autoantibodies titers = N1-297 0.515/0.155; α298–470 0.252/0.159; C471-577 0.430/0.144, P < 0.01). The levels of moesin autoantibodies against N1-297 and C471-577 in ITP patients were also markedly higher than in patients with non-immune thrombocytopenia (Mean of autoantibodies titers = N-1-297 0.515/0.168; C471-577 0.430/0.103, P < 0.05). However, the titer of autoantibodies against moesin ? 298–470 helix domains was similar in ITP, non-immune thrombocytopenia and in patients with other hematologic diseases. When an autoantibody cut-off value of ±2D in normal control subjects (n=50) was assigned, the serum levels of moesin autoantibodies in ITP patients were found to be elevated in 70% (103/148) positive for N-1-297, 44% (65/148) positive for C471-577 and only 6.1% (9/148) positive for α 298–470. Moreover, patients with non-immune thrombocytopenia (n=9), anaphylactic purpura (n=11) and myelodysplasticsyndrome, MDS (n=12) were all negative for moesin autoantibodies. In other groups of patients with hematologic diseases, multiple myeloma (n=15), pure red cell aplasia (n=2), and autoimmune hemolytic anemia (n=18), only autoimmune hemolytic anemia demonstrated 4.5% (3/18) positive for N-1-297 and all were negative for C471-577. Notably, severe ITP patients with iron deficiency anemia had high serum moesin autoantibodies against N-1-297 and C471-577. We also found 15.6% (6/38) positive moesin autoantibodies against C471-577 in ITP patients with systemic lupus erythematosus (SLE). To validate the ELISA results, we examined the specificity of moesin autoantibodies in ITP by Western blot analysis. Three polypeptides of moesin were run on SDS-PAGE and transferred onto nitrocellulose membrane. The immunoblotting showed autoantibodies against ITP that specifically recognized the moesin C471-577 or N1-297 polypeptide. In conclusion, this is the first study to show the elevation of serum moesin autoantibodies in patients with ITP. We propose that moesin autoantibodies specific for C471-577/N1-297 may be specific serum biomarkers for clinical diagnosis and differentiation of ITP from non-immune thrombocytopenia and other hematologic diseases. Disclosures:No relevant conflicts of interest to declare.

Catastrophic Antiphospholipid Syndrome in a Patient with Immune Thrombocytopenic Purpura

A 47-year old Caucasian male with 7-year history of Immune Thrombocytopenic Purpura (ITP) presented with acute onset pain and purplish-blue discoloration of the left fifth toe and pleuritic chest pain. At the time of ITP diagnosis, he was positive for lupus anticoagulant (LA) and high titer of IgG anticardiolipin antibodies (aCL). However, his platelet count had previously remained stable at approximately 40,000/μL and he never required treatment. His examination was normal except for dusky cyanosis and coolness of the left fifth toe associated with extreme tenderness. Abnormal laboratory studies on admission included leukocytosis (11.610/μL), thrombocytopenia (76,000 /μL) and elevated D-dimer (770 ng/mL FEU). Cardiac enzymes, EKG and Chest X-ray were normal. A lower extremity arterial study done prior to admission was normal.

Abstract 1885: Malignancies associated with immune thrombocytopenic purpura

Abstract Background: Cancer and Immune thrombocytopenic purpura (ITP) are two common disorders. However, the relationship between these two diseases has rarely been reported in the literature. The purpose of this retrospective study was to determine the association between cancer and ITP. Methods: We retrospectively reviewed the charts of 307 patients diagnosed with ITP in our institution between 2005 and 2009. The diagnosis of ITP was defined by a platelet count less than 140.109/l with normal or increased number of megakaryocytes on bone marrow aspirate, after exclusion of thrombocytopenia-induced medications or disorders, and absence of splenomegaly. Results: 32 patients (10.4 percent) were found to have cancer. Of these 32 patients, breast cancer accounted for 28.1 percent, prostate cancer for 18.8 percent, skin cancer for 15.6 percent, gastrointestinal cancer and multiple cancer history for 12.5 percent each, bladder cancer and lymphoma for 6.25 percent each. 12 patients (37.5 percent) had ITP before cancer diagnosis, and 16 patients (50 percent) after cancer diagnosis. Both diseases were concomitant in 4 patients (12.5 percent). Conclusion: 10.4 percent of patients with ITP have cancer. Breast cancer accounted for most of the cases followed by prostate cancer. Our data suggest an association between cancer and autoimmune platelet destruction, and further investigation is warranted to understand the exact mechanism. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1885. doi:10.1158/1538-7445.AM2011-1885

Thrombotic thrombocytopenic purpura complicating immune thrombocytopenic purpura—A case report

A 60-year-old male was evaluated for episodes of gingival bleed. Past medical history was significant for hypertension currently treated with clonidine and aliskiren and early stage prostate cancer. Social and family histories were noncontributory. Review of systems was negative except for bleeding. Physical examination was unremarkable. Platelet count was 8 × 109/l and peripheral smear demonstrated thrombocytopenia with few large platelets. Immune Thrombocytopenic Purpura (ITP) was diagnosed, and the patient was treated with prednisone 40 mg/day with significant improvement in his platelet count. Prednisone was then tapered to 5 mg/day. Six months later, the patient developed gingival bleed, chest pain, shortness of breath, and hematuria. Physical examination revealed elevated blood pressure (200/104 mm of Hg), gingival bleeding, and a hematoma of the tongue. Laboratory tests showed platelet count 6 × 109/l, Lactate Dehydrogenase (LDH) 1348 u/l, Antinuclear Antibody (ANA) titers 1:160, and total bilirubin 6 mg/dl. Coagulation profile, hepatitis panel, Thyroid-stimulating hormone (TSH), Human immunodeficiency virus (HIV), Rh factor, and direct antiglobulin test were negative. The diagnosis of ITP, myocardial infarction, and uncontrolled hypertension was made. Prednisone was increased to 60 mg/day, and blood pressure control was optimized. On admission Day 2, the patient developed altered mental status and fever. Computerized Axial Tomography (CAT) scan of head revealed intracranial bleed. His hemoglobin level fell by 2 g/dl and serum creatinine increased. Peripheral smear confirmed the diagnosis of Thrombotic Thrombocytopenic Purpura (TTP). Plasmapheresis was initiated, mental status returned to baseline, and renal function remained stable. ADAMTS -13 (Is a metalloproteinase also known as von Willebrand factor-cleaving Protease) activity obtained before plasmapheresis was 12%, and von Willebrand factor cleaving inhibitor level was 1.4 (normal less than 0.4). Plasmapheresis was continued for 12 exchanges with modest recovery of platelet count from. The patient remained anemic, LDH levels remained high, and 2+ schistocytes persisted on peripheral blood smear. Therapy with rituximab (4 weekly doses of 375 mg/m2), methylprednisone (1 mg/kg/day) and intravenous immunoglobulin G was initiated. After the fourth course of this regimen, the platelet count was 107 × 109/L, LDH levels decreased, the hematocrit remained stable, and peripheral smear showed no fragmented red blood cells. The patient was successfully tapered off prednisone and has remained well. TTP and ITP existing in the same patient are uncommon. Seventeen cases have been reported in the literature with both conditions occurring at different times or concurrently (only one case). Baron et al. [1] reviewed 11 cases of TTP, six of which had an underlying autoimmune disorder. Baron suggested that these six cases represented a distinct clinical syndrome, “mixed immune thrombocytopenia,” due to disturbed immune regulation. Our patient initially presented with isolated thrombocytopenia and positive ANA titers suggestive an immune-mediated disease that responded transiently to steroids. On readmission, he was diagnosed with TTP and started on appropriate therapy with good clinical outcome. In conclusion, emphasis should be placed on a thorough re-evaluation of each recurrence of thrombocytopenia. Overlapping of these two distinct clinical entities may be misleading and can delay appropriate treatment. As evidenced by existing literature, the patient who presents with an initial episode of either ITP or TTP, may subsequently present with either of these syndromes at relapse. Avani Changela*, Kuppuswamy Jagarlamudi , Gina Villani , Meena Alhuwalia , Ashraf Elnawawi , * The Brooklyn Hospital Center, Internal Medicine, Brooklyn, New York 11201, The Brooklyn Hospital Center, Hematology and Oncology, Brooklyn, New York 11201, The Brooklyn Hospital Center, pathology, Brooklyn, New York 11201.