Diagnosis Of Primary Immune Thrombocytopenia Research Articles

Clinical significance of IPF% or RP% measurement in distinguishing primary immune thrombocytopenia from aplastic thrombocytopenic disorders.

The diagnosis of primary immune thrombocytopenia (ITP) is based on differential diagnosis. Although the measurement of percentages of reticulated platelets (RP%) by flow cytometry is useful as a supportive diagnostic test, this method is nonetheless a time-consuming, laboratory-based assay. To identify alternative assays that are useful in daily practice, we compared three methods in parallel, IPF% measured by XE-2100 [IPF% (XE), Sysmex Corp.], IPF% measured by new XN-1000 [IPF% (XN)], and RP%. We examined 47 patients with primary ITP, 28 patients with aplastic thrombocytopenia (18 aplastic anemia and 10 chemotherapy-induced thrombocytopenia) and 80 healthy controls. In a selected experiment, we examined 16 patients with paroxysmal nocturnal hemoglobinuria (PNH) to examine the effect of hemolysis. As compared with IPF% (XE), IPF% (XN) showed better within-run reproducibility. The sensitivity and specificity for the diagnosis of ITP were 83.0 and 75.0% for IPF% (XE), 85.1 and 89.3% for IPF% (XN), and 93.6 and 89.3% for RP%, respectively. Examination of PNH patients revealed that hemolysis and/or red blood cell fragments interfered with IPF% (XE) values, but not with IFP% (XN) values. Our results suggest that IPF% measured by XN-1000 may be of comparable value with RP% as a supportive diagnostic test for ITP.

Value of vanin-1 assessment in adult patients with primary immune thrombocytopenia

The diagnosis of primary immune thrombocytopenia (ITP) is clinical and cannot be established by any specific laboratory assay. Perhaps the best diagnostic study is assessment of the patient’s response to ITP therapy. Oxidative stress-related pathways were among the most significant chronic ITP-associated pathways. Overexpression of VNN1 gene, an oxidative stress sensor in epithelial cells, was most strongly associated with progression to chronic ITP. To address this issue, we tested the hypothesis that blood vanin-1 protein level could distinguish between chronic responders and non-responders ITP patients as well as between ITP patients and healthy controls. Vanin-1 protein levels were determined in peripheral blood leukocytes of 80 adult subjects (16 newly diagnosed ITP patients, 24 chronic responders ITP patients, 24 chronic non-responders ITP patients and 16 healthy controls) by enzyme-linked immunesorbent assay (ELISA). Blood vanin-1 protein levels were lower in controls (median = 18.39 ng) than in ITP patients (median = 58.78 ng) with a highly significant p value (p < 0.001). Vanin-1 levels were highly significantly elevated in newly diagnosed ITP patients (median = 188.62 ng) in comparison to chronic responders (median = 26.90 ng) and chronic non-responders (median = 73.87 ng). Vanin-1 level at a cut-off value of >20.73 ng was found to be 100% sensitive and 93.7% specific in discriminating between newly diagnosed ITP patients and healthy controls. Vanin-1 level was found to be 100% sensitive and 100% specific in differentiating between responders and non-responders with a cut-off value of ≤34.5 ng. Our results suggest that vanin-1 can distinguish between chronic responders and non-responders ITP patients as well as between newly diagnosed ITP patients and healthy controls. These findings demonstrate that vanin-1 may contribute to the pathogenesis of ITP, indicating that vanin-1 is an important target for further investigation.

Pathophysiology and diagnosis of primary immune thrombocytopenia

Pathophysiology and diagnosis of primary immune thrombocytopenia

Determining a definite diagnosis of primary immune thrombocytopenia by medical record review

The objective of this study is to establish a method to identify patients with primary immune thrombocytopenia (ITP) utilizing administrative data from diverse data sources that would be appropriate for epidemiologic studies of ITP, regardless of patients' age and source of health care. Medical records of the Oklahoma University Medical Center, 1995-2004, were reviewed to document the accuracy of the administrative code ICD-9-CM 287.3 for identifying children and adults with ITP, using novel, explicit levels of evidence to identify patients with a definite diagnosis. The proportion of patients diagnosed by hematologists compared to non-hematologists and the proportion of patients diagnosed as outpatients compared to inpatients were determined. For children, age <16 years, 323 outpatient medical records were reviewed; 225 adult outpatient medical records were reviewed. The positive predictive value for the administrative code for identifying patients with a definite diagnosis of ITP by a hematologist was 0.72 in children and 0.69 in adults. In 98% of children and 92% of adults seen as outpatients, the definite diagnosis of ITP was established by a hematologist. One hundred eighteen child and 141 adult inpatient medical records were reviewed. In 95% of children and 83% of adults, the definite diagnosis of ITP by a hematologist was established as an outpatient. This study confirmed the previously reported positive predictive value for the administrative code for identifying patients with ITP. Additionally, it was determined that analysis of hematologists' outpatient administrative codes identified most children and adults with ITP. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

The Utility of Bone Marrow Examinations for the Diagnosis of Immune Thrombocytopenia.

AbstractAbstract 3691 Background:The utility of bone marrow examinations for the investigation of patients with immune thrombocytopenia (ITP) is a matter of debate. We designed an agreement study to evaluate the inter-rater reliability of bone marrow biopsies and aspirates for the diagnosis of ITP. Methods:Histological slides of bone marrow biopsies from patients with ITP and controls were prepared from stored tissue blocks and corresponding aspirate slides were retrieved for blinded, duplicate, independent pathological review. Patients had a diagnosis of primary ITP, were 18 years of age or older with a platelet count less than 100 ×109/L as measured within 4 weeks before the date of bone marrow biopsy procurement. Patients with splenomegaly, myelodysplastic syndrome, lymphoproliferative disease, HIV, hepatitis B or C, drug-induced thrombocytopenia or previous treatment with hematopoietic growth factors or thrombopoietin receptor agonists were excluded. Control bone marrow samples were selected from patients 18 years of age or older with stage I to III lymphoma or monoclonal gammopathy of undetermined significance who had a normal platelet count within 4 weeks before bone marrow biopsy procurement. Prior treatment with anti-neoplastic agents or hematopoietic growth factors were exclusions. Bone marrow slides from ITP patients and controls were coded and arranged in random order. A standardized pathological assessment form was used to capture bone marrow cellularity (in deciles), diagnosis [‘ITP’ or ‘within normal limits (wnl)‘], megakaryocyte number (increased, decreased or wnl), morphology (abnormal or wnl), distribution (abnormal or wnl) and megakaryocyte assessment on aspirate (abnormal or wnl). The form was piloted by a third independent hematopathologist (n=10 bone marrow examinations) and revised prior to duplicate review. All reviewers were pathologists with at least 5 years experience reading bone marrows. Chance-corrected agreement between reviewers was calculated using kappa (k) and chance-independent agreement was calculated using phi (φ) with 95% confidence intervals (CI). Results:Bone marrow slides were prepared from 30 ITP patients and 53 controls. Agreement on marrow cellularity (to within 20%), which was used to ensure calibration of assessors, was good (k= 0.75, 95% CI. 0.65–0.85). Of 81 evaluable bone marrows, pathologists agreed on the diagnosis for 69 cases (85.2%); overall agreement was fair (φ = 0.52; 95% CI: 0.10–0.78). Of the 30 ITP bone marrows, pathologists correctly agreed on the diagnosis in 2 (6.7%) cases, incorrectly agreed on 20 (66.7%) and disagreed on 8 (26.7%). Of the 51 control bone marrows, pathologists correctly agreed on the diagnosis in 46 (90.2%) cases, incorrectly agreed on 1 (2.0%) and disagreed on 4 (7.8%). Agreement on megakaryocyte number, morphology and distribution was fair. Conclusions:Inter-rater reliability of bone marrow examinations for the diagnosis of ITP was fair. Pathologists often incorrectly agreed that ITP bone marrows were considered to be within normal limits. These data suggest that ITP bone marrows often do not exhibit any distinguishing features. Disclosures:No relevant conflicts of interest to declare.

Pathobiology and Treatment of Hepatitis Virus-Related Thrombocytopenia

Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV) infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy.