Clinical definitions and terminology vary greatly in clinical studies on idiopathic thrombocytopenic purpura (ITP). An objective assessment of this heterogeneity may be of interest, providing a basis for standardizing ITP terminology. A systematic review of the recent literature on ITP in adults was carried out. The following items were extracted from the articles for comparison: platelet count cut-off values to decide treatment and type of response; timing for evaluating the response to treatment; evaluation of bleeding symptoms; criteria to define initial, chronic and refractory forms. A total of 79 papers, among those published or referenced from 2000 to 2006, were considered eligible. No consensus among the different authors was found on several issues, including:platelet count for definition of ITP; grading of severity; definition of chronic ITP; platelet threshold to start treatment; platelet count to define response to treatment and timing for evaluating the response to therapy. There was only major consensus for the length of disease duration required to diagnose chronic ITP, the criteria for splenectomy and the definition of refractory ITP. Confusing terminology and an unacceptable heterogeneity of clinical definitions used for management decisions and to describe outcomes were evident in recent ITP literature. This makes it very difficult to compare different studies and to share data and clinical experiences. A standardization of terminology and definitions used in ITP is urgently needed.Key words:idiopathic thrombocytopenic purpura, ITP, systematic review, diagnosis, therapy, terminology.Citation: Ruggeri M, Fortuna S, Rodeghiero F. Heterogeneity of terminology and clinical definitions in adult idiopathic thrombocytopenic purpura: a critical appraisal from a systematic review of the literature. Haematologica. 2008 Jan; 93:(1) 98-103.

ABSTRACTexpressed in early stages of CLL than in advanced CLL 17 and that its expression is lower in patients with high-risk CLL. 16

The oxygen sensing pathway modulates erythropoietin expression. In normal cells, intracellular oxygen tensions are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins. PHD2 isozyme has a key role in tagging hypoxia-inducible factor (HIF)-α subunits for polyubiquitination and proteasomal degradation. Erythrocytosis-associated PHD2 mutations reduce hydroxylation of HIF-α. The investigation of 67 patients with isolated erythrocytosis, either sporadic or familial, allowed the identification of three novel mutations in the catalytic domain of the PHD2 protein. All new mutations are germ-line, heterozygous and missense, and code for a predicted full length mutant PHD2 protein. Identification of the disease-causing genes will be of critical importance for a better classification of familial and acquired erythrocytosis, offering additional insight into the erythropoietin regulating oxygen sensing pathway. Sequencing analysisThe PCR products were purified. Sequencing reactions were carried out using Big Dye ® sequencing kit (Applied Biosystems). Direct sequencing was performed in both directions for all samples on an automated sequencer ABI Prism ® 3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). Electropherograms were compared with the PHD2 (NCBI GenBank accession n. NM_022051), VHL (NCBI GenBank accession n. NM_000551) and HIF2A (NCBI GenBank accession n. NC_000002) wild-type sequences. Mutations were named in accordance with the standard international nomenclature guidelines recommended by the Human Genome Variation Society (HGVS, http://www.hgvs.org/mutnomen/). Characterization of the new PHD2 mutationsTo confirm the identity of the newly identified mutations, allele-specific PCR (AS-PCR) was performed for each allelic variant ( Figure 1B). Reaction mixtures were run on a GeneAmp ® PCR System 2700 at standard conditions and PCR fragments were analyzed by agarose gel. Primer sequences and PCR fragment lengths are listed in Online Supplementary Table S1.The germ-line origin of these new genetic lesions was confirmed by their identification on DNA obtained from epithelial cells (buccal cotton-swab sampling) of the probands.DNA samples from peripheral blood mononuclear cells from 100 normal controls with the same ethnic background were also screened for the novel mutations, by means of AS-PCR. Control DNA was obtained from the DNA samples stored in a biobank of healthy subjects at San Bortolo Hospital. Informed consent from the donors to the biobank had already been obtained for research purposes. Results and DiscussionIn this study, three different new germ-line heterozygous mutations of PHD2 were found in a cohort of 67 patients with IE, including 14 and 5 cases subsequently reclassified as PV on the basis of JAK2 V617F or exon 12 mutations. None of the PHD2 mutated subjects was JAK2 V617F positive while one co-harbored JAK2-exon 12 mutation. Main clinical and laboratory features of mutated patients are listed in Table 1.In Patient 1, molecular studies revealed a C>G missense mutati...

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We have carried out a literature review on diagnosis and treatment of idiopathic thrombocytopenic purpura (ITP) in adults, based on the articles published during the years 2000-2005, aimed at assessing the variability in the terminology and clinical definitions. A total of 85 articles were considered eligible. In particular, the platelet level for initiating treatment, the definition of response to treatment in terms of platelet count and timing, the evaluation of bleeding symptoms, the criteria to define chronic and refractory forms were compared in the different articles. The study revealed confounding terminology and an unacceptable heterogeneity for clinical definitions relevant to management decisions and outcomes reporting.