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In a recent study we found elevated thrombopoietin (TPO) levels along with a trend toward correlation between serum TPO and some acute phase reactants (APR) in patients with reactive thrombocytosis. In order to further clarify the behaviour of TPO in reactive conditions and to highlight the eventual drawbacks of serum TPO (sTPO) against plasma TPO (pTPO) measurements, serial measurements were made of sTPO, pTPO, interleukin (IL)-6, C-reactive protein (CRP), fibrinogen (FBG), and erythrocyte sedimentation rate (ESR) in 12 patients before and at the 3rd, 7th, 14th, 45th day after hip replacement surgery. Platelet count, sTPO and pTPO were also measured in 30 healthy donors. As expected sTPO were significantly higher than pTPO levels (approximately 30% on average) both in controls (P0.00001) and in patients (P0.00001). Overall a very good correlation (r = 0.975, P0.00001) was found between serum and plasma TPO, whereas no correlation was found between platelet count and the sTPO/pTPO ratio indicating that the difference between sTPO and pTPO is independent from platelet count. So both serum and plasma seem to be suitable samples for TPO measurement if it is taken into account that sTPO are about 30% higher than pTPO. All the parameters we measured in our patients increased during the post-surgery period and returned to the basal value at the 45th day. pTPO levels peaked at the 3rd day, preceding by 11 days the peak in platelet count. A significant correlation was found between pTPO and ESR (P = 0.012), pTPO and FBG (P = 0.044), pTPO and CRP (P = 0.033), and a nearly significant correlation between pTPO and IL-6 (P = 0. 054). These results indicate that, in the course of reactive conditions, an early rise in TPO precedes and probably induces a later increase in platelet count. Moreover, the significant correlations along with the similarity in the chronological variations between TPO and some APRs suggest that TPO behave like an APR.

Despite the fact that several prognostic systems for myelodysplastic syndromes (MDS) have been proposed, few studies have been designed to test their effectiveness in independent patient populations. The aim of this study was to compare the prognostic value of 8 previously described prognostic systems in a series of consecutive MDS patients observed at a single institution over a 10-year period.One hundred and forty-three patients were diagnosed as having myelodysplastic syndrome (MDS) according to the French-American-British (FAB) criteria. They were studied retrospectively in order to assess the prognostic value of the FAB classification and 7 other prognostic systems.On the basis of data at diagnosis, all investigated systems effectively stratified patients into groups with different life expectancies and identified a subset of patients with poor clinical outcome. However, the systems had different outcomes concerning median survival of patients classified as low-risk, ranging from less than 3 years for the Mufti scoring system to more than 8 years for the FAB classification modified according to Rosati et al. Moreover, patient distribution into different risk categories was quite different with the different prognostic systems.When applied to our case series, some of the prognostic systems had a much lower prognostic value than in the patient population from which they derived. This evidence suggests that testing of prognostic systems in independent case series is necessary before using the systems in clinical practice.

A patient with Guillain-Barré syndrome associated with autoimmune hemolytic anemia following post-transfusional acute viral HBsAg- positive hepatitis improved dramatically and subsequently recovered from both diseases after plasmapheresis and steroid therapy. This case supports an autoimmune mechanism of Guillain-Barré syndrome.

Membrane glycoprotein structure regulates the fate in the circulation of mammalian erythrocytes: the mechanism of this phenomenon was observed in rabbit and human red cells by in vivo and in vitro experiments. Glycoprotein remodeling can occur as a reversible desialylation process, produced by different events, or as an irreversible process consisting in a loss of sialoglycopeptides. The effect of these two phenomena on the viability of the red cell in the circulation was the subject of our investigation.

Platelet membranes were isolated by the glycerol lysis technique and incubated in Krebs-Ringer phosphate buffer, to determine their chemical modifications occurring during "in vitro" incubation. The main changes observed at the end of the incubation consist in a significant loss of protein components and in the nearly equimolar decrease of sialic acid and galactosamine. Aminoacid analysis indicate that mainly polar aminoacids are lost. SDS-polyacrylamide gel electrophoresis indicates that high molecular weight proteins disappear after incubation, while no relevant differences in the relative ratios between PAS-stained bands were evident. The reported modifications are quite similar to those described in the membranes of in vivo and in vitro aged red cells.

51Cr rabbit erythrocytes were treated with different amount of neuraminidase and reinjected into the animal. The survival curves after the removal of more than 50% membrane sialic acid show a characteristic behaviour: after a rapid decrease, blood radioactivity increases again reaching a maximum level 50-80 h after reinjection, then tends to decrease with a slope similar to that of control curves. Liver radioactivity determined before the rise of blood radioactivity is evidently higher than the value determined after radioactivity elevation. Similar results were obtained with phenylhydrazine-induced young erythrocytes.

A murine monoclonal antibody against glycoproteins IIb-IIIa of platelet membrane completely abolished platelet aggregation induced by epinephrine, arachidonic acid, and low concentration of collagen and thrombin, but it had only minor inhibitory effects on aggregation induced by ADP, higher amounts of collagen and thrombin, and these agents combined in pairs. The simultaneous studies of aggregation and ATP secretion demonstrated that aggregation plays an essential role in stimulating the platelet-release reaction, except for the thrombin-induced ATP secretion that seems to be largely dependent on fibrinogen binding to platelet surface.

Glycopeptides were extracted by papain digestion from erythrocyte "ghosts" of subjects suffering from hematological disorders involving shortened red cell survival time. Chemical characterization demonstrated significant alterations.

The diagnosis of inherited thrombocytopenias is difficult, for many reasons. First, as they are all rare diseases, they are little known by clinicians, who therefore tend to suspect the most common forms. Second, making a definite diagnosis often requires complex laboratory techniques that are available in only a few centers. Finally, half of the patients have forms that have not yet been described. As a consequence, many patients with inherited thrombocytopenias are misdiagnosed with immune thrombocytopenia, and are at risk of receiving futile treatments. Misdiagnosis is particularly frequent in patients whose low platelet count is discovered in adult life, because, in these cases, even the inherited origin of thrombocytopenia may be missed. Making the correct diagnosis promptly is important, as we recently learned that some forms of inherited thrombocytopenia predispose to other illnesses, such as leukemia or kidney failure, and affected subjects therefore require close surveillance and, if necessary, prompt treatments. Moreover, medical treatment can increase platelet counts in specific disorders, and affected subjects can therefore receive drugs instead of platelet transfusions when selective surgery is required. In this review, we will discuss how to suspect, diagnose and manage inherited thrombocytopenias, with particular attention to the forms that frequently present in adults. Moreover, we describe four recently identified disorders that belong to this group of disorders that are often diagnosed in adults: MYH9-related disease, monoallelic Bernard-Soulier syndrome, ANKRD26-related thrombocytopenia, and familial platelet disorder with predisposition to acute leukemia.

To the editor: Since the discovery that mutations in the 5′ untranslated region (UTR) of ANKRD26 are responsible for an autosomal-dominant form of thrombocytopenia ( ANKRD26 -RT),[1][1] 21 affected families were reported.[2][2] A study analyzing this series of patients suggested that ANKRD26 -RT

Abnormalities of platelet size are one of the distinguishing features of inherited thrombocytopenias (ITs), and evaluation of blood films is recommended as an essential step for differential diagnosis of these disorders. Nevertheless, what we presently know about this subject is derived mainly from anecdotal evidence. To improve knowledge in this field, we evaluated platelet size on blood films obtained from 376 patients with all 19 forms of IT identified so far and found that these conditions differ not only in mean platelet diameter, but also in platelet diameter distribution width and the percentage of platelets with increased or reduced diameters. On the basis of these findings, we propose a new classification of ITs according to platelet size. It distinguishes forms with giant platelets, with large platelets, with normal or slightly increased platelet size, and with normal or slightly decreased platelet size. We also measured platelet diameters in 87 patients with immune thrombocytopenia and identified cutoff values for mean platelet diameter and the percentage of platelets with increased or reduced size that have good diagnostic accuracy in differentiating ITs with giant platelets and with normal or slightly decreased platelet size from immune thrombocytopenia and all other forms of IT. Fil: Noris, Patrizia. University of Pavia; Italia Fil: Biino, Ginevra. Consiglio Nazionale Delle Ricerche. Istituto di Genetica Molecolare; Italia Fil: Pecci, Alessandro. University of Pavia; Italia Fil: Civaschi, Elisa. University of Pavia; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Istituto Di Ricovero e Cura a Carattere Scientifico Burlo Garofolo; Italia Fil: Seri, Marco. Università di Bologna; Italia Fil: Melazzini, Federica. University of Pavia; Italia Fil: Loffreddo, Giuseppe. Pausilipon Hospital; Italia Fil: Russo, Giovana. Università degli Studi di Catania; Italia Fil: Bozzi, Valeria. University of Pavia; Italia Fil: Notarangelo, Lucia Dora. Spedali Civili. Ospedale dei Bambini; Italia Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Kunishima, Shinji. National Hospital Organization Nagoya Medical Center; Japón Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia Fil: Bussel, James. Cornell University; Estados Unidos Fil: de Candia, Erica. Universita Cattolica del Sacro Cuore; Italia Fil: Cagioni, Claudia. University of Pavia; Italia Fil: Ramenghi, Ugo. Università di Torino; Italia Fil: Barozzi, Serena. University of Pavia; Italia Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Balduini, Carlo L.. University of Pavia; Italia

Inherited macrothrombocytopenia (IMTP) is a highly heterogeneous group of inherited disorders characterized by a low platelet count and abnormally platelet size. Even though IMTP-causing mutations have been reported in several genes, only 50% of patients have to date a molecular diagnosis. In March 2013 Kunishima and colleagues identified alpha-actinin 1 (ACTN1) as a new gene responsible for IMTP which accounted for 5,5% of cases in Japanese population. To evaluate the frequency of ACTN1 mutations in the Italian population, we performed a screening in 160 probands in which all the known forms of IMTP were previously excluded. Ten, including 8 novel, different missense have been identified in 11 patients. All except one (p.D666V) segregated with the macrotrombocytopenia within the families. In vivo transfection experiments in Hela cells were performed to demonstrate the pathogenicity of the variants identified. Except for p.D666V, preliminary data indicate that the missense mutations are associated with disorganization of cytoskeleton, as determined different co-localization of mutant and wild type actinin-a with actin. Further studies will be needed to determine how these mutations may lead to the onset of disease.