Francesco Rodeghiero

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..The aim of this study was the validation of the criteria defining a significant mucocutaneous-bleeding history in type 1 von Willebrand disease (VWD)...

..It seems however that a new paradigm in the treatment of ITP has been established where the focus is not on reducing platelet consumption but on increasing platelet production...

..However, a splenectomy-sparing approach is also emerging for ITP, and recent guidelines recommend that this procedure is deferred until ≥ 12 months from ITP diagnosis, to allow sufficient time for possible remission...

..Finally, Dr James will review the development of quantitative analysis in children, a particularly important and difficult application, but one that needs to be tackled urgently...

..The most needed areas concern VWD and platelet function disorders, which suffer from inadequate diagnostic standardization, hampering widespread diagnostic capability in both Western and non-Western countries...

..Ifosfamide-based regimens are also being evaluated in the treatment of newly diagnosed patients in sequential, response-based protocols, using many non-cross-resistant drugs...

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..On the basis of these results and through a series of illustrative examples, the clinician will be able to select the best approach for the optimal management of VWD, according to the patient's characteristics and clinical circumstances...

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..Innovative approaches, combining into a single probability phenotypic and genetic data, could possibly estimate better the bleeding risk in specific disorders...

..However, quantitative analysis of the importance of VWF antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo) levels in the diagnosis is lacking...

..The actuarial probability of thrombosis was significantly influenced by leukocytosis (P = .017) and not by platelet count, indicating that platelet number does not seem of prime relevance in the definition of ELN response...

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..The strong synergistic effect of bendamustine and cytarabine on MCL cells provides a rationale for developing schedules combining these agents in the treatment of MCL...

..9% after the first ASCT but no deaths occurred after the second.Our experience suggests that elective up-front single ASCT followed by second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients...

..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...

..These data challenge the theory that elevated platelet count increases thrombosis risk in ET and suggest prospective clinical trials to support this hypothesis...

..In conclusion, similar to patients with type 1 VWD, also in patients with increased VWF clearance desmopressin maintains a major therapeutic role...

..A high proportion of PV and ET surgeries was complicated by vascular occlusion (7.7%) or by a major hemorrhage (7.3%). Prospective investigations analyzing the optimal prophylaxis in these patients are suggested...

..4%) were carriers of the G20210A prothrombin allele. APC resistance not due to FV Leiden is a frequent and consistent phenotype in the general population, with a possibly strong genetic influence...

..The presence of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD...

..CONCLUSIONS: Quantitative analysis of bleeding symptoms is potentially useful for a more accurate diagnosis of type 1 VWD and to develop guidelines for its optimal treatment...

..01). Bendamustine and ara-c are highly synergistic on T- and B-cell lymphoma cells and cell lines, similar to MCL, overcoming resistance to the single agents...

..In the light of our observations, when CIK and UC-MSC will be used in clinical trials, timing and sequencing of their infusion should be considered...

..We analyzed the effect of four different medium supplements on the expansion and differentiation of adipose tissue-derived MSC (ADSC) in order to avoid the use of xenogeneic serum...

..Therefore, BS represent a promising clinical tool for the analysis of bleeding in VWD, although further validation is warranted before an extensive use in clinical practice could be purported...

..5 mg/dl. A persistent increase of plasma fibrinogen is associated with an increased risk of early atherosclerosis...

..Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases...

..Our model-based hypothesis provides a useful approach for the investigation of the phenotype-genotype relationship in myeloproliferative disorders involving JAK2...

..With this approach, vascular complications were no higher than in other published series, and secondary leukemia/myelodysplasia or cancer was not observed during a follow-up of 14 years...

..They can be isolated from several tissues, but it is always necessary to expand them for clinical practice...

..Patients with CLL and IT had poorer survival than other patients with CLL (5-year overall survival 64% vs 82%, P < .001), and this effect was independent from common clinical prognostic variables...

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..Further studies are urgently required to better define the causal association of these new agents with hemostatic complications and to establish the best prophylactic strategy...

..No additional rearrangements or mutations in the rearranged gene were found during follow-up. An identical clonal IGH gene rearrangement may precede CLL diagnosis by several years...

..However, the risks for developing polycythemia vera, essential thrombocythemia, or associated vascular complications in persons with erythrocytosis or thrombocytosis were low...

..66, 064, and 0.59, respectively). We confirm the clinical utility of the HCT-CI score that could also identify patients at low NRM risk possibly benefiting from an HSCT-based treatment strategy...

..0 (false-positive rate less than one-half). Validation of this approach and of its clinical utility is, however, required by analysis in other cohorts of well-characterized type 1 VWD patients...

..These mutations are truly recessive and cause bleeding only in the compound heterozygous or homozygous state...

..To assess biologic features related to the development of immune thrombocytopenia (ITP) in patients with chronic lymphocytic leukemia (CLL)...

..So far, only few preliminary data are available on a strategy to prevent hemorrhage and thrombotic event...

..In addition, careful reporting of haemostatic complications during treatment with new anti-angiogenic drugs is warranted...

..Pregnancy in von Willebrand's disease may carry a significant risk of bleeding. Information on changes in factor VIII and von Willebrand factor and pregnancy outcome in relation to von Willebrand factor gene mutations are very scanty...

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..We investigated CD56 expression in a cohort of AML patients in order to assess its frequency and prognostic relevance...

..It also identified perceived shortcomings of existing therapies and the need to establish an evidence base for newer interventions that could potentially make lasting response to treatment with fewer adverse effects an achievable goal...

..01-1.30). In conclusion, in subjects with G20210A mutation APC resistance is significantly increased, correlates with plasma prothrombin level and the carriers with the lowest APC resistance values have an increased risk of VTE...

..These data confirm that genotypic analysis is mandatory in patients with phenotypic severe APC resistance before these patients are definitely classified as homozygotes for FV Leiden and that further genotypic analysis is advisable...

..Thrombotic events in patients with inherited severe hypofibrinogenemia are rather frequent, may be severe and not associated with the use of replacement therapy...

..We report our experience with 12 families with clearly recessive inheritance, but definitely measurable factor VIII and VWF, which is not typical for severe type 3 VWD...

..Recent evidence suggests that liver and spleen macrophages are responsible for VWF clearance through uptake and endocellular degradation, but it is still not known why some VWF mutants are more prone to increased clearance...

..The relationship of the biologic response to desmopressin with the F8 mutation and physiological characteristics has been poorly investigated in patients with mild hemophilia A...

..01). Pseudohomozygosity for APC resistance carries a significantly higher risk for venous thromboembolism in comparison to normal subjects, but probably not in comparison to heterozygous FV Leiden carriers...

..Further research should clarify whether in families with more severe clinical and laboratory phenotype a clear association with markers of VWF is found...

..Both mutations were identified in severe HA. F8 mRNA analysis is a useful tool for the characterization of the mechanisms by which splice site mutations affect the phenotype, while in silico analysis may not be always reliable...

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..The patients responded well to desmopressin infusion. The C1130F mutation might have a dominant negative effect on the secretion of the normal protein that desmopressin would appear to overcome...

..The R854Q mutation is the most frequent cause of this phenotype...

..7-5.41; P = 0.1). In conclusion, the presence of the prothrombin mutation seems to increase the risk of VT carriers of protein S deficiency, although additional families are required to fully estimate the magnitude of risk...

..Accurate measurement of von Willebrand factor (VWF) is a critical requirement for the diagnosis of von Willebrand disease (VWD)...

..Female gender was significantly associated with a poorer likelihood to respond (P = 0.0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to first-line IS treatment...

..In conclusion, the mutation C2362F is frequently observed in compound heterozygosity with null alleles in patients with recessive VWD in the Veneto region and cause bleeding only in the compound heterozygous or homozygous state...

..These results further emphasize the extreme heterogeneity of the molecular basis of haemophilia A. The low prevalence of intron 22 inversion in Albanian patients with severe haemophilia A should be addressed by further studies...

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..Structural analysis shows that Pro186Leu mutation leads to the replacement of the rigid proline pyrrolidine ring by the larger and more flexible leucine side chain and Ser708Asn may probably disrupt the hydrogen bond with Ala291...

..No data on FVIII/VWF changes after desmopressin and during pregnancy in patients with phenotypic VWD Vicenza has been reported...

..While VWD mutations acting at the protein level have been deeply investigated, fewer data are available on genetic defects affecting VWF mRNA...

..Furthermore, the sensitivity reached is up to 1 log higher than that of the conventional approach with nested-PCR, even though two steps of specificity are maintained...

..The study revealed confounding terminology and an unacceptable heterogeneity for clinical definitions relevant to management decisions and outcomes reporting...

..FV Leiden mutation is a risk factor for VTE before and at time of diagnosis and for VTE recurrences. Screening for FV Leiden may be considered to identify PV and ET patients at higher risk of recurrences...

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..In conclusion, the proposed method is sufficiently simple, rapid, sensible, specific and cost effective for the evaluation of mixed chimerism after BM or PBSC transplant in a clinical setting...

..We present a practical approach to diagnosis, based on scientific evidence and direct experience. The implications of the diagnosis of von Willebrand disease for the patient's quality of life are also considered...

..In 30% of VTE cases, at least two easily recognizable risk factors are present. Clinical assessment of risk factors remains the mainstay of VTE prevention...

..A better understanding of the responsible mechanisms leading to ITP in each disease may allow for targeted treatment decisions, avoiding unwarranted immunosuppression and bleeding complications...

..In spite of 12 HSCTs, there was no long-term survivor. 'ABC' salvage proved feasible and comparable to reported rescue chemotherapic regimens, but the achievement of cure in refractory/relapsing ALL remains an outstanding clinical task...

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..CONCLUSIONS: Age-specific reference limits provide better estimate of vascular risk in the population and correlation with established risk factors...

..Diffuse large B-cell lymphoma (DLBCL) has been correlated to hepatitis C virus (HCV) infection in few series, but characteristics and outcome of these patients remain undefined...

..These concentrates are clinically effective and safe, although they do not always correct the BT...

..The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype...

..These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation...

..About one third of the type 1 VWD cases recruited could be reconsidered as type 2. The remaining group could be considered "true" type 1 VWD, although mutations were found in only 55%...

..A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial...

..Efforts are needed to develop national registries and make at least basic services for diagnosis and treatment widely available...

..Statements are graded according to the strength of the supporting evidence and uncertainty is explicitly declared...

..018). Double heterozygosity for HR2 and a factor V defect, including factor V deficiency, increased the thrombotic risk afforded by HR2...

..Prior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal strategy for prevention of recurrence...

..Considering the lack of a phenotype and the costly screening procedure, we recommend that thrombomodulin defects be sought only for research purposes...