Hepatocellular carcinoma (HCC) is an increasingly frequent cause of mortality in hemophiliacs with chronic viral hepatitis. Early diagnosis of the tumor at an initial stage is known to improve the outcome of HCC treatment. Because all HCC cases detected in a previous study based upon annual ultrasound (US) surveillance of hemophiliacs with elevated alanine aminotransferase levels were multinodular, this study was designed to evaluate if a more intense surveillance with US and alphafetoprotein (AFP) serum levels of all the patients infected with the hepatitis C virus (HCV) improved the identification of single nodule tumors. A multicenter cohort of 559 HCV-infected hemophiliacs was divided into 2 arms, one followed up at 6-month intervals and one at 12-month intervals depending on the choice and available facilities of each treatment center. During a 6-year surveillance period, HCC was diagnosed in 5 (2.4%) of 210 patients in the 6-month group and in 3 (0.9%) of 349 patients in the 12-month group. The overall incidence rate of HCC was 239 per 100 000 per year (397 per 100 000 per year in the 6-month group and 143 per 100 000 per year in the 12-month group; differences not statistically significant). By multivariate analysis, HCC risk was increased 12.9-fold with alcohol intake more than 80 g/d and 15.2-fold with AFP levels higher than 11 ng/mL. Liver-related death occurred in 8 cases (1.4%), including 3 with HCC. Still alive and tumor free after 24 to 34 months from diagnosis are 3 patients with multinodular tumors treated with repeat chemoembolization followed by orthotopic liver transplantation. In conclusion, 6-month surveillance with US did not increase the chances of detection of single nodule tumors, but it is reasonable to assume that successful treatment of multinodular tumors based upon debulking with chemoembolization and liver transplantation was facilitated by this approach. (Blood. 2003;102:78-82)

Along with haemophilia A and B, von Willebrand disease (VWD) and rare bleeding disorders (RBDs) cover all inherited bleeding disorders of coagulation. Bleeding tendency, which can range from extremely severe to mild, is the common symptom. VWD, due to a deficiency and/or abnormality of von Willebrand factor (VWF), represents the most frequent bleeding disorder, mostly inherited as an autosomal dominant trait. The diagnosis may be difficult, based on a bleeding history and different diagnostic assays, which evaluate the pleiotropic functions of VWF. Different treatment options are available for optimal management of bleeding and their prevention, and long-term outcomes are generally good. RBDs are autosomal recessive disorders caused by a deficiency of any other clotting factor, apart from factor XII, and cover roughly 5% of all bleeding disorders. The prevalence of the severe forms can range from 1 case in 500,000 up to 1 in 2–3 million, according to the defect. Diagnosis is based on bleeding history, coagulation screening tests and specific factor assays. A crucial problem in RBDs diagnosis is represented by the non-linear relationship between clinical bleeding severity and residual clotting levels; genetic diagnosis may help in understanding the phenotype. Replacement therapies are differently available for patients with RBDs, allowing the successful treatment of the vast majority of bleeding symptoms.

We have identified a cell population expressing erythroid (TER-119) and megakaryocyte (4A5) markers in the bone marrow of normal mice. This population is present at high frequency in the marrows and in the spleens involved in the erythroid expansion that occurs in mice recovering from phenylhydrazine (PHZ)-induced hemolytic anemia. TER-119⁺/4A5⁺ cells were isolated from the spleen of PHZ-treated animals and were found to be blast-like benzidine-negative cells that generate erythroid and megakaryocytic cells within 24-48 hours of culture in the presence of erythropoietin (EPO) or thrombopoietin (TPO). TER-119⁺/4A5⁺ cells represent a late bipotent erythroid and megakaryocytic cell precursors that may exert an important role in the recovery from PHZ-induced anemia.

Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10–50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (P<0.001 and P=0.03, respectively), while that with less than 10 hemarthrosis was higher in hemophilia B (P<0.0001). World Federation of Hemophilia (36.6 vs. 20.2; P<0.0001) and ultrasound (10.9 vs. 4.3; P<0.0001) score mean values were significantly higher in hemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (P<0.0001 and P=0.006, respectively). Osteoprotegerin expression was markedly reduced in synovial tissue from hemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A.

Background Gaucher disease is the first lysosomal storage disease for which specific therapy became available. Over 4800 patients have been treated with enzyme replacement therapy. Analysis of Gaucher disease registry data has outlined the clinical heterogeneity of the disease and the different responses to treatment from patient to patient, and for different organs. This variability in clinical response justifies the development of a severity score index to assess disease activity, stage and prognosis, and to quantify the effects of treatment. Design and Methods The new scoring system proposed here, the “Gaucher Disease Severity Score Index – Type I” (GauSSI-I), is based on the clinical experience of the authors and an extensive literature review, including data from the International Gaucher Registry. In particular for skeletal disease, all the available scoring systems have been reviewed and compared in order to provide a skeletal scoring system that allows use of any of the different methods on an equivalent basis. Results The new scoring system, GauSSI-I, was developed. Six specific domains, in which different items were scored according to their impact on morbidity, were characterized. GauSSI-I was evaluated in 53 type I Gaucher patients treated with imiglucerase, and it was compared to the Zimran score, the only severity index score so far available. Conclusions The GauSSI-I is a reliable method for staging the severity of adult type I Gaucher disease, and it is more sensitive than the Zimran score for monitoring the response to treatment.

Objective. To characterize the clinical manifestations of patients with antiphospholipid antibody syndrome (APS) and pulmonary hemorrhage (PH). Methods. We performed a retrospective, single-center analysis of patients with APS who were followed up from 1980 to 2011. Of these patients, only those who fulfilled the Sydney criteria for APS were included. Patients with APS that manifested with PH were called the PHAPS group. The rest of the patients with APS served as controls. Clinical manifestations were compared between the PHAPS group and controls. Results. Sixty-three patients fulfilled the criteria for APS. Thirteen experienced PH and were included in the PHAPS group. Seventy-five percent of the patients with PHAPS and 22% of the controls had mitral valve disease (p = 0.001). Central nervous system (CNS) involvement (cerebrovascular accident, seizures) was present in 61% and 16% of the patients with PHAPS and controls, respectively (p = 0.001). Skin involvement (livedo reticularis, chronic leg ulcers) was present in 54% and 8% of the patients with PHAPS and controls (p = 0.001). Pregnancy morbidity occurred in 87.5% and 32.5% of the patients with PHAPS and controls (p = 0.005). Ninety-two percent and 83% of the patients with PHAPS had high-titer immunoglobulin γ (IgG) anticardiolipin and β₂-glycoprotein I IgG antibodies compared to 43% and 30% of the controls (p = 0.002, p < 0.001, respectively). Conclusion. Patients with PHAPS were more likely than controls to have mitral valve disease, skin disease, CNS involvement, and pregnancy morbidity as well as high-titer APS. PHAPS seems to be a unique subgroup of all patients with APS.