We retrospectively studied 181 patients with polycythaemia vera (n=67), essential thrombocythaemia (n=67) or primary myelofibrosis (n=47), who presented a first episode of splanchnic vein thrombosis (SVT). Budd–Chiari syndrome (BCS) and portal vein thrombosis were diagnosed in 31 (17.1%) and 109 (60.3%) patients, respectively; isolated thrombosis of the mesenteric or splenic veins was detected in 18 and 23 cases, respectively. After this index event, the patients were followed for 735 patient years (pt-years) and experienced 31 recurrences corresponding to an incidence rate of 4.2 per 100 pt-years. Factors associated with a significantly higher risk of recurrence were BCS (hazard ratio (HR): 3.03), history of previous thrombosis (HR: 3.62), splenomegaly (HR: 2.66) and leukocytosis (HR: 2.8). Vitamin K-antagonists (VKA) were prescribed in 85% of patients and the recurrence rate was 3.9 per 100 pt-years, whereas in the small fraction (15%) not receiving VKA more recurrences (7.2 per 100 pt-years) were reported. Intracranial and extracranial major bleeding was recorded mainly in patients on VKA and the corresponding rate was 2.0 per 100 pt-years. In conclusion, despite anticoagulation treatment, the recurrence rate after SVT in myeloproliferative neoplasms is high and suggests the exploration of new avenues of secondary prophylaxis with new antithrombotic drugs and JAK-2 inhibitors.

below the mean BMD in young adults (20-40 years old) of the same gender. The Z-score denotes how many SDs a person's BMD is above or below the mean BMD in the matched population. The coefficient of variation (CV) for the areal BMD measurements ranged from 0.5 to 3%, depending on application.Peripheral quantitative computerized tomography. The volumetric BMD (g/cm 3 ) of the nondominant distal arm (the radial bone) and distal leg (the tibial bone) was measured by pQCT (XCT-2000, Stratec Medizintechnik, GmbH, Pforzheim, Germany). The pQCT-device was calibrated once a week using a standard phantom and once every 30 day using a cone phantom provided by the manufacturer. A 2-mm-thick single tomographic slice was scanned with a voxel size of 0.50 mm. The cortical volumetric BMD was measured using a scan through the diaphysis at 25% of the bone length in the proximal direction of the distal end of the radial and tibial bones, respectively. Trabecular volumetric BMD was measured using a scan through the metaphysis at 4% of the bone length in the proximal direction of the distal end of the radial and tibial bones, respectively. All pQCT analyses were performed by a single technician using a single pQCT device. The CVs were less than 1% for all pQCT measurements, as previously reported [25].Statistics. Paired two-sided t-tests and Wilcoxon signed rank tests were performed to evaluate differences over time in each group. Unpaired twosided t-tests and Mann-Whitney U were performed to compare CML patients and controls. Fischer's exact test was used to compare the number of individuals with hyperparathyroidism in 2007 and 2011, respectively. A P < 0.05 was considered statistically significant. All data shown are mean values ± standard error of mean (SEM) unless otherwise stated.

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN-CVT) to 87 with MPN and other venous thrombosis (group MPN-VT) and 178 with MPN and no thrombosis (group MPN-NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN-CVT and MPN-VT than in MPN-NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN-VT, MPN-CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow-up period (6.1 vs. 10.3 years, P = 0.019), a higher long-term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN-CVT than in MPN-VT group (8.8% and 4.2% patient-years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05-3.72 and 2.09, 1.09-4.00, respectively).

An increase of angiogenesis has been shown in idiopatic myelofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (median 1208 ng/ml vs 138 ng/ml, P Ͻ 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count Ͻ300 × 10 9 /l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one. Leukemia (2001) 15, 976-980.