Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients

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

Stepwise Optimization of the Procedure for Assessment of Circulating Progenitor Cells in Patients with Myocardial Infarction

The number and functional activity of circulating progenitor cells (CPCs) is altered in diabetic patients. Furthermore, reduced CPC count has been shown to independently predict cardiovascular events. Validation of CPCs as a biomarker for cardiovascular risk stratification requires rigorous methodology. Before a standard operation protocol (SOP) can be designed for such a trial, a variety of technical issues have to be addressed fundamentally, which include the appropriate type of red blood cell lysis buffer, FMO or isotype controls to identify rare cell populations from background noise, optimal antibody dilutions and conditions of sample storage. We herein propose improvements in critical steps of CPC isolation, antigenic characterization and determination of functional competence for final application in a prospective investigation of CPCs as a biomarker of outcome following acute myocardial infarction.In this validation study, we refined the standard operating procedure (SOP) for flow cytometry characterisation and functional analysis of CPCs from the first 18 patients of the Progenitor Cell Response after Myocardial Infarction Study (ProMIS). ProMIS aims to verify the prognostic value of CPCs in patients with either ST elevation or non-ST elevation myocardial infarction with or without diabetes mellitus, using cardiac magnetic resonance imaging (MRI) for assessment of ventricular function as a primary endpoint. Results indicate crucial steps for SOP implementation, namely timely cell isolation after sampling, use of appropriate lysis buffer to separate blood cell types and minimize the acquisition events during flow cytometry, adoption of proper fluorophore combination and antibody titration for multiple antigenic detection and introduction of counting beads for precise quantification of functional CPC activity in migration assay.With systematic specification of factors influencing the enumeration of CPC by flow cytometry, the abundance and migration capacity of CPCs can be correctly assessed. Adoption of validated SOP is essential for refined comparison of patients with different comorbidities in the analysis of risk stratification

Safety perspectives on presently considered drugs for the treatment of COVID‐19

Intense efforts are underway to evaluate potential therapeutic agents for the treatment of COVID‐19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm–benefit ratios that may be encountered when treating COVID‐19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life‐threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID‐19

Thrombosis in primary myelofibrosis: incidence and risk factors

We assessed frequency and predictive factors for major cardiovascular (CV) events in 707 patients with primary myelofibrosis (PMF) followed in 4 European institutions. A total of 236 deaths (33%) were recorded for an overall mortality of 7.7% patient-years (pt-yr). Fatal and nonfatal thromboses were registered in 51 (7.2%) patients, with a rate of 1.75% pt-yr. If deaths from non-CV causes were considered as competing events, we estimated that the adjusted rate of major thrombotic events would have been 2.2% pt-yr. In a multivariable model, age older than 60 years (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.24-4.39, P = .01) and JAK2 mutational status (HR, 1.92; 95% CI, 1.10-3.34; P = .02) were significantly associated with thrombosis, whereas the strength of the association between leukocyte count higher than 15 x 10(9)/L and CV events was of borderline significance (HR, 1.72; 95% CI, 0.97-2.72; P = .06). The highest incidence of fatal and nonfatal thrombosis was observed when the mutation was present along with leukocytosis (3.9% pt-yr; HR, 3.13; 95% CI, 1.26-7.81). This study is the largest hitherto carried out in this setting and shows that the rate of major CV events in PMF is comparable with that reported in essential thrombocythemia, and it is increased in aged patients and those with JAK2 V617F mutation and leukocytosis

Impact of ruxolitinib on survival of patients with myelofibrosis in the real world: Update of the ERNEST Study

19sinonenoneGuglielmelli P.; Ghirardi A.; Carobbio A.; Masciulli A.; Maccari C.; Mora B.; Rumi E.; Triguero A.; Finazzi M.C.; Pettersson H.; Paoli C.; Mannelli F.; Vanni D.; Rambaldi A.; Passamonti F.; Alvarez-Larran A.; Andreasson B.; Vannucchi A.M.; Barbui T.Guglielmelli, P.; Ghirardi, A.; Carobbio, A.; Masciulli, A.; Maccari, C.; Mora, B.; Rumi, E.; Triguero, A.; Finazzi, M. C.; Pettersson, H.; Paoli, C.; Mannelli, F.; Vanni, D.; Rambaldi, A.; Passamonti, F.; Alvarez-Larran, A.; Andreasson, B.; Vannucchi, A. M.; Barbui, T