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Summary. Background: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). Objectives and methods:In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. Results: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0-1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patientyears (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). Conclusions: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.

Controversies still exist regarding definition of the thrombotic risks in Ph-(BCR/ABL1-) myeloproliferative disorders with thrombocythemia (MPD-T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD-T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 9 10 9 /L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2 V617F mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V 'Leiden' and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (AE aspirin), we documented a decrease in both venous (6.7-fold) and arterial events (1.8-fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.

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Background and purpose of the workshopConcern about the venous thromboembolism (VTE) risk of new hormonal contraceptive options shortly after their entry into the market has triggered a number of 'pill scares', each of which resulted in panic stopping of the formulations in question and a spike in unplanned pregnancies, yet with no subsequent reduction in VTE rates among women of reproductive age.Perhaps the best example of a recent pill scare that resulted in enormous harm from a public health perspective was the 'third-generation pill scare' that occurred in many countries in Europe and around the world in 1995. At that time the new third-generation pills were promoted as being less androgenic and as possibly having fewer adverse effects on cardiovascular and metabolic parameters and thereby potentially being safer than existing pills.Shortly after the introduction of these third-generation pills, reports of a possible increased risk of VTE began to appear. Such reports brought the progestogen component of these pills under scrutiny and inevitably a phenomenon known as 'stimulated reporting' occurred. Physicians with patients on these new pills were more likely to send their patients for assessment of any leg pain or swelling and more likely to report any VTE episodes to regulatory authorities because of heightened awareness of the possible risk. What followed was an international pill scare when regulatory authorities in a number of countries issued alerts about the possible increased risk of VTE with thirdgeneration pills. Panic stopping of pills by millions of women resulted in an abrupt and alarming rise in unplanned pregnancy as evidenced by sudden increases in deliveries and abortions, 1-3 each with their attendant increased risks of VTE.The history of this unfortunate episode is well documented. After class action lawsuits and lengthy trials, at which experts in epidemiology debated the findings, there emerged an awareness that studies examining VTE risks, in particular, required an understanding of the epidemiology of VTE and the possible biases that might systematically result in findings which diverged from the 'truth'. 4,5 The precise effects of different hormonal contraceptives on the haemostatic system continue to be studied and debated 6,7 but because compelling data for an increased risk have not been demonstrated the lawsuits were ultimately thrown out 8 and third-generation pills remain on the market and are widely prescribed today. 9 In 2009, anecdotal reports of VTE episodes in women using an ethinylestradiol/drospirenone (EE/DRSP)-based oral contraceptive (Yasmin ® ) were followed by publications with conflicting findings about the risk of VTE with this product. This led the manufacturer to invite experts in gynaecology, reproductive endocrinology, haematology and epidemiology to a workshop to critically review these recent publications to understand the reasons for divergent results and to produce a consensus statement about the likely comparative risk of this new formulation and other mar...

The results confirm that venous thromboembolism is a multifactorial disease in which thrombophilia screening is needed in young symptomatic women on the pill with thrombosis. The results also emphasize the value of proper thromboprophylaxis in women while on oral contraceptive in situations of increased risk for venous thromboembolism.

Background: Interferon alfa (IFNa) based therapies have been successfully applied in myeloproliferative neoplasms (MPN) for over thirty years. Several uncontrolled phase II trials have independently shown high rates of hematologic, splenic and sustained mutant JAK2 molecular responses in Polycythemia vera (PV) patients. However, a head-to-head assessment versus other treatment options in confirmatory trials has been lacking so far. Here we report 12 month data from a randomized controlled phase III trial comparing the novel, long-acting Ropeginterferon alfa-2b (AOP2014) with hydroxyurea (HU) in PV patients. Study design: Randomized, controlled, parallel group multicenter phase III trial assessing efficacy, safety and tolerability in patients diagnosed with PV according to WHO2008 criteria, either naïve to cytoreduction or HU experienced (but neither intolerant nor complete responders, cumulative HU exposure max. 3 years). The primary endpoint was non-inferiority of AOP2014 vs. HU at 12 months of therapy in terms of complete hematological response (CHR) rate. CHR was defined as normal hematocrit, leukocyte and platelet counts, spleen size and absence of phlebotomy in the preceding 3 months. As important secondary endpoint the effect of treatment on mutant JAK2 allele burden was assessed as rate of complete and partial molecular response (C/PMR) rate according to modified ELN criteria. Both cohorts are followed up further maintaining the original randomization for assessing effects of prolonged therapy. Results: 257 patients were randomized in 48 sites in 13 European countries and treated with response-driven escalating doses of either AOP2014, or HU. 62% of patients were naïve to cytoreduction, 38% HU experienced; 19% had a previous thrombotic event. Response-driven dose escalation was done in both treatment arms applying up to 10 dose levels (50-500µg AOP2014 every other week, or 250-3000 mg HU daily). Both treatments were well tolerated. The drop-out rate after 12 months was low with ~15% in both arms, the majority of drop-outs were due to administrative reasons (bi-weekly hospital visits). This presentation will provide the detailed analysis of primary and secondary endpoints of the trial, which is still blinded as of 4th Aug 2016. Preliminary pooled analysis revealed that at 12 months 45% of patients had a hematologic response: mean Hct values dropped from 48% to 42%, leukocyte counts from 12 to 6 *109/L and platelets from 530 to 260 *109/L. Need for phlebotomy within 3 months dropped from 86% to 6%. 37% of patients achieved a JAK2 molecular response (PMR or CMR), mean mutant JAK2 allele burden went from 42,5% to 28,7%. Conclusions: This is the first phase III trial formally assessing efficacy, safety and tolerability of Ropeginterferon alfa-2b versus HU. Both cohorts are followed-up for prolonged treatment duration, and it is expected that the currently available and emerging data will establish the role of Ropeginterferon alfa-2b as first-line treatment for PV. Disclosures Gisslinger: AOP Orphan Pharmaceuticals AG, Novartis, Celgene, Baxalta: Consultancy, Honoraria, Research Funding. Klade:AOP Orphan: Employment. Georgiev:Alnylam Pharmaceuticals: Consultancy. Illes:University of Debrecen faculty of medicine department of hematology: Employment. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding. Grohmann-Izay:AOP Orphan Pharmaceuticals AG: Employment. Kralovics:AOP Orphan: Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees. Kiladjian:Novartis: Research Funding; AOP Orphan: Research Funding.

In patients with large artery IS treated with the MT using stent-retrievers, bridging therapy with IVT preceding MT and higher platelet count were associated with significant changes of the histological structure of blood clots.