scholarly journals Incidental venous thromboembolism: is anticoagulation indicated?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Marcello Di Nisio ◽  
Marc Carrier
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Pulmonary Arteries ◽  
Bleeding Risk ◽  
Preliminary Evidence ◽  
Vein Thrombosis ◽  
Incidental Pulmonary Embolism ◽  
Recurrent Vte ◽  
Deep Vein

Abstract Patients with cancer have a high risk of venous thromboembolism (VTE) and about one-half of these events are incidentally detected. The prognosis of incidental VTE appears to be similar to symptomatic events, with comparably high rates of recurrent VTE in this patient population. In the absence of major contraindications, anticoagulant treatment with low-molecular-weight heparin for 3 to 6 months is generally recommended for incidental proximal deep vein thrombosis as well as for incidental pulmonary embolism that involves multiple subsegmental or more proximal pulmonary arteries. The decision of whether to extend treatment beyond 3 to 6 months should be evaluated on a case-by-case basis after periodic reassessment of the risks factors for bleeding and recurrent VTE while also taking into account patient preferences. The clinical relevance of a single incidental subsegmental pulmonary embolism without concomitant deep vein thrombosis is uncertain and either a watchful approach or a shorter course of anticoagulation to minimize the bleeding risk may also be considered. Preliminary evidence suggests that anticoagulation treatment may be beneficial for cancer patients with incidental distal deep vein thrombosis or incidental splanchnic vein thrombosis.

scholarly journals Duration of anticoagulation after isolated pulmonary embolism

2016 ◽  
Vol 47 (5) ◽  
pp. 1429-1435 ◽  
Author(s):  
Gualtiero Palareti ◽  
Benilde Cosmi ◽  
Emilia Antonucci ◽  
Cristina Legnani ◽  
Nicoletta Erba ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Subgroup Analysis ◽  
Italian Study ◽  
Index Event ◽  
Vein Thrombosis ◽  
Recurrent Vte ◽  
Deep Vein ◽  
D Dimer

In the D-dimer and ULtrasonography in Combination Italian Study (DULCIS), serial D-dimer measurement in combination with assessment of residual thrombosis (in patients with deep vein thrombosis (DVT)) identified patients who safely discontinued anticoagulation after an unprovoked venous thromboembolism (VTE).In this subgroup analysis, the value of D-dimer tests was assessed in patients with isolated pulmonary embolism (PE) compared with those with DVT, with or without PE (DVT/PE). The DULCIS database was reanalysed in relation to this target.26.8% of the DULCIS patients had isolated PE as the index event; this was more prevalent in females (34.1%) than in males (21.1%; p<0.0001). The rate of positive D-dimer was similar in isolated PE and DVT/PE. The rate of recurrences was not different in isolated PE or DVT/PE patients (4.8% ppy versus 3.8% ppy; nonsignificant) who stopped anticoagulation for negative D-dimer, but it was markedly high (11.2% ppy; p<0.0001) in those with isolated PE who remained without anticoagulation despite positive D-dimer. Recurrences were more frequently new isolated PE in patients with isolated PE than with DVT/PE (six (46.2%) out of 13 versus two (7.4%) out of 27; p=0.0085).Serial D-dimer assessment can inform on the risk of recurrent VTE and help determine the duration of anticoagulation in patients with isolated PE.

Incidence of venous thromboembolism among patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer

2020 ◽  
Vol 30 (4) ◽  
pp. 491-497 ◽  
Author(s):  
Julia Rose Salinaro ◽  
Kourtnie McQuillen ◽  
Megan Stemple ◽  
Robert Boccaccio ◽  
Jessie Ehrisman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Primary Outcome ◽  
Vein Thrombosis ◽  
Deep Vein

ObjectivesNeoadjuvant chemotherapy may be considered for women with epithelial ovarian cancer who have poor performance status or a disease burden not amenable to primary cytoreductive surgery. Overlap exists between indications for neoadjuvant chemotherapy and known risk factors for venous thromboembolism, including impaired mobility, increasing age, and advanced malignancy. The objective of this study was to determine the rate of venous thromboembolism among women receiving neoadjuvant chemotherapy for epithelial ovarian cancer.MethodsA multi-institutional, observational study of patients receiving neoadjuvant chemotherapy for primary epithelial ovarian, fallopian tube, or peritoneal cancer was conducted. Primary outcome was rate of venous thromboembolism during neoadjuvant chemotherapy. Secondary outcomes included rates of venous thromboembolism at other stages of treatment (diagnosis, following interval debulking surgery, during adjuvant chemotherapy, or during treatment for recurrence) and associations between occurrence of venous thromboembolism during neoadjuvant chemotherapy, subject characteristics, and interval debulking outcomes. Venous thromboembolism was defined as deep vein thrombosis in the upper or lower extremities or in association with peripherally inserted central catheters or ports, pulmonary embolism, or concurrent deep vein thrombosis and pulmonary embolism. Both symptomatic and asymptomatic venous thromboembolism were reported.ResultsA total of 230 patients receiving neoadjuvant chemotherapy were included; 63 (27%) patients overall experienced a venous thromboembolism. The primary outcome of venous thromboembolism during neoadjuvant chemotherapy occurred in 16 (7.7%) patients. Of the remaining venous thromboembolism events, 22 were at diagnosis (9.6%), six post-operatively (3%), five during adjuvant chemotherapy (3%), and 14 during treatment for recurrence (12%). Patients experiencing a venous thromboembolism during neoadjuvant chemotherapy had a longer mean time to interval debulking and were less likely to undergo optimal cytoreduction (50% vs 80.2%, p=0.02).ConclusionsPatients with advanced ovarian cancer are at high risk for venous thromboembolism while receiving neoadjuvant chemotherapy. Consideration of thromboprophylaxis may be warranted.

P6461The long-term clinical comparisons of symptomatic patients of pulmonary embolism with and those without deep vein thrombosis: from the COMMAND VTE Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Murata ◽  
Y Yamashita ◽  
T Morimoto ◽  
H Amano ◽  
T Takase ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Acute Phase ◽  
Clinical Presentation ◽  
Vein Thrombosis ◽  
Significant Difference ◽  
Severe Clinical Presentation ◽  
Recurrent Vte ◽  
Deep Vein

Abstract Background Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), has significant morbidity and mortality. Acute PE, in particular, is fatal if we miss it, and symptomatic patients of PE sometimes have concomitant DVT. Purpose This study compared the risk of mortality in symptomatic patients of PE with and those without DVT in the long term. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. Patients with both PE and DVT (N=1334) were regarded as PE patients, and the current study population consisted of 1715 PE patients and 1312 DVT patients. Results There were 1203 symptomatic patients of PE, including 381 without and 822 with DVT. In our cohort, the mean age was 67.9±14.9 years, 63% was female, 44% had hypertension, 12% diabetes mellitus, 5% history of VTE. There were 20% of active cancer. Baseline characteristics were well matched except for dyslipidemia (18% vs. 23%, p=0.021) and atrial fibrillation (8% vs. 5%, p=0.045). Patients without DVT had a more severe clinical presentation compared to those with DVT, including hypoxemia, shock and arrest. Moreover, Initial parenteral anticoagulation therapy in the acute phase was administered less frequently in patients without DVT (89% vs. 96%, P=0.0001). Two groups received thrombolysis (20% vs. 26%, P=0.18) and mechanical supports (Ventilator 14% vs. 5%, p<0.001, PCPS 5% vs. 3%, p<0.001, respectively). During follow-up, 93 (8%) patients experienced recurrent VTE events and 98 (8%) major bleeding events, and 323 (27%) patients died. The most frequent cause of death was cancer (11%). There were a significant differences in the cumulative incidences of all-cause death between the groups (32% vs. 24%, P=0.006), whereas there was significant difference in VTE-related death (13% vs. 4%, p<0.001). Estimated freedom rates from death for patients of PE without and those with DVT were as follows: 88% vs 99% at 10-day, 86% vs 95% at 1-month, 75% vs 83% at 1-year, and 64% vs 71% at 5-year, respectively. Landmark analysis Conclusions In symptomatic patients of PE, there was a difference in mortality between groups, but no difference in recurrent VTE. Patients without DVT had a more severe clinical presentation compared to those with DVT, and many VTE-related deaths in the acute phase. The one-month mortality rate differed statistically between groups, but there was no significant difference in long-term survival beyond one month. Most of deaths were due to underlying diseases, mainly cancer, and less commonly due to VTE in the long term. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Venous Thromboembolism

2017 ◽  
Author(s):  
Guillermo A. Escobar ◽  
Peter K. Henke ◽  
Thomas W. Wakefield
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Lower Extremity ◽  
The United States ◽  
Laboratory Evaluation ◽  
Individual Risk ◽  
Vein Thrombosis ◽  
Clinical Scenarios ◽  
Deep Vein

Deep vein thrombosis (DVT) and pulmonary embolism (PE) comprise venous thromboembolism (VTE). Together, they comprise a serious health problem as there are over 275,000 new VTE cases per year in the United States, resulting in a prevalence of one to two per 1,000 individuals, with some studies suggesting that the incidence may even be double that. This review covers assessment of a VTE event, initial evaluation of a patient suspected of having VTE, medical history, clinical presentation of VTE, physical examination, laboratory evaluation, imaging, prophylaxis against perioperative VTE, indications for immediate intervention (threat to life or limb), indications for urgent intervention, and management of nonemergent VTE. Figures show a modified Caprini score questionnaire used at the University of Michigan to determine individual risk of VTE and the indicated prophylaxis regimen; Wells criteria for DVT and PE; phlegmasia cerulea dolens secondary to acute left iliofemoral DVT after thigh trauma; compression duplex ultrasonography of lower extremity veins; computed tomographic angiogram of the chest demonstrating a thrombus in the pulmonary artery, with extension into the right main pulmonary; management of PE according to Wells criteria findings; management of PE with right heart strain in cases of massive or submassive PE; treatment of DVT according to clinical scenario; a lower extremity venogram of a patient with May-Thurner syndrome and its subsequent endovascular treatment; and various examples of retrievable vena cava filters (not drawn to scale). Tables list initial clinical assessment for VTE, clinical scenarios possibly benefiting from prolonged anticoagulation after VTE, indications for laboratory investigation of secondary thrombophilia, venous thromboembolic risk accorded to hypercoagulable states, and Pulmonary Embolism Rule-out Criteria Score to avoid the need for D-dimer in patients suspected of having PE.   This review contains 11 highly rendered figures, 5 tables, and 167 references. Key words: anticoagulation; deep vein thrombosis; postthrombotic syndrome; pulmonary embolism; recurrent venous thromboembolism; thrombophilia; venous thromboembolism; PE; VTE; DVT 

scholarly journals Venous Thromboembolism in Denmark: Seasonality in Occurrence and Mortality

TH Open ◽  
2019 ◽  
Vol 03 (02) ◽  
pp. e171-e179 ◽  
Author(s):  
Nils Skajaa ◽  
Erzsébet Horváth-Puhó ◽  
Kasper Adelborg ◽  
Paolo Prandoni ◽  
Kenneth J. Rothman ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Seasonal Pattern ◽  
Cerebral Vein ◽  
Cerebral Vein Thrombosis ◽  
Splanchnic Vein Thrombosis ◽  
Vein Thrombosis ◽  
Winter Peak ◽  
Deep Vein

Background Many cardiovascular conditions exhibit seasonality in occurrence and mortality, but little is known about the seasonality of venous thromboembolism. Methods Using Danish registries, we identified all patients with deep vein thrombosis, pulmonary embolism, splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis during 1977–2016. We tallied monthly deaths occurring within 90 days of the venous thromboembolism diagnosis. We estimated peak-to-trough ratios and timing of the peak of both diagnoses and deaths summed over all years of the study period. The departure from 1.0 of the peak-to-trough ratio measures the intensity of any seasonal pattern. Results We estimated a peak-to-trough ratio of 1.09 (95% confidence interval: 1.07–1.11) for deep vein thrombosis and 1.22 (1.19–1.24) for pulmonary embolism occurrence. The peak-to-trough ratios for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence were 1.10 (1.01–1.20), 1.19 (1.00–1.40), and 1.12 (1.07–1.17), respectively. The occurrence of all conditions peaked during winter or fall. In time trend analyses, the peak-to-trough ratio increased considerably for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence. In associated mortality, the peak-to-trough ratio for deep vein thrombosis was larger (1.15, 1.07–1.23) than that for pulmonary embolism (1.04, 1.01–1.08). Discussion Excess winter risks were modest, but more marked for pulmonary embolism occurrence than for deep vein thrombosis occurrence. The seasonal pattern intensified throughout the study period for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis. The winter peak in mortality following pulmonary embolism was smaller than that for deep vein thrombosis.

scholarly journals Long-term recurrence of venous thromboembolism after short-term treatment of symptomatic isolated distal deep vein thrombosis: A cohort study

2017 ◽  
Vol 22 (6) ◽  
pp. 518-524 ◽  
Author(s):  
Marco P Donadini ◽  
Francesco Dentali ◽  
Samuela Pegoraro ◽  
Fulvio Pomero ◽  
Chiara Brignone ◽  
...  
Keyword(s):  
Cohort Study ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Vein Thrombosis ◽  
Recurrent Vte ◽  
Deep Vein

Isolated distal deep vein thrombosis (IDDVT) is a common clinical manifestation of venous thromboembolism (VTE). However, there are only scant and heterogeneous data available on the long-term risk of recurrent VTE after IDDVT, and the optimal therapeutic management remains uncertain. We carried out a retrospective cohort study of consecutive patients diagnosed with symptomatic IDDVT between 2004 and 2011, according to a predefined short-term treatment protocol (low molecular weight heparin (LMWH) for 4–6 weeks). The primary outcome was the occurrence of recurrent VTE. A total of 321 patients were enrolled. IDDVT was associated with a transient risk factor or cancer in 165 (51.4%) and 56 (17.4%) patients, respectively. LMWH was administered for 4–6 weeks to 280 patients (87.2%), who were included in the primary analysis. Overall, during a mean follow-up of 42.3 months, 42 patients (15%) developed recurrent VTE, which occurred as proximal DVT or PE in 21 cases. The recurrence rate of VTE per 100 patient-years was 3.5 in patients with transient risk factors, 7.2 in patients with unprovoked IDDVT, and 5.9 in patients with cancer ( p=0.018). At multivariable analysis, unprovoked IDDVT and previous VTE were significantly associated with recurrent VTE (HR 2.16, 95% CI 1.12–4.16 and HR 1.97, 95% CI 1.01–3.86, respectively). In conclusion, the long-term risk of recurrent VTE after IDDVT treated for 4–6 weeks is not negligible, in particular in patients with unprovoked IDDVT or cancer. Further studies are needed to clarify whether a longer, but definite treatment duration effectively prevents these recurrences.

Risk of recurrent venous thromboembolism among deep vein thrombosis and pulmonary embolism patients treated with warfarin

2014 ◽  
Vol 31 (3) ◽  
pp. 439-447 ◽  
Author(s):  
Beth L. Nordstrom ◽  
Michael A. Evans ◽  
Brian R. Murphy ◽  
Edith A. Nutescu ◽  
Jeff R. Schein ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Vein Thrombosis ◽  
Recurrent Venous Thromboembolism ◽  
Deep Vein

More than one in two venous thromboembolism treated in French hospitals occurs during the hospital stays

2015 ◽  
Vol 31 (6) ◽  
pp. 390-396 ◽  
Author(s):  
Francois-André Allaert ◽  
Eric Benzenine ◽  
Catherine Quantin
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Hospital Stay ◽  
Principal Diagnosis ◽  
Vein Thrombosis ◽  
Icd 10 ◽  
Hospital Stays ◽  
Deep Vein

Objective The objective was to describe the prevalence of venous thromboembolism, pulmonary embolism, and deep vein thrombosis among hospitalized patients and the percentages of those occurring during the hospital stays. Methods French DRG gave now the opportunity to investigate the frequency of venous thromboembolism occurring during the hospital stay. Statistics are issued from the national PMSI MCO databases encoded using the CIM10. Since 2010–2011 it is possible to differentiate the reason for hospital admission from the pathologies which secondly occurred. Any stay with the ICD-10 codes selected was considered as a hospital-occurred thrombosis unless it was the principal diagnosis of the first medical unit summary. To eliminate outpatient consultations or in day care, stays of <48 h were excluded. Results The results pertain to the 78,838,983 hospitalizations in France from 2005 to 2011 and on the 18,683,603 hospital stays in 2010–2011. The incidence of hospital stays came to 860,343 (1.09%) for venous thromboembolism, with 428,261 (0.543%) for deep vein thrombosis without pulmonary embolism and 432,082 (0.548%) for pulmonary embolism. It corresponds to an incidence of 189 per 100,000 inhabitants. Out of 100 hospital stays involving venous thromboembolism, for 40.3% venous thromboembolism was the cause of hospitalization whereas 59.7% can be considered to have occurred during hospital stay. These distributions are of 25.6 and 74.4% for deep vein thrombosis, respectively, 53.8 and 46.2% for pulmonary embolism. Conclusion The high proportion of hospital-occurred venous thromboembolism is an alarming situation that should question the quality of prevention and/or its effectiveness.

Late consequences of venous thromboembolism: Measuring quality of life after deep vein thrombosis and pulmonary embolism

2018 ◽  
Vol 164 ◽  
pp. 170-176 ◽  
Author(s):  
Waleed Ghanima ◽  
Hilde Skuterud Wik ◽  
Mazdak Tavoly ◽  
Tone Enden ◽  
Lars-Petter Jelsness-Jørgensen
Keyword(s):  
Quality Of Life ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Vein Thrombosis ◽  
Deep Vein

Subgroup Analysis of Patients with Cancer in Xalia - a Non-Interventional Study of Rivaroxaban in Routine Treatment of Deep Vein Thrombosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1438-1438 ◽  
Author(s):  
Alexander G G Turpie ◽  
Lorenzo G Mantovani ◽  
Sylvia Haas ◽  
Reinhold Kreutz ◽  
Danja Monje ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Research Funding ◽  
Incidence Rates ◽  
Vein Thrombosis ◽  
All Cause Mortality ◽  
Recurrent Vte ◽  
Deep Vein ◽  
Active Cancer

Abstract Background: XALIA is a prospective, non-interventional study of rivaroxaban in the treatment of acute deep vein thrombosis. The overall XALIA results showed that rivaroxaban was associated with similarly low rates of major bleeding and symptomatic recurrent venous thromboembolism (VTE) as standard anticoagulation. A subset of patients in XALIA had active cancer at the time of enrolment into the study. Purpose: To describe the demographics, clinical characteristics, treatment strategies and outcomes of patients in XALIA with cancer and VTE. The primary outcomes were major bleeding, recurrent VTE and all-cause mortality. Methods: Patients with deep vein thrombosis with or without concomitant pulmonary embolism aged ≥18 years who had active cancer and were scheduled to receive ≥3 months of anticoagulation with rivaroxaban or standard therapy were eligible. Therapy type, dose and duration were at the physician's discretion. For the purpose of this substudy, we defined the following treatment cohorts: rivaroxaban cohort (patients treated with rivaroxaban alone or who received heparin/fondaparinux for ≤48 hours before switching to rivaroxaban); early switchers cohort (patients treated with rivaroxaban who received heparin/fondaparinux for >48 hours-14 days and/or a vitamin K antagonist [VKA] for 1-14 days before changing to rivaroxaban); standard anticoagulation cohort (patients treated with heparin/fondaparinux and a VKA or a VKA only); and heparin/fondaparinux cohort (patients treated with heparin/fondaparinux alone). Results: Of 5136 patients in XALIA who received study medication, 587 (11.4%) had active cancer at baseline. Of these, 146 (24.9%) received rivaroxaban, 30 (5.1%) were early switchers, 167 (28.4%) received standard anticoagulation (of which 26 [4.4%] received a VKA only) and 244 (41.6%) received heparin/fondaparinux only, of whom 223 (38.0%) received low molecular weight heparin and the remainder other heparins or fondaparinux. Demographics are shown in Table 1. The most common type of active cancer at baseline in all cohorts was genitourinary, with the exception of the heparin/fondaparinux cohort where gastrointestinal cancer was the most common type (Table 2). The incidence rates for the primary outcomes for each cohort are shown in Figure 1. The rates of major bleeding were highest in the standard anticoagulation cohort (n=8 [4.8%]) and lowest in the early switchers (no major bleeding events occurred). The rates of recurrent VTE were similar in the in the rivaroxaban, early switcher and standard anticoagulation cohorts (n=5 [3.4%], n=1 [3.3%] and n=6 [3.6%], respectively) and were highest in the heparin/fondaparinux cohort (n=12 [4.9%]). All-cause mortality was highest in the heparin/fondaparinux cohort (n=61 [25.0%]) and lowest in the early switchers (no deaths occurred). Conclusions: In the real-world XALIA study, 38.0% of patients with cancer received treatment with low molecular weight heparin, which was in line with guidelines. The remaining patients received rivaroxaban, standard anticoagulation or were early switchers. For the three primary outcomes, the lowest incidence rates were observed in the early switcher cohort. The highest rates were in the standard anticoagulation cohort for major bleeding and the heparin/fondaparinux cohort for recurrent VTE and all-cause mortality; rates for all three primary outcomes were low in the rivaroxaban cohort, suggesting that rivaroxaban may be a safe and effective treatment option for patients with VTE and active cancer. Figure 1 Primary outcomes in patients with active cancer at baseline by treatment group. VTE, venous thromboembolism. Figure 1. Primary outcomes in patients with active cancer at baseline by treatment group. / VTE, venous thromboembolism. Disclosures Turpie: Janssen Research & Development, LLC: Consultancy, Honoraria; Bayer Pharma AG: Consultancy, Honoraria. Mantovani:Janssen-Cilag Ltd: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Consultancy; Bayer Pharma AG: Consultancy; Pfizer Inc: Research Funding. Haas:Sanofi SA: Consultancy; Pfizer Inc: Consultancy; Daiichi Sankyo: Consultancy; Bristol-Myers Squibb: Consultancy; Bayer Pharma AG: Consultancy; Aspen Pharmacare: Consultancy. Kreutz:Bayer Pharma AG: Honoraria; Servier Laboratories Ltd: Consultancy; Lundbeck Ltd: Consultancy; Daiichi Sankyo: Consultancy; Berlin-Chemie Menarini: Consultancy; Bayer Pharma AG: Consultancy; Bristol-Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria. Monje:Bayer Pharma AG: Employment. Schneider:Bayer Pharma AG: Employment. van Eickels:Bayer Pharma AG: Employment. Gebel:Bayer Pharma AG: Employment. Ageno:Boehringer Ingelheim: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Bayer Pharmaceuticals: Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Bayer Pharma AG: Consultancy, Honoraria.

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