2013 XXIV Wednesday Page Netherlands CONGRESS JULY 3 1 ISTH2013NEWS

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Tissue factor pathway ISTH 2015 Toronto Congress Women’s issues Optimising anticoagulation inhibitor and Protein S » Overview with Sam Schulman » in thrombosis » in the elderly »

Tweet of the day #ISTH2013

Jane Skov @JaneSkov1 Impressive plenary talk by Denise Wagner at #ISTH2013 including  amazing pictures of neutrophils  casting their NETs

Recipients of the Biennial Awards for Contributions to Hemostasis (BACH)

Initiated in 1982, the BACH Awards recognize individuals who have made significant contributions to research and education in blood coagulation. The awards are presented in two categories:

• The Investigator Recognition Awards recognize ISTH members whose accomplishments are internationally regarded as exemplary models of excellence in research and teaching. • The Distinguished Career Awards recognize ISTH members whose ca- reer contributions have significantly advanced the scientific community’s understanding of the diseases and At this edition of the ISTH congress paperless disorders affecting hemostasis. 2013 Awards conferencing has really taken off. Distinguished Career • Lawrence Brass, MD, PhD • Philip G de Groot, PhD At this edition of the ISTH congress of innovation of the ISTH 2013 congress ISTH congress visitor Elena Salabeno • Marcel Levi, MD, PhD paperless conferencing has really taken Tilman Hackeng is very satisfied with the from Italy agrees with him and adds: • Peter Newman, PhD off. Paper posters have completely been overwhelming atmosphere in the central “These electronic poster presentations • Zaverio Ruggeri, MD replaced by electronic poster boards, e-poster hall and says: “This is just what are fantastic. I had a large attendance facilitating a more attractive visualiza- we expected. E-posters provide a plat- when showing my poster and everybody Investigator Recognition tion of research results and enabling form for better interaction between the was able to clearly see my graphs • Wolfgang Bergmeier, MD video animation and interactive features presenter and those who are interested and photographs.”. • Christian Gachet, MD, PhD on posters. During the manned poster in the poster. Also, people can see every • Joseph Italiano, PhD sessions congress attendees can discuss poster any time during the congress, • Bernhard Nieswandt, PhD posters on the 74 poster boards while which is a great improvement compared AMC Disclaimer: • Thomas Renné, MD, PhD having a drink and some snacks. Director to temporary paper display. Third time http://www.amc.nl/disclaimer 2013 XXIV Wednesday Page 2013 XXIV Wednesday Page Netherlands CONGRESS JULY 3 2 Netherlands CONGRESS JULY 3 3

The Ratnoff-MacFarlane Plenary Lecture: The ISTH’s Journal HemopHilia SolutionS Tissue factor of Thrombosis and pathway Hemostasis (JTH) Debuts a New Cover inhibitor and Protein S As part of the excitement at this year’s Congress, the JTH unveiled its new, TAKE HOLD beautifully designed journal cover. This design will also be featured as part OF THE FUTURE of its year State-of-the-Art issue. The new cover features modern imagery, We are committed to helping people with updated branding and a crisp white hemophilia because at Hemophilia Solutions background that allows the artwork and by Bayer, we never lose sight of the human factor. wording to pop off the page and engage readers with ease. See the new journal cover at the JTH desk in the ISTH booth, 500, or online in July.

RESEARCH MANAGE SUPPORT What to do and see in Amsterdam-tourism tips

Eat a raw herring You simply must try raw herring. We don’t want to hear any excuses. The best time Tilman. It is a pretty unusual first name. Only seven men and boys in the Netherlands ences to work as a research fellow at the Department of Biochemistry at the Maastricht to try one is between May and July when the new catch hits the stands. There’s are registered having “Tilman” as their official first name, according to the Dutch First University. In 2002 he received a prestigious mid-career grant from the Netherlands a quality fish stall or store around most corners. This fish is a bargain snack and Name Database of the Meertens Institute. It is actually a Frisian name (Friesland is a Organisation for Scientific Research (NWO). Currently, he is head of the Department of makes for an authentic Dutch eating experience. province in the north of the Netherlands) and, according to the always helpful Wiki- Biochemistry were he studies the anticoagulant protein C/protein S/TFPI pathways and pedia website, the strain is derived from the Oldfrisian word “til”, meaning good, fair applies total chemical protein synthesis to the development of peptide/protein-based Artistic icons in a serene setting or reliable. An appealing symbolic name to have when one is working in the field of contrast agents for imaging of cardiovascular disease. He is a board member of the The Hermitage Amsterdam is the Dutch branch of the world-famous Hermitage in biochemistry. It is also representative for the many contributions that the presenter of Cardiovascular Research Institute Maastricht (CARIM), and president of the Nether- St. Petersburg, Russia. Located on the banks of the Amstel River, the Hermitage today has made to the field of thrombosis and haemostasis. “The Ratnoff-MacFarlane lands Society on Thrombosis and Haemostasis. Amsterdam is a beautiful exhibition space and cultural education centre with a focus Bayer and the Bayer Cross are registered trademarks of Bayer. plenary lecture”, named after Drs Ratnoff and MacFarlane who are best known for © 2013 Bayer HealthCare Pharmaceuticals Inc. All rights reserved. on Russian history and culture. 04/13 G.SM.HEM.05.2013.0027 their discovery of the coagulation cascade, will be given by professor Tilman Hackeng Protein S, named after Seattle where it was first discovered, is a vitamin K-dependent Hermitage Amsterdam | Amstel 51 | Open daily 10:00-17:00 | www.hermitage.nl (Maastricht University, The Netherlands). protein that acts as a cofactor of the anticoagulant protein Activated Protein C (APC). However, protein S also exhibits anticoagulant activity in the absence of APC. In his Listen to the sounds of swing It is exactly 20 years ago (1993) that he defended his PhD thesis entitled “The protein lecture, Tilman will address what was originally described as “the APC-independent ac- Tonight, we’re taken back to the 1950s and the arrival of jazz in the venerable concert C pathway on endothelial cells” at the Utrecht University. Thereafter he left the Neth- tivity of protein S” and which was later uncovered to be a specific anticoagulant cofac- hall. American-born jazz vocalist and Grammy Award winner Kurt Elling follows in erlands to continue his career in the USA, where he worked as a Postdoctoral Fellow tor activity for Tissue Factor Pathway Inhibitor (TFPI) in the inhibition of factor Xa. After Frank Sinatra’s vocal steps with the Kurt Elling s(w)ings Frank Sinatra, emphasizing and later as a Senior Research Scientist at the Scripps Research Institute in La Jolla, an historical perspective, the inhibition of extrinsic tenase complex as well as the role the singer’s loose and free style. But Elling – a true jazz singer, one of the last of his CA. It is in these labs where his love for synthetic protein chemistry started. In 1998 he of platelet TFPI/protein S will be described. In addition the physiological importance of kind – is not an imitator: Sinatra’s interpretations are simply a starting point. came back to the Netherlands on a Fellowship for the Royal Academy of Arts and Sci- the TFPI/protein S anticoagulant pathway will be discussed. Concertgebouw | Concertgebouwplein 10 | Wednesday 3 July 20:00 | 24 to 42 Euros | www.concertgebouw.nl R E S Wednesday July 3, 2013 | Program at a glance

08:00-09:30 Oral Communications Thrombus resolution and stroke G104-105 Tips & Funny facts about the Dutch “ I believe in innovation and the way you Contact activation G106-107 Coagulation and complement Elicium 1 Endothelial cells G104-105 Treatment of von Willebrand disease Forum get to innovation is you fund research Immune thrombocytopenic purpura Mondriaan II Major bleeding Auditorium How do you make and keep Dutch friends? and you learn the basic facts” Inhibitor development in haemophilia A Auditorium Venous thrombosis and cancer Elicium 2 It’s all in the body language plus a few natty lines. New acquaintances should be BILL GATES Modifications in factors VIII, IX and XI Emerald Clot structure E102 greeted with a handshake. As for longer-term friends, a 3-point kiss - that’s cheek- New developments in thrombus formation Elicium 2 Thrombosis and haemostasis in the Asian-Pacific Emerald to-cheek-to-cheek, is commonplace. When leaving a Dutch home, always part with Non-inherited risk factors for venous thrombosis Elicium 1 Thrombosis and haemostasis in the G106-107 a dag (day), or shout a more informal doei (bye). Hug/cuddle at your own peril. Novel platelet receptors Mondriaan III developing world Pregnancy and coagulation G102-103 Nurses symposium E108 LEKKER! Rare bleeding disorders - II E102 14:30-15:30 Oral Communications If you spend some time in the lowlands, you will definitely hear the word “lekker”. Recurrent venous thrombosis - II E104-107 Alternative treatments of haemophilia A Auditorium This seemingly innocent word is ubiquitous in the Netherlands. Thrombin generation tests Mondriaan IV Coagulation factor XIII G106-107 A R Von Willebrand factor – I Forum Coagulation factor: Structure and function G102-103 “Lekker” in its original form refers to food and can be roughly translated as tasty E Disseminated intravascular coagulation Mondriaan III 09:45-10:30 Ratnoff-MacFarlane Lecture or yummy. The Germans and Belgians still use “lekker” in this form, however, over Mondriaan I Haemophilia B Forum time Dutch people have taken incredible liberties with the word and now essentially 10:30-11:00 Coffee/Booth Visit Management of venous thrombosis Elicium 2 use it to describe, well, just about everything! A warm meal on a cold fall day can of 11:00-12:00 State-of-the-Art Lectures Microparticles Mondriaan IV course be “lekker”, but so can a feeling, an experience, a place and even a person! New and old anticoagulants Mondriaan I Natural anticoagulants Emerald Word of warning: don’t go around calling your colleague “lekker” as the original Booths: Microparticles Mondriaan II Novel approaches in vascular biology G104-105 translation of yummy or tasty still does apply! 204 & 255 Genetics: Humans and mice Elicium 1 Pediatric thrombosis Elicium 1 C H Women’s issues in bleeding and thrombosis Elicium 2 Platelet signalling - II Mondriaan II

As you see, lekker is a highly versatile little fellow and can be used in endless HG-NED-0004-COM Vessel wall biology Forum RNA and coagulation E102 instances. You will see that the original translation does not always hold true: Gene therapy Auditorium Thrombophilia - I E104-107 • lekkere broodje (tasty sandwich) – this is an easy one Come to the Biogen Idec and Sobi booths 12:00-13:00 Lunch/Booth Visit 15:30-16:00 Coffee/Booth Visit • lekker rustig (yummy calm, pleasant calm) to find out more about developments 13:00-14:15 Abstract Symposia 16:00-16:45 Plenary Lecture Mondriaan I • lekker weer (tasty weather, great weather) in haemophilia. Contact activation 2.0 E104-107 17:00-18:30 ePoster Sessions ePoster area • niet lekker (not yummy, not nice, not well) Assays for haemostatic drugs Mondriaan III 19:00-01:00 All Congress Party (Ticket needed) Beurs van Berlage • slaap lekker (sleep tasty, sleep well, sleep tight) Platelet response to injury Mondriaan IV • … and the list can go on! Thrombocytopenia Mondriaan II Genetics in coagulation G102-103 2013 XXIV Wednesday Page 2013 XXIV Wednesday Page Netherlands CONGRESS JULY 3 4 Netherlands CONGRESS JULY 3 5

ISTH 2013 Congress App

JTH starts a new era with editors Rosendaal and Reitsma The ISTH 2013 Congress features a free mobile app for attendees. The app conveniently provides iPhone/ In 2013 Frits Rosendaal and Pieter Lane, and we believed we could improve diatrics, pulmonology, obstetrics, etc etc. iPad, BlackBerry, Windows, Android Reitsma took over the editorship of the on this concept even further, since we are The impact of a journal is not just deter- and other smartphone and tablet us- Journal of Thrombosis and Haemostasis in the same centre but from different dis- mined by its impact factor (which is now ers with on-the-go access to the ISTH (JTH), the official scientific journal of the ciplines each giving our own perspective. at 6.081), but also by the image of the 2013’s most exciting, informational and ISTH, thereby ending the successful edi- Once a week, we discuss all submitted journal as the voice of the ISTH. JTH is interactive features, such as program torial period of Mike Greaves and David manuscripts (which have previously been seen as a serious and authoritative jour- overviews, speaker and abstract infor- Lane. We speak with the new editors-in- distributed along the lines of ‘clinical’ and nal, and we will do what we can to keep it mation, general meeting and exhibitor chief about their view of JTH and their ‘basic’ by our editorial assistants) and de- that way and to make it even better. information, venue and city maps. plans for the coming years. cide which ones to send on to Associate The Congress organizers are excited to Editors for further handling, and which What do you consider as the main tasks provide this platform to attendees, and What do you like most as Editors in ones to reject immediately. of the Editors in Chief and what changes hope that all attendees will download Chief? do you envision for the future? it for themselves. The mobile app is What is most interesting is the broad What is the role of JTH in the ISTH? The editors’ task is simple and limited: try now available via Apple and Google view of the field and the best impres- The ISTH is the leading organisation in to get the best papers submitted to the stores. Simply search “ISTH 2013” and sion what is happening at the forefront the field of thrombosis and haemostasis Journal, and try to select the best for pub- download to today to begin using of thrombosis and haemostasis research and the Journal is its voice. An important lication from those that are submitted. it right away! that one gets. What is most rewarding aspect is that in contrast to many other At the moment, we are also organising is the, albeit small, contribution one can specialty journals, there is not ‘a profes- the ISTH 2013 Congress, so we decided make to improve papers and the visibility sion’, like in, say, a journal of orthopae- to postpone any major new initiatives till ISTH 2015 Toronto Congress What will be the main features of the ISTH 2015 Congress? of the ISTH. dics, but many. We serve not only basic after that. Luckily, there is no immediate Canada has for several decades shared the leading role in thrombosis research. scientists and clinicians, but also people need for major changes either, and it is This has often been achieved in international collaboration. We will expand this part- Why two editors rather than one? working in fields quite different from good to get accustomed to the job first . Overview with Congress iPhone/ipad Android AllDevices nership with other nations to provide the attendees with the newest and most impor- We have seen how well a dual editorship thrombosis and haemostasis per se, such President Sam Schulman tant research data in thrombosis and hemostasis. The ISTH 2015 Congress will strongly worked with Mike Greaves and David as haematology, vascular medicine, pae- encourage the young scientists and junior clinicians in our field to join and learn.

Will there be any specific innovations or new aspects introduced at the Congress? For the ISTH 2015 Congress, we will bring in neighboring specialties and hopefully also attendees from these specialties. These include clinical cardiology, stroke neurol- Access to Insight Prizes for Research and ogy and transfusion medicine. The allied health professionals will have their program better announced and their track highlighted. The trainees will also experience an Education Talent in Haemostasis enhanced recommended track to guide them through the Congress.

What can you recommend to see and do in Toronto when attending the Congress? Toronto has the advantage of a centrally located convention center with many On the afternoon of July 2, 2013 the win- Faculty: Nigel Key, Christopher Ludlam, from the Core Faculty complimented winners will strongly benefit from their hotels within walking distance. Moreover, this downtown area offers many theatres, ners of the Access to Insight initiative Stephanie Seremetis, and Ognenka Kozar the scientists for their excellent work training and improve management of museums and restaurants of various ethnicities. The 553 m high CN tower attracts 2 were celebrated. Sponsor Novo Nordisk Markovikj. and meaningful results. haemophilia and rare bleeding disorders million visitors annually. For most of them a walk on a glass floor 342 m above ground and members of the initiative’s Core • The Access to Insight Training Schol- upon return to their home countries and satisfies their need of thrills. The most daring can do the edge walk, hands free 356 m Faculty and Review Board congratulated The recent prizes and recipients are: arship is awarded to physicians who institutes. above ground, but book it well in advance! At the base of the tower, Ripley’s Aquarium the candidates for their outstanding ap- • The Basic Research Grant provides would like to conduct training in the of Canada is about to open this summer. Also close to the convention center is the plications and presented them with their funding of € 70,000 and is awarded to a management of haemophilia and other Novo Nordisk announced that an ad- Hockey Hall of Fame. Two hours from Toronto you can see the beautiful Niagara falls, award certificates. project of basic science or translational haemostatic disorders in a renowned ditional clinical research grant will be or travel north a few hours and experience true wild life in Algonquin Provincial Park research relevant to the understanding haemophilia treatment centre. Funding awarded from the next application cycle - a quarter of Belgium in size. Learn more about Toronto here! http://www.seetoron- Access to Insight is a funding initiative of the pathophysiology and treatment is available for a maximum of € 70,000 going forward. Ambitious health care tonow.com. founded in 2008. Its goal is to promote of haemostatic disorders. In 2012 Karin for 12 months. professional providing care for haemo- research and education in haemophilia Fijnvandraat from Amsterdam and in philia and rare bleeding disorder patients, and other bleeding disorders by offering 2013 Christina Baumgartner from Mil- Recipients of 6-months including nurses, physiotherapists, and funding opportunities especially tailored waukee, Wisconsin received the grant scholarships were: psychologists will have the opportunity to to the needs of talented haemostasis phy- for their interesting research projects. • Majid Naderi from Zahedan, Iran receive funding of € 70,000 – 140,000 for sicians and researchers. Every year there • The Harold R. Roberts award for 2012 • Datta Dharmadhikari from Gaborone, a 12-24 month research project focusing are three separate funding opportunities: was awarded to Yesim G. Dargaud from Botswana on patient outcomes, quality of life, and Be sure to visit the ISTH 2015 website, one Basic Research Grant, one Award Lyon and the Ulla Hedner award 2013 to • Moe Hein from Mandalay, Myanmar social impacts of haemophilia and rare and one Training Scholarship, which are Mettine Bos from Leiden for their excel- • Martin Hendelmeier from Altdorf, bleeding disorders. www.isth2015.org awarded to outstanding applications from lent abstracts submitted to the WFH Germany physicians and researchers. The applica- and ISTH conferences, respectively. Further information about the initiative is over the coming months for additional details! tions are reviewed by an independent Re- The recipients of these awards receive Christopher Ludlam from the Core available at access-to-insight.com view Board, which is headed by the Core €15,000. The reviewers and Nigel Key Faculty expressed his belief that these 2013 XXIV Wednesday Page 2013 XXIV Wednesday Page Netherlands CONGRESS JULY 3 6 Netherlands CONGRESS JULY 3 7

lecture, because Dr Vandendriessche will format to some national funding initia- and clotting disorders. And, if you be- talk about new and improved strategies tives in specific EU countries.” come a member while at the Congress, to boost the performance of gene therapy Not a Member Yet? you will receive a very special ISTH gift vectors for haemophilia using novel If money were not an issue, what collabo- and will be entered into a raffle to win synthetic biology and computational rations would you like to set up? Join the ISTH as a an iPad Mini. Don’t wait! approaches. Using these ‘out-of-the-box’ “The successful development of gene New Member at the The ISTH offers numerous benefits, approaches, his group has now gener- therapy from bench to bedside requires including subscription to the ISTH’s ated some of the most robust vectors to a multi-disciplinary approach. I would Congress and Re- highly-regarded publication, Journal of date for gene therapy of haemophilia A establish a comprehensive collaborative Thrombosis and Haemostasis (JTH), and B. network that focuses on ‘finding the cure’ ceive a Special Gift timely information regarding throm- for haemophilia A and B. I think such a botic and bleeding disorders, targeted With regard to your research, what chal- comprehensive collaborative network, educational programs, discounted lenges will you be facing in the future? possibly transatlantic, is important to har- Membership in the ISTH is impor- rates, networking opportunities and “One of the major challenges relates to ness the complementary expertise from tant at every stage in your career. access to e-learning platforms. the decreasing funds for (biomedical) molecular biologists, immunologists, With more than 3,500 members in 84 research. In particular, I had previously clinicians, industrial stakeholders, regula- countries around the world, the ISTH Learn more about membership in the obtained several EU grants in the con- tors, and - last but not least - patient provides you with the opportunity to ISTH onsite at the congress at booth text of the framework 6 and 7 programs. organisations and representatives. The become part of a global membership 500 or online at www.isth.org. These past EU funding programmes offer ISTH conferences are an ideal forum to community of specialists in bleeding a unique opportunity for academia and plant the seeds of such collaborations.” industrial stakeholders in Europe to har- ness complementary expertise and work Art lecture on Wednesday the 4th of July Diagnostic and management strategies dose of LMWH, whether monitoring of Editors ISTH2013 News Gene therapy for haemophilia: together towards a common objective • Louise Bannon (ISTH) Women’s issues she will discuss specific women’s issues which apply to the non-pregnant popula- anti-Xa levels or dose adjustments are with important translational implications. • Goda Choi in venous thromboembolism. Her lecture tion are not suitable for pregnant women. required as the pregnancy progresses This format allowed EU researchers to • Alev Karasu will emphasise many knowledge gaps For instance, there are no definitive data and body weight increases. finally arrived? • Maurits van Montfoort in thrombosis maintain a competitive position globally. regarding women and thrombosis that on the ruling out of venous thromboem- Thirdly, professor Middeldorp will review • Dafna Groeneveld However, securing EU funding has be- • Mandy Lauw urgently need to be addressed. She will bolism during pregnancy using a clinical anticoagulant therapy in women with Ever since Watson & Crick published their responses (inhibitory antibodies), meth- come increasingly competitive to the ex- • Tobias Bonten Despite the clear differences between the do so by discussing three specific clinical probability assessment combined with unexplained recurrent miscarriages. double helix model in 1953, physicians ods of gene delivery, appropriate animal tent that it is virtually impossible to make • MCI-Amsterdam sexes with respect to the occurrence of questions in relation to venous thrombo- the D-dimer test. Therefore, excluding Several studies have shown that antico- and biomedical researchers have sought models, and sustained expression of the a distinction between the top ranked • Frits Rosendaal venous thromboembolism, many stud- embolism and female sex. pulmonary embolism in pregnant women agulants offer no benefit in these women • Marcel Levi to determine best ways of treating pa- gene of interest. consortia solely on the basis of objective ies on aetiology, diagnosis and treatment First, the contribution of hormone use to without the need for diagnostic imag- and should not be prescribed. However, tients with either hereditary or acquired criteria. Consequently, the current format Design have focused on men. Therefore, several venous thromboembolism. Oral contra- ing is not possible, which will expose it is not known whether anticoagulation defects in their DNA. Gene therapy has In today’s State of the Art lecture, Dr of the EU funding programs falls short of • wardtaal.com aspects of the diagnostic and therapeu- ceptives are a well established risk factor these women to substantial radiation at a prevents recurrent miscarriage in throm- been the main focus of many research Thierry Vandendriessche will provide a achieving its goals if only 1 or 2 consortia tic management of women with venous for venous thromboembolism; however, young age. bophilic women or women with severe groups, and recently we are experienc- concise historic overview of some of the are selected for funding. In the long run, Photography thrombosis are uncertain. The life time careful prescribing of safe preparations She will also discuss the optimal duration pregnancy complications like HELLP • martinstacho.com ing the first patients who are successfully key studies that define the state of the this may ultimately undermine the EU risk of venous thromboembolism is simi- can reduce the risk of hormone-related and intensity of anticoagulant treatment syndrome. treated, including those with haemophil- art and discuss the different approaches research pipeline and EU’s competitive- Print lar for men and women, but women are venous thromboembolism. Professor and prophylaxis of pregnancy-related Many question for women with regard to ia. To achieve these major breakthrough that we can use to address the remaining ness. A more sustainable funding format • JPPJ at higher risk during their fertile years, Middeldorp will also address some uncer- venous thromboembolism with low mo- their risk of venous thrombosis remain. successes, researchers had to overcome bottlenecks. Those interested in the latest is needed that allows for more structural when they are exposed to reproductive tainties with respect to the risk of certain lecular weight heparin (LMWH). For preg- The State of the Art lecture by professor certain barriers, including immune developments should certainly attend the support in an EU-wide fashion similar in risk factors, e.g. hormonal contraception low-dose progestagens and transdermal nant patients, several aspects of the use Saskia Middeldorp discusses the knowl- and pregnancy. hormone preparations. of therapeutic doses of LMWH remain edge gaps in 2013 and is a must for every Professor Saskia Middeldorp’s research Secondly, she will discuss the diagnosis, controversial. These include the uncer- clinician treating pregnant women with has focused on these differences between treatment and prevention of pregnancy- tainty whether a pre-pregnancy weight venous thrombosis. Prescribing Information For people with congenital haemophilia with inhibitors… NovoSeven® 1 mg (50 KIU) powder and solvent for solution for injection Factor VII de ciency: men and women and in her State of the related venous thromboembolism. can be used to determine the appropriate NovoSeven® 2 mg (100 KIU) powder and solvent for solution for injection The recommended dose range is 15 - 30 μg per kg body weight every 4 - 6 ® NovoSeven® 5 mg (250 KIU) powder and solvent for solution for injection hours until haemostasis is achieved. Dose and frequency of injections should NovoSeven responds with speed NovoSeven® 8 mg (400 KIU) powder and solvent for solution for injection be adapted to each individual. Composition: Eptacog alfa (activated), Eptacog alfa (activated) is Glanzmann’s thrombasthenia: 1–4 recombinant coagulation factor VIIa (rFVIIa) produced in baby hamster The recommended dose is 90 µg (range 80 - 120 µg) per kg body weight at kidney cells (BHK Cells) by recombinant DNA technology, 1 mg/vial, 2 mg/ intervals of two hours (1.5 - 2.5 hours). At least three doses should be MIT and Harvard. In 2008, he joined the CVD exhibit a simple pattern of inherit- to control their bleeds vial, 5 mg/vial, 8mg/vial (corresponds to 50 KIU/vial, 100 KIU/vial, 250 KIU/ administered to secure effective haemostasis. The recommended route of vial, 400 KIU/vial). 1mg/ml eptacog alfa (activated) after reconstitution. administration is bolus injection as lack of effi cacy may appear in connection research faculties of the MGH Cardio- ance suggestive of a single causal gene List of excipients: with continuous infusion. For those patients who are not refractory, platelets ® are the fi rst line treatment for Glanzmann’s thrombasthenia. NovoSeven , the rst and only recombinant bypassing Powder: Sodium chloride, Calcium chloride dihydrate, Glycylglycine, vascular Research Center and the MGH that confers a large effect on the phe- agent, resolves bleeds rapidly and effectively1–4 Polysorbate 80, Mannitol, Sucrose, Methionine, Hydrochloric acid, Sodium Contraindications: Hypersensitivity to the active substance, or to any of hydroxide the excipients, or to mouse, hamster or bovine protein. Center for Human Genetic Research. notype. For many of these Mendelian Solvent: Histidine, Hydrochloric acid, Sodium hydroxide, Water for injections Interaction with other medicinal products and other forms of interaction: Based on a non-clinical study it is not Dr Kathiresan’s research seeks to discover forms of CVD, direct DNA sequencing and Indications: treatment of bleeding episodes and prevention of bleeding in recommended to combine rFVIIa and rFXIII. There are no clinical data those undergoing surgery or invasive procedures in the following patient available on interaction between rFVIIa and rFXIII. the genes responsible for inter-individual linkage analysis have successfully yielded groups: Want to ride bikes Undesirable effects: to the park? • patients with congenital haemophilia with inhibitors to coagulation factors differences in the risk for cardiovascular the causal gene and mutation. VIII or IX >5 BU; Rare (> 1/10,000, < 1/1,000): Disseminated intravascular coagulation and related laboratory fi ndings including elevated levels of D-dimer and • patients with congenital haemophilia who are expected to have a high decreased level of AT, coagulopathy, hypersensitivity, headache, arterial disease (CVD) and particularly myocardial However, most cardiovascular diseases, anamnestic response to factor VIII or factor IX administration; thromboembolic events (myocardial infarction, cerebral infarction, cerebral infarction (MI). Through genetic studies such as MI, show a complex inherit- Yeah! • patients with acquired haemophilia; ischaemia, cerebral artery occlusion, cerebrovascular accident, renal artery • patients with congenital FVII defi ciency; thrombosis, peripheral ischaemia, peripheral arterial thrombosis and in populations, he and collaborators have ance, suggestive of an interplay between • patients with Glanzmann’s thrombasthenia with antibodies to GP IIb-IIIa intestinal ischaemia), angina pectoris, nausea, injection site reaction and/or HLA, and with past or present refractoriness to platelet transfusions. including injection site pain, increased fi brin degradation products, increase discovered 45 gene regions related to multiple genes and nongenetic factors. in alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase Posology: Cool, meet me by and prothrombin. the risk for hmyocardial infarction and 95 Mapping gene loci associated with the slide. Haemophilia A or B with inhibitors or expected to have a high Uncommon (> 1/1,000, < 1/100): Venous thromboembolic events (deep anamnestic response: vein thrombosis, thrombosis at i.v. site, pulmonary embolism, thromboembolic gene regions related to cardiovascular complex traits requires substantial levels Mild to moderate bleeding episodes (including home therapy): events of the liver including portal vein thrombosis, renal vein thrombosis, Early intervention has been shown to be effi cacious in the treatment of mild thrombophlebitis, superfi cial thrombophlebitis and intestinal ischaemia), risk factors including blood cholesterol of information and analysis, but since to moderate joint, muscle and mucocutaneous bleeds. Two dosing regimens rash (including allergic dermatitis and rash erythematous), pruritus and OK, see you there! can be recommended: urticaria, therapeutic response decreased, pyrexia. and triglycerides. By means of genetic 2007, approaches to accomplish this goal 1) Two to three injections of 90 µg per kg body weight administered at three- Inhibitory antibody formation: In post-marketing experience, there have been hour intervals. If further treatment is required, one additional dose of no reports of inhibitory antibodies against NovoSeven® or FVII in patients studies in families, he has identified a have matured, and genetic mapping for 90 µg per kg body weight can be administered with congenital haemophilia A or B with inhibitors. Development of inhibitory 2) One single injection of 270 µg per kg body weight antibodies to NovoSeven has been reported in a post-marketing gene responsible for extremely low levels complex traits in humans has become The duration of the home therapy should not exceed 24 hours. There is no observational registry of patients with congenital FVII defi ciency. of LDL cholesterol. He has utilszed gene a reality, for instance by the application Braxton Nelson, 9 years old, clinical experience with administration of a single dose of 270 µg per kg Not known: Intracardiac thrombus, anaphylactic reaction, ushing, has congenital haemophilia with body weight in elderly patients. angioedema. variants to show that some means of rais- ofa systematic genome-wide screen of inhibitors and likes to ride his bike Serious bleeding episodes: Overdose: Three cases of overdose have been reported in patients with haemophilia in 13 years. The only complication reported in connection with ing HDL cholesterol may not lower the common variants (genome-wide associa- and play the drums. An initial dose of 90 µg per kg body weight is recommended and could be administered on the way to the hospital where the patient is usually treated. an overdose was a slight transient increase in blood pressure in a 16 year-old The following dose varies according to the type and severity of the patient receiving 24 mg rFVIIa instead of 5.5 mg. No cases of overdose have risk of disease. Finally, he has identified a tion study (GWAS)). Although GWAS has haemorrhage. Dosing frequency should initially be every second hour until been reported in patients with acquired haemophilia or Glanzmann’s clinical improvement is observed. If continued therapy is indicated, the dose thrombasthenia. In patients with factor VII defi ciency, where the A rare view of coding panel of gene variants that can be used to identified several genetic markers associ- interval can then be increased to 3 hours for 1 - 2 days. Thereafter, the dose recommended dose is 15 – 30 µg/kg rFVIIa, one episode of overdose has interval can be increased successively to every 4, 6, 8 or 12 hours for as long been associated with a thrombotic event (occipital stroke) in an elderly assess future risk for MI. In tandem with ated with CVD risk and cardiovascular risk (> 80 year) male patient treated with 10 – 20 times the recommended dose. Please see adjacent page for as treatment is judged as being indicated. A major bleeding episode may be treated for 2 - 3 weeks but can be extended beyond this if clinically In addition, the development of antibodies against NovoSeven and FVII has variation and the risk of his research, his clinical focus is the pri- factors, the observed effect sizes of these Prescribing Information. warranted. been associated with overdose in one patient with factor VII defi ciency. The dose schedule should not be intentionally increased above the recommended mary prevention of myocardial infarction variants are generally smaller than may Invasive procedure/surgery: doses due to the absence of information on the additional risk that may be An initial dose of 90 µg per kg body weight should be given immediately incurred. in individuals with a family history of MI. have been expected, and account for only This is an advert. before the intervention. The dose should be repeated after 2 hours and then Storage: 3 years shelf life when product is stored below 25°C. 2 years shelf myocardial infarction at 2 - 3 hour intervals for the fi rst 24 - 48 hours depending on the life when product is stored below 30°C. Store powder and solvent vial / pre- a small fraction of the variance in disease intervention performed and the clinical status of the patient. In major surgery, fi lled syringe below 30°C. Store powder and solvent vial / pre-fi lled syringe the dose should be continued at 2 - 4 hour intervals for 6 - 7 days. The dose protected from light. Do not freeze. It is recommended the product be used His lecture will focus on the discovery risk (e.g. ~10% for CVD). Gene-gene inter- References: interval may then be increased to 6 - 8 hours for another 2 weeks of immediately after reconstitution. treatment. Patients undergoing major surgery may be treated for up to 2 - 3 Sekar (‘Sek’) Kathiresan, a clinical car- School. He received his medical degree of genes and coding variation elated to actions have been proposed as a poten- 1. Bysted BV et al., Haemophilia 2007; 13(5): 527 – 532. 2. Windyga J et al., Ef cacy and safety of rFVIIa, used as comparator in Way of delivery: Medical prescription. development of a new rFVIIa analogue: data from a phase 3 trial on vatreptacog alfa in haemophilia patients with inhibitors. Poster weeks until healing has occurred. Authorisation holder: Novo Nordisk A/S, Bagsvaerd, Denmark. presented at: WFH 13th International Musculoskeletal Congress 2013; 2013 April 18–21, Chicago, IL, USA. 3. Young G et al., Acquired Haemophilia: diologist and human geneticist, is the from Harvard Medical School in Boston, cardiuovascular disease in humans. Two tial source of the remaining heritability. Date of last revision: April 2013. Haemophilia 2008; 14(2): 287 – 294. 4. NovoSeven® Summary of Product Characteristics. NovoSeven should be given as early as possible after the start of a bleeding director of Preventive Cardiology at Mas- MA, USA, and completed his clinical major approaches—linkage analysis and The importance of genetic markers, gene- episode. The recommended initial dose, administered by intravenous bolus For more detailed information please consult the EMEA injection, is 90 µg per kg body weight. Following the initial dose of product information. NovoSeven further injections may be given if required. The duration of sachusetts General Hospital (MGH) and a training in internal medicine and cardiol- genetic association—have been used. The gene interactions, and the usefulness of treatment and the interval between injections will vary with the severity of Novo Nordisk® is a registered trademark owned by Novo Nordisk A/S. ® choice of the optimal approach depends genetic information to understand biolog- the haemorrhage, the invasive procedures or the surgery being performed. NovoSeven is a registered trademark owned by Novo Nordisk Health Care genetics researcher in the Broad Insti- ogy at MGH. He pursued research train- The initial dose interval should be 2 - 3 hours. Once haemostasis has been AG, Thurgauerstrasse 36-38, 80 Zürich, Switzerland, Tel +41432224300. tute’s Program in Medical and Population ing in cardiovascular genetics through a on the pattern of segregation, whether ic mechanisms and to improve preventive achieved, the dose interval can be increased successively to every 4, 6, 8 or 12 hours for as long as treatment is judged to be indicated. 5146_NovoSeven_May 2013_ISTH 2013 Journal Ad Genetics. Furthermore, he is associate combined experience at the Framingham consistent with the ratios described by cardiac care, will be discussed. professor of medicine at Harvard Medical Heart Study and the Broad Institute of Mendel or more complex. Some forms of

NOVOISTH-5734_M03_CNews_Tuesday.indd PRINTED @: None INKS NOVOISTH-5734_M03_CNews_Tuesday.indd 1 Cyan, Magenta, 5/24/13 10:39 AM SAVED @: 5-21-2013 4:18 PM FROM:bljbuttino5551 BY:John Buttino / Chuck Aaron Yellow, Black JOB INFORMATION FONTS, IMAGES & INKS CLIENT CODE None IMAGES CLIENT None Braxton_Sitting_HR.tif (CMYK; 1058 ppi; 28.35%), NovoSeven-Logo-EU-CMYK.eps (44%), NN_2c_CMYK_Coated.eps (15.4%), PATIENT_Blue_SHORT.ai (72.38%), PATIENT_Blue_LONG.ai (72.38%), FRIEND_LightBlue_LONG.ai (72.38%), Stamp_HR.tif (CMYK; BLEED None 581 ppi; 51.6%) TRIM 267 mm x 185 mm SAFETY None FONTS Frutiger LT Std (45 Light, 47 Light Condensed, 66 Bold Italic, 46 Light Italic, 65 Bold, 67 Bold Condensed, 55 Roman, 56 Italic) # COLORS None 2013 XXIV Wednesday Page Netherlands CONGRESS JULY 3 8

drugs have been shown to be at least as good as, if not better than, warfarin in the prevention of embolic stroke in patients Optimising with atrial fibrillation and treatment of venous thrombosis. These anticoagulants anticoagulation may offer benefits and increased con- venience for elderly patients. No need for in the elderly routine monitoring may be a beneficial consequence of the predictable pharma- cology of new agents, but the ability to accurately measure a drug effect when needed would be highly desirable.”

Optimising anticoagulation in the elderly is still challenging, and new anticoagulant drugs have not been extensively studied in the multimorbid geriatric population. For example, the risk of falling and bleed- ing may be higher among elderly pa- tients, which makes it difficult to balance the risks and benefits of anticoagulation. The State-of-the-Art lecture of Wednes- The incidence of thrombotic disorders with atrial fibrillation, particularly in Cognitive decline could argue against day 3 July will be provided by Elaine increases with age, and use of long-term elderly patients. Risk of haemorrhage anticoagulation, because the success of Hylek from the Boston University Medi- anticoagulation has increased in elderly and erratic control are frequently cited anticoagulation depends partly on the cal Center, Boston, USA. Dr Hylek will patients. Vitamin K antagonists (VKAs) reasons for physicians not prescribing an- patient’s understanding of the risks and present her most recent work on antico- are the only oral anticoagulants currently ticoagulants to patients in this age group. benefits of this medication and mainte- agulant treatment in the elderly. available for the long-term prevention of And, as a result, states Dr Hylek, a leading nance of INR within therapeutic range. stroke in patients with atrial fibrillation, anticoagulant authority, there is a press- Elaine M. Hylek received her MD from and the primary VKA is warfarin. Howev- ing need for convenient new well-tolerat- In summary, it cannot be denied that the the University of Pittsburgh School Of er, although effective, warfarin is associ- ed and effective oral anticoagulants that new oral direct factor inhibitor anticoagu- Medicine and a Masters in quantitative ated with various challenges to its use in do not require frequent dose adjustment lants offer pharmacokinetic characteris- methods in Public Health from Harvard routine clinical practice. There are several and routine coagulation monitoring. tics of interest to patients and clinicians. University School of Public Health. Dr pharmacological and physiological fac- However, there are enough unknowns Hylek completed her residency training tors that influence its therapeutic efficacy Dr Hylek says: “Anticoagulation treat- at the present time to caution healthcare in internal medical at Massachusetts and safety, especially in the multimorbid ment has changed in the past years, as providers. Certainly, Dr Hylek could en- General Hospital and Harvard Medical geriatric population. several promising new drugs have been lighten us all during her State-of-the-Art School in Boston, Massachusetts. She is approved, such as dabigatran, a direct lecture on Wednesday. currently the Director of the Thrombosis Regardless of the evidence that warfa- thrombin inhibitor, and inhibitors of fac- and Anticoagulation Service at Boston rin is effective, numerous studies have tor Xa such as rivaroxaban, apixaban, University Medical Center. shown that it is underused in patients PRT054021, YM150 and DU-176b. These

Nurses Forum at the ISTH Congress Balancing the Dynamics of Anticoagulation The Nursing programme at the ISTH was necessarily include the need to educate initiated at the XX ISTH conference in on the nature of the disease, choice Sydney, Australia in 2005, to provide a of appropriate products used to treat, unique forum for nurses internationally to techniques for self-therapy, indications share practice related knowledge pertain- for acute treatment versus on-the-spot ing to disorders of haemostasis in both prophylaxis, availability of home care paediatric and adult populations. To date, services, financial coverage for treatment the ISTH and its congress organising and life planning (career selection, partici- committees recognise that nurses play pation in sports, etc). a key role in the care of and in promot- The programme very well illustrated the ing adherence in patients with chronic purpose of the ISTH Nurses Forum, i.e disorders of haemostasis. Nurses are vital to promote, support, and sustain sharing in their role to assess, educate, advocate, and adoption of, evidence-based practice; and optimise care for patients and are thereby facilitating knowledge translation integrally involved in clinical research. to direct patient care. This will be provid- On Saturday and Sunday preceding the ed globally through mentorship to nurses ISTH 2013 congress the Nurses Forum in their role to teach, coach, individualise, presented a comprehensive programme and intervene in applying evidence based of presentations focused at nursing practice to meet the unique needs of pa- activities in the area of thrombosis and tients with disorders of haemostasis. haemostasis. There were several presen- tations focusing on practical aspects on In addition, the Nurses Forum will sup- An innovative educational resource clinical work in haemostasis and throm- port systematic evaluation and dis- for healthcare professionals bosis, such as injections in small children, semination of practical and actionable e-learning and telemedicine applications, standardised or targeted interventions treatment adherence, and family care. for this unique patient population that is www.CoagulationCenter.com From all presentations it was clear that provided by nurses. nurses are important members of the care team because of their direct involve- Form more information refer to: https:// ment in information flow, and by virtue of www.isth.org/?page=NursesBackground their direct, one-on-one interactions with © Daiichi Sankyo Europe GmbH ∙ Zielstattstr. 48 ∙ 81379 Munich ∙ Germany patients and their families . Interactions Phone +49 89 78080 ∙ Fax +49 89 7808288 ∙ [email protected] · www.daiichi-sankyo.eu