Thrombosis News - Sylvia Haas's Antithrombotics Weekly
Emeritus Professor Sylvia Haas, MD
Sylvia Haas is Emeritus Professor of Medicine and was Director of the Haemostasis and Thrombosis Research Group at the Institute for Experimental Oncology and Therapy Research, Technical University of Munich, Germany. Her scientific focus is the development of new antithrombotic therapies, laboratory monitoring of anticoagulants, biomarkers, and tumour-associated thrombosis. She is a member of several international professional societies and is on the editorial boards for several peer-reviewed journals. Click here for a full biography.
Aspirin: Use in patients with non-valvular atrial fibrillation in GARFIELD-AF
London 19th September 2016
The use of antiplatelets – even aspirin – is not risk-free. Aspirin increases the risk of major bleeding by up to 70% and provides fairly minimal stroke protection as a trade-off. While the ESC Guidelines for the management of atrial fibrillation (AF) do not recommend the use of antiplatelet therapies for stroke prevention in patients with CHA2DS2-VASc =1, the AHA Guidelines suggest aspirin, oral anticoagulants, or no antithrombotic therapy in such low-risk patients. The indicated use of antiplatelet therapy relates to patients who have a history of peripheral vascular artery disease, acute coronary syndromes (ACS), coronary artery disease, and/or stroke in addition to non-valvular AF.
Find full article here: GARFIELD-AF Symposium ESC (Week 25)
GARFIELD Score: A novel machine-learning tool for risk stratification
London 12th September 2016
The recent update to the ESC guidelines for the Management of Atrial Fibrillation (AF) highlights the need for improved risk stratification to determine which patients at low risk of stroke will do well on anticoagulation. Identifying patients with AF and truly low thromboembolic risk is challenging, and these patients are usually poorly characterised by the CHA2DS2-VASc score.
Find full article here: GARFIELD-AF Symposium at ESC (Week 24)
Can we do better at identifying who might benefit from anticoagulation?
London 5th September 2016
The need to better stratify the risk of stroke to anticoagulate the right patients
While anticoagulation is effective at reducing the risk of atrial fibrillation-related stroke, it carries the risk of potentially dangerous bleeding. This means we can’t simply give everybody an anticoagulant. We need to carefully choose which patients receive an anticoagulant, so that the reduction in stroke risk outweighs the increase in the risk of critical bleeding.
Find full article here: GARFIELD-AF Symposium ESC (Week 23)
The need to do more
London 29th August 2016
The latest GARFIELD-AF data were presented and discussed at the GARFIELD symposium held at the European Society of Cardiology’s meeting in Rome. One presentation addressed the issue of evaluation of prescribing of NOACs and VKAs. The prospective patient enrollment into GARFIELD-AF started in 2010, i.e. at the end of the vitamin K antagonist (VKA)-only era, providing insights into changes in treatment patterns. GARFIELD-AF is able to show us how prescribing of anticoagulants has changed over the last 5 years, and importantly, what informs prescribing decisions. With these data we can see if the right patients are getting the right drugs, and if not, see if there’s anything we can do about it.
Find full article here: GARFIELD-AF Symposium at ESC in Rome (Week 22 Part Two)
Real-world evidence and the GARFIELD-AF Symposium at ESC in Rome
London 29th August 2016
Over the last few months we’ve seen how the first, faltering steps towards targeted therapeutic prevention and treatment of blood clots have taken us to where we are today: on the cusp of a new era of safer and more effective anticoagulation. What we need to ask ourselves now is, are the novel anticoagulants having the desired effect in clinical practice? Are the people who need them most actually being given the opportunity to benefit? And… how can we answer such questions?
Find full article here: GARFIELD-AF Symposium ESC in Rome (Week 22 Part One)
NOACS in the Real World: What if an anticoagulated patient bleeds?
London 22nd August 2016
Bleeding in anticoagulated patients is common: major bleeding is reported to occur in 1–5% of patients with atrial fibrillation per year, and intracranial bleeding occurs in 0.5–1.2%. Furthermore, bleeding is an independent risk factor of subsequent cardiovascular events: major bleeding is associated with a 3 to 5-fold increase in thrombotic events and death.
Find full article here: Thrombosis Management Barcelona (Week 21)
How do we optimise combination antithrombotic therapy in patients with atrial fibrillation and a requirement for stenting?
London 15th August 2016
This question has become the most frequently asked, turning up in every educational meeting I have attended! Providing the best care for patients with non-valvular atrial fibrillation (NVAF) and a need for percutaneous coronary intervention or with acute coronary syndromes (PCI/ACS) is a challenging unmet clinical need.
Find full article here: Thrombosis Management Barcelona (Week 20)
NOACs in the real world – What are the dosing issues?
London 8th August 2016
In contrast to vitamin K antagonists, NOACs don’t require individual laboratory-adjusted dosing. However, guidance is provided by all manufacturers, in the summaries of product characteristics, for dosing in special patient populations. In the pivotal phase III trials of NOACs for the prevention of stroke in patients with non-valvular atrial fibrillation, reduced doses were tested according to different patient characteristics.
Find full article here: Thrombosis Management Barcelona (Week 19)
NOACs in the real world. What if … I have valvular AF?
London 1st August 2016
The term non-valvular atrial fibrillation (NVAF) is being used with increasing frequency in the context of patients with an indication for stroke prevention with NOACs. The term itself was not clearly defined before the pivotal NOAC trials were performed. This created uncertainty regarding in which patients the NOACs could actually be used. It was only recently that the European Society of Cardiology (ESC) and American Heart Association (AHA) Guidelines became less vague regarding what we mean by ‘non-valvular’ (Savelieva I and Camm AJ. Clin Cardiol. 2014;37:32-47; January CT et al. J Am Coll Cardiol. 2014;64:e1-76).
Find full article here: Thrombosis Management Barcelona (Week 18)
NOACs in the real world. What if … I have reduced kidney function?
London 25th July 2016
Preventing strokes with anticoagulants needs a two-sided risk assessment: that is, balancing the risk of major bleeding against the risk of stroke. This can be a dilemma in patients with atrial fibrillation (AF), because a high risk for stroke correlates with a high risk of bleeding. For example increasing age and decreasing renal function are major contributors to both.
Find full article here: Thrombosis Management Barcelona (Week 17)
Can AF trial results be translated into clinical practice?
London 18th July 2016
As we concluded in week 12 and week 15, NOACs have a favourable risk-benefit profile, showing significant reductions in stroke, intracranial haemorrhage and mortality. They have similar overall major bleeding as VKAs, although gastrointestinal bleeding rates were higher under clinical trial conditions. The relative efficacy and safety of these compounds was consistent across a wide range of patients with different clinical characteristics.
Find full article here: Thrombosis Management Barcelona (Week 16)
What is the burden of atrial fibrillation, and what has been achieved with NOACs?
London 11th July 2016
A severe burden
Atrial fibrillation (AF) is the most common heart rhythm disorder. The lifetime risk for developing AF is 1 in four for people 40 years and older. In the USA, about 2.2 million adults have AF. This number is predicted to increase to almost triple by the year 2050, as the proportion of elderly people in the population increases.
Find full article here: Thrombosis Management Barcelona (Week 15)
The female heart beats to a different drum...
London 4th July 2016
Interestingly, women generally have a lower age-adjusted incidence and prevalence of atrial fibrillation (AF) than men (Ko D et al. Nature Reviews Cardiology doi:10.1038/nrcardio.2016.45). However, women with AF are more likely to present with symptoms including weakness, fatigue, dyspnoea, palpitations, light-headedness and chest discomfort. They will often experience symptoms for longer than men, leading to a poorer quality of life.
Find full article here: Cardio Femme Congress in Haifa June 23, 2016 (Week 14)
Can VTE trial results be translated into clinical practice?
London 27th June 2016
As we were reminded at Thrombosis Management, phase III clinical trials have shown NOACs to be at least as efficacious as, and safer than, standard of care (SoC) for the treatment and secondary prevention of venous thromboembolism (VTE). Clinical trials have restrictive inclusion and exclusion criteria, however, and observational studies (phase IV and registries) are needed to see how the results of clinical trials work out in everyday clinical practice – in patients in the "real world". We refer to such studies collectively as ‘real-world’ evidence or experience.
Find full article here: Thrombosis Management Barcelona (Week 13)
What is the burden of venous thromboembolism and what has been achieved with NOAC?
London 20th June 2016
As we saw back in April, the disease of venous thromboembolism (VTE) has been recognized since ancient times. However, we only began to understand its pathogenesis as we learned to treat it effectively, in the middle of the previous century. VTE is a common condition. It is associated with an immense personal and healthcare system burden. In Europe alone, over half a million people die from VTE (most likely pulmonary embolism; PE) each year. The global mortality is estimated at 3 million every year – one person every 10 seconds.
Find full article here: Thrombosis Management Barcelona (Week 12)
So at last we come right up-to-date, with the annual Thrombosis Management meeting.
London 13th June 2016
Thrombosis Management is a CME-accredited educational meeting that brings together healthcare professionals from all over the world. It gives them the opportunity to learn about and discuss the latest clinical developments in thromboembolic disease management, and –most importantly – explore how best to put them into practice for the benefit of their patients.
Find full article here: The Modern Era (Week 11)
Progress in Anticoagulation: From Blood Sucking Animals to Pill
London 6th June 2016
Leeches have been used in medicine for thousands of years. But their anticoagulant effect was not reported until 1884, when John Berry Haycraft described the difficulty of stopping bleeding from leech bites. It took another 20 years before Carl Jacoby and Friedrich Franz were able to prepare an extract from leech heads that mirrored the anticipated anticoagulant activity – an extract they named hirudin.
Find full article here: From serendipity to targeted drugs (Week 10 Part Two)
Progress in Anticoagulation: From shotgun to single target anticoagulation
London 6th June 2016
For decades, there were only two anticoagulants, both discovered by chance: unfractionated heparin (UFH) and the vitamin K antagonists (VKAs). Despite their substantial limitations, they led to great advances in medicine. For example, haemodialysis and extracorporeal circulation would have been impossible without heparin; heparin and VKAs are inseparable partners in the treatment of venous thromboembolism (VTE); and VKAs remain an essential part of stroke prevention in atrial fibrillation.
Find full article here: From serendipity to targeted drugs (Week 10)
Coagulation Cascade: Numbers and Names
London 30th May 2016
For the development of safer and more effective anticoagulation, a better understanding of the coagulation process was needed. While the two-phase process reported by Paul Morowitz in 1904 was accepted, there was still some uncertainty about the details of the components involved.
Find full article here: From serendipity to targeted drugs (Week 9)
Warfarin: From rat poison to life saver
London 23rd May 2016
Just as Ed Carlson’s odyssey through the snowstorm to meet Karl Link triggered Link’s breakthrough discovery, the clinical development of warfarin was also sparked by a memorable incident. In 1951, a marine attempted suicide with warfarin, but was unsuccessful. In fact, he made a complete recovery, and this surprising outcome prompted the first clinical studies of warfarin as a therapeutic anticoagulant. Warfarin was soon registered under the trade name Coumadin®, and in 1954 it was approved by the US Food and Drug Administration (FDA) for medical use.
Find full article here: From serendipity to targeted drugs (Week 8)
From herds of cattle to warfarin:
The discovery and early development of coumarin derivatives
London 16th May 2016
The history of another effective pharmacological anticoagulant is no less complex, or apparently random, than that of heparin. In the 1920s, cattle in the US and Canada were dying in mysterious circumstances. Veterinary investigations blamed internal bleeding, supposedly caused by feeding the animals inadequately dried sweet-clover hay, giving rise to the name “sweet-clover disease”. In the past farmers had simply disposed of damp, mouldy hay; however, many were forced to use it as animal feed during the economic depression of the 1920s and 30s. In 1929, veterinary surgeon Lee Roderick showed that the acquired coagulation disorder was caused by what he called a “plasma prothrombin defect”. The advice from veterinarians was simple: don’t feed mouldy hay to animals.
Find full article here: From serendipity to targeted drugs (Week 7)
Standardisation of heparin: Weighing gold on a cattle balance
London 9th May 2016
In the 1920s, the road from the laboratory to the hospital was much shorter than it is today. After Jay McLean’s discovery in 1916, and further development by William Howell, heparin was soon available commercially to treat thrombosis, even though not adequately purified and standardised.
Find full article here: From serendipity to targeted drugs (Week 6)
Thrombosis and its management in the early 20th century - Initial steps towards thromboprophylaxis and -treatment
London 2nd May 2016
The theory of infectology was dominant at the beginning of the early 20th century, with many scientists believing that infection played a role in thrombus development. Avoiding infection was seen as an early method of thromboprophylaxis. At this time, the awareness of the relationship between contemporary methods of trauma treatment and thrombosis was low.
Find full article here: From serendipity to targeted drugs (Week 5)
Rudolf Virchow – The ‘Thrombosis Adviser’ most comprehensive in scope?
London 25th April 2016
When Rudolf Virchow described changes in blood composition, changes in blood flow and changes in the vascular wall as the three pillars of thrombogenesis in his classic book Thrombose und Embolie in the 19th century, his focus was exclusively on venous thromboembolism.
Find full article here: From serendipity to targeted drugs (Week 4)
“If we go to the last frontier, where there are still elements with the character of totality… we come to the cells.” — Rudolf Virchow
London 18th April 2016
It was 160 years ago that Rudolf Virchow introduced the modern view of thromboembolism, in his classic book Thrombose und Embolie. He proposed the three pillars of thrombogenesis, which have established themselves in history as “Virchow’s Triad”: changes in the composition of the blood; changes in the flow of the blood; and changes in the blood vessel wall.
Find full article here: From serendipity to targeted drugs (Week 3)
“I retested again and again until I was satisfied that an extract of liver… possessed a strong anticoagulant action” — Jay McLean
London 11th April 2016
First I want to thank you so much for your great feedback on my first post last week. I received dozens of private messages which is very motivating to continue. Thus, let's start with this week’s installment of our tour of the history of anticoagulation, where I want to take a quick look at what we may call the start of the modern era of pharmacological anticoagulation.
Find full article here: From serendipity to targeted drugs (Week 2)
From serendipity to targeted drugs
London 3rd April 2016
This year marks 100 years since the discovery of heparin. I have dedicated some decades of my life to the exciting and fast-evolving field of antithrombotic therapies as a Professor of Medicine at the Technical University of Munich. Now I would like to take the opportunity of this centenary to share with you some personal thoughts about the history of thrombosis and coagulation research. This foray into the past is my way of describing the ‘stony road’ of anticoagulation, but it also opens the possibility for comments and discussion. I would be pleased to invite my many fellows and companions to join me on what I hope will become a virtual journey – from serendipity to targeted antithrombotics.
What can you expect? Find full article here: From serendipity to targeted drugs (Week 1)