Scientific and Standardisation Committee 2006 Report
52nd Annual Meeting of the Scientific and Standardisation Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH).
Held Oslo, Norway, June 28 - July 1, 2006
Dr Emmanuel J Favaloro
Institute of Clinical Pathology & Medical Research (ICPMR), Westmead Hospital, NSW 2145
Well, Australia didn't win the 2006 World Cup, although we did better than we have in the past. I have a suggestion for improving our chances in 2010, but more on that later. I actually missed that Italy vs Australia game, as I was in transit towards Oslo. The first leg (Sydney-Bangkok) was a Qantas flight, and the captain kept us informed. We were still 0-0 by the time the plane landed in Bangkok. Couldn't find out any information from the terminal; the TV was set to CNN and the game was not mentioned. The second leg was on a Scandinavian Airlines flight. No mention of the game until an hour before landing, when the passenger next to me (a male Swede) congratulates me on Australia winning the match 1-0, the goal coming late in the match. Apparently, the captain (speaking in some Scandinavian language) had just summarised the current World Cup status. We won! 15min later, the captain (now speaking in English) again summarises the current World Cup status and informs us that Italy won the match 1-0, the goal coming late in the match. The Swede next to me turns his head and mutters a form of apology, but re-affirming that he was sure the captain said we had won.
We lost? Well, it's a tough call. For an Australian of Italian descent, it was a no-win (no-loss?) situation. Actually, my entire family (like many others, no doubt) were caught-up in the game, and we were staunchly backing Australia to win.
The 52nd annual Scientific and Standardisation Committee (SSC) meeting of the International Society on Thrombosis and Haemostasis (ISTH) was held in Oslo, Norway, and was held between June 28th- July1st. The previous meeting (the 51st) was held in Sydney in 2005, and I reported on that meeting in an earlier issue of this newsletter. Unlike the 51st meeting, which was held in conjunction with the XXth Congress of the ISTH, this was a stand-alone SSC meeting, albeit with a plethora of satellite meetings. That is, the SSC meets every year, but the ISTH meets only every second year. I try not to attend the SSC-only meetings. Not that they are not worthwhile, but funding is always an issue, and these old bones are finding it harder and harder to cope with ‘Economy Class Syndrome'. I calculated 30 hours from door (home) to door (Oslo hotel). Nevertheless, I had some professional commitments to attend to, and so Oslo, here I am. I discovered, on later review of the participant list, that I am one of less than a dozen Australians attending the meeting. Oh well, we beat New Zealand (grand total of two participants). Overall, however, around 1500 participants are here (mostly Europeans, but a fair contingent from the USA). This is a big SSC meeting. As is the case with such meetings, there are still some concurrent sessions so it is impossible to attend them all, and so one becomes fairly selective. The following report is therefore a personal reflection of the meeting as seen by me.
I arrived the day before the conference started to help acclimatise. Recognising that Norway, at this time of year, enjoys some 21 hours of daylight may explain why this might be so. The city of Oslo does not seem to sleep. It's still light at midnight! The meeting began with a Symposium on von Willebrand Disease (vWD) - my favourite topic - on Wednesday 28th June. The Symposium was held in honour of the first publication in 1926 by Erik von Willebrand, where he describes the condition we now know as vWD, but which he called ‘hereditar pseudohemofili'. Chaired by Augusto Federici, there were talks by several ‘heavies' in the field: Robert Montgomery, Zaverio Ruggeri, David Ginsburg, Evan Sadler, Francesco Rodeghiero, Ian Peake, Dominique Meyer, and Pier Mannucci. Topics included: synthesis, structure and function of vWF; modulation of vWF function by ADAMTS-13; an update on the classification of vWD; epidemiology, clinical aspects and therapeutic management of VWD; clinical, laboratory and molecular markers of VWD; plus some room for discussion. I keep pretty up to date with the literature on vWD, so I guess I didn't ‘learn' a lot, but nevertheless a pleasure to hear the talks from such an august collection of individuals.
The next day (Thursday 29th June) was a full day. I started with an educational symposium titled: "Diet, omega-3 fatty acids & atherothrombosis" that took up the entire morning. I guess the fact that my wife (a nutritionist) asked me to attend this session was only partly to blame, as I also have some interest in nutrition related thrombosis risk. This was a very interesting session, in part perhaps because I cannot keep up with the literature, and hence did learn something. Since I don't keep up to date, the speaker's names were new to me: Frank Brosstad, Raffaele De Caterina, Ingebjørg Seljeflot, Harald Arnesen, Giovanni deGaetano, José María Ordovás. One speaker from the USA, and the remainder from Italy and Norway. Topics comprised: atherosclerosis and the haemostatic system; mechanisms of diet and n-3 PUFAs on vascular wall, platelets and atherosclerosis; mechanisms of diet and n-3 PUFAs on coagulation and fibrinolysis; results from clinical studies with omega-3 PUFAs and diet; nutrigenetics and atherothrombotic disease.
The role of diet and omega-3 in haemostasis presents with conflicting data; but, overall the studies confirm that both play a significant role. The biggest problem relates to issues of study control- compliance in diet studies, selection of appropriate controls, complexity of diets so that the contribution of individual nutrients are difficult to assess, etc, etc. Overall, however, there are many points within haemostasis that omega-3's may play a role: eg to dampen platelet activation; to reduce the expression of adhesive molecules (thus reducing potential plaque development); to reduce various markers of inflammation; affect intra-cellular expression of COX-2; reduction of cytokines; dampening of arachidonic acid pathway; reduction in tissue factor expression; reduction in serum triglycerides, PAI-1 and fibrinogen; elevation of HDL (ie the ‘good') cholesterol; etc. Much of the early work originated in Norway, when it was recognised that Eskimos had ~10% of the myocardial infarction rate of the Scandinavian population, and thought to be reflective of the high fish (oil) diet they ‘enjoyed'. I particularly enjoyed the talk by deGaetano, who spoke on the benefits of olive-oil (as an Australian of Italian descent, don't I already know this?), the ‘French Paradox' (high fat diet but relatively low CHD mortality), and the health benefits of wine consumption (in moderation, but the exact amount of ‘moderation' is not clear). Again, as a descent of Italian stock, did I not know this already? Nice to have it re-affirmed by the experts.
deGaetano went on to describe some unknown benefits of moderate wine consumption, showing comparative data of performance in the 2002 World Cup versus per capita wine consumption. There was a strong relationship! Those countries having the highest wine consumption per capita were most likely to find success in the World Cup. In contrast, the trend for beer consumption was (if anything) the reverse (countries having the highest beer consumption per capita were most likely to not succeed in the World Cup). Was deGaetano pulling our collective legs? I had to test the theory, but waited until the completion of the 2006 World Cup to gather the data. It's true! As clearly shown in the Figure below, confirmatory data for 2006 indicates that there is a strong relationship between wine consumption and the chances of success at the World Cup. Note to Australians: to ensure we do better in the 2010 World Cup, ‘drink a red before bed' (and hold back on the beer; it doesn't help).
A lunchtime Symposium on platelet function testing was of some interest (and they provided lunch - a bonus), but the highlight of the day was the afternoon session (Part 1 of the vWF/vWD SSC meeting). This was a full session, and chaired by various members of the vWF/vWD SSC, including yours truly. There were a series of reports on the recent laboratory test exercise undertaken by the vWF/vWD SSC, and involving 32 participant laboratories worldwide. Our laboratory was the sole Australian laboratory. My earlier request for them to include a few more Australian laboratories was essentially ignored for reasons unknown. The exercise was similar to that undertaken in the past by our own RCPA QAP [summarised in 1,2], in so far as a series (n=8) of plasma samples were distributed for blind testing in assays used in vWD diagnosis, and the return of test results and ‘diagnostic interpretations' by participants for analysis by the vWF/vWD SSC. The difference was that this was not a QA exercise. The laboratories involved were all considered ‘expert' vWD-testing labs, and test panels used by most of the laboratories were fairly comprehensive. All laboratories (ie 100%) performed VWF:Ag and VWF:RCo. 25 (78.1%) laboratories performed VWF:CB. 18 (56.3%) laboratories performed VWF:multimers. 20 (62.5%) laboratories performed VWF:FVIIIB. 15 laboratories (ie 46.9%) performed all five assays. Six (18.8%) laboratories performed VWF:Ag, VWF:RCo, VWF:CB and VWF:multimers (ie no VWF:FVIIIB). Three (9.4%) laboratories performed VWF:Ag, VWF:RCo and VWF:multimers (ie no VWF:FVIIIB or VWF:CB). One laboratory (3.1%) performed VWF:Ag, VWF:RCo and VWF:CB (ie no VWF:FVIIIB or VWF:multimers). Two (6.3%) laboratories performed VWF:Ag and VWF:RCo (ie no VWF:FVIIIB or VWF:CB or VWF:multimers).
The study was hoping to determine which tests, test methodologies and test panels, are best at identifying and subtyping vWD (?sounds familiar; [1,2]). I was pleased to report that the vWF:CB outperformed the vWF:RCo in terms of identifying the loss of high molecular weight (HMW) vWF associated with Types 2A and 2B vWD (have you heard this before? [1,2]). Type I (/III mixture collagens) performed better than purified Type III collagens (again, sounds familiar; [3,4]). However, the vWF:RCo was better at identifying the Type 2M vWD sample. Overall, efficacy of performance of vWF:CB was collagen-source related, whereas performance of vWF:RCo was more random-event related (high variability) plus related to poor sensitivity at low levels of vWF (I know, you have heard it all before). As mentioned, there were several other speakers (Augusto Federici, Jeroen Eikenboom, Christine Lee, Ken Friedman, Giancarlo Castaman, Ulrich Budde, Claudine Mazurier, Caroline Sabin) that provided information about other aspects of the study (eg vWF:Ag, vWF:RCo, multimers, statistics, diagnosis). The data is planned to be published in the Journal of Thrombosis and Haemostasis (JTH) later this year. If you want to ‘hear' more about it, I intend to give a talk updating vWF/vWD at both the forthcoming HSANZ meeting (October 14th at the ASTH Workshop) and the AIMS meeting (also October; possibly a breakfast session?) in Hobart later this year.
I gave another talk at this (Part 1) vWF/vWD session on pre-analytical variables in vWD testing, and highlighted the issue of cold-transport/storage of whole citrate blood related problems. Later speakers at this session included: Evan Sadler, who spoke on the updated vWD classification scheme (as well, a vote was undertaken in favour to publish this update in JTH); Anne Goodeve, Lysiane Hilbert and David Lillicrap, who spoke on vWF molecular biology and expression studies; Zaverio Ruggeri and Armin Reininger, who spoke on laboratory assays dependent on shear stress - perhaps the future? There was also a talk on the use of vWF propeptide as a marker of vWF survival in certain vWD subtypes. This was a session at which I did learn or consolidate knowledge on vWF/vWD!
The meeting part of the day was over, and we all hurried to the Oslo Town Hall to be officially welcomed to Oslo. The mayor gave a resounding speech in the building where they award the Nobel prizes. I am not likely to be here again, so I wandered through the palatial building with some colleagues. After the Welcome ceremony, I had my first Norwegian beer with some UK colleagues including one currently based in Australia. (I know, didn't I say we should preference the red?). Beers are very expensive in Oslo, as are most things. Did I mention that Oslo is now considered the most expensive city in the world, having recently overtaken Tokyo? At least the cost of beer prevents you from over-doing it. Around 11:30 pm (although the sun was still up and it felt like around 6pm) I bid my colleagues farewell. I felt I needed to get some sleep. Unfortunately, all the ‘Oslo-ians' had a different idea, and it didn't quieten down till around 3 in the morning.
The next day, a little weary-eyed, I also braved another very full day. The day began with Part 2 of the vWF/vWD SSC meeting, with most of the session devoted to ADAMTS13 and TTP. Several speakers presented data on this topic. I'm sure that some of the data was the same as that presented last year in Sydney. The FRETS-VWF73 assay seems among the most promising. It's now available commercially, but is very expensive and requires a fluorescence plate reader. I guess I will wait a few more years before I do this assay in my lab. The rest of the session was taken up by some short presentations on acquired vWD, auto-antibody assays in acquired vWD, use of vWF pro-peptide in helping to characterise vWD patients, and various working party reports (DDAVP in vWD; allo-antibodies in Type 3 vWD; and vWD prophylaxis). I was brain-full when the current vWF/vWD SSC chairman, Augusto Federici, finally concluded the program.
Lunch was a ‘committee meeting', comprising representatives from an international collection of haemostasis related external QAPs. I was representing our RCPA QAP (haemostasis) at this meeting. We are trying to foster co-operation and collaboration among the various EQAPs. The hope is to develop some consensus towards ‘world best practice' as well as to possibly conduct some international QA exercises that would be unlikely to be done internally. As an example, this group hopes to get together to run an exercise for vWD Type 2N. In our geographic region, there are only a few labs (?2-4) doing the test (vWF:FVIII binding assay), so it is unlikely that the RCPA QAP can conduct a meaningful test exercise on its own; however, the exercise would be quite valuable as a broad international exercise.
For me, the afternoon was a mixture of sessions. vWD/vWF was ‘done', but a variety of other sessions was available. I settled into the factor VIII and IX session, to hear about detection of factor inhibitors. We heard of the usual problems. Poor reproducibility and wide scatter of results, using data from a recent ECAT survey. NIBSC has been recently involved in attempting to generate a FVIII inhibitor standard. Again, there is wide scatter of data even among the experts. The RCPA QAP recently conducted an exercise in inhibitor identification in 2005 that has recently been published . Alison Street presented the data on behalf of the RCPA QAP at a recent international meeting (the World Federation for Haemophilia meeting; held in Vancouver, Canada, in May, 2006). She reported that the talk was well received. The opportunity to present the data at the ISTH SSC meeting did not present itself.
Back at the hotel that evening I discovered that the World Cup was being telecast at a decent time (~6-7pm), so settled in to watch some soccer. The next day, Saturday 1st July marked the last day of the meeting. Again, there were more concurrent sessions, and again, it was a case of moving around. I was beginning to get home sick, so my heart may not have been in it any more. Most participants left Oslo later that day as the meeting concluded around midday. I couldn't get a flight back this day (possibly all the Aussie World cup participants were coming home?), so had to wait until late the next day to depart. There was nothing else for it, so I went museum hopping... the Kon-Tiki museum, the Fram polar ship/Maritime Museum and the Viking Museum, plus a tour of Oslo was in order. In the evening, another World Cup game of soccer!
A long flight back to Australia (another 30hrs door to door), and welcomed home early morning (~6am landing time). I'm a work-aholic, so I admit to going to work that day. I survived until around 9pm. In support of the cause, I had a red (or two) before bed. World cup 2010 here we come!
See you in Hobart in October (at the HSANZ ASTH Workshop and/or the AIMS meeting).
- Favaloro EJ, Bonar R, Kershaw G, Sioufi J, Thom J, Baker R, Hertzberg M, Street A, Lloyd J, Marsden K (on behalf of the RCPA QAP in Haematology). Laboratory diagnosis of von Willebrand Disorder: Use of multiple functional assays reduces diagnostic error rates. Laboratory Hematology, 2005; 11: 91-97.
- Favaloro EJ, Bonar B, Kershaw G, Sioufi J, Baker R, Hertzberg M, Street A, Marsden K (on behalf of the RCPA QAP in Haematology) . External peer review quality assurance testing in VWD: the experience of the RCPA Quality Assurance Program. Seminars in Thrombosis and Hemostasis, 2006; 32: 505-513.
- Favaloro EJ. Collagen binding assay for von Willebrand Factor (VWF:CBA): Detection of von Willebrands Disease (VWD), and discrimination of VWD subtypes, depends on collagen source. Thrombosis & Haemostasis, 2000; 83: 127-135.
- Favaloro EJ. Detection of von Willebrand Disorder (VWD) and identification of qualitative von Willebrand Factor (VWF) defects: Direct comparison of commercial ELISA-based ‘VWF:Activity' options. American Journal of Clinical Pathology, 2000; 114: 608-18.
- Favaloro EJ, Bonar R, Duncan E, Earl G, Low J, Aboud M, Just S, Sioufi J, Street A, Marsden K (on behalf of the RCPA QAP in Haematology Haemostasis Committee). Identification of factor inhibitors by diagnostic haemostasis laboratories: A large multi-centre evaluation. Thromb Haemost 2006; 96: 73-78.