Hemostasis and Malignancy

Chairperson: Martin H Prins (NL)

Co-Chairpersons: Giancarlo Agnelli (IT), Dominique Claire Farge (FR), Charles W Francis (US), Alok A. Khorana (US), Agnes Y. Y. Lee (CA)

Moderator: Martin H. Prins (NL)
Coagulation as a biological target for cancer therapy Frederick R. Rickles (US)	8:00 - 8:30 AM
Predicting cancer patients at risk for venous thromboembolism: Strategies for prophylaxis Alok A. Khorana (US)	8:30 - 9:00 AM
Diagnosis and management of cancer-associated thrombosis Agnes Y. Y. Lee (CA)	9:00 - 9:30 AM

This session will discuss the relationship between cancer and coagulation. Thrombosis is not only a common complication of cancer but coagulation might also play a role as a biological target for cancer therapy. Experimental and clinical evidence for the role of anticoagulants in cancer therapy will be discussed. While it is clear that cancer patients who have surgery should receive prophylaxis, it is unclear which cancer patient (if at all) deserves prophylaxis in the absence of surgery. Hence, it might be important to identify cancer patients at risk for venous thromboembolism to improve research in strategies for prophylaxis. Finally, the issues specific to cancer patients in the diagnosis and management of their thrombosis will be discussed.

 

Program unavailable at time of printing. Go to www.isth.org for the most current program.

Vascular Biology

Chairperson: Jean-Marie Freyssinet (FR)
Co-chairpersons: Michael C. Berndt (IE), Françoise Dignat-George (FR), John H. Griffin (US), Peter J. Newman (US)

Shed proteins/receptors as clinical biomarkers of vascular disease Moderator: Peter J. Newman (US)
Exploring the platelet sheddome Lawrence Brass (US)	8:00 - 8:30 AM
Translating the mechanism of GPVI shedding: Soluble GPVI as a clinical biomarker Michael Berndt (IE)	8:30 - 9:00 AM
Platelet aging and ectodomain shedding Simone Schoenwaelder (AU)	9:00 - 9:30 AM

There is growing realization that certain cell surface receptors are shed from the surface of blood and vascular cells as a result of their activation - perhaps as a mechanism to dampen the adhesive properties of the cell. A second consequence of platelet activation is the secretion of the contents of specialized granules, some of which have the potential to support endothelial cell growth, stem cell differentiation, and tumorigenesis. This 90 minute session will highlight recent progress in the identification and characterization of the so-called platelet sheddome and platelet secretome, with an emphasis on how such fluid-phase proteins can both affect vascular physiology and report vascular disease.

Predictive Variables in Cardiovascular Disease

Chairperson: Gordon D. Lowe (UK)

Co-Chairpersons: James Douketis (CA), Veikko Salomaa (FI), Alberto Tosetto (IT)

Women's Health in Thrombosis and Hemostasis

Chairperson: Andra H. James (US)

Co-Chairpersons: Margareta Blomback (SE), Benjamin Brenner (IL), Jacqueline Conard (FR), Sabine Eichinger (AT), Barbara A. Konkle (US), Claire McLintock (NZ), Claire S. Philipp (US)

  

Introduction and Overview
Chairperson: Andra H. James (US)
Welcome Purpose and function of SCC's What constitutes issues in women's health in thrombosis and hemostasis Introduction of co-chairs and their comments	8:00 - 8:15 AM
Educational Activities
Chairperson: Benjamin Brenner (IL)
Report on the Women's Health Issues in Thrombosis and Haemostasis Symposia	8:15 - 8:30 AM
Report on publications Update on registries	8:30 - 8:45 AM

  

Pregnancy outcome in women with mechanical heart valves	8:45 - 8:55 AM
Mirena IUD for menorrhagia in women with bleeding disorders Rezan Kadir (UK)	8:55 - 9:05 AM
Corpus luteum bleeding in women with bleeding disorders	9:05 - 9:15 AM
Update on ongoing international collaborations
Menorrhagia in women affected by bleeding disorders Flora Peyvandi (IT)	9:15 - 9:25 AM
Other new and proposed projects including registries 2 randomized trials of anticoagulation in women with a history of poor pregnancy
HEPRIN Anne McLeod (CA)	9:30 - 9:40 AM
TIPPS	9:40 - 9:50 AM
Laboratory analyses in habitual abortion Margareta Blombäck (SE)	9:50 - 10:00 AM
Break	10:00-10:30 AM

Moderator: Andra H. James (US)   

Identifying women with menorrhagia for hemostatic evaluation
Claire S. Philipp (US)	10:30 - 11:00 AM
Anticoagulation during pregnancy/ Debate: Inherited thrombophilia and pregnancy complications - anticoagulation? (Yes)
Benjamin Brenner (IL)	11:00 - 11:30 AM
Anticoagulation during pregnancy/ Debate: Inherited thrombophilia and pregnancy complications - anticoagulation? (No)
Marc A. Rodger (CA)	11:30 - 12:00 AM

Dr. Philipp will discuss her experience developing a screening tool for stratifying women with unexplained menorrhagia for hemostatic testing for underlying bleeding disorders. Recently, she and her colleagues completed a study of 146 women with a physician diagnosis of menorrhagia who underwent comprehensive hemostatic testing for the diagnosis of bleeding disorders, including von Willebrand disease, platelet dysfunction, and coagulation factor deficiencies. Bleeding symptoms with high predictive values for laboratory hemostatic abnormalities were combined and used as single variables to calculate sensitivity, specificity, and positive and negative predictive values in order to develop a short screening tool. Dr. Phillip will discuss the results of the study. A combination of 8 questions in 4 categories resulted in a sensitivity of 82% (95%CI 75-90) for bleeding disorders. Adding a pictorial blood assessment chart score > 100 increased the sensitivity of the screening tool to 95% (95%CI 91-99). Adding the PFA-100 did not increase the sensitivity for bleeding disorders overall, though sensitivity for VWD was increased.

Dr. Brenner will present one side of the debate: Inherited thrombophilia and pregnancy complications - anticoagulation? (Yes) Inherited thrombophilias are associated with gestational vascular complications including three or more first trimester losses, two or more second trimester losses, or any stillbirth; early, severe or recurrent preeclampsia and severe intrauterine growth restriction. Furthermore, low-molecular-weight heparin is safe and effective in preventing pregnancy loss and decreasing the recurrence of placental-mediated complications in women with both acquired and inherited thrombophilia.

Dr. Rodger will present one side of the debate: Inherited thrombophilia and pregnancy complications - anticoagulation? (No) Inherited thrombophilias are not yet established as a cause of placenta-mediated pregnancy complications, such as fetal growth restriction, preeclampsia, abruption, and pregnancy loss. An inherited thrombophilia is only one of many factors that lead to development of these diseases and is unlikely to be the unique factor that should drive management in subsequent pregnancies. The paucity of evidence for benefit, coupled with a small potential for harm, suggests that low molecular weight heparin should be considered an experimental drug for these indications until data from controlled trials are published. At present, women with a history of placenta-mediated pregnancy complications, with or without a thrombophilia, should be followed closely without routine prophylactic low molecular weight heparin other than for prevention of venous thromboembolism in limited circumstances.

Platelet Immunology

Chairperson: Andreas Greinacher (DE)

Co-Chairpersons: Beng H. Chong (AU), Yves Gruel (FR), Volker Kiefel (DE), Hartmut Kroll (DE), Theodore Warkentin (CA)

   

Welcome
Andreas Greinacher (DE)	8:00 - 8:05 AM
PART 1. Autoimmune thrombocytopenia
Chairpersons: Beng Chong (AU) and Hartmut Kroll (DE)
Standardization of terminology and definitions in ITP: On which topics has a consensus been reached and what are the open issues Francesco Rodeghiero (IT)	8:05 - 8:20 AM
Discussion: Does the Platelet Immunology SSC agree with the consensus?	8:20 - 8:30 AM
Update: PARC study new lessons learned, new questions arising from systematically collecting and following ITP adult and pediatric ITP patients Paul Imbach (CH) and T. Kühne (CH)	8:30 - 8:45 AM
Discussion: Are there specific questions of the Platelet Immunology SSC which could be answered by the PARC study?	8:45 - 8:55 AM
Platelet antibodies in well-defined populations of patients with ITP Donald Arnold (CA)	8:55 - 9:05 AM
Discussion	9:05 - 9:10 AM
GPIIbIIIa and GPIbIX glycoproteins sufficient for platelet autoantibody
testing?	9:10 - 9:20 AM
Discussion	9:20 - 9:25 AM
Break	9:25 - 9:35 AM
Discussion for a Statement of the Platelet Immunology SSC on the role of platelet antibody testing in the time of new therapeutic options for ITP: Is there a role for platelet autoantibody testing in patients with ITP?
Discussion	9:35 - 10:00 AM
Statement for the SSC chair Volker Kiefel (DE)	10:00- 10:05 AM
PART 2.	10:05- 10:45 AM
Heparin-induced thrombocytopenia

Chairpersons: Yves Gruel (FR) and Theodore Warkentin (CA)
How to improve the clinical use of antigen assays in HIT

Combining quantitative interpretation of PF4-dependent EIA's and high heparin Karina Althaus (DE)	10:05-10:20 AM
Towards genetics in HIT Yves Gruel (FR)	10:20-10:35 AM
Last Minute Contributions	10:35-11:00 AM

 

Moderator: Volker Kiefel (DE)
Laboratory testing for heparin-induced
thrombocytopenia
Theodore E. Warkentin (CA)	11:00 - 11:30 AM
Drug-induced immune thrombocytopenias
Richard Aster (US)	11:30 - 12:00 PM

The educational session will focus on two important issues related to drug-induced immune reactions towards platelets. Heparin-induced thrombocytopenia is by far the most frequent drug induced antibody response, and the lecture will provide a comprehensive overview on the different assays currently available and an appraisal of their role in clinical practice. Drug-induced immune thrombocytopenias are less frequent but can be associated with severe bleeding. Recent data provide new concepts on the understanding of the pathogenesis of the immune response. Both speakers are internationally respected experts in these topics.

Factor VIII and IX

Chairperson: Alok Srivastava (IN)

Co-Chairpersons: Charles Hay (UK), Christine Lee (UK), Claude G. Negrier (FR), Johannes Oldenburg (DE), Flora Peyvandi (IT), Jean-Marie Saint-Remy (BE), Edward G D Tuddenham (UK)

    

Note: An additional Factor VIII and IX SSC Business Session, and Educational Program, will be held on Saturday 2:00 - 6:00 PM.
Part 1
Welcome and Introduction
Alok Srivastava (IN)	8:00 - 8:05 AM
Completed/Submitted reports and recommendations
Alok Srivastava (IN)	8:05 - 8:10 AM
Rare bleeding disorders
Chairpersons: Flora Peyvandi (IT) and Christine A. Lee (UK)
Overview
Flora Peyvandi (IT) and Christine A. Lee (UK)	8:10 - 8:15 AM
European Network of Rare Bleeding Disorders (ENRBDs)
Flora Peyvandi (IT)	8:15 - 8:30 AM
North American Registry of Rare Bleeding Disorders
Amy Shapiro (US)	8:30 - 8:45 AM
Standardization of assays: FVII and FXI
Steven Kitchen (UK)	8:45 - 9:00 AM
Thrombin Generation in RBDs
Waander van Heerde (NL)	9:00 - 9:15 AM
A new Factor X concentrate: Clinical issues
Clive Dash (UK)	9:15 - 9:30 AM
Recombinant FXIII: Early data
Kim Jacobsen (DK)	9:30 - 9:45 AM
General discussion / Future directions	9:45 - 9:55 AM

Break	9:55- 10:00 AM
Factor VIII/IX: Clinical issues- I (Assay / EQA / Phenotype)
Chairpersons: Claude Negrier (FR) and Alok Srivastava (IN)
Overview: Tests of global hemostasis
Claude Negrier (FR) and Alok Srivastava (IN)	10:10- 10:15 AM
Systematic approach to the assay discrepancies between one and two-stage assays
Johannes Oldenburg (DE)	10:15- 10:30 AM
Factor VIII assay - A new paradigm
Edward Gomperts (US) and Kenneth Mann (US)	10:30- 10:45 AM
Assays for global hemostasis in hemophilia: Correlation with adjuvant therapeutic options
Benny Sorensen (UK)	10:45- 11:00 AM
Comparison of TEG / TGT / Wave form analysis in clinical samples of hereditary bleeding disorders
Sukesh C. Nair (IN)	11:00- 11:15 AM
Global hemostasis tests in hemophilia Early data and a systematic study plan
Claude Negrier (FR)	11:15- 11:30 AM
General discussion	11:30- 11:40 AM
General discussion The agenda of the SSC: What are the priorities?
General discussion	11:40- 12:00 PM

 

APSTH-ISTH Symposium

Moderator: Yukio Ozaki (JP)
Coagulopathy in Malaria Pantep Angchaisuksiri (TH)	12:15 - 12:40 PM
Use of Asian snake venom inhibitors in studies of blood coagulation mechanism Takashi Morita (JP)	12:40 - 1:05 PM
Coagulopathy induced by snake bites and its management Geoff Isbister (AT)	1:05 - 1:25 PM
Genetic disorders related to coagulopathy prevalent in the Far East Toshiyuki Miyata (JP)	1:25 - 1:45 PM

The Asian-Pacific Society on Thrombosis and Hemostasis (APSTH) was founded 11 years ago, and with the help of ardent activities of its members, it has contributed immensely to the development of research and clinical studies related to thrombosis and hemostasis in Asian-Pacific countries. The APSTH has the membership of more than 350 members from Australia, Cambodia, China, India, Indonesia, Japan, Korea, Malaysia, Mongol, Philippines, Singapore, Taiwan, Thailand, and Vietnam. We have had 5 APSTH Conferences in Taiwan, Korea, Thailand, China, and Singapore, and the 6th Conference of APSTH will be held in Indonesia in 2010. Please visit the website of APSTH: http://www.jsth.org/apsth/index.html The APSTH-ISTH joint symposium was held at the Sydney ISTH Conference in 2005, and at the Geneva ISTH Conference in 2007, focusing on the diseases related to thrombosis and hemostasis prevalent in the Asian-Pacific area. The joint symposium at the Boston ISTH Conference will deliver to the audience comprehensive introduction on coagulopathy in malaria, use of Asian snake venom inhibitors in studies of blood coagulation mechanism, coagulopathy induced by snake bites and its management, and genetic disorders related to coagulopahty prevalent in the Far East.

 

Genomics 101

Moderator: Willem Ouwehand (UK)

The genetic architecture of thrombosis and bleeding:   

Rare mutations and common SNP's
Pieter H. Reitsma (NL)	12:15 - 12:45 PM
The architecture of genome-wide SNP studies: New examples including fibrinogen, vWD, FVII and VFII
Andrew Johnson US)	12:45 - 1:15 PM
Small steps in a long journay: The discovery of risk loci for cardiovascular disease
Willem Owehand (UK)	1:15 - 1:45 PM

A large number of common diseases have a substantial heritability. It has however until recently not been possible to identify loci which contribute to disease risk. The sequencing of the human genome, and the cataloguing of sequence variation within and between populations, has provided the information which was needed for the design of genome-wide typing arrays. These high density arrays have been used to test large numbers of DNA samples from cases with disease and healthy controls for common sequence variation. Three distinguished speakers will review the results of the first Genome-Wide Association Studies (GWAS) and how this type of study has lead to the discovery of novel loci implicated in cardiovascular disease, hemostasis and thrombosis. In a stepwise process you will be familiarized with the principle categories and extent of common sequence variation, the design of GWAS and the statistical approach used for the analysis of large scale genotyping results. Finally, we will show how these results have altered our insight in disease pathophysiology of thrombosis and hemostasis.

 

In silico Drug Design

Moderator: Gerry AF Nicolaes (NL)

Application of in silico methods in blood coagulation

research: From virtual proteins to wet protein chemistry Gerry AF Nicolaes (NL)	12:15 - 12:45 PM
In silico screening of compound collections: Methods and applications for drug discovery and chemical biology Bruno Villoutreix (FR)	12:45 - 1:15 PM
Protein-Protein complexes: Druggable or undruggable targets? Xavier Morelli (FR)	1:15 - 1:45 PM

Structural bioinformatics meanwhile play a role across the entire drug discovery pipeline. A major application of structural bioinformatics is the design of ligands that bind specifically and tightly to a binding site on a protein target. In silico techniques such as molecular docking and virtual ligand screening (VLS) have established themselves as novel computational techniques that can predict protein-ligand interactions. Advances in calculation power of computer systems have made these techniques possible for researchers, both in academia and in industry. During this session, the basic rules and considerations that are of importance to this rapidly developing field of science will be discussed.

 

Translating Evidence into Practice

Moderators: Gerhard J. Johnson (US) and James Douketis (CA)

Developing Clinical Practice Guidelines

GRADE system experiences Roman Jaeschke (CA)	12:15 - 1:00 PM
Incorporating practice guidelines into the realm of arterial and venous thromboembolism predictors: What do we have? What is missing? Gordon Lowe (UK)	1:00 - 1:45 PM

The session on 'translating evidence into practice' begins with a general overview of how evidence from clinical trials and observational studies is incorporated into clinical practice guidelines. This discussion will focus on the practical aspects of developing practice guidelines, including how grades of evidence are established and how guideline committees work to interpret available evidence, especially controversial evidence, in formulating simple and easy-to-use practice guidelines. The session ends with a discussion of how clinical practice guidelines have been applied to the area of clinical predictors of venous and arterial thromboembolism. This discussion will focus on currently used predictors and the evidence for their recommended use as well as gaps in knowledge and future research.

The Illusion of Disclosure

Moderator: Bruce Furie (US)

The illusion of disclosure- Conflict of intersts in clinical investigation: Perspectives of a journal editor Robert S. Schwartz, Deputy Editor, New England Journal of Medicine (US)

12:15 - 1:15 PM

This session will discuss the conflict of interest in medical publishing from an editor's point of view, the recent Institute of Medicine report on conflict of interest, and some new questions about the tension between conflict of interest and ethical conduct of clinical trials.

 

Fibrinogen and Factor XIII

Chairperson: Moniek P. M. de Maat (NL)

Co-Chairpersons: Robert A S Ariens (UK), Aida Inbal (IL), Hans P. Kohler (CH), Jaap Koopman (NL), Muriel Maurer (US), Leonid Medved (US), Marguerite Neerman-Arbez (CH), Rainer Seitz (DE), John W. Weisel (US)

Moderator: Moniek deMaat (NL)
Fibrin gels and bioengineering/clinical applications John Weisel (US)	2:00 - 2:30 PM
Non-coagulation activities of Factor XIII Aida Inbal (IL)	2:30 - 3:00 PM

Weisel: Fibrin gels have unique structural and rheological properties that make them well suited for numerous biomaterials applications in medicine and engineering. Fibrin is highly extensible with non-linear elasticity, and polymerization can be modulated to produce a variety of soft substrates. Fibrin is commonly used as a sealant to stem bleeding and promote wound healing. Newer applications include its use as a matrix for drug delivery, cell migration and differentiation, tissue engineering, and patterning.

Inbal: Factor XIII (FXIII) is a plasma transglutaminase that catalyzes the cross link formation between fibrin chains to stabilize the clot. Beside its function in hemostasis FXIII has a role in wound healing and embryo implantation processes that involve angiogenesis. In this review the role of FXIII in angiogenesis and wound repair as well as the molecular mechanisms underlying these effects will be discussed. Finally, a novel activity of FXIII-protein disulfide isomerase (PDI) will be described.

 

Diagnosis of factor XIII deficiency; Outline of a position paper Laszlo Muszbek (HU) and Hans P. Kohler (CH)	3:30 - 3:20 PM
FXIII values in patients with heterozygous deficiency Vytautas Ivaskevicius (DE), Arijit Biswas (DE) and Johannes Oldenburg (DE)	3:20 - 3:40 PM
Measurement of Factor XIII activation peptide (FXIII-AP) in patients with acute ischemic stroke using a new FXIII-AP ELISA Verena Schroeder (UK), Elisabeth Ortner (CH) and Hans P. Kohler (CH)	3:40 - 4:00 PM
Measuring the B-unit in standards Robert Ariens (UK)	4:00 - 4:20 PM
Break	4:20 - 4:40 PM
Fibrinogen
PT-derived and Clauss assay and dysfibrinogens Wolfgang Miesbach (DE)	4:40 - 5:00 PM
Update Characterization Marguerite Neerman-Arbez (CH) and Johannes Oldenburg (DE)	5:00 - 5:20 PM
Fibrin Structure Marlien Pieters (ZA)	5:20 - 5:40 PM
2nd International Standard Fibrinogen Plasma (98/612) - replacement Sanj Raut (UK)	5:40 - 5:50 PM
1st International Standard Fibrinogen Concentrate (98/614) - replacement Sanj Raut (UK)	5:50 - 6:00 PM

Plasma Coagulation Inhibitors

Chairperson: Herbert C. Whinna (US)

Co-chairpersons: Francesco Bernardi (IT), Elaine Gray (UK), Tilman M. Hackeng (NL), Steven Kitchen (UK), Richard Marlar (US), Piet Meijer (NL), Laurent O. Mosnier (US)

Differences in protein S activity assay outcomes in the external quality assessment programme of the ECAT Foundation
Piet Meijer, PhD	2:00 - 2:20 PM
Proposal for a scoring system of the analytical performance of coagulation inhibitor testing
Piet Meijer, PhD	2:20 - 2:45 PM
Thrombin generation testing: Sample collection and processing
Peter Cooper, CSci FIBMS	2:45 - 3:05 PM
Thrombin generation in mouse plasma
S. N. Tchaikovski, PhD	3:05 - 3:30 PM
Report from the Working Party on Thrombin Generation Tests	3:30 - 4:30 PM
Pre-analytical variables for Thrombin Generation Tests
Barry Woodhams, PhD	3:30 - 3:45 PM
Collaborative study to investigate the behaviour of FEIBA in FVIII inhibitor plasma by thrombin generation tests
Katalin Varadi, PhD	3:45 - 4:00 PM
Thrombin Generation Tests – overview of ISTH abstracts
Peter Giesen, PhD	4:00 - 4:15 PM
Availability of reference plasmas for thrombin generation tests
Elaine Gray, PhD	4:15 - 4:30 PM

   

Moderator: Elaine Gray (UK)
Antithrombin and heparin Co-factor II: Structure
and function
Trevor Baglin (UK)	4:30 - 5:00 PM
Molecular mechanisms of thrombosis risk
in protein S deficiency
Elisabetta Castoldi (NL)	5:00 - 5:30 PM
Laboratory investigation of thrombophilia
Peter Cooper (UK)	5:30 - 6:00 PM

The first presentation by Dr. Baglin will focus on how the structure of antithrombin and heparin-cofactor II and their interactions with sulphated polysaccharides such as heparin influence their function as important serine protease inhibitors. Dr. Castoldi will address the role of protein S, a major anticoagulant protein that acts as a cofactor of both activated protein C and tissue factor pathway inhibitor. The increased risk of venous thrombosis as a result of congenital protein S deficiency will be reviewed. Dr. Kitchen will cover the standardization of laboratory tests for investigation of thrombophilia. The advantages/disadvantages of tests employing different principles of analysis including clotting/chromogenic PC assays, protein S activity assays, and antithrombin assays employing thrombin or factor Xa. The issues will be illustrated using genuine cases and data from external quality assessment involving several hundred laboratories.

Factor VIII and IX

Chairperson: Alok Srivastava (IN)

Co-Chairpersons: Charles Hay (UK), Christine Lee (UK), Claude G. Negrier (FR), Johannes Oldenburg (DE), Flora Peyvandi (IT), Jean-Marie Saint-Remy (BE), Edward G D Tuddenham (UK)

Moderator: Alok Srivastava (IN)
Management of hemophilia and assessment of outcomes Kathelijn Fischer (NL)	2:00 - 2:30 PM
Factor concentrates for hemophilia Current products and newer technologies Edward G D Tuddenham (UK)	2:30 - 3:00 PM
Gene therapy of hemophilia B: Overview and new possibilities Arun Srivastava (US)	3:00 - 3:30 PM

This program will review three important aspects of the management of hemophilia. First, Dr. Fischer will discuss the different approaches to prophylactic factor replacement therapy, describe the assessment of musculoskeletal outcome after such therapy and tell us if we are anywhere near defining an optimal protocol. Dr. Tuddenham will then review the current options of products for replacement therapy and discuss their advantages and potential drawbacks. He will also mention some of the newer products and how they may impact care of people with hemophilia. Finally, Dr. Srivastava will look at the possibility of cure from this condition. He will review the possibilities for gene therapy of hemophilia, describe the experience so far and discuss some of the ways to move this field forward.

Perinatal/Pediatric Hemostasis

Chairperson: Gili Kenet (IL)

Co-chairpersons: Janna M. Journeycake (US), Prasad Mathew (US), Paul Monagle (AU), Wolgang Muntean (AT), Ulrike Nowak-Gottl (DE), Nicole Schlegel (FR)

Moderator: Gili Kenet (IL)
Developmental Hemostasis Gili Kenet (IL)	2:00 - 2:30 PM
Pediatric venous thromboembolism and thrombophilia Ulrike Nowak-Gottl (DE)	2:30 - 3:00 PM
Anticoagulant therapy in children Paul Monagle (AU)	3:00 - 3:30 PM

Kenet: Haemostasis is a dynamic process, which begins in-utero. The pro-coagulant capacity of new-borns is reduced. This fact, theoretically increasing the risk of bleeding, is balanced by the protective physiologic deficiencies of coagulation inhibitors, as well as by decreased fibrinolytic capacity. The variations in levels and activity of hemostatic components affecting the clinical settings in neonates will be high-lightened.

Nowak-Gottl: The annual incidence of venous thromboembolism (VTE) in children was estimated as 0.07 to 0.14 per 10,000 children, 5.3 per 10,000 hospital admissions, and 24 per 10,000 admissions of neonates. VTE in children often occurs as a complication of a severe underlying medical condition. The potential role of inherited thrombophilias as risk factors, also affecting recurrence rates in children, will be presented.

Monagle: The current standard anti-thrombotic therapy in children consists of initial short-term intravenous administration of either un-fractionated heparin (UFH) or LMWH, followed by long-term oral anticoagulants or continued LMWH. New drugs deserve attention, yet data regarding their pharmacokinetics, efficacy and safety in paediatric patients are to be elucidated. The difficulties and controversies regarding “tailoring” of anticoagulant treatment in children will be discussed.

  

Quality of Life tool for children receiving anticoagulant therapy Aisha Bruce (CA) and Fiona Newall (AU)	3:30 - 3:45 PM
Trial design and outcomes for evaluation of anticoagulant drugs for use in children Christoph Male (AT)	3:45 - 4:05 PM
Break	4:05 - 4:20 PM
Pediatric thrombosis and stroke - Suggestions, definitions and trials
Chairpersons: Janna Journeycake (US) and Guy Young (US)
Limitations and definitions in pediatric thrombosis studies Lesley Mitchell (CA)	4:20 - 4:40 PM
A validated pediatric PTS outcome instrument N Goldberg (US)	4:40 - 4:40 PM
Kids -DOTT trial N Goldberg (US)	4:40 - 4:50 PM
Genetic association studies for juvenile thrombosis and stroke Monika Stoll (DE)	4:50 - 5:00 PM
Neonatal Thrombosis

 

Chairpersons: Anthony K. Chan (CA) and Mariana Bonduel (AR)
Neonatal Renal Vein Thrombosis Keith Lau (CA)	5:00 - 5:15 PM
Neonatal Portal Vein Thrombosis Suzan Williams (CA)	5:15 - 5:30 PM
Neonatal CSVT Mahendranath Moharir (CA)	5:30 - 5:45 PM

Animal Models

Chairperson: Timothy Charles Nichols (US)

Co-chairpersons: Edward M. Conway (BE), Shaun Coughlin (US), Jay L. Degen (US), Nigel Mackman (US), Eva-Maria Muchitsch (AT), Susan Smyth (US), Hugo Ten Cate (NL), Hartmut Weiler (US)

Moderators:

Nigel Mackman (US), Hartmut Weiler (US), Timothy C. Nichols (US)

Human gamma fibrinogen in mouse coagulation Hartmut Weiler (US)	2:00 - 2:15 PM
Coagulation protease-inhibitor effects in models of cardiovascular disease Hugo Ten Cate (NL)	2:15 - 2:30 PM
Intra-articular factor IX protects hemophilia B mice from developing hemophilic synovitis Paul Monahan (US)	2:30 - 2:45 PM
Tissue factor and tissue-specific hemostasis Nigel Mackman (US)	2:45 - 3:00 PM
Novel ultrasound methods to monitor hemostasis Caterina Gallippi (US)	3:00 - 3:30 PM
Hemophilia A in sheep Graca Almeida-Porada (US)	3:30 - 3:45 PM
Canine hemophilia A and B Timothy C. Nichols (US)	3:45 - 4:00 PM
Break	4:00 - 4:30 PM

Moderators: Hartmut Weiler (US) and Timothy C. Nichols (US)

Modifying murine von Willebrand factor A1 domain for in vivo assessment of human platelet therapies Thomas G. Diacovo (US)	4:30 - 5:00 PM
Key questions for animal models of hemostasis in developing new drugs and obtaining approval Eva-Marie Muchitsch (AT)	5:00 - 5:30 PM
Stressing the limits of mice models of hemophilia: When mice are not small people Mortimer Poncz (US)	5:30 - 6:00 PM

The focus of this Animal Models Subcommittiee educational session is to discuss the strengths and limitations of animal models in hemostasis research. The approach to cross species interactions of murine VWF and human platelets will be discussed by Dr. Diacovo. Issues to be considered in the utilization of animal models in developing new hemostatic agents and obtaining approval for use will be discussed by Dr. Muchitsch. Dr. Poncz will discuss key differences between murine and human hemophilia.

Lupus Anticoagulant / Phospholipid-Dependent Antibodies

Chairperson: Vittorio Pengo (IT)

Co-chairpersons: Ph G De Groot (NL), Thomas Ortel (US), Jacob H. Rand (US), Guido Reber (CH), Armando Tripodi (IT)

Opening Vittorio Pengo (IT)	2:00 - 2:15 PM
Round Table Chairperson: Armando Tripodi (IT)
Standard reference material for detecting antiphospholipid antibodies: Problems and possible solutions Katrien Devreese (BE), Emmanuel Favaloro (AU), Elaine Gray (UK), Silvia Pierangeli (US), Guido Reber (CH)	2:15 - 3:00 PM

Laboratory diagnosis: Coagulation assays (new guidelines) Armando Tripodi (IT)	3:00 - 3:30 PM
Detection of antibodies against domain I of beta2- glycoprotein I improves the diagnosis of APS: An international multileft study Bas de Laat (NL)	3:30 - 3:45 PM
Predictive value of the Antiphospholipid Score Tatsuya Atsumi (JP)	3:45 - 4:00 PM
Break	4:00 - 4:30 PM

 

Moderator: Vittorio Pengo (IT)
Antiphospholipid antibodies: Historical background Thomas Ortel (US)	4:30 - 4:50 PM
Mechanism of action of antiphospholipid antibodies Jacob H. Rand (US)	4:50 - 5:10 PM
Laboratory diagnosis Ph. G. de Groot (NL)	5:10 - 5:30 PM
Clinical features Vittorio Pengo (IT)	5:30 - 6:00 PM

Four speakers will cover all the relevant aspects of the antiphospholipid syndrome. An Historical background will initially be given by Dr. Ortel starting from the discovery of antiphospholipid antibodies at the beginning of past century. To follow Dr. Rand will describe the current hypotheses on the pathogenesis of the syndrome. Dr. de Groot will then discuss the very important issue on the laboratory diagnosis of the syndrome and finally Dr. Pengo will describe the clinical features to diagnose the disease as well the infrequent associated clinical manifestations.

Biorheology

Chairperson: Johan W.M. Heemskerk (NL)

Co-chairpersons: Thomas Diacovo (US), Marc Hoylaerts (BE), Michael King (US), Gerard B. Nash (UK), J. J. Zwaginga (NL)

Moderator: Johan W.M. Heemskerk (NL)
Adhesion of platelets and leukocytes to the vessel wall:  

Rheological principles and critical parameters Gerard B. Nash (UK)	2:00 - 2:30 PM
Thrombus formation and the different ways to measure this
Johan W.M. Heemskerk (NL)	2:30 - 3:00 PM

The first lecture discusses key principles of blood flow-dependent processes and quantitative parameters of rheology, including (arterial and venous) shear stress and shear rate. Subsequently, an overview will be given of how the blood flow determines adhesion of platelets and leukocytes to the vessel wall. The second lecture overviews recent literature on the various stages of flow-dependent thrombus formation. In vivo, different procedures are used to provoke thrombus formation experimentally. To study human thrombus formation ex vivo or in vitro, various types of flow-based devices (flow chambers, capillary systems) are developed. It will be discussed how thrombus formation can be measured in both in vivo and in vitro assays.

Section 1. Flow-dependent experimental thrombosis models and translation. How to use flow-dependent thrombosis models?

Chairpersons: Marc Hoylaerts (BE) and Johan Heemskerk (NL)

Novel molecular interactions in thrombus formation Shaun Jackson (AU)	3:00 - 3:15 PM
Comparison of in vivo and in vitro thrombosis models Beatrice Hechler (FR) and Pierre Mangin (FR)	3:15 - 3:30 PM
Using flow-dependent models in vitro and in vivo to explore new ideas about platelet activation Lawrence Brass (US)	3:30 - 3:45 PM

    

Limitations of animal thrombosis models: The need for alternatives Marc Hoylaerts (BE)	3:45 - 4:00 PM
Break	4:00 - 4:25 PM
Section 2. Determination of flow-dependent molecular interactions. Processes relying on flow
Chairpersons: Michael King (US) and Thomas Diacovo (US)
Platelet-fibrin-thrombus formation in arterial flow requires high and low shear regions Armin Reininger (DE)	4:25 - 4:40 PM
Flow-based measurement of VWF binding to collagen Birte Fuchs (DE)	4:40 - 4:55 PM
Flow-dependent function of VWF after gene therapy Karen Vanhoorelbeke (BE)	4:40 - 5:10 PM
Section 3. Standardization of thrombus formation under flow. How to use flow devices?
Chairpersons: J.J. Zwaginga (NL) and Gerald Nash (UK)
Measurement of thrombus formation on (ruptured) atherosclerotic plaques Judith Cosemans (NL)	5:10 - 5:25 PM
Use of quantitative flow assays to study unknown bleeding disorders Mark Roest (NL)	5:25 - 5:40 PM
The analysis of shear-dependent thrombus deposition on synthetic collagen surfaces Richard Farndale (UK)	5:40 - 5:55 PM

Disease-Specific Molecular Mechanisms in Disseminated Intravascular Coagulation (DIC)

Chairperson: Cheng-Hock Toh (UK)

Co-chairpersons: Nigel S. Key (US), Hyun Kyung Kim (KR), Jorn Dalsgaard Nielsen (DK), Hideo Wada (JP)

Moderator: Cheng-Hock Toh (UK)
Role of IL-17 in Sepsis Peter A. Ward (US)	8:00 - 8:30 AM
New concepts in trauma induced coagulopathy Karim Brohi (UK)	8:30 - 9:00 AM
Acute Promyelocytic Leukemia: Mechanisms of coagulopathy Katherine A. Hajjar (US)	9:00 - 9:30 AM

From the earliest clinical observations, it has long been recognized that the outcome of any primary disease state is worsened by the development of a coagulopathy. In translating this into a standardized format of recognition, the ISTH Scientific and Standardization Sub-Committee has developed a DIC diagnostic criteria that has now been well-validated. Studies have shown that recognizing DIC, irrespective of its aetiology, has clinical value in the improved stratification of patient management. However, the emerging evidence is that the molecular pathogenesis of DIC can be different and can be disease-specific. This session is focused on understanding these differences in order to enable the next stage of translational medicine, i.e. in facilitating pathway-specific therapy. Examples will be described of where complement-mediated mechanisms, pro or anticoagulant pathways and fibrinolytic systems may be physiologically important and clinically-relevant targets.

Chairman's report Cheng-Hock Toh (UK)	10:00- 10:15 AM
A. STANDARDIZATION
Evaluation of non-overt DIC criteria Hideo Wada (JP)	10:15- 10:30 AM
Experience of evolving scores of hemostatic dysfunction in critical care Gary Kinasewitz (US)	10:30- 10:45 AM
Impact of the ISTH DIC score in children with critical illness Robinder Khemani (US)	10:45- 11:00 AM
Impact of method for platelet count determination in DIC Hyun K. Kim (KR)	11:00- 11:15 AM
B. COLLABORATIONS
With SSC in plasma coagulation inhibitors and UK NEQAS on Protein C and Antithrombin measurements Tina Dutt (UK)
With SSC in vascular biology on procoagulant microparticles Nigel Key (US)
Summation and Closing	11:45- 12:00 PM

von Willebrand Factor (VWD)

Chairperson: David Lillicrap (CA)

Co-chairpersons: Thomas Abshire (US), Imre Bodo (HU), Giancarlo Castaman (IT), Jorge DiPaola (US), Jeroen C.J. Eikenboom (NL), Emmanuel J Favaloro (AU), Anne Goodeve (UK), Bernhard Lämmle (CH), Reinhard Schneppenheim (DE)

Moderator: David Lillicrap (CA)
Clinical aspects of VWD diagnosis Francesco Rodeghiero (IT)	8:00 - 8:30 AM
Laboratory testing of the hemostatis phenotype in VWD Robert R. Montgomery (US)	8:30 - 9:00 AM
Genetic analysis as an aid in VWD diagnosis Anne Goodeve (UK)	9:00 - 9:30 AM

The diagnosis of the most common inherited bleeding disorder, von Willebrand disease (VWD), is often complicated. In theory, there are three components to the diagnostic definition: a personal history of excessive mucocutaneous bleeding, a family history of the disease and a set of laboratory tests demonstrating quantitative and/or qualitative abnormalities of von Willebrand factor. In this educational session, experts in the field will address each of these diagnostic areas. Dr. Rodeghiero will discuss an optimal approach to the evaluation of the clinical symptoms manifest in VWD. Dr. Montgomery will then review the appropriate hemostasis testing strategy to evaluate quantitative and qualitative abnormalities of von Willebrand factor. Finally, Dr. Goodeve will discuss the role of molecular genetic analysis in making a diagnosis of (VWD).

1. VWF Assays for VWD Diagnosis
Chairperson: Emmanuel Favaloro (AU)
Standardization of ristocetin-based VWF assays RIPA Augusto Federici (IT)	9:30 - 9:40 AM
Automated VWF: RCo Andreas Hillarp (SE)	9:30 - 9:40 AM
Alternative functional assays - GPIb binding assays:
Robert Montgomery (US)	9:40 - 9:50 AM
Hans Deckmyn (BE)	9:50 - 10:00 AM
Discussion 10:00 - 10:05 AM
2. VWF Propeptide Studies
Chairperson: Jeroen Eikenboom (NL)
Standardization and Clinical utility
Robert Montgomery (US)	10:15- 10:25 AM
Bas De Laat (NL)	10:25- 10:35 AM
Discussion	10:35- 10:40 AM
3. Standarized Bleeding Scores (joint session with Pediatric SSC)
Chairperson: Tom Abshire (US)
Bleeding scores
Adult
Francesco Rodeghiero (IT)	10:40- 10:50 AM
Pediatric
Paula James (CA)	10:50- 11:00 AM
Discussion	11:00- 11:10 AM
4. VWF Plasma and Concentrate Standards
Chairperson: Anne Goodeve (UK)
Discussant Tony Hubbard (UK)	11:10- 11:15 AM
Discussion	11:15- 11:20 AM
5. ADAMTS13
Chairperson: Bernhard Laemmle (CH)
ADAMTS13 assays Koichi Kokame (JP)	11:20- 11:30 AM
ADAMTS13 antibody assays Bas De Laat (NL)	11:30- 11:40 AM
Discussion	11:40- 11:45 AM
6. VWF and VWD Registries
Chairperson: Imre Bodo (HU)
Discussant
VWD registry Anne Goodeve (UK)	11:45- 11:50 AM
Discussion	11:50- 11:55 AM

Control of Anticoagulation

Chairperson: Trevor Patrick Baglin (UK)

Co-chairpersons: Walter Ageno (IT), Job Harenberg (DE), Clive Kearon (CA), Aharon Lubetsky (IL), John Olson (US), Gualtiero Palareti (IT), Sam Schulman (CA), A.M.H.P. van den Besselaar (NL)

Chairpersons: Trevor Baglin (UK) and Sam Schulman (CA)

Introduction and update on activities of the SSC including overview of progress of Working Parties and future plans Trevor Baglin (UK)	8:00 - 8:10 AM
Registry Report - Splanchnic vein thrombosis Walter Ageno (IT)	8:10 - 8:20 AM

Discussion / Potential registry - Cerebral VeinThrombosis - duration of anticoagulation Walter Ageno (IT)	8:20 - 8:30 AM
Working Party Report - Recommendation for requirements on biosimilar Anticoagulants / Working Party Report - Standardization of methods to determine direct factor Xa inhibitors Job Harenberg (DE)	8:30 - 8:40 AM
Working Party Report - Results of international collaborative study for calibration of two candidates for International Standard for thromboplastin, human, plain Ton Van Den Besselaar (NL)	8:40 - 8:50 AM
Working Party Report - Variability of INR in stabilized patients and requirements for INR analytical precision Ton Van Den Besselaar (NL)	8:50 - 9:00 AM
Discussion / New Working Party - Reporting INRs in liver disease Armando Tripodi (IT)	9:00 - 9:10 AM
New Oral Anticoagulants Introduction to the Working Party: General and specific aims Trevor Baglin (UK)	9:10 - 9:20 AM
Overview of drug development programs Harry Buller (NL)	9:20 - 9:35 AM
Monitoring, bleeding and reversal Jeffrey Weitz (CA)	9:35 - 9:50 AM
Patient education, concordance and compliance (role of thrombosis centres / anticoagulation clinics) Jack Ansell (US)	9:50 - 10:00 AM
What to recommend for phase IV studies in collaboration between companies and anticoagulation clinics Gualtiero Palareti (IT)	10:00- 10:10 AM
Break	10:10- 10:30 AM

Moderators: Trevor Baglin (UK) and Sam Schulman (CA)
Atrial fibrillation and antithrombotic therapy: Which drug and when? Elaine Hylek (US)	10:30 - 10:45 AM
Interruption of oral VKA therapy requires bridging therapy (for) David Keeling (UK)	10:45 - 11:00 AM
Interruption of oral VKA therapy requires bridging therapy (against) Clive Kearon (CA)	11:00 - 11:15 AM
Warfarin dosing and pharmacogenetic testing (for) Brian Gage (US)	11:15 - 11:30 AM
Warfarin dosing and pharmacogenetic testing (against) David A Garcia (US)	11:30 - 12:00 PM

This educational symposium focuses on three controversies frequently encountered in clinical practice: when to give vitamin K antagonists therapy for atrial fibrillation; how to initiate therapy; and when to bridge with heparin. Dr. Hylek will consider the issue of antithrombotic therapy in patients with atrial fibrillation in terms of which drug and when. How do clinical trial results translate into treatment of individual patients? Dr. Gage and Dr. Garcia will debate whether pharmacogenetic testing has a role when initiating oral VKA therapy. Is there evidence of added value? Dr. Keeling and Dr. Kearon will debate whether heparin bridging is ever necessary when oral VKA therapy is interrupted. What is the clinical evidence? These issues are so common and relevant to routine clinical practice that all three might be encountered in relation to a single patient. It is hoped that the session will bring clarity and provide guidance.

Fibrinolysis

Chairperson: Colin Longstaff (UK)

Co-chairpersons: Carl-Erik H. Dempfle (DE), Ann Gils (BE), Dirk Hendriks (BE), Osamu Matsuo (JP), Michael E. Nesheim (CA), Tetsumei Urano (JP)

  

WHO International Standards
Report on a new WHO International Standard for Streptodornase Colin Longstaff (UK)	8:30 - 8:40 AM
Update on standardization of PAI-1 antigen determinations in plasma Colin Longstaff (UK)	8:40 - 8:50 AM
Approaches to dual labeling of International Standards for enzymes and inhibitors Craig Thelwell (UK)	8:50 - 9:00 AM
TAFI/CPU
Update on the functional assay for plasma TAFIa Michael Nesheim (CA)	9:00 - 9:25 AM
Determination of CPU/TAFIa in plasma samples Evelien Heylen (BE) and Dirk Hendriks (BE)	9:25 - 9:45 AM
D-dimer
Update on the NEQAS EQA for D-dimer Ian Jennings (UK)	9:45 - 10:00 AM
General Discussion and Break	10:00 - 10:30 AM

Moderator: Carl-Erik H. Dempfle (DE)
D-dimer in the emergency room (venous thromboembolism exclusion, aortic dissection) Carl-Eric Dempfle (US)	10:30 - 11:00 AM
Fibrin generation markers in the perioperative setting Wolfgang Korte (CH)	11:00 - 11:30 AM
D-dimer as prognostic parameter in venous thromboemolism, pregnancy and cancer Saskia Middledorp (NL)	11:30 - 12:00 PM

D-dimer currently is the most prevalent marker for detection of coagulation activation. Various assay systems are available, including automated assays for high throughput laboratory instrumentation, as well as point of care or near patient assays. Quantitative assays are the current standard. D-dimer may discriminate conditions associated with intravascular fibrin formation from conditions without intravascular fibrin formation. Examples are exclusion of venous thrombosis or pulmonary embolism, or differential diagnosis of acute chest pain. In the perioperative setting, D-dimer and other markers of fibrin generation may identify patients with high clinical risk, including patients prone to thromboembolic complications. Finally, D-dimer measurement has emerged as a prognostic tool in secondary prevention of venous thromboembolism, for monitoring of pregnancy complications, and in cancer. The educational session will focus on the primary clinical applications of D-dimer and related assay systems from a practical perspective.

Platelet Physiology

Chairperson: Marco Cattaneo (IT)

Co-chairpersons: Joel S. Bennett (US), Paul Harrison (UK), Catherine P. M. Hayward (CA), Dermot Kenny (IE), Alan D. Michelson (US), Diane Nugent (US), Steve Watson (UK)

Chairpersons: Marco Cattaneo (IT) and Alan D. Michelson (US)

Discussion of the Consensus of Experts on LTA Standardization Marco Cattaneo (IT), Chiara Cerletti (IT), Paul Harrison (UK), Catherine P.M. Hayward (CA), Dermot Kenny (IE), Alan D. Michelson (US), Diane Nugent (US), Paquita Nurden (FR), Koneti A. Rao (US), Alvin Schmeier (US), Steve Watson (UK)	8:00 - 9:45 PM
Proposal on formation of an SSC Working Party on Diagnosis of Platelet Function Disorders Marco Cattaneo (IT)	9:45 - 10:00 AM
Break	10:00- 10:30 AM
New BCSH (British Committee for Standards in Haematology) guidelines for platelet function testing Paul Harrison (UK)	10:30- 11:00 AM

 

Moderator: Marco Cattaneo (IT)
Platelet function as a guide to thrombotic risk Alan D. Michelson (US)	11:00 - 11:30 AM
Recent advances in the understanding and diagnosis of inherited platelet function disorders Catherine P. M. Hayward (CA)	11:30 - 12:00 PM

Platelets play an important role in hemostasis, because both inherited and acquired abnormalities of their number and/or function are associated with excessive bleeding. Platelets also play an important pathogenic role in thrombosis, as shown by the results of several randomized clinical trials, which showed that drugs inhibiting platelet function reduce the risk of arterial thrombosis. Several laboratory methods for the evaluation of platelet function are available. Aims of the Educational Session of the Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis are the following: 1) to update on the diagnostic work-up of patients with clinical suspicion of inherited platelet function defects; 2) to review the clinical usefulness of the currently available platelet function tests in the identification of patients at risk of thrombosis.

Plasma Kallikrein-Kinin system

Chairperson: David Gailani (US)

Co-chairpersons: Keith R McCrae (US), Thomas Renné (SE), Alvin Schmaier (US)

Introduction. Description of the meeting organization. Business issue - Changing the name of Subcommittee to "Plasma Contact Activation System" Subcommittee David Gailani (US)	8:00- 8:15 AM
The pathophysiology of hereditary angioedema Alvin Davis (US)	8:15- 8:45 AM
The platelet ApoER2' receptor and factor XI binding to platelets Owen McCarty (US)	8:45- 9:15 AM
Targeting factor XI in primate and murine models of pathologic coagulation Andras Gruber (US)	9:15- 9:45 AM
Break	9:45- 10:00 AM
Contact activation in arterial thrombosis - An update on clinical studies José Govers-Riemslag (NL)	10:00- 10:30 AM
Assays for over-sulfated chondroitin sulfate in heparin Cornelius Kluft (NL)	10:30- 11:00 AM

 

Moderator: David Gailani (US)
Misfolded proteins as a trigger for contact activation Martijn F.B.G. Gebbink (NL)	11:00 - 11:30 AM
Role of leukocytes and platelets in contact system activation Thomas Renne (SE)	11:30 - 12:00 PM

The term Contact Activation describes the conversion of the plasma protease zymogens factor XII, factor XI and prekallikrein (PK) to their active forms (factor XIIa, factor XIa and _-kallikrein, respectively) in the presence of an activating surface and the plasma protein high molecular weight kininogen (HK). This process can trigger activation of several host defense mechanisms including vasoactive kinin formation and blood coagulation. Contact activation initiates thrombin generation and fibrin formation in the classic cascade/waterfall models of coagulation, and in the partial thromboplastin time assay used to screen for plasma coagulation defects in the clinical setting. However, for many years, the importance of this process has been considered minimal because of the absence of bleeding or other clinical disorders in patients with complete deficiency of factor XII, PK or HK. This school of thought is reflected in the decision of the ISTH SSC on Contact Activation to change its name several years ago to the SSC on The Plasma Kallikrein-Kinin System. However, recent studies with genetically engineered mice demonstrate that factor XII, while not required for normal hemostasis, makes important contributions to pathologic coagulation in a number of vascular injury/thrombosis models. Similar results with factor XI deficient mice raise the distinct possibility that a process similar to classic contact activation is operating in these models. The nature of the trigger for factor XII activation in vivo is an area of active research. Traditional plasma assays typically use purified earths such as kaolin or celite to trigger contact activation. A number of physiologically relevant compounds including collagen, RNA, and polyphosphates from platelet granules have been implicated as triggers of factor XII activation at sites of vascular injuries. It is the goal of this educational session to further explore biologically relevant mechanisms for factor XII activation. Our first speaker, Dr. Gebbink of the University Medical left in Utrecht will discuss the role of misfolded proteins, such as occur in amyloidosis, in activation of factor XII and prekallikrein. Then, Dr. Renné of the Karolinska Institute will speak on the role of platelets and leukocytes in initiating contact activation, and the implications for vascular thrombosis.

Registry of Exogenous Hemostatic Factors

Chairperson: Mary Ann McLane (US)

Co-Chairpersons: Kenneth J. Clemetson (CH), Manjunatha R. Kini, (SG), Francis S. Markland Jr. (US), Takashi Morita (JP)

Welcome

Record of last meeting (Vienna, 3 July 2008)

Progress report and planning for 4th International Conference on Exogenous Factors Affecting Thrombosis and Hemostasis (25th Anniversary), Boston 2009

Mary Ann McLane (US)

Final Report on classification and nomenclature of C-type lectins

Kenneth Clemetson (CH) and Takashi Morita (JP)

Interaction of disintegrins with natural killer cell activity

Mary Ann McLane (US)

Next Registry meeting (ISTH schedule: Cairo Egypt 5/22-5/25/2010)

Next EFATH meeting (ISTH schedule: Amsterdam, Netherlands 6/29 - 7/4/2013)

Future projects for the Registry: Nomenclature of Venom Metalloproteases

Manjunatha Kini (SG)

Moderator: Mary Ann McLane (US)

Transcriptomics and functional genomics of salivary  

glands from hematophagous arthropods Ivo Francischetti (US)	10:30 - 11:15 AM
Fibrolase and its evolution to clinical trials:
A long and winding road Francis S. Markland, Jr. (US)	11:15 - 12:00 PM

Francischette: Transcriptome and proteomic studies of the salivary gland from blood sucking arthropods have provided new insights in our understanding of saliva pharmacopea. Currently available sialomes from mosquitoes, sand flies, bugs, soft and hard ticks indicate that protein families such as Kunitz inhibitors are common to most hard ticks, while lipocalins are the most abundant proteins in soft ticks. Several proteins with unique sequences have also been found in distinct genera, and their functions have now been identified. Ixolaris inhibits the initiation of the coagulation cascade through inhibition of tissue factor in a FX/FXa-dependent manner, while RPAI-1 binds with high affinity to ADP and inhibits platelet aggregation. In addition, mosquito aegyptin specifically binds to the collagen sequence that mediates its interaction with von Willebrand factor (vWf). These molecules are being tested in vivo for inhibition of thrombus formation, cancer and metastasis. Markland: Fibrolase is a direct-acting fibrinolytic enzyme from southern copperhead (Agkistrodon contortrix contortrix) snake venom. The enzyme has no thrombin-like activity, does not activate protein C or platelets, does not activate nor degrade plasminogen, and has no hemorrhagic or hemolytic activity. Alfimeprase is the recombinant form of fibrolase made in yeast that is virtually identical to fibrolase with respect to enzymatic activity. However, the altered amino acid sequence stabilizes the structure of alfimeprase for prolonged shelf-life. In an acute carotid arterial thrombosis model, administration of alfimeprase produced significantly more rapid clot lysis than urokinase (UK) in rats, piglets or dogs. In a porcine model of peripheral arterial occlusion of the carotid artery, alfimeprase (but not(UK)) achieved close to complete thrombus resolution and flow restoration within 30 min. However, in clinical trials for peripheral arterial occlusion, alfimeprase did not meet target end points and further clinical development was ended in 2008.

McLane: Naturally occurring animal venoms from snakes, leeches, spiders, caterpillars, ticks and scorpions have been recognized for centuries as significant modulators of thrombosis and hemostasis. It is only within the past 40 years, however, that research techniques have allowed definitive insights into structure-function relationships of molecules from these sources, and their adaptation for clinical use. This session will highlight recent advances in molecular analyses and translational opportunities for proteins isolated from the southern copperhead viper (Agkistrodon contortrix contortrix) and blood sucking arthropods (mosquitoes, sand flies, ticks).