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Berzelius symposium 91
International Conference on
Thrombosis and Embolism
17–18 November 2016 in Stockholm · Sweden
Programme · General information · Lectures abstracts · Poster abstracts
The symposium is arranged by the Swedish Society of Medicine in cooperation with Karolinska Institutet
and supported by Bristol-Myers Squibb Pfizer · MSD · Bayer · Leo Pharma
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Berzelius symposium 93
International Conference on
Thrombosis and Embolism
This international conference will cover advances, breakthroughs and important
aspects of thrombosis and embolism in the context of pathogenesis and treatment
of diverse medical conditions. The scope of the conference will range from basic
studies at cellular and molecular levels, through clinical manifestations and diagnostic considerations, to the treatment and follow-up of selected medical conditions.
Diverse topics including clinical conditions in different patient groups and challenging clinical situations will be covered. The conference will be of interest for the
beginners as well as for the experts, from scientists engaged in basic research to the
bedside clinicians, in this important field of medicine.
Welcome to Stockholm in November!
Organizing committee:
Md. Shahidul Islam (chair) Sweden, Marika Bajc, Sweden, Alun H. Davies, UK,
Søren Hess, Denmark, Paolo Prandoni, Italy, Raveena Ravikumar, UK
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We thank our sponsors for the educational grants!
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Programme
Thursday, 17 November 2016
07.30–09.00 Registration
09.00–09.10 Welcome addresses
09.10–12.10 Morning session
Chair: Paolo Prandoni
09.10–09.50 Bengt Zöller, Lund University, Sweden
Epidemiology of familial aggregation of venous thromboembolism
09.50–10.30 Wade S. Smith, UCSF, USA
Atrial appendage ligation for the prevention of stroke from atrial fibrillation
10.30–10.50 Coffee break
10.50–11.30 Wade S. Smith, UCSF, USA
Endovascular stroke therapy
11.30–12.10 Thomas Renné, Karolinska Institutet, Sweden
Revival of the contact system of coagulation: new perspectives
for safe anticoagulation
12.10–13.10 Lunch
13.10–17.00 Afternoon Session
Chair: Raveena Ravikumar
13.10–13.50 Poul Henning Madsen, Vejle Hospital, Denmark
Who to test for pulmonary embolism?
The view of a practicing respiratory physician
13.50–14.30 Søren Hess, Odense University Hospital, Denmark
State-of-the-art imaging in PE, e.g. SPECT/CT vs. CT angiography
14.30–15.10 Christopher Kabrhel, Harvard University, USA
The value of pulmonary embolism response team
15.10–15.30 Coffee break
15.30–16.05 Massimo Miniati, University of Florence, Italy
Pulmonary infarction: an often unrecognized clinical entity
16.05–17.00 Sam Schulman, McMaster University, Canada
Update on treatment of venous thromboembolism
19.00–21.00 Reception at the Stockholm City Hall hosted by a member of the
Presidency of the City Council and co-hosted by Stockholm’s County
Council.
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Friday, 18 November 2016
08.30–12.00 Morning session
Chair: Bengt Zöller
08.30–09.10 Jonathan Coutinho, University of Amsterdam, The Netherlands
Cerebral venous thrombosis
09.10–09.30 Timothy R. Smith, Harvard University, USA
High grade glioma patients: treatment options for VTE prevention
09.30–09.50 David J. Cote, Harvard University, USA
An overview of VTE in patients undergoing craniotomy for brain tumors
09.50–10.30 Vlad C Radulescu, University of Kentucky, USA
Venous thromboembolism in children
10.30–10.50 Coffee break
10.50–11.20 Raveena Ravikumar, Imperial College London, U.K.
Post thrombotic syndrome
11.20–12.00 Paolo Prandoni, University of Padova, Italy
The optimal duration of anticoagulation in patients with unprovoked
venous thromboembolism
12.00–13.00 Lunch
13.00–17.00 Afternoon Session
Chair: Søren Hess
13.00–13.35 Raveena Ravikumar, Imperial College London, U.K.
Catheter directed thrombolysis and Pharmacomechanical thrombolysis
13.35–14.10 Maria Boddi, University of Florence, Italy
Deep vein thrombosis in intensive care
14.10–14.55 Paolo Prandoni, University of Padova, Italy
Controversies in the management of venous thromboembolism
in patients with cancer
14.55–15.15 Coffee break
15.15–16.15 Sam Schulman, McMaster University, Canada
Bleeding complications and management on anticoagulant therapy
16.15–17.00 Panel discussion: questions and answers session
Moderated by Sam Schulman
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General information
When & Where?
17–18 November 2016 at the Swedish Society of Medicine (SSM),
Klara Östra Kyrkogata 10 in Stockholm, Sweden.
Lunches and coffee are included in the participation cost and
will be served at the SSM.
The Society’s building in Stockholm
Organizing Committee
Md. Shahidul Islam (chair) Sweden, Marika Bajc, Sweden,
Alun H. Davies, UK, Søren Hess, Denmark, Paolo Prandoni, Italy,
Raveena Ravikumar, UK.
Symposium secretariat
Annie Melin, the Swedish Society of Medicine (SSM),
P.O. Box 738, SE-101 35 Stockholm.
Phone +46 (0) 8 440 88 78,
[email protected],
Symposium website: http://www.sls.se/thrombosis
The conference Hall
The Stockholm City Hall is one of Sweden’s most
famous buildings, and one of the capital's most visited
tourist attractions. It is famous for its grand ceremonial halls and unique art pieces and is the venue of the
Nobel Prize banquet held on 10th of December each
year. It also houses offices for 200 people including the
Municipal Council.
Social programme
Thursday, 17 November 2016 at 7 p.m (sharp!)
Reception in the Stockholm City Hall, hosted by the City and the
County of Stockholm.
Address: Hantverkargatan 1 in Stockholm.
The Reception is free of-charge and open to participants wo have
registered within the stipulated time.
The number of participants is limited.
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Speakers abstracts
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Epidemiology of Familial Aggregation of Venous Thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Bengt Zöller, Lund University, Sweden
Left atrial appendage ligation for the prevention of cardioembolic stroke . . . . . . . . . . . . . . . . . . . . . . 10
Wade Smith, University of California, San Francisco
Endovascular Stroke Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Wade Smith, University of California, San Francisco
Revival of the contact system of coagulation: new perspectives for safe anticoagulation
Thomas Renné, Karolinska Institutet, Sweden
..
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Who To Test for Pulmonary Embolism? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Poul Henning Madsen, Senior consultant, FSPSP, Dept. of Medicine,
Division of Respiratory Medicine, Vejle Hospital, Denmark
State-of-the-art imaging in PE: Radionuclide vs. radiologic imaging
Søren Hess, Odense University Hospital, Denmark
...............................
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Pulmonary Embolism Response Teams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Christopher Kabrhel, Harvard University, USA
Pulmonary infarction: an often unrecognized clinical entity
Massimo Miniati, University of Florence, Italy
.........................................
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Update on the treatment of venous thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Sam Schulman, McMaster University and Thrombosis and Atherosclerosis
Research Institute, Hamilton, ON, Canada
Celebral venous thrombosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Jonathan Coutinho, University of Amsterdam, the Netherlands
High grade glioma patients: treatment options for VTE prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Timothy R. Smith, Harvard University, USA
Venous thromboembolism in patients undergoing craniotomy for brain tumors:
a U.S. nationwide analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
David J. Cote, Harvard University, USA
Venous thromboembolism in children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Vlad C Radulescu, University of Kentucky, USA
Post thrombotic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Raveena Ravikumar, Imperial College London, UK
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Page
The optimal duration of anticoagulation in patients with unprovoked venous
thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Paolo Prandoni, University of Padua, Italy
Catheter directed thrombolysis and Pharmacomechanical thrombolysis . . . . . . . . . . . . . . . . . . . . . . . . . 24
Raveena Ravikumar, Imperial College London, UK
Deep vein thrombosis in Intensive Care Unit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Maria Boddi, University of Florence, Italy
Controversies in the management of venous thromboembolism
in patients with cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Paolo Prandoni, University of Padua, Italy
Bleeding complications and management on anticoagulant therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Sam Schulman, McMaster University and Thrombosis and
Atherosclerosis Research Institute, Hamilton, ON, Canada
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Epidemiology of Familial Aggregation of Venous Thromboembolism
Bengt Zöller, MD, PhD, Lund University, Sweden
Venous thromboembolism (VTE) is the third most frequent cardiovascular disease
after coronary heart disease and stroke. The incidence of VTE is 1 to 2 per 1000 individuals in the general population. Familial aggregation, i.e. the clustering of VTE within
families, was reported by Briggs already in 1905. Insight into the molecular mechanism
was first gained in 1965, when Egeberg discovered the rare inherited deficiency of
antithrombin. Protein C and protein S deficiencies, which are equally rare, were discovered in 1981 and 1984, respectively. However, it was not until Dahlbäck discovered
resistance to activated protein C in 1993 that it became evident that genetic variants
are frequent determinants of VTE. The classical or major thrombophilias (gene defects
of antithrombin, protein C, protein S, factor V, and prothrombin genes) only partially
explain the familial aggregation of VTE. The epidemiology of the familial aggregation
of VTE exhibits typical characteristics of complex or multifactorial traits, i.e. VTE does
not exhibit classical Mendelian dominant or recessive inheritance due to a single gene
locus. For instance, the family history of VTE in a first-degree relative is associated with
a 2-3 times increased familial relative risk (FRR). Moreover, the FRR of VTE is higher
in early onset cases, increases with the number of affected relatives, decreases as the
familial relatedness becomes more distant, increases with severity (unprovoked), and
exhibits slightly stronger male transmission (Carter effect). Very high FRR is reported
in individuals with two or more siblings with VTE (FRR > 50). Familial aggregation
is the sum of effects of family environmental and genetic factors. However, studies in
twins, extended families, adoptees, and spouses indicate a weak contribution of shared
familial environmental factors to the familial aggregation of VTE. Moreover, familial
aggregation of VTE fulfills the Bradford Hill’s criteria for causation confirming its importance as a major determinant of VTE. In conclusion, familial aggregation of VTE is
not only an important research tool but also a clinical relevant risk factor for VTE.
References
1.
Zöller B, García de Frutos P, Hillarp A, Dahlbäck B. Thrombophilia as a
multigenic disease. Haematologica 1999;84:59-70.
2.
Dahlbäck B. Advances in understanding pathogenic mechanisms of throm
bophilic disorders. Blood 2008;112:19-27.
3.
Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The
value of family history as a risk indicator for venous thrombosis. Arch Intern
Med 2009;169:610-5
4.
Zöller B, Li X, Sundquist J, Sundquist K. Age- and gender-specific familial risks
for venous thromboembolism: a nationwide epidemiological study based on
hospitalizations in Sweden. Circulation 2011;124:1012-20.
5.
Mannucci PM, Franchini M. Classic thrombophilic gene variants. Thromb
Haemost 2015;114:885-9.
6.
Zöller B, Li X, Ohlsson H, Ji J, Sundquist J, Sundquist K. Family history of
venous thromboembolism as a risk factor and genetic research tool. Thromb
Haemost 2015;114:890-900.
7.
Morange PE, Suchon P, Trégouët DA.Genetics of Venous Thrombosis: update
in 2015. Thromb Haemost 2015;114:910-9
8.
Zöller B, Li X, MD, Ohlsson H, Ji J, Memon AA, Svensson PJ, Karolina Palmer
K, Dahlbäck B, Sundquist J, Sundquist K. Epidemiology of familial aggregation
of venous thromboembolism. Semin Thromb Hemost 2016 (In press).
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Left atrial appendage ligation for the prevention of
cardioembolic stroke
Wade Smith, University of California, San Francisco, USA
The connection between acute embolic ischemic stroke and atrial fibrillation is well
established. Additionally, the evidence basis for primary and secondary stroke prevention with antithrombotic medications is among the most studied area in stroke
research. Oral anticoagulant medications are superior in this regard, but are overall
less effective because of compliance and access to medications, leaving up to a third of
all eligible patients untreated and therefore at high risk of large vessel stroke. Targeting
therapies that prevent stroke without requiring oral anticoagulation therefore may be
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impactful in stroke prevention .
The exact source of cardioembolism in atrial fibrillation is not established with certainty. For many years, the left atrial appendage has been implicated as the major source
of clot formation with a minority of emboli felt to arise from the atrium itself, or perhaps
2,3
even the pulmonary veins . It is rare that one actually sees a clot release from the heart
in real time, so a causal connection is based on inference. However, a growing line of
evidence is reducing this conundrum. I will review the evidence that the left atrial appendage is the major source of cardioembolism and review endovascular strategies to
exclude the appendage from the circulation including the Lariat procedure, thoracos4, 5, 6
copic atrial appendage ligation, and direct suturing of the appendage
. I will review
early data on the impact of these treatments in stroke prevention, especially for those
patients who cannot tolerate oral anticoagulation. Lastly, I will show that atrial fibrillation per se is likely not the cause of cardioembolism; rather it is likely the atrial cardo7
pathy that causes clot formation, and atrial fibrillation is a secondary phenomenon .
References
1. Investigators AWGotA, Connolly S, Pogue J, et al. Clopidogrel plus aspirin versus oral
anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with
Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled
trial. Lancet 2006;367:1903–12.
2. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical
patients with atrial fibrillation. The Annals of thoracic surgery 1996;61:755–9.
3. Stoddard MF, Dawkins PR, Prince CR, Ammash NM. Left atrial appendage thrombus is not uncommon in patients with acute atrial fibrillation and a recent embolic
event: a transesophageal echocardiographic study. Journal of the American College of
Cardiology 1995;25:452–9.
4. Reddy VY, Mobius-Winkler S, Miller MA, et al. Left atrial appendage closure with
the Watchman device in patients with a contraindication for oral anticoagulation: the
ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage
Closure Technology). Journal of the American College of Cardiology 2013;61:2551-6.
5. Bartus K, Gafoor S, Tschopp D, et al. Left atrial appendage ligation with the next
generation LARIAT(+) suture delivery device: Early clinical experience. International
journal of cardiology 2016;215:244–7.
6. Mokracek A, Kurfirst V, Bulava A, Hanis J, Tesarik R, Pesl L. Thoracoscopic
Occlusion of the Left Atrial Appendage. Innovations (Phila) 2015;10:179–82.
7. Kamel H, Okin PM, Elkind MS, Iadecola C. Atrial Fibrillation and Mechanisms of
Stroke: Time for a New Model. Stroke; a journal of cerebral circulation 2016;47:895–900.
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Endovascular Stroke Therapy
Wade Smith, University of California, San Francisco, USA
The treatment of acute ischemic stroke by endovascular means now has extensive evi1
dence of efficacy thanks to remarkable, collaborative international research . This presentation will review these results but also provide a personal experience in the odyssey
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of bringing endovascular therapy to the bedside . Many differences in the regulatory
climate exist between countries, as do the approach to clinical trials. Without the international collaboration in research it is likely that endovascular therapy would have been
set back many years.
Our focus now should be on treating large vessel stroke more quickly. The steep decline in
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clinical outcome as a function of time to vessel opening is clear . Many improvements
in patient flow within the hospital have been successful in reducing door-to-needle
time for IV t-PA. Similar process improvements for reducing time to endovascular care
are in process in comprehensive stroke centers throughout the world. However, these
in-hospital improvements are meeting the problem only half way. Prehospital system
innovations hold the key to even more improvements that will likely translate to better
4
outcomes. Use of in-field CT imaging, pioneered by the Berlin group , is rapidly undergoing study, and use of pre-hospital clinical scales has improved paramedic accuracy in
diagnosing stroke. Research into non-invasive “stroke detectors” is underway as well.
Coupling more accurate field diagnosis with direct triage to the endovascular suite is
the obvious solution to minimizing delays. Internationally, we should set our goals
(commensurate with our cardiology colleagues) of opening the cerebral vessel within 90
minutes of stroke onset.
References
1. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after largevessel ischaemic stroke: a meta-analysis of individual patient data from five randomised
trials. Lancet 2016;387:1723–31.
2. Smith WS, Furlan AJ. Brief History of Endovascular Acute Ischemic Stroke Treatment. Stroke 2016;47:e23–6.
3. Khatri P, Yeatts SD, Mazighi M, et al. Time to angiographic reperfusion and clinical
outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial. The Lancet Neurology 2014;13:567–74.
4. Kunz A, Ebinger M, Geisler F, et al. Functional outcomes of pre-hospital thrombolysis
in a mobile stroke treatment unit compared with conventional care: an observational
registry study. The Lancet Neurology 2016;15:1035–43.
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Revival of the contact system of coagulation: new perspectives for
safe anticoagulation
Thomas Renné, MD PhD
Department of Molecular Medicine & Surgery, L2:05, Karolinska Hospital,
171 72 Stockholm, Institute of Clinical Chemistry, O26, UKE Hamburg,
20251 Hamburg
Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII,
Hageman factor) is a plasma serine protease that initiates the contact system. This system starts a cascade of procoagulant and proinflammatory reactions via the intrinsic
pathway of coagulation, and the bradykinin producing kallikrein-kinin system, respectively. The contact system biochemistry in vitro is well understood, however its in
vivo functions are just beginning to emerge. This presentation will summarize recent
functions of the FXII-driven contact system in vivo.
Genetically altered mice and large animal models have shown that FXII is essential for
thrombus formation while being dispensable for hemostatic processes that terminate
blood loss. Challenging the dogma of a coagulation balance, targeting FXII protected
from cerebral ischemia and ischemic heart disease without interfering with hemostasis.
Targeting FXII provides thromboprotection in preclinical settings without therapyassociated increased bleeding. In contrast, to deficiency in FXII providing thromboprotection excess FXII activity is associated with a life threatening inflammatory disorder, hereditary angioedema. Platelet polyphosphate (an inorganic polymer), neutrophil
extracellular traps (NETs) and mast cell heparin activate FXII with implications on the
initiation of thrombosis and edema. Targeting polyphosphate interferes with arterial
and venous platelet-driven thrombosis in a FXII-dependent manner.
A key aspect of the presentation will be the analysis of common principles, regulation
and cross-talk of FXII-driven protease cascades in coagulation and inflammation and
its therapeutic implications. Targeting FXII and polyphosphate interferes with thrombosis and inflammation in a broad array of clinical settings without increasing bleeding
risk. Elucidating the FXII-driven contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory diseases.
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Who To Test for Pulmonary Embolism?
Poul Henning Madsen, Senior consultant, FSPSP, Dept. of Medicine,
Division of Respiratory Medicine, Vejle Hospital, Denmark
Contemporary management of pulmonary embolism includes – among many other
interventions – modern imaging techniques, novel anticoagulants and in some centers
even pulmonary embolism response teams. However, before these measures can be
initiated, the clinician must suspect that pulmonary embolism can be the cause of the
clinical presentation of the patient. Basic knowledge of pulmonary embolism is therefore relevant to most practicing physicians, as many medical specialties care for patients
with increased risk of pulmonary embolism.
Sudden onset dyspnea, chest pain, syncope and hemoptysis are essential symptoms of
pulmonary embolism, and in most of these patients basic investigations like arterial
blood gas analysis, electrocardiogram, chest x-ray and biochemical analyses are appropriate to reveal important differential diagnoses to pulmonary embolism and to assess
severity. In addition, lung ultrasound and echocardiography are indicated in the initial
evaluation in many of these patients. The information available from the medical history, clinical assessment and basic investigation form the basis on which the decision
about further diagnostic imaging and intensity of treatment and monitoring can be
made. These decisions can be guided by clinical scoring systems like the Wells score,
revised Geneva score and the PESI.
Reference
Madsen PH, Hess S. Symptomatology, clinical presentation and basic work up in
patients with suspected pulmonary embolism. Adv Exp Med Biol 2016 [Epub ahead
of print].
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State-of-the-art imaging in PE: Radionuclide vs. radiologic imaging
Søren Hess, Odense University Hospital, Denmark
Diagnostic imaging is essential in suspected pulmonary embolism due to the notoriously non-specific symptoms and clinical findings. Over the years, several modalities
have been employed, but currently the choice has been narrowed to either radionuclide
or computer tomographic methods, i.e. ventilation/perfusion scintigraphy with single
photon emission computed tomography with or without additional low-dose CT (V/Q
SPECT or SPECT/CT) and contrast-enhanced computer tomography angiography
(CTA). Both methods display advantages and shortcomings, and controversies remain
regarding first-line imaging. This talk provides basic insights into V/Q SPECT and CTA
methodology, basic clinical considerations, interpretation criteria, overall clinical value, and ongoing controversies, i.e. radiation exposure, the issues of subsegmental pulmonary embolism, non-diagnostic studies, and various challenges in specific patient
populations.
References
Hess S, Madsen PH. Radionuclide Diagnosis of Pulmonary Embolism. Adv Exp Med
Biol 2016 (E-pub ahead of print)
Hess S, Frary EC, Gerke O, Madsen PH. State-of-the-Art Imaging in Pulmonary Embolism: Ventilation/ Perfusion Single-Photon Emission Computed Tomography versus
Computed Tomography Angiography – Controversies, Results, and Recommendations
from a Systematic Review. Semin Thromb Hemost 2016 (in press)
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Pulmonary Embolism Response Teams
Christopher Kabrhel MD MPH, Harvard University, USA
Since the creation of the first Pulmonary Embolism Response Teams (PERT) at
Massachusetts General Hospital in 2012, this novel model of care delivery has spread
across the United States, Europe, and South America. PERTs provide rapid assessment
and treatment of patients with life-threatening pulmonary embolism (PE). The multidisciplinary nature of PERTs ensures that diverse opinions are considered when making
complex treatment decisions – especially when robust data comparing treatments are
not available. If needed, PERTs facilitate the mobilization of resources like the catheterization lab and the operating suite. This talk will describe the PERT model, including
examples of how a PERT can benefit patients. The speaker will provide a framework for
creating a PERT at any institution. We will discuss the various treatment options for
PE that can be employed by a PERT, including: anticoagulation, systemic and catheter
directed thrombolysis, suction and surgical thrombectomy and extracorporeal membrane oxygenation. We will review data describing our institution’s initial experience
with PERT, as well as data describing the diversity of PERT programs now participating
in a large consortium of teams. At the end of this talk, audience members will have an
understanding of the PERT model, it’s potential benefits, and will have the tools necessary to create a PERT at their hospital.
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Pulmonary infarction: an often unrecognized clinical entity
Massimo Miniati, MD, PhD.
Department of Experimental and Clinical Medicine, University of Florence,
50134 Florence, Italy
Pulmonary infarction occurs in nearly one third of the patients with acute pulmonary
embolism. Infarcts are still often mistaken for pneumonia or lung cancer bacause of
the deeply rooted belief that they ought to be triangular in shape. In reality, the apical
portion of an embolized region is spared from infarction thanks to sufficient collateral
blood flow. Infarcts are always arranged peripherally along the surface of the visceral
pleura (costal, diaphragmatic, mediastinal or interlobar). Their free margin is sharp
and convex towards the hilum, casting a semicircular or cushion-like density on chest
radiography or computed tomography (CT). Focal areas of hyperlucency within the infarction are often seen on CT. Clinical presentation is nonspecific. Pleuritic chest pain,
either isolated or in combination with abrupt dyspnea, is the most frequent presenting
symptom, whereas hemoptysis is much rarer. Recent data indicate that younger age,
increasing body height, and active cigarette smoking are independent predictors of infarction in the setting of acute pulmonary embolism. Correct recognition of pulmonary
infarction is fundamental because pleural-based consolidations suggestive of infarction
may be the first manifestation of pulmonary embolism.
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Update on the treatment of venous thromboembolism
Sam Schulman, MD, PhD
Department of Medicine, McMaster University and Thrombosis and
Atherosclerosis Research Institute, Hamilton, ON, Canada
During the past 7 years, results from phase III trials comparing non-vitamin antagonist
K oral anticoagulants (NOACs) with vitamin K antagonists (VKAs) or with placebo, including 34,900 patients, have been published. Recent guidelines have been updated and
now suggest treatment with NOACs rather than with VKA. Other updates in the guidelines concern the initial thrombolytic treatment for selected patients with deep vein
thrombosis or pulmonary embolism as well as the possibility to withhold anticoagulation for minimal venous thromboembolism. The optimal duration of anticoagulation
after an unprovoked event is still debatable, depending on values and preferences assigned to recurrent thromboembolism versus bleeding complications. The choice is
essentially between a short duration of 3 or perhaps 6 months for extensive thromboembolism and indefinite duration. Several clinical prediction rules have been developed
to aid in this choice but they all address only the risk of recurrent thrombosis without
weighing in the risk of bleeding. This review provides an update on recent systematic
reviews, meta-analyses and guidelines on treatment of venous thromboembolism.
Key words: venous thromboembolism, thrombolysis, anticoagulation, clinical
prediction rules
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Celebral venous thrombosis
Jonathan Coutinho, University of Amsterdam, the Netherlands
Cerebral venous thrombosis (CVT) is rare location of venous thromboembolism (VTE)
and an important cause of stroke in young adults and children. In contrast to more
common locations of VTE, such as leg-vein thrombosis and pulmonary embolism,
women are affected three times more often than men. Clinical manifestations vary
considerably between patients, but most patients present with headache, seizures or
focal neurological deficits. Diagnosis of CVT is usually established by MRI+MR-venography or CT-venography. Approximately 30–50% of patients have an intracerebral
hemorrhage, which can range from a small juxtacortical hemorrhage to a large spaceoccupying lesion. Based on limited evidence from randomized trials, the primary
therapy for CVT is anticoagulation with heparin. Uncontrolled studies have shown
promising results for the use of endovascular treatment in severely affected patients,
confirmation in prospective clinical trials is required. In patients who develop clinical
and radiological signs of impending herniation decompressive surgery can be both lifesaving and result in a good functional outcome. The optimal duration of anticoagulation is unclear, but most patients are treated for 3–12 months. Despite the fact that many
patients are severely affected in the acute phase, long-term prognosis is favorable for
most cases, although chronic headache and mild cognitive complaints occur relatively
frequently.
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High grade glioma patients:
treatment options for VTE prevention
Timothy R. Smith, MD, PhD, MPH, Harvard University, USA
Venous thromboembolism (VTE), incorporating both deep vein thrombosis (DVT)
and pulmonary embolism (PE), is a common, morbid, and potentially fatal condition.
Patients undergoing surgery are at increased risk of VTE due to many peri-operative
factors, and patients undergoing surgery for high grade glioma have been found to be at
an even higher risk than general surgical patients. Chemical prophylaxis of VTE during
the post-neurosurgical period remains one of the major dilemmas in modern neurosurgical practice, due to a potential increased risk of devastating intracranial hemorrhage
in the setting of anticoagulation. In this review, we aim to summarize the prevalence
of VTE in patients with high grade glioma, and discuss relevant risk factors for development of VTE after surgery for high grade glioma. We also review options for VTE
prophylaxis in the post-operative period and discuss appropriate management of these
complex patients.
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Venous thromboembolism in patients undergoing craniotomy for
brain tumors: a U.S. nationwide analysis
David J. Cote, Harvard University, USA
Patients who undergo craniotomy for brain tumor have an increased risk of developing
venous thromboembolism (VTE). Using the National Surgical Quality Improvement
Program (NSQIP) registry, patients undergoing craniotomy for brain tumor from
2006–2014 were analyzed to identify risk factors for post-operative VTE. The study
population, identified by Current Procedural Terminology (CPT) codes, included all
NSQIP-reported patients who underwent a craniotomy for brain tumor resection.
There were 629 instances of VTE among 19,409 craniotomies for brain tumor (3.2%) recorded in NSQIP. Occurrence of VTE was associated with other post-operative complications on univariate analysis. On multivariate analysis, independent predictors of VTE
included older age, higher body mass index (BMI), functional dependence, ventilator
dependence, steroid use, prior sepsis, and longer operative time. In this presentation
we will discuss the benefits and limitations to the use of big data for evaluating medical
complication post-operatively, using VTE after craniotomy as an example.
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20
Venous thromboembolism in children
Vlad C Radulescu, University of Kentucky, USA
Pediatric thromboses have particular features, stemming from distinct risk factors
and age-dependent physiologic differences of the hemostatic system.
Venous thromboembolism (VTE) is uncommon in children compared to the adult
population, though its incidence showed a significant increase over the past two
1
decades .
The VTE incidence has a bimodal age distribution with peaks in infancy and adolescence. The risk factors, associated conditions and impact of inherited thrombophilia
2
are different for these two populations .
The treatment of pediatric VTE is, to a large extent, modeled on the adult experience.
Given the rarity of the condition, most of the pediatric trials are small and underpowered. The current treatment guidelines, while valuable in providing a framework for the
practicing physicians, have recommendations that are often based on expert opinion
3, 4
and low quality evidence .
The most commonly used anticoagulant agents in children are the low molecular
5
weight heparins and vitamin K antagonists . The non-vitamin K antagonist oral anticoagulant drugs (NOACs) are not yet approved for pediatric use, there is limited pharmacologic data form initial studies in children, and there are several ongoing clinical
6
trials of NOACs for prevention and treatment of VTE .
1
Raffini, L., et al., Dramatic increase in venous thromboembolism in children's hospitals
in the United States from 2001 to 2007. Pediatrics, 2009. 124(4): p. 1001–8.
2
Klaassen et al., Manifestations and clinical impact of pediatric inherited thrombophilia.
Blood 125 (7): p. 1073–1077.
3
Monagle, P., et al., Antithrombotic therapy in neonates and children: Antithrombotic
Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines. Chest, 2012. 141(2 Suppl): p. e737S–801S.
4
Giglia, T.M., et al., Prevention and treatment of thrombosis in pediatric and congenital
heart disease: a scientific statement from the American Heart Association. Circulation,
2013. 128(24): p. 2622–703.
5
Law, C. and L. Raffini, A guide to the use of anticoagulant drugs in children. Paediatr
Drugs, 2015. 17(2): p. 105–14.
6
von Vajna, E., R. Alam, and T.Y. So, Current Clinical Trials on the Use of Direct Oral
Anticoagulants in the Pediatric Population. Cardiol Ther, 2016. 5(1): p. 19–41.
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Post thrombotic syndrome
Raveena Ravikumar, Imperial College London, UK
AH Davies, Imperial College London, UK
Introduction
Post thrombotic syndrome (PTS) is a collection of signs and symptoms seen as a long
term sequel of deep venous thrombosis (DVT). Symptoms can range from mild swelling
with minimal impact on quality of life, to debilitating pain and ulceration. PTS is associated with significant morbidity and treatment cost.
Methods
Literature review on the pathophysiology, clinical features, prevention and management of PTS of the lower limb.
Results
The incidence of PTS varies from 30-40% with distal DVT to 50-60% in patients with
proximal DVT. PTS presents normally within 2 years of the index DVT event. Multiple scoring systems are available to evaluate the severity of PTS including the Villalta,
Ginsberg, Brandjes, Widmer and CEAP scoring systems. Diagnosis is supported by
investigations including ruplex ultrasound, computerised tomography (CT) and magnetic resonance (MR) venography, as well as ascending and descending venography.
Management of PTS aims to reduce ambulatory venous pressure using exercise therapy,
compression hosiery and multilayer bandaging. Pharmacological adjuncts such as
Daflon and Pentoxyfiline have been shown to improve ulcer healing rates in combination with compression. Endovascular interventions aim to improve venous patency.
Deep venous bypass procedures including bypass procedures and valvuloplasty have
variable outcome and can carry significant operative morbidity.
Conclusion
The new challenge in managing the long term outcome of patients with DVT is improving the quality of life of patients and preventing the sequelae of PTS, particularly
venous ulceration. Greater awareness of its morbidity has to be made to allow for new
techniques to develop in managing this disease.
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22
The optimal duration of anticoagulation in patients with
unprovoked venous thromboembolism
Paolo Prandoni, Department of Cardiovascular Sciences
Vascular Medicine Unit, University of Padua, Italy
Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE)
over years approaches 50% of all patients with a first episode of unprovoked VTE. The
persistence of residual vein thrombosis at ultrasound assessment has consistently been
shown to increase the risk, as do persistently high values of D-Dimer. Although the latest international guidelines suggest indefinite anticoagulation for most patients with
the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify a substantial proportion of subjects in whom anticoagulation can be safely discontinued. For those patients
in whom anticoagulation cannot be discontinued, new opportunities are offered by the
availability of low-dose anti-Xa compounds, which have been found to possess an extremely favourable benefit/risk profile.
T H RO M B O S I S A N D E M B O L I S M · 17–18 N OV E M B E R 2 016
23
Catheter directed thrombolysis and Pharmacomechanical
thrombolysis
Raveena Ravikumar, Imperial College London, UK
AH Davies, Imperial College London, UK
Introduction:
Deep vein thrombosis is associated with significant morbidity and mortality.
Conventional treatment involves anticoagulation and compression stockings.
Despite best medical therapy, 20–50% of patients develop post thrombotic syndrome (PTS), which can lead to venous ulceration. Iliofemoral DVT increases the
risk of PTS by x fold. Early thrombus removal has been advocated to prevent this
sequelae.
Methods:
Review of literature on the use of catheter directed thrombolysis (CDT) and pharmacomechanical thrombolysis (PMT) in patients with iliofemoral DVT.
Results
Catheter directed thrombolysis (CDT) involves intrathrombus administration of
thrombolytic agent Pharmacomechanical thrombolysis (PMT) employs a whole host
of adjuncts to enhance thrombus dissolution and can be categorised into rotational
thrombectomy, aspiration thrombectomy, rheolytic devices and ultrasound accelerated
thrombolysis. The results have shown that CDT compared to standard anticoagulation
improves venous patency, preserves valve function and reduces the risk of PTS. PMT
with or without CDT has been shown to have similar complete thrombus removal and
primary patency at 1 year rates. PMT reduces hospital stay and cost compared to CDT.
Discussion
Proximal DVT is a significant cause of morbidity and mortality in patients. CDT and
PMT offer a safe new approach to treating these patients. Whilst the evidence for CDT
is strongly supported by randomised controlled trials, the evidence for PMT is still
awaiting the results of the ATTRACT trial, an open label, randomised controlled trial
comparing the use of PMT and CDT to standard anticoagulation.
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Deep vein thrombosis in Intensive Care Unit
Maria Boddi, MD,PhD, Department of Experimental and Clinical Medicine,
University of Florence, Italy
Thromboembolism (TE) continues to be an emergency for all hospitalized medical and
surgical patients; however the issue of “thromboembolism in intensive care units” deserves dedicated treatment because of some peculiar characteristics of critical patients.
We synthesize the most relevant: a) critical patients are a heterogeneous population and
in critical care patients not receiving thromboprophylaxis a DVT prevalence ranging
between 10 and 80% was shown. In these last years attention has been focused on medical-surgical ICU setting where a failure rate of prophylaxis as high as 5 to 15% was reported ; b) in ICU DVT can rarely be diagnosed through clinical data owing to the fact
that patients very often cannot communicate symptoms due to their underlying conditions, pharmacotherapy and mechanical ventilation; signs such as oedema are common
in the ICU setting. Diagnosis of DVT needs ultrasound screening that must be scheduled so that the ratio cost/benefit ratio can be sustainable. c) risk assessment models
for DVT diagnosis that are used for out-patients (Wells score) or hospitalized medical
(Padua score), surgical (Caprini modified score) or trauma patients cannot be applied
to critically ill patients. Pretest probability scores developed and validated outside ICU
for diagnosis of pulmonary embolism (PE) do not correlated with clinically suspected
PE in ICU. In ICU patients not only baseline risk factors such as personal or family history of VET or illness score severity at admission, but also time dependent factors due to
newly acquired pathologies such as acute kidney injury (AKI) or infection and iatrogen
interventions and therapies concur to determine thrombotic risk which is dynamic and
can change from day to day. d) many ICU patients are at risk of major bleeding and this
limit the use of anticoagulants.The balance between thrombotic and haemorrhagic risk
must be evaluated daily, as it can change suddenly.e) compliance with thromboprophylaxis is crucial for ICU patients and dedicated strategies to improve it such as programs
of continued education for physicians and nurses and /or electronic order sets and reminders must be adopted in each ICU.
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Controversies in the management of venous thromboembolism
in patients with cancer
Paolo Prandoni, Department of Cardiovascular Sciences
Vascular Medicine Unit, University of Padua, Italy
Cancer associated thrombosis (CAT) is a frequent complication among cancer patients.
It is associated with increased morbidity, mortality, and psychological burden. Lowmolecular-weight heparin monotherapy for the initial 6 months is considered the standard of care for the acute and long-term management of CAT. For patients at high risk
of recurrent CAT (e.g. active cancer or still undergoing anti-cancer therapy) beyond the
initial 6 months of treatment, continuation of anticoagulation therapy for secondary
prevention is usually recommended. The management of anticoagulation therapy is
more challenging in patients with cancer. Cancer patients are more likely to have recurrent events despite anticoagulation, thrombocytopenia due to their chemotherapy
regimens or have incidental pulmonary embolism diagnosed on their staging imaging.
Expert consensuses and opinions in order to guide clinicians on how to tailor the management of CAT in these special circumstances will be presented and discussed.
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26
Bleeding complications and management on anticoagulant
therapy
Sam Schulman, MD, PhD
Department of Medicine, McMaster University and Thrombosis and
Atherosclerosis Research Institute, Hamilton, ON, Canada
Patients treated with anticoagulants have an unavoidable risk of bleeding complications. There are for all oral anticoagulants several potential options for management
of major bleeding. The first action is, however, to assess the relative role of the anticoagulant for the current bleeding. Supportive measures have been assessed in several
post-hoc analyses of the phase III pivotal trials with the non-vitamin K antagonist oral
anticoagulants (NOACs). Those results will be reviewed here together with emerging
data on the efficacy and safety of the specific antidotes idarucizumab (for dabigatran)
and andexanet α (for factor Xa inhibitors). Regular or activated prothrombin complex
concentrates are also evaluated and might have a role as alternatives for management
of NOAC-associated major bleeding if the antidote is not available. Once hemostasis
has been achieved it is imperative to assess the possibility and timing of resumption of
anticoagulation, since these patients have a prothrombotic state and a non-negligible
proportion of the patients will have thromboembolic complications already during the
first month after the hemorrhage. Many factors will have to be taken into account for
this decision and unfortunately the guidelines in this respect are very weak if at all available. Hopefully, this review will provide some assistance in the management of major
bleeding and the post-hemorrhage care.
Key words: Bleeding, reversal, resumption, warfarin, NOACs
T H RO M B O S I S A N D E M B O L I S M · 17–18 N OV E M B E R 2 016
27
Poster abstracts
Page
Is it safe to withhold long-term anticoagulation therapy in patients
with small pulmonary emboli diagnosed by SPECT lung scintigraphy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
R.Ghazvinian, A. Gottsäter, J. Elf, Sweden
Point of care coagulation test using electrical signal analysis in blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Achyut Sapkota, Ngyuen Huu Dung, Osamu Maruyama, Masahiro Takei, Japan
Treatment of massive pulmonary embolism associated with hypotension – results from
a newly introduced multidisciplinary Standard Operating Procedure (SOP) . . . . . . . . . . . . . . . . . . . . . 31
Kristina Tempelman Svennerholm, MD, PhD; Carl Johan Malm, MD;
Bengt Redfors, MD, PhD; Charlotte Sandström, MD; Karin Zachrisson Jönsson, MD;
Lisa Hägerström, CCN; Christian Rylander, MD, PhD, Sweden
Post-Stroke as well as Acute Stroke IgG as a Potential Effector of Haemostasis System . . . . . 32
Katrii Tetiana PhD-student, Savchuk Olexiy Prof., Vovk Tetiana PhD,
Taras Shevchenko National University of Kyiv, Ukraine
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28
Is it safe to withhold long-term anticoagulation therapy in patients
with small pulmonary emboli diagnosed by SPECT lung scintigraphy?
R.Ghazvinian, A. Gottsäter and J. Elf.
Division of Vascular medicine, Skåne University Hospital, Ruth Lundskogs
Gata 10, S-205 02 Malmö, Sweden
[email protected]
Background
Long-term anticoagulation therapy (AC) in patients with subsegmental pulmonary
embolism (SSPE) diagnosed by computer tomography (CT) has been questioned, as
these patients run low risk for recurrent venous thromboembolism (VTE) during
3 months of follow-up. Whether this applies also to patients with small PE diagnosed
with lung scintigraphy has not been evaluated.
Methods
We retrospectively evaluated 54 patients (mean age 62±19 years, 36 [67%] women) with
small PE diagnosed by ventilation/perfusion (V/P) single photon emission computed
tomography (SPECT) lung scintigraphy who had not received conventional long-term
AC. Either the SPECT result was interpreted as falsely positive for technical reasons,
the perfusion defect was thought to represent an old and no longer relevant embolization, or the embolization was thought to be too irrelevant to merit treatment. Thirty-six
(67%) received less than 48 hours of AC, 11 (20%) patients were treated for 2–4 days, and
7( 13%) for 15–30 days. D-dimer was negative in 18 (33%), positive in 10 (19%), and not
analyzed in 28 (52%) patients, and 7 (13%) had malignancy. Phlebography had been
performed with negative result in one patient.
Results
No deaths or PE occurred during 90 days. Seven patients were readmitted to hospital, in
5 cases (9%) for suspected VTE. Four patients (7%) underwent phlebography or ultrasound of the lower extremities, whereof two (2/54 [4%]) were diagnosed with deep
venous thrombosis (DVT) necessitating long-term AC. One 71 year old man who had
received AC for 24 hours was readmitted 38 days hereafter with external iliac vein DVT,
and a 92 years old woman who had received AC for 20 days was readmitted 52 days hereafter with common femoral vein DVT.
Conclusion
Withholding long-term AC therapy in patients with SSPE diagnosed by V/P SPECT
resulted in 4% risk for recurrence of VTE during 90 days of follow up, and can therefore
currently not be recommended.
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29
Point of care coagulation test using electrical signal analysis
in blood
Achyut Sapkota1*, Ngyuen Huu Dung2 , Osamu Maruyama3,
2
Masahiro Takei
1
Department of Information and Computer Engineering, National
Institute of Technology, Kisarazu College, Kisarazu, Chiba Japan
2
Division of Artificial Systems Science, Graduate School of Engineering
Chiba University, Chiba, Japan
3
Artificial Organ Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
*Presenting author: Doctor of Engineering(Dr.Engg), [email protected],
[email protected]
Extracorporeal blood flow circulation systems such as heart-lung machine and hemodialyzers need real time understanding of the coagulation risk. Activated clotting time
(ACT), prothrombin time (PT) and thromboelastography tests are the conventional
coagulation tests in these and other related procedures. In one hand, these tests are time
consuming and expensive to be performed in parallel for several samples. For example,
in any clinical setting, one of the factors that limit the number of patients, taking hemodialysis treatment in the similar time frame, is the management of coagulation tests
and administration of anticoagulation therapy. On the other hand, in essence, these
tests results can’t be called real-time results. This study is about the exploitation of
electrical properties of the blood undergoing coagulation. We conducted coagulation
experiments in bovine and swine blood samples. Experiments were conducted in static as as well as with the blood circulating in the mock extracorporeal circulation. The
blood samples were treated with trisodium citrate immediately after withdrawal and
coagulation risks were varied by the the gradual addition of aqueous solution of calcium
chloride during experiments. The response of the blood, under multifrequency electrical signals, were recorded and analysed. Change in characteristic frequencies of the
blood undergoing thrombosis were different from the normal blood. Bifurcation was
observed at time T in the change in characteristic frequencies of blood undergoing coagulation. This time on the basis of ACT tests and biophysical/biochemical simulations
could be correlated to the clot formation (RBC aggregation stage after fibrin formation).
These results indicate that the measurement of characteristic frequency of the blood
can be an effective point of care coagulation testing. It has potential to provide real-time
monitoring of coagulation risk. Additionally, it can be implemented, without complicated extension, for the parallel measurements of multiple samples using multiplexing
techniques of electrical engineering.
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Treatment of massive pulmonary embolism associated with
hypotension – results from a newly introduced multidisciplinary
Standard Operating Procedure (SOP)
1
Kristina Tempelman Svennerholm, MD, PhD; 2Carl Johan Malm, MD;
3
Bengt Redfors, MD, PhD; 4Charlotte Sandström, MD; 4Karin Zachrisson
1
1
Jönsson, MD; Lisa Hägerström, CCN; Christian Rylander, MD, PhD
1
Anaesthesia and Intensive Care, 2 Thoracic Surgery, 3 Thoracic Anaesthesia
4
and Intensive Care, Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden
Background
If not promptly treated, massive pulmonary embolism with circulatory failure (defined
as systemic systolic blood pressure below 90 mmHg at any time) carries a mortality
approaching 50% in the acute phase. First line treatment is intravenous thrombolysis
but if thrombolysis is contraindicated or turns out ineffective, alternatives need to be
readily accessible. For this purpose, we introduced a new official SOP in the Western
Region (VGR) of Sweden in 2013. Intravenous thrombolysis in the intensive care unit
(ICU) is usually initiated by the referring physician and the intensivist in charge. When
alternative or further treatment is warranted, their next step is immediate consultation
by a dedicated multidisciplinary team with senior consultants in thoracic anaesthesia
and surgery, interventional radiology and intensive care medicine. Their task is to consider the options and assign the patient to either catheter-based intervention, surgical
embolectomy or extracorporeal circulatory support (ECMO). In this abstract, we report
the results from the first two years of this SOP being in use.
Method
Retrospective data collection from hospital records of patients treated for pulmonary
embolism in the four ICUs of Sahlgrenska University Hospital 2014–2015.
Results
The search identified 92 patients of which 44 (48%) were hemodynamically compromised with systolic blood pressure below 90 mmHg at admission. Their treatment
and hospital outcome is listed below; seven patients were subjected to more than one
method. Five patients had an inferior vena cava filter installed. The deaths all occurred
in the acute phase in spite of active intensive care. The patients who survived all recovered without sequels.
Method Patients
Survivors
Deceased
Intravenous thrombolysis32
43
(74%)
11
Catheter fragmentation 12
7 (58%)
5
Surgical embolectomy 2
1 (50%)
1
Veno-arterial ECMO
5
1 (20%)
4
Anticoagulation only 48
36 12
(75%)
Conclusion
The hospital survival after intravenous thrombolysis for acute massive pulmonary
embolism was in line with international results. The number of patients treated by
alternative techniques is still too small for any firm conclusion about outcome.
Catheter-based intervention was associated with a slightly lower fraction of survival
than in published case series. ECMO was used for the most critical cases in cardiac
arrest. The patient who did not survive surgical embolectomy suffered from both
acute and chronic pulmonary embolism.
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31
Post-Stroke as well as Acute Stroke IgG as a Potential Effector of
Haemostasis System
Katrii Tetiana PhD-student, Savchuk Olexiy Prof., Vovk Tetiana PhD
Department of Biochemistry, Educational and Scientific Center ‘Institute of
Biology’, Taras Shevchenko National University of Kyiv, Ukraine.
01601. 64/13, Volodymyrska Street, Phone: +3849-521-35-98.
Fax: +3849-521-35-98.
Contact: Tetiana B. Katrii, PhD-student
[email protected]
Background: The ischemic stroke development leads to serious changes in haemostasis
cascade. Appearance of a large number of molecules proteins and fragments unusual to
healthy physiological condition in the blood are the outcomes of haemostasis dysfunction. The circulation of these molecules in the bloodstream may lead to their representation as antigenic determinants on the surface of macrophages. As a result antibodies to
proteins or molecules actually of its own body appeared in the bloodstream.
These autoantibodies could potentially possess effector properties to the individual
components of haemostasis, platelet receptors or endothelial cells. The constant presence of these molecules in the bloodstream, even past-stroke, creates a potential threat
to launch non-specific mechanisms of regulation of certain haemostasis reactions.
Methods and Results. Three fractions of immunoglobulin class G were separated:
from the blood plasma of healthy donors, patients with atherothrombotic and cardioembolic ischemic stroke in acute phase as well as one year past acute phase. The influence of the separated fractions on the amidolytic activity of the key haemostatis factors:
thrombin, activated protein C and factor Xa were tested. The fact that IgG obtained
from the donors plasma did not influenced tested process meaningful was proved previously.
Conclusions: The current results, confirmed the hypothesis about appearance of in
the bloodstream of autoantibodies with effector properties relative to the individual
components of the haemostasis system even 1 year after the occurrence of an ischemic
stroke.
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32
Who was Berzelius?
He also found that elements combine with each other
according to fixed numerical relationships. In addition to this, in his striving for order and method, with
his talent for simplicity and clarity in expression, he
created the chemical symbolic language in 1813, which
since that time has been an essential instrument of
chemistry.
With time he became a practised lecturer but preferred
to express himself in writing and this he did superbly.
Impressive are the great scientific works where he also
demonstrated his interest and ability to spread knowledge about the latest advances of natural sciences.
Berzelius delight in research and debate was united
with a great humility before the great scientific questions. Both his attitude and artistry of formulation is
illustrated by the following passage in his Manual of
Cheamistry (vol 3, 1818):
»All our theory is but a means of conistently conceptualizing the inward processes of phenomena, and
it is presumable and adequate when all scientifically
known facts can be deduced from it. This mode of conceptualization can equally well be false and, unfortunately, presumable is so frequently. Even though, at a
certain period in the development of science, it may
match the purpose just as well as a true theory. Experience is augmented, facts appear which do not agree
with it, and one is forced to go in search of a new mode
of conceptualization within which these facts can also
be accomodated; and in this manner, no doubt, modes
of conceptualization will be altered from age to age, as
experience is broadened, and the complete truth may
perhaps never be attained. But even if the goal can never be reached, let us never abondon our endeavor to
get closer to it.«
Jöns Jacob Berzelius, one of the most prominent natural scientists of the 19th century, was born in 1779 in
Väversunda, in the county of Östergötland in southern Sweden, a region with rich cultural traditions.
Orphaned at an early age, he went to several fosterhomes and received his schooling in nearby Linköping. After graduating in medicine at the University
of Uppsala, he moved to Stockholm, where he became
assistent master without pay at the so-called »Surgical School«, and worked as a doctor for poor people.
At the age of 28 he became professor of medicine and
pharmacy.
In 1808 Berzelius was one of the seven men who
founded The Swedish Society of Medicine »For the
perfection of science through mutual mediation of
knowledge and collective experience, for the promotion of friendly confidence between doctors«.
Berzelius have enriched our knowledge of nature
of life phenomena, established the atomic weights
of most of the known elements, presented his electrochemical theory for the understanding of the nature of chemical compounds and laid the foundation for the sciences of the chemistry of rock types.
Parts of this text is found in: Berzelius – Creator of the
chemical language, by Carl Gustaf Bernhard, the Royal
Swedish Academy of Sciences
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T H RO M B O S I S A N D E M B O L I S M · 17–18 N OV E M B E R 2 016
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History of the SSM building
In 1879, the Swedish Society of Medicine moved
from what was then the home of Karolinska Institutet at Norr Mälarstrand to its own premises in
Jakobsgatan in Stockholm. It soon outgrew this
location and a search for new premises was resumed. On Walpurgis night in 1889, six men were
inside the Katarina lift at Slussen in Stockholm.
A fault developed in the machinery, causing
the lift cage to fall. One of the passengers, Carl
Westman, was injured, but a fellow passenger,
Johan Rissler, a surgeon and member of the
building committee of the Society of Medicine,
immediately assisted him.
In 1904, the Society announced an architectural competition for a building on a site it had
purchased in Klara Östra Kyrkogata.
The winner was Carl Westman, and the building
was finished two years later.
The Society’s building which dates from 1906, was
a breakthrough for the architect Carl Westman and
the national romantic style architecture he favoured.
The building itself is work of art – from its facade of
handmade brick and Christian Eriksson’s granite
reliefs in the entrance to its mosaic floors, carved
balustrades, chandeliers, and ventilation grilles
– all Westman signatures. The building today is a
Swedish, turn of the century architectural treasure.
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Svenska Läkaresällskapet
Box 738, Klara Östra Kyrkogata 10, SE-101 35 Stockholm Sweden
T H RO M B O S I S A N D E M B O L I S M · 17–18 N OV E M B E R 2 016
http://www.sls.se
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