Heart and Blood Vessels

(1)

Heart and Blood Vessels

Development, Disease and State of the Art Therapies

Module coordinators:

Prof. Dr. van Zonneveld Prof. Dr. D.E. Atsma Drs. R.G. de Bruin [email protected] [email protected] [email protected]

M O D U L E B O O K

Bachelor Medicine, third year

Course year 2014-2015

(2)

Behoudens de in of krachtens de Auteurswet van 1912 gestelde uitzonderingen, mag niets uit deze uitgave worden verveelvoudigd en/of openbaar gemaakt worden door middel van druk, Photographkopie, microfilm, web-publishing of op welke andere wijze dan ook en evenmin in een gegevensopzoeksysteem worden opgeslagen zonder voorafgaande schriftelijke toestemming van de houder van de copyrights.

Voor vragen of informatie kunt u contact opnemen met:

Directoraat Onderwijs en Opleidingen, PB 9600, 2300 RC Leiden

(3)

Module committee and teachers

Module coordinators

Prof. Dr. A.J. van Zonneveld (Anton-Jan) Discipline: Experimental Vascular Nephrology [email protected]

Room C7-29

Telephone: 071-5265196

Prof. Dr. D.E. Atsma (Douwe) Discipline: Interventional Cardiology [email protected]

Room C5-32

Drs. R.G. de Bruin (Ruben)

Discipline: Experimental Vascular Medicine [email protected]

Room C7-36

Module committee: Week coordinators

Prof. dr. D.E. Atsma, Dr. D.A. Pijnappels, Prof. dr. H.C.J. Eikenboom, Prof. dr. M.V. Huisman, Prof. dr. P.H.

Reitsma, Prof. dr. M.J.T.H. Goumans, Prof. dr. P.H.A. Quax, Prof. dr. J.F. Hamming, Prof. dr. P.C.N. Rensen, Prof. dr. A.M. Pereira, Prof. dr. H. Pijl, Prof. dr. Ir. J.A.P. Willems van Dijk and Prof. dr. A.J. van Zonneveld.

Teachers

Department of Nephrology Dr. H.C. de Boer

Dr. Ir. R. Bijkerk Dr. M.A. Engelse Prof. H. de Fijter Dr. A. Gaasbeek

Prof. Dr. E.J.P. de Koning M. Moses

Prof. A.J. Rabelink Dr. M.E.J. Reinders Dr. T.C. Rothuizen Dr. J.I. Rotmans Dr. E.P. van der Veer Y. Abdallah

Department of Cardiology Dr. R. Alizadeh Dehnavi Dr. S.L.M.A. Beeres Dr. B.O. Bingen Dr. G. de Grooth Prof. J.W. Jukema Dr. F. van der Kley Dr. P. Steendijk Dr. S.A.I.P. Trines Dr. H.F. Verwey Dr. A.A.F. de Vries Prof. K. Zeppenfeld

(5)

2 Department of Anatomy & Embryology

Prof. Dr. C.L. Mummery J.C. van Munsteren Prof. Dr. M.C. de Ruiter L.J. Wisse

Department of Molecular Cell Biology Prof. Dr. M.J.T.H. Goumans

Dr. A.M. Smits

Department of Endocrinology Dr. J.F.P. Berbée

Dr. N.R. Biermasz Drs. M.R. Boon Dr. O.C. Meijer Dr. D. Mook Dr. Y. Wang

Department of Thrombosis & Haemostasis Dr. M.H.A. Bos

Dr. F.A. Klok

Dr. F.J.M. van der Meer Dr. H.H. Versteeg Dr. B.J.M. van Vlijmen

Department of Human Genetics Dr. V.J.A. Van Harmelen Dr. Ir. J.B. van Klinken

Department of Surgery Dr. J.H.N. Lindeman Dr. A.Y. Nossent Dr. A. Schepers Dr. Ing. M.R. de Vries Dr. C.Y. Wong

Department of Clinical Epidemiology Dr. Ir. R. de Mutsert

LACDR, Biopharmaceutics Prof. Dr. J. Kuiper

Dr. P. Vulto

Department of Pathology Dr. H. Baelde

Department of Neurology M.J.H. Wermer

(6)

3

Introduction

In ten consecutive weeks the students will be introduced to the most current concepts in the pathogenesis, diagnosis and therapy of the most common forms of cardiovascular disease. The course will start with a basic introduction into the anatomy, physiology and haemostatic mechanisms in the cardiovascular system. Next, the students will be introduced in the pathogenesis of macrovascular disease (e.g. atherosclerosis, coronary artery disease, ischemic peripheral disease) and microvascular diseases (e.g. ischemic heart disease, heart failure).

Current options for diagnosis and therapy will be discussed as well as the current approaches in epidemiology and the use of biomarkers for cardiovascular disease.

A special feature of this ½ minor is that we will also aim to update the students on various “molecular medicine”

approaches that are currently employed to develop novel experimental therapies. Last days of the week will be devoted to introduce the students to innovative preclinical (animal) models that are used by the members of the profile area to study the pathophysiology and experimental therapies of the topic of the week. Where relevant, current insights in molecular backgrounds of the innovative strategies will be reviewed.

At the beginning of the course each of the students will receive a case description of a patient that typifies the cardiovascular disease states that are addressed in the consecutive weeks (e.g. acute coronary syndrome, hearth failure, diabetes with cardiovascular complications etc.). Following every weekly course, the students are requested to write a blog in which they list and discuss the relevance of the topics reviewed in the past week to the case they were assigned to study. These blogs will be assessable to dedicated teachers (teachers will be assigned to provide feedback on the blog of a limited number of students) who will give short comments or feedback that can be helpful to the student and helps to make sure they do not forget to update their blogs). In the course of the ½ minor this blog will accumulate into a document that includes aspects of the etiology, epidemiology, pathogenesis diagnosis and therapeutic approaches that are relevant to the individual cases of the particular student. In the final week the student will be asked to write a comprehensive case report including diagnosis, etiology, potential treatment, prognosis and future therapeutic options. This case report will serve a main part of the examination process.

(7)

(8)

5

Module overview

Half minor: Heart and blood vessels: development, diseae and state of the art therapiesAtsma, van Zonneveld, de Bruin

Week 1 Development and anatomy of the cardiovascular system, molecular medicine Atsma, van Zonneveld, de Brui 2-5 Sept

Embryology of the cardiovascular system de Ruiter

Genetic variations in cardiovascular development van Wisse, van Munsteren

Endothelial cell biology Van Gils, Rabelink

Mechanisms in vascular maintenance and repair van Zonneveld, de Boer

The basics of molecular cell biology and gene expression van der Veer

The technique of PCR de Bruin, van Vlijmen

Week 2 Physiology of heart and vessels Atsma, Pijnappels

8-12 sept

Heart function Pijnappels, de Vries, Steendijk

Electrophysiology Ypey, Trines, Feola,

Blood pressure regulation and hypertension Rotmans, Jangsangthong

Experimental therapeutic approaches in hypertension Majumder, Askar

Week 3 Hemostasis and thrombosis Eikenboom, Huisman, Reitsma

15-19 sept

Pathophysiology of Blood Coagulation Versteegh

Clinical and laboratory diagnostics in hemostasis Huisman, Bos,

Hemophilia and clinical management van der Meer, Klok

Acute severe derangement of hemostasis van Vlijmen

Exam week 1-3

Week 4 Macrovascular disease: atherosclerosis 1 Rensen, Willems van Dijk,

Pereira 22-26 sept

Dyslipidemia Jukema, Pijl, Huisman

Obesity, Metabolic syndrome and Type 2 diabetes Van Harmelen, Kuiper

Pathogenesis of atherosclerosis Boon

Inflammation, Risk factors

Week 5 Macrovascular disease: atherosclerosis 2 Rensen, Willems van Dijk

29 sept-3 oct

Cerebrovasculair incident Wermer, van Walderveen

Genetics and epidemiology Mutsert, Kruyt

Central mechanisms Biermasz, van Zonneveld

Rationale and design of the NEO study Mook, van Klinken

Week 6 Clinical diagnosis and therapy Atsma, Pijnappels

13-17 oct

Acute coronary syndrome and heart failure Jukema, Beeres,Steendijk

Clinical management of ACS Verwey, de Grooth

Cardiac arrhythmia's Alizadeh, Zeppenfeld

Conventional therapies (angioplasty, bypass, medication) van der Veer, de Vries

Experimental models for neointimal hyperplasia Bingen

Exam week 4-6

Week 7 Vascular surgery and peripheral artery disease Hamming, Quax

13-17 oct

Introduction in vascular surgery Schepers, de Vries

Post-interventional vascular remodeling Lindeman

Aneurysma's Rotmans, Rothuizen

Vascular access in CKD Chun Yu Wong, Nossent

Week 8 Microvascular disease Goumans

20-24 oct

Cardiovascular complications of type 1 diabetes De Koning, van Zonneveld

Pathophysiology of Diabetic Nephropathy de Fijter

Cardiac manifestations of microvascular disease Gaasbeek

Microvacular rarefaction and fibrosis Baelde

Experimal animal models in microvascular disease Bijkerk

Week 9 Innovative therapeutic strategies Atsma

27-31 oct van Zonneveld

Concept of personalized medicine

Models for drug testing in CVD Mummery

Innovative therapies for the heart Vulto, Reinders

Innovative therapies for the heart and beyond Goumans

Transplantation of islets to treat hyperglycemia Engelse

Final exam

Week 10 Case Report Atsma, van Zonneveld

3-7 nov Write and submit your case report Present case report

(9)

6

Overall learning objectives

1. Evaluate the pathogenic molecular mechanism(s) that might underlie the complaints of a patient diagnosed with a cardiovascular disorder and relate these pathogenic mechanisms to signs and symptoms

2. Be able to motivate and interpret conventional and innovative diagnostic plans that could be applied based on a differential diagnosis

3. Develop a “state of the art” therapeutic plan based on the results from diagnostic tests and corresponding diagnosis and describe the method to check the effect of the intervention

4. Critically assess and communicate recent high impact publications in cardiovascular medicine with regard to methodology, pit falls and limitations.

5. Explain the molecular mechanisms underlying innovative therapeutic strategies and relevant experimental animal models for cardiovascular disease

6. Be able to make an evaluation of the feasibility, clinical potential and societal and legislative relevance of novel innovative therapeutic strategies for specific patient cases.

7. Write a case-report with emphasis on the integration of conventional and innovative diagnostics and therapeutic strategies.

8. Identify relevant literature related to the topics of the course and the selected case report.

9. Demonstrate the ability to implement feedback to the blog and case report.

(10)

7

Tests and examinations

Test matrix

Assignment Paper presentations

Knowledge test 1, 2

Final

knowledge test

Cumulative blog Case report

Type of exam Oral presentation Written exam over week 1-3 and 4-6 All open questions.

Written exam over week 1-9 All open questions.

Up to 500 word reflections of relevance weekly topics to case descriptions

Written case description (see below)

Area Academic skills, communication, collaboration

Knowledge Knowledge, Academic skills

Knowledge, Academic skills, communication

Time Week 2,4,5,6,7 Week 3,6 Week 9 Week

2,3,4,5,6,7,8 and 9

Week 10

Length During 1.5 hr workgroups

1.5 hr 1.5 hr 2 hr 20 hour

preparation Weight

(% of total)

Pass/Fail 25% 25% Pass/correct and

pass

50%

Collaboration Group (5P) Individual basis Individual basis Individual basis Individual basis

Assessed by Minor teachers by teachers by teachers Mentor dedicated to student

Mentor dedicated to student Number

of question

N.a. Open (10) Open (10) N.a. N.a.

(11)

8

Further specification to learning objectives

Type of exam Paper

presentations

Knowledge tests (3x)

Cumulative blog

Case report

evaluate the pathogenic molecular mechanism(s) that might underlie the complaints of a patient diagnosed with a cardiovascular disorder and relate these pathogenic mechanisms to signs and symptoms (academic)

X X X X

able to motivate and interpret conventional and innovative diagnostic plans that could be applied based on a differential diagnosis

X X X

develop a “state of the art” therapeutic plan based on the results from diagnostic tests and corresponding diagnosis and describe the method to check the effect of the intervention

X X X

critically assess and communicate recent high impact publications in cardiovascular medicine with regard to methodology, pit falls and

limitations (academic, communicator)

X X

explain the molecular mechanisms underlying innovative therapeutic strategies and relevant experimental animal models for cardiovascular disease (academic)

X X X

able to make an evaluation of the feasibility, clinical potential, societal and legislative relevance of novel innovative therapeutic strategies for specific patient cases (academic, communicator)

X X X

write a case-report with emphasis on the integration of conventional and innovative diagnostics and therapeutic strategies (academic, medical expert, communicator)

X

(12)

9 identify relevant literature related to the

topics of the course and the selected case report. (academic)

X X

demonstrate the ability to implement feedback to the blog and case report (academic, communicator)

X X

Detailed description of tests and examinations

Knowledge tests

Exam (1; covering week 1-3 and 2; covering week 1-6) consists of 10 open questions based on a pre-evaluated question and answer model.

Rating: mark 1-10

Assessed by: at least two minor teachers.

Final knowledge test

Exam covers the content of the complete course consists of 10 open questions based on a pre-evaluated question and answer model.

Rating: mark 1-10

Assessed by: at least two minor teachers.

Case report

A written case description of 3000-4000 words that describes the differential diagnosis, epidemiology, pathogenesis, therapeutic plan, prognosis and a discussion of potential innovative therapeutic perspectives that are relevant to the case that was handed out to the student in week 2. Where relevant references are included to the published literature. Case descriptions are prepared by the students on an individual basis and are based on the cumulative information and feedback given by the dedicated teacher collected in the weekly blogs (see below).

Recommendations and criteria for writing the case description are described in appendix 3.

After completion, cases (four different case descriptions are handed out to the students) are discussed with the students in a plenary session by a clinical minor teacher.

Rating: mark 1-10

Assessed by: pairs of 3 minor teachers (at least one with a clinical and one with a fundamental background).

Assessment criteria: case reports will be evaluated on criteria of clinical, scientific and writing skills.

Calculation of overall mark

Overal the final mark should be ≥ 5.5 and at least 3 out of 4 elements need to be ≥ 5.5.

Knowledge test 1 = 12.5 %

Knowledge test 2 = 12.5 %

Final knowledge test = 25 %

Case report = 50 %

Additional tests

Paper presentations

At five occasions students will be handed out scientific papers related to the topics of the week. In groups of 5 students per group they will study the papers and prepare 10 minute presentations to explain the content and implications of the reported studies/reviews to their fellow students. The papers will be presented by a single student such that every student will get its turn during the course. All students of the presenting group will participate in the ten minute discussion sessions following the presentations.

The sessions will be chaired by minor teachers of the week.

(13)

10 Assessment: pass/fail based on participation and contribution Assessed by: minor teachers of the week

Blog

In the beginning of week 2 the student will be handed out one of four case descriptions of patients with various forms of cardiovascular disease. At the end of each week the students have to write a blog (up to 500 words per contribution) and report what aspects of the current week are relevant for the case descriptions they have received. The blogs are posted as a shared file in the blackboard module.

Assessed by: Each student will get weekly feedback on their blogs by a dedicated mentor who will also coach the student throughout the ten weeks of the course.

Assessment: Pass/Fail

Presence

Presence and participation during the modules of the half minor will be recorded. From the paper presentation session only one out of five can be missed (with prior notice) and should be compensated by an alternative assignment. Absence is only allowed after permission by email of one of the block-coordinators.

Re-examinations

Knowledge tests

In case of insufficient scoring for the knowledge tests a second chance exam will be organized. This will however be only one test that, like the final knowledge test covers the theory and practice of the entire course.

The format will be equal to the final knowledge test. The scoring will be based on the knowledge percentages that the students achieved during the regular final knowledge exam.

Case report

When the submitted case report is insufficient (≤ 5.5) the student will get the opportunity to improve the weaknesses of the report on the basis feedback provided by the teachers that assessed the report. The coordinator will determine the deadline for submitting the modified case report.

Additional tests and feedback

• Paper presentation and discussion workgroups (week 2, 4, 5, 6 and 7) are selected and supervised in a way to optimize self-study of the study topic of the week. Feedback will be given on the content and form of the presentations on a group and individual basis. Student should actively participate in the discussions. If not the student will be urged by the teacher to adopt this and will try to get the student involved by direct questions and/or the guidance of discussions among the students. Getting involved in the discussions will train the student to cope with scientific questions and help to learn to evaluate diagnostic and therapeutic plans. These activities are meant to train the students in a way that helps them to write their case reports.

• The weekly blogs are meant as a repeated learning/evaluation activity regarding the study material that is offered that particular week. The fact that the student will have to evaluate what presented weekly issues is/are relevant to their particular case and that they will get feedback on this by their designated personal mentor will help the students to place the presented information in a context.

(14)

11

Prerequisites (not obligatory to join this minor, but highly recommended)

Previous Bachelor modules

Mechanisms of disease 1 & 2 Academic and Scientific Education Vraagstukken Bewegen

Vraagstukken Buik Vraagstukken Borst en nier

Vraagstukken Geestelijke gezondheid

Place in the curriculum

The module will be held in the first 10 weeks of the third year of the Bachelor of Medicine. This half minor will be an overview in the most current concepts in cardiovascular disease and is therefore useful for anyone interested in this particular field of medicine.

Study books

Kumar, Abbas and Fausto. Robbins and Cotran, Pathologic Basis of Disease. Elsevier Saunders, 8^th edition, 2009

Literature

Published papers that are referred to during the lectures will be provided through blackboard

Relevant websites

www.uptodate.com/contents/search www.ncbi.nlm.nih.gov/pubmed/

www.medicaleducation.nl: TRC Pharmacology Database www.blackboard.leidenuniv.nl

(15)

(16)

13

Themes

Week 1: Development and Anatomy, Molecular Medicine Week 2: Physiology of Heart and Vessels

Week 3: Hemostasis and Thrombosis Week 4: Macrovascular disease 1/2 Week 5: Macrovascular disease 2/2

Week 6: Clinical diagnosis and therapy of macrovascular disease Week 7: Vascular Surgery and Peripheral Artery Disease

Week 8: Microvascular disease

Week 9: Innovation week, novel therapeutic strategies in CVD

Week 10: Case-report

(17)

14

Week 1 Development and anatomy of the cardiovascular system, molecular medicine

Clinical coordinators Atsma Topics LE Lecture

Scientific coordinators van Zonneveld, de Bruin Embryology of the cardiovascular system SS Self Study

Genetic variations in cardiovascular development DE Demonstration

Other teachers involved Rabelink, van Gils Endothelial cell biology WO Workgroup

van der Veer Mechanisms in vascular maintenance and repair PR Practical work

De Ruiter, de Boer, van Wisse, van Munsteren

The basics of molecular cell biology and gene expression DB Debate

Bijkerk The technique of PCR

van Vlijmen Animal models in vascular biology

Monday Opening of the Academic Year 01-Sep

Tuesday The vascular endothelium 02-Sep

9.00-9.45 LE Introduction by the block coördinators

The outline of the minor will be presented: what you can expect, what is expected of you, and what do you expect to learn.

V4-50 van Zonneveld, Atsma, de Bruin

9.45-10.00 Break

10.00-10.45 LE The vascular endothelium In this lecture you will learn that the vascular endothelium is more then just a structural barrier between the vascular wall and blood

V4-50 van Zonneveld 10.45-11.00 Break

11.00-12.00 LE The glycocalyx The essential luminal layer V4-50 Rabelink

12.00-13.30 Lunch

13.30-15.30 SS Molecular biology Study material related to the coming molecular biology class and PCR workshop

V4-46 van der Veer, de Bruin

Wednesday Vasculogenesis

03-Sep

9.00-9.45 LE The start of the heart In this hour, you will learn about the stages of embryonal development of the human heart

V4-62 de Ruiter 9.45-10.00 Break

10.00-10.45 LE The origin and differentiation of the vasculature

In this hour, you will learn about the stages of embryonic development of the vascular system

V4-62 de Ruiter 10.45-11.00 Lunch

11.00-12.00 LE Vascular regeneration The role of endothelial progenitor cells in vascular maintenance and repair V4-62 de Boer 12.00-13.30 Lunch

13.30-15.30 PR Development mouse embryo

Digital microscopy of cardiovascular development in the mouse embryo.

BRING LAPTOP

V4-18/22 DeRuiter, van Wisse, van Munsteren Thursday Introduction to molecular medicine

04-Sep

9.00-9.45 LE From DNA to protein 1/2 This lecture will give an overview of the central dogma in molecular cell biology.

Gene transcription and translation will be discussed.

V4-62 van der Veer 9.45-10.00 Break

10.00-10.45 LE Novel concepts in Post- transcriptional regulation

Complex organisms have only developed flowing the introduction of post- transcrptonal regulation. Defects in post-transcriptional regulation cause disease and offers novel therapeutic targets

V4-62 van der Veer

10.45-11.00 Break

11.00-12.00 PR Introduction to PCR An introduction to the technique of PCR will be given, that you will perform yourself this afternoon

V4-62 de Bruin, Bijkerk 12.00-13.30 Lunch

13.30-15.30 PR Hands on molecular cell biology 1/2

A tour through a molecular cell biology laboratory will be hosted by researchers and you will perform a PCR experiment to determine gene expression in

D2-19 de Bruin, Bijkerk

Friday Molecular medicine

05-Sep

9.00-10.30 PR Hands on molecular cell biology 2/2

The PCR performed on Tuesday will be finished and evaluated V2-34 de Bruin, Bijkerk 10.30-10.45 Break

11.00-12.00 LE Transgenic mouse models in cardiovascular disease

siRNA and conditional knock-out models are increasingly important in experimental animal models here you will learn their principles

V2-34 van Vlijmen 12.00-13.00 Lunch

13.00-13.45 LE microRNAs in vascular homeostasis

An illustration of how microRNA-126 is a critical regulator of vascular regeneration

V2-34 Bijkerk

13.45- 17.00 SS time to work on your blog home/library

(18)

15

Week 1: Development and anatomy of the cardiovascular system, molecular medicine

Coordinator(s): van Zonneveld, Atsma

Teachers: Rabelink, van der Veer, de Bruin, de Ruiter, van Wisse, van Munsteren, van Vlijmen, Bijkerk Outline

Next to a detailed introduction into the goals and format of the half minor, this week will be devoted to review the development and anatomy of the cardiovascular system focusing on the heart and blood vessels. Also students will be introduced into how genetic variation can impact on cardiovascular development and lead to defects in mice and man. We will review the central role of the endothelium in vascular homeostasis and discuss how endothelial integrity is maintained in post-natal life.

Also, to provide the basic knowledge needed to understand the molecular-medicine based novel therapeutic approaches that will be discussed throughout the course, lectures and a practical assignment will be devoted to review current concepts in molecular biology. In particular, this effort aims to help the students understand novel RNA-based regulatory mechanism that are increasingly recognized to be involved in pathogenesis of human disease and are currently demonstrated to provide potent therapeutic tools.

Topics

• Embryology of the cardiovascular system

• Genetic variations in cardiovascular development

• The biology of the endothelium

• Mechanisms in vascular maintenance and repair

• The basics in current molecular cell biology and gene expression

• The technique of PCR

• Animal models in vascular biology Evaluation

• Evaluation of blog contribution

• Multiple choice exam week 3

• Evaluation of paper presentation

Day to Day program

Monday 1 September

Free: Opening of the academic year Tuesday 2 September

Theme: The vascular endothelium

9.00-9.45 Introduction

Title Introduction to the half minor by the block coordinators Instructors D.E Atsma (Cardiology), A.J. van Zonneveld (Nephrology)

Description The outline of the course will be presented: what you can expect, what is expected of you and what can you expect to learn

10.00-10.45 Lecture

Title The vascular endothelium

Instructor A.J. van Zonneveld (Nephrology)

Description The vascular endothelium is more than a structural barrier between the vascular wall and the bloodstream. It serves to regulate vascular tone, permeability, leukocyte migration and vascular homeostasis. The basics of these processes will be discussed.

Literature Basic: Kumar, Abbas en Fausto and Clark Chapter 11 “Blood vessels” part 1”vascular wall cells and their response to injury”.

Preparation Additional reading: Endothelial function and dysfunction, Deanfield et al. Circulation, 2007 (115) 1285-1295

(19)

16 11.00-12.00 Lecture

Title The glycocalyx

Instructors T.J. Rabelink (Nephrology)

Description The endothelial surface layer (ESL) is a negatively charged carbohydrate rich layer on the luminal side of the endothelium and is present throughout the whole vasculature. The ESL is located in between the circulating blood and the endothelium with its underlying tissues which supports the hypothesis that the ESL has a vital role in the vasculature. The surface layer has been proposed to be the first barrier for circulating components and protects the endothelium from direct contact with leukocytes and platelets. Consequently it is also suggested to be the first target for damaging agents present within in the vasculature and therefore potentially an interesting candidate as early endothelial damager marker. It has been demonstrated that the ESL is involved in mechano-sensing of the flowing blood, contributes to the endothelial permeability properties and has a protective function against inflammation and coagulation.

Therefore, it can be reasoned that the ESL plays an important role in endothelial function and vascular stability. Perturbation of these functions have been implicated in the development of cardiovascular disease (CVD) and kidney disease. This pathophysiology of the ESL and its possible implications for clinical medicine will be discussed in the lecture

13.30-15.30 Self-study

Title Molecular Biology and PCR workshop Instructors E.P. van der Veer, R. de Bruin Nephrology)

Description Study material related to the coming molecular biology class and PCR workshop

Wednesday 3 September Theme: Vasculogenesis 9.00-9.45 Lecture

Title The start of the heart

Instructor M.C. de Ruiter (Anatomy and Embryology)

Description The embryonic heart develops from the splanchnic mesoderm in close relationship with the developing gut. It starts with a 2D network of endothelial precursors covered by a layer of myocardial cells which remodels into a 3D heart tube. This heart tube is the first functional organ in the embryo. This primary heart tube with an common venous inlet and an arterial outlet has to be septated to obtain a four chambered heart with valves. Both intrinsic cardiac remodelling processes and extracardiac cellular contributions are major key players for proper cardiac septation. Multiple signalling pathways have to be framed in exact spatiotemporal windows during development. A small deviation in one of these processes can easily affect cellular differentiation or contribution and harm normal development resulting in dramatic congenital cardiac malformations and even embryonic lethality. We will discuss the consequences of disturbed developmental processes with the help of major cardiac malformations.

10.00-10.45 Lecture

Title The origin and differentiation of the vasculature Instructor M.C. de Ruiter (Anatomy and Embryology)

Description All blood vessels in the develop from a small endothelial tube within an undifferentiated mesenchyme. The interaction between these two cell populations in combination with an increasing blood flow determines the ultimate composition of the vessel wall. Various embryonic cell populations (e.g. neural crest, epicardium, second heart field, endothelium) contribute to the smooth muscle and fibroblasts compartments of the vessel wall. These contributions are strictly regulated processes and have sharp topographic boundaries. A change in cellular contribution coincides in a change in morphology, basic cellular signalling processes and function. Moreover most of the cells contributing to the vessel wall also contribute to the developing heart which explains that many congenital cardiac malformations are associated with vascular malformations like abnormal venous or arterial patterning and/or composition

(20)

17 11.00-11.45 Lecture

Title Vascular regeneration Instructors H.C. de Boer (Nephrology)

Description Endothelial progenitor cells contribute to the maintenance of the vascular system.

You will get insight into the definition and origin of endothelial progenitor cells and the consequences of exhaustion of these cells.

Literature Basic: “Regeneration of the vascular compartment”. Authors: Becher, Nickenig and Werner.

Herz, 2010 (35):342-351.

Preparation Additional reading: “Restoring the renal microvasculature to treat chronic kidney disease”.

Authors: Long, Norman and Fine. Nature Review Nephrology, 2012 (8): 244-250.

13.30-15.30 Practicum

Title Digital microscopy of cardiovascular development in the mouse embryo Instructor M.C. deRuiter, B.Wisse, C. van Munsteren (Anatomy and Embryology)

Description Developmental biologists frequently use transgenic and knock out mouse models to study the role of specific molecular signalling pathways. In this practical lesson you will be introduced in one of the research methods to study normal and abnormal cardiovascular development.

First a series of transverse sections of a normal 15 days old mouse embryo will be studied. You will focus on the various cell populations within the cardiac outflow tract and the great arteries (aorta and pulmonary arteries). After you have proven to be able to recognize all essential structures in the thorax you will be challenged to determine the cardiovascular malformations in one or more knock out models (e.g. VEGF, PDGF, LRP2 knock out mice). In a general discussion you will present your findings to the other students and relate the abnormalities with the known developmental processes.

Thursday 4 September

Theme: Current concepts in molecular biology

9.00-9.45 Lecture

Title From DNA to protein 1/2 Instructor E.P. van der Veer (Nephrology)

Description The central dogma of cellular biology proposed by Francis Crick in the 1950’s details a process whereby DNA in the nucleus is transcribed into RNA, which is subsequently translated into protein in the cytoplasm. It is now clear that this chronological view of DNA to protein is a simplification. This lecture will provide insight into the molecular mechanisms by which encrypted genomic information in the DNA leads to functional elements (RNA and protein) that drive multitudes of cellular functions.

Literature Manel Esteller. Non-coding RNAs in human disease. Nature Reviews Genetics, 12, 861-874, 2011.

10.00-10.45 Lecture

Title Novel concepts in post-transcriptional regulation Instructor E.P. van der Veer (Nephrology)

Description The broad-scale introduction of post-transcriptional regulatory mechanisms is what defines complex organisms (eukaryotes) as compared to their more primitive counterparts (prokaryotes and eubacteria). This lecture is designed to introduce the wide arsenal of tools the cell employs to modulate gene expression at the RNA level, influencing the stability and localization of targets. Light will also be shed on how defects in post-transcriptional regulation can be causal for various diseases and how targeting RNA is considered to be a new frontier in the treatment of disease.

Literature Esteller, M. Non-coding RNAs in human disease. Nature Reviews Genetics, 12, 861-874, 2011.

Kafasla, P, et.al. Post-transcriptional coordination of immunological responses by RNA- binding proteins. Nature Immunology, 15(6), 492-502, 2014.

(21)

18 11.00-12.00 Practicum

Title Introduction to PCR

Instructor R. de Bruin, R. Bijkerk (Nephrology)

Description An introduction to the technique of PCR will be given, that you will perform yourself this afternoon

13.30-15.30 Practicum I

Title Hands-on molecular biology

Description A tour through a molecular cell biology laboratory will be hosted by researchers and you will perform a PCR experiment to determine gene expression in endothelial cells and smooth muscle cells. Half of the students will perform qRT-PCR, the other qPCR and electrophoresis.

Friday 5 September

Theme: Molecular Medicine

9.00-10.30 Practicum II

Title Hands-on molecular biology

Description The PCR performed on Tuesday will be finished and evaluated.

11.00-12.00 Lecture

Title Transgenic mouse models in cardiovascular disease Instructor B.J.M. van Vlijmen

Description The mouse has been used as an experimental model for cardiovascular research for a only a short time; however, the sophisticated genetics of this species has resulted in a number of innovative approaches that are not possible with other models. The availability of inbred and mutant strains has resulted in the discovery of a number of genes affecting cardiovascular disease. More importantly, the newer genetic technologies such as transgenic mice and gene- targeted mice are producing important insights into cardiovascular disease. This lecture focuses on murine models of cardiovascular disease and will briefly discuss the several technologies that are now available to generate such models (transgenesis, (conditional) knockout, CRISPR, and RNA interference). We will summarize a number of mouse models of hyperlipidemia, atherosclerosis and thrombosis and discuss the contribution of these models to development of novel therapies.

13.00-13.45 Lecture

Title MicroRNAS in vascular homeostasis Instructor R. Bijkerk (Nephrology)

Description The role of microRNAs in maintaining healthy blood vessels. This is illustrated by microRNA- 126, that acts as a critical regulator of vascular regeneration

Literature Hematopoietic MicroRNA-126 Protects against Renal Ischemia/Reperfusion Injury by Promoting Vascular Integrity. J Am Soc Nephrol, 2014.

Preparation Additional reading: Pervasive roles of microRNAs in cardiovascular biology. Small & Olson.

Nature, 2011.

(22)

19

(23)

20

Week 2 Physiology of heart and vessels

Clinical coordinators Atsma Topics LE Lecture

Scientific coordinators Pijnappels Heart function SS Self Study

Electrophysiology 1 and 2 DE Demonstration

Other teachers involved Steendijk, de Vries Blood pressure regulation WO Workgroup

Ypey, Trines, Feola, Molecular medicine PR Practical work

Jangsangthong, Rotmans, DB Debate

Majumder, Askar, PhD studs

Monday Heart function

08-Sep

9.00-9.45 LE Introduction by week coordinators and hand out of case descriptions V4-50 Atsma, Pijnappels

9.45-10.00 Break

10.00-10.45 LE Cardiac function V4-50 Steendijk

10.45-11.00 Break

11.00-12.00 LE Cardiac function - coronary circulation V4-50 ?

12.00-13.30 Lunch

13.30-15.30 SS A state-of-the-art scientific paper

State of the art scientific papers will be handed out and sub-groups will be formed. Use this time to prepare short presentations (max 15 minutes)

V4-50

Tuesday Electrophysiology 1

09-Sep

9.00-9.45 LE Electrophysiology of the heart V4-50 Pijnappels

9.45-10.00 Break

10.00-10.45 LE Electrical function and ECG V4-50 Ypey

10.45-11.00 Break

11.00-12.00 LE Supraventricular arrhythmias V4-50 Trines

12.00-13.30 Lunch

13.30-15.30 LE/DE Experimental techniques (Patch-clamp and Optical mapping) V4-50 Feola/Jangsangthong

Wednesday Blood pressure regulation 10-Sep

10.00-10.45 LE Mechanisms in blood pressure regulation V4-50 Rotmans

10.45-11.00 Break

11.00-12.00 LE Cardiovascular complications of hypertension V4-50 Rotmans

12.00-13.30 Lunch

13.30-15.30 WO Paper discussion session This time feedback will be given on the presentations by dr. van de Veer to help set the standard for the coming weeks

V4-50 Pijnappels

Thursday Electrophysiolog 2 11-Sep

9.00-9.45 LE In silico models of cardiac arrhythmias V4-62 Majumder

9.45-10.00 Break

10.00-10.45 LE In vitro models of cardiac arrhythmias V4-62 Askar

10.45-11.00 Break

11.00-12.00 LE PhD student projects V4-62 PhD students (3)

12.00-13.30 Lunch

13.30-14.30 DE/PR Lab visit (Exp. Cardiology, D4) V4-62 Lab members

Friday Molecular medicine

12-Sep

10.00-11.00 LE Experimental approaches in hypertension V4-50 Rotmans

11.00-11.05 Break

11.05-12.00 LE Gene therapy for cardiac diseases: Background V4-50 de Vries

12.00-13.30 Lunch

13.30-14.30 LE Gene therapy for cardiac diseases: (Pre)clinical application V4-50 de Vries

14.30- 17.00 SS Writing a (short) blog Use this time to work on your blog and case report home/library

(24)

21

Week 2: Physiology of The Heart and Blood Vessels

Coordinator(s): Atsma, Pijnappels

Teachers: Steendijk, de Vries, Pijnappels Ypey, Trines, Feola, Jangsangthong, Rotmans, Majumder, Askar, PhD students

Outline

This week will begin with handing out the case-descriptions that will serve as the background for the weekly personal blogs and the final case report that will be submitted in the final week of the course. The theme of week two involves key features of the physiology of the cardiovascular system including the mechanical and electrical function of the heart. The electrical conduction system will be demonstrated in particular, as many of the diseases that are discussed in this half minor are the result of congenital or acquired anomalies in these areas.

Also, the (advanced) therapies that are discussed target these processes. Deviations in cardiac physiology resulting from (genetic) disease will be discussed. The basic mechanisms underlying the occurrence of arrhythmias and their clinical presentation are outlined.

Also we will outline the physiology of blood pressure regulation and talk about the epidemiology, current and novel treatment options, as well as complications of hypertension.

The students will be introduced to the basic disease models that are employed in the lab to further investigate the basic underlying disease mechanisms, and novel insights and hypotheses will be discussed.

To stimulate self-study, state of the art papers on a topic that relate to the theme of the week will be distributed to the students (groups of 4) with the assignment to prepare a presentation that discusses content, strength and weaknesses of the studies.

At the end of the week, the students will update their blogs describing which pathophysiological concepts that were discussed are relevant to their selected patient case.

Topics

• Heart function

• Electrophysiology of the heart

• Arrhythmias

• Regulation of blood pressure and hypertension Evaluation

Day to Day program

Monday 8 September Theme: Heart Function

9.00-9.45 Introduction

Title Introduction by week coordinators and hand out of case descriptions Instructor D.E. Atsma, D.A. Pijnappels

Description Instruction on the role of the case descriptions and how to use them when writing the weekly blogs. Week by week these blogs will cumulate into a useful document that can form the basis for the case reports. Also the coordinators will outline the theme of the week.

10.00-10.45 Lecture Title Cardiac function Instructor P. Steendijk

Description General principles and mechanisms of cardiac physiology are outlined.

Literature Boron and Boulpaep, Medical Physiology (2^nd ed.), chapters 9, 22 and 25.

Preparation Reading literature 11.00-11.45 Lecture

Title Cardiac function – Coronary circulation Instructor P. Steendijk

Description The role of coronary of circulation in normal cardiac physiology is discussed, as well as coronary dysfunction in heart disease.

(25)

22

Literature Boron and Boulpaep, Medical Physiology (2^nd ed.), chapter 24 – p581-583.

Preparation Reading literature

13.30-15.30 Self-study

Title State-of-the-art scientific paper Instructor D.A. Pijnappels

Description State of the art scientific papers will be handed out and sub-groups will be formed. Use this time to prepare a short presentation for Wednesday (max 15 minutes)

Tuesday 9 September

Theme: Electrophysiology 1

9.00-9.45 Lecture

Title Electrophysiology of the heart Instructor D.A. Pijnappels

Description The heart is an organ that generates and propagates electrical signals in a highly organized manner, thereby favouring optimal pump function. However, disturbances in these electrical processes may contribute to heart rhythm disturbances, which can be lethal. A good mechanistic understanding in these disorders is essential for effective treatment, but also for the development of new therapeutics.

Literature Boron and Boulpaep, Medical Physiology (2^nd ed.), chapter 21 Preparation Reading literature

10.00-10.45 Lecture

Title Electrical function and ECG Instructors D.L. Ypey

Description As the origin of cardiac electrical function lays excitability, the property of a cell to generate an action potential by subsequent in and effluxes of ions, and propagation, the property of a tissue to conduct an electrical current by means of excitation and coupling. Although occurring in the heart, these processes can be detected and recorded outside the body, thereby producing an electrocardiogram (ECG).

Literature Boron and Boulpaep, Medical Physiology (2^nd ed.), chapter 21 Preparation Reading literature

11.00-12.00 Lecture

Title Narrow complex tachyarrhythmias Instructors S.A.I.P. Trines

Description Heart rhythm disturbances could affect the atria, ventricles or both. Those that involve the atria, including the atrioventricular node, are refered to as narrow complex tachyarrhythmias.

ECG analyses are often used to identify the origin and nature of such arrhythmias.

Literature Uptodate.com: “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”

13.30-15.30 Lecture (Demonstration)

Title Experimental techniques (patch-clamp and optical mapping) Instructors W. Jangsangthong and I. Feola

Description Whole-cell patch-clamp is one of the most definite techniques in basic electrophysiology research. A small glass electrode and a sophisticated microscopy/electrophysiological setup are used to measure and record electrical activity in single cells and tissues. The optical mapping technique makes use of voltage- or calcium-sensitive probes, light-sensitive camera’s and a dedicated microscopy setup.

Literature Physiological Research (Karmazinova et al. 2010. Suppl 1:S1-7) and Circulation Research (Herron et al. 2012. 110(4); 609-623)

(26)

23 Wednesday 10 September

Theme: Blood pressure regulation

10.00-10.45 Lecture

Title Mechanisms in blood pressure regulation Instructor J.I. Rotmans (Nephrology)

Description Mechanisms of blood pressure regulation will be discussed as well as pathophysiological mechanisms of hypertension

Literature Basic: Kumar and Clark Chapter 12, p597-599 (eighth edition)

Additional: T.M. Coffman. Under pressure: the search for the essential mechanisms of hypertension. Nature Medicine 2011; Nov 7;17(11):1402-9

Title Cardiovascular complications of hypertension Instructor J.I. Rotmans (Nephrology)

Description Complications and treatment options for hypertension will be discussed.

Literature Basic: Kumar and Clark Chapter 14, p777-784 (eighth edition) Additional literature:

1. A. Myat. Resistant hypertension. BMJ 2012;345:e7473

2. Lewington S et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002 Dec 14;360(9349):1903-13

Preparation reading literature 13.30-15.30 Workgroup

Title Paper presentation and Discussion session 1 Instructor D.A. Pijnappels and E.P van der Veer Preparation Powerpoint presentation (15 min)

Thursday 11 September

Theme: Electrophysiology 2

9.00-9.45 Lecture

Title In silico models of cardiac arrhythmias Instructor R. Majumder

Description The degree of complexity of certain biological/electrophysiological processes becomes so high that a human brain can no longer comprehend these processes. One way to deal with such processes is to develop realistic computer models that are based on numerical reasoning.

Studies on the underlying mechanisms of cardiac arrhythmias have benefited a lot from such so-called in silico studies as new therapeutic were proposed, which indeed turned out to be of significant biological and therapeutic relevance.

Literature Am J Phyiol Heart Circ Physiol (Roberts et al. 2012. 303(7); H766-H783.

Title In vitro models of cardiac arrhythmias Instructor S.F.A. Askar

Description The heart is an extremely complex 3D organ that is both electrically and mechanically active.

Mechanistic studies on the origin and termination of cardiac arrhythmias are hampered by the 3D nature of cardiac tissue as the interpretation of data is seriously affected. One way to reduce this complexity is to culture the cardiac cells of interest in confluent monolayers (no a- cellular space), allowing standardized and controllable studies on the underlying mechanisms of rhythm disorders. Such an approach certainly becomes with trade-offs, but studies have shown that key features of cardiac arrhythmias can be studied in such monolayers and have resulted in important novel insights.

Literature Cardiovasc Res (Askar et al. 2013. 97(1); 171-181.

(27)

24 11.00-12.00 Lecture

Title PhD student projects Instructor 3 PhD students

Description You might want to pursue a PhD training upon finishing your Master/Medical studies. During this lecture, 3 PhD students from the Department of Cardiology will present their recent work and share some of their experiences with you.

13.30-14.30 Demonstration/practical work Title Lab visit (Exp. Cardiology, D4) Instructor Lab members

Description The laboratory of Experimental Cardiology is part of the Department of Cardiology and accommodates scientists of various kinds. They will show you the various experimental setups and models that are used to study cardiac disease and to identify novel therapeutic targets.

Friday 12 September

Theme: Molecular Medicine

10.00-11.00 Lecture

Title Experimental approaches in hypertension Instructor J.I Rotmans

Description New therapeutic strategies to control hypertension will be discussed.

Literature 1. S. Laurent. New drugs, procedures, and devices for hypertension. Lancet 2012; 380: 591–

600

2. D.L. Bhatt. A controlled trial of renal denervation for resistant hypertension. NEJM 2014;

370;393-401 Preparation Reading literature 11.05-12.00 Lecture

Title Gene therapy for cardiac diseases: Background Instructor A.A.F. de Vries

Description The rationales behind gene therapy will be discussed, as well as the methods and techniques used to accomplish the aims of gene therapy.

Literature Vannucci L, Lai M, Chiuppesi F, Ceccherini-Nelli L, Pistello M. Viral vectors: a look back and ahead on gene transfer technology. New Microbiol 2013;36:1-2

Title Gene therapy for cardiac diseases: (Pre)clinical application Instructor A.A.F. de Vries

Description Various cardiac diseases have been target by gene therapy using viral vectors. Although most of these studies were performed in pre-clinical stages, a growing number of clinical studies have been published with promising results.

Literature Publication in Circulation Research (Zacchigna et al. 2014. 114:1827-1846) Preparation Reading literature

14.30-17.00 Self-study

Title Blog update

Instructor Assigned mentor

Description Use this time to work on your blog and case report

(28)

25

Week 3 Thrombosis and Hemostasis

Clinical coordinators Eikenboom, Huisman Topics LE Lecture

Scientific coordinators Reitsma Coagulation and fibrinolysis SS Self Study

Venous thrombosis DE Demonstration

Other teachers involved van der Meer Anticoagulant therapy WO Workgroup

van Vlijmen Hemophilia and clinical management PR Practical work

Bos, Huisman Acute coagulation disorders DB Debate

Klok, Versteeg

Monday Pathophysiology of Blood Coagulation 15-sep

09.00-09.45 LE Primary hemostasis and its disorders V4-18/22 Eikenboom

09.45-10.00 Break

10.00-10.45 LE Secondary hemostasis and fibrinolysis V4-18/22 Versteeg

10.45-11.00 Break

11.00-11.45 LE Disorders of secondary hemostasis; bleeding and thrombosis V4-18/22 Van Vlijmen

11.45-13.30 Lunch

13.30-15.30 SS Assignments and preparation patient demonstrations V3-36 Eikenboom

Tuesday Clinical and laboratory diagnostics 16-sep

09.00-09.45 PD Patient with venous thromboembolism V3-18/22 Huisman

09.45-10.00 Break

10.00-10.45 LE Imaging diagnostics in thrombosis and clinical decision rules V3-18/22 Huisman

10.45-11.00 Break

11.00-12.00 LE Laboratory diagnosis of coagulation disorders V3-18/22 Bos/Eikenboom

12.00-13.30 Lunch

13.30-15.30 WO Interactive case presentations V2-10/14 Klok/Eikenboom

Wednesday Treatment of coagulation disorders 17-sep

09.00-09.45 PD Patient with (inherited) bleeding disorder V4-50 Van der Meer

09.45-10.00 Break

10.00-10.45 LE Prohemostatics V4-50 Van der Meer

10.45-11.00 Break

11.00-12.00 LE Anticoagulants and profibrinolytic treatment V4-50 Huisman

12.00-13.30 Lunch

13.30-15.30 WO Interactive case presentations V4-46 van der Meer/Klok

Thursday Acute derangement of hemostasis and new biologicals 18-sep

09.00-10.30 LE TTP, aHUS and HIT V2-10/14 Eikenboom

10.30-10.45 Break

10.45-12.15 LE Novel anticoagulant- and hemostatic biologicals V2-10/14 Bos/Reitsma

12.15-13.00 Lunch

13.00- 17.00 SS Writing a (short) blog Use this time to work on your blog

Friday Exam

19-sep

11.00-12.00 EX Knowledge test 1 Covering week 1-3 V2-34

(29)

26

Week 3: Thrombosis and Hemostasis

Coordinator(s): Eikenboom, Huisman, Reitsma

Teachers: Van der Meer, Huisman, Klok, van Vlijmen, Bos, Versteeg Outline:

The week will begin with an in-depth instruction of the workings of the hemostatic and fibrinolytic systems with the goal to give the student a detailed working knowledge of blood coagulation and fibrinolysis. The second day will start with a patient demonstration in which a case with venous thrombosis is presented. This is followed by lectures that deal with diagnostics, with an emphasis on imaging techniques, laboratory analyses, and clinical decision rules. The afternoon session will follow an interactive case presentation format, which will allow the student to learn how to correctly apply the diagnostic tools in a clinical setting. The third day will follow a similar format, but the patient demonstration will focus on a patient with a bleeding disorder and the subsequent lectures and interactive cases will be focussed on treatment of coagulation disorders.

The fourth day will be devoted to acute severe derangements of the coagulation system such as heparin-induced thrombocytopenia (HIT), thrombotic thrombocytopenic purpura (TTP), and atypical hemolytic uremic syndrome (aHUS). In addition the latest developments in the innovation of treatment for thrombotic and bleeding disorders will be presented. In the afternoon there will be time to work on the Blog that is part of the requirements of the minor.

Topics:

• Coagulation and fibrinolysis

• Venous thrombosis

• Anticoagulant therapy

• Hemophilia and clinical management

• Acute coagulation disorders Evaluation

• Evaluation of participation in the interactive case presentations

Day to Day program

Monday, September 15

Theme: Pathophysiology of Blood Coagulation

09.00-9.45 Lecture

Title Primary hemostasis and its disorders

Instructor H.C.J. Eikenboom (Thrombosis and Hemostasis)

Description This lecture will introduce the hemostatic system with emphasis on primary hemostasis and its most common disorders.

Literature Relevant sections from the following books and journal article:

Robins and Cotran, Pathologic basis of disease, 8th edition 2010; chapter 4, pages 115-133 and chapter 14, pages 666-674

Kumar and Clark, Clinical Medicine, 8^th edition 2012; chapter 8, pages 414-429

McPhee, Pathophysiology of disease, 6^th edition 2010; chapter 6, pages 111-122, 131-137 New fundamentals in hemostasis. Henri H. Versteeg et al. Physiol Rev 2013;93: 327–358 Preparation Reading of the literature

10.00-10.45 Lecture

Title Secondary hemostasis and fibrinolysis

Instructor H.H. Versteeg (Thrombosis and Hemostasis)

Description This lecture will expand on the lecture on primary hemostasis and discuss secondary hemostasis and fibrinolysis

Robins and Cotran, Pathologic basis of disease, 8th edition 2010; chapter 4, pages 115-133 and

(30)

27 chapter 14, pages 666-674

McPhee, Pathophysiology of disease, 6^th edition 2010; chapter 6, pages 111-122, 131-137 New fundamentals in hemostasis. Henri H. Versteeg et al. Physiol Rev 2013;93: 327–358 Preparation Reading the literature

11.00-11.45 Lecture

Title Disorders of secondary hemostasis; bleeding and thrombosis Instructor B.J.M. van Vlijmen (Thrombosis and Hemostasis)

Description This lecture will expand on the introduction to secondary hemostasis and teach the most common disorders of secondary hemostasis

McPhee, Pathophysiology of disease, 6^th edition 2010; chapter 6, pages 111-122, 131-137 New fundamentals in hemostasis. Henri H. Versteeg et al. Physiol Rev 2013;93: 327–358 Preparation Reading the literature

13.30-15.30 Self-study

Title Assignments and preparation patient demonstrations Instructor Not applicable

Description On the first day of the course the self-study assignments for the preparation of the patient demonstrations will be given.

Literature To be announced Preparation NA

Tuesday, September 16

Theme: Clinical and laboratory diagnostics

09.00-9.45 Patient demonstration Title Patient with venous thombosis

Instructor M.V. Huisman (Thrombosis and Hemostasis)

Description A patient with venous thrombosis will be presented and clinical details will be discussed. The students will have an opportunity to ask questions.

McPhee, Pathophysiology of disease, 6^th edition 2010; chapter 6, pages 111-122, 131-137 New fundamentals in hemostasis. Henri H. Versteeg et al. Physiol Rev 2013;93: 327–358 Preparation Reading the literature. Completing the self-study assignments of Monday

10.00-10.45 Lecture

Title Imaging diagnostics in thrombosis and clinical decision rules Instructors M.V. Huisman (Thrombosis and Hemostasis)

Description The imaging options that are available for the diagnosis of venous thrombosis will be presented, and also the laboratory investigations. Clinical decision rules that are commonly used will also be presented.

Heart and Blood Vessels