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MS&A – Modeling, Simulation and Applications 18

Antonio Fasano · Adélia Sequeira

Hemomath
The Mathematics of Blood
MS&A

Volume 18

Editor-in-Chief

Alfio Quarteroni

Series Editors
Tom Hou
Claude Le Bris
Anthony T. Patera
Enrique Zuazua
More information about this series at http://www.springer.com/series/8377
Antonio Fasano • Adélia Sequeira

Hemomath
The Mathematics of Blood

123
Antonio Fasano Adélia Sequeira
Fabbrica Italiana Apparecchi Biomedicali Instituto Superior Técnico
(FIAB) Universidade de Lisboa
UniversitJa degli Studi di Firenze Lisboa, Portugal
Firenze, Italy

ISSN 2037-5255 ISSN 2037-5263 (electronic)

MS&A - Modeling, Simulation & Applications
ISBN 978-3-319-60512-8 ISBN 978-3-319-60513-5 (eBook)
DOI 10.1007/978-3-319-60513-5

Library of Congress Control Number: 2017951447

© Springer International Publishing AG 2017

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
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The publisher, the authors and the editors are safe to assume that the advice and information in this book
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the editors give a warranty, express or implied, with respect to the material contained herein or for any
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claims in published maps and institutional affiliations.

Cover illustration: The Copyright is with Stanislava Novotny

Printed on acid-free paper

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The registered company is Springer International Publishing AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Will all great Neptune’s ocean wash this
blood clean from my hand? (Macbeth,
William Shakespeare, Act 2, Scene 2,
1605-6).
Preface

Medicine is a fascinating field whose progress has been exponentially accelerated

from the moment it met technology. Mathematics, along with physics and chemistry,
participates in such an exciting experience, which actually started long ago.1
In the present book we focused our attention on one of the most intriguing
branches of medicine: hematology. Blood has an extremely complex behavior at all
scales. It is complicated as a fluid (to the point that many different, often mutually
contrasting, rheological models have been proposed), it contains very smart cells,
able to perform a huge number of operations, and it carries a great number of
large and small molecules, each with one or more tasks. Moreover, it constantly
interacts with all organs providing oxygen and nutrients, exchanging gases in the
lungs, carrying throughout the body hormones synthesized by endocrine glands,
and cells defending the organism from the attack of foreign agents. Blood also takes
metabolites to their final destination (the kidneys).
Such a monumental physiology goes in parallel with an even more intricate
pathology, since there are so many different ways of perturbing a system which
works perfectly in a rather narrow range. In this framework mathematics can play
an important role. In which way? It is not so simple to describe some general rule
for the construction of a mathematical model. It is not just a matter of choosing the
appropriate equations. Putting together a number of appropriate equations could
lead to a system which is simply not manageable. Moreover equations contain
coefficients and if the model has to give practical answers, then such coefficients
must be known from experiments. Therefore quite often completeness is in conflict
with practice. The more difficult are the phenomena to be studied, the more
necessary is to simplify equations, and simplifications always need to be justified
and kept within a tolerance degree guaranteeing that the reduced model is still
meaningful, at least for some specific target.

1
See the recent book: F.A. Duck. Physicists and Physicians: A History of Medical Physics from
the Renaissance to Röntgen. Institute of Physics and Engineering in Medicine, 2013.

vii
viii Preface

Blood-related topics are so numerous and each subject has been so widely
studied that it would be unthinkable to write an encyclopedic book. We will just
deal with some aspects of particular importance, showing old and new approaches
of mathematicians. We found extremely interesting, and also quite amusing, to
examine the historical development of the branches of medicine we dealt with. Of
course in a very synthetic way. Sometimes old ideas may look ridiculous, and we
confess that here and there we have played around the striking contrast between old
and new, emphasizing the naivety of our ancestors. Nevertheless, we want to stress
that the old civilizations and their masters were facing a task which was extremely
arduous and that even mistakes of great minds may have contributed in a way to
the progress of science. If on the contrary they have been an obstacle to the path
towards truth those who have to be blamed are not Hippocrates, Aristotle, Galen,
and the other fathers of medicine, but the strenuous vacuity of their followers.
On the other hand, when we “ultrafiltrate” history (to anticipate a term we will
extensively use in the chapters on kidneys and dialysis) the view emerging from
such a compressed perspective is so distorted that we should abstain from hastily
judging those who have mistakenly opposed the genial ideas mining their obsolete
world. Obstinate blindness is nothing but the natural and often justifiable instinct
of preserving the cultural environment we are born in, which pushes us to react
negatively to what may look the arrogant extravagance of self-appointed innovators.
Indeed, in sciences as in the arts, among the crowd of those proposing new ideas,
very few are really able to change the course of history, because this requires an
exceptional mind and the exceptional bravery of taking on seemingly impossible
challenges. We will encounter some of these towering characters on our path and
we will try to communicate our personal admiration, so that the reader does not get
the impression of being just looking at tombstones, but can somehow imagine the
excitement of the great people who made medicine what is today.
Due to its interdisciplinary character, the book is addressed to a large audience.
To clinicians, with the hope of elucidating the practical importance of mathematics
in medicine, to mathematicians with a taste for applications, but also to all scientists
(engineers, biologists, technicians, etc.) working in or close to medical areas. In
addition, even people with no scientific background can enjoy at least the pages
dedicated to the history of the relevant branches of medicine and the biological
introductions to the various subjects. A last remark is about footnotes. There are
many. In a sense they make a parallel book, containing a lot of lateral thoughts
and pieces of information, frequently of historical character, which in our opinion
provide answers to questions that may arise naturally.
The book deals with several specific aspects: blood rheology, blood coagulation,
blood ultrafiltration (natural and artificial), gas exchanges, the role of blood in heat
transfer, blood generation, and leukemia. All chapters follow the scheme: historical
background, physiological basis (including pathologies), mathematical modeling.
The subject of ultrafiltration is divided in two chapters: one small (kidneys) and, one
large (hemodialysis) for the reason that the two processes are significantly different.
The literature on kidney modeling is not large and we illustrated our own approach
to the problem, resulting from the applications of concepts on microcirculation
Preface ix

illustrated in the first chapter. This explains why it is much shorter than all other
chapters. Nevertheless we kept it separate because of its absolute peculiarity.
The authors are indebted to various eminent physicians for their advice. Among
them we quote in particular Dr. Jeremy Mizerski (cardiosurgeon in Warsaw)
and Prof. Rosanna Abbate (Head of the Consult and Laboratory Service for
Atherothrombotic Disorders for the Hospital and Medical School of the Uni-
versity of Florence, Italy). We also thank several colleagues for their interest
and encouragement. A precious support came from the personnel of the Library
of the Department of Mathematics & Informatics U. Dini of the University
of Florence, who efficiently provided hundreds of papers. The company FIAB
(Firenze, Italy) has also to be thanked for the help in retrieving research mate-
rial on electrophysiology. We acknowledge the partial financial support of the
Portuguese FCT—Fundação para a Ciência e a Tecnologia through the PHYS-
IOMATH project “Mathematical and Computational Modeling of Human Physiol-
ogy” (EXCL/MAT-NAN/0114/2012) http://www.physiomath.com, and the project
UID/Multi/04621/2013 of the CEMAT—Center for Computational and Stochastic
Mathematics, Instituto Superior Técnico, University of Lisbon.
We want also to deeply acknowledge Prof. Willi Jäger and Prof. Alfio Quarteroni
for their useful suggestions and their favorable comments.
Finally, we thank two persons at Springer, Annika Elting and Elena Griniari, who
have been particularly helpful in solving some important practical problems during
the final stage of publication.

Firenze, Italy Antonio Fasano

Lisboa, Portugal Adélia Sequeira
Contents

1 Hemorheology and Hemodynamics .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1

1.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1
1.2 The Human Circulatory System . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 14
1.2.1 Systemic Circulation . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 14
1.2.2 Mathematical Models for Blood Flow Dynamics .. . . . . . . . . . . . 17
1.3 Blood Rheology .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 38
1.3.1 Blood Components . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 38
1.3.2 Non-Newtonian Properties of Blood .. . . . . .. . . . . . . . . . . . . . . . . . . . 40
1.3.3 Constitutive Models for Blood . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 44
1.4 Hemodynamics and Microcirculation .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 50
1.4.1 A New Approach to Modeling Microcirculation .. . . . . . . . . . . . . 50
1.4.2 The Microcirculation Model . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 52
1.5 Vasomotion .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 55
1.5.1 The Elusive Phenomenon of Vessel Oscillations .. . . . . . . . . . . . . 55
1.5.2 Arterioles .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 58
1.5.3 Venules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 60
1.6 Atherosclerosis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 62
1.6.1 The Pathogenesis of Atherosclerosis . . . . . .. . . . . . . . . . . . . . . . . . . . 63
1.6.2 Mathematical Modeling . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 64
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 67
2 Blood Coagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 79
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 79
2.2 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 81
2.3 Cells and Proteins Intervening in the Formation
and Dissolution of Clots . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 88
2.3.1 Blood Cells and Coagulation .. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 89
2.3.2 Platelets Regulators .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 94
2.3.3 The Coagulation Factors . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 95
2.3.4 Fibrinolysis Factors .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 100
2.3.5 Factors Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 101

xi
xii Contents

2.4 The Cell-Based Model for Secondary Hemostasis . . . . . . . . . . . . . . . . . . . . 102

2.4.1 Secondary Hemostasis . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 103
2.4.2 Fibrinolysis.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 108
2.5 Bleeding Disorders .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 109
2.6 The 3-Pathway Cascade Model . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 117
2.7 Anticoagulant Drugs, Thrombolytic Drugs,
Hemophilia Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 120
2.7.1 Anticoagulant Drugs .. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 120
2.7.2 Thrombolytic Drugs . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 124
2.7.3 Hemophilia Therapies . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 124
2.8 Mathematical Models for Blood Coagulation . . . . .. . . . . . . . . . . . . . . . . . . . 125
2.8.1 ODE’s Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 126
2.8.2 PDE’s Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 131
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 146
3 Blood Filtration in Kidneys .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 159
3.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 159
3.2 General Structure of Kidneys .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 161
3.3 Calculating Glomerular Filtration Rate . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 165
3.4 The Steady Flow and the Glomerular Filtration Rate . . . . . . . . . . . . . . . . . 168
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 170
4 Extracorporeal Blood Ultrafiltration . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 171
4.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 171
4.2 The Hollow Fibers Dialyzer . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 174
4.2.1 General Description of the Apparatus . . . . .. . . . . . . . . . . . . . . . . . . . 174
4.2.2 A Mathematical Model Based on the Upscaling
Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 177
4.2.3 Modeling the Device . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 179
4.2.4 Modeling the Body Reaction .. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 190
4.2.5 Modeling the Evolution of Masses and Volumes.. . . . . . . . . . . . . 192
4.3 Numerical Simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 196
4.4 Going Further . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 199
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 201
5 Extracorporeal Blood Oxygenation .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 205
5.1 About Extracorporeal Blood Treatments.. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 205
5.2 Gases in Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 206
5.3 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 206
5.4 Mathematical Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 212
5.4.1 Heart-Lung Machine.. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 212
5.4.2 ECMO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 215
5.4.3 IMO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 220
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 222
6 Blood and Heat Transfer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 227
6.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 227
Contents xiii

6.2 The Bioheat Equation .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 231

6.3 Hyperthermia: General Characteristics and Historical
Information .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 234
6.4 Mathematical Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 237
6.4.1 Hyperthermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 237
6.4.2 Assessing the Thermal Damage .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 241
6.4.3 Therapeutic Hypothermia . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 243
6.4.4 Laser Induced Thermal Therapy (LITT).. .. . . . . . . . . . . . . . . . . . . . 245
6.5 Treatments by High Intensity Focused Ultrasound (HIFU) .. . . . . . . . . . 250
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 255
7 Thermal Ablative Procedures in the Treatment of Heart
Arrhythmia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 265
7.1 Physiological and Historical Notes. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 265
7.2 Importance of Mathematical Models.. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 275
7.3 RF Ablation Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 278
7.4 Cryoablation Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 283
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 287
8 Blood and Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 295
8.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 295
8.2 Hematopoiesis and Types of Blood Cancer .. . . . . . .. . . . . . . . . . . . . . . . . . . . 298
8.3 Mathematical Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 307
8.3.1 Hematopoiesis: Onset of Leukemic Disorders . . . . . . . . . . . . . . . . 307
8.3.2 Cyclic Leukemic Disorders . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 309
8.3.3 Treatment of Leukemic Disorders . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 313
8.3.4 Leukemia and the Immune Response . . . . . .. . . . . . . . . . . . . . . . . . . . 319
8.3.5 Bone Marrow/HSCs Transplantations . . . . .. . . . . . . . . . . . . . . . . . . . 322
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 324

Index . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 331
Acronyms

ABM Agent Based Model

ADP Adenosine-Di-Phosphate
AF Atrial Fibrillation
AIDS Acquired Immune Deficiency Syndrome
ALE Arbitrary Lagrangian Eulerian
ALK Anaplastic Lymphoma Kinase
ALL Acute Lymphoblastic Leukemia
AML Acute Myeloid Leukemia
AMP Adenosine-Mono-Phosphate
APC Activated Protein C
APL Acute Promyelocytic Leukemia
APTT Activated Partial Thromboplastin Time
ASA Acetylsalicilic Acid
AT Antithrombin
ATP Adenosine-Tri-Phosphate
AVNRT Atrio-Ventricular Nodal Reentrant Tachycardia
BMI Body Mass Index
BSA Body Surface Area
BW Body Weight
CD Cluster of Differentiation
CEM Cumulative Equivalent Minutes
CLL Chronic Lymphocytic Leukemia
CLP Common Lymphoid Progenitor
CML Chronic Myelogenous Leukemia
CMP Common Myeloid Progenitor
CSC Cancer Stem Cell
CSF Colony Stimulating Factor
CT Computed Tomography
DAE Differential Algebraic Equation
DIC Disseminated Intravascular Coagulation
DLBCL Diffuse Large B-Cell Lymphoma

xv
xvi Acronyms

DPD Dissipative Particles Dynamics

DTI Direct Thrombin Inhibitors
DVT Deep Venous Thrombosis
EBV Epstein-Barr Virus
ECBF Extracorporeal Blood Flow
ECG Electrocardiogram
ECM Extracellular Matrix
ECMO Extracorporeal Membrane Oxygenator
ELPT Euler-Lagrange Particle Tracking
ETL Esophageal Thermal Lesion
FAB French-American-British (leukemia classification system)
FPM Fluid Particle Model
FSI Fluid-Structure Interaction
FU Forming Unit
GFR Glomerular Filtration Rate
GVHD Graft-vs-Host-Disease
HDL High-Density-Lipoprotein (good cholesterol)
HHV Human Herpes Virus
HIFU High Intensity Focused Ultrasound
HIT Heparin Induced Thrombocytopenia
HIV Human Immunodeficiency Virus
HL Hodgkin Lymphoma
HMWK High Molecular Weight Kininogen
HSC Hematopoietic Stem Cells
HSP Heat Shock Protein
IB Immersed Boundary
IFE Immersed Finite Elements
IMO Intravenous Membrane Oxygenator
ITP Idiopathic (or Immune) Thrombocytopenic Purpura
IVOX Intravenous Oxygenator
LBM Lattice Boltzmann Method
LDL Low-Density-Lipoprotein (bad cholesterol)
LET Luminal Esophageal Temperature
LITT Laser Induced Thermal Therapy
LMWH Low Molecular Weight Heparin
MMP Matrix Metalloproteinase
MPN Myeloproliferative Neoplasms
MRT Magnetic Resonance Tomography
NHL Non-Hodgkin Lymphoma
NKC Natural Killer Cell
NOACS Novel Oral Anticoagulants
NS Navier-Stokes
NSCHL Nodular Sclerosis Classical Hodgkin Lymphoma
ODE Ordinary Differential Equation
PAI Plasminogen Activator Inhibitor
Acronyms xvii

PC Protein C
PDE Partial Differential Equation
PLA Plasmin
PLS Plasminogen
PRCP Prolyl-Carboxypeptidase
PS Protein S
PT Prothrombin Time
PTLD Posttransplantation Lymphoproliferative Disorders
PTT Partial Thromboplastin Time
PVI Pulmonary Vein Isolation
PZ Protein Z
RBC Red Blood Cell
RFA Radiofrequency Ablation
RSC Reed-Sternberg Cell
SCA Sickle-Cell Anemia
SMC Smooth Muscle Cell
SVT Supraventricular Tachycardia
TAFI Thrombin Activatable Fibrinolysis Inhibitor
TAR Thrombocytopenia with Absent Radius
TD Thermal Damage
TF Tissue Factor
TFPI Tissue Factor Pathway Inhibitor
TIMP Tissue Inhibitor of Metalloproteinase
tPA tissue Plasminogen Activator
TTP Thrombotic Thrombocytopenic Purpura
TXA Thromboxane
VA Venous-Arterial (ECMO)
VT Ventricular Tachycardia
VV Veno-Venous (ECMO)
vWF von Willebrand Factor
WBC White Blood Cell
WHO World Health Organization (leukemia classification system)
WPWS Wolff-Parkinson-White syndrome
WSS Wall Shear Stress
Chapter 1
Hemorheology and Hemodynamics

Abstract In this first approach to the subject we start describing a few basic facts
about blood composition and about the circulatory system. Such notions will be
enriched in the rest of the book, when needed. Concerning modeling, this chapter
is devoted to the debatable question of the rheological properties of blood and to
the various ways the circulatory system has been described in a mathematical way,
both at the scale of main vessels and at the level of microcirculation. The peculiar
phenomenon of vessels oscillation (vasomotion) will be considered briefly, and the
literature on the mathematical modeling of diseases like atherosclerosis, affecting
blood flow through arteries, will be illustrated.

1.1 Historical Remarks

The importance of blood for life must have been clear to human kind from the most
remote antiquity, with a lot of implications at the religious level. In the Leviticus
(the third book of the Torah) it is stated that “life is in blood” as a strong motivation
not to eat meat containing fresh blood. In the ancient world health and diseases
have been expressions of supernatural powers, depending on the will of gods and
demons. These views have dominated for millennia before medicine could acquire
a scientific basis. In this mix of logic and magic blood always had a fundamental
role. Think of the rites of blood offering and of blood drinking, common to many
ancient civilization. While these cruel rites have (almost) completely disappeared,
the belief in blood related miracles has survived to our days. Indeed, still today
astonishing miracles involving blood are the subject of great debates, in a number
and a variety of forms which is simply amazing, as everybody can realize by a quick
search on the web.1

1
Perhaps the most emblematic case is the miracle of the “liquefaction” of Saint Januarius’ blood.
It is less known that the blood of many other saints periodically exhibits the same phenomenon.
Saint Januarius (San Gennaro), the patron of Naples, died as a martyr around 305 AD , beheaded
at the Solfatara Crater. According to the legend, his blood was collected by a pious woman
(Eusebia) and preserved till our days (after many vicissitudes) in a sealed transparent container.
A thousand of years later the saint’s relics ended in Naples and in 1389 chronicles started reporting
the miracle. In our days the blood is exposed three times a year and upon mild agitation (most
of the times) the reddish dust turns into liquid. Many explanations have been attempted for this

© Springer International Publishing AG 2017 1

A. Fasano, A. Sequeira, Hemomath, MS&A 18,
DOI 10.1007/978-3-319-60513-5_1
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