Clinical Aspects and Laboratory – Iron Metabolism, Anemias

207 Pages·2012·1.94 MB·English

W

Manfred Wick
Wulf Pinggera
Paul Lehmann
Clinical Aspects and Laboratory –
Iron Metabolism, Anemias
Concepts in the anemias of m alignancies
and renal and rheumatoid d iseases
Sixth, revised and updated edition
With contributions by
Volker Ehrhardt
Dr. Manfred Wick
Institute of Clinical Chemistry, Klinikum Grosshadern,
University of Munich, Germany
Univ.-Prof. Dr. Wulf Pinggera
Maria Taferl, Austria
Dr. Paul Lehmann
Mainz, Germany
With contributions by
Dr. Volker Ehrhardt
Roche Diagnostics GmbH, Mannheim, Germany
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Foreword
Anemias are a worldwide problem. Severe anemia aff ects mainly older
women and men. Th e WHO defi nes anemia as a hemoglobin concen-
tration of less than 12 g/dL in women and less than 13 g/dL in men
(World Health Organization. Nutritional Anemias. Technical Reports
Series 1992; 503). According to these criteria, 10–20% of women and
6–30% of men above the age of 65 years are anemic. In this book, we
place a new emphasis on the diagnosis and treatment of anemias of
chronic disease (ACD) and renal anemias. Nevertheless, iron defi ciency
remains globally the most important cause of anemia.
Th ere have been so many advances in the diagnosis and, in particu-
lar, the therapy of the anemias in recent years that it appeared necessary
to e xtend the spectrum of therapies and diagnostic methods d escribed.
Apart from renal and infl ammatory anemias, new insights regarding the
role of transferrin receptor, the physiology of erythropoietin produc-
tion, and the genetic defect as well as the pathogenesis of hemochroma-
tosis demanded a major update of the book.
Th e authors are grateful to Annett Fahle and Ralf Röddiger of Roche
Diagnostics GmbH for their committed c ooperation and their support in
the publication of this book.
November 2010 M. Wick
W. Pinggera
P. Lehmann

Table of Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Iron Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Absorption of Iron. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Iron Transport in the Circulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Transferrin, Iron-Binding Capacity and Transferrin Saturation. . . . . . . . . . . 5
Iron Storage – Ferritins, Isoferritins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Distribution of Iron in the Body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Iron Requirement and Iron Balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Transferrin Receptor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Soluble Transferrin Receptor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Hepcidin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
s
l
Erythropoiesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 a
t
Physiological Cell Maturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 n
e
Hemoglobin Synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
m
Erythropoietin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
a
Erythrocyte Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 d
Phagocytosis of Old Erythrocytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 n
u
Hemoglobin Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 FF
D isturbances of Iron Metabolism/Disturbances
of Erythropoiesis and Hemolysis. . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Disturbances of Iron Balance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Iron Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Disturbances of Iron Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Anemias of Malignancies and Anemias of Chronic Diseases. . . . . . . . . . . . 28
D ifferentiation between Shortage of Depot Iron
and Functional Iron Deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
VIII Table of Contents
Disturbances of Iron Utilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Renal Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Pathophysiology of Erythropoietin Synthesis. . . . . . . . . . . . . . . . . . . . . . . 34
Iron Overload. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
s
l Primary Hemochromatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
a
t Other Hereditary States of Iron Overload . . . . . . . . . . . . . . . . . . . . . . . . . 39
n
e Other Disturbances of Erythropoiesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
m Disturbances of Stem Cell Proliferation. . . . . . . . . . . . . . . . . . . . . . . . . . . 40
a Vitamin B and Folic Acid Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
d 12
Hemoglobinopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
n
u Disturbances of Porphyrin Synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
FF
Pathologically Increased Hemolysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Haptoglobin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Features of Severe Hemolysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Causes of Hemolysis (Corpuscular/Extracorpuscular). . . . . . . . . . . . . . . . . 48
Diagnosis of Disturbances of Iron Metabolism. . . . . . . . . . . . . . . . 50
Iron Balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Case History and Clinical Findings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
F erritin, Transferrin, Transferrin Saturation, Soluble Transferrin
Receptor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
L aboratory Diagnostics of Suspected Disturbances of Iron
s Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
ct Most Frequent Disturbances of Iron Metabolism and E rythropoiesis . . . . . 66
e Hypochromic, Microcytic Anemias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
p
s
A Iron Deficiency – Diagnosis and Therapy . . . . . . . . . . . . . . . . . . . . 68
l Laboratory Diagnostics in Cases of Suspected Iron Deficiency. . . . . . . . . . . . 68
a
c Clinical Pictures of Iron Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
i Oral Administration of Iron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
n
i Parenteral Administration of Iron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
l
C
Side-Effects and Hazards of Iron Parenteral Therapy. . . . . . . . . . . . . . . . . 78
Disturbances of Iron Distribution and Hypochromic Anemias . . . . . .80
Iron and Cellular Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Activation of the Immunological and Inflammatory Systems . . . . . . . . . . . 85
Therapy with Erythropoietin and i.v. Iron Administration. . . . . . . . . . . . . . 88
Table of Contents IX
AAnneemmiiaass ooff IInnffeeccttiioonn aanndd MMaalliiggnnaannccyy .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 9911
Biological Activity of Tumor Necrosis Factor. . . . . . . . . . . . . . . . . . . . . . . 92
Hemoglobin in Therapies with Cytostatic Drugs . . . . . . . . . . . . . . . . . . . . 93
Erythropoietin and Iron Replacement in Tumor Anemias . . . . . . . . . . . . . . 95
AAnneemmiiaass ooff CChhrroonniicc IInnffllaammmmaattoorryy PPrroocceesssseess .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 110011
Anemias of Rheumatoid Arthritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Erythropoietin and Iron Therapy of Rheumatoid Arthritis. . . . . . . . . . . . . 104
Disturbances of Iron Utilization . . . . . . . . . . . . . . . . . . . . . . . . . . 106
s
Uremic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 t
c
Therapy of Uremic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 e
p
s
Iron Overload . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 A
Primary Hematochromatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 l
a
Secondary Hematochromatosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 c
i
n
Non-Iron-Induced Disturbances of Erythropoiesis. . . . . . . . . . . . . 117 i
l
C
MMaaccrrooccyyttiicc,, HHyyppeerrcchhrroommiicc AAnneemmiiaa .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 111188
Folic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Vitamin B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
12
NNoorrmmoocchhrroommiicc,, NNoorrmmooccyyttiicc AAnneemmiiaa.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 112266
Extracorpuscular Hemolytic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Corpuscular Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Erythropoietin Therapy of Other Diseases. . . . . . . . . . . . . . . . . . . . . . . . 130
Methods of Determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
SSeerruumm//PPllaassmmaa PPaarraammeetteerrss .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 113322 y
Iron. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 r
o
Iron Saturation (Total Iron-Binding Capacity and Latent t
a
Iron-Binding C apacity). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 r
o
Iron-Binding Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 b
Ferritin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 a
L
Transferrin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Transferrin Saturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Soluble Transferrin Receptor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
Haptoglobin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142