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Pathophysiology of Blood Disorders
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A concise full-color review of the mechanisms of blood diseases and disorders – based on a Harvard Medical School hematology course
2015 Doodys Core Title!
4 STAR DOODYS REVIEW!
This is a superb book. Deceptively small, yet packs a wallop. The emphasis on principles instead of practice is welcome....The text is clear, concise, and surprisingly approachable for what could have been a very dense and dry discussion. I could not put this book down and read it entirely in one sitting. When was the last time anyone found a hematology textbook so riveting?--Doodys Review Service
Hematological Pathophysiology is a well-illustrated, easy-to-absorb introduction to the physiological principles underlying the regulation and function of blood cells and hemostasis, as well as the pathophysiologic mechanisms responsible for the development of blood disorders. Featuring a strong emphasis on key principles, the book covers diagnosis and management primarily within a framework of pathogenesis.
Authored by world-renowned clinician/educators at Harvard Medical School, Hematological Pathophysiology features content and organization based on a hematology course offered to second year students at that school. The book is logically divided into four sections:: Anemias and Disorders of the Red Blood Cell, Disorders of Hemostasis and Thrombosis, Disorders of Leukocytes, and Transfusion Medicine; it opens with an important overview of blood and hematopoietic tissues.
Features
- Succinct, to-the-point coverage that reflects current medical education
- More than 200 full-color photographs and renderings of disease mechanisms and blood diseases
- Each chapter includes learning objectives and self-assessment questions
- Numerous tables and diagrams encapsulate important information
- Incorporates the feedback of 180 Harvard medical students who reviewed the first draft -- so you know youre studying the most relevant material possible
Data sheet
- Publication date
- 2011
- Issue number
- 1
- Cover
- paperback
- Pages count
- 352
- Dimensions (mm)
- 188 x 236
- Weight (g)
- 610
Table of Contents
Chapter 1 – Overview of Blood and Hematopoietic Tissues
(Aster and Bunn)
Impact of blood in health and disease
Red blood cell
White blood cells
Platelets
Blood clotting proteins
The bone marrow
The spleen
The thymus
Lymph nodes
Chapter 2 – Hematopoiesis and the Bone Marrow
(Scadden)
Hematopoietic cell diffrerentiation
Myeloid lineage
Erythroid lineage
Megakaryocyte-platelet lineage
Lymphoid lineages – B, T, and NK cells
The biology of the stem cell
Self-renewal
Stem cell ontogeny
Stem cell trafficking
The regulation of blood cell formation
The bone marrow niche and cell-cell interactions
Cytokines in early hematopoietic differentiation
Lineage specific cytokines
Cytokine therapy
Stem cell therapy
Section I – Anemias and Disorders of the Red Blood Cell
Chapter 3 – Overview of the Anemias
(Bunn)
(See full sample chapter)
Definition of anemia
Adaptations to anemia
Alterations in blood flow
Changes in oxygen unloading
Stimulation of erythropoiesis
Signs and symptoms of anemia
Pathophysiology of anemia
Anemia due to blood loss
Anemia due to decreased red cell production
Microcytic
Macrocytic
Normocytic
Anemia due to increased red cell destruction
Chapter 4 - Anemias due to Bone Marrow Failure or Infiltration
(Bunn)
Congenital causes of bone marrow failure
Acquired aplastic anemia and pure red cell aplasia
Myelophthisis
Myelodysplasia
Leukemias
(Myelodysplasia and the leukemias will be covered in detail in Chapters 21 and 22).
Chapter 5 – Iron Homeostasis:: Deficiency and Overload
(Heeney)
Normal iron homeostasis
Iron binding proteins:: transferrin; ferritin
The iron cycle
Role of hepcidin in iron regulation
Iron utilization in erythropoiesis
Laboratory evaluation of iron status
Serum iron and transferrin saturation
Serum ferritin
Bone marrow and liver iron stores
Serum transferrin receptor
Iron deficiency
Etiology
Clinical features – signs and symptoms
Hematological features
Treatment
Iron overload
Primary – inherited mutations in proteins regulating iron homeostasis
Secondary – transfusional hemosiderosis
Chapter 6 - Megaloblastic Anemias
(Heeney)
Biochemistry of vitamin B12 and folate
Pathophysiology
Megaloblastic marrow and peripheral blood morphology
Vitamin B12 and folate absorption
B12 deficiency
Etiology
Clinical presentation (signs and symptoms)
Laboratory evaluation
Treatment
Folate deficiency
Etiology
Clinical presentation (signs and symptoms)
Laboratory evaluation
Treatment
Chapter 7 - Anemias associated with Chronic Disease
(Heeney and Bunn)
Anemia of chronic inflammation
Infection
Cancer
Connective tissue disorders
Pathophysiology – role of hepcidin
Lab features
Treatment
Anemia of renal insufficiency
Cause
Erythropoietin levels
Treatment with erythropoietin and iron
Anemia of chronic liver disease
Anemia of endocrine hypofunction
Chapter 8 – Thalassemia
(Nathan)
Ontogeny of globin gene expression
Organization of alpha and beta globin genes
Definition and classification of the thalassemias
Mutations responsible for the thalassemias
Beta thalassemia
Beta+ versus beta0
Beta thal major
Cellular pathogenesis
Clinical presentation
Laboratory evaluation
Complications
Treatment
Red cell transfusion
Iron chelation
Stem cell transplant
Prevention – prenatal diagnosis
Beta thal intermedia
Beta thal minor
Interacting beta thalassemias – Hb S and Hb E
Alpha thalassemia
Four degrees of gene deletion – correlate with clinical presentation
Three alpha gene deletion - Hb H disease
Four alpha gene deletion – Hydrops fetalis
Prevention – prenatal diagnosis
Chapter 9 – Sickle Cell Disease and other Disorders of Hemoglobin Structure
(Bunn)
Inheritance – beta globin structural mutation:: b6 Glu ® Val
The sickling disorders:: SS, Sb0Thal, Sb+Thal, SC, AS
Molecular pathogenesis
Structure of the sickle fiber
Kinetics of fiber formation
In vivo significance of polymer formation
Cellular aspects of in vivo sickling and vaso-occlusion
Contribution of Hb F
Sickle cell – endothelial cell adhesion
Clinical manifestations
Constitutional:: growth, development and susceptibility to infections
Hemolytic anemia
Vaso-occlusion
Acute pain crises
Acute chest syndrome
Chronic organ damage
Stroke
Bone – aseptic necrosis
Renal:: impaired concentrating ability; impaired glomerular function
Pulmonary hypertension
Treatment
Supportive – analgesia, oxygen, fluid and pH balance
Prophylaxis:: penicillin and vaccinations
Hydroxyurea – induction of Hb F
Novel therapeutic strategies
Chapter 10 – Other Inherited Hemolytic Anemias
(Lux)
Disorders of the red cell membrane
Molecular anatomy of the red cell membrane
Hereditary spherocytosis – mutations in spectrin, band 4.1, band 3
Other inherited membrane disorders
Disorders of red cell metabolism
Hexose monophosphate shunt and G6PD deficiency
Glycolytic pathway – pyruvate kinase deficiency
Chapter 11 – Acquired Hemolytic Anemias
(Bunn)
Acquired membrane disorders
Paroxysmal nocturnal hemoglobinuria
Spur cell anemia
Traumatic hemolytic disorders
Thrombotic thrombocytopenic purpura (Covered in detail in Chapter 14)
Hemolytic uremic syndrome
Disseminated intravascular coagulation (Covered in detail in Chapter 16)
Heart valve hemolysis
Immune hemolytic anemias
Pathophysiologic principles
Clinical presentation and course
Warm antibody hemolysis
Cold antibody hemolysis
Lab diagnosis
Treatment
Chapter 12 - Erythrocytosis (Polycythemia)
(Bunn)
Pathophysiologic principles:: Algorithm for evaluating patients with erythrocytosis
Primary erythrocytosis – polycythemia vera
(See Chapter 20 for coverage of molecular pathogenesis, Chapter 22 for clinical presentation and course, diagnosis and treatment)
Secondary erythrocytosis
Appropriate erythropoietin production
High altitude hypoxemia
Pulmonary hypoxemia
Cardiac hypoxemia (right to left shunt)
Mutant hemoglobin with high oxygen affinity
Inapproriate erythropoietin production
Tumors:: renal, hepatic
Von Hippel Lindau syndrome
Inherited disorders of oxygen sensing HIF pathway
Section II – Disorders of Hemostasis and Thrombosis
Chapter 13 – Overview of Hemostasis
(Furie)
Phases of clot formation and dissolution
Platelet plug
Coagulation
Fibrinolysis
Molecules that participate in clot formation and clot lysis
Platelet activation
Adhesion
Aggregation
Secretion
Laboratory evaluation of platelet function
Platelet aggregation
Bleeding time
Blood Coagulation
In vitro coagulation cascade
Laboratory evaluation
Partial thromboplastin time
Prothrombin time
Thrombin time
Fibrinogen
Factor assays
Factor VIII panel:: activity, antigen, ristocetin cofactor, multimer assay
D-dimer assay
Mixing studies – identification of circulating anticoagulant
Anticoagulent/fibrinolytic drugs
Warfarin
Heparin and heparin mimetics (see Chapter 17)
Fibrinolytic agents
Chapter 14 – Platelet Disorders
(Furie)
Acquired Platelet Disorders
Thrombocytopenia
Decreased production
Drugs, toxins
Aplasia (Chap 4), myelodysplasia (Chap 22), PNH (Chap 11)
Sequestration (hypersplenism)
Increased consumption/destruction
Immune thrombocytopenia
Chronic ITP
Acute ITP
Drug induced
Alloimmune
Clinical presentation and course
Treatment
Thrombotic thrombocytopenic purpura
Molecular pathogenesis
Diagnostic criteria
Clinical presentation and course
Therapy
Acquired qualitative platelet disorders
Drug induced defects in platelet secretion:: aspirin, NSAID
Uremia
Hereditary Platelet Disorders
Defective adhesion:: Bernard-Soulier
Defects of release and of storage pools
Defective aggregation:: Glanzmanns thrombesthenia
Chapter 15 – Inherited Coagulation Disorders
(Furie)
Factor VIII deficiency (hemophilia A, classic hemophilia)
Genetics
x-linked
mutations responsible for hemophilia A
Clinical manifestions of disease
Laboratory monitoring
Therapy
Factor VIII infusion
Supportive care
Complication of therapy
HIV, viral hepatitis
Acquired inhibitors (inducible and uninducible)
Factor IX deficiency (hemophilia B, Christmas disease)
Genetics
x-linked
mutations responsible for hemophilia B
Clinical manifestions of disease
Laboratory monitoring
Therapy
Factor IX concentrate infusion
Supportive care
Complication of therapy:: HIV, viral hepatitis
Chapter 16 – Acquired Coagulation Disorders
(Furie)
Impaired synthesis of coagulation factors
Liver disease
Drugs
Vitamin K deficiency
Usual clinical setting
Hemorrhagic disease of the newborn
Factitious or accidental warfarin ingestion
Disseminated intravascular coagulation
Etiology
Lab diagnosis
Treatment
Factor X deficiency and amyloid
Coagulation factor deficiencies due to specific inhibitor
Acquired Factor VIII deficiency
Others:: V, vWD, etc
Lupus anticoagulant/anti-cariolipin (see Chapter 17)
Chapter 17 – Thrombotic Disorders
(Bauer)
Principles of thrombosis and thrombotic disorders
Nation-wide and world-wide impact
Virchows triad
Inhibitors/regulators of coagulation
Anti-thrombin III – effect of heparin
Protein S, activated protein C cleavage of Va and VIIIa
Tissue factor protein inhibitor
Fibrinolysis
Risk factors for venous thrombosis
Inherited thrombotic disorders
Assay measurements
Protein C deficiency – warfarin skin necrosis
Protein S deficiency
Factor V Leiden
Prothrombin gene mutation:: 20210 G-> A
Impact of inherited defects on thrombotic risk
Acquired thrombotic disorders
Antiphospholipid antibody syndrome (lupus anticoagulant; anti-cardiolipin antibody)
Clinical presentation
Laboratory diagnosis
Treatment
Heparin-induced thrombocytopenia
Pathogenetic mechanism
Clinical presentation
Laboratory diagnosis
Treatment
Section III – Disorders of Leukocytes
Chapter 18 – Leukocyte Function and Non-malignant Leukocyte Disorders
(Berliner)
Distribution of cells within the myeloid/neutrophil compartment
Marrow compartment
Peripheral compartment
Circulating
Marginating
Determinants of peripheral neutrophil count
Production
Margination
Sequestration
Destruction
Evaluation of neutrophilia
Primary hematologic disorders
Congenital – e.g. Downs syndrome, inherited defects in leukocyte adhesion
Acquired – e.g. chronic myeloid leukemia
Secondary to other disorders
Infection
Stress
Drug induces
Chronic inflammation
Post-splenectomy
Approach to patient with neutrophilia
Evaluation of neutropenia
Congenital
Constitutional, benign
Severe congenital neutropenia
Neutrophil elastase mutations
Kostmanns syndrome
Cyclic neutropenia
Others
Acquired neutropenia
Post-infection
Drug-induced
Vitamin B12, folate deficiency
Hypersplenism
Immune related
Auto-immune
Isoimmune – newborns
Associated with immune disorders
Dignostic evaluation
Treatment of neutropenias
Depends on severity
Wide range of options:: supportive, steroids, IgG, G-CSF, stem cell transplant
Qualitative abnormalities of neutrophil function
Disorders of respiratory burst:: chronic granulomatous disease, myeloperoxidase def
Abnormalities of leukocyte adhesion and chemotaxis
Defects in structure and function of neutrophil granules
Non-malignant lymphocyte disorders
Lymphocytosis
Reactive lymphocytosis; cytomegalovirus, HIV, toxoplasmosis
Infectious mononucleosis
Lymphopenia:: steroid therapy, immunodeficiency syndromes
Histiocytic disorders – hemophagocytic lymphohistiocytosis
Chapter 19 – Introduction to Hematologic Malignancy
(Fleming)
Classes of hematologic malignancies
Acute leukemias
Myelodysplastic syndromes
Chronic myeloproloferative disorders
Lymphomas
Diagnostic criteria
Lineage of the malignant cell (cell of origin)
Molecular genetic features
Clinical features
Clinical subtypes of disease
Leukemia versus lymphoma
Acute versus chronic leukemia
Indolent versus aggressive lymphoma
Clonality in hematologic malignancies
Critical for distinguishing some neoplasms from reactive proliferations
Established by a number of techniques
X-chromosome inactivation (rarely used clinically)
Conventional and molecular cytogenetics
Acquired mutations of pathogenetic significance:: e.g., JAK2 mutation in PCV
B cells:: production of monoclonal immunoglobulin protein
B cells or T-cells:: detection of monoclonal antigen receptor gene rearrangements
Chapter 20 – Molecular Mechanisms underlying Hematologic Malignancies
(Aster)
Chronic myeloproliferative disorders:: tumors caused by mutations in tyrosine kinases
Pathophysiology:: hyperproliferation of hematopoietic progenitors with preserved differentiation
Chronic myeloid leukemia:: BCR-ABL fusion oncoproteins
Polycythemia vera:: gain of function JAK2 mutations
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