Overview of Hematology
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Transcript Overview of Hematology
Overview of Hematology
Dr. Gamal Badr
PhD in Immunology (Paris Sud University, France)
Associate Professor of Immunology
Assiut University, Egypt
Tel: +2 01110900710
Fax: +2 0882344642
E-mails: [email protected] or [email protected]
Websites:
http://www.aun.edu.eg/membercv.php?M_ID=393
https://www.researchgate.net/profil/Gamal_Badr/
http://scholar.google.com.eg/citations?hl=en&user=dz13dkQAAAAJ
orcid.org/0000-0002-6157-7319
Hematology
Hematology, also spelled haematology,
is the branch of internal medicine,
physiology, pathology, clinical
laboratory work, and pediatrics that is
concerned with the study of blood, the
blood-forming organs, and blood
diseases. Hematology includes the
study of etiology, diagnosis, treatment,
and prevention of blood diseases.
Topics
Hematopoiesis
Complete blood count
(CBC)
Anemia
Polycythemia
Leukopenia
Leukemia and lymphoma
Myeloma
Coagulation
Transfusion
BLOOD IS A TYPE OF CONNECTIVE TISSUE
WHAT DOES BLOOD DO?
Transportation
Oxygen
Nutrients
Hormones
Waste Products
Regulation
Fluid, electrolyte
Acid-Base balance
Body temperature
Protection
Coagulation
Fight Infections
Components of Blood
Suspension of cells in a solute of
water, proteins, and electrolytes
Average volume is 5 liters
70mL per kg body weight
Blood components are:
A. Liquid component -Plasma (55%)
Plasma is a yellow colored solution
containing a mixture of water, amino acids,
proteins, clotting factors, carbohydrates,
lipids, vitamins, hormones, electrolytes, and
cellular wastes.
B. Cellular component
(45%)
Thrombocytes/Platelets
Leukocytes/ white blood
cells (WBCs)
Erythrocytes/ red blood
cells (RBCs)
Complete Blood Count (CBC)
White blood cells (WBCs) Normal 4,000 -11,000 /µℓ
Differential cells: Neutrophils, lymphocytes, monocytes, eosinophils,
basophils, Dendritic cells.
•
Red blood cells (RBCs) ♂ 4.5 – 5.5 x 106/µℓ ♀ 4.0 – 5.0 x 106/µℓ
Hemoglobin (Hgb), Hematocrit (Hct)
The hematocrit is the percent of whole blood that is composed of red
blood cells. The hematocrit is a measure of both the number of RBCs
and the size of red blood cells.
Mean corpuscular volume (MCV)
is a measure of the average volume of a red blood corpuscle
Platelets (PLT) Normal 15,000 -400,000 /µℓ
Hematopoiesis
Development of all blood cells and other formed
elements
Sites vary throughout development
Before birth: liver, spleen
Adult: bone marrow (BM) of axial skeleton.
Stem cells
Primitive; self-replicate and differentiate to become
increasingly specialized progenitor cells which form mature
cells
Process regulated by growth factors (interleukins, erythropoietin,
thrombopoietin, G-CSF)
Early lineage division between progenitors for lymphoid and
myeloid cells
Hematopoiesis
Thrombocytes/Platelets
Must be present for clotting to occur
Involved in hemostasis
Leukocytes/White Blood Cells (WBCs)
o Granulocytes
Contain granules in their
cytoplasm
Basophils
Eosinophils
Neutrophils
Agranulocytes
Contain no granules in their
cytoplasm
Monocytes
Lymphocytes
Types and Functions of Leukocytes
TYPE
CELL FUNCTION
Granulocytes
Neutrophil
Eosinophil
Basophil
Phagocytosis: early phase of inflammation
Phagocytosis: parasitic infections
Inflammatory response, allergic response
Agranulocytes
Lymphocyte
Monocyte
Cellular and humoral immune response
Phagocytosis: cellular immune response
Erythrocytes/Red Blood Cells (RBCs)
Immature RBC (circle and nucleated), while mature
RBC is circle and non nucleated
Composed of hemoglobin (Hb or Hgb)
Erythropoiesis is the production of RBCs
Stimulated by hypoxia (decrease of O2 in the blood)
Controlled by erythropoietin (hormone synthesized in kidney)
Hemolysis is the destruction of RBCs
Releases bilirubin into blood stream
Normal lifespan of RBC = 120 days
Structures of the Hematologic System
Bone Marrow a primary lymphoid organ (Hematopoiesis)
• Soft connective tissue in core of bones
• The production of all types of blood cells (Hematopoiesis) generated by
a remarkable self-regulated system that is responsive to the demands
put upon it.
Liver
Receives 24% of the cardiac output (1500 ml of blood each minute)
Liver has many functions. The hematologic functions:
Liver synthesis plasma proteins including clotting factors and albumin
Liver clears damaged and non-functioning RBCs/erythrocytes from
circulation
Spleen a secondary lymphoid organ exerts many functions:
Hematopoietic function: Produces fetal RBCs
Filter function: Filter and reuse certain cells
Immune function: Lymphocytes, monocytes
Storage function: 30% platelets stored in spleen
RBCs (erythrocytes)
Mature RBCs are biconcave disks that contain
oxygen-carrying hemoglobin, discard their nuclei
during development and so cannot reproduce or
produce proteins.
In the embryo and fetus, RBCs production occurs in the
liver and spleen; but after birth, it occurs in the bone
marrow. Normal lifespan = 120 days
Reticulocytes (Immature red blood cells)
o Calculating proportion within circulation assists
in determining cause of anemia
Normal % is 1-2%
Low % (< 0.4%) suggests decreased production
(i.e. nutritional or marrow problem)
High % (< 3%) suggests bleeding or premature
destruction of red blood cells (i.e. hemolysis)
Red Blood Cells
Blood
RBCs
Bone marrow
1 – 2%
RBC Production and Its Control
The total number of red blood cells remains relatively constant due to a negative
feedback mechanism utilizing he hormone erythropoietin, which is released from the
kidneys and liver in response to the detection of low oxygen levels.
Factors Affecting RBCs Production
Dietary Vitamins B12 and folic acid are needed for DNA synthesis, so
they are necessary for the reproduction of all body cells, especially in
hematopoietic tissue.
Dietary Iron is needed for hemoglobin synthesis.
Destruction of RBCs with age, RBCs become increasingly fragile and
are damaged by passing through narrow capillaries.
Macrophages in the liver and spleen phagocytize damaged red blood
cells.
Hemoglobin from the decomposed RBC is converted into heme and
globin.
Heme is decomposed into iron which is stored or recycled and
biliverdin and bilirubin which are excreted in bile.
RBCs Disorders
WBCs Disorders
Anemias
Benign &
Malignant
&Others
Hematological
Disorders
Hemostatic
Disorders 1ry & 2ry
Transfusion
Medicine
RBCS DISORDERS
RBCs Disorders
Anemia
Anemia is defined as a reduction in one or more of the major RBC
measurements: Hgb, Hct, or RBC count
Normal Hgb concentration– 15 in males ; 14 in females
Patients are “anemic” when Hgb is < 12 g/dL
Determining reticulocyte count and MCV are first steps in
determining etiology
MCV = 10 x HCT(percent) ÷ RBC numbers (millions/µL)
Almost 1/3 of the world population is anemic!
RBCs Disorders - Anemia
Manifestations related to duration and severity of anemia:
May provide important clues as to etiology
Body has physiologic responses to chronic anemia such that
many patients are asymptomatic until Hgb < 8 g/dL
Fatigue, pallor, dyspnea, dizziness, ischemic pain, cognitive
abnormalities
Two main approaches that are not mutually exclusive:
1. Morphological approach.
2. Biologic or kinetic approach.
Anemia - (Morphological approach)
By calculation from an independently-measured RBCs count and
hematocrit:
MCV (femtoliters) = 10 x HCT(percent) ÷ RBC (millions/µL)
The normal MCV (76 -100 fL)
Microcytosis – small cells (MCV <80) – microcytic anemia
Macrocytosis – large cells (MCV >100) – macrocytic
anemia
Normocytic anemia
is defined as an anemia with a MCV of 80-100 which is the normal range, but the
HCT and Hbg is decreased
Microcytic Anemia (MCV <76 fL)
The normal MCV (76 -100 fL)
Microcytosis – small cells (MCV <80)
Most common type of anemia encountered in primary
care
Differential diagnosis
Hemoglobinopathy (inherited)
Iron deficiency
Chronic disease (may also be normocytic)
Inflammation
Lead poisoning
Microcytic Anemia
Peripheral blood smear
Microcytosis, Hypochromic (are paler than usual)
Macrocytic Anemia
Macrocytosis – large cells (MCV >100)
Differential diagnosis
B12 deficiency
Pernicious anemia: (Biermer's anemia, Addison's anemia) is caused
by loss of gastric parietal cells, which are responsible for the secretion of
factors that are responsible for absorption of vitamin B12 in the ileum.
Folate deficiency
Check vitamin B12, RBC folate, fasting homocysteine (HC), and
methylmalonic acid (MMA)
HC and MMA are elevated in subclinical B12 and folate
deficiency
Anemia - (kinetic approach)
Anemia
Abnormality?
Production of RBCs
Survival/Destruction of RBCs
(hypoproliferation)
The key test is the reticulocyte count
Mechanisms of Anemia
Decreased erythrocyte production
Erythrocyte loss
Decreased erythropoietin production
Hemorrhage
Inadequate marrow response to erythropoietin
Hemolysis
Anemia - (kinetic approach)
Mechanisms
Short survival/Destruction of RBCs/ loss of RBCs
Blood loss / hemorrhage
Accidents
Ulcer or surgery in Gastrointestinal tract (GI), menstruation
Hemolysis
•
Shortened RBC survival time.
Decreased production (hypoproliferative)
Nutritional deficiency (iron, B12, and folate)
Systemic illness (chronic kidney disease (CKD), cancer, rheumatologic
disease, etc.)
Bone marrow disorders
RBCs Disorders - Anemia
Marrow production
Thalassemias
Myelodysplasia
Myelophthisic
Aplastic anemia
Nutritional
deficiencies
Red cell destruction
(hemolytic)
Hemoglobinopathies
Enzymopathies
Membrane disorders
Autoimmune
RBCs Disorders - Red cell destruction
Causes:
Elevated reticulocyte count
Mechanical
Autoimmune
Drug
Congenital
Red cell destruction -Hemolytic Anemia
History and physical findings
Hemolytic anemias are either acquired or congenital. The laboratory
signs of hemolytic anemias include:
Increased LDH (Lactate dehydrogenase).
Increased bilirubin.
Increased reticulocyte count.
Decreased haptoglobin.
Urine hemosiderin
Jaundice is common
Occasional pain in the left upper abdominal region .(splenomegaly)
Red cell destruction -Hemolytic Anemia
Congenital
Membrane defects
Hereditary spherocytosis : auto-hemolytic anemia characterized by
the production (RBCs) that are sphere-shaped, rather than bi-concave
disk shaped
Hereditary elliptocytosis: also known as ovalocytosis, is an inherited
blood disorder in which an abnormally large number of the patient's
RBCs are elliptical rather than the typical biconcave disc shape.
Enzyme defects
Glucose-6-phosphate dehydrogenase (G6PD) deficiency: X-linked
recessive hereditary disease.
Pyruvate kinase deficiency: is an inherited metabolic disorder of the
enzyme Pyruvate kinase which affects the survival of RBCs and causes
them to deform into echinocytes on peripheral blood smears.
Red cell destruction -Hemolytic Anemia
Congenital
Hemoglobin defects: diagnosed by hemoglobin electrophoresis.
Thalassemias: Genetic defect in hemoglobin synthesis
decreased synthesis of one of the 2 globin chains ( or )
Imbalance of globin chain synthesis leads to depression of hemoglobin
production and precipitation of excess globin (toxic)
“Ineffective erythropoiesis”
Found in people of African, Asian, and Mediterranean heritage
Fe stores are usually elevated
The only treatments are stem cell transplant and simple transfusion.
Chelation therapy (administration of chelating agents to remove heavy
metals from the body) to avoid iron overload has to be started early.
Red cell destruction -Hemolytic Anemia
Congenital
Hemoglobin defects:
Sickle cell disease
Single base pair mutation results
in a single amino acid change.
Under low oxygen, Hgb becomes
insoluble forming long polymers
This leads to membrane changes
(“sickling”) and vasoocclusion
OXY-STATE
DEOXY-STATE
Red cell destruction -Hemolytic Anemia
Aquired
Classified according to site of RBC destruction and whether
mediated by immune system
Intravascular
Extravascular
Autoimmune
Non-immune
Many causes… be aware of these –
Transfusion of incompatible blood
Prosthetic valves
Cancer
Drugs
RBCs Disorders - Anemia
Marrow production
Thalassemias
Myelodysplasia
Myelophthisic
Aplastic anemia
Nutritional
deficiencies
Red cell destruction
(hemolytic)
Hemoglobinopathies
Enzymopathies
Membrane disorders
Autoimmune
Marrow Production - Aplastic Anemia
Aplastic anemia is a disease in which the bone marrow, and the blood stem
cells that reside there, are damaged. This causes a deficiency of all three blood
cell types: red blood cells (anemia), white blood cells (leukopenia), and platelets
(thrombocytopenia).
Acquired
Immunological
Toxins – Benzene
Drugs – methotrexate, chloramphenicol
Viruses – EBV, hepatitis
Hereditary
Fanconi anemia (FA) is the result of a genetic defect in a cluster of
proteins responsible for DNA repair
Marrow Production - Aplastic Anemia
All lineages affected.
Most patients require red cell transfusions.
Transplant when possible.
Transfusions should be used selectively to avoid
sensitization (no family donors!).
Polycythemia / Erythrocytosis
Polycythemia is increased total RBC mass - Hct > 65%
Above 65% blood viscosity rises exponentially
Complications: Polycythemic hyperviscosity is increased viscosity of the
blood resulting from increased numbers of RBCs
Polycythemia occurs in 2-4% of newborns, half of them are symptomatic
Clinical signs result from regional effects of hyperviscosity and from the
formation of microthrombi
Tissue hypoxia, Acidosis, Hypoglycemia
Organs affected: CNS, kidneys, adrenals, cardiopulmonary system, GI tract
Treatment
Phlebotomy (to cut a vein) is the process of making an incision in a vein
.
Myelosupressive agents: new therapeutic agents such as: interferon
alfa-2b (Intron A) therapy, agents that target platelet number (e.g.,
anagrelide [Agrylin]), and platelet function (e.g., aspirin).
Benign WBCs Disorders
Leukopenia (Leukocytopenia) Leukopenia: is a decrease in the number of WBCs
Neutropenia is most common cause
Absolute neutrophil count (ANC) < 1.5 x 109 cells/L
Many causes
Benign racial neutropenia common
African Americans and Yemenite Jews may have ANC as low as 1.0
Viral infections
Epstein-Barr, Hepatitis B, HIV
Drugs
Careful review of medications ; be suspicious of any medication
recently started in patient with acute onset neutropenia
Splenomegaly
Autoimmune disorders
SLE (lupus), Rheumatoid Arthritis, etc.
Bone marrow disorders
Leukocytosis
Leukocytosis: is an increase in the number of WBCs
WBC count > 11,000
Determine which type of WBC is leading to the leukocytosis
Neutrophilia = most common
Causes:
Infection
Connective tissue disorders
Medications (especially steroids, growth factors)
Cancer Myeloproliferative disorders
Cigarette smoking
Stress (physiologic)
Pain, trauma
Idiopathic (unknown cause)
Leukocytosis
Patients with acute bacterial infection often present
with neutrophilia and band formation
Bands = young neutrophils
Viral infections are usually associated with low
WBCs ; leukocytosis may suggest complications
Ex: bacterial pneumonia with underlying influenza infection
Leukocytosis
Lymphocytosis: is an increase in the number or
proportion of lymphocytes in the blood
Causes:
Viral infections: HBV, HCV, EBV, CMV
Tuberculosis
Pertussis
Drug Reaction
Stress (physiologic): Trauma, cardiac arrest, etc
Malignancy: ALL, CLL, lymphoma
Malignant WBCs Disorders
Types of Hematopoietic Malignancies
Leukemias
•
Acute leukemias
•
Acute myeloid leukemia
•
Acute lymphoblastic leukemia
•
Chronic leukemias
•
Chronic myeloproliferative disorders
•
Chronic lymphoproliferative disorders
Lymphomas
•
Non-Hodgkin's lymphoma
•
Hodgkin's disease
Plasma cell disorders
•
Myeloma
Myeloid vs. Lymphoid
Myeloid malignancies
•
Acute myeloid leukemia
•
Chronic myeloproliferative disorders
Lymphoid malignancies
•
B-cell malignancies
•
Acute lymphoblastic leukemia, B-cell type
•
Non-Hodgkin’s lymphoma, B-cell types
•
Myeloma
•
T-cell malignancies
•
Acute lymphoblastic leukemia, T-cell type
•
Non-Hodgkin’s lymphoma, T-cell types
•
Hodgkin’s disease
Leukemia
Leukemia is a type of cancer of the blood or bone
marrow characterized by an abnormal increase of
immature WBCs called “blasts".
Leukemia is a broad term covering a spectrum of
diseases. In turn, it is part of the even broader group of
diseases affecting the blood, bone marrow, and lymphoid
system.
Chronic Leukemia
Chronic myelogenous leukemia (CML)
Translocation between long arms of chromosomes 9 and 22 ;
“Philadelphia Chromosome” ; bcr/abl protein
Chronic Leukemia
Chronic lymphocytic leukemia (CLL)
Clonal malignancy of B-lymphocytes
Course is usually indolent ; affects older patients, average age at diagnosis is
70 years
Often found incidentally
Fatigue, lymphadenopathy common
Hepatosplenomegaly
Immunodeficiency is major clinical concern
Lymphocytes are defective ; do not make antibodies in response to
antigens
Treatment
Observation
Indications for therapy include progressive fatigue, symptomatic
lymphadenopathy, anemia, or thrombocytopenia
Gamma globulin (IVIG) used in patients with recurrent or severe bacterial
infections
Allogeneic BMT is potentially curative but reserved for select patients
Prognosis improving ; survival is 10-15 years with early disease
Acute Leukemia
Acute Myelogenous Leukemia (AML)
Most common in adults
Usually no apparent cause
Exposure to radiation, benzene, and certain chemotherapy drugs (alkylators)
associated with leukemia
Underlying myelodysplastic syndrome (MDS) is risk factor
Symptoms and signs
Related to replacement of marrow space by malignant WBCs
Patients often very ill for period of just days or weeks
Skeletal pain
Bleeding
Gingival hyperplasia
Infection
Pancytopenia with circulating blasts is hallmark ; bone marrow biopsy
required
• Auer rods on peripheral smear are pathognomonic
Acute Leukemia
AML
Management
Immediate referral to hematologist
Patients often hospitalized for therapy
Anthracycline (daunorubicin or idarubicin) plus cytarabine
results in CR in 80% of patients < 60 years
Additional high dose chemotherapy following CR leads to cure rate
of 35-40%
Acute Lymphocytic Leukemia
More often seen in children
(ALL)
Lymphoma
Hodgkin’s disease
Malignancy of B-lymphocytes
Reed-Sternberg cells
Various subtypes ; “nodular sclerosing” is
most common
Non-Hodgkin’s Lymphoma (NHL)
Heterogeneous group of cancers affecting
lymphocytes
Usually classified by histologic grade (low to high)
Follicular lymphoma
Small lymphocytic lymphoma
Diffuse large B-cell lymphoma
Burkitt’s lymphoma
Many others
Myeloma
Malignancy of plasma cells
Abnormal paraproteins are created leading to systemic
problems
IgG – 60%
IgM – 20%
Primarily disease of elderly (median age 65 years)
Most common hematologic malignancy among African
Americans ; #2 among Caucasians