Hematological Diseases

Diseases of Red Diseases of

Cells Diseases of Platelets White Cells
& Coagulation
Proteins

anemias Leukemias

Bleeding /Thrombosis

Myeloproliferative Diseases Multiple Meyloma

Red blood cells = Erythroid cells = Erythrocytes

• Most abundant cells in blood

• RBC count: 4.5-6.5 x 1012 / L

• Red cells: disc shape, biconcave

• Do not have a nucleus

• Colored red because of presence of hemoglobin

Red Blood Cells - Site of Production

Bone marrow

process called = Erythropoeisis

(Erythropoeisis = synthesis of red blood

cells’precursors marrow)
 Formation of Red Cells - Erythropoiesis

stem cell late stem cell proerthroblast

basophilic
(pronormoblast)
erythroblast

polychromatophilic orthocromatophilic orthochromatic

reticulocyte
erythroblast erythroblast erythroblast (polychromat
(Normoblast) extruding its mature
ophilic
nucleus erthrocyte) red
cells
 Erythropoiesis
• the development of mature red blood cells (erythrocytes).
• The first cell that is morphologically recognizable as specifically leading
down the red cell pathway is the proerythroblast .

• As development progresses, the nucleus becomes smaller and the

cytoplasm becomes more basophilic

• As the cell begins to produce hemoglobin, the cytoplasm attracts both basic
and eosin stains, and is called a polychromatophilic erythroblast . The
cytoplasm eventually becomes more eosinophilic, and the cell is called an
orthochromatic erythroblast

• This orthochromatic erythroblast will then extrude its nucleus and enter the
circulation as a reticulocyte . Reticulocytes are so named because these
cells contain reticular networks of polyribosomes.

• As reticulocytes loose their ribosomes they become mature red blood cells.
Erythropoiesis
 Functions of Blood:
• Distribution of nutrients, hormones and
O2

• Transport medium for metabolic

wastes
• Transport medium for specialized
defense cells
 Blood = connective tissue

extracellular specialized cells:
matrix: (Formed elements)
Plasma RBCs 
WBCs
Platelets
 RBCs = Erythrocytes
Most abundant blood
cell: 1000 RBCs/1 WBC

No nucleus = anucleate

Lifespan ~ 120 days

Erythropoiesis – Growth Factors
Erythropoiesis – Growth Factors
• Erythropoietin – (EPO) is the hormone
produced by kidney to stimulate RBC
production
 Regulation of Red Cell Production
Kidney Bone Marrow Multi-potent
Epo stem cell
mRNA
Erythroid
Epo stem cell
Oxygen
sensor
3-4
days
Blood vessel

Peripheral
blood

RBC survival
120 days
 RBC Shape

Disc shape

RBC in
capillaries

Fig 20­2
Hemoglobin:

A complex protein, composed of heme + globin

(2α + 2β) chains

Carries oxygen from lungs to tissues and CO2

from tissues to lungs
 Hemoglobin (Hb)

β
Fe ion
in heme
group
reversibly
binds O2

How many oxygen

α
molecules can 1
 haem
globin
chains

Haem= protoporphyrin ring+ iron

Heme Synthesis

+ globin
 Red Cell Metabolism
(Anaerobic Glycolysis)
 Anemia - Definition

Reduction below normal of Hb

and/or hematocrit appropriate for
age and ethnic group
Males: 135 – 165 g/L
Females : 12-14 g/L
Anemia- Physiologic Definition

Decrease in oxygen carrying capacity

and thus oxygen availability to tissues

 Anemias

Clinical Consequences Of Anemia Depends On:

** Hemoglobin concentration
(the reduction in the oxygen carrying capacity of the blood)

**The rapidity with which the anemia has developed

**Age of the patient

** The compensatory mechanisms of the body

** The underlying cause of the anemia

 Anemia

Acute Chronic

symptoms as chronic IDA ( iron

develop defficiency ) ,
quickly over a Pernicious anemia
short period of patients can tolerate
time lower levels of Hb
Symptoms and signs of Anemia

Fatigue , palpitations , headaches

Dizziness

Dyspnea on exertion

Pallor of skin and mucous membranes

Chest pains and angina

Features specific to underlying cause

Adapting to Anemia

The body can adapt to decrease in O2

carrying capacity by:
Hb gives O2 more readily to tissues by
increase in 2,3DPG
 Adapting to Anemia
As a compensatory measure, heart rate
increases ( tachycardia ) as well as
respiratory rate (tachypnea). This occurs
at rest or with small exertion
Oxygen Dissociation Curve of Hb
 Anemia-Classification
1: Based on cause
2: Morphologic: red cell size:
microcytic / normocytic/ macrocytic
3: Pathophysiologic: decreased production,
increased destruction, blood loss and
sequestration
4: Inherited (congenital) , acquired
Classification of anemia based on cause :

1) Anemia due to blood loss

from stomach, G.I tract, trauma, etc.
2) Nutritional anemia
Iron deficiency anemia
Megaloblastic anemia
3) Hemolytic anemia
Red cell membrane disorders
Red cell enzyme disorders
Hemoglobinopathies
4) Bone marrow disease
bone marrow failure (Aplastic anemia)
bone marrow infiltration
(leukemia / malignancy)
5) Anemia due to systemic illness
liver / kidney disease / ACD
 Blood Loss
• Acute or chronic
• Can be
– internal: joints, trauma, hematomas
– external: GI, renal, menses, bleeding disorder

• symptoms are mainly secondary to

hypovolemia
• Clinical features
– pallor - usually noticed by observer who has
not seen child recently
– may be hard to recognize if chronic
 Blood Loss- Evaluation
• CBC
(if blood loss is acute, anemia is usually
normocytic, normochromic)
• If bleeding causes chronic iron deficiency,
anemia would be hypochromic, microcytic

• PT, PTT
• Blood type and cross match
 Treatment
• If bleeding massive or life-threatening:
– IV access, start fluids
– control active bleeding
– IV albumin while waiting for blood (no longer
in practice)
• If in shock: give O negative blood
 Anemia- Morphologic Classification

• microcytic: iron deficiency, lead toxicity

and thalasemia
• normocytic: blood loss, hemolysis, chronic
disease, infiltrative, sequestration
• macrocytic: Vit B12 and folate def, liver
disease, hemolysis, uremia, drugs,
hypothyroid, aplastic anemia,
dyserythropoeisis
 Anemia-Decreased Production
• decreased substance/nutrient: iron,
B12, folate, protein (ascorbic acid)
• bone marrow suppression: congenital
abn (aplastic), infection (parvovirus),
drugs, asphyxia, chronic disease
• bone marrow replacement: malignancy,
bony (osteopetrosis), infiltrative
(mylofibrosis)
• dyserythropoiesis: sideroblastic anemia
 Anemia-Loss

• sequestration
– spleen, hemangiomas
 Hemolytic Anemia

Hemolysis : short red cell life span

(normal = 120 days)

= premature red cell breakdown

 Hemolytic Anemias
Inherited / Congenital causes
1
1. Membrane Disorders: 2
– Spherocytosis, Elliptocytosis 3

2. Hemoglobin Disorders:
– Hemoglobinopathies - Sickle cell, HbC
etc.
– Thalassemia Syndromes - α, β, δ
3. Enzyme disorders:
– G6PD, PK deficiency
 Hemolytic Anemias
Acquired causes

• Autoimmune (cold & warm antibody)

• Mechanical, drugs & toxins
• Transfusion reaction
 Laboratory Evaluation of
Anemia

• Complete blood count

• Reticulocyte count

• Peripheral smear
CBC Hematology Analyzer
CBC :
Complete
Blood Count
 MCV= mean cell volume
determines size of red cell

MCH = (mean cell hemoglobin)

MCHC = (mean cell hemoglobin concentration)

(MCH & MCHC determine color or amount of Hb

in red cell)
Blood Smear / film