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Hematology

RBC disorders

Dr. Mehzabin Ahmed


Anemia

 Def: Reduction in the circulating red cell mass


is called anemia.
 Thus there is a reduced oxygen carrying
capacity of the RBCs
 Compensatory changes:
 Decreased affinity of hemoglobin for the oxygen
 Increased cardiac output
 Attempted increase in the RBC production.
Common features of anemias

Symptoms Signs
 Easy fatiguibility  Pallor
 Dyspnoea on  Rapid bounding pulse
exertion  Systolic murmurs
 Faintness vertigo  Dependent edema
Erythroid hyperplasia seen in the bone marrow in anemia
Classification of anemia
 Reduced production  Increased destruction
 Deficiency of hematinics  Hemolytic anemia
 Iron deficiency  Intrinsic causes
 Folate & B12 deficiency  Membrane defects
 Dyserythropoiesis  Enzyme deficiencies
 Anemia of chronic disorders  Hemoglobinopathy
 Myelodysplasia  Extrinsic causes
 Sideroblastic anemia  Immune reactions
 Marrow infiltration  Microangiopathic
 Failure of production  Parasitic
 Aplastic anemia  Hypersplenism
 Pure red cell aplasia  Bleeding
Anemia due to deficiency of hematinics-
Iron deficiency
 Iron deficiency is the most common cause of anemia & is due to chronic
blood loss, deficient intake, and increased demand (pregnancy &
lactation)
 Chronic blood loss is the most common cause of iron deficiency in
adults (peptic ulcers, cancers of the stomach & colon, menorrhagia,
urinary tract lesions)
 Microcytic hypochromic anemia with a low serum total iron, increased
iron binding capacity, and decreased serum ferritin indicating reduced
iron stores
 Clinical features: Angular cheilits, atrophic glossitis, esophageal webs,
koilonychia and brittle nails, fatigue, dyspnoea on exertion, tachycardia
Microcytes- small
RBCs
Hypochromic- RBCs
with a large central
pallor

Koilonychia- Spoon shaped nails


Anemia due to deficiency of hematinics-
Vitamin B12 & folic acid
 Causes megaloblastic anemia
 Synthesis of DNA in the marrow precursors is impaired
 Pernicious anemia due to deficiency of intrinsic factor expressed on the
gastric parietal cells which results in malabsorption of vitamin B12
 Autoimmune atrophic gastritis (resulting in the destruction of the gastric
parietal cells) &
 Partial gastrectomy result in Disease/ surgical removal of terminal ileum
Folic acid deficiency may be due to deficient intake / increased demand
 Pancytopenia with megaloblastic erythropoiesis is seen
 Vitamin B12 deficiency is associated with neurological disease & impaired
cardiac function
Large oval RBCs
Anemia due to Dyserythropoiesis
 Anemia of chronic disorders is the second most common cause of
anemia.
 Disorders associated with anemia:
 Autoimmune disorders like rheumatoid arthritis;

 Chronic infections like TB, malaria, schistosomiasis;

 Neoplasms like lymphoma and some carcinomas

 Myelodysplastic syndromes:
 Production of abnormal clones of marrow stem cells which form

defective blood cells that are destroyed prematurely.


 Results in refractory anemias & pancytopenias.

 It progress to leukemia

 Sideroblastic anemia :defective heme synthesis in the RBC precursors.


 Causes include- Toxins- lead, alcohol, Drug- isoniazid, Associated

with neoplasm, Due to myelodysplasia


Anemia due to failure of production
 Aplastic anemia: there is a failure of the marrow stem cells.
 The marrow is replaced by fat.
 Patients develop pancytopenia and have a life threatening disease.
 Many are idiopathic
 Causes of secondary aplastic anemia:
 Radiation
 Chemotherapeutic agents
 Drugs like chloramphenicol, gold, NSAIDs
 Toxins like benzene
 Viruses like papovavirus, HIV-1
 Fanconi’s anemia- Autosomal recessive disease
Aplastic anemia

Aplastic anemia: hypocellular bone marrow is largely devoid


of hematopoietic cells; often only fat cells, fibrous stroma,
Anemia due to hemolysis
Increased destruction/ reduced red cell survival in the blood.
Causes:
1) Intravascular hemolysis occurs in:
 Hemolytic anemia

 Intrinsic causes

 Membrane defects- hereditary spherocytosis

 Enzyme deficiencies- glucose 6 phosphate dehydrogenase deficiency

 Hemoglobinopathies- thalassemia, sickle cells anemia

 Extrinsic causes

 Immune reactions- autoimmune hemolytic anemia

 Microangiopathic- DIC

 Parasitic

2) Extravascular hemolysis
 Hypersplenism

 Bleeding- trauma and accidents


Hereditary spherocytosis Spherocytes
G6PD deficiency
Heinz bodies Bite cells- schistocytes
Sickle cell Anemia Sickle cells
General clinical features of Hemolytic Anemias

 Anemia
 Jaundice: excessive breakdown of RBCs results in the
release of Hb, which is converted in the liver to bilirubin
& this, gives the yellowish discoloration to the tissues.
 Pigment gall stone formation
 Hepatosplenomegaly is seen due to extramedullary
hemopoiesis
Thalassemia
 Inherited defect in the synthesis of globin chains of the hemoglobin.
 Common in the Mediterranean, Middle and Far East and South East Asia.
 Mutations in the genes coding for the synthesis of α & β globin chains
(normal adult Hb- 2α & 2β chains).
 Two types: depending on the chain affected (reduced or absent)
 α Thalassemia
 β Thalassemia
 β Thalassemia is of 2 types
 major (microcytic hypochromic anemia with severe hemolysis,
hepatosplenomegaly, skeletal deformities and iron overload) and
 minor (mild disease with microcytic hypochromic anemia).
Clinical features of Thalassemia
 Microcytic hypochromic anemia
 Hemosiderosis: the deposition of iron in the tissues like
 The endocrine glands results in the development of diabetes mellitus, failure of
sexual development.
 Deposition in the heart and liver results in their failure.
 It is treated by iron chelation using desferroxamine.
 Facial deformities: like
 frontal bossing and prominent maxillae resulting from the extramedullary
hemopoieis in the flat bones (like the skull bones, the ribs, etc) due to the
hemolysis & severe anemia.
 Expansion of the bone marrow results in the cortical thinning and new bone is
formed which is deposited in the outer aspect of the bone. Cortical thinning
predisposes to fractures.
 Hepatosplenomegaly is seen due to extramedullary hemopoiesis
 Hydrops fetalis: In extreme cases were all 4 chains are absent and in utero death
Thalassemia

Puffy cheeks & frontal bossing

Pencil Target Microcytic


shaped cells hypochromic
RBCs RBCs

Hair on end appearance of the skull on X-ray-


due to extramedullary hematopoiesis
Sickle cell anemia

 Point mutation in the gene coding for β globin chain resulting in an


abnormal type of hemoglobin, HbS. This HbS polymerizes when
exposed to low oxygen tension making the RBC rigid and becomes
sickle shaped.
 The abnormal forms undergo lysis and anemia results.
 Microvasculature (capillaries) get occluded (blocked) and infarction
(ischemic necrosis) of the tissues ( as in the spleen and bone marrow)
can occur
Sickle cell crises

Patterns of acute deterioration


 Sequestration crises: sudden pooling of the RBCs in the spleen causes a
rapid fall in the Hb which can result in death
 Infarctive crises: obstruction of the small blood vessels leads to
infarcts, especially in the bone (femoral head), spleen (resulting in
atrophy), skin ( ulcer formation) and in the bowel (acute abdominal
pain)
 Aplastic crises: splenic atrophy due to repeated infarction predisposes
to infections which depresses the RBC production further reducing the
Hb
Hemolysis due to defects outside the RBCs-
Extrinsic causes of hemolysis
These include the acquired causes of the hemolytic anemias:
 Immune mediated hemolytic anemias: these may be autoimmune or
may be due to mismatched blood transfusion or hemolytic disease of
the newborn ( Rh incompatibility of the mother’s blood and the fetal
RBC).
 Physical trauma: as in burns and in artificial heart valves
 Microangiopathic anemia: in DIC
 Infections like malaria and rarely clostridia
 Toxicity
Extravascular due to chemicals like lead, snake venom, and spider bites.
hemolysis
 Hyperslenism: Causes anemia due to increased functioning of the spleen in
the sequestering of the RBCs. Platelets & WBCs may also be decreased.
Schistocyte
Microangiopathic Trauma Seen in DIC were the fibrin
Direction of strands formed
blood flow
intravascularly results in
the tearing up of the RBCs

Fibrin

Malarial parasite with in the RBCs


Polycythemia

 It is the increase in the RBC mass above the normal levels.

 The Hb concentration & the packed cell volume/ hematocrit are raised.

 The blood is viscous (thick) and does not flow easily, predisposing to

thrombosis and thereafter infarction of organs like the brain, heart and

spleen.
Classification of polycythemias
 Primary: It is due to increased proliferation of the precursors of the RBCs,
WBCs and the platelets in the bone marrow (myeloproliferative disease). This
is known as Polycythemia rubra vera.
 Secondary to increased erythropoietin levels: erythropoietin is a hormone
secreted by the kidney and it acts on the bone marrow simulating the RBC
production (erythropoiesis). It may be raised in
 Hypoxic conditions like smoking, high altitude, lung diseases (like severe
chronic bronchitis, emphysema), congenital heart diseases
 Tumors of the kidney, liver or brain resulting in increased production of
the erythropoietin.
 Relative: it is seen when the plasma volume is depleted as in dehydration &
stress.
At the end of the lesson on RBC Disorders,
the student should be able to:
1. Define anemias and classify them based on the mechanisms of their
production

2. Enumerate the clinical features of anemias in general

3. Enumerate the hemolytic Anemias

4. Describe briefly pathogenesis thalassemias and sickle cell Anemia

5. Enumerate the skeletal changes and complications in the thalassemia


and sickle cell anemia

6. Define polycythemia and classify it.