HematologyRBC 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.

Symptoms

Easy fatiguibility

Dyspnoea on exertion

Faintness vertigo

Common features of anemias

Signs

Pallor

Rapid bounding pulse

Systolic murmurs

Dependent edema

Erythroid hyperplasia seen in the bone marrow in anemia

Reduced production Deficiency of hematinics

Iron deficiency Folate & B12 deficiency

Dyserythropoiesis Anemia of chronic disorders Myelodysplasia Sideroblastic anemia

Marrow infiltration Failure of production

Aplastic anemia Pure red cell aplasia

Increased destruction Hemolytic anemia

Intrinsic causes Membrane defects Enzyme deficiencies Hemoglobinopathy

Extrinsic causes Immune reactions Microangiopathic Parasitic

Hypersplenism Bleeding

Classification of anemia

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

Koilonychia- Spoon shaped nails

Microcytes- small RBCs

Hypochromic- RBCs with a large central pallor

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

Anemia due to deficiency of hematinics- Vitamin B12 & folic acid

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: hypocellular bone marrow is largely devoid of hematopoietic cells; often only fat cells, fibrous stroma,

Aplastic anemia

Anemia due to hemolysisIncreased 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 & globin chains (normal adult

Hb- 2 & 2 chains).

Two types: depending on the chain affected (reduced or absent)

Thalassemia

Thalassemia

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 of the fetus

occurs.

Thalassemia

Hair on end appearance of the skull on X-ray- due to extramedullary hematopoiesis

Microcytic hypochromic RBCs

Puffy cheeks & frontal bossing

Pencil shaped RBCs

Target cells

Sickle cell anemia

Point mutation in the gene coding for 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 due to chemicals like lead, snake venom, and spider bites.

Extravascular hemolysis 

Hyperslenism: Causes anemia due to increased functioning of the spleen in

the sequestering of the RBCs. Platelets & WBCs may also be decreased.

Direction ofblood flow

Fibrin

SchistocyteMicroangiopathic Trauma Seen in DIC were the fibrin

strands formed intravascularly results in the tearing up of the RBCs

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.