Rbc Disorders

Hematology RBC disorders Dr. Mehzabin Ahmed

Anemia 

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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

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Easy fatiguibility

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Pallor

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Dyspnoea on exertion

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Rapid bounding pulse

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Systolic murmurs

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Faintness vertigo

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Dependent edema

Erythroid hyperplasia seen in the bone marrow in anemia

Classification of anemia 

Reduced production 

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Deficiency of hematinics 

Iron deficiency

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Folate & B12 deficiency

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Increased destruction 

Hemolytic anemia 

Dyserythropoiesis 

Anemia of chronic disorders

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Myelodysplasia

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Sideroblastic anemia

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Intrinsic causes 

Membrane defects

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Enzyme deficiencies

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Hemoglobinopathy

Extrinsic causes 

Immune reactions

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Marrow infiltration

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Microangiopathic

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Failure of production

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Parasitic

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Aplastic anemia

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Hypersplenism

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Pure red cell aplasia

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Bleeding

Anemia due to deficiency of hematinicsIron deficiency 

Iron deficiency is the most common cause of anemia & is due to chronic blood loss, deficient intake, and increased demand (pregnancy & lactation)

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Chronic blood loss is the most common cause of iron deficiency in adults (peptic ulcers, cancers of the stomach & colon, menorrhagia, urinary tract lesions)

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Microcytic hypochromic anemia with a low serum total iron, increased iron binding capacity, and decreased serum ferritin indicating reduced iron stores

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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 hematinicsVitamin B12 & folic acid 

Causes megaloblastic anemia

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Synthesis of DNA in the marrow precursors is impaired

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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) &

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Partial gastrectomy result in Disease/ surgical removal of terminal ileum Folic acid deficiency may be due to deficient intake / increased demand

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Pancytopenia with megaloblastic erythropoiesis is seen

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Vitamin B12 deficiency is associated with neurological disease & impaired cardiac function

Large oval RBCs

Anemia due to Dyserythropoiesis 

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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 

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Aplastic anemia: there is a failure of the marrow stem cells. 

The marrow is replaced by fat.

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Patients develop pancytopenia and have a life threatening disease.

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Many are idiopathic

Causes of secondary aplastic anemia: 

Radiation

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Chemotherapeutic agents

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Drugs like chloramphenicol, gold, NSAIDs

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Toxins like benzene

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Viruses like papovavirus, HIV-1

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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

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Anemia

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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.

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Pigment gall stone formation

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Hepatosplenomegaly is seen due to extramedullary hemopoiesis

Thalassemia 

Inherited defect in the synthesis of globin chains of the hemoglobin.

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Common in the Mediterranean, Middle and Far East and South East Asia.

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Mutations in the genes coding for the synthesis of α & β globin chains (normal adult Hb- 2α & 2β chains).

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

α Thalassemia

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β Thalassemia

β Thalassemia is of 2 types 

major (microcytic hypochromic anemia with severe hemolysis, hepatosplenomegaly, skeletal deformities and iron overload) and

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minor (mild disease with microcytic hypochromic anemia).

Clinical features of Thalassemia 

Microcytic hypochromic anemia

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Hemosiderosis: the deposition of iron in the tissues like

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The endocrine glands results in the development of diabetes mellitus, failure of sexual development.

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Deposition in the heart and liver results in their failure.

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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.

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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.

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Hepatosplenomegaly is seen due to extramedullary hemopoiesis

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Hydrops fetalis: In extreme cases were all 4 chains are absent and in utero death

Thalassemia

Puffy cheeks & frontal bossing Pencil shaped RBCs

Target cells

Microcytic hypochromic RBCs

Hair on end appearance of the skull on X-raydue 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.

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The abnormal forms undergo lysis and anemia results.

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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

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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)

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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 RBCsExtrinsic 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).

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Physical trauma: as in burns and in artificial heart valves

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Microangiopathic anemia: in DIC

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Infections like malaria and rarely clostridia

 Toxicity due to chemicals like lead, snake venom, and spider bites. Extravascular hemolysis

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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 Direction of blood flow

Fibrin

Malarial parasite with in the RBCs

Seen in DIC were the fibrin strands formed intravascularly results in the tearing up of the RBCs

Polycythemia

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

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

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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.

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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

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Tumors of the kidney, liver or brain resulting in increased production of the erythropoietin.

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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

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Enumerate the clinical features of anemias in general

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Enumerate the hemolytic Anemias

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Describe briefly pathogenesis thalassemias and sickle cell Anemia

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Enumerate the skeletal changes and complications in the thalassemia and sickle cell anemia

6.

Define polycythemia and classify it.