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AnemiaKristine Krafts, M.D.

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• Background facts about blood

• Anemia: general information

• Anemia: specific types

Anemia Outline

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• Background facts about blood

Anemia Outline

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Normal blood cells

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Complete Blood Count (CBC)

RBC Hemoglobin Hematocrit

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MCV MCHC

microcytic normocytic macrocytic normochromichypochromic

Complete Blood Count (CBC)

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Size variation

Additional Red Blood Cell Properties

Shape

anisocytosis poikilocytosis

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Normal red blood cells

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• Background facts about blood

• Anemia: general information

Anemia Outline

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An (without) -emia (blood):

a reduction below normal in hemoglobin or red blood cell number.

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Symptoms of Anemia

Pale skin, mucous membranesJaundice (if hemolytic)

TachycardiaBreathlessness

DizzinessFatigue

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• Background facts about blood

• Anemia: general information

• Anemia: specific types

Anemia Outline

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Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Make too little blood• Too few building blocks• Too few erythroblasts• Not enough room

Three Ways to Get Anemic

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Lose blood

Three Ways to Get Anemic

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Anemia of Blood Loss

• Cause: traumatic, acute blood loss• At first, hemoglobin is normal!• After 2-3 days, see reticulocytes• Chronic blood loss is different

(it causes iron deficiency anemia).

Things you must know

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Reticulocytes

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Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Three Ways to Get Anemic

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• Intracorpuscular vs. extracorpuscular

• Chronic vs. acute

• Signs of destruction: ↑ bilirubin, ↑ LDH, ↓ haptoglobin

• Signs of production: ↑ reticulocytes, nucleated red cells in blood

Hemolytic Anemias

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Reticulocytes (supravital stain)

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Lose blood

Destroy too much blood• Extracorpuscular reasons

Three Ways to Get Anemic

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Microangiopathic Hemolytic Anemia

• Physical trauma to red cells• Schistocytes• Find out why!

Things You Must Know

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Red cells snagged on fibrin strand

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Schistocytes

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Triangulocyte

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• Artificial heart valve

• Malignancy

• Obstetric complications

• Sepsis

• Trauma

Causes of MAHA

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• Warm AIHA• IgG• Spleen• Spherocytes

• Cold AIHA• IgM, complement• Intravascular hemolysis• Agglutination

Autoimmune Hemolytic Anemia

Things You Must Know

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Warm AIHA

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Warm AIHA

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Warm AIHA

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Cold AIHA

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Cold AIHA

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patient red cells + AHG = agglutination

Direct antiglobulin test (DAT)

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Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Three Ways to Get Anemic

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• Hemoglobinopathy (qualitative defect in hemoglobin)

• Single amino acid substitution in beta chain of hemoglobin

• Can be heterozygous or homozygous

• Sickle cells are nasty:• Fragile (burst easily)• Get stuck in vessels

Sickle Cell Anemia

Things You Must Know

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Hemoglobin

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Point mutation in b chain gene

abnormal b chains (substitution of valine for glutamate)

Hgb S

Aggregates and polymerizes on deoxygenationRed cell becomes sickle shaped

Sickles clog up vessels……plus, they are fragile

Nasty!

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Sickle cell anemia

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Sickle cell anemia: foot lesion

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Sickle cell anemia: spleen

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Clinical Findings in Sickle Cell Anemia

• Blacks (8% are heterozygous)• Severity of disease is variable• Chronic hemolysis, vaso-occlusive disease,

and ­ infections (autosplenectomy)• Treatment: prevent triggers, vaccinate,

transfuse

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Thalassemia

• Quantitative defect in hemoglobin

• Can’t make enough α or β chains

• Variable disease severity

• Hypochromic, microcytic anemia with increased RBC and target cells

Things You Must Know

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Hemoglobin chain development

birth

Hgb F = α2γ2 Hgb A2 = α2δ2 Hgb A = α2β2

α

δ

βγ

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Thalassemia

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Thalassemia: Medullary expansion

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Hereditary Spherocytosis

• Tons of spherocytes• Spectrin defect• Splenectomy is curative

Things You Must Know

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z

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Hereditary spherocytosis

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Splenomegaly in hereditary spherocytosis

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Glucose-6-Phosphate Dehydrogenase Deficiency

• ¯ G6PD → ­ peroxides → cell lysis• Oxidant exposure• Bite cells (removal of Heinz bodies)• Self-limiting

Things You Must Know

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• Some patients asymptomatic• Others have episodic hemolysis• Triggers: broad beans (favism),

drugs (antibiotics, aspirin)• Spontaneous resolution

Clinical Findings in G6PD Deficiency

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Child with G6PD deficiency: jaundiced sclera

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• They can’t reduce nasties• Nasties attack hemoglobin bonds• Heme breaks away from globin• Globin denatures, sticks to red cell

membrane (“Heinz body”)• Spleen bites out Heinz bodies

Why Do G6PD-Deficient Red Cells Die?

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G6PD deficiency: Heinz bodies

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G6PD deficiency: bite cells

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Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Make too little blood• Too few building blocks

Three Ways to Get Anemic

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Iron-Deficiency Anemia

Things You Must Know

• Most important cause: GI bleeding • Microcytic, hypochromic anemia• Must find out why patient is iron deficient!

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Iron-deficiency anemia

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Atrophic glossitis in iron-deficiency anemia

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Koilonychia in iron-deficiency anemia

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• Decreased iron intake• bad diet• bad absorption

• Increased iron loss• GI bleed• menses• hemorrhage

• Increased iron requirement• pregnancy

Causes of Iron Deficiency

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Anemia of Chronic Disease

• Infections, inflammation, malignancy• Iron metabolism disturbed• Normochromic, normocytic anemia• Anemia usually mild

Things You Must Know

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Megaloblastic Anemia

Things You Must Know

• Defective DNA synthesis• Nuclear/cytoplasmic asynchrony• ¯ B12/folate• Macrocytic anemia with oval macrocytes

and hypersegmented neutrophils

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FH4

methylene FH4 FH2

methyl FH4

dUMP dTMP DNA

B12

Need B12 to make DNA!

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retarded DNA synthesis unimpaired RNA synthesis

BIG cells!

immature nucleusmature cytoplasm

Megaloblastic Anemia

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Megaloblastic anemia

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Megaloblastic anemia

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Atrophic glossitis in megaloblastic anemia

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homocysteine

­­ homocysteine

endothelial damage

atherosclerosisthrombosis

What else is B12 good for?

methionine

¯¯methionine

myelin damage

subacute combined degeneration

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Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Make too little blood• Too few building blocks• Too few erythroblasts

Three Ways to Get Anemic

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Aplastic Anemia

• Pancytopenia

• Empty marrow

• Most are idiopathic

Things You Must Know

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Blood smear in aplastic anemia

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Empty bone marrow in aplastic anemia

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Empty bone marrow in aplastic anemia

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• Idiopathic• Drugs• Viruses• Pregnancy• Fanconi anemia

Causes of Aplastic Anemia

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Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Make too little blood• Too few building blocks• Too few erythroblasts• Not enough room

Three Ways to Get Anemic

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Bone marrow full of fibrosis

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