Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first,...

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Anemia Kristine Krafts, M.D.

Transcript of Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first,...

Page 1: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

AnemiaKristine Krafts, M.D.

Page 2: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Background facts about blood

• Anemia: general information

• Anemia: specific types

Anemia Outline

Page 3: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Background facts about blood

Anemia Outline

Page 4: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Normal blood cells

Page 5: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss
Page 6: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Complete Blood Count (CBC)

RBC Hemoglobin Hematocrit

Page 7: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

MCV MCHC

microcytic normocytic macrocytic normochromichypochromic

Complete Blood Count (CBC)

Page 8: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Size variation

Additional Red Blood Cell Properties

Shape

anisocytosis poikilocytosis

Page 9: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Normal red blood cells

Page 10: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Background facts about blood

• Anemia: general information

Anemia Outline

Page 11: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

An (without) -emia (blood):

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

Page 12: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Symptoms of Anemia

Pale skin, mucous membranesJaundice (if hemolytic)

TachycardiaBreathlessness

DizzinessFatigue

Page 13: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Background facts about blood

• Anemia: general information

• Anemia: specific types

Anemia Outline

Page 14: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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

Page 15: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Lose blood

Three Ways to Get Anemic

Page 16: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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

Page 17: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Reticulocytes

Page 18: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Three Ways to Get Anemic

Page 19: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Intracorpuscular vs. extracorpuscular

• Chronic vs. acute

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

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

Hemolytic Anemias

Page 20: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Reticulocytes (supravital stain)

Page 21: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Lose blood

Destroy too much blood• Extracorpuscular reasons

Three Ways to Get Anemic

Page 22: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Microangiopathic Hemolytic Anemia

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

Things You Must Know

Page 23: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Red cells snagged on fibrin strand

Page 24: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Schistocytes

Page 25: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Triangulocyte

Page 26: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Artificial heart valve

• Malignancy

• Obstetric complications

• Sepsis

• Trauma

Causes of MAHA

Page 27: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Warm AIHA• IgG• Spleen• Spherocytes

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

Autoimmune Hemolytic Anemia

Things You Must Know

Page 28: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Warm AIHA

Page 29: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Warm AIHA

Page 30: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Warm AIHA

Page 31: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Cold AIHA

Page 32: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Cold AIHA

Page 33: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

patient red cells + AHG = agglutination

Direct antiglobulin test (DAT)

Page 34: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Three Ways to Get Anemic

Page 35: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• 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

Page 36: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Hemoglobin

Page 37: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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!

Page 38: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Sickle cell anemia

Page 39: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Sickle cell anemia: foot lesion

Page 40: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Sickle cell anemia: spleen

Page 41: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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

Page 42: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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

Page 43: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Hemoglobin chain development

birth

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

α

δ

βγ

Page 44: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Thalassemia

Page 45: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Thalassemia: Medullary expansion

Page 46: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Hereditary Spherocytosis

• Tons of spherocytes• Spectrin defect• Splenectomy is curative

Things You Must Know

Page 47: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

z

Page 48: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Hereditary spherocytosis

Page 49: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Splenomegaly in hereditary spherocytosis

Page 50: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Glucose-6-Phosphate Dehydrogenase Deficiency

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

Things You Must Know

Page 51: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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

drugs (antibiotics, aspirin)• Spontaneous resolution

Clinical Findings in G6PD Deficiency

Page 52: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Child with G6PD deficiency: jaundiced sclera

Page 53: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss
Page 54: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• 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?

Page 55: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

G6PD deficiency: Heinz bodies

Page 56: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

G6PD deficiency: bite cells

Page 57: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Lose blood

Destroy too much blood• Extracorpuscular reasons• Intracorpuscular reasons

Make too little blood• Too few building blocks

Three Ways to Get Anemic

Page 58: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Iron-Deficiency Anemia

Things You Must Know

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

Page 59: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Iron-deficiency anemia

Page 60: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Atrophic glossitis in iron-deficiency anemia

Page 61: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Koilonychia in iron-deficiency anemia

Page 62: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Decreased iron intake• bad diet• bad absorption

• Increased iron loss• GI bleed• menses• hemorrhage

• Increased iron requirement• pregnancy

Causes of Iron Deficiency

Page 63: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Anemia of Chronic Disease

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

Things You Must Know

Page 64: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Megaloblastic Anemia

Things You Must Know

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

and hypersegmented neutrophils

Page 65: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

FH4

methylene FH4 FH2

methyl FH4

dUMP dTMP DNA

B12

Need B12 to make DNA!

Page 66: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

retarded DNA synthesis unimpaired RNA synthesis

BIG cells!

immature nucleusmature cytoplasm

Megaloblastic Anemia

Page 67: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Megaloblastic anemia

Page 68: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Megaloblastic anemia

Page 69: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Atrophic glossitis in megaloblastic anemia

Page 70: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

homocysteine

­­ homocysteine

endothelial damage

atherosclerosisthrombosis

What else is B12 good for?

methionine

¯¯ methionine

myelin damage

subacute combined degeneration

Page 71: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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

Page 72: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Aplastic Anemia

• Pancytopenia

• Empty marrow

• Most are idiopathic

Things You Must Know

Page 73: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Blood smear in aplastic anemia

Page 74: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Empty bone marrow in aplastic anemia

Page 75: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Empty bone marrow in aplastic anemia

Page 76: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

• Idiopathic• Drugs• Viruses• Pregnancy• Fanconi anemia

Causes of Aplastic Anemia

Page 77: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

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

Page 78: Anemia · 2019-10-14 · Anemia of Blood Loss • Cause: traumatic, acute blood loss • At first, hemoglobin is normal! • After 2-3 days, see reticulocytes • Chronic blood loss

Bone marrow full of fibrosis