Anemia Overview

The Third Hospital of Sun Yat-sen University Ruozhi_xiao@yahoo.com

Ruozhi Xiao

2013/4/28

Erythrocytes parameters
RBC = red blood cells Hgb= hemoglobin Mean corpuscular volume (MCV)
N: 80-100 fl

RDW(Red cell Distribution Width) Mean corpuscular hemoglobin (MCH)

N: 27-34 pg

Mean corpuscular hemoglobin concentration (MCHC)

N: 310 370 g/lRBC (31-37 g/dl)

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Survival and Production of RBC

Formed in bone marrow Life span is 120 days (+/-20 days) Cleared in spleen Reticulocytes are newly formed RBC in circulation If no new production, Hgb drops 1 gm/week

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ERYTHROPOIESIS
In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages

*
Stem cell Proerythroblast Early Intermediate erythroblast erythroblast

Late Reticulocyte RBC erythroblast

-blast is the common suffix for an immature form of a cell

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Hematocrits
Plasma White cells Red cells

Normal, Hemorrhage, IDA, Leukemia, Hemolysis, B12, P Vera

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Definitinon
Low blood Anemia is simply a hemoglobin level lower than the normal range for a particular age and sex of the patient. Most common hematologic disorder by far

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The normal range for Hb and RBC

Hb Males 120160g/L Females 110150g/L Neonates170200g/L
RBC

(4.0-5.5)x 1012/L (3.5-5.0)x 1012/L (6.0-7.0)x 1012/L

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Anemia classification
Based on general mechanisms morphological classification

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morphological classification

Anemia

Microcytic

Normocytic
Macrocytic

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morphological classification
Type MCV fl MCH pg MCHC%

Macrocytic anemia Normocytic anemia

Microcytic anemia

100 80-100 80

32 27-32 27

32-35 32-35 32

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Normal Red Blood Cells - Peripheral Blood Smear

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Normal Red Blood Cells

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Microcytic anemia

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Thalassemia
Thalassa = the sea Defective globin synthesis

Normal a = b (a/b = 1) a, b, db, gdb thalassemia

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b-Thalassemia

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Macrocytic anemia

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General mechanisms of anemia

1. RBC Loss without RBC destruction 2. Deficient RBC production: Marrow failure 3. Increased RBC destruction over production: Hemolysis

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Causes - Cytoplasmic Protein Production

ANEMIA

Decreased hemoglobin synthesis

Disorders of globin synthesis Disorders of heme synthesis

Heme synthesis
Decreased Iron Iron not in utilizable form Decreased heme synthesis

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Pathophysiology
a. b. c. a. b. c.

Decreased RBC production Iron deficiency Folic acid deficiency Aplastic anemia Increased RBC loss or destruction sickle cell anemia blood loss infection

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:trauma,surgery :cancer and ulcer,menstrual periods

:Renal disease :Leukemia

: Malaria

:SLE :Lead poisoning :PNH

The third hospital of Sun yat-sen university

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Bone Marrow Disorders

Aplastic anemia Myelodysplastic Syndromes

Acute

Leukemia

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Aplastic Anemia

Blood
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Bone Marrow Biopsy

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Bone Marrow (BM) Biopsy

Normal Aplastic

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Definitions

Aplastic Anemia (AA)

Pancytopenia Hypocellular bone marrow

Myelodysplastic Syndrome (MDS)

Cytopenias with hypercellular bone marrow

Acute Leukemia (AL)

Malignant proliferation of immature cells
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Aplastic Anemia: Signs and Symptoms

Anemia (low Hb, Hct)

fatigue, lassitude, dyspnea

Thrombocytopenia (low platelets)

bruises, petechiae serious bleeding

Neutropenia (low neutrophils, a type of white cell)

infections

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Acquired Aplastic Anemia

Drugs Chemicals Viruses Immune diseases Paroxysmal nocturnal hemoglobinuria (PNH) Pregnancy IDIOPATHIC

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Myelodysplastic Syndromes (MDS)

Clonal diseases Neoplastic Refractory anemias Potential for acute myeloid leukemia (AML)

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Anemia Check MCV

MCV < 80 Microcytic anemia

MCV 80 - 100 Normocytic anemia

MCV > 100 Macrocytic anemia

Defective synthesis of:

Globin chains thalassemias

HbE

Heme

Fe

iron deficiency anemia anemia of chronic disease

sideroblastic anemia lead poisoning
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Clinical features
Mild:Mild dyspnea on exertion, palpitation Moderate: As with MILD ANEMIA, may also have excessive dyspnea Severe:Anemia:Dyspnea at rest, tachycardia with pounding pulse, weakness, dizziness, headache, insomnia

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Diagnosis of Anemia

History Diet Blood loss Family history Recent illness or immunization History of anemia and cause
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Diagnosis of Anemia

Physical Examination

Evaluate conjunctiva and mucous membranes for paleness Cardiovascular system for murmur Liver Spleen Nodes Look for jaundice or purpura
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Diagnosis of Anemia

Labs Complete blood count with differential and platelets Evaluation of smear with red cell indices Reticulocyte count

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Diagnosis of Anemia

Other tests Serum bilirubin, LDH, urinary hemosiderin, hgb electrophoresis, quantitative hgbA2 and F

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Common treatment to All Anemias

Support
Hematopoietic growth factors Blood transfusions, blood substitutes Iron

Cure
Stem cell transplant Gene therapy

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IRON DEFICIENCY ANEMIA

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Terms
Fe = iron TIBC = total iron binding capacity RDW = red cell distribution width

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CASE 1

A 50 year old man comes to see you because of fatigue and a change in bowel habit. He is found to have a hemoglobin of 105 g/L (normal 120-170) and MCV of 78 fL (80-100). Peripheral blood film shows microcytes and hypochromia. He previously had a hemoglobin of 165 g/L three years ago, with a normal MCV.
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Case 1 Question 1

What is your approach to the history and physical examination?

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Case 1 - Question 1 Discussion

iron deficiency most likely symptoms suspicious for lower GI tract malignancy. still ask about chronic inflammatory diseases ask about melena, hematochezia, weight loss, family history of colon ca rectal exam indicated

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CASE 1 - Question 2

What other investigations are appropriate?

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Investigations
serum ferritin iron TIBC transferrin sat.

12 ug/L (30-400) 8 umol/L (10-28) 80 umol/L (38-76) 10 % (20-55)

Conclusion: Iron deficiency anemia

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IRON DEFICIENCY ANEMIA

Prevalence
Country S. India N. India Latin America Israel Poland Sweden USA Men (%) Women (%) 6 4 14 35 64 17 29 7 13 Pregnant Women (%) 56 80 38 47 22

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IRON
Functions as electron transporter; vital for life Must be in ferrous (Fe+2) state for activity Ferric (Fe+3) ions cannot transport electrons or O2

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IRON DEFICIENCY ANEMIA

IRON METABOLISM
ABSORPTION IN DUODENUM TRANSFERRIN TRANSPORTS IRON TO THE CELLS FERRITIN AND HEMOSIDERIN STORE IRON

10% of daily iron is absorbed

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Iron Metabolism

Heme Iron
Hemoglobin and myoglobin

Non-heme Iron
Breast milk Cow milk All supplements

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Iron Absorption

Heme Iron
Well absorbed Not dependent on Iron deficiency status Not limited by diet

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Iron Absorption

Non-heme Iron
Absorption is sporadic, generally poor Improved absorption
Iron deficient status Heme iron (ie red meat, fish, chicken) Vitamin C

Worsened absorption
Cows milk, cheese Cereal Tea
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Body Compartments - 75 kg man

Stores 1000mg
Absorption < 1 mg/day

IRON

Tissue 500 mg

3 mg

Excretion < 1 mg/day

Red Cells 2300 mg

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Iron deficiency anemia

Causes: inadequate dietary iron intake Malabsorption: gastrectomy, chronic diarrhea, increased iron needs: pregnancy and lactation chronic occult blood loss: bleeding ulcers, GI inflammation, hemorrhoids, cancer, chronic hemoglobinuria Menstrual blood loss

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Most body iron is present in hemoglobin in circulating red cells The macrophages of the reticuloendothelial system store iron released from hemoglobin as ferritin and hemosiderin Small loss of iron each day in urine, faeces, skin and nails and in menstruating females as blood (1-2 mg daily)

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IRON DEFICIENCY ANEMIA

ETIOLOGY:
CHRONIC BLEEDING
MENORRHAGIA PEPTIC ULCER STOMACH CANCER ULCERATIVE COLITIS INTESTINAL CANCER HAEMORRHOIDS

DECREASED IRON INTAKE INCREASED IRON REQUIRMENT (JUVENILE AGE, PREGNANCY, LACTATION)
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IRON DEFICENCY - STAGES

Prelatent
reduction in iron stores without reduced serum iron levels Hb (N), MCV (N), iron absorption (), transferin saturation (N), serum ferritin (), marrow iron ()

Latent
iron stores are exhausted, but the blood hemoglobin level remains normal Hb (N), MCV (N), TIBC (), serum ferritin (), transferrin saturation (), marrow iron (absent)

Iron deficiency anemia

blood hemoglobin concentration falls below the lower limit of normal Hb (), MCV (), TIBC (), serum ferritin (), transferrin saturation (), marrow iron (absent)

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IRON DEFICIENCY ANEMIA

GENERAL ANEMIAS SYMPTOMS:

FATIGABILITY DIZZENESS HEADACHE IRRITABILITY ROARING PALPITATION CHD, CHF

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CHARACTERISTICS SYMPTOMS
GLOSSITIS, STOMATITIS
DYSPHAGIA ( Plummer-Vinson syndrome)

ATROPHIC GASTRITIS DRY, PALE SKIN SPOON SHAPED NAILS, KOILONYCHIA, BLUE SCLERAE HAIR LOSS PICA (APETITE FOR NON FOOD SUBSTANCES SUCH AS AN ICE, CLAY) SPLENOMEGALY (10%) INCREASED PLATELET COUNT

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KOILONYCHIA

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Smooth tongue

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IRON DEFICIENCY ANEMIA

MCV MCH

MCHC N
Fe

TIBC TRANSFERIN SATURATION 2013/4/28 FERRITIN

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BLOOD ROUTINE

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BLOOD AND BONE MARROW SMEAR

BLOOD:
microcytosis, hipochromia, anisocytosis poikilocytosis

BONE MARROW
high cellularity mild to moderate erythroid hyperplasia (25-35%; N 16 18%) polychromatic and pyknotic cytoplasm of erythroblasts is vacuolated and irregular in outline (micronormoblastic erythropoiesis) absence of stainable iron

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Anemia: Lab Evaluation

Normal Periperhal Smear

Iron Deficiency Anemia

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IDA blood smear

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IDA bone marrow

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Normal store iron(blue)

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IDA

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Reticulocytes up

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Using special stains such as methylene blue or brilliant cresyl blue, reticulocytes stain with dark blue granules whereas mature erythrocytes evenly stain pale blue.

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Management

History and physical examination is sufficient to exclude serious disease (e.g pregnant or lactating women, adolescents) - CURE ANEMIA

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Management

History and/or physical examination is insufficient (e.g old men, postmenopausal women) - FIND ETIOLOGY OF ANEMIA AND CURE (CAUSAL TREATMENT)
Benzidine test Gastroscopy Colonoscopy Gynaecological examination

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IRON DEFICIENCY ANEMIA CURE

ORAL
300 mg of iron daily after meal How long? 3-6 months to restore iron reserve Absorption
is enhanced: vit C, meat, orange juice, fish is inhibited: tea, milk

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IRON DEFICIENCY ANEMIA CURE

PARENTERAL IRON SUBSTITUTION

Bad oral iron tolerance (nausea, diarrhoea) Negative oral iron absorption test Necessity of quick management (CHD, CHF)

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Remember:
Iron deficiency anemia is a manifestation of an underlying process. Look for and treat the cause of the iron deficiency.
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Look for the cause

colonoscopy reveals colon carcinoma which is subsequently resected.

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Iron Deficiency anemia

Diagnostics: Iron levels Total iron-binding capacity (TIBC) Serum Ferritin Medications: Iron supplements, oral or parenteral Vit. C
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