You are on page 1of 5

IRON-DEFICIENCY ANEMIA I. Hypoproliferative anemia: normocytic, normochromic a. Anemia of acute/chronic inflammation i. serum iron ii. Normal/ TIBC iii.

. transferrin saturation iv. Normal/ serum ferritin b. Mild to moderate IDA i. serum iron ii. TIBC iii. transferrin saturation iv. serum ferritin c. BM damage due to drugs, infiltrative diseases/BM aplasia i. Peripheral smear ii. BM smear, aspirate iii. BM biopsy Maturation disorders: RPI; erythroid hyperplasia (BM aspirate) a. Nuclear maturation defects: macrocytosis, abn marrow devt i. Vit B12 deficiency ii. Folic acid deficiency iii. Drug damage: methotrexate, alkylating agents b. Cytoplasmic maturation defects i. Severe & prolonged IDA 1. Hypoproliferative anemia: mild-moderate IDA w/ erythroid marrow proliferation 2. Anermia due to ineffective erythropoiesis: severe, prolonged IDA, hyperplastic erythroid marrow produciton ii. Abnormalities in globin/heme synthesis 1. Myelodyslpasia 2. Sideroblastic anemia

a. b. c.



Anemia from acute blood loss RPI Anemia from chronic blood loss: iron deficiency > RBC production Anemia from hemolytic disease i. Extravascular hemoylsis: efficient Fe recycling from destroyed RBCs ii. Intravascular hemolysis: loss or Fe limit BM response (paroxysmal nocturnal hemoglobinuria) Hemoglobinopathies: RPI but inappropriately low for eryhroid production i. Sickle-cell disease ii. thalassemia Chronic hemolytic disease (hereditary spherocytosis): no anemia bt prolonged RBC destruction

CLASSIFICATION OF ANEMIA I. By MCV a. Microcytic i. IDA ii. Thalassemia iii. Anemia of chronic disease b. Macrocytic i. Megaloblastic Vit B12 deficiency Folate deficiency ii. Non-megaloblastic Myelodsyplasia, chemotherapy Liver disease reticulocytosis myxedema c. Normocytic: many causes Physiologic a. Microcytic/Hypochromic i. Chronic blood loss ii. IDA iii. Thalassemia b. Macrocytic (Megaloblastic)/Hyperchromic i. Pernicious anemia (Vit B12 def)




Blood loss/Hemolysis


ii. Folic acid def Normocytic/Normochromic i. Hemolytic ii. Aplastic iii. Myelophthisic iv. Acute blood loss v. Chronic renal failure Pathophysiologic a. production i. HB synthesis IDA Thalassemia Anemia of chronic disease ii. DNA synthesis Megaloblastic anemia iii. Stem cell Aplastic anemia Myeloproliferative leukemia iv. BM infiltration Carcinoma lymphoma v. Pure red cell aplasia b. destruction i. Blood loss ii. Hemolytic (intrinsic) Membrane Hereditary spherocytosis elliptocytosis Hb Sickle-cell Unstable Hb Glycolysis Pyruvate kinase def Oxidation G6PD def iii. Hemolytic (extrinsic) Immune c.

Warm antibody Cold antibody Microangiopathic Thrombotic thrombocytopenic purpura Hemolytic-uremic syndrome Mechanical cardiac valve Paravalvular leak Infection clostridial hypersplenism

Disease IDA

Essentials of Dx 1. Serum ferritin < 12mc/L 2. Caused by bleeding in adults unless otherwise proven 3. Responds to Fe therapy

Causes BLOOD LOSS: most impt cause 1. demand 2. Inadequate intake 3. Impaired absorption 4. loss

S/Sx 1. 2. 3. 4.

Easy fatifability Tachycardia Palpitations Tachypnea on exertion

Lab findings Negative Fe balance 1. serum ferritin <30mcg/L 2. NORMAL serum Fe, TIBC, RBC indices, RBC morphology 3. BM biopsy rarely done 4. Anemia w/ no change in RBC size Fe-def erythropoiesis 1. Serum iron <30mcg/dL 2. Transferrin saturation <15-20% (impaired Hb synthesis) 3. Serum ferritin <15mcg/L (BM iron stores absent) 4. Peripheral smear: microcytic IDA 1. Hb & Hct 2. Transferrin saturation= 10-15% 3. MCV initially normal, falls progressively Moderate anemia (Hb=10-13g/dL) = hypoproliferative BM Severe anemia (Hb=7-8g/dL) =hypochromic, microcytic/target cells/anisocytosis/poikilocytes/nucleated RBCs; platelet count Severe prolonged IDA =erythroid hyperplasia of BM 1. Anemia variable severity 2. Hct may be normal 3. Reticulocytosis ALWAYS present 4. Peripheral smear: SPHEROCYTES 5. Microcytosis 6. MCHC 7. indirect bilirubin 8. Negative Coombs test


Hereditary spherocytosis

1. 2. 3.


(+) family hx Splenomegaly Sperocytes & reticulocytes on peripheral blood smear Microcytic, hypochromic

Glucose-6Phosphate Dehydrogenase Deficiency

1. 2. 3. 4.

X-linked: American black men Episodic hemolysis: oxidant drugs/infection Minimally abn blood smear G6PD in bet. hemolytic episodes

Autosomal dominant Often dx in childhood 3. Milder cases dx in adults 4. Anemia may/may not be present 5. Chronic hemolysis = cholecystitis & palpable/enlarged spleen 1. px w/o anemia or splenomegaly 2. hemolysis: result of oxidative drugs (infection or exposure) 3. hemolytic episode

1. 2.

Folic acid Splenectomy

1. 2.


bet. hemolytic eps: normal blood hemolytic eps: reticulocytosis serum bilirubin peripheral smear: bite cells Heinz bodies

Not necessary except to avoid oxidant drugs

4. Autoimmune Hemolytic Anemia 1. 2. 3. acquired anemia fr. IgG antibody spherocytes & reticulocytosis on blood smear Positive Coombs test

chronic hemolytic anemia


specific enzyme assays for G6PD (preferably weeks after hemolysis has resolved) 1. Anemia (rapid onset/variable severity) 2. Jaundice 3. Splenomegaly 4. Reticulocytosis 5. Spherocytosis (blood smear) 6. Severe hemolysis (stressed BM: nucleated RBCs) 7. indirect bilirubin 8. 10% Evans syndrome (immune thrombocytopenia) 9. Positive Direct Coombs test 10. Indirect Coombs may/may not be (+)

Prednisone Blood transfusion Splenectomy Rituximab/Danazol Immunosuppresive drugs IV immune globulin @ high dose Long term prognosis: GOOD

Microangiopathic 1. Hemolytic 2. Anemia

Aplastic Anemia

RBC fragmentation Intravascular anemia w/ hemoglobinemia,hemoglobin uria, methemalbuminemia 3. Hallmark: Fragment RBCs 4. Most impt: Thrombotic thrombocytopenic purpura 1. Pancytopenia 2. No abn cells seen 3. Hypocellular BM

1. 2. 3. 4. 5.

Congenital Autoimmune SLE Chemo/radiotherapy Toxins: benzene, insecticides 6. Drugs 7. Posthepatitis 8. Pregnancy 9. Paroxysmal nocturnal hemoglobinuria 10. Direct stem cell injury 11. AUTOIMMUNE SUPPRESSION OF TCELL MEDIATED CELL MECH: most common pathogenesis

1. 2. 3. 4.

Anemia Neutropenia Thrombocytopenia Pallor, purpura, petecchiae

1. 2. 3. 4. 5.

Pancytopenia HALLMARK BM biopsy/aspirate: hypocellular, scant amt of normal hematopoietic progenitors w/o abn cells Severe anemia: reticulocytes Unremarkable RBC morphology neutrophils & platelets but no immature/abn forms seen

Mild 1. RBC & platelet transfusions 2. Antibiotics Severe 1. Immunosupression w/ ATG 2. High dose immunosupression

ABSENT: Hepatosplenomegaly Lymphadenopathy Bone tenderness

Polycythemia vera

1. 2. 3.

RBC mass Splenomegaly Normal arterial O2 saturation

1. 2. 3. 4.

Hct above nomal (>60%) HALLMARK Normal RBC morphology WBC count = 10,000-20,000/mcL; normal morphology platelet count = >1M; normal morphology

1. 2. 3.

Phlebotomy Myelosuppressive drugs Alkylating drugs


WBC & platelet count

5. 6. 7. 8. 1. 2. 3. Cobalamin deficiency Folate def Defects of DNA synthesis 1. 2. 3. 4. Megaloblastic anemia: hallmark Mucosal changes: glossitis GI: anorexia, diarrhea Neurologic Paresthesia Diff. in balance Dementia 1. 2. 3.

Hypercellular BM Panhyperplasia of all elements VitB12 - transcobalamin III hyperuricemia



Megaloblastic anemia

VitB12 deficiency

1. 2.


Macrocytic anemia Macro-ovalocytes & hypersegmented neutrophils on smear Serum vitB12 = <100pg/mL


Folic acid deficiency

1. 2.

3. 4.

Macrocytic anemia Macro-ovalocytes & hypersegmented neutrophils on smear Normal serum VitB12 levels folate levels in RBCs/serum

Clinical feats similar to VitB12 def 1. Megaloblastic anemia 2. Megaloblastic changes in mucosa 3. Absent neurological abnormalities

5. 6. 1. 2.

Anemia of variable severity MCV Abn blood smear anisocytosis/ poikilocytosis hypersegmented neutrophils reticulocyte count pancytopenia = WBC & platelet Abn BM morphology Erythroid hyperplasia Megaloblastic: abn large cell size & asynchronous maturation of nucleus&cytoplasm serum LDH Modest indirect bilirubin Normal serum VitB12 levels RBC folate = <150ng/mL

Folic acid = 1mg/d