Anemia Flashcards
Etiology of Anemia
- Blood loss
- Acute
- Loss of blood volume
- Chronic
- Only when regenerative capacity exceeded by blood loss or iron reserves depleted
- Acute
- Deficiency of Hb building blocks
- Fe ⇒ iron deficiency
- Porphyrin ⇒ sideroblastic
- Globin ⇒ Thalassemias
- Deficiency of DNA buidling blocks
- Vit B12/Folate
- Marrow failure
- Primary failure
- Aplasia, neoplasia, toxic suppression, infiltration
- Secondary failure
- Renal, endocrine, chronic inflammation, hepatic, drugs and poisons, infections, cancer
- Excess destruction ⇒ hemolytic anemia
- Congenital ⇒ mutation in RBC membrane, Hb, or RBC enzymes
- Acquired
- Primary failure
Hypochromic Microcytic Anemias
- Anemia with low MCV
- Failure of marrow precursors to make Hb
- Fe, porphyrin, globin
- Differential dx
- Iron deficiency
- Thalassemias
- Sideroblastic anemia

Iron Deficiency Anemia
Pathogenesis
- Dec. Fe ⇒ marrow can’t make Hb ⇒ anemia
- Causes ⇒ blood loss > nutritional lack
- Who
- Infants ⇒ Fe deficient diet
- Adolescent girls/Premenopausal women ⇒ Menses/pregnancy
- Post-menopausal women and all men ⇒ GI blood loss

Iron Deficiency Anemia
Dx
- CBC
- Blood smear ⇒ paler/smaller, central clearing larger, anisocytosis
- Iron studies ⇒ Fe low, TIBC high, Ferritin low, RDW high

Thalassemias
- Hypochromic, microcytic anemia
- Dec or absent synthesis of alpha or beta globin chains
- Alpha ⇒ Africa and SE Asia
- Beta ⇒ Mediterranean region
- Thalassemia trait ⇒ mild anemia w/ hypochromic microcytic RBC
- Thalassemia major ⇒ severe anemia in childhood, hepatosplenomegaly, jaundice, marked bone changes

Beta-Thalassemia Minor
Dx
- Hb 10-13
- RBC slightly elevated
- MCV 60-70
- Smear ⇒ microcytosis, hypochromia, target cells, RBC with basophilic stippling
- Hb electrophoresis ⇒ slight dec Heb A, Inc. Hgb A2, Hgb F normal or slightly elevated
Beta-Thalassemia Major
Dx
- Severe anemia in childhood ⇒ Hb 3
- Smear
- Markedly hypochromic with marked anisocytosis
- Poikilocytosis
- Stippled cells
- Target cells
- Ellipitcal cells
- Tear drop calls
- Hypochromic cells with polychormatophilic rims
- Nucleated RBCs
- Hb electrophoresis
- Absent or small amount of Hgb A
- Slighrly increased Hgb A2
- Rest Hgb F

β-Thalassemia Major
Pathogenesis
- Dec. B-globin ⇒ excess A-globin ⇒ insoluble aggregates in erythroblasts
- Anemia d/t ineffective erythropoiesis & extravascular hemolysis
- Systemic iron overload
- Skeletal deformities ⇒ inc. EPO and bone marrow expansion

Alpha Thalassemia
- Results from alpha gene deletion
- Single ⇒ silent
- 2 ⇒ trait
- 3 ⇒ Hb H disease
- All 4 ⇒ Hydrops fetalis
- Hb electrophoresis only Hgb Barts
- Mild microcytic anemia w/ normal to elevated RBC
- MCV 60-70
Sideroblastic Anemia
- Porphyrin impairment ⇒ abnormal RBC iron metabolism
- Causes
- Hereditary
- Acquired ⇒ lead poisoning, ETOH, drugs
- Neoplasia ⇒ refractory sideroblastic anemia, sign of myelodysplastic syndromes
- Clinical findings
- Inc. Fe, Normal TIBC, Inc. ferritin
- Ringed sideroblasts in bone marrow
- Treatment ⇒ remove offending agent if possible, treat myelodysplasias

Macrocytic Anemias
Anemia w/ high MCV
Pathophysiology ⇒ megaloblastic vs nonmegaloblastic
Megalobastic Anemia
- Failure of DNA synthesis ⇒ async. maturation of nucleus and cytoplasm
- Caused by Vit B12 or folate deficiency
- See macrocytosis w/ low retic count
- Severe
- Neutropenia
- Thrombocytopenia
- Hypersegmented neutrophils

Vit B12 Deficiency
Pathogenesis
- Cofactor for homocysteine ⇒ met
- Liver stores lasts 3+ years
- From fish and meat
- Absorbed bound to IF in terminal ileum
- Clinical Features
- Macrocytic megaloblastic anemia
- Glossitis
- Neuropathy
- Loss of position/vibratory sensation in LE, ataxia, UMN signs
- Urinary/fecal incontinence
- Impotence
- Dementia
- Neutropenia/thrombocytopenia
Vit B12 Deficiency
Etiology
- Pernicious anemia
- Total gastrectomy
- Malabsorption disease
- Terminal ileum disease or removal
- Pancreatic insufficiency
- Drug induced malabsorption
- Food malabsorption
Vit B12 Deficiency
Dx
- Peripheral smear
- Macrocytic RBC w/ MCV > 100
- Hypersegmented polys
- Serum B12 levels low
- Serum MMA high
- Serum homocysteine high
- Schillings test
Folate Deficiency
- Mainly from green vegetables
- Takes only a few months to develop
- ETOH, nutritional failure, malabsorption, anticonvulsant therapy, pregnancy, hemolytic anemias, antifolate drugs
- Same as Vit B12 def. except no neurological sx
- Dx ⇒ peripheral smear / serum folate
- Tx ⇒ daily oral folate
Normochromic Normocytic Anemias
- Anemia w/ normal MCV and MCHC
- Path ⇒ most from marrow failure, some d/t hemolysis
- Check corrected reticulocyte count (CRC)
- CRC = pt’s retic x pt’s Hct/nl Hct
- CRC <4% ⇒ Marrow failure
- Differentials
- Anemia of chronic disease
- Primary blood dyscrasias
- Hemolytic Anemias
Hypoproliferative Normocytic Anemia
Etiologies
Marrow failure
- Primary bone marrow stem cell d/o
- Aplastic anemia
- Myelodisplasia
- Leukemia
- Marrow failure due to disease in the body
- Autoimmune d/o
- Chronic infections
- Neoplasms
- Renal disease
- Endocrine d/o
Anemia of Chronic Disease
- Pathogenesis
- Chronic inflammation/infection ⇒ cytokines ⇒ liver makes Hepcidin ⇒ poor Fe absorption ⇒ anemia
- Most common anemia in hospitalized pts
- Diagnosis
- Fe low / TIBC low / >10% Sat / Ferritin NOT LOW
- Tx ⇒ treat underlying condition, EPO not that effective
Hemolytic Anemias
-
Anemia d/t shortened RBC survival
- Marrow compensation ⇒ high retics
- MCV normal or high depending on % retics
- Classification
- Based on site of hemolysis
- Intravscular vs extravascular
- Based on mech
- Acquired vs inherited
- Based on site of hemolysis
- Morphological features
- Marked inc. in normoblasts
- High EPO ⇒ High erythropoiesis
- Accum. Hb breakdown byproducts
- Reticulocytosis
- Cholelithiasis
- Hemosiderosis

Hemolytic Anemias
Dx
- History and Clinical Findings
- Signs and sx of aenmia
- Fhx
- Dark urine
- Jaundice
- Hx of gallstones
- Hepatosplenomegaly
- Lymphadenopathy
- Tests
- Anemia w/ high retic count
- Check Smear for ⇒ sickled RBCs, schistocytes/helmet cells
- Dec. haptoglobin ⇒ if intravascular
- Inc. LDH
- Inc. unconjugated bilirubin
- Direct Coombs test

Immune Hemolysis
-
RBC coated w/ Ab or complement
- IgG ⇒ warm Ab
- Idipathic, autoimmune, lymphoproliferative, drugs
- Spherocytes seen on smear
- IgM ⇒ cold Ab
- Usu. post-infectious
- IgG ⇒ warm Ab
- Direct Coombs’ test positive
Non-Immune Hemolysis
-
Microangiopathic Hemolysis
- RBCs destroyed as they pass through small vessels
- Causes ⇒ Thrombocytic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), pregnancy, drugs, metastatic cancers
- See schistocytes on smear
- Mechanical hemolysis
- Infection ⇒ malaria, babesiosis, etc
- Hypersplenism / Trauma

Hereditary Hemolytic Anemias
- Hemoglobinopathies
- Thalassemias
- Hgb S, Hgb C, Hgb S-Hgb-C
- Enzyme deficiencies
- Pyruvate kinase or G6PD
- Membrane defects
- Hereditary spherocytosis/elliptocytosis/stomatocytosis
Sickle Cell Anemia
Overview
- Autosomal recessive
- Point mutation ⇒ glu to val sub
- Heterozygotes asymptomatic
- Dx ⇒ Hgb electrophresis for Hgb S

Sickle Cell Anemia
Clinical Issues
- Severe hemolytic anemia
- Jaundice
- Inc. sickling w/ dehydration, hypoxia, acidosis, fever, infection
- Most acute complications are vaso-occlusion
- Chronic hyperbilirubinemia
Sickle Cell Anemia
Acute Complications
-
Vaso-occlusive crises
- Painful crisis due to hypoxic injury and infarction
- Bones, lungs, liver, spleen, brain, penis can be affected
- Acute chest syndrome ⇒ pumonary vasculature involvement
- Aplastic crises ⇒ parvovirus B19
- CVA
- Splenic sequestration ⇒ occurs in childhood, later functionally asplenic

Sickle Cell Anemia
Chronic Complications
- Infection w/ encapsulated organisms
- Renal disease
- Pulmonary disease
- Retinopathy
- Avascular necrosis of bone
- Skin ulcers
- Pigmented gallstones
- Hepatitis
- Heart ⇒ tachy, flow murmurs
- CNS ⇒ inc risk of stroke
Sickle Cell
Pathology
- Bone marrow ⇒ erythroid hyperplasia
- Extramedullary hematopoiesis can occur
- Erythrostasis in sleen ⇒ thrombosis, infarction, autosplenectomy
- Infarction 2/2 vascular occlusion and anoxia
Sickle Cell
Lab Findings
- Hb 5-11%
- Inc bilirubin
- Inc. retic count
- Nucleated RBCs
- Howell-Jolly bodies
- Leukocytosis and throbocytosis
- Hb electrophoresis
- Hgb S 75-95%
- No Hb A
- Nomral Hb A2 and Hb F

Sickle Cell Trait
Dx
- Normal CBC
- No sickled cells on smear
- Dithionate test ⇒ inc. turbidity of RBC
- Sickle Cell preparation ⇒ see sickles after sodium metabisulfite
- Hb electrophoresis ⇒ gold standard
- 60-70% Hb A
- 30-40% Hb S
G6PD Deficiency
- Abnormal HMP shunt or glutathione metabolism
- X-linked recessive ⇒ almost always in men
- RBCs sensitive to oxidateive stress ⇒ hemolysis
- Infection, drugs, fava beans
- Clinical issues
- Jaundice
- Dark urine
-
Episodic hemolysis associated w/ meds
- Sulfa, nitrofurantoin, primaquine
- Smear
- Heinz bodies ⇒ abnormal Hgb precipiates in RBC
- Bite cells

Hereditary Spherocytosis
- Intrinsic defect in spectrin ⇒ abnl RBC membrane
- Autosomal dominant
- See spherical RBCs
- Increased osmotic fragility
- Extravascular hemolysis
- Clinical issues
- Hemolytic anemia
- Splenomegaly
- Jaundice
- Pigmented gallstones
- Hemolytic crises
- Dx
- Inc retics / inc. MCHC / neg direct Coombs
- Spherocytes on smear
- Osmotic fragility test positive
- Treatment ⇒ splenectomy
