Blood loss Acute Loss of blood volume Chronic Only when regenerative capacity exceeded by blood loss or iron reserves depleted 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

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

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

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

Anemia Flashcards by Quynh Tran

Etiology of Anemia

Blood loss
- Acute
  - Loss of blood volume
- Chronic
  - Only when regenerative capacity exceeded by blood loss or iron reserves depleted
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

How well did you know this?

Not at all

Perfectly

Hypochromic Microcytic Anemias

Anemia with low MCV
Failure of marrow precursors to make Hb
- Fe, porphyrin, globin
Differential dx
- Iron deficiency
- Thalassemias
- Sideroblastic anemia

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Iron Deficiency Anemia

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Beta-Thalassemia Minor

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

How well did you know this?

Not at all

Perfectly

Beta-Thalassemia Major

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Macrocytic Anemias

Anemia w/ high MCV

Pathophysiology ⇒ megaloblastic vs nonmegaloblastic

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Vit B12 Deficiency

Etiology

Pernicious anemia
Total gastrectomy
Malabsorption disease
Terminal ileum disease or removal
Pancreatic insufficiency
Drug induced malabsorption
Food malabsorption

How well did you know this?

Not at all

Perfectly

Vit B12 Deficiency

Peripheral smear
- Macrocytic RBC w/ MCV > 100
- Hypersegmented polys
Serum B12 levels low
Serum MMA high
Serum homocysteine high
Schillings test

How well did you know this?

Not at all

Perfectly

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
Morphological features
- Marked inc. in normoblasts
- High EPO ⇒ High erythropoiesis
- Accum. Hb breakdown byproducts
- Reticulocytosis
- Cholelithiasis
- Hemosiderosis

Hemolytic Anemias

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
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