Anemia Flashcards
RBC Indices of Anemias
1) Microcytic/Hypochromic (MCV <80 fl, MCHC <31 g/dl)
2) Normocytic/Normochromic (MCV = 80-100 fl, MCHC = 31-37 g/dl)
3) Macrocytic/Normochromic (MCV >100 fl, MCHC 31-37 g/dl)
Anemia Based on Reticulocyte Count and DAT
Evaluation of Microcytic Anemia = MCV <80 fl
Evaluation of Macrocytic Anema - MCV >100 fl
Evaluation of Normocytic Anemia
Anemias Classified as Microcytic/Hypochromic
1) Iron deficiency
2) Sideroblastic Anemia
3) Thalassemia
Macrocytic/Normochromic
1) Megaloblastic Anemia
2) Liver disease
3) Any hemolytic diseases can have increased MCV but lots of polys
Normocytic/Normochromic
1) Blood loss, endocrine disease
2) Renal disease
3) Aplastic anemia
3) RBC Aplasia
4) Myelophthisic anemia
Non-immune Extrinsic Anemia
1) Infectious Agents: Malaria, Babesia, Bartonella, Clostridum
2) Venoms
3) Chemicals and Drugs
4) Abnormal lipid issues causing membrane abnormalities: Spur Cell Anemia, Abetalipoproteinemia, Lecithin-cholesterol acyl transferase (LCAT)
Non-Immune Physical Anemia
1) Microangiopathic Hemolytic Anemia
2) HELLP syndrome
3) Extreme exercise, hypertension, hypersplenism
4) Hemolytic Uremic Syndrome
Immune Hemolytic Extrinsic Anemia
1) Alloimmune: HDN, Drug induced, Transfusion, Warm autoimmune hemolytic anemias, Cold autoimmune, Raynauds, PCH
Non-Immune Hemolytic Intrinsic, Membrane Anemia
Decreased stability, loss of membrane, variation in shape, decreased flexibility, altered permeability
1) Hereditary Spherocytosis
2) Hereditary Elliptocytosis
3) Hereditary Stomatocytosis
4) Hereditary Pyropoikilocytosis
5) PNH
Non-Immune Intrinsic, Enzyme Anemia
1) Glucose-6-phosphate Dehydrogenase deficiency (G6PD)
2) Pyruvate Kinase Deficiency
Non-immune Intrinsic, Hemoglobinopathy Anemias
Gene mutation that leads to abnormal function
1) Sickle Cell Anemia
2) Sickle Cell Trait
3) Hgb C Disease
4) Hgb C Trait
5) Hgb SC
6) Hgb D disease
7) Hgb E
8) Unstable Hgbs
Non-Immune Intrinsic
Thalassemias
Gene mutation that leads to decreased synthesis of globin chains
1) Beta Thal major
2) Beta Thal minor
3) Beta Thal + Hgb S
4) Alpha Thal major
5) Alpha Thal Trait
Silent carriers
6) Hgb H disease
7) Hydrops fetalis
8) Hereditary persistence of Fetal Hgb
Porphyrias - Not Hemolytic Intrinsic
Problem with any 8 enzymes needed to change porphyrins into heme - leads to build up
1) Acute porphyrias - affects nervous system
2) Cutaneous porphyrias - mainly affect the skin
G6PD (Glucose-6-Phosphate Dehydrogenase)
Normocytic/Normochromic
Inherited x-linked
Deficiency of G6PD (buildup of oxidants)
Hgb converted to methgb (Heinz bodies)
Increased retic, bilirubin, hgburia, hgemia, “bite” cells
Treatment - avoid oxidant drugs
Pyruvate Kinase Deficiency
Normocytic/Normochromic
AR (autosomal recessive)
Alteration RBC membrane = K+ loss
Increased 2,3 DPG
Jaundice
Increased retic, decreased haptoglobin, Burr cells
Treatment - none required, transfuse if needed
Hereditary Spherocytosis
Normocytic/Normochromic
AD (autosomal dominate)
Deficiency in spectrin = unstable membrane
Membrane loss = decreased S:V ratio
Increased permeability to Na+
Hgb = normal to decreased
Hereditary Elliptocytosis
Normocytic/Normochromic
AD inherited
Increased permeability to Na+
+/- Hgb
Mildly increased retic
Elliptocytes >25%
Treatment: None, Splenectomy
Hereditary Stomatocytosis
Normocytic/Normochromic
AD inheritance
Less flexible, osmotic lysis in spleen
Increased permeability to Na+ & K+
Hgb 8-10 g/dl - mild to moderate
Increased retic, bilirubin
Stomatocytes (10-50%)
Treatment: None, Splenectomy
Hereditary Pyropoikilocytosis (HPP)
Rare AR disease
Severe subtype of Hemolytic Enzyme
Primarily African descent
Thermal stability (cells fragment at 45-46 C)
Disintegrate when incubated at 37 C for >6 hrs
2 Defects- one from each parent: Deficiency of alpha-spectrin, mutant spectrin
Striking poikilocytes (budding, fragments, microspherocytes, elliptocytes, triangulocytes, bizarre forms)
MCV (25-55 fL due to RBC fragments)
Osmotic fragility - thermal sensitivity
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Acquired: Idiopathic, Post bone marrow dmg
Abnormal clone of stem cells
Mutation in PIG-A gene causing deficiency in GPI anchor proteins
Abnormal sensitivity to complement lysis
Sleep associated hemolysis, Abdominal/low back pain, Thrombosis, Infection, Bone marrow hypoplasia
Hgb (8-10 mg/dl)
Increased retic, nRBCs, hemosiderinuria,
Testing: Sugar Water test, Acid Serum test (Ham’s), Immunophenotyping
Extrinsic Defects
1) Chemicals & Drugs
2) Oxidant Drugs, Gasses, Lead
3) Venoms
4) Infectious Agents: Babesiosis, Bartonella, Clostridium, Malaria
Identification: Thin and Thick smears
Abnormal Plasma Lipids
Normocytic, Normochromic
Spur Cell Anemia
Severe Liver disease
Increased cholesterol RBC membrane: Decreased deformability
Hgb 5-10 g/dl
Increased retic, bilirubin, abnormal liver function tests
Target Cells
Leptocytes
Spur Cell
Acanthocyte
Abnormal Plasma Lipids Abetalipoproteinemia
Normocytic, Normochromic
AR inheritance
Absence of Beta-lipoprotein = abnormal membrane
+/- Decreased Hgb
Acanthocytes
LCAT (Lecithin-Cholesterol Acyl Transferase) deficiency
Low HDL - serum lipoprotein A1 and A2
Elevated levels of APO E
Numerous macrocodocytes (Target Cells)
Physical Injury
Usually Normocytic/Normochromic
Intravascular hemolysis
Fragments
Helmet cells
Microangiopathic Hemolytic Anemia
Lesion in circulation, mechanical injury, hypertension
Artificial Heart Valves
Thrombotic Thrombocytopenic Pupura (TTP)
Disseminated Intravascular Coagulation (DIC)
Burns
Fragments
Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) Syndrome
Obstetric patients
Similar to TTP and HUS
Malignant Hypertension
Elevated Blood Pressure
March Hemoglobinuria
Post extreme exercise
Usually no fragments
Hypersplenism
Splenic sequestration of RBCs
Hemolytic Uremic Syndrome (HUS)
Normocytic/Normochromic
Usually occurs in children
In adults - associated with bacterial infection, SLE, cancer
Acute Renal Failure (clots in kidney)
Decreased platelets
Increased retics, Decreased haptoglobin, hemoglobinemia, Hemoglobinuria
Increased BUN & Creatinine
Casts in urine
Immune Hemolytic Anemia - Alloimmune
Transfusion Reaction
Hemolytic Disease of the Newborn - mother’s antibodies causing issues
Immune Hemolytic Anemia - Drug Induced
Drug Protein Complex
Antibodies
Kleihauer-Betke Stain for Fetal RBCs
Maternal Blood sample examined for presence of fetal RBCs
Fetal RBCs may cause/increase maternal antibody production that could affect pregnancy/future pregnancies
Warm, Autoimmune Hemolytic Anemia (WAIHA)
Normocytic/Normochromic
IgG Antibody
Extravascular hemolysis
Idiopathic: associated with SLE, CLL, viral illness
Increased retics
Spherocytes
Cold, Autoimmune Hemolytic Anemia
Cold Agglutinin disease
IgM directed against I antigen
Extravascular hemolysis or Complement lysis
Idiopathic: associated with mycoplasma, MPD, viral illness
Raynaud’s Phenomenon
Anemia
Increased MCV
Corrects with higher temperature
Paroxysmal Cold Hemoglobinuria (PCH)
Biphasic IgG Antibody: Donath Landsteiner Antibody
Reacts with RBC @ <15 C; hemolysis at body temperature
Idiopathic: associated with viral infection, tertiary syphilis
Massive hemolysis with exposure to cold
Hemoglobinopathies
Abnormality in globin part of hemoglobin molecule
Amino Acid substitution in globin chain
Affects solubility, function stability of Hgb
Associated with chronic hemolytic anemia
Usually Inherited
Sickle Cell (SS) Comments
Most Common Hemoglobinopathy
Hgb S precipitates with deoxygenation
Organ/tissue infarction: Necrosis, Autosplenectomy
Hgb (6-10 g/dl)
MCV may be increased
Sickle Cell (homozygous) Amino Acid substitution
Valine for Glutamic Acid on #6 Beta chain (Hgb S)
Hemoglobin C Disease (CC) Comments
3rd Most Common
Decreased Hgb solubility
Splenomegaly, Joint Pain
Hgb 8-12 g/dl
Increased retics
Hemoglobin C Disease Amino Acid substitute
Lysine for Glutamic Acid at #6 Beta chain
Hemoglobin S-C Disease Comments
Normocytic/Normochromic
Hgb 10-14 g/dl