Heme/Onc - Week 2 Review - Part 3 - Anemia Flashcards
Classifications of Mean Corpuscular Volume (MCV) - 3
Microcytic < 80
Normocytic - 80 to 100
Macrocytic > 100
Microcytic Anemia - 5 Types
1) Iron Deficiency Anemia
2) Anemia of Chronic Disease
3) Sideroblastic Anemia
4) Thalasemia
5) Lead Poisoning
Macrocytic Anemia - 2 Subdivisions - 5 Anemias
Megaloblastic Macrocytic - B12 and Folate
Non-Megaloblastic Macrocytic - Liver Disease + EtOH + Drugs (5-FU)
Normocytic Anemia with Extravascular Hemolysis (5)
1) Heriditary Spherocytosis
2) Sickle Cell
3) Hemoglobin C
4) Beta Thalessemia (Microcytic)
5) Immune Hemolytic Anemia - IgG Mediated
Normocytic Anemia with Intravascular Hemolysis (5)
1) Paroysmal Nocturnal Hemoglobinuria
2) G6PD Deficiency
3) Immune Hemolytic Anemia - IgM Mediated
4) Microangiopathic Anemia
5) Malaria
Normocytic Anemia with Underproduction (2)
1) Parvovirus B19
2) Aplastic Anemia
Classic S/Sx of Anemia (5)
1) Weakness
2) Fatigue
3) Pale Conjuntiva/Skin
4) Lightheaded/Headache (CNS Hypoxia)
5) Anigina (with preexisting CAD)
Microcytic Anemia - 4 Major Types to Review + Associated Defect
1) Iron Deficiency - Lack of Heme
2) Anemia of Chronic Disease - Lack of Heme
3) Sideroblastic Anemia - Lack of Protoprphorin
4) Thalesemia - Lack of Globulin Chain
Pathway of Iron Absorption
1) Absorbed in the duodenum via DMT1 transporters
2) Transported into the blood via ferroportin
3) Transferrin binds free Iron
4) Ferritin stores Iron
Major Laboratory Measures of Blood (4)
1) Serum Iron
2) Serum Ferratin (Stored Iron)
3) TIBC = Total Iron Binding Capacity - Amount of Transferritin
4) % Saturation = Amount of Transferrin bound by iron - normally 33%
Iron Lab Values in Iron Deficiency Anemia vs. Anemia of Chronic Disease
Iron Deficiency
1) Reduced Serum Iron + Saturation
2) Reduced Ferritin (Nothing to Store)
3) Elevated Transferritin (body looking or more iron
Chronic DIsease
1) Reduced Serum Iron
2) Increased Ferritin (all stored)
3) Decreased Transferritin (TIBC)
Major Causes of Iron Deficiency (7)
Absorption Issue
1) Breast Milk (infants)
2) Children (poor diet)
3) Malabsorption (Celiac)
4) Gastrectomy (Loss of stomach = less acid = less Fe2+ Iron = Less Absorbed)
Leech Issue
5) Peptic Ulcer
6) Hookworm
7) Colon Polyp/Carcinoma (Bleeds)
Change in Non-Iron Labs in Iron Deficiency Anemia (3)
1) Increased Free Erythrocyte Protoporphyrin (Still made but with not heme to bind)
2) Increased RDW (Cell Sizes Vary)
3) Low Hb/Hct
Additional Key Iron Deficiency S/Sx (2)
1) Pica - Eat dirt due to psychological drive to get iron
2) Koilonychias (Spoon Shaped Nails)
Plummer Vinson Syndrome - Triad
1) Iron Deficiency Anemia
2) Glossitis
3) Esophageal Webs
Typically presents as dysphagia with anemia
Anemia of Chronic Disease - Pathophisiology
Chronic inflammation activates immune system - Immune system responds by increasing hepcidin
Hepcidin hides Iron (with Ferritin) - Done to prevent bacteria from using the Iron
Sideroblastic Anemia - Mechanism of Anemia + Causes (4)
Mechanism - Decreased Protoporphyrin production - can’t make heme - Iron still goes into the mitochondria and gets trapped (Sideroblasts formed) - Free radial damage from the iron causes cell rupture
Causes
1) Congenital - ALAS Deficiency
2) Alcoholism (MItochondrial Poisoning)
3) Lead Poisoning (Inhibits ALAD + Ferrochetalase)
4) B6 Deficiency (ALAS Co-Factor - Common with Isoniazad Therapy for TB)
Protoporphyrin Synthesis - Key Steps (3)
1) Succinyl CoA - Converted to Aminoleuvinic Acid (ALA) via ALA Synthase (ALAS) + Vitamin B6 (Co-Factor)
2) ALA Converted to Porphobiligin via ALAD
3) Eventually transitioned to protophorin - made to heme via Iron addition (ferrochetalase) - Step Occurs in Mitochondria
Lab Findings in Sideroblastic Anemia (4)
Lab Findings - All Due to Iron Overloaded State (Ruptures Membrane)
1) Increased Serum Fe (Cell Lysis)
2) Increased % Saturation + Ferritin (Stored cause you can’t use)
3) Low TIBC (Low Transferritin) - Lots circulating, don’t want to promote more
Histology - SIderoblastic Microcytic RBCs (Ringing with Blue Iron)
Alpha Thalassemia - Mutation and Gene Location
Mutation of Chromosome 16 - 4 Possible Genes
Alpha Thalassemia - Results of # of Mutations
1 Deletion - Asymptomatic
2 Deletions - Mild Anemia - Cis (Asian) is worse - both on same chromosome
3 Deletions - Severe Anemia - Beta Chain Tetromeres (HbH) Damage RBCs
4 Deletions - Fetal Death (Hydrops Fetalisis) - Gamma Chain Tetromeres (HbBarts)
Beta Thalassemia - Mutation + Gene Location
Point Mutation - Can be Beta+ or Beta-Null
Chromosome 11
Beta Thalassemia Minor - Genetics + Presentation
Genetics - B/B+ - Most Mild Form
Asymptomatic with increased RBC Count - Microcytic Hypochromic Cells
Target Cells on Smear
Beta Thalassemia Major - Genetics + Sub-Populations + Labs (3)
Major = Beta-Null/Beta+
African Populations - Alpha and Beta Thalassemia
Mediterranean = Beta Thalassemia
Labs for Beta Major
Microcytic Hypochromic RBCs
Nucleated RBCs (Splenic Production)
Target Cells
Beta Thalassemia Major - Presentation + Findings (5)
Presentation - Presents after HbF Drops
Findings
1) Alpha Tetramers Aggregate - Extravascular Hemolysis
2) Massive Erythoid Hyperplasia - Skull hematopoeisis = Crew-Cut Skull
3) Facial Bone Hematopoeisis - Chipmunk Facies
4) Hepatosplenomegaly
5) High risk of Aplastic Crisis with Parvovirus B19 Infection
Major Causes of Macrocytic Anemia (2)
Folate and B12 Deficiency (Megoblastic)
Folate/B12 Pathway
Folate Absorbed as Tetra-Dihydrofolate - THF-Methylated for circulation - B12 removes the Methyl allowing for DNA Synthesis - B12 Produces Methionine from Homocystine in the Processs
Impacts of Impaired DNA Synthesis (3)
1) Impaired RBC Synthesis - Macrocytic Anemia
2) Impaired Division of Granulycytic Precursors - Hyper-segmented Neutrophils (>5 Lobes)
3) Gut Enlargement of intestinal epithelium
Folate Deficiency Causes (3)
1) Poor Diet - EtOH + Elderly
2) Increased Demand - Pregnancy - No Folate leads to congenital defects
3) Drugs (Methotrexate)
Folate Deficiency Alternative Name
1) Giardiasis
Folate Deficiency Findings (5)
1) Macrocytic RBCs
2) Hyper-Segmented Neutrophils
3) Low Serum Folate
4) Elevated Serum Homocystine (Not used by B12)
5) Glossitis
Vitamin B12 Absorption Pathway - 5 Steps
1) Salivary Amylase Liberated B12
2) R-Binder holds B12 through the stomach
3) Pancreatic Proteases free B12
4) B12 Binds Gastric Parietal Cell Produced Intrinsic Factor
5) B12-IF Absorbed in the ileum
Causes of B12 Deficiency (4)
1) Precocious Anemia = #1 Cause - Autoimmune Destruction of Parietal Cells (3 P’s - Proton Pump + Pink + Precocious Anemia
2) Pancreatic Insufficiency (No Removal of R-Binder Protein)
3) Diet (Vegan) - Rare
4) Damage to the Ileum (Crohn’s Disease)
B12 Deficiency - Clinical Findings (3)
1) Macrocytic Anemia with Hyper-segmented Neutrophils
2) Glossitis
3) Sub-Acute Combined Degeneration of SC - Methylmalonic acid Build but destroys DCMLT + CST)
B12 Deficiency - Keys Labs (4) + Key Test
1) Smear - Macrocytic Anemia with Hyper-segmented Neutrophils
2) Low Serum B12
3) High Homocystine (no Methionine ProductioN)
4) High Serum Methylmalonic Acid (No Succinyl CoA Production)
Schilling Test - Give Pt. Labeled B12 - Check if it makes it to the urine - If not give with IF and see if it makes it
Give IF - See B12 in Urine - Means Precocious Anemia (with lack of IF)
Reticulocyte Count - Definition + Calculation + Impact of Corrected Count
Reticulocyte = Pre-mature RBC (24 hours) - Bluish cytoplasm from RNA - Normally 1-2% of RBCs
Calculation of Corrected Count =
(Reticulocyte Count * Hct) / 45
Normal Hct = 45
Corrected > 3% = Bone Marrow responding = Hemoylsis
Corrected < 3% = Bone Marrow not responding = Underproduction
Extravascular Hemolysis - Location + Impacts + Major Findings (4) + Causes (4)
Macrophages destroy cells in Spleen/Liver/Lymph Nodes
Globin Broken down in AA and Heme in Iron (Recycled) And Protoporphoryin (bilirubin)
Findings
1) Anemia with splenomegaly
2) Jaundice (Elevated Bilirubin
3) Gallstones (Supersaturated with Bilirubin)
4) Marrow Hyperplasia
Causes
1) Hereditary Shpherocytosis
2) Sickle Cell
3) Hemoglobin C
Intravascular Hemolysis - Location + Impacts + Major Findings (3) + Causes (5)
Occurs in the vessel - Initial change results in low haptaglobin (haptaglobin binds up all the free hemoglobin)
Findings
1) Hemoglobinemia (Lots of Hemoglobin in the blood
2) Hemoglobinuria (in the urine)
3) Hemosiderinuria (RT Cells pick up Hb and hold for a few days before they die
Causes
1) PNH
2) G6PD
3) Immune Mediated
4) Microangiopathic Anemia
5) Malaria
Hereditary Spherocytosis - Type of Anemia + Pathophysiology
Normocytic Anemia with Extravascular Hemolysis
Defect in Ankyrin/Spectrin/ or Band 3:1 - Leads to issues with cytoskeletal teething of RBCs —- Creates membrane blebs which are removed by the spleen - Cells become round vs. dumbbell - Can’t pass splenic capillaries causing lysis
Hereditary Spherocytosis - Clinical Findings (3) + Labs (3)
Clinical
1) Hepatosplenomegaly
2) Jaundice
3) Increased risk for aplastic crisis with Parvovirus B19
Labs
1) Spherocytes on smear
2) Increased RDW - Cell Sizes Vary
3) Increased Mean Corpuscular Hb Concentration (MCHC) = More Red
Hereditary Spherocytosis - Diagnosis + Treatment (2)
Dx - Fragility Test - Hypotonic solution causes spherocyte rupture but not normal RBCs
Treatment - Spleenectomy - Howell-Jolly Bodies Reamin (RBCs DNA Left-Overs normally clearned by the spleen
Sickle Cell Anemia - Type of Anemia + Genetics
Normocytic Anemia with Extravascular Hemolysis
Genetics - Autosomal Recessive
Single AA Substitutions in Hb on Chromosome 11 (Valine replaces a Glutamic Acid) - Beta Globin Gene
Sickle Cell Anemia - Pathophysiology + Triggers (4)
HbS - Occurs with 2 Defective Genes –> Polymerizes under oxidative stress + Aggregates into needle stick struckes - continuously sickles + unsickles
Triggers
1) Cold
2) Hypoxemia
3) Acidosis
4) Dehydration
Sickle Cell Anemia - Clinical Findings (5) + Causes
AREAS
A - Autosplenectomy (Increased Infections) + Target Cells + Howell Jowell Bodies
R - Renal Papillary Necrosis - From Howell Jowell Bodies
E - Encapsulated Organism Infection (Strep. Pneumoniae + Haemophilus Influenza)
A - Asplenic Anemia Risk (Parvovirus B19)
S - Salmonella Osteomyletis
Sickle Cell Anemia - Lab Findings (4)
1) Target Cells - Asplenia + Blebs
2) Skull = Crew-Cut + Chipmunk Face
3) Metabisulfite Screen - Any amount of HbS will sick - Shows Triat and Disease
4) Hb Electrophoresis shows if it is trait of disease
Hemoglobin C - Type of Anemia + Genetics
Normocytic Anemia with Extravascular Hemolysis
Genetics - Autosomal Recessive Beta Globin (Chromosome 11) AA Mutation
Glutamic Acid - Lysine (vs. Valine in HbS)
Hemoglobin C - Lab Findings (3)
1) Normocytic Anemia with Extravascular Hemolysis
2) Target Cells
3) HbC Crystals on Smear - Little Rectangles
Paroxysmal Nocturnal Hemoglobuinuria (PNH) - Type of Anemia + Pathophysiology
Normocytic Anemia with Intravascular Hemoylysis
Acquired defect in the myeloid stem cell = loss of GPI (which holds DAF-CD55) on the RBC - No DAF means compliment can attack and lyse RBCs
PNH Markers + Gene
Markers - Loss of CD55 and CD59
Genetics - PIG-A Gene (GPI Production
PHN Clinical Features (4)
1) Night Time Hemolysis (Acidosis)
2) Morning Hemoglobinuria (Red Urine)
3) Sucruse Screening Test
4) Complications = Iron Deficiency Anemia + Risk of AML (Myeloid keeps mutating)
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) - Type of Anemia + Pathophysiology
Normocytic Anemia with Intravascular Hemoylysis
Loss of GP6D = Loss of ability to produce NADPH
No NADPH = Can’t recycle glutathione
No Glutathione = High susceptibility to oxidative stress
G6PD - Genetics + Variants (2) + Stress Triggers (4)
Genetics - X-Linked Recessive
Variants
African = Mild
Mediterranean - Severe
Triggers
1) Fava Beans
2) Acidosis (DKA)
3) Primaquin
4) Sulfonamides
G6PD - Lab Findings (3)
1) Normocytic Anemia with Intravascular Hemoylysis
2) Heinz Bodies (Hb accumulations in the cells)
3) Bite Cells - Macrophages take bites out to try and remove Heinz Bodies
Immune Hemolytic Anemia - Type of Anemia + Types (2)
Normocytic Anemia with Intravascular or Extravascular Hemoylysis
IgG - Macrophage Induced - Extravascular - Warm Agglutinate
IgM - Compliment Induced - Intravascular - Cold Agglutinate
IgG Mediated Hemolytic Anemia - Type of Anemia + Key Points (2)
Warm Agglutinate + Extravascular Hemolysis
Consumption via splenic macrophages creates spherocytes
IgG Mediated Hemolytic Anemia - Causes (4) + Treatment (3)
Causes
1) SLE
2) CLL
3-4) Drugs (Methyldopa + Cephalosporin)
Treatment
1) Cessation of Drug
2) IVIgG - Throw dog a bone and keep macrophages busy
3) Spleenectomy
IgM Mediated Hemolytic Anemia - Type of Anemia + Key Point + Causes (2)
Cold Agglutinate - Intravascular Hemolysis
Fixes Compliment
Causes - Mycoplasma Pneumonia + EBV
Microangiopathic Hemolytic Anemia - Type + Pathophysiology + Causes (4)
Normocytic Anemia with Intravascular Hemolysis
RBCs are sheered by the microthrombi as they pass in circulation - results in schistocyte (Helmet Cells)
Causes - Micro-Thormbi Disease
1) TTP
2) HUS
3) DIC
4) HELLP
Normocytic Anemia Due to Underproduction - Key Finding + Causes (4)
Reticulocyte Count - Low - Not Corrected for Anemia
1) Parvovirus B19
2) Aplastic Anemia
3) Microcytic Anemia (falls in this category)
4) Macrocytic Anemia (falls in this category)
Aplastic Anemia - Mechanism + Findings (4)
Damage to HSCs - Triggers Pancytopenia
Pancytopenia
1) Anemia
2) Thrombocytopenia (Bleeding)
3) Leukopenia (Infection)
4) Bone Biopsy - Empty Marrow + <10% Cellularity
Aplastic Anemia - Causes (4) + Treatment (2)
Causes
1) Viral Infection (Parvovirus B19)
2) Drugs
3) Chemicals
4) Autoimmune - T-Cell Based
Treatment - Transfusion + Marrow Stimulation (GM-CSF)
