RBCs Diseases Flashcards
Aplastic Anemia
Bone marrow failure causing pancytopenia w/ hypocellular bone marrow
Mechanism: Bone Marrow Failure
Characteristic: Pancytopenia - Dec. RBCs, WBCs, Platelets
Classification
- Acquired - Idiopathic (no known cause), Secondary (chemicals, drugs)
- Inherited - Fanconi Anemia, Dyskeratosis Congenita, Shwachman Bodian Diamond Syndrom (SBDB)
Aplastic - Shwachman - Bodian Diamon Syndrome (SBDS)
* Mutation:
* Mechanism:
* Characteristic:
* Findings:
Mutation: Biallelic Mutation in SBDS gene
Mechanism: Mitotic Spindle Destabilization - short telomers in GRANULOCYTES
Characteristic: Pancreatic Insufficiency - GI Malabsorption
Findings:
Neutropenia
Hypocellular
Increase Fat Excretion, HbF
Paroxysmal Cold Hemoglobinuria (PCH)
Other name: Donath-Landsteiner Hemolytic Anemia
Common: Children
Cause: Anti-P autoantibody (IgG autohemolysin)
Mechanism: IgG Hemolysion targeting P antigen in RBCs at 4C (cold) or 37C (warm)
Diagnosis:
+ Anti-P Test (hemolysis)
+ DAT - Complement (C3b) only
+ Coombs Test
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Mutation: Phospatidylinositol Glycan Class A gene
Characteristics: Hemolysis during SLEEP
Mechanism: Deficiency in Glycosylphosophatidyl Inositol (GPI) that inactivates complement activity - CD 55, CD 59 - COMPLEMENT MEDIATED HEMOLYSIS
Hb C Disease
Mechanism: GA to Lysine in 6th position
PBF: SHORT THICK RBCs
Characteristic: Hexagonal/ Pyramid shaped pointed end Crystals
Diagnosis: HPLC/Hb Electrophoresis
HbS Diseases - Sicke Cell Anemia
Mutation: Beta Chain in GA to Valince in 6th position
Mechanism: Deoxygenatiom triggers Sickling of RBCs that results to low O2 Saturation and affecting HbS polymerization which then transforms to liquid crystalline (tactoids).
Characteristic: Normochromic Normocytic
Hallmark: Vasso-occlusions
G6PD Deficiency
Mutation: G6PD gene at Long arm X chromosome at Xq28 locus (most common enzymopathy)
Mechanism: Def G6PD results Dec. NADPH making susceptible to Oxidative stress (cannot detoxify H2O2) –> OXIDATIVE DAMAGE
Characteristic: Heinz Bodies (insoluble complex)
Gold Standard: Qualitative Spectrophotometric Assay - Fluorescence: Inc. NADPH
Other Test:
Fluorescence Spot Test
Methemoglobin Reductase Test (Dye Reduction - Brown: G6PD Deficient)
Pyruvate Kinase Deficiency (PKD)
Mutation: PKLR gene
Mechanism: Cannot generate ATP -> Dehydration -> SHRINKAGE
Characteristics:
(+) Howell Jolly Bodies, Papenheimer Bodies
(+) Echinocyte, Target Cells, Burr Cells
Diagnosis: NAD+ is proportional to PK activity (No fluorescence)
1. Quantitative PK Assays:
2. Qualitative PK Assays
Overhydrated Hereditart Stomatocytosis (OHS)
Mutation: RHAG gene
Deficiency: Stomatin (regulation of ion channels)
Mechanism: Cation Permeability with Increase - Na+, Decrease - K –> Swelling
Findings: Decrease - OFT, Increase - EMA
Dehydrated Hereditary Stomatocytosis/Hereditary Xeroxytosis
Mutation: PEIZO1 gene
Mechanism: Net DECREASED cation - Increased K+, Decreased: Na+ –> Shrinkage
Findongs: Decreased - OFT, EMA
Three major mechanism of Anemia
Blood Loss
Impaired red cell production
Accelerated red cell destruction
Three major laboratory findings of Anemia
Decreased RBC, Hb, and Hct
Hemoglobin is a more reliable indicator of anemia
Absolute reticulocyte count
Determine the mechanism of Anemia
Absolute Reticulocyte Count
* High
* Low
Absolute Reticulocyte Count
* High - Excessive RBC loss
* Low - decreased RBC production
Anisochromia
Variation in Hemoglobin concentration
Poikilocytosis
variation in shape
Anisocytosis
variation in size
Microcytic Hypochromic Anemia
IDA
most common anemia
Loss or insufficient Fe that results to ineffective Hb production
Cuases - IDA
Chronic Blood Loss
Increased Iron utilization
* Pregnancy
* Adolescent growth
Impaired Iron absorption
* Celiac
* Achlorhydria
Parasitic Infection
* Hookworm: N. americanus, A. duodenale
* T. trichiura
* Schistosoma: S. mansonii, S. haematobium
Pathophysiology - IDA
* Stage 1/Pre-latent
* Stage 2/Latent
* Stage 3/Anemia
Pathophysiology - IDA
* Stage 1: Storage - Iron depletion (Prelatent)
* Stage 2: Transferrin - Iron deficient eryhthropoiesis (Latent)
* Stage 3: Functional - Anemia
Laboratory Findings - IDA
* RBCs
* Poikilocytes
* Decreased
* Increased
Laboratory Findings - IDA
- RBCs: Microcytic Hypochromic cells
- Poikilocytes: Target cells, Elliptocytes, Ovalocyte, Dacrocyte
- Decreased: Reticulocyte count, Serum Iron, Serum Ferritin
- Increased: RDW, TIBC
70%
Functional iron in Hb
PERCENTAGE OF HYPOCHROMIC RED BLOOD CELLS (% HYPO)
MOST
SENSITIVE and SPECIFIC parameter of Functional Iron Deficiency.
Soluble transferrin receptor (sTfR):
provide **differentiation of IDA from anemia of
chronic inflammation disorders
Increased in IDA, Decreased in ACD
Anemia of Inflammation
Anemia of Chronic Disease
Inability to use iron due to low iron absorption with Increased hepcidin
Hepcidin
key molecule that regulate (inhibiting) iron absorption by inactivating ferroportin
causing to impaired release of iron in blood circulation
Causes - ACD
Infection (TB, Fungal)
Malignancy (MM, Cancer)
Autoimmune (SLE, RA, Sarcoidosis)
Laboratory Findings - ACD
* RBCs:
* Increased:
* Decreased:
Laboratory Findings - ACD
* RBCs: normocytic normochromic
* Increased: Storage Iron, Ferritin, ESR
* Decreased: TIBC, Serumn Iron, sTfr
Serum iron is low because recycling of iron from macrophages is impaired
Mechanism - Sideroblastic Anemia
Ineffective erythropoiesis due to enzyme deficiency - 5 aminolevulinic acid synthase & uroporphyrinogen decarboxylase, that result to Iron overload
5 amino livulenic acid synthetase & auropophyrinogen decarboxylase
Enzyme defciency in Sideroblastic anemia
Lab Findings - Sideroblastic Anemia
* Increased:
* Decreased:
Lab Findings - Sideroblastic Anemia
* Increased: Serum Iron, Ferritin
* Decreased:** TIBC**
Differentiated to ACD - Serum Iron
Beta-thalassemia Trait
a.k.a. Minor beta-thalassemia
One beta gene deletion with mild anemia
CARRIER STATE
HbA2
Increased hemoglobin in beta-thalassemia minor
Beta-thalassemia Minor
* Deletion:
* Anemia:
* Increased hemoglobin
Minor beta-thalassemia
* Deletion: 1 beta chain deletion
* Anemia: Mild/Silent
* Increased hemoglobin: HbA2
Mild Cooley’s Anemia
Beta-thalassemia intermedia
Beta-thalassemia Intermedia
* Deletion:
* Anemia:
* Lab Findings:
Beta-thalassemia Intermedia
* Deletion: Bothe genes are variant
* Anemia: Moderate anemia
* Lab Findings: Microcytosis, Splenomegaly, Low indices, High RDW
Beta thalassemia Major
a.k.a Cooley’s Anemia/Mediterranian Anemia
Absence of beta chains with severe anemia
No HbA is produced
HbF (90%)
Increased Hb (compensatory) in beta-thalassemia major
Laboratory Findings - Beta thalassemia Major
* RBC:
* Anemia:
* Poikilocytes:
* BM:
* Hb:
* Increased:
Laboratory Findings - Beta thalassemia Major
* RBC: Microcytic hypochromic
* Anemia: Severe Anemia
* Poikilocytes: Target cells, teardrop cells
* Inclusions: Basophilic stippling, Howell-Jolly bodies, Papenheimer bodies
* BM: Hypercellular
* Hb: 2-3 mg/dL
* Increased: Serum Iron, Bilirubin
Beta thalassemia major is **transfusion dependent **
4 Classification of a-thalassemia
- Silent carrier - 1 alpha gene deletion
- a-thalassemia minor - 2 alpha gene deletion
- Hb H disease - 3 alpha gene deletion
- a-thalassemia major - 4 alpha gene deletion
Silent carrier
a.k.a heterozygous alpha thalassemia
1 alpha gene deletion without signs and symptoms of anemia
Alpha thalassemia Minor
a.k.a alpha thalassemia trait
2 alpha gene deletion with Mild anemia
Thalassemia common in Souteast Asian
alpha thalassemia minor
Laboratory findings - Alpha thalassemia Minor/Trait
* RBCs:
* Anemia:
* Hb:
* Low:
* Poikilocytes:
Laboratory findings - Alpha thalassemia Minor/Trait
* RBCs: Mild microcytic, hypocheomic
* Anemia: Mild anemia
* Hb: 12-13 g/dL
* Low: MCV, MCH, MCHC
* Poikilocytes: Target cells
HbH disease
3 alpha gene deletion with moderate - severe anemia
4 beta chains
HbH
RBC characteristic in HbH Disease
Pitted Gold ball
Laboratory Findings - HbH Disease
* RBC:
* Anemia:
* Hb:
* Low:
Laboratory Findings - HbH Disease
* RBC: Golf-ball appearance
* Anemia: Mild-Severe anemia
* Hb: 7-10 g/dL
* Low: Indices, HbA2 with basophilic stipplingh
Alpha thalassemia Major
a.k.a Bart’s Hydrops Fetalis
4 alpha gene deletion with severe anemia
No HbA and HbF
Predominant hemoglobin in a-thalassemia major
Hb Barts
(4 gamma chains)
4 gamma chains
Hb Barts
Inhibited enzymes - Lead Poisoning
ALA synthetase
Ferrocheletase
Megaloblastic Anemia
Macrocytic normochromic
Impaired DNA synthesis that results to slow/abnormal nuclear maturation caused by Vit. B12 and Folate deficiency. Deficiency results to decreased Thymidine production which slows nuclear replication then impairs DNA synthesis.
Common Cause of Megaloblastic Anemia
- Vitamin B12 (Cobalamin) deficiency
- Vitamin B9 (Folate) deficiency
Most Common Disorder of cobalamin deficiency
Pernicious Anemia
Laboratory Findings - Megaloblastic Anemia
* RBCs:
* BM:
* Inclusions:
* Increased:
Laboratory Findings - Megaloblastic Anemia
* RBCs: Macrocytic normochromic with oval macrocytes & teardrop cell
* Hypersegmented Neutrophils
* BM: Pancytopenia
* Inclusions: Howell-jolly bodies, Cabot rings
* Increased: MCV, LDH
Pernicious anemia
Autoimmune disease with anti-IF that destroys parietal cells to release IF which blocks binding of IF and cobalamin
Detects Pernicious anemia
Schiling’s test
Aplastic Anemia
Bone marrow failure causing pancytopenia in the presence of hypocellular bone marrow.
Most common inherited Aplastic Anemia
Fanconi Anemia
Fanconi Anemia
Congenital Aplastic Anemia
All cells are decreased: RBC, WBC, Platelets
Fanconi Anemia
* Hematologic Classification:
* Onset:
* BM biopsy:
* BM aspirate:
* PBS:
* Mutation:
Fanconi Anemia
* Hematologic Classification: Congenital Aplastic anemia
* Onset: 5 years old
* BM biopsy: Hypoplastic - Aplastic
* BM aspirate: Pancytopenia
* PBS: Pancytopenia
* Mutation: Abnormality in chromosone 9q & 20q
Congenital Pure Red cell Aplasia
Diamond Blackfan Syndrome/Congenital Hypoplastic Anemia
RBC is only decreased
Diamond Blackfan Syndrome
* Hematologic Classification:
* Onset:
* BM biopsy:
* BM aspirate:
* PBS:
* Mutation:
Diamond Blackfan Syndrome
* Hematologic Classification: Congenital Pure red cell aplasia
* Onset: <1 yr. old
* BM biopsy: Cellular
* BM aspirate: Decreased RBC erythroid precursors
* PBS: Decreased in RBC only
* Mutation: No chromosomal abnormality
Most Common Hereditary Hemolytic Anemia
Hereditary Spherocytosis
Hereditary Spherocytosis
Defect in Vertical support in membrane proteins - spectrin & ankyrin.
Decrease surface-to-volume ratio
5 Mutations in HS:
* Cytoskeletal proteins
* Transmembrane proteins
Mutations in HS:
* Cytoskeletal proteins: Ankyrin, a-spectrin, b-spectrin, Protein 4.2
* Transmembrane protein: Band 3
Hereditary Elliptocytosis/Ovalocytosis
Defect in the Horizontal support of membrane proteins and polarization of cholesterol at the end of the cell.
Elliptocyte: - Cigar shape/Pencil shape; Ovalocyte - Egg shape
Autosomal Recessive Hereditary Elliptocytosis
Hereditary Pyropoikilocytosis
Hereditary Stomatocytosis
a.k.a Overhydrated Stomatocytosis
Defect in cation membrane permeability with excessive permiability to Na+ and **reduced K+ concentration **which makes the cell to swell that result to stomatocytosis
Increase Na, Decrease K
Hereditary Xerocytosis
a.k.a Dehydrated Hereditary Stomatocytosis
Defect in cation membrane permeability with excessive permiability to K+ and **reduced Na+ concentration **which makes the cell dehydrated
Increase K+, Decrease Na+
Overhydrated Hereditary Stomatocytosis (OHS)
* Mutation:
* RBC:
* Increase (cation):
* Decrease (cation):
Overhydrated Hereditary Stomatocytosis (OHS)
* Mutation: RHAG gene
* RBC: Hydrated cell - Swells
* Increase (cation): Sodium - Na
* Decrease (cation): Potassium - K
Dehydrated Hereditary Stomatocytosis (DHS)
* Mutation:
* RBC:
* Increase (cation):
* Decrease (cation):
Dehydrated Hereditary Stomatocytosis (DHS)
* Mutation: PIEZO1 gene
* RBC: Dehydrated
* Increase (cation): Potassium - K+
* Decrease (cation): Sodium - Na+
Hereditary Acanthocytosis
Defect on RBC membrane lipid with increased cholesterol due to abetalipoproteinemia
Seen in alcoholic cirrhosis
Glucose 6 phosphate dehydrogenase (G6PD)
Reduced glutathione decreases NADPH that increase peroxide level and oxidizes hemoglobin to methemogloblobin that denatures hemoglobin producing heinz bodies
Most common enzyme deficiency in HMP
Pyruvate Kinase (PK) deficiency
Reduced ATP caused by mutation in PKLR gene with impaired cation pump resulting to RBC shrinkage reducing lifespan
Most common enzyme deficiency in EMP
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Loss of complement inhibition of CD55 and CD59 due to mutation in PIG-A gene that results to *RBCs highly sensitive to complement binding *
Paroxysmal Cold Hemoglobinuria
* Mechanism:
* Mutation:
* Test:
Paroxysmal Cold Hemoglobinuria
- Mechanism: Loss of complement inhibition of CD55 & CD59 due to deficiency in glycosylphosphatidylinositol
- Mutation: Phospatidylinositol Glycan class A
- Test:
Sugar water Test (Screening Test)
Sucrose Hemolysis Test (Confirmatory)
Flow Cytometry (Gold Standard)
SPHEROCYTIC erythrocytes
hallmark abnormality in hemolytic anemia
Most common Hemogloninopathy
Sick Cell anemia
Hb SS
* HbS:
* HbA:
Homozygous - Sickle Cell Disease
Hb SS
* HbS: 80-100%
* HbA: No HbA
Hb SA
* HbS:
* HbA:
Heterozygous - Sickle Cell Trait
Hb SA
* HbS: 40%
* HbA: 60%
Substitution - Hb S
6th position of beta chain from Glutamate - Valine
Substitution - Hb C
6th position in beta chain from Glutamate - Lysine
Substitution - Hb E
26th position in beta chain from Glutamate - Lysine
Substitution - Hb O
**121st position **of beta chain from Glutamate - Lysine
Substitution - Hb D
**121st position **of beta chain from Glutamate - Glysine
Echinocyte
evenly spaced round projections (10-12)
a.k.a Burr cell
Acanthocyte
**unevenly **spaced pointed projection (3-12)
a.k.a** Thorn cell/Spur cell**
Codocyte
Increase surface area-to-volume ratio
Bull’s eye appearance with central staining area
a.k.a Target cell/Mexican Hat cell
Leptocyte
thinner variant of Codocyte
Dacryocyte
Pear shaped cells with one blunt projection
a.k.a Tear drop cell/tennis racket cell
Spherocyte
Decrease surface area-to-volume ratio
small RBC
a.k.a Bronze cell
Elliptocyte/Ovalocyte
Polirization of cholesterol at the end of the cell
Cigar shaped (elliptocyte), Egg shaped (ovalocyte)
a.k.a Pencil cell (thinner variant)
Stomatocyte
Elongated slit-like appearance in the central pallor
a.k.a **Mouth cell **
Drepanocyte
Crescent shaped and pointed ends
a.k.a Sick cell
Schistocyte
Fragmented RBCs
a.k.a Bite cell/Helmet cell/Horn cell
Schistocyte
Fragmented RBCs
a.k.a Bite cell/Helmet cell/Horn cell
Causes in Schistocyte
“MUSD”
M - Microangiopathic (MAHA)
U - Uremic syndrome
S - Severe burns
D - DIC
Others: Bite Cell - G6PD
Causes in Stomatocytes
“RASH”
R - Rh null phenotype
A - Alcoholism
S - Severe Liver disease
H - Hereditary Stomatocytosis
Caused by Dacryocyte
Myelopthisic anemia
Causes of Echinocyte
“PUCA”
P - PK Deficiency
U - Uremia
C - Cancer of stomach
A - Acute blood loss
causes Artifactual or drying of smear
Orthochromic normoblast (Metarubricyte)
Commonly seen nucleated RBC
RBC Inclusion - DNA remnants
Howell-jolly bodies
Seen in: Post-splenomegaly, Hemolytic anemia, megaloblastic anemia
RBC Inclusion - RNA remnants
Basophilic stippling
RBC Inclusions - Iron granules
Pappenheimer bodies
RBC Inclusion - Cabot Rings
Abnormal mitosis with loop of eight shape
Seen in: Megaloblastic anemia
RBC inclusion - Hexagonal/Bar of Gold
Hb C Crystal
RBC inclusion - Washington monument crystals
Hb SC Crystal
RBC Inclusion - Denatured hemoglobin
Heinz bodies
Seen in: G6PD, beta thalassemia major, Hb H disease
