Red Cell Disorders Flashcards
Microcytic Anemia
Low MCV (<80)
Iron deficiency anemia
Anemia of chronic disease
Thalassemia
Sideroblastic anemia
Macrocytic Anemia
- MCV > 100
- Megaloblastic
- b12 and folate deficiency
- Non megaloblastic
MCH
Mean Corpuscular Hemoglobin
hb/rbc
MCHC
Mean corpuscular hemoglobin concentration
hb/hct
Iron Deficiency Anemia
- fatigue, atrophic glossitis, PICA, koilonychias
- Most common in USA from blood loss
- Pregnant women need more women
- Labs
- decrease in Fe, ferritin, % Fe saturation
- decrease MCV
- increase TIBC, transferrin, and EDW
- (serum iron also dec. in ACD, but ferretin increased in ACD)
Ferritin
in increased with inflammation, so be careful.
look at saturation instead
Anemia of Chronic inflammation
- Iron stuck in macrophages because of chronic inflammation
- Hepcidin blocks movement of iron from machrophges
- decreased response to EPO
- Labs
- increased ferritin
- decrease TIBC, transferrin
- N transferring receptor
- often normocystic but usually microcytic
*
Sideroblastic anemia
- Fe in RBC mitochondria from abnormalities in porphyrin metabolism, blocks heme sysnthessis
- iron overload, inc. ferritin, low tibc
- blood basophilic stippling
- decreased pyridoxine b6
- decreased MCV unless there is MDS
- Causes
- Alcohol, most common
- MDS, drugs, toxins (lead, zinc, copper)
Macrocytic Anemia
- Megaloblastic
- b12
- folate
- mds
- others where cells are more oval
- Non megaloblastic
- more round
- alcohol, liver biases, aplastic anemia, hypothyroid.
- more common than megaloblastic
Megaloblastic anemia
- macrocytic anemia resulting from disorder in DNA synthesis
- Macroovalocytes
- hypersegment neutraphils (1 with 6 lobes or >5% with 5 lobbies)
- associates with MDS
- b12
- usually from pernicious anemia or other malabsortion
- takes longer
- neurologic problems, peripheral neuropathy,
- folate
- diet problem, green leafy vegatables
- develops faster than b12 deficiency
Megaloblastic anemia
- macrocytic anemia resulting from disorder in DNA synthesis
- Macroovalocytes
- hypersegment neutraphils (1 with 6 lobes or >5% with 5 lobbies)
- associates with MDS
- b12
- usually from pernicious anemia or other malabsortion
- takes longer
- neurologic problems, peripheral neuropathy,
- folate
- diet problem, green leafy vegatables
- develops faster than b12 deficiency
Megaloblastic Anemia Labs
- serum b12, folate
- RBC folate better than serum
- homocysteine (increased in both folate and b12 def)
- methylmalonic acid (normal in folate def)
- these may be easiest changes (before blood changes)
Pernicious Anemia
- Auto immune dz with anti-intrinsic factor and anti-parietal cell antibodies and chronic atrophic gastitis
- Anti-intrinsic factor Ab (most specific but insensitive)
- Anti-parietal cell Ab (more sensitive but less specific, positive in other autominnume dz)
- Schilling test (normalizes when give intrinsic factor)
Normocytic anemia
- abnormal break down of rbcs
- inc. reticulocytes (do methylene blue , other super vital)
- Hemolytic anemia
- dec haptoglobin
- inc. LDH
- inc. bilirubin
Hereditary Spherocytosis
- problem with vertical interactions with RBC membrane in hereditary (ankryn)
- normal MCV
- also see in autoimmune hemolytic anemia
- DAT positive
- dec. MCV
- Osmotic fragility test, cells lyse when put in low tonic strength fluid
- EMA test is new (eosin-5-meleimide binding)
- lower update of a dye
- flow cytometry
Elliptocytes
- Abnormal horizontal interactions with cytoskeleton
- abnormal spectrum or protein 4.1
- usually only mild hemolysis
- 25% of cells
- differential: iron deficiency anemia (pencil cells)
Stomatocyte
- Hereditary stomatocytosis
- AD
- Defect in Na/K permeability of rbc membrane
- Alcohol and liver dz.
- Rh null disease
RBC enzyme effects
- Defective pyruvate kinase for ATP
- and g6pd deficiency for NADPH
- needed for good membrane integrity
Heinz body and bite cell
- heinz body is denatured hgb
- removed by spleen, making bite cell, blister cells
- seen in g6pd deficiency
- x-linked
- reticulocytes are normal in enzyme activity, need to test well after hemolytic episode
- problems with oxidation, so episodes with certain drugs, fava beans, infection
- also seen in unstable hemoglobins
- hgb barts, H, alpha thal
Echinocyte
- multiple projects from cell membrane
- also called burr cell
- pyruvate kinase deficiency
- impaired embed hofmeyer pathway
- cannot make ATP, NAD
- but increase 2,3 DPG so good o2 carrying
- impaired embed hofmeyer pathway
- also seen in renal dz., drying artifact
Acanthocytes
- More prominent but fewer projections that echinocytes
- “spur” cells
- liver disease
- post splenectomy
- McCloud syndrome (mutated Kx gene on X chromosome leads to weak Cell antigens)
- Abetalipoproteinemia
- mutated microsomal triglyceride transfer protein cannot absorb fat from food)
Normal HgB
- HbA a2Beta2 globin chains, 97% in normal adult
- HbA2 a2delta2 globin chains, 3% in normal adult
- HbF a2gamma2 global chains, not in normal adult
Hemoglobin Electrophoresis
- Alkaline - ph 8.5 (cellulose acetate)
- Claus Santa Fat A
- S also runs with D,G, Lapore, India, Hasheron
- C also runs with A2, E, O (“a ceo”)
- Slow running at far left - Constant Spring
- Fast moving at far right - N, I, H, Barts
- Acid - ph 6.0 (citrate agar)
- Christmas Safe A For
- HbA runs with D,A2,G,E,N,I,H, Lepore
Sickle cell dz.
- point mutation in B-globulin chain
- Glutamic acid replaced by valine at position 6
- Hemolytic anemia
- auto-infarcted spleen
- vaso-occlusive crisic
- associated with renal medullary carcinoma
- Hb-F no sickling (infants, hydroxyurea txmt)
- Labs
- in SS, SA (trait), and HbC harlem
- Metabisulfate sickling test
- add Na metabisulfite (causes sickling)
- sickle solubility (dithionite solubility)
- cannot see lines in fluid, examine grossly (also SC, and trait)
Sickle cell disease vs. Trait
- Sickle cell dz (HbSS)
- Hb S > 80%
- Hb F < 20%
- Hb A2 < 4%
- Hb A = 0
- only one band in S position on electrophoresis
- Sickle cell trait (HbAS)
- Hb S 35-45%
- Hb F < 2%
- Hb A2 < 4%
- Hb A 50-60%
- Two bands at S and A
- No sickling on peripheral smear
Hb C
- trait
- asymptomatic
- normal CVC
- target cells and crystals
- Hb C 50%, Hb A 50%
- dz.
- mild anemia, splenomegaly
- garget cells and crystals
- Hb C 90%, Hb F 3%, Hb A 0%
Hb S heterozygosity
- SC disease
- 50% HbS, 50% HbC
- Intermediate severity between SS and SA
- S with a-thal
- less severe
- <35% HbS
- S with B-thal
- more severe
- > 50% HbS
Target Cells
- “codocytes”
- Too much cell membrane
- HbC, E, S dz
- Liver dz.
- hyperlipidemia
- thalessemia
Hg E Dz.
- Mild anemia
- Thalessemia indices
- (MCV <75, erythrocytosis RBC > 5.5 x 10^12)
- Target cells
- common in southeast asia
- HbE runs with HbC on alkaline gel
Thalassemia
- Anemia from improper synthesis of one of the globin chains making up hemoglobin
- CBC
- Thalessemia indeces
- Microcytic (MCV < 70)
- Erythrocytosis (RBC > 5.5 x 10 ^12)
- Thalessemia indeces
- Hb electrophoresis
- a-thalessemia (not making alpha globulins)
- Hb H = beta tetramers, Hb Barts = gamma tetramers
- Normal HbA, HbA, and HbF
- electrophoresis can be normal, or can show fast bands for H and barts
- gene deletion, better prognosis
- beta-thal (not making beta globulin)
- alpha tetramers
- electrophoresis, dec. A, increased A2 and F
- Point mutation, worse diagnosis
- a-thalessemia (not making alpha globulins)
alpha-thalassemia genetics
- -a/aa - silent carrier - normal CVC, normal electrophoresis
- -a / -a - trait - Thal indices, normal electrophoresis
- / - a - HbH dz. - thal indices, Hb H 20%, HbA 80%
- golf ball inclusions on super vital stains
- / - - Hb Barts dz. - thal indices, Hb Barts 100%
- not compatible with life
- trans better than cis (trans in AA, cis in Asians)
Beta thalassemia
- B null cannot make any Beta chains
- B plus can make some Beta chains
- Syndromes
- Beta thal minor
- asymptomatic, mild microcytic anemia
- 94% HbA, 6% HbA2
- normal peripheral smear
- Beta thal intermedia
- not transfusion dependent
- Beta thal major
- No normal beta chain production
- Cooley’s anemia, severe, transfusion dependent
- Hb F 98%, Hb A2 2%
- peripheral smear anisopoikilocytosis, nucleated abcs, target cells, tear drop cells, basophilic stippling
- Beta thal minor
Paroxysmal Nocturnal Hemoglobinuria
- Acquired mutation in PIG-A on chromosome X
- encodes GPI anchor
- anchor serves to link many proteins to cell surface
- CD 55 and CD 59 on flow
- intravascular hemolysis
- complement mediated, chronic hemosidernurva, fe def.,
- thrombophilia
- marrow failuare
- aplastic anemia, aml, mds
*
- aplastic anemia, aml, mds
Diagnosis of PNH
- Complement mediated RBC lysis tests
- HAM acidified serum lysis test (six test tubes look in tube 2 which is red and 5 is not red)
- sucrose lysis test
- Now use flow
- loss of cd55, 59, 16, 66, 14
- FLARE (florescence-labeled aerolysin binds to GPI anchor, so its decreased in PNH)
Aplastic Anemia
- Pancytopenia and hypo cellular bone marrow
- absolute neutrophil count < 500/ml
- platelets < 20 x 10^0
- reticulocytes < 1%
- BM cellularity < 25%
- Many causes, but mostly T-cell mediated autoimmune dz.
- tx with cyclosporin and anti T-cell treatments
- can develop MDS, PNH, or AML
Howell-Jolly Body
single dense inclusion in rbc
msde on DNA
seen in MDS, post splenectomy, SS Dz, ect.
Basophilic stippling
- punctate basophilia
- seen in lead poisoning, pyrimidine 5’ nucleotides dificiency
- MDS, infusion, sideroblastic anemia
- Made of RNA
- multiple blue dots throughout the cell
Pappenheimer body
- multiple inclusions in RBC, usually irregularly distributed
- made of iron (positive on Fe stain)
- seen in iron overload and post splenectomy
Cabot Ring
- Ring shaped inclusion, can look like an 8
- microtubule, remnants of mitotic spindle
- seen in megaloblastic anemia, CDA and lead poisoning
Autoagglutination
- Clumping of RBCs
- May be due to cold agglutins
- IgM
- Patients with Mycoplasma, infections mononucleosis, etc.
- CBC incorrect values
- dec. RBC count
- inc. MCV
- Treat by warming
Congenital dyserythropoietic anemia
- CDAs are a group of rare hereditary disorders
- anima with evidence of ineffective erythroipoisis
- BM shows erythroid hyperplasia, variable internuclear bridging, budding and multi nucleation bridging
- abnormalities at birth but may not be present until middle age
- skeletal abnormalities and dysmorphic features
- Testing
- genetic testing for CDAN1 mutations
- EM for nuclear membrane changes
- CDAN1, SEC23B, CDAN3
- gigantic erythroid, bridging, various weird red cell crap.