Glossary of Hemolytic Anemias
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- What is the definition of a hemolytic anemia?
- Anemia due to the Decreased life span of a RBC, due to increased destruction.
- What are the most important lab findings in a hemolytic anemia?
- SIGNS OF INCREASED DESTRUCTION
- What signs of increased destruction do blood cells exhibit in hemolytic anemias?
(3 things in spcfc re: Red cell (production/shape), and Bone marrow)
- 1. Increased erythropoeisis: polychromasia, incr. retic count, nRBCs
2. BM Hyperplasia - incidental increase in WBCs and plts
3. RBC poik and fragments
- What Chemistry tests show increased destruction? (4)
- 1. Decreased haptoglobin
2. Increased bilirubin
3. Increased urobilinogen
4. Increased LD!*
- What are 4 clinical symptoms of Hemolytic anemia seen in patients?
1. Jaundice (from bilirubin)
2. Associated symptoms
- What are 4 associated symptoms of hemolytic anemia?
- What are 5 systems for classifying hemolytic anemias?
1. **Hereditary vs. Acquired**
2. Extra vs. intravascular
3. Extrinsic vs. Intrins cause
4. Immune vs. Non-immune
5. Acute vs. Chronic
- what are 3 causes/categories of Hereditary Hemolytic Anemias based on physiologic defect?
- 1. RBC membrane defects
2. Metabolism defects
3. Hemoglobin defects
- What are the 6 types of
RBC Membrane defect HA?
- 1. Acanthocytosis
-ALL ARE HEREDITARY
- What is the DAT test?
What is it for?
- Direct Antiglobulin Test
-determines if Immunoglobulins are coating red blood cells to see if the anemia is an IMMUNE process.
- Is Hereditary Spherocytosis an immune process? How do you know?
- No: it is DAT neg.
- What genetically causes HS?
- autosomal dominant genetics OR a spontaneous mutation
- What is the basic problem that causes HS?
- an Unstabilized cell membrane
- What 4 things destabilize the cell membrane in hereditary spherocytosis?
- -Damage to the Spectrin lattice
-Loss of surface area
-Change in cell's normal volume
- What is the purpose of spectrin?
- to allow flesibility and deformibility - depends on ATP
- What is Splenic conditioning?
- Trapping of dmgd cells b/c less deformable; leads to more damage and loss of membrane when the spleen picks at it.
- What is the characteristic RBC morphology of a spherocyte?
- -Very round, but normo/normo.
- What is the PB smear like in Hered sphero, how does it affect the MCHC, MCV, RDW, and RPI??
- -Increased MCHC but normal MCV
-Normo/normo just smaller
-Incr. retics, high RPI
-Spheros, stomatos, shistos
- what are some clinical symptoms of HSphero?
- Jaundice, splenomegaly, anemia
- What are diagnostic tests for HS?
- Osmotic fragility
-Initial = .65%
-Complete = .35%
DAT = neg
- If a patient with HS has a splenectomy, what would you see on the periph blood smear?
-When would you splenectomize?
- -Howell jollies
-As a last resort therapy
- What's a normal Osmotic fragility?
- -Initial: .45%
- What is the HS osm. fragility?
- Initial: .65%
- Why does hemolysis increase as NaCl% decreases?
- Because water is increasing and this is what causes hemolysis.
- What are 4 circulatory complications of HS that can occur?
1. Obstructive jaundice
3. Hemolytic crisis
4. Aplastic crisis due to infctn
- What is HE?
- Hereditary elliptocytosis
- How is HE inheredited?
- As an autosomal dominant gene.
- What is the basic cause of abnormality in HE?
- Spectrin association is impaired and it can't recover from the shear force of going through the spleen - remains oval as result.
- What are two subcategories of HE?
- -Infantile Poikilocytosis
-Southeast Asian Ovaolocytosis
- What does infantile poik look like?
- a burn patient, but self-fixes in a year. then it's normal heredit. elliptocytosis
- what do cells look like in SAO?
what benefit is there to this?
- southeast asian ovalocytosis... cells are spoon-shaped discs, w/ double slits.
Band-3 defect confers malaria resistance.
- How is Hereditary Pyropoikilocytosis inherited?
- As a DOUBLE HETEROZYGOTE - one defect from each parent.
- What causes the membrane defect in Hereditary pyropoikilocytosis?
- -An excess in spectrin dimers
-Membrane is unstable and lyses at 45 C instead of the normal 49 C.
- What does the blood smear look like in hereditary Pyropoik?
- LIKE A SEVERE burn patient
- What is the prescription for HP?
- What causes the membrane defect in hered. acanthocytosis?
- Increased surface area because cells can't synthesize Beta-lipoprotein B.
- How does the body respond to the increased SA in HAcanth?
- By increasing extravascular hemolysis.
- What causes acquired acanthocytosis?
- Changes in cholesterol levels (plasma).
Increased cholesterol causes RBC membrane projections - fat clumps on the outer phospholipid layer.
- What is the membrane defect that causes hered. stomatocytosis?
- Defective Na/K pump -> H2O in RBCs increases -> Makes cells plump so only one side is concave.
- What test supports herid stomatocytosis finding?
- -Increased osmotic fragility
- What are 4 things that can cause acquired stomatocytosis?
- 1. Liver disease
3. other hematolog. problems
4. Artifact from drying
- what the heck is hereditary XEROCYTOSIS?
- Condition where RBCs are dehydrated b/c of low potassium levels.
- what happens to the hemoglobin in xerocytosis?
- it puddles; so you'll see targets and spiculated cells too.
- What other lab values are indicative of xerocytosis?
- Increased MCHC
Decreased osmotic fragility (cells are more viscous like sickle cells for instance)
- what hemoglobinapathy does xerocytosis kinda look like?
- Hgb C
- What are 3 hemolytic anemias due to METABOLISM DEFECTS?
- 1. Pyruvate Kinase deficiency
2. G6PD deficiency
- how is pyruvate kinase deficiency inherited?
- As an autosomal recessive gene - must have two to express it.
- What is the problem in PKD?
What cells are affected?
- -Cells can't produce enough ATP.
-Older cells affected.
-Severity can vary
- What is the typical morphology seen in PKD?
- There isn't any.
Might see acanthocytes if post splenectomy.
- What lab value in particular is elevated in PKD?
- Total bilirubin - unconjugated bilirubin is increased.
- What metabolism pathway is PK deficient in, and what is the result?
- Embden-meyerhof glucose pathway; only generates 2 ATP inst. of 3
- How does the body respond to decreased o2 transfer in PKD?
- Increases 2,3-DPG levels to 2x the normal amount
- what tests are used to confirm PKD?
- -PK assay
- How is g6PD deficiency inherited?
- As a sex-linked recessive gene - so only MALES get it.
- How is G6PD deficiency expressed
- Females have variable activity cuz its sex-linked recessive.
Males have full expression.
- Why is G6PD important?
what does its decrease result in?
- It protects Hgb from oxidants.
Decrease means oxidant stress.
- What type of cells do you see in G6PD?
- COOKIE BITE CELLS.
- When a patient has a G6PD episode, what 4 symptoms will you see?
(2 patient-related, 2 blood smear related)
-Heinz bodies w/ supravital
- What induces hemolytic episodes in Mediterraneans with G6PD deficiency?
- FAVA BEAN EXPOSURE
- For G6PD defic, what are
-3 screening tests
-1 confirmatory test
1. Ascorbate Cyanide
2. Florescent spot
3. Heinz Body
Confirmatory: G6PD assay
- How is a Heinz body test performed? (2 steps)
- 1. Expose cells to an oxidizing substance.
2. Stain with Cresyl or methyl violet.
3. Evaluate number of cells w/ Heinz bodies
- what is a Normal heinz body test, what is abnormal?
- Normal: a FEW cells w/ multiple heinz bodies
Abnormal: MANY w/ them
- How is a G6PD assay run?
- 1. Add G6P and NADP to sample; the G6PD will convert it to 6-phosphogluconate and NADPH which flouresces.
- Other than genetic inheritance, how can G6PD deficiency be acquired?
- By taking oxidant drugs, and dehydration.
- What are 2 other Metabolism defects that cause hemolytic anemias (other than PK and G6PD)
- 1. Pyrimidine 5 Nucleotidase
2. Embden-Meyerhof pathway enzyme deficiencies
- What are the 4 categories of acquired hemolytic anemias?
- 1. Immune
2. Drug induced
- What 3 various "Agents" can cause hemolytic anemia?
- 1. Physical
- What are the 2 types of Immune HA?
- 1. Allo (nonself)
2. Auto (self)
- What's actually causing hemolysis in auto-immune HA?
- 1. Humoral antibody coats cells and complement lysis or RES phagocytosis ensues.
- What 2 antibodies are the culprits of cell death in auto HA?
- IgM = activates complement
IgG = activates RES
- How does IgM and IgG action differ, and which is immediate or delayed?
- IgM = immediate; causes INTRAVASC hemolysis by activating complement.
IgG = delayed; causes EXTRAVASC hemolysis by coating cells for RES phagocytosis.
- What test determines if allo-immune HA is IgM of IgG mediated? How?
- DAT - determines if Ab and Complement are coating cells (polyspecific). If positive, do monoclonal to find out which.
- What happens in a DAT test?
- 1. Add Anti-IgG/complement antibody to sample.
2. Add Antibody to previous reagent
3. If IgG/complement are on RBCs, agglutination. test further to see which.
- What 2 major things will cause an alloimmune reaction HA?
- 1. transfusion reaction
2. HDN hemolytic disease of newborn.
- What are 2 categories of HDN, and which is more severe?
- ABO group - shows spherocytes
Rh group - nRBCs b/c reaction is stronger.
- How is AUTO-immune HA classified? (2 types)
Which is more common?
- by temperature:
Warm (hemolysis at 37)
Cold (hemolysis at 4)
-Warm is more common.
- What antibody type is active in WAIHA?
What triggers this to happen?
- IgG; triggered by virus infection.
- What 3 lab findings characterize WAIHA?
- -DAT can be pos or false neg.
- What antibody type is active in CAIHA?
- IgM and Complement
- What lab findings do you NOT see in CAIHA that are in WAIHA?
- spherocytes and nRBCs.
- What causes CAIHA, and in whom?
- it's idiopathic, generally in old people w/ infections and malignant disease.
- WHAT IS THE MOST COMMON CULPRIT OF CAIHA?
- mycoplasma pneumonia (contaminant on brian/haley's cultures?)
- How will DAT vary for CAIHA and WAIHA?
- If monoclonal is added, will show C' and IgM for CAIHA versus only IgG for WAIHA.
- what type of hemolysis occurs in CAIHA?
- extra AND intravascular
- what is a very big hint on the PBS and indices that a patient has CAIHA?
- very high MCHC and agglutinated cells - autoagglut. occurs below room temp.
- What is PCH?
What population is it seen in?
What antibody causes it?
- -Paroxysmal cold hemoglobinurea
-Biphasic IgG Donath Landsteiner
- How does IgG cause PCH?
- It binds RBCs after exposure to cold and then binds complement for MAC attack when it warms up. Hb then spills into urine.
- What characterizes PCH?
What likely triggers it?
- Dark urine - hemoglobinurea.
Assoc. with respiratory viral infections.
- What drugs induce HA?
(2 actual drugs, one sideeffect)
-Immune Complexes activate C' and cause intravasc. hemolysis
- What are 7 immune complexes that can cause HA?
- 1. Babesiosis
- What do chemicals that cause HA do to red cells?
- 1. Oxidize/denature Hb
2. Cause Heinz bodies
3. Cause bite cells
- What Wisconsin bug causes Venom-induced HA?
-what type of hemolysis?
- -Brown recluse spider
- What are 4 physical agents that cause HA?
- 1. Heat (burns)
3. Prosthetic devices
- What is the pathologic process that causes MAHA?
What type of hemolysis?
- Microangiopathic HA -->
Fibrin in vessels tears up RBCs.
Intravasc AND Extravascular
- What are some cuases of MAHA?
- 1. Hypertension
2. Disseminated carcinoma
3. Hemolytic Uremic Syndrome (from ecoli)
4. Thromb. Thrombocytopenia Purpura (Herriod's daughter)
- what is "PNH"?
What is pretty unique about it?
- Paroxysmal Nocturnal Hemoglobinurea
-an ACQUIRED membrane defect
- How can a membrane defect (in formation) be acquired?
- By damage to stem cells in the bone marrow at a previous time.
- What cells are affect in PNH?
- Stem cells -> so everything down stream: RBCs, WBCs, plts.
- What causes the hemolysis in PNH?
- cells are susceptible to complement lysis.
- what are patients with PNH mostly suffering from
- waking up every morning with rust colored urine.
- what kind of blood picture and lab findings do you see in PNH?
- -Increased retics/polychromasia
-Incr. bilirubin, decr. haptogbn
-Hbemia, Hburia, Hmsiderinurea
- What 3 tests are used to diagnose PNH?
- 1. Sucrose hemoysis test (screening test)
2. Ham's test
3. CD59 w/ flow cytometry
- What's the basic principle of the Sucrose hemolysis test?
- Cells are susc. to complement; adding complement in sugar water will causes >5% lysis in 30 min.
- What's the difference betwen the Sucr. hemolysis test and Ham's?
- Ham's is acidified - cells are even more C' susceptible in acid.
- what is CD 59?
- a complement regulating protein that is missing on PNH cells; unregulated complement lyses RBCs.
- What's the only visible morphology in PNH?
- polychromasia; that's it.
- what patient popln is PNH most seen in?
- older people.
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