Diseases of RBCs Flashcards
Characteristics of Pathologic Cold Agglutinins.
- Broad thermal range
- Spontaneous autoagglutination at RT
- Titer >1,000 at 4 degrees
Cryoglobulinemia:
-Blood smears
Pale purple, cloudy aggregates of protein
Stomatcoytic type of HE (SAO) facts (2).
- Band 3 protein defect
- Protection against P. vivax malaria
At what % of total Hi does cyanosis occur?
10% of total Hb (or 1.5 G/dL)
Thalassemic indices: RDW
Normal to slight increase
*Markedly INCREASED in IDA
What is the % HbF at 6 months; 1 year?
- <10%
- <5%
What causes PCH?
-IgG biphasic hemolysin (Donath-Lansteiner Ab)
Hereditary persistence of HbF (HPFH) is caused by what?
Delayed switch from gamma (y) to beta or delta chains
What and where are Type I Cryoglobulins found?
- Monoclonal Immunoglobulins
- MM or Waldenstrom
MC etiology in Hereditary Stomatocytosis.
Abnormal Na+/K+ permeability
*Ass w/ Rh null phenotype
Hereditary Spherocytosis (HS) gene mutation.
ANK1 (ankyrin)
Autosomal Dominant
T/F: Single gene deletions are asymptomatic with a normal CBC and normal electrophoresis.
True
Lab findings in G6PD.
- Poikilocytosis, bite cells, blister cells
- Heinz bodies (w/ supravital dyes)
- Extravascular hemolysis (Jaundice, Increased LD)
Explain the Donath-Landsteiner Test.
2 Vials of blood
- Vial 1 at 37; Vial 2 at 4 for 30 minutes
- both at 37 for 30 minutes
- Positive test - Hemolysis in Vial 2
What are the findings in Hb Bart?
- Severe Hemolytic anemia
- Hb Bart on electrophoresis
Secondary CAIHA is a transient condition associated with infection. Which organisms is associated with:
- IgM anti-I
- IgM anti-i
Mycoplasma pneumonia (anti-I) EBV (anti-i)
What are Type II Cryoglobulins made up of?
Mixture of 2 polyclonal Igs
Thalassemic indices: P. Smear
- Microcytosis
- Target cells
- Basophilic stippling
The Donath-Landsteiner Ab has specificity for what?
Anti-P
HbC disease (homozygous CC) Hb ratios
HbC - 90%
HbF - 7%
HbA2 - 3%
HbA - 0%
Hemoglobin Lepore runs with what on alkaline gel?
HbS, usually only 15% of total Hb
*Actual HbS is rarely present at this quantity, so suspect Lepore in this scenario
3 alpha gene deletions result in ___ disease.
HbH
How many gene deletions are result in alpha-thalasemia TRAIT; and what are the findings?
- 2 gene deletions
FINDINGS:
-thalassemic indices
-Normal HbA2 percentage
4 alpha gene deletions result in ___ disease.
Hb Bart
T/F: HbF exerts an inhibitory effect on HbS polymerizaiton.
True
What causes Cold Autoagglutinin disease (CAD)/CAIHA?
-IgM antibodies to anti-I (most commonly)
Average lifespan of HbSS RBC
17 days
HbG and HbD run with what on alkaline gel?
HbS (do sickle cell screen or citrate gel)
What are causes of secondary WAIHA? (70% of cases)
- Hematolymphoid (CLL/SLL)
- Inherited immunodeficiencies (CVID,IgA,etc.)
- Collagen vascular disease
- Thymoma
The membrane defects in PNH is caused by what?
Decreased Glycosyl Phosphatidyl Inositol (GPI) anchors
Cryoglobulinemia is a systemic immune complex disease characterized by a distinctive clinical syndrome, what are the symptoms? (7)
- Palpable purpura (leukocytoclastic vasculitis)
- Arthralgia
- Hepatosplenomegaly
- Lymphadenopathy
- Anemia
- Sensorineural deficits
- Glomerulonephritis
Beta-Thalasemia trait (Heterozygotes) has what changes in Hb ratios? (what if also Iron Deficient)
HbA2 - >3.5%
HbF - Normal to INcreased
*If iron deficient the HbA2 may be normal
alpha or beta Thalassemia??
Manifestations are present at birth.
- Alpha
* Beta become evident >6 months
What causes a warm autoimmune hemolytic anemia (WAIHA)?
warm reacting IgG autoantibody
3 types of Hereditary Elliptocytosis
- Common type (HPP; African Americans)
- Spherocytic type
- Stomatocytic type (Southeast Asian Ovalocytosis)
Sickle Cell Disease (genotype SS) Hb ratios.
HbS - >80%
HbA - 0%
HbA2 - 1-4%
HbF - 1-20%
Positive or Negative:
What is the DAT in WAIHA?
Positive (nearly ALL cases)
*usually polyspecific and anti IgG reagents
What is the presentation of PCH?
Paroxysmal episodes of hemoglobinuria associated with COLD Exposure
Which type of Cryoglobunimia is most commonly seen?
Type 2
HbSC disease Hb ratios
HbS - 50%
HbC - 50%
Beta-Thalasemia
There is a total of # copy of the __- gene on each chromosome __, for a total of __ productive genes.
1, Beta, 11, 2
*There i a total of on copy of the B gene (HBB) on chromosome 11, for a total of 2 productive genes.
G6PD inheritance
X-linked recessive
Sickle Cell Trait (genotype SA) Hb ratios.
HbS - 30-45%
HbA - 50-65%
HbA2 - <3%
Homozygotes (Beta-Thal) hs what Hb ratios?
HbF - 50-85%
HbA - little to NONE
HbA2 - Normal to INcreased
Hereditary Elliptocytosis/Ovalocytosis gene mutation.
Spectrin a-chain
Autosomal Dominant
Mutation in Hemoblobin Constant Spring
mutation in the alpha globin STOP codon; producing abnrmally long transcript
Which population is is most common in Paraxysmal Cold Hemoglobinuria (PCH) and what is it associated with?
- Children
- Post-Viral (Measles, Mumps, VZV, Mono)
*originally described in syphilis
Abnormality in Methemoglobin (Hi, hemiglobin)
Iron is in the Oxidized ferric (Fe3+) state instead of usual ferrous (Fe2+) state.
Incapable of combining with Oxygen
HbSC disease manifestations
Between SS and SA
In alpha-thalassemia 1 (a0 thalassemia), chromosome 16 has __ deleted alpha genes. What race is this prevalent in?
- 2
- Asians
What are Type II Cryoglobulin made up of?
Mixture of Monoclonal IgM and Polyclonal IgG
alpha-thalasemia:
There are __ copies of the __ gene on each chromosome __, for a total of __ genes.
2, a, 16, 4
*There are 2 copies of the alpha gene on each chromosome 16, for a total of 4 genes.
What characteristic finding of PCH may be seen on P. smear?
Intraneutrophilic hemophagocytosis
What clinical condition is the MCC of Type II cryoglobinemia?
HCV
What is seen in renal biopsies of cryoglobulinemia?
- Membranoproliferative Glomerulonephritis (MPGN)
* Deposits may produce the appearance of thrombotic microangiopathy
How are Beta-Thal Major and Intermedia distinguished ?
Transfusion dependence (MAJOR)
Characteristics of Nonpathologic Cold Agglutinins.
- React most strongly at 4, up to 22 degrees
- Titer <64 at 4 degrees
Thalassemic indices: MCV/RBC count ratio
<13 favors thalassemia
*>15 favors IDA
What antigens does the pathogenic antibody in WAIHA usually have broad reactivity with?
Rh Antigens
HbC disease manifestations.
- Mild hemolytic anemia
- Splenomegaly
- Target cells (numerous)
- Hexagonal or Rod-shaped CRYSTALS
What is the abnormality in Hb Lepore?
fusion between Delta and Beta genes
Intravascular or Extravascular Hemolysis in WAIHA?
Extravascular
Hemoglobin S alteration.
B6 glu->val
HbG is a defect in what chain?
Alpha
What are the findings in HbH?
- Hemolytic anemia
- Fast moving HbH on electrophoresis
Thalassemic indices: RBC count
Normal to Increased RBC count
What is the % of HbF at term?
30-40%
Most alleles with thalassemic phenotype result from what type of a mutation?
Point
HbD is a defect in what chain?
Beta
T/F: Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired clonal red cell disorder.
True
Incidence of Sickle Cell Trait in AA.
10%
What is the mutation/gene associated with PNH?
-PIG-A on X chromosome
What is the 2nd MC abnormal Hemoglobin worldwide (after S)?
HbE (B26 glu->lys)
*Southeast Asia common
What is the treatment for Methemoglobin?
Methylene blue, reduces Hi to Hb
The leukocyte alkaline phosphatase (LAP) score is (increased/decreased) in PHN.
Decreased
Pyruvate Kinase (PK) deficiency findings & Inheritance
- Chronic hemolysis (varied severity)
- Echinocytes (dessicocytes)
- Extravascular Hemolysis
- Audosomal Recessive
What is the % of HbF in Combine HbSS/HPFH and what are symptoms?
- 25%
- MILD symptoms (No anemia or vasoocclusive episodes)
HS lab values.
- MCHC Increased
- Reticulocyte count Increased
- MCV & MCH normal
Fluorescent aerolysin (FLAER), obtained from what, binds specifically to GPI?
Aeromonas hydrophila
Flow cytometry markers for PNH:
- RBCs
- Granulocytes/monocytes
- CD55,59
- CD14,15,16,33
Combined Sickle cell (HbSS) and HPFH is found in what percentage of homozygous HbSS?
1 percent (~1 in 100)
Definition of cryoglobulins.
Immunoglobulins that precipitate reversibly at Low Temperatures
How do you detect cyroglobulins?
- Blood drawn at 37 and kept till clotted
- Centrifuge at 37
- Serum stored at 4 for >3 days
- Centrifuge at 4
- Any precipitate that forms is cryoprecipitate
- Electrophoresis for characterization
In alpha-thalassemia 2 (a+ thalassemia), chromosome 16 has __ normal and __ deleted alpha gene. It is the most common genotype in what race?
- 1, 1
- African Americans
After age 2 what is the normal % of HbF?
<1%
In all tissues, what is the basic pathologic lesion in cryoglobulinemia?
-what is seen on EM?
Vasculitis
*EM - Subendothelial immune complex deposits with a fibrillary or tubular structure in a fingerprint like pattern
MOA of hydroxyurea in SS.
Increase HbF and lessen severity of SS.
PNH may evolve into what?
- Aplastic Anemia (and or)
- AML
