Diseases of red blood cells Flashcards
1
Q
Hereditary spherocytosis
- Clinical presentation
- Incidence
- Inheritance
- Gene affected
- Laboratory findings
A
-
Clinical presentation
- neonatal jaundice
- adult with gallstones and splenomegaly
- anemia or compensating reticulocytosis
- Incidence in US is 1 in 5,000
- common in Northern Europe with incidence of 1 in 1,000
- most common red cell disorder in person of northern European descent
- Autosomal dominant usually
- ANK1 (ankyrin)
-
Labs
- increased MCHC
- MCV and MCH are normal
- elevated retic
-
extravascular hemolysis findings
- increased LDH
- increased bilirubin
- osmotic fragility and autohemolysis tests abnormal
- unlike autoimmune hemolytic anemia, which also shows spherocytes, the DAT is negative
2
Q
Hereditary elliptocytosis/hereditary ovalocytosis
- Inheritance
- Mutation
- Laboratory findings
- Incidence
- Types and clinical presentation
A
- Usually autosomal dominant
- Mutations in spectrin alpha chain
- Labs
- elliptocytes are twice as long as they are wide, comprise >25% of red cells
- mild extravascular hemolysis
- 1 in 2,500 in the US to 1 in 100 in parts of Africa
- Types
-
common type
- African Americans
- hereditary pyropoikilocytosis
- sensitivity of red cells to heat
- this is a transient neonatal expression of common HE
-
spherocytic type
- double heterozygosity for HS and HE
-
stomatocytic type, aka Southeast Asian Ovalocytosis
- Malaysia
- caused by band 3 protein defect
- confers protection against P vivax
-
common type
3
Q
G6PD deficiency
- G6PD is needed for
- pathophysiology
- Labs
- Geographic distribution
- Inheritance pattern
- Testing should be done when?
A
- G6PD is needed for production of NADPH and reduced glutathione for protection from oxidants
- G6PD deficient red cells are hypersensitive to oxidant stress, including
- medications
- methylene blue
- sulfa drugs
- nitrofurantoin
- primaquine
- fava beans
- infection
- medications
- Hemolysis is episodic, precipitated by oxidant stress
- Labs
- poikilocytosis
- bite cells
- blister cells
- heinz bodies (with supravital stains)
- findings of extravascular hemolysis (jaundice, increased LDH)
- Prevalent in Africa, southern Europe, Middle East, Southeast Asia, and Oceania
- X linked recessive inheritance
- testing for this shoud be done when patient is not hemolyzing to avoid false negative from reticulocytes with adequate G6PD
4
Q
Pyruvate kinase deficiency
- PK does what?
- Labs
- Inheritance pattern
- Geographic distribution
A
- PK catalyzes rate limiting step in the Embden-Meyerhof (glycolysis) pathway; main source of red cell ATP
- Labs
- chronic hemolysis (extravascular) - jaundice, elevated LDH
- echinocytes (dessicocytes)
- Autosomal recessive
- Worldwide
5
Q
Hemoglobin S
- amino acid change
A
- valine encoded instead of glutamate at position 6 of the beta chain (glu to val)
6
Q
Sickle cell trait
- % of hemoglobin types
- CBC and smear
- Screening test
- Clinical manifestations
A
- Genotype SA
- Hemoglobin types
- 35-45% HbS
- 50-65% HbA
- <3% HbA2
- Normal CBC and smear
- Screening tests are positive
- metabisulfite test
- dithionate test
- Clinical presentation
- usually asymptomatic
- increased incidence of
- hematuria
- isothenuria
- papillary necrosis
- medullary carcinoma of the kidney
- exercise induced rhabdomyolysis
- splenic infarcts in hypoxic conditions, such as exposure to high altitude
7
Q
Sickle Cell Disease
- Genotype
- Length of time of RBC survival
- Hemoglobin types
A
- SS
- RBC survival is 17 days instead of 120 days
- Types of hemoglobin
- >80% HbS
-
1-2% HbF
- inhibits HbS polymerization
- at birth HbF prevents development of clinical symptoms
- by 6 months HbS > 50%, when symptoms start
- combined sickle cell disease hereditary persistence of fetal hemoglobin (SS-HPFH) is clinically mild
- treatment with hydroxyurea is meant to increase HbF
- 1-4% HbA2
- 0% HbA
8
Q
Hb SC disease
A
- 50% HbS and 50% HbC
- clinical manifestations are intermediate in severity between SS and SA
9
Q
Hemoglobin SA/alpha thalassemia
percentages of hemoglobin types
A
- decreased percentage of HbS as compared to SA
- in single gene alpha deletion, there is 30%-35% HbS
- in 2 alpha gene deletions there is 25%-30% HbS
10
Q
SA/beta thalassemia
A
- increased proportion of HbS (>50%)
- 1-15% HbF
- disease manifestations can be severe
11
Q
Hemoglobin C
- amino acids
- trait (hemoglobin percentages, symptoms, smear)
- disease (hemoglobin percentages, symptoms, smear)
A
- glutamate becomes lysine at position 6 on beta chain
-
Hemoglobin C trait (AC)
- 40-50% hemoglobin C
- generally asymptomatic
- peripheral smear has target cells
-
Hemoglobin C disease (CC)
- Types
- 90% HbC
- 7% HbF
- 3% HbA2
- 0% HbA
- Mild hemolytic anemia
- Splenomegaly
- Numerous target cells
- Hexagonal or rod shaped crystals
- Types
12
Q
Hemoglobin E
- amino acids
- geographic distribution
- prevalence
- CBC
- smear
- symptoms
A
- Beta 26 glutamate to lysine
- Southeast Asia
- 2nd most common abnormal hemoglobin worldwide (after S)
- CBC shows thalassemic indices and the peripheral smear numerous target cells
- typically mild, but coinheritance with beta thalassemia may be severe
13
Q
Hemoglobin D and G
A
- Clinically normal
- HbD is beta chain defect
- HbG is an alpha chain defect
- Both run with HbS on alkaline gel
- absence of HbS can be determined by sickle screen study or by citrate gel
14
Q
Hemoglobin Lepore
- CBC
- geographic distribution
- electrophroesis
- genes
A
- Thalassemic red cell indices
- Mediterranean, especially Italy
-
Runs with HbS on alkaline gel, but usually only ~15% of total Hb
- Actual HbS is rarely present in this quantity, so Lepore should be suspected
- Sickle screening tests are negative
- Hb Lepore is result of fusion between delta and beta genes
15
Q
Hemoglobin Constant Spring
A
- thalassemic red cell indices
- Southeast Asia
- mutation in alpha gene stop codon, producing abnormally long transcript
16
Q
Unstable hemoglobins
- smear (also seen in what conditions?)
- types of Hb
A
- result in Heinz bodies and bite cells
- Hb Hammersmith, Ann Arbor, Koln
- Note: Hb Bart and HbH (severe alpha thal) are also associated with Heinz body anemia
17
Q
Methemoglobin
- what is it
- % of total Hb
- low level maintained by
- hereditary versus acquired
- appearance of blood
- ways to measure it
- treatment
A
- Hemoglobin with iron in the oxidized ferric (Fe+++) state
- Cannot combine with O2
- Normally, up to 1.5% of total Hb is Hi (methemoglobin)
- low level maintained by the action of the NADH dependent methemoglobin reductase system
-
hereditary methemoglobinemia
- deficient methemoglobin reductase or abnormal HbM upon which this enzyme cannot act
- cyanosis appears at 6 months of age
-
acquired methemoglobinemia
- exposure to drugs or chemical that increase formation of Hi
- nitrites, quinones, phenacetin, and sulfonamides
- blood is grossly chocolate brown
- cooximeter can measure methemeglobin directly (pulse ox and ABG cannot detect Hi)
- treatment = methylene blue, which reduces Hi to Hb
18
Q
Sulfhemoglobin
- what is it
- smear
- % total hemoglobin normally and when cyanosis occurs
- precipitated by
A
- hemoglobin oxidized in presence of sulfur
- when further oxidized, SHb preciptates to form Heinz bodies
- SHb cannot transport oxygen
- normally, SHb <1% of total Hb
- cyanosis manifests at 3-4% or 0.5 G/dl
- SHb may increase after exposure to sulfonamides and in presence of C perfingens bacteremia (enterogenous cyanosis)
19
Q
Carboxyhemoglobin
A
- CO binds tightly to hemoglobin forming carboxyhemoglobin (HbCO)
- CO has even greater avidity for fetal hemoglobin
- CO directly toxic to intracellular oxidative mechanisms
- toxic effects vary with proportion of HbCO
- Normally HbCO is <=1%
- ABG and pulse ox cannot detect HbCO
- Smokers have up to 6%
20
Q
Thalassemic indices
A
- Microcytosis
- Low hematocrit
- Normal to elevated RBC count
- RDW normal to slightly increased (in contrast, markedly increased in IDA)
- MCV/RBC count ratio < 13 favors thalasemmia
- MCV/RBC count ratio > 15 favors IDA
- Smear shows microcytsosis, target cells, basophilic stippling
21
Q
Beta thalassemia
- genetics (chromosome, alleles, mutations)
- symptoms start when
- heterozygotes vs homozygotes (HbA2, HbF, HbA)
- intermedia vs major
- delta-beta thalassemia
- Hb Lepore - relative amounts of Hb
- tetramers in Beta thal
A
- one copy of the beta gene on each chromosome 11, which make two genes
- most beta thal results from point mutation
- pathogenic alleles Bo or B+
- Symptoms not be apparent until 6 months of age
-
Heterozygotes (Beta thal trait) have
- high HbA2 (>3.5%)
- normal to increased HbF
- may show normal A2 if patient is iron deficient
-
Homozygotes have
- increased HbF (50-95%)
- normal to elevated HbA2
- little to no HbA
- Beta thal intermedia and major are distinguished by dependence of the latter on transfusion
- in delta-beta thalassemia (deletion of delta and beta) there is a
- normal HbA2
- elevated HbF (5-20%)
- In Hb Lepore (fusion of delta and beta) there is
- normal quantity of HbA2
- slightly elevated HbF
- band in S region comprising 6-15% (Hb Lepore)
- Form alpha tetramers
22
Q
Alpha thalassemia
- describe genes
- genetic alteration
- haplotypes
- symptoms and labs in single gene, 2 gene, 3 gene, and 4 gene deletions
A
- 2 copies of the alpha gene on each chromosome 16
- most thalassemia result from large structural deletion
- haplotypes characterized as
-
alpha thal 2 (alpha+ thalassemia)
- chr. 16 has one normal and one deleted alpha gene
- most common genotype in African Americans
-
alpha thal 1 (alpha0 thal)
- chr 16 has 2 deleted alpha genes
- Asians
-
alpha thal 2 (alpha+ thalassemia)
-
single gene deletions
- asymptomatic
- normal CBC
- normal electrophoresis
-
2 gene deletions
- alpha thal trait
- thalassemic indices
- normal percentage of A2 (normal electrophoresis)
- in absence of iron deficiency, this can be interpreteted as c/w alpha thal trait
-
3 gene deletions
- HbH disease (beta tetramers)
- hemolytic anemia
- Heinz bodies
- fast moving HbH on electrophoresis
-
4 gene deletions
- Hb Bart disease
- fetal (gamma) hemoglobin tetramers
- severe hemolysis - hydrops fetalis
- hypochromic nRBCs
- Hb Bart on electrophoresis