Congenital Hemolytic Anemias

Front 1

What is erythropoiesis?

Back 1

The process of red blood cell formation

Front 2

Generally, what is the balance between creation and destruction of RBCs? What's the turnover rate?

Back 2

Equivalent

1%

Front 3

What's the main stimulus for erythropoiesis?

Back 3

O2 deficiency

Front 4

What's the sensor in oxygen deficiency that causes erythropoiesis?

Back 4

The kidney

Front 5

What system removes old RBCs from the circulation?

Back 5

Reticluendotheilial system

Front 6

What is hemolysis?

Back 6

Accelerated destruction and/or clearance of RBCs

Front 7

What are the secondary effects of hemolysis?

Back 7

Decreased O2 delivery to tissues--> hypoxia --> erythropoietin --> increased RBC production by marrow

Front 8

What's typically released from RBCs during hemolysis?

Back 8

Hgb

LDH

Front 9

What protein does free Hgb bind to in the serum?

Back 9

Haptoglobin

Front 10

What is the breakdown product of hemoglobin?

Back 10

Iron + unconjugated bilirubin

Front 11

What are the laboratory findings during hemolysis?

Back 11

Elevated serum free Hgb
High serum LDH
Low serum haptoglobin
High unconjugated bilirubin

High reticulocyte count

Front 12

What are some of the ways that bilirubin is excreted?

Back 12

Fecally: urobilinogen
Urine: urobilinogen

Front 13

What is the pathway that bilirubin takes to be excreted?

Back 13

1. Breakdown in blood
2. Unconjugated bilirubin (or bilirubin conjugated to Z protein,glucuronic acid) transported toliver
3. Enters biliary system
4. In small intestine broken down by a bacterial protease
5. 90% excreted inFECES

If lots and lots of bilirubin, you can have excretion in the kidney

Front 14

What is the definition of compensating hemolysis?

Back 14

Hemolysis without anemia/mild decrease in Hg

Accelerated destruction is matched by increased production

Front 15

How much of the RBC volume can the marrow compensate for?

Back 15

10%

Front 16

What is the definition of a hemolytic anemia?

Back 16

The destruction of RBC >> production

Front 17

What are the different types of congenital anemias?

Back 17

Sickle cell
Thalassemia
Spherocytosis
G6PD deficiency

Front 18

What are some of the different types of acquired hemolytic anemias?

Back 18

Autoimmune hemolysis
MAHA
Drug induced

Front 19

What are some of the differences that you'll find between an intravascular hemolytic anemia and extravascular?

Back 19

Intravascular: hemoglobinemia, hemoglobinuria, consumption of the haptoglobin

Front 20

What are some of the intrinsic causes of hemolytic anemias?

Back 20

RBC membranes
RBC cytoplasmic enzymes
Abnormal Hgb

Front 21

What are some of the extrinsic factors that can cause hemolytic anemias?

Back 21

Acquired coditions
Oxidation
Immune-mediated
Mechanical destruction

Front 22

What are some labs that you should order up to determine the etiology of a hemolysis?

Back 22

Blood smear
Hgb electrophoresis
RBC fragility test
RBC enzyme level assay
Specific mutation studies
Coomb's test

Front 23

What congenital hemolytic anemias show abnormalities in hemoglobin? What's the test for this?

Back 23

Thalassemias
Sickle cell disease

Test: Hgb electrophoresis

Front 24

What congenital hemolytic anemias show abnormalities in the RBC membrane? What's the test for this?

Back 24

Hereditary spherocytosis
Hereditary elliptocytosis

Test: osmotic fragility test

Front 25

What congenital hemolytic anemias show abnormalities in RBC enzymes? What's the test for this?

Back 25

G6PD deficiency
Pyruvate kinase deficiency

Test: enzyme levels

Front 26

Where are the thalassemias typically found?

Back 26

Where malaria is endemic

Possibly protective

Front 27

What are the different kinds of hemoglobin chains found?

Back 27

Alpha
Beta
Gamma Delta

Front 28

What are the types of hemoglobin that are normally found in adults?

Back 28

Hg A: Alpha2, Beta2 (96-98%)

Hg A2: Alpha2, Delta2 (2-3%)

Hg F: Alpha2, Gamma2 (0-1%)

Front 29

How many copies of each of the Hgb genes does each person have?

Back 29

Beta chain: 2 copies

Alpha chain: 4 copies

Front 30

What are the different kinds of thalassmias?

Back 30

Beta

Alpha

Front 31

What types of mutations typically cause the thalassmias?

Back 31

Point mutations

Front 32

What does a peripheral blood smear look like for a thalassemia?

Back 32

Hypochromia
Microcytosis

Also, you can have hemolysis

Front 33

Who typically gets beta thalassmias?

Back 33

Mediterannean people

Africans

Front 34

What type of a mutation happens in Beta thalassemias?

Back 34

Mutation; not a deletion

Front 35

What are the different subtypes of beta thalassemias?

Back 35

2 phenotypes:

Thalassemia beta minor (trait): heterozygous
Thalassemia beta intermediate: homozygous mutated; not as severe
Thalassemia beta major: homozygous mutated; very severe

Front 36

What are the symptoms of thalassema beta major?

Back 36

Severe anemia

Multi-organ failure at a young age

Front 37

What population does not show the effects of a beta thalassemia?

Back 37

Fetus/infants:

Switching to the beta chain causes the symptoms to come out.

Front 38

What are the findings on Hg electrophoresis in beta thalassemias?

Back 38

HgA is decreased
HgA2 is mildly increased
HgF is mildly increased

Front 39

What are the typical numbers for Hg in a person who is normal, trait, and major?

Back 39

Front 40

What are the subtypes of alpha thalassemia?

Back 40

Silent carrier: "-a/aa"
Thal-alpha trait: "-a/-a" OR "--/aa"
Hg H disease: "--/-a"
Hydrops fetalis: "--/--"

Front 41

What are the findings in thal-alpha trait?

Back 41

"-a/-a" OR "--/aa"

Mild decrease of alpha chain production
No "new" Hg
Mild anemia/low-normal Hg
Marked microcytosis (decreased MCV)

Front 42

What are the findings in HgH disease?

Back 42

"--/-a"

Severereduction in alpha chain production
Hg (4 beta chains); decreased O2affinity
Mild-severe hemolytic anemia
Hg Bart's (4 gamma chains) in infants; severe disease

Front 43

What are the findings in hydrops fetalis?

Back 43

"--/--"

Absence of alpha
Intrauterine hypoxia
Hg bart's: 4 gammas
Not compatible with life

Front 44

What's the pattern of hemoglobin amounts in the alpha thalassemias?

Back 44

Front 45

What are the typical lab findings in someone with a thalassemia?

Back 45

Microcytosis +/- anemia
Hemolysis
Hg electrophoresis findings
Positive FH
Molecular genetics confirm

Front 46

What are the findings of thalassemias on peripheral blood smears?

Back 46

Microcytosis
Hypochromia
Target cells
Heinz bodies

Front 47

What's the treatment for thalassemias?

Back 47

Chronic transfusions
Folic acid supplementation
BOne marrow treatment

Front 48

What complications result from chronically transfusing people?

Back 48

Iron overload!
-Multiorgan failure
-CHF, liver cirrhosis

Treatment:
Iron chelators

Front 49

What are some of the iron chelators used in this disease?

Back 49

Defroxamine
Deferasirox

They're used for the beta thalassemias

Front 50

What population is most commonly affected by sickle cell syndrome?

Back 50

African american population

Front 51

What mutation takes place in sickle cell anemia?

Back 51

V->E (valine-->glutamic acid) at 6th position of the beta globin gene

Front 52

What is the effect of the sickle cell mutation?

Back 52

Less soluble hemoglobin leads to precipitation of the Hgb-->sickling of the cells

Front 53

What is the effect of sickling on RBCs?

Back 53

Shorter lifespan
Infarction all over the body

Front 54

What is the typical presentation of someone with sickle cell trait?

Back 54

It's asymptomatic.

Front 55

What is hemoglobin C?

Back 55

Similar disease to sickle cell, except that it's an E for K (glutamic acid for lysine) substitution at position 6

Front 56

What are thesymptoms of hemoglobincarriers?

Back 56

Anemia
Ulcers
Splenomegaly

Front 57

What are the different sickle cell diseases?

Back 57

Hg SS: homozygous S
Hg SC: heterozygous S, heterozygous C
Hg S/B. thal disease: heterozygous S+B0/homozygous B+

Front 58

When do people present with sickle cell disease?

Back 58

As infants, when the Hgb F declines to less than 50%

Front 59

What are some types of sickle cell crises?

Back 59

Pain/vaso-occlusive crisis
Visceral sequestration crisis
Aplastic anemia
Hyperhemolytic crisis

Front 60

What are some other kinds of problems that sickling blood cells can cause?

Back 60

Recurrent infections
Pulmonary HTN
Renal failure

Front 61

What are some infections that sickle cell people are more prone to?

Back 61

Parvovirus B19
Encapsulated bacteria: (strep, h. flu, meningococcus)

Front 62

What are some of the vaso-occlusive crises that can happen with sickle cell disease?

Back 62

When there's vasoocclusion due to the sickling of blood cells inside the vasculature; normally pain
-Bones
-Spleen
-Stroke
-Skin ulceration

Front 63

What is the management for sickle cell pain crises?

Back 63

Pain meds
Correcting the precipitating factors: (dehydration,infection, etc.)

Front 64

What is the treatment of people with sickle cell in relation to their increased number of infections?

Back 64

Prophylactic penicillin until 18

Immunizations

Front 65

What is the treatment ofr an acute chest syndrome in a person with sickle cell disease?

Back 65

Blood exchange

Front 66

What's the treatment for sickle cell disease?

Back 66

Hydroxyurea: increases HbF; decreased HgS
Exchange transfusion (acute management)
Pain management
Blood transfusions

Front 67

What are some of the reasons that people with sickle cell don't comply with meds?

Back 67

The side effects are quite severe.

Front 68

What is the cause of hereditary spherocytosis?

Back 68

Defect in vertical interactions:
-Spectrin
-Protein 3
-Protein 4.2

Defect in Spectrin-Protein 4.2 binding

Front 69

What is the cause of hereditary elliptocytosis?

Back 69

Defects in horizontal interactions:
-Protein 4.1
-Protein 3
-Glycoprotein C, D

Defects in spectrin/spectrin-ankyrin binding

Front 70

Who gets hereditary elliptocytosis more commonly?

Back 70

Africans/mediterraneans

Front 71

What problems happen in people with HS/HE?

Back 71

The RBCs get stuck in the spleen and then get destroyed

Front 72

What tests do you order up to diagnose hereditary elliptocytosis or spherocytosis?

Back 72

Negative Coomb's test
Abnormal osmotic fragility test
Family history

Front 73

What's the inheritance of Hereditary spherocytosis, elliptocytosis?

Back 73

Autosomal dominant

Front 74

What are the clinical findings of HS/HE?

Back 74

Anemia
Jaundice
Chronic hemolysis
Severe:
-Splenomegaly
-Gallstones

Front 75

What are the treatments for HS/HE?

Back 75

If asymptomatic, don'ttreat
Folic acid supplementation
Splenectomy (delay as long as possible.)

Front 76

What are some of the immunizations that people with HS/HE should get? What meds should they be on?

Back 76

Immunizations:
-H. influenza
-Meningococcus
-P. pneumoniae

Penicillin prophylaxis

Front 77

What are the two most significant enzyme defects in RBCs?

Back 77

G6PD
Pyruvate kinase deficiency

Front 78

What's the inheritance of G6PD?

Back 78

X-linked

Multiple mutations

Front 79

What different variants of G6PD exist?

Back 79

African-American
Mediteranean
Southeast asian

Front 80

What is the function of G6PD?

Back 80

Maintain glutathione levels

Prevent free radical damage

Front 81

What's the cause of RBC damage in people with pyruvate kinase deficiency?

Back 81

Decreased ATP-->rigid red cells-->hemolysis

Front 82

What's the inheritance of pyruvate kinase deficiency?

Back 82

Autosomal recessive

Front 83

What are the symptoms of pyruvate kinase deficiency?

Back 83

Hemolysis
Splenomegaly
Neonatal jaundice