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Essential Haematology > 4. Inherited Haemolytic Anemias- Haemoglobinopathies > Flashcards

4. Inherited Haemolytic Anemias- Haemoglobinopathies Flashcards

1
Q

List two main types of factors that affect red blood cell survival

A

Intrinsic

Extrinsic

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2
Q

What are three intrinsic factors affecting red blood cell survival

A

Enzymes for glucose metabolism
Normal phospholipid membrane
Normal hemoglobin

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3
Q

What are the three types of hemoglobin that normal adult blood contains

A 
Hemoglobin A  (α2β2)
Hemoglobin F   (α2γ2)
Hemoglobin A2 (α2δ2)
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4
Q

What percentage of adults hemoglobin does Hemoglobin A (a2β2) account for

A

98%

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5
Q

Describe a qualitative haemoglobin disorder

A

Structural defect of Alpha or Beta Globin Chain

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6
Q

Describe a quantitative haemoglobin disorder

A

Deficiency of alpha or beta globin chain

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7
Q

What is the diagnosis for:
A 2yr old boy that presents with
- Failure to thrive and progressive pallor
- Was well up to age 4 months
- Physical examination shows prominent maxillae
- Moderate splenomegaly noted

A

Beta Thalassemia

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8
Q

What is the definition of Thalassemia

A

A decrease in the production of either alpha or beta subunits

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9
Q

Which chromosome is affected in Beta Thalassemia

A

Chromosome 11

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10
Q

Which population is Beta Thalassemia most common in

A

Mediterranean
Middle Eastern
Asia

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11
Q

What type of mutation causes severe anemia in Beta Thalassemia?

A

Point mutation, where a stop codin is introduced early in the coding sequence and therefore terminates the protein sequence ( in this case Beta Globin sequence is terminated)

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12
Q

Is Beta Thalassemia Heterozygous or Homozygous

A

Both

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13
Q

What are the three types of Beta Thalassemia

A

Thalassemia Major (β0/β0)
Minor
Intermedia

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14
Q

Is Beta Thalassemia Major Heterozygous or Homozygous

A

Homozygous

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15
Q

Is Beta Thalassemia Intermedia Heterozygous or Homozygous

A

Heterozygous

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16
Q

Is Beta Thalassemia minor Heterozygous or Homozygous

A

Homozygous

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17
Q

What is the level of Microcytic RBCs in Beta Thalassemia minor

A

Increased Microcytic RBCs

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18
Q

What are the symptoms of Beta Thalassemia Minor

A

Asymptomatic or Mild Anemia

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19
Q

What are the changes in Adult Haemoglobin seen in Beta Thalassemia Minor

A 
Haemoglobin A (α2 β2) decreases
Haemoglobin A2 (α2 δ2) increases
Haemoglobin F (α2 γ2) increases
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20
Q

Which test shows an increase in HbA2 and HbF in Beta Thalassemia Minor

A

Haemoglobin Electrophoresis

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21
Q

What is another name for Beta Thalassemia Major

A

“Cooley’s Anemia”

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22
Q

Which Anemia is known as “Cooley’s Anemia”

A

Beta Thalassemia Major

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23
Q

Is there Beta Globin production in Beta Thalassemia Major

A

Nope, None

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24
Q

What is the major Haemoglobin formed in Beta Thalassemia Major (β0/β0)

A

Haemoglobin F

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25
What condition of the Spleen and Liver is evident in β Thalassemia Major (β0/β0)
Splenomegaly | Enlargement of Liver
26
Why is the liver and spleen enlarged in β Thalassemia Major
It is as a result of excessive red cell destruction
27
If both parents are the carrier of the β-Thalassemia trait, what is the chance of a β- Thalassemia Major offspring
1 in 4
28
What is the effect of the excessive α-chain precipitation in β-Thalassemia Major
The α - chains precipitate in erythroblasts and in mature red cells causing the severe ineffective erythropoiesis and hemolysis
29
What is the relationship between α-chain excess and anemia
Greater the α-chain excess the more severe the anemia
30
The production of which globin chain helps to “mop up” the excess α-chains in β- Thalassemia major?
γ-chains (gamma chains found in Haemoglobin F)
31
True or False | Thalassemia Major is often the result of inheritance of two different mutations, each involving β-globin synthesis
True
32
What are six clinical features of β-Thalassemia Major
``` Severe Anemia Enlargement of Liver and Spleen Expansion of Bones Iron overload (for patients sustained by blood transfusion) Increased susceptibility to infection Osteoporosis ```
33
Severe anemia in a β-Thalassemia Major patient becomes apparent at which age
3-6mths after birth
34
Why does β-Thalassemia Major become apparent at 3-6 mnths
Because this is when the switch from γ- to β-chain production should take place
35
One Clinical Feature of β-Thalassemia Major is splenomegaly, how does this affect the blood requirements
It increases blood requirements by increasing red cell destruction and pooling and by causing expansion of the plasma volume
36
What causes the expansion of bones in β- Thalassemia Major
Caused by intense marrow Hyperplasia (in an attempt to correct the anemia) Leading to Thalassemic Facies
37
Expansion of bones is a clinical feature of β-Thalassemia Major What effect does it have on bone structure, and bones like the maxilla and skull
Thins the bone cortex (increasing susceptibility to fracture) Protruding Maxilla Bossing of skull with hair- on - end appearance on X-ray
38
Which therapy is administered to β- Thalassemia Major patients along with their sustained blood transfusions to prevent iron overload
Chelation Therapy
39
What is the effect of iron overload
``` Failure of growth Delayed or absent puberty Diabetes Hypothyroidism Hypoparathyroidism ```
40
What changes in skin pigmentation are seen in an early stage of iron overload
Slately grey
41
What causes the Slate Grey appearance in an early stage or iron overload
Excess melanin and haemosiderin
42
Which test can be done to observe Iron overload in Liver or heart
T2 Magnetic Resonance Images
43
What is the reticulocyte percentage in β-Thalassemia
Raised
44
What type of anemia is seen in β- Thalassemia Major
Hypochromic | Microcytic anemia
45
Which iron test is used to assess iron overload
Serum Ferritin
46
For patients with Thalassemia Major you should attempt to keep the iron level in what range
1000 - 1500 ug/L Normal is 30-620 ug/L in males 20-220 ug/L in premenopausalfemales
47
List eight treatment options for Thalassemia Major
1) Blood Transfusions 2) Regular Folic acid 3) Iron Chelation therapy 4) Vitamin C 5) Splenectomy 6) Endocrine Therapy 7) Immunization against Hep B 8) Allogenic bone marrow transplantation
48
How many units of blood and how often are these units administered to β- Thalassemic Major patients
2-3 units every 4-6 weeks
49
What type of blood is used in the Blood Transfusion for Beta Thalassemic Major patients
Fresh blood | No WBCs
50
If the Beta Thalassemic Major Pt has a folic acid poor diet what is the amount prescribed per day
5mg/day
51
List three options for Iron Chelators
Deferasirox ( oral ) - best option Deferiprone (oral) Deferoxamine (iv)
52
Why is Vitamin C apart of the treatment for Beta Thalassemia Major
It increases the excretion of iron by Deferoxamine [It is believed that vitamin C can reduce both ferric (Fe(3+)) and ferrous (Fe(2+)) ions, and also facilitate the accessibility of iron to chelators through increase of iron release from the reticuloendothelial system.]
53
Splenectomy is a form of treatment for Beta Thalassemia Major, however this should not be performed in children until after what age
Age 6
54
Why is splenectomy an option for treatment in patients with Beta Thalassemia Major
To reduce blood requirements (Remember the spleen destroys rbcs and releases the blood requirements back into the plasma, this is excessive in Beta Thalassemia Major)
55
Why is Endocrine Therapy an option for Beta Thalassemia Major pts
It is given either as replacement because of end organ failure OR To stimulate the pituitary if puberty is delayed
56
What is the blood picture of Beta Thalassemia minor
Hypochromic | Microcytic
57
``` What are the relative values for Mean Cell Volume MCV Mean Cell Haemoglobin MCH Red Cell Count RBC Haemoglobin ``` in Beta Thalassemia Minor
MCV is low MCH is low RBC is high Haemoglobin is a bit low
58
A raised level in what type of Haemoglobin confirms the diagnosis for Beta Thalassemia Minor
Hb A2 (>3.5%)
59
Describe Thalassemia intermedia
Thalassemia of moderate severity who do not need regular transfusions
60
In β-Thalassemia Major Management the Haemoglobin is maintained at what level
12g/dl
61
True or False All Beta Thalassemic Intermedia patients are transfusion dependent
False Not all are
62
Diagnose this patient Results > Hb 8.0g/dl > MCV 65fl ; MCH 18pg > Blood film: hypochromic, microcytic with occasional nucleated RBCs > Serum iron, TIBC normal (total iron binding capacity) > Electrophoresis: Hb H
α-thalassemia
63
What is the genetic cause of α-thalassemia
All are due to gene deletion
64
What are Thalassemias
These are heterogenous group of genetic disorders that result from a reduced rate of synthesis of α or β chains
65
What is the effect of the loss of all four α globin genes on α-chain synthesis
Completely suppresses α-chain synthesis Leads to death in utero (hydrops fetalis)
66
What is the result of 3 α gene deletions
Leads to a moderately severe microcytic, hypochromic anemia
67
What is the condition associated with Four gene deletion α-Thalassemia
Hydrops fetalis
68
What type of Haemoglobin is observed in α-Thalassemia
Hb H [H (β4) - four β globulin chains]
69
What type of Haemoglobin is observed in α-Thalassemia of the fetus [loss of all 4 α globin chains]
``` Hb Barts (γ4) (Hydrops fetalis) ``` Four gamma chains
70
Describe what causes α-Thalassemia trait
Caused by loss of one or two genes and are not usually associated with anemia
71
True or False MCV and MCH are low in α- Thalassemia trait
True
72
What is the cause of in utero death of fetuses with α-Thalassemia
``` Severe hypoxia due to Hb Barts (γ4) that has High oxygen affinity ```
73
Describe α+ trait thalassemia
1 α globulin gene deleted
74
Describe homozygous α+ trait
2 α globulin genes deleted | 1 from opposite chromosomes
75
Describe heterozygous α0 thalassemia trait
2 α genes deleted | Both deleted genes from same chromosome
76
Describe Hb H disease
3 alpha globulin genes deleted
77
Diagnose this patient ``` Hb 7.5g/dl; sickled cells on film Wbc 28.6 x 10^9/L Plats 295 x 10^9/L Retic 18% Sickle solubility test positive Hb electrophoresis S and A2 ```
Sickle Cell Disease
78
Define Sickle Cell Anemia
It is a group of hemoglobin disorders in which the sickle β-globin gene is inherited
79
What is the most common type of sickle cell anemia
``` Hb SS (homozygous sickle cell) (i.e. Hb α2β2 s) ```
80
What happens to Hb S when exposed to low oxygen tension
Forms crystals
81
Substitution of which amino acid causes the sickle β-globin abnormality
Substitution of Valine for Glutamic Acid in position 6 in the β chain
82
What percentage of West Africans have Sickle Cell Anemia
25%
83
Why is the 25% occurrence of sickle cell disease in West Africa maintained
Because of the protection against malaria that is afforded by the carrier state
84
Which Haemoglobin type gives up O2 more readily to tissues Hb S or Hb A
Hb S | O2 dissociation curve shifted to the right
85
List four clinical features of Sickle Cell Anemia
Painful Vaso-occlusive crises Visceral sequestration crises Aplastic Crises Haemolytic Crises
86
What is vaso-occlusive crisis
When the microcirculation is obstructed by sickled RBCs, causing ischemic injury to the organ supplied and resultant pain
87
Painful vaso occlusive crises of the sickle cell anemic patient are often precipitated by what factors
Infection Acidosis Dehydration Deoxygenation
88
What are some states of deoxygenation that can cause vaso occlusive crises in the sickle cell anemic patient
``` Altitude Operations Obstetric delivery Stasis of the circulation Exposure to cold Violent exercise ```
89
What are the most serious sites of vaso occlusive crises
Brain | Spinal cord
90
Which test can be used to detect abnormal blood flow that is indicative of arterial stenosis
Doppler Ultrasonography
91
What is typically the first presentation of sickle cell disease HbSS
‘Hand-foot’ Syndrome
92
What causes dactylitis in HbSS pts
Infarcts of the small bones
93
What causes sequestration crises
Sickling within organs and pooling of blood, often with severe exacerbation of anemia
94
What is the most common cause of death from Homozygous Sickle cell disease after puberty
Acute Sickle Chest Syndrome
95
What is the clinical presentation of Acute sickle chest syndrome
Dyspnoea Falling arterial Po2 Chest pain Pulmonary infiltrates on chest X ray
96
What is the treatment for Acute Sickle Chest Syndrome
Analgesia Oxygen Exchange transfusion and ventilatory support
97
What is Aplastic Crises
An aplastic crisis is when the body does not make enough new red blood cells to replace the ones that are already in the blood. [These occur as a result of infection with parvovirus or from folate deficiencies]
98
How is Aplastic Crises characterized
Fall in reticulocytes | Fall in Haemoglobin
99
What is a Haemolytic crises
Increased rate of haemolysis with a fall in Haemoglobin but rise in reticulocytes
100
List four Laboratory Findings of Homozygous Sickle cell Disease HbSS
Haemoglobin is usually low (6-9g/dL) Sickle cells and Target cells present in blood Screening test for sickling positive when the blood is dehydrated Haemoglobin Electrophoresis: in HbSS, no HbA detected Moderate to severe normochromic anemia Polychromasia and nucleated red cells Leucocytosis Thrombocytosis
101
List four prophylactic treatments for Homozygous Sickle Cell Anemia
Avoid factors known to precipitate crises Folic acid Good general nutrition and hygiene Pneumococcal, haemophilus and meningococcal vaccine, also hep b
102
What are four simple treatments for HbSS crises
Rest Warmth Rehydration by oral fluids/ intravenous normal saline Antibiotics if infection is present
103
Analgesics is administered to pts with HbSS crises, which drugs are suitable
Paracetamol | Non-steroidal anti-inflammatory agent and opiates
104
What is the role of Hydroxyurea treatment in HbSS treatment
Can increase Hb F levels and has been shown to improve the clinical course of children or adults who are having three or more painful crises each year NB// hydroxyurea should NOT be used during pregnancy
105
Which treatment is know to cure HbSS
Stem Cell Transplantation
106
What is the mortality rate of stem cell transplantation
Less than 10%
107
What is the most common symptom of Sickle cell trait
Haematuria Caused by minor infarcts of the renal papillae
108
List four varieties of Sickle Cell Disease
Sickle Cell Anemia (HbSS) Sickle -Hb C disease Sickle β 0 Thalassemia (S β0) Sickle β+ Thalassemia (S β+)
109
List five reasons why Sickle Cell disease is clinically silent until age 6mths
``` Chronic hemolytic anemia of variable severity Ischemic strokes Pulmonary infection and infarction Chronic leg ulcers Impaired growth and development ```
110
What are the symptoms of Hand Foot Syndrome in HbSS crises
Sudden pain and swelling of extremities | Results in shortened digits in later life

Essential Haematology (14 decks)

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