Hemoglobinopathies Flashcards
1
Q
definition of thalassemia
A
- genetically heterogenous condition resulting from imbalance between amounts of alpha and beta globin chains that are synthesized
2
Q
thalassemias arise from
A
- mutations which partially or completely inactivate production of alpha or beta globin chains
3
Q
inactivation of alpha chain is generally
A
- full deletion
4
Q
inactivation of beta chain is generally
A
- point mutations
5
Q
ways to classify thalassemias
A
- severity of clinical manifestations
- major hemoglobin species formed
- genotype
6
Q
symptoms of thalassemia minor
A
- mild symptoms if any
7
Q
symptoms of thalassemia major
A
- severe symptoms
- patients are transfusion dependent
8
Q
symptoms of thalassemia intermedia
A
- between major and minor
- patients not transfusion dependent
9
Q
B^0 thalassemia
A
- mutations cause absent beta globin synthesis
10
Q
B+ thalassemia
A
- mutations cause decreased (but still present) beta globin synthesis
11
Q
another name for beta thalassemia major
A
- Cooley’s anemia
12
Q
genotype of beta thalassemia major
A
B^0/B^0
13
Q
when does severe anemia develop in beta thalassemia major
A
- 2-12 months
- infants make gamma, delta, and alpha, not beta yet
14
Q
beta thalassemia major seen in which population
A
- mediterraneans
15
Q
beta thalassemia major diagnosis by
A
- hemoglobin electrophoresis showing alpha 4 tetramers
- absence of normal hemoglobin A
16
Q
beta thalassemia major symptoms
A
- anemia
- splenomegaly - worsens due to sequestration
- bony deformities
- iron overload issues
17
Q
iron overload issues
A
- bronze skin
- liver failure
- endocrine failure
18
Q
instability of alpha tetramers leads to
A
- ineffective erythropoiesis
- destruction of produced RBCs
19
Q
infective erythropoiesis example
A
- intramedullary hemolysis
20
Q
intramedullary hemolysis
A
- hemolysis of RBC precursors inside marrow
21
Q
anemia leads to
A
- increased epo production
- more ineffective erythropoiesis
22
Q
bone deformities caused by
A
- marrow expansion
23
Q
iron overload develops due to
A
- transfusions
- iron hyper absorption from gut
24
Q
beta thalassemia minor (trait) genotype
A
- B+/B^0
25
beta thalassemia trait symptoms
- generally asymptomatic
| - not so many alpha 4 tetramers
26
beta thalassemia trait MCV
- microcytic
| - around 70
27
beta thalassemia trait anemic
- may or may not be
| - mild if present
28
beta thalassemia trait RBC count
- very elevated
29
beta thalassemia trait RDW
- normal
| - since all cells will be microcytic and hypochromic
30
beta thalassemia trait diagnosis by
- hemoglobin electrophoresis
31
beta thalassemia trait - hemoglobin electrophoresis in adults shows
in newborns
- unregulation of delta chains
- around 4-8% Hgb A2
not seen in newborns since species are predominantly HbF
32
alpha thalassemia one gene deletion symptoms
- typically silent
| - maybe minimal microcytosis
33
alpha thalassemia one gene deletion anemia
- anemia not present
34
alpha thalassemia one gene deletion Hb electrophoresis result
- normal
35
alpha thalassemia two gene deletion symptoms
- mildly anemic
36
alpha thalassemia two gene deletion MCV
anemic?
- mildly microcytic
- MCV around 70
mildly anemic (Hg 10-11)
37
alpha thalassemia two gene deletion Hb electrophoresis in adults
- normal
38
alpha thalassemia two gene deletion Hb electrophoresis in newborns
- abnormal
| - will make hemoglobin Barts (gamma 4)
39
alpha thalassemia two gene deletion seen in africans
- a-/a-
| - trans deletion
40
alpha thalassemia two gene deletion seen in asians
- aa/--
| - cis deletion
41
hemoglobin H disease genotype
- a-/--
| - three gene deletion
42
hemoglobin H disease results
Hemoglobin H = Beta 4 tetramers
43
hemoglobin H (beta 4 tetramers) form
causes
- Heinz bodies
| - causes bite cells and hemolytic anemia
44
hydrops fetalis genotype
--/--
45
hydrops fetalis result
- 4 gamma tetramers
- Hemoglobin barts
- no alpha chains form
46
hydrops fetalis in utero
- intrauterine death
47
hydrops fetalis treatment
- treated in utero
| - exchange transfusions
48
hemoglobin S amino acid switch
- Glu 6 changed to Val 6
49
deoxy HbS compared to HbA
- less soluble
| - polymerizes and forms long fibers
50
hemoglobin C amino acid switch
- Glu 6 to Lys 6
51
hemoglobin C result
- leads to increased cellular dehydration
52
hemoglobin C cells found
population targeted
- target cells
- hemoglobin c crystals
west African descent
53
HbS polymerizes and cell sickle in conditions under
- hypoxia
| - acidosis
54
Leads to cellular dehydration
- multiple cycles of sickling and unsickling
55
cells in HbS eventually become
- irreversibly sickled
| - obstruct small blood vessels
56
sickled and unsickled red cells suffer
- hemolysis
57
sickled cells and endothelial cells
- abnormal adhesion to endothelial cells
58
sickle cell disease genotype
- homozygous SS
59
S/B^0 thalassemia
- indistinguishable from SS
60
S/B+ thalassemia
- milder disease
| - some normal beta chains are produced
61
the presence of HbC and HbS
- leads to more intracellular dehydration
| - worsening sickling
62
if Hgb falls below patient's baseline in sickle cell disease
- look for other causes
- Parvovirus B19
- splenic or hepatic sequestration
- acute chest syndrome
63
leukocytes and platelets in sickle cell disease
- leukocytosis - elevated WBC
| - thrombocytosis - elevated platelets
64
spleen in SS adult patients
- functionally asplenic
| - spleen has infarcted
65
cells seen in functionally asplenic patients
- Howell jolly bodies
66
sickle cell disease thromboses
- increased risk for venous clots
| - risk present in sickle cell trait as well
67
sickle cell crises
- splenic sequestration crisis
- aplastic crisis
- painful (vaso-occlusive) crisis
68
splenic sequestration crisis in children
- rapid and extensive trapping of RBCs in spleen
69
splenic sequestration crisis symptoms
- profound anemia
- massive splenomegaly
- hypovolemic shock
- occurs quickly
70
which sickle cell crisis is most common
- painful (vaso-occlusive) crisis
71
painful crisis
how to treat
- periodic episodes of acute vascular occlusion
- treat pain
- supplemental O2
- folate replacement
- replace fluid
72
painful crisis usually affects
- bones and large joints
73
painful crisis triggers
- exercise
- dehydration
- infection
- cold
- stress
- menstruation
- surgery/trauma
- pregnancy
74
autospenectomy from sickle cell disease makes patient more susceptible to infections by
- infections by encapsulated organisms
75
sickle cell disease makes patient more susceptible to sepsis by
- encapsulated organisms
76
sickle cell disease infection by ______ if undergoing iron chelation therapy
- yersinia
| - vibrio
77
sickle cell disease osteomyelitis and septic arthritis caused by
- salmonella osteomyelitis
78
respiratory complication of sickle cell disease
- acute chest syndrome
| - pulmonary hypertension
79
most common cause of death in patients with sickle cell disease
- acute chest syndrome
80
acute chest syndrome definition symptoms
- hypoxemia
- new infiltrate on CXR
- new fever, chest pain, dyspnea, or cough
81
infections in acute chest syndrome usually with
- atypical organisms
| - chlamydia and mycoplasma
82
acute chest syndrome etiologies
- fat embolism from necrotic bone marrow
- sequestration of sickled red cells
- pulmonary infarction
- hypoventiliation from rib infarct, narcotic administration
- pulmonary edema from fluid overload
83
treatment of acute chest syndrome
- antibiotics, oxygen
| - simple transfusion to lower HbS concentration
84
pulmonary hypertension occurs in what fraction of SCD adults
- 1/3
85
median age of stroke in SCD patients
- 5 years old
86
stroke cause in SCD patients
- disordered blood vessels
| - not due to atherosclerosis
87
acute treatment of stroke in SCD patients
- exchange transfusion
88
chronic treatment of stroke in SCD patients
- chronic regular transfusions
89
if transcranial dopplers show narrowing in the circle of Willis then chronic regular transfusions will prevent
- chronic regular transfusions prevent first instance of stroke
90
in an adult, one unit of blood raised Hb by
1
91
complications of transfusion in SCD
- iron overload
- allo-immunization
- leg ulcers
- renal
- AVN
- priapism
- proliferative retinopathy
92
organ damage associated with iron overload
- heart failure
- liver failure
- endocrine failure
93
treatment for iron overload
- chelation
94
how to avoid allo-immunization in AA
- transfuse blood negative for C, E, Kell blood groups
| - reduce frequent transfusion in AA
95
treatment of sickle cell
- hydroxyurea
96
how hydroxyurea works
- increases amount of HbF
| - decreases concentration of HbS
97
effects of hydroxyurea
- increases baseline hemoglobin values
- reduces number of sickle cell crises
- reduces episodes of acute chest syndrome
- prevent pulmonary hypertension
- reduces mortality
98
side effect of hydroxyurea
- bone marrow suppression
99
contraindications for hydroxyurea
- pregnancy
| - poor/erratic followup
