Haem Flashcards
(206 cards)
1
Q
presentation ALL
A
CHILDREN lymphadenopathy hepatosplenomegaly pallor ecchymoses or petechiae fatigue dizziness
2
Q
Ix for ALL
A
bone marrow aspirate - immunophenotyping
3
Q
what is ALL
A
clonal malignancy of lymphoid precursors
4
Q
what is AML
A
clonal malignancy of myeloid precursors
5
Q
presentation AML
A
ADULTS hepatosplenomegaly pallor ecchymoses or petechiae fatigue dizziness
6
Q
Auer rods on peripheral blood smear
A
AML
7
Q
CD24+ve on immunophenotyping
A
AML
8
Q
smudge cells on peripheral blood smear
A
CLL
9
Q
presentation CLL
A
often asymptomatic!!
10
Q
common myeloid progenitor produces … what two further groups of progenitor cells?
A
megakaryocyte erythrocyte progenitor
myelocyte progenitor
11
Q
megakaryocyte erythrocyte progenitor produces what cell types
A
erythrocytes (RBC) & platelets
12
Q
myeloid progenitor produces what cell types?
A
Granulocytes
- neutrophils
- eosinophils
- basophils
Macrophages
13
Q
common lymphoid progenitor produces what cell types?
A
B cells
T cells
NK cells
Dendritic cells
14
Q
RBC lifespan
A
120d
15
Q
hormone regulating erythropoiesis
A
erythropoietin (from the kidneys) - detects reduced O2 and stimulates RBC production in the bone marrow
16
Q
where does the nucleus of RBCs disintegrate
A
In the bone marrow
17
Q
what is a reticulocyte
A
the earliest RBC in the blood stream - larger and blue appearance due to RNA
18
Q
structure of Hb
A
4 globin subunits with a single haem molecule
19
Q
what is a haem molecule composed of
A
single Fe2+ ion, surrounded by a porphyrin ring
20
Q
breakdown products of RBC
A
amino acids
iron
unconjugated bilirubin (secreted into bile for conjugation in the liver to be excreted)
21
Q
platelet lifespan
A
7-10 d
22
Q
neutrophil appearance on blood film
A
segmented nucleus
23
Q
eosinophil appearance on blood film
A
bi-lobed nucleus
24
Q
basophil appearance on blood film
A
large granules that obscure nucleus
25
monocyte appearance blood film
kidney bean nucleus
26
lymphocyte appearance blood film
small spherical nucleus
27
cause of a microcytic anaemia
cytoplasmic defect (Hb is made in the cytoplasm)
therefore there is a problem with haemoglobinisation
lack of availability of:
haem (iron, porphyrin ring) or globin
28
causes of iron deficiency anaemia
diet deficiency
blood loss
malabsorption
29
presentation iron deficiency anaemia
fatigue
hair loss
nail changes (koilonychia)
pica (craving non food items)
30
koilonychia
spoon nails
31
blood results in iron deficiency
low Hb, low MCV (microcytic anaemia)
low ferritin
low retic count
low transferrin saturation
32
ferritin
measure of iron storage
33
Mx iron deficiency anaemia
ferrous fumarate for 3-6m (tds)
34
s/e of ferrous fumarate
black stools
35
causes of porphyrin ring synthesis problems
lead poisoning
| v rare
36
causes of globin chain synthesis problems
thalassemia's (reduced rate of production globin chain)
sickle cell anaemia (abnormal structure of globin chain)
37
inheritance of thalassaemia
autosomal recessive
38
HbA
2 alpha chains
| 2 beta chains
39
HbA2
2 alpha chains
| 2 delta chains
40
HbF
2 alpha chains
| 2 gamma chains
41
what forms of Hb are affected in alpha thal
all forms!
| all contain alpha
42
alpha thal trait
1 or 2 genes missing
- carrier state
- no Tx needed
43
HbH disease (alpha thal)
only one gene left
- mild anaemia
- jaundice
- splenomegaly
44
Hb Barts hydrops fetalis (alpha thal)
no functional genes
- severe anaemia
- growth retardation
- most die in utero
45
what forms of Hb are affected in beta thal
only HbA
| the only one to contain beta
46
forms of beta thal
beta thal trait
beta thal intermedia
beta thal major
47
beta thal trait presentation
asymptomatic
| no/mild anaemia
48
beta thal intermedia presentation
requires occ transfusion
49
beta thal major presentation
present aged 6-24m (HbF stores have depleted)
failure to thrive
pallor
extramedullary haemopoeisis
50
Mx beta thal major
regular lifelong transfusions + iron chelation (desferrioxamine)
51
inheritance of sickle cell anaemia
autosomal recessive
52
forms of sickle cell anaemia
sickle cell trait
| sickle cell anaemia
53
sickle cell trait presentation
HbAS (one normal beta gene, one abnormal)
- asymptomatic carrier state
- may sickle in severe hypoxia
54
sickle cell anaemia presentation
HbSS (both beta genes abnormal)
- vascular occlusions and episodes of tissue infarct
55
Mx sickle cell anaemia
hydroxycarbamide (induces HbF)
penicillin
folic acid
56
Ix for thalassaemia
HPLC test
57
cause of a megaloblastic anaemia
nuclear defect - there is a problem with cell division
therefore there is abnormally large nucleated red cell precursors with an immature nucleus.
58
causes of a megaloblastic anaemia
B12 or folate deficiency
pernicious anaemia
59
vit B12 deficiency causes - what symp?
neurological problems
60
where is B12 absorbed
terminal ileum
61
what does B12 need to bind to for absorption
intrinsic factor (produced by gastric parietal cells)
62
where is folate absorbed
jejunum
63
blood film appearance in B12 or folate deficiency
hyper-segmented polymorphs
| macro-ovalocytes
64
Mx B12 deficiency
IM hydroxocolbalamin (3xwk for 2w)
65
Mx folate deficiency
folic acid 5mg/day for 4m
66
why should you never give folic acid w/out checking B12 level
can induce subacute degeneration of the spinal cord
67
what is pernicious anaemia
autoimmune condition -
| autoantibodies against gastric parietal cells, therefore no IF produced, therefore no B12 absorption
68
autoantibodies in pernicious anaemia
anti-intrinsic factor (specific, not sensitive)
anti-gastric parietal cells (sensitive, not specific)
69
Mx pernicious anaemia
B12 inj for life (hydroxocolbalamin)
70
causes of a non megalobastic macrocytic anaemia
alcohol
liver disease
marrow failure
hypothyroidism
71
cause of a false (spurious) macrocytic anaemia
cold agglutinins
| haemolysis
72
when is haemolysis said to have progressed to haemolytic anaemia
when breakdown of RBCs exceeds response!
73
what are the normal responses to RBC breakdown
reticulocytosis and erythroid hyperplasia
74
what is extravascular haemolysis
excessive breakdown of RBC at the NORMAL site of destruction (spleen +/- liver)
therefore
you get the NORMAL breakdown products, but in excess:
- unconjugated bilirubinaemia
- urobilogenuria
75
causes of extravascular haemolysis
hereditary spherocytosis
sickle cell disease
autoimmune haemolysis
76
inheritance of hereditary spherocytosis
autosomal dominant
77
pathology of hereditary spherocytosis
RBCs are sphere shaped rather than biconcave disc, causing membrane disruption and destruction by the spleen.
78
blood film hereditary spherocytosis
spherocytes
79
Mx hereditary spherocytosis
RBC transfusions + folate replacement
80
autoimmune haemolysis
warm temperatures = IgG
cold temperatures = IgM
81
what is intravascular haemolysis
excessive breakdown of RBC within the circulation i.e. ABNORMAL site
```
therefore
you get ABNORMAL breakdown products in excess:
- haemoglobinaemia
- methylalbuminaemia
- haemoglobinuria
- haemosiderinuria
```
82
causes of intravascular haemolysis
G6PD deficiency
ABO incompatability
DIC
HUS
83
inheritance of G6PD deficiency
X-linked
84
pathology of G6PD deficiency
inborn error of metabolism, unable to deal with oxidative stress
85
blood film G6PD deficiency
Heinz bodies
86
Mx G6PD deficiency
supportive + folic acid
87
what does FFP contain
all coagulation factors
88
what is cryoprecipitate
blood component prepared from FFP
89
indications for receiving FFP
bleeding
surgery in liver disease with impaired coag
DIC
90
universal donor
group O
91
universal recipient
group AB
92
cause of an immediate haemolytic transfusion reaction
ABO incompatibility
93
Mx of an immediate haemolytic transfusion reaction
discontinue transfusion, leave line in
flush saline 0.9%
94
cause of a febrile non-haemolytic transfusion reaction
antibodies are contaminated with white cells
95
presentation of a febrile non-haemolytic transfusion reaction
0/5 - 1 h after starting transfusion, get shivers and fever
96
Mx of a febrile non-haemolytic transfusion reaction
slow or stop the transfusion
pcm
97
Mx of an allergic/urticarial transfusion reaction
slow or stop the transfusion
| chlorphenamine 10mg IV
98
presentation of a delayed haemolytic transfusion reaction
5-10 d after transfusion, low Hb, fever, jaundice
99
G+S
blood group is established and serum checked for Ab
| this is a provision which allows rapid blood delivery in an emergency
100
crossmatch
testing before a blood transfusion to determine if the donor's blood is compatible with the blood of the intended recipient
101
inheritance of hereditary haemochromatosis
autosomal recessive
102
what gene is affected in hereditary haemochromatosis
HFE gene - affects hepcidin - can't downregulate ferroportin
103
pathology of hereditary haemochromatosis
iron is laid down in tissues rather than being stored in ferritin
104
presentation of hereditary haemochromatosis
```
"bronze diabetes" - from iron deposition in pancreas
weakness
fatigue
joint pains
impotence
cirrhosis
diabetes
cardiomyopathy
```
105
Ix hereditary haemochromatosis
1. serum transferrin saturation (raised)
| 2. serum ferritin (acute phase protein so is raised by other conditions, not specific)
106
Mx hereditary haemochromatosis
venesection (exhaust iron stores)
107
main cause of secondary iron overload
rptd red cell transfusions
108
Mx of secondary iron overload
iron chelation Desferioxamine
109
why is venesection not a Mx option for secondary iron overload
the pts are already anaemic, hence they are receiving transfusions
110
Mx ALL
chemotherapy - long duration (2-3y)
111
Mx AML
chemotherapy - intensive cycle
112
what lineage does hodgkins lymphoma arise from
mature B cells
113
presentation Hodgkin's lymphoma
painless lymphadenopathy
itch without rash
alcohol-induced pain
'B symptoms' - wt loss, fever, night sweats
114
Ix hodgkins lymphoma
lymph node biopsy
- Reed Sternberg cells
- Immunohistochemistry (CD 30 +ve)
115
CD 30 +ve cells on immunohistochemistry
Hodgkin's lymphoma
116
reed Sternberg cells
hodgkins lymphoma
117
Mx Hodgkin's lymphoma
monoclonal Ab (brentuximab) + chemo
118
what lineage does non hodgkins lymphoma arise from
90% - B cell lines
119
presentation non hodgkins lymphoma
B symptoms - night sweats, fever, wt loss
120
follicular lymphoma gene
non-hodgkins lymphoma -
t(14;18) between the bcl-2 gene
121
Burkitts lymphoma
non-hodgkins lymphoma -
c-myc gene on (8;14)
122
CD 20 +ve cells on immunohistochemistry
Burkitt's lymphoma
123
Mx non-Hodgkin's lymphoma
monoclonal Ab (rituximab) + chemo
incurable apart from the early stage
124
what is hyposplenism
reduced or absent splenic function
125
causes of hyposplenism
```
congenital absence
surgical removal
trauma
immune
infarction (sickle cell)
infiltration (lymphoma, amyloid)
drugs (methyldopa, chemo)
```
126
blood film hyposplenism
Howell Jolly bodies
| (inclusion of nuclear chromatin remnants)
127
infection prophylaxis in hyposplenism
pneumoccal + HiB vaccines
long term oral penicillin
128
what is hypersplenism
enhanced filtration, pathological pooling or shortening of RBC lifespan
129
causes of hypersplenism
cirrhosis
lymphoma
TB
CTDs and inflammatory disease
130
presentation of pancytopenia
anaemia - fatigue, SOB, CVS compromise
neutropenia - infection
thrombocytopenia - bleeding
131
congenital cause of bone marrow failure
Fanconi's anaemia
132
inheritance of fanconis anaemia
autosomal recessive
133
presentation fanconi's anaemia
short stature
hyperpigmentation
skeletal abnormalities
increase in solid tumours + leukaemia
134
acquired causes of primary bone marrow failure
aplastic anaemia
myelodysplastic syndromes
135
what is aplastic anaemia
autoimmune attack against the haemopoietic stem cell
136
bone marrow appearance aplastic anaemia
hypocellular
137
what are myelodysplastic syndromes
a group of cancers, where there is apoptosis of the mature cells
138
bone marrow appearance myelodysplastic syndromes
hypercellular - lots of immature cells due to ineffective erythropoiesis
139
causes of secondary bone marrow failure
drugs - chemo, chloramphenicol, alcohol
B12/folate deficiency
lymphoma
HIV
140
what is multiple myeloma
cancer of plasma cells
141
the presence of ?-? characterizes multiple myeloma?
IgG monoclonal antibody (paraprotein)
142
presentation multiple myeloma
Direct tumour effects:
- bone lesions (punched out lytic lesions)
- hypercalcaemia
- bone pain
- marrow failure
Paraprotein effects:
- renal cast nephopathy
- immune suppression
- hyper viscosity
- amyloid
143
Ix multiple myeloma
serum/urine electrophoresis - bence jones proteins
144
bence jones proteins
serum/urine electrophoresis
| - multiple myeloma
145
RBC appearance multiple myeloma
roleaux formation
146
monoclonal gammopathy of uncertain significance (MGUS)
```
high paraprotein (<30g/L)
NO clinical features of myeloma
```
147
waldenstrom's macroglobulinaemia
clonal disorder of intermediate cells between a lymphocyte and plasma cell
148
paraprotein in waldenstrom's macroglobulinaemia
IgM
149
what is amyloidosis
mutation in the light chain of plasma,
| leads to accumulation of the mutated protein in tissues - eventual organ failure & death
150
Ix amyloidosis
organ biopsy
| - Congo red stain with apple green birefringence under green light
151
what is CML
a myeloproliferative disorder
clonal malignancy of myeloid precursors
152
important mutation in CML
Philadelphia chromosome (9;22) translocation
BCR-ABL +ve
153
presentation CML
splenomegaly
wt loss
excessive sweating
gout (due to purine breakdown)
154
Mx CML
tyrosine-kinase inhibitor (imatinib)
155
what is polycythaemia
a myeloproliferative disorder
a true increase in red cell mass
156
causes of primary polycythaemia
polycythaemia rubra vera
157
JAK 2 mutation
polycythaemia rubra vera
158
causes of a secondary polycythaemia
smoking
COPD
altitude
159
causes of a pseudo polycythaemia
dehydration
obesity
diuretic therapy
160
presentation of polycythaemia
aquagenic pruritus
thrombosis
gout
161
Mx polycythaemia rubra vera
hydroxycarbamide + aspirin
162
what is essential thrombocythemia
a myeloproliferative disorder
a true increase in platelets
163
Mx essential thrombocythaemia
if plt < 1500 x 10^9/L and no prev thrombosis - no Tx
low risk of thrombosis - aspirin
high risk of thrombosis - hydroxycarbamide
164
what is myelofibrosis
reactive + reversible process
abnormal production of all 3 lineages due to marrow scarring
- therefore there is extramedullary haemopoiesis
165
presentation myelofibrosis
massive splenomegaly
166
blood film appearance myelofibrosis
leucoerythroblastic cells
| teardrop RBCs
167
Mx myelofibrosis
stem cell transplant
168
what is responsible for primary haemostasis
platelets
169
process of primary haemostasis
vessel wall damage
release of vWF from vessel wall
platelets have receptors to vWF
170
screening test for primary haemostasis
platelet count
171
what is responsible for secondary haemostasis
coagulation cascade
172
explain process of coagulation cascade
INTRINSIC PATHWAY:
Tissue Factor (III) is released from damaged vessels.
Activates Factor VII (VIIa).
Activates Factors V and X (Va & Xa).
Activates prothrombin (II) to thrombin (IIa).
Activates fibrinogen (I) to fibrin (Ia).
EXTRINSIC PATHWAY:
Factors VIII and IX are activated (VIIIa & IXa).
Potentiates the activation of Va and Xa even more.
173
screening test for the intrinsic coagulation pathway
prothrombin time (PT)
174
screening test for the extrinsic coagulation pathway
activated partial thromboplastin time (aPTT)
175
connection between vWF and Factor VIII
vWF has a role in binding to Factor VIII and protecting it
176
what is responsible for the breakdown of fibrin clots
plasmin
(plasminogen produced by the liver,
converted to plasmin by tissue plasminogen activator)
177
natural anticoagulants
anti thrombin
protein c and protein S
178
role of anti thrombin
inhibits thrombin (IIa) and Factor Xa
179
role of protein c and protein s
inhibits Factor Va and Factor VIIIa
180
what activates protein c and protein s
the presence of thrombin
181
disorders of primary haemostasis
VASCULAR PROBLEMS
- inherited (marfans)
- acquired (HSP)
PLATELET PROBLEMS
- reduced number (thrombocytopenia)
- reduced function (renal failure, nsaids, aspirin)
VON WILLEBRAND'S DISEASE
182
inheritance of von willebrands
autosomal dominant
183
presentation von willebrands
bruising
epistaxis
menorrhagia
increased bleeding post-tooth extraction
184
Ix for von willebrands
APTT - prolonged
| factor VIII has a protective factor on VIII
185
causes of a prolonged APTT and PT
multiple clotting factor deficiency
| liver failure, vit K deficiency, DIC
186
inheritance of haemophilia
x-linked
187
haemophilia A
factor VIII deficiency
188
haemophilia B
factor IX deficiency
189
presentation haemophilia
recurrent haemarthroses
| recurrent soft tissue bleeds
190
factor V leiden disease
inherited thrombophilia
point mutation in Factor V, so protein C can't inhibit it
191
anti phospholipid syndrome predisposes to what type of thrombosis?
both arterial and venous !
192
heparin mode of action
potentiates anti-thrombin
193
monitoring heparin
LMWH - anti Xa levels
unfractionated heparin - APTT
194
Mx bleeding on heparin
stop heparin (has a short half life)
if bleeding severe - protamine sulphate
195
mode of action of rivaroxaban
factor Xa inhibitor
196
mode of action of apixaban
factor Xa inhibitor
197
mode of action of dabigatran
direct thrombin inhibitor
198
mode of act ion of warfarin
antagonizes vitamin K
199
why does warfarin have a prothrombotic effect in the first few days
inhibits protein C
200
monitoring warfarin
PT
201
Mx bleeding on warfarin
stop warfarin
give Vit K (takes 6h to work)
give prothrombin complex concentrates (works immediately)
202
aspirin mode of action
inhibit the COX pathway
| - COX is needed to make thromboxane A2, which is released from platelets when they aggregate.
203
s/e of aspirin
bleeding
| blockage of prostaglandins - ulceration, bronchospasm
204
mode of action of clopidogrel
ADP receptor antagonist
205
mode of action of dipyradimole
phosphodiesterase inhibitor
206
equations to work out cause of shock
MAP = CO x TPR
CO = HR x SV
