Haematology Flashcards
1
Q
what is the defect in paroxysmal nocturnal haemoglobinuria?
A
acquired genetic defect in GPI
GPI: helps anchor biomolecules to red cell membrane
2
Q
what is polychromasia? what does it mean?
A
blueish appearance
= reticulocytes
3
Q
what does haptoglobin do? what does low levels mean?
A
binds, removes free Hb
low haptoglobins = high levels of free Hb
4
Q
features of hereditary spherocytosis and cells
A
vertical interaction
ankyrin
cells lack area of central pallor, polychromatic cells
5
Q
what test is used in hereditary spherocytosis?
A
osmotic fragility test
6
Q
features of hereditary elliptocytosis
A
horizontal interaction
spectrin
no polychromasia
7
Q
what is hereditary pyropoikilocytosis?
A
homozygous form of HE
poikilocytosis
severe HA
8
Q
what would a blood film show in G6PDD? what stain?
A
Heinz bodies
denatured Hb
methyl violet stain
9
Q
blood film in pyruvate kinase deficiency
A
echinocytes (red cells have short projections)
10
Q
clinical feature of pyruvate kinase def
A
chronic HA
11
Q
what are 2 causes of basophillic stippling?
A
pyridine 5’nucelotidase deficiency
lead poisoning
12
Q
what is the test used for PNH?
A
Ham’s test
13
Q
what are some indications for splenectomy?
A
- PK def
- hereditary spherocytosis
- severe elliptocytosis/pyropoikilocytosis
- thalassaemia syndromes
- immune HA
14
Q
what are type 1 abnormalities ?
A
promote proliferation and survival (anti-apoptosis)
15
Q
what are type 2 abnormalities?
A
block differentiation
accumulation of blast cells
16
Q
translocation in acute promyelocytic leukaemia
A
t(15;17)
PML-RARA fusion gene
17
Q
features of acute promyelocytic leukaemia
A
abnormal promyelocytes
contain multiple Auer Rods
associated with DIC
18
Q
good prognostic factors in ALL
A
hyperdiploidy
T(12;21)
T(1;19)
19
Q
bad prognostic factors in ALL
A
hypodiploidy
T(4;11)
20
Q
what treatment can be given in Philadelphia Chromosome?
A
imatinib
21
Q
what does vessel injury stimulates?
A
- vasoconstriction
- platelet activation
- activation of coagulation cascade
22
Q
what is the function of the endothelium?
A
- barrier between blood and procoagulant sub endothelial structures
- synthesis of PGI2, vWF, plasminogen activators, thrombomodulin
- exposure = platelet aggregation
23
Q
what is the lifespan of a platelet and the significance of this?
A
10 days
anti-plt drugs need stopping 10 days before surgery
24
Q
what are the platelet surface glycorproteins?
A
GpIa
GpIb
GpIIb/IIIa
25
what are the 2 ways platelets can adhere to sub-endothelial structures?
- directly: through GIp1a
| - indirectly: by binding vWF via GIp1b
26
what happens when platelets adhere to subendothelial structures?
release of ADP and thromboxane A2
| = platelet aggregation (via GIpIIb/IIa aka fibrinogen receptor)
27
why are ADP receptors important?
ADP receptors important for platelet aggregation
| e.g. clopidogrel, ticagrelior
28
what is the rate limiting step for fibrin formation?
factor Xa
29
what is the coagulation pathway triggered by?
trace amounts of thrombin
30
what are the effects of thrombin?
- activates fibrinogen
- activates platelets
- activates pro-cofactors (F5, F8)
- activates zymogens (F7, 11, 13)
All link together = PROTHROMBINASE COMPLEX
this causes a burst of prothrombin to thrombin
31
what happens in the initiation phase?
1. damaged endothelium = exposed TF
2. TF + F7 = F7a
3. TF/F7a complex = activation of F9 and F10
4. F10 and F5a complex formed
32
what happens in the amplification phase?
1. F10a/F5a complex = prothrombin to thrombin (small amount)
2. Thrombin then: activates platelets, activates F11/F8/more F5a, F11 activates F9
3. F5a, F8a and F9a bind to activated platelet
33
what are the steps in the propogation stage?
1. activated platelet with F5a/8a/9a recruits F10a
2. = THROMBIN burst
3. thrombin causes fibrinogen to fibrin (forms table fibrin clot)
34
what 2 uncommon things can cause vitamin K deficiency?
antibiotics
| biliary tree obstruction
35
what converts plasmingogen to plasmin?
tPA
| urokinase
36
what does plasmin do?
breaks fibrin down to fibrin degradation products
37
what inhibits tPA and urokinase?
plasminogen activator 1 + 2
38
what is plasmin inhibited by?
alpha 2 antiplasma
| alpha 2 microglobulin
39
what is the most active antithrombin? what also to note about this?
anti-thrombin 3
| heparin augments this
40
how are activated 5 and 8 inactivated?
through protein C and S pathway
| protein S allows full activation of protein C
41
what is the issue in F5 Leiden?
- activated protein C resistance
- F5 resistant to breakdown
= prothrombotic state
42
what is tissue factor pathway inhibitor?
activated to neutralise TF/F7a complex as this complex is not needed for very long
43
plt disorder vs coagulation disorder signs
- platelet disorder: petechiae, purpura
| - coagulation disorder: haemothrosis/ecchymoses
44
what are the different causes of defective plt function?
- acquried (e.g. aspirin/ESRF)
- congenital (e.g. thrombasthenia)
- cardiopulmonary bypass
45
what is the main aim of plt activation?
GIpIIb/IIIa activation
46
what are the causes of immune-mediated thrombocytopaenia?
- idiopathic
- drug induced (e.g. quinine, rifampicin)
- connective tissue disease (e.g. RA, SLE)
- lymphoproliferative disease
- sarcoidosis
47
where is the defect in haemophillia? what do test results show?
INTRINSIC pathway
| prolonged APTT, normal PT
48
main clinical symptom of vWD
mucocutaenous bleeding
49
3 types of vWD
1. PARTIAL quantitative
2. QUALITATIVE
3. TOTAL quantitative
50
what is the relationship between F8 and vWF?
binding of F8 to vWF protects F8 from destruction
51
treatment of high INR
Omit warfarin, Vit K, PCC
52
what is myeloproliferation?
- proliferation
- full differentiation
(fully functional)
53
what is leukaemia?
prolfieration, no differentiation
| not functional
54
what is myelodysplastic syndrome?
ineffective proliferation
| ineffective differentiation
55
what weird symptoms can PV cause and why?
increase histamine release
| = aquagenic pruritus, peptic ulceration
56
what investigation results in PV?
- bone marrow biopsy = inc cellularity (no fat spaces)
- low EPO
- JAK2 V617F mutation (exon 14)
57
what mutation in erythrocytosis?
exon 12 Jak 2 (only some)
58
treatment of PV
venesection
cytoreductive therapy
aspirin
59
treatment of idiopathic erythrocytosis
venesection ONLY
60
treatment of essential thrombocythaemia
- aspirin (prevent thrombosis)
- anagrelide (inhibits plt formation)
- hydroxycarbamide (antimetabolite, mildly leukaemogenic)
- alpha interferon (<40 yrs)
61
SEs of anagrelide
palpitation
flushing
can accelerate myelofibrosis
62
chronic idiopathic myelofibrosis
chronic myeloproliferative disease
reactive bone marrow fibrosis
extramedullary haemopoiesis
63
blood film findings in myelofibrosis
leucoerythoblastic
tear drop poikilocytes
giant plt, circulating megakaryocytes
64
treatment of myelofibrosis
- symptomatic
- cytoreductive therapy (e.g. hydroxycarbamide, thalidomide)
- BM transplant
65
what are BAD prognostic signs of myelofibrosis?
- severe anaemia
- thrombocytopaenia <100 x109/l
- massive splenomegaly
66
what are the features of a leucoerythroblastic picture?
- tear drop poikilocytes (aniso + poikilocytosis)
- nucleated RBCs
- immature myeloid cells
67
what are diseases that do not cause a neutrophillia?
- brucella
- typhoid
- many viral infections
68
what are the signs of a reactive neutrophillia?
- band cells
- toxic granulation
- signs of infection/inflammation
69
what are the causes of a monocytosis?
- TB, brucella, typhoid
- Viral: CMV, VZV
- sarcoidosis
- chronic myelomonocytic leukaemia
70
fusion gene in chronic eosinophilic leukaemia
FIP1L1 - PDGFRa
71
describe the lymphocytes in infectious mononucleosis
mature atypical lymphocytes
72
symptoms of thromboplebitic syndrome
recurrent pain
swelling
ulcer
73
what anticoagulant molecules do the blood vessels normally express?
- thrombomodulin
- endothelial protein C receptor
- TFPI
- Heparans
74
what are the effects of inflammation/injury on the vessel wall?
makes vessel wall prothrombotic
- anticoagualnt molecules down regulated
- adhesion molecules upregulated
- TF expressed
- prostacyclin production decreased
75
what does stasis cause?
platelet adhesion
| leukocyte adhesion and transmigration
76
what effect does hypoxia have on the endothelium?
inflammatory effect
77
which VTE have higher risk of recurrence?
men have higher recurrence compared to women
| proximal higher rate than distal
78
what is MDS?
development of a clone of marrow stem cells with abnormal maturation
results in:
- functionally defective blood cells
- numerical reduction
79
bone marrow morphological features in MDS
- Pelger-huet anomaly (bilobed neutrophils)
- dysgranulopoiesis of neutrophils (failure of granulation)
- dyerythropoiesis of red cells
- dysplastic megakaryocytes
- inc proportion of blast cells in marrow (<5%)
80
features of the international prognostic scoring system in MDS
- BM blasts
- Karotype
- Hb
- Platelets
- Neutrophils
81
2 treatments for MDS that may prolong life
allogenic SCT
| intensive chemo
82
what is the treatment of MDS?
- supportive care (blood, GFs, anti-microbial therapy)
- biological modifiers (immunosuppressive agents)
- oral chemo (hydroxyurea)
- low dose chemo
- intensive chemo/SCT (high risk MDS)
83
what medication is used in 5q minus syndrome?
lenalidomide
84
causes of primary bone marrow failure and the cell affected
- Fanconi anaemia (multipotent stem cell)
- Diamond-Blackfan (red cell progenitors)
- Kostmann's syndrome (neutrophil progenitor)
85
inherited causes of aplastic anaemia
- dyskeratosis congenita
- Fanconi anaemia
- Schwann-Diamond
86
secondary causes of aplastic anaemia
```
radiation
cytotoxic agents
chloramphenicol
NSAID
hepatitis
SLE
```
87
what is the management of BM failure?
- immunosuppressive therapy = older pt (e.g. anti-lymphocyte globulin, ciclosporin)
- SCT = younger patients
88
the gene mutations in Fancoi Anaemia result in?
- abnormalities in DNA repair
| - chromosomal fragility
89
what is the phenotype of Fanconi's Anaemia?
- short stature
- hypopigmented spots, cafe au lait spots
- abnormality of thumbs
- micro/hydrocephaly
- hypogonadism
- developmental delay
90
triad in dyskeratosis congenita
- skin pigmentation
- nail dystrophy
- leukoplakia
+ BM failure
91
what is the pathology behind DC?
telomere shortening
92
name 4 malignant genes
Bcl2
Bcl6
Myc
Cyclin D1
93
cause of adult T cell leukaemia
HTLV1
94
what is the process of B cells in the B cell area?
- mantle zone = naive unstimulated B cells
- they then migrate into germinal centre
- in germinal centre = encounter APCs and undergo activation and selection
- lots of cell turnover in germinal centre
95
CD marker of B cells
CD20
96
CD markers of T cells
CD3, CD5
97
name the low grade B cell NHL
- follicular lymphoma
- small lymphocytic/CLL
- marginal zone lymphoma
- mantle zone lymphoma
98
name the high grade B cell NHL
diffuse large B cell lymphoma
99
name the intermediate B cell NHL
Burkitts
100
features of follicular lymphoma
- lymphadenopathy in middle aged
- follicular pattern, germinal centre cell origin
- centrocytes and centroblasts
101
translocation of follicular lymphoma
t(14;18) --> Bcl-2 (anti-apoptosis gene)
102
Treatment of follicular lymphoma
at presentation = watch and wait
| R-CVP
103
features of SLL/CLL
- small lymphocytes (CD5, CD23 +ve)
- smudge cells
- associated with hypogammaglobulinaemia (non-functioning B cells)
- Richter transformation risk
104
Tx of SLL/CLL
supportive
| watch and wait
105
features of mantle cell lymphoma and translocation
aggressive B cell lymphoma
often presents with disseminated disease
t(11;14) --> cyclin D1 overexpression
106
translocation and microscopy in Burkitt's
- c-myc translocation
- t(8;14) most common
- microscopy = starry sky
107
features of diffuse Large B cell lymphoma
large lymphocytes
t(14;18)
2 types (linked to latent EBV and HHV8)
108
Good and poor prognostic signs in DLBL
Good: germinal centre phenotype
Poor: p53/high proliferation fraction
109
what are the special forms of T cell lymphoma?
- adult T cell leukaemia/lymphoma
- enteropathy-associated T cell lymphoma
- cutaneous T cell lymphoma
- anaplastic large cell lymphoma
110
features of anaplastic large cell lymphoma
large epitheliod lymphocytes
t(2;5)
Alk-1 protein expression (= better prognosis)
111
what are the subtypes of classical Hodgkin lymphoma?
nodular sclerosing
mixed cellularity
lymphocyte rich depleted
112
what to remember about lymphocyte predominant?
some relationship to NHL
113
features of classical HL
young/middle aged
single group of LNs
Associated with EBV
Reed-sternberg cells
114
diagnostic markers in classical HL
CD30, CD15
115
features of nodular lymphocyte predominant Hodgkin lymphoma
isolated lymphadenopathy
not associated with EBC
can transform to higher grade B cell lymphoma
116
Treatment of HL
ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine)
| +/- Radiotherapy
117
what is important to remember about radiotherapy?
increase chance of secondary malignancy
118
DLBCL international prognostic index
- age > 60 years
- serum LDH > normal
- performance status 2-4
- stage III or IV
- more than one extranodal site
119
DLBCL treatment
```
R-CHOP
Rituximab (anti-CD20)
Cyclophosphamide
Doxorubicin
Vincristine
Prednisolone
```
120
features of Enteropathy Associated T cell lymphoma
coeliac
mature T cells
responds to chemotherapy
121
CD makers of normal mature B cells
CD19 +ve
| CD5 -ve
122
CD makers of normal mature T cells
CD3 +ve
CD19 -ve
CD5 +ve
123
what CD marker do B cells continue to express in CLL?
CD5
124
what is binet staging for CLL?
A: <3 lymphoid areas
B: >3 lymphoid areas
C: Hb < 100g/l, plt <100 x109/l
125
what is the significance of unmutated VH?
half of CLL patients have unmutated VH (arising from pre-germinal centre cells)
unmutated = worse prognosis
126
what are the high risk CLL cases?
- TP53/17p deletion
| - refractory disease/ early relapse (<24 months)
127
treatment of high risk CLL cases
- ibrutinib (bruton TK inhibitor) = B cell depletion
- venetoclax (anti-Bcl2)
- CAR-T (T cells kill and deplete B cells)
128
Philadelphia -ve myeloproliferative neoplasms
PV
ET
PMF
129
Philadelphia positive myeloproliferative neoplasms
CML
130
CML presentation
```
lethargy
hypermetabolism
thrombotic event
mono-ocular blindness
CVA
bruising
bleeding
massive splenomegaly/hepatomegaly
```
131
what is the natural course of CML?
1. Chronic phase (cells proliferate but able to differentiate into mature cells)
2. Accelerates phase (10-19% blasts due to additional mutation)
3. Blast crisis (>20% blasts)
132
what is the philadelphia chromosome?
t(9;22)
codes bcr-abl
drives replication in cells containing this chromosome
133
CML treatment
1. 1st gen TK inhibitor e.g. Imatinib
2. 2nd gen e.g. Dasatinib
3. 3rd gen e.g. Bosutinib
4. Consider allogenic SCT
134
what are the FBC changes in pregnancy?
- mild anaemia
- macrocytosis
- neutrophilia
- thrombocytopaenia (+ inc in platelet size)
135
what are the causes of thrombocytopaenia in pregnancy?
- physiological (most common)
- pre-eclampsia
- ITP
- microangiopathic
136
platelet count needed for epidural and delivery
>50 x109/L for delivery
| >70 x109/L for epidural
137
how does pre-eclampsia cause thrombocytopaenia?
due to increase activation and consumption
| is proportionate to severity
138
ITP in pregnancy
- may precede pregnancy
- baby may be affected
- Tx (for bleeding or delivery): IVIg, steroids, anti-D
139
treatment of TTP
requires plasma exchange
140
what are the coagulation changes in pregnancy?
= procoagulation state = increase rate of thrombosis
- inc thrombin generation
- inc fibrin cleavage
- dec fibrinolysis
141
what are factors seen in every one that increase the risk of thrombosis in pregnancy?
- change in blood coagulation
- decrease venous return
- vessel wall
142
what are factors that increase the risk of thrombosis in pregnancy that are variable between patients?
- hyperemesis/ dehydration
- pre-eclampsia
- multiple pregnancy
- increase age
- IVF: OHS
143
what can you give women with APL syndrome in pregnancy?
aspirin and heparin
144
what is placenta accreta, increte and percreta?
accreta: through endometrial lining
increta: through uterine wall
percreta: through uterine wall, stick to other organs
145
what is thought to trigger the changes in amniotic fluid embolism?
DIC triggered by TF within amniotic fluid
146
what are centroblasts?
activated B cells
147
features of immature plasmablastic cells
myeloma cells with:
- prominent nucleoli
- reticular chromatin
- less abundant cytoplasm
148
what is important to remember about plasmablastic myeloma?
POOR prognosis
149
what are myeloma cells positive for?
CD138
| light chain restriction
150
what are myeloma cells negative for?
CD19
CD20
surface Ig
151
what are the 4 main treatment domains in MM?
- cytostatic drugs e.g. mephalan
- steroids
- immunomodulators e.g. thalidomine, lenalidomide
- protease inhibitors
152
what is the importance of the proteasome?
- fishes out misfolded proteins and degrades them into amino acids = ER associated degradation
- in myeloma = lots of protein secretion, if misfolded they can accumulate in ER and cause fatal ER stress
153
what do proteasome inhibitors do?
e.g. Bortezomib
| inhibit proteasome = accumulation of misfolded proteins in myeloma cells = myeloma cell death
154
what is the MoA of thalidomied?
targets turnover of TFs that are important for myeloma cell survival
155
what type of reaction is RhD in blood?
delayed haemolytic transfusion reaction
156
what is the process of reverse grouping?
known A + B group RBCs mixed with patient plasma (IgM Abs)
| causes agglutination if positive
157
how do you screen patient plasma?
using indirect antiglobulin technique
158
what are the different cross match techniques?
- full cross match (uses IAT)
- immediate spin (only detect ABO)
- electronic cross match
159
how should red cells be stored and transfused?
- 4 degrees for 35 days
- must be transfused within 4 hours of leaving fridge
- transfuse 1 unit RBC over 2-3 hours
160
do platelets need cross matching?
do not need crossmatch because antigens are weakly expressed
| should be D compatible
161
how should platelets be transfused and why?
transfuse 1 unit over 20-30 mins
| stored at room temp so contaminate quick
162
what matching needs to be done for plasma?
- give ABO compatible
| - D group doesn't matter
163
universal donor for plasma
AB
164
what reaction is most likely with plasma transfusion?
- is frozen = 30/40 mins to thaw
| - allergic reaction most likely (not contaminated by microbes)
165
what is the effect of 1 unit RBC?
10g/L increase in Hb
166
what are 2 contraindications to platelet transfusion?
- heparin induced thrombocytopaenia
| - TTP
167
what is the effect of 1 unit of platelets?
increase by 30-40 x109/L
168
what does FFP contain?
all clotting factors
169
what blood product to reverse warfarin?
PCC
170
what are the acute transfusion reactions (<24 hours)?
- acute haemolytic (ABO incompatible)
- allergic/anaphylaxis
- infection (bacterial)
- febrile non-haemolytic
- TACO
- TRALI
171
what are the delayed transfusion reactions (>24 hrs)?
- delayed haemolytic (Abs)
- infection
- TA-GvHD
- post transfusion purpura
- iron overload
172
what is the cause and treatment of FNHTR?
- caused by release of cytokines from white cells during storage
- Tx: slow/stop transfusion, paracetamol
173
cause and treatment of allergic transfusion reaction
cause: allergy to plasma protein in donor
Tx: slow/stop tranfusion, IV antihistamines
174
what causes acute intravascular haemolysis (IgM)?
wrong blood
175
what is the cause of bacterial contamination reaction?
bacterial growth can cause endotoxin production
| = immediate collapse
176
what is the cause of TRALI? how do you prevent?
anti-WBC Abs in donor blood interact with WBCs in patient
aggregates stuck in capillaries
= release of enzymes and metabolites = lung damage
prevent: male doctors
177
cause of delyaed HTR
- previous transfusion = IgG formed
| - second transfusion with same antigens = RBC destruction = extravascular haemolysis
178
which patients does post transfusion purpura affect? Tx?
affects HPA-1a negative pt
| Tx: IVIG
179
what is the CD marker of stem cells?
CD34
180
indications of autologous stem cells
- myeloma
- lymphoma
- CLL
181
indications of allogenic stem cells
when pt disease unlikely to be eradicated from bone marrow by standard chemo
- acute and chronic leukaemia
- myeloma
- lymphoma
- BM failure
- congenital immuno def
182
what are the factors affecting outcome of bone transplant? what is the risk score called?
EBMT Risk score
- age
- disease phase
- gender of R/D (female into male = point)
- time to BMT
- donot (sibling = 0, VUD = 1)
183
who gets the worst GvHD?
male donors with female patients
184
treatment of GvHD
corticosteroids
cyclosporin A
mycophenolate
185
what is transient abnormal myelopoiesis?
congenital leukaemia
common in Down syndrome
tends to remit spontaneously within first 2 months
186
what is haemoglobinopathy?
structurally abnormal Hb
187
HbA and when oresent
alpha 2, beta 2
| late fetus, infant, child, adult
188
HbA2 and when present
alpha 2, delta 2
| infant, child, adult
189
how much HbA2 should an adult have?
<3.5% of total adult Hb
190
HbF and when present
alpha 2 gamma 2
191
how much HbA at birth?
1/3 Hb
| rapidly increase after
192
what is the effect of hypoxia in SCD?
hypoxia leads to polymerisation of HbS
| = crescent shaped RBC, blocked blood vessels
193
what is HbSC
sickling disorder
| slightly milder than HBSS
194
what does sickle cell anaemia present differently in children vs adult?
- different destruction of red bone marrow (contains haemopoietic precursors = susceptible to infarction = bone pain)
- infant still has functioning spleen (child: splenic sequestration = acute pooling of RBCs in spleen)
195
bone pain in adults and infants
```
adults = central skeleton
infants = all way down to finger tips
```
196
what is acute chest syndrome?
infarction in ribs and lungs
197
treatment of SCA
- vaccinate
- folic acid
- penicillin
198
what does beta thalassemia present?
after 6 months of life
199
clinical features of poorly controlled beta thalassaemia major
- anaemia: HF, growth retardation
- EPO drive: bone expansion, hepato/splenomegaly
- Fe overload: HF, gonadal failure
200
inheritance pattern of G6PD and what this means?
X-linked
| most suffers are males
201
triggers of G6PD
- infections
- drugs
- napthalene
- fava beans
202
which is more common in haemophillia A or B?
A x4 more common
203
which leukaemia needs CNS directed therapy?
ALL
204
pathophysiology of ACD
IFN-gamma, IL1, TNF = dec erythroid precursors, dec EPO, impaired iron utilisation
205
causes of pancytopaenia
- aplastic anaemia
- leukaemia
- infiltration (e.g. lymphoma, carcinoma)
- drugs (e.g. chemo)
- B12/folate def
