Haematology Flashcards
1
Q
What effect does DIC have on D-Dimer?
Why?
A
D-Dimer is elevated, as it reflects an increase in fibrin degradation products with the pathological and extensive fibrinolysis that occurs
2
Q
What is the hallmark of DIC on coagulation profile?
A
Decreased fibrinogen
3
Q
What will the blood film show in DIC?
A
Schistocytes / helmet cells due to microangiopathic haemolysis
Thrombocytopaenia
4
Q
What do smudge cells on blood film indicate?
A
Chronic Lymphocytic Leukaemia
5
Q
What is the difference between SLL and CLL?
A
SLL - primarily nodal, <5 lymphocytes in blood
CLL - primarily blood, >5 lymphocytes in blood
6
Q
What haematological condition is venetoclax used for?
A
Refractory CLL
7
Q
Which agent is used for MDS with del5q?
A
Lenalidomide
8
Q
What are some side effects of imatinib?
A
Weight gain, nausea, diarrhoea, oedema, muscle cramps
9
Q
What is the role of OCT-1?
A
It is the main transporter for imatinib.
High OCT-1 activity is associated with better response to imatinib
10
Q
What is the most common finding on presentation of multiple myeloma?
A
Anaemia
11
Q
What is daratumumab? What is its role in multiple myeloma?
A
Anti-38 monoclonal ab
Approved for use in relapsed MM
12
Q
What is the main cause of hypercalcaemia in multiple myeloma?
A
Primarily due to increased osteoclastic bone resorption
13
Q
What are the two main prognostic markers in multiple myeloma?
A
Beta 2 microglobulin + albumin
14
Q
What do Dohle bodies in white cells indicate?
A
Toxic granulation
Seen in leukamoid reaction = immature cells in the blood due to
- severe infection
- severe sepsis
- massive haemorrhage
- bone marrow infiltration
15
Q
What condition predisposes to warfarin-induced skin necrosis?
A
Protein C deficiency
16
Q
Blood film = target cells + teardrop cells
A
Thalassaemia
17
Q
Blood film = pencil cells
A
iron deficiency
18
Q
Blood film = Bite cells
A
Caused by Heinz bodies, seen in oxidative haemolysis e.g. G6PD deficiency
19
Q
Blood film = Spur cells (irregular projections)
A
Liver disease
20
Q
Blood film = burr cells / echinocytes (regular projections_
A
Uraemia
21
Q
Blood film = tear drop cells
A
Extramedullary haematopoiesis or thalassaemia
22
Q
Blood film = nucleated RBCs
A
Severe haemolysis, hypoxia, stress or PMF
23
Q
Blood film = Howell-Jolly bodies
A
Hyposplenism
They are nuclear remnants of RBCs usually removed by spleen
24
Q
Blood film = any blasts
A
NEVER NORMAL on peripheral smear
Suggests haematological malignancy
25
Blood film = Auer rods
Acute myeloid leukaemia
26
Blood film = schistocytes
Microangiopathic haemolysis
27
What haem malignancy is HTLV-1 associated with?
Acute T-lymphoblastic Leukaemia / Lymphoma
28
What haem malignancy is EBV associated with?
Burkitt lymphoma
PTLD
Hodgkin lymphoma
29
What haem malignancy is HIV associated with?
DLBCL
Burkitt lymphoma
Hodgkin lymphoma
Primary CNS lymphoma
30
What haem malignancy is HHV-6 associated with?
Primary effusion lymphoma
31
What haem malignancy is benzene associated with?
Multiple myeloma
32
What haem malignancy is hair dye associated with?
Follicular lymphoma
33
What cytogenetic marker is associated with APML?
t(15,17)
34
What is the strongest adverse prognostic factor in AML?
Age >60
35
What is the biggest risk factor for recurrent DVT/PE?
Unprovoked VTE
36
What are the high risk inherited thrombophilias?
- AT deficiency
- Protein C / S deficiency
- Factor V Leiden homozygote
- Prothrombin gene mutation homozygote
- Double heterozygotes for FVL and PGM
37
What kind of thrombosis are APLS at risk of?
Arterial AND venous
38
What are the APLS ab to test for?
Anti-Beta 2 glycoprotein 1
Anti-cardiolipin
Lupus anticoagulant
Must be repeated after 12 weeks to make diagnosis
39
What are the initial laboratory findings in lupus anticoagulant?
Prolonged APTT that does not correct with mixing.
| Prolonged reptilase time, normal TCT
40
What are the 3 causes of prolonged APTT?
Factor deficiency
Inhibitor
Drugs
41
What are the 2 possible inhibitors that would prolong APTT?
Lupus anticoagulant
| Specific factor inhibitor
42
Which of the APLS ab have the weakest correlation with thrombosis?
Anti-cardiolipin ab
43
What is the greatest risk factor for VTE in pregnancy?
Prior VTE
44
What are the direct thrombin inhibitors used in HITS?
Danaparoid
Argatroban
Bivalirudin
45
What is the main use of fondaparinux?
In patients with HITS + normal renal fx
46
Which DOAC is most reliant on renal function for excretion?
Dabigatran
47
What is the anticoagulant of choice in prosthetic heart valves?
Warfarin
48
What are 2 GpIIb/IIIa inhibitors?
| What is their use?
Abciximab
Tirofiban
Coronary angiography
49
What type of bleeding is more characteristic of factor deficiencies?
Haemarthroses, deep muscle bleeds
50
What type of bleeding is more characteristic of platelet / vWF disorders?
Epistaxis + GI bleeding, skin, genito-urinary
51
Umbilical stump bleeding -> classic deficiency?
Factor 13
52
What are the factors involved in the common coagulation pathway?
Factor X, factor V, factor II (prothrombin), and factor I (fibrinogen)
**think of our currency, $1, $2, $5, $10
53
Which pathway does the APTT measure?
| Which factors are involved?
Intrinsic pathway + common
Factor XII, XI, IX, VIII
Factor 1, 2, 5, 10
54
Which pathway does the PT measure?
| Which factors are involved?
Extrinsic + common
Factor 7, TF
Factor 1, 2, 5, 10
55
Which factor drops first in warfarin administration?
Factor 7
56
Why is there a theoretical risk of pro-thrombotic state with warfarin initiation?
___
57
What level of Factor is present in 'severe' haemophilia?
<1%
58
Which type of haemophilia more commonly develop inhibitors?
Haemophilia A
59
What is the mechanism of tranexamic acid?
Forms a reversible complex that displaces plasminogen from fibrin -> inhibition of fibrinolysis
Also inhibits the proteolytic activity of plasmin
60
What is vWF's role related to Factor VIII?
Acts as "chaperone" which binds Factor VIII to prevent its premature degradation
61
Which blood group has lower levels of vWF?
Group O blood group has lower vWF
62
What is the 1st line therapy for mild vWD?
DDAVP - releases vWF and FActor 8 from storage sites
63
What is the defect in Bernard-Soulier Disease?
| What is it phenotypically similar to?
Glycoprotein 1b-IX-V
vWD
64
What is the defect in Glanzmann thrombasthenia?
| What is the phenotype?
Glycoprotein 2b/3a complex
Severe bleeding diathesis
65
Which therapy raises platelets fastest (other than platelets) in ITP?
IVIG (faster than steroids)
66
What is the indication (in Australia) for TPO-mimetics in ITP?
For failed splenectomy or splenectomy contraindicated
67
What is the main treatment for TTP?
Plasma exchange
68
What is the main treatment for atypical HUS?
Eculizumab - C5 inhibitor
69
What is the pathogenesis of HITS?
Results from an auto-antibody against Platelet Factor 4 (PF4) in complex with heparin
70
What are the 4 Ts in the score for HITS?
Thrombocytopaenia severity
Thrombosis
Timing of onset after exposure
Other cause for thrombocytopaenia
71
Alternatives to heparin in HITS?
Direct thrombin inhibitors - bivalirudin, argatroban
Danaparoid
Fondaparinux
72
Which blood groups can AB people receive PRBC from?
ALL
73
Which ABO antibodies are in serum of O group?
Anti-A and Anti-B
74
Which ABO antibodies are in serum of AB group?
None
75
What are the VTE-prevention recommendations for a pregnant woman with no personal history of VTE, but a FHx and a Factor V Leiden mutation?
Observation antepartum
| Only consider postpartum prophylaxis if other risk factors
76
What are the VTE-prevention recommendations for a pregnant woman with no personal Hx VTE who has antithrombin deficiency?
Therapeutic LMWH antepartum + 6/52 postpartum
77
What are the VTE-prevention recommendations for a pregnant woman with no personal Hx VTE who has a Protein C or S deficiency?
Prophylactic LMWH antepartum + 6/52 postpartum
78
What are the VTE-prevention recommendations for a pregnant woman with single prior provoked VTE (not during pregnancy)?
Observation antepartum, and prophylactic LMWH 6/52 postpartum
79
What are the VTE-prevention recommendations for a pregnant woman with single prior pregnancy-provoked VTE?
Prophylactic LMWH antepartum + 6/52 postpartum
80
What are the VTE-prevention recommendations for a pregnant woman with recurrent unprovoked VTE?
Therapeutic anticoagulation throughout
81
What is Andaxenet Alfa?
Recombinant FXa molecule
Works as FXa antidote by being a decoy for the drug to bind to
82
Where does Factor VII work in the coagulation cascade?
Initiation of clotting
Binds to Tissue Factor, which activates Factor X
83
What is the role of platelets in coagulation?
Platelets provide binding sites for coagulation factors and a phospholipid surface that promotes assembly of multicomponent complexes (i.e. X-ase, Prothrombinase)
84
What is contained in the prothrombinase complex?
Factor Xa + Factor Va
85
What is contained in the Extrinsic X-ase complex?
Factor VIIa + TF
86
What is contained in the Intrinsic X-ase complex?
Factor VIIIa + Factor IXa
87
What is the other name for Factor II and IIa?
Prothrombin -> Thrombin
88
What is the other name for Factor I?
Fibrinogen
89
What is the substance exposed at site of wound endothelium which initiates haemostasis?
Tissue factor
90
What is Protein C's role in coagulation?
Activated protein C binds to its co-factor protein S, which then inhibits factors Va and VIIIa -> slows the coagulation process
91
How is Protein C activated?
Thrombomodulin binds to thrombin, changing its identity from procoagulant to anticoagulant. Thrombin then cleaves Protein C to activate it.
92
What is the effect of Factor V Leiden mutation on coagulation?
Factor V Leiden is not as susceptible to cleavage by activated protein C and is therefore inactivated more slowly, resulting in a hypercoagulable state
93
What does Reptilase Time measure?
Like TCT but uses reptilase instead of thrombin
Used in prolonged APTT that doesn't correct.
Unaffected by heparin, thus if NORMAL -> prolonged APTT likely due to heparin
94
What are the labelled uses of NovoSeven?
Factor 8 or 9 deficiency or inhibitor
95
When should treatment for ITP be initiated?
PLts <30 or bleeding sx
96
What is the classic pentad of TTP?
```
Fever
MAHA
Thrombocytopaenia
Renal involvement
Neuro sx
```
97
What is the role of ADAMTS13 in TTP?
ADAMTS13 cleaves vWF multimers. Severe deficiency of ADAMTS13 activity in TTP which results in large vWF multimers which cause endothelial injury
98
What is the management of INR >10 with no bleeding?
Withhold warfarin
| Give Vitamin K
99
What is the management of INR 9 with no bleeding?
Withhold warfarin
100
What does leukodepletion of PRBC help to avoid?
Febrile non-haemolytic reactions
101
What does irradiation of blood products help to avoid?
Transfusion-associated GVHD
102
What key substances does cryoprecipitate contain?
Fibrinogen
Factor 8
Factor 13
vWF
103
What is the key treatment for low fibrinogen?
Cryoprecipitate
104
What is the main use of Prothrombinex?
| What does it contain?
Warfarin reversal
| Factors 2, 7, 9, 10 (TV channels)
105
What is the most common point of error resulting in ABO incompatibility?
Incorrect check at bedside of patient
106
What is the cause of febrile non-haemolytic transfusion reaction?
Antibodies against donor leukocytes
107
What is the most common blood product to cause sepsis?
Platelets (1/75,000)
108
What is the presumed aetiology of TRALI?
Donor antibodies to recipient leukocytes, which are then primed and sequestered in the lungs.
Neutrophils are activated and release ++ cytokines, leading to capillary leakage
109
What is the standard ratio of PRBC : FFP : Platelets in massive transfusion?
4 PRBC : 2 FFP : 1 platelets
110
Where is iron absorbed from principally in the gut?
Duodenum
111
Where is the largest pool of iron storage within body?
Red blood cells
112
Where is hepcidin produced?
What is its role?
Liver.
Downregulates Ferroportin at BASOLATERAL membrane of enterocyte. Thus decreases uptake of iron by transferrin, reduced systemic absorption. In this setting, iron is trapped in enterocyte, and will be lost in enterocyte slouging
113
What happens to iron at enterocyte brush border?
Reduced from Fe 3+ to Fe 2+, taken in by DMT1
114
What is the effect of inflammation on hepcidin?
It is elevated. Acute phase reactant
| Leads to functional iron deficiency
115
What is the common iron state in polycythaemia vera?
Iron deficiency. DO NOT replace iron
116
Is ferritin more specific or sensitive?
Specific, not sensitive
117
Which element of iron studies will be most deranged in haemachromatosis?
Transferrin saturation -> will be very high
118
What effect does liver disease have on transferrin?
Low -> liver produces transferrin
| May lead to high TSat
119
What is the favoured form of PO iron replacement?
How long will it generally take to replenish iron stores?
Ferrous sulphate
~6 months
120
Which out of iron deficiency or thalassaemia will result in lower MCV compared to Hb level?
Thalassaemia lowers MCV out of proportion to Hb
121
What is the key test to differentiate between iron deficiency and anaemia of chronic disease?
Soluble transferring receptor saturation
- in IDA -> transferring receptors become upregulated due to cells being "hungry for iron".
- in ACD this level will be normal
122
What is the key test finding in pure red cell aplasia?
Reticulocytes -> will be low
123
3 causes of normocytic anaemia?
Acute blood loss
Anaemia of chronic disease
Pure red cell aplasia
124
What is the role of Transcobalamin II ?
Binds functional B12 in ??__intestinal cell, transfers it to tissues and bone marrow
125
What environment is required to liberate B12 from food?
Acidic environment
| Affected by PPI
126
What is role of IF in B12 metabolism?
Acts as chaperone for B12 to intestinal cell
127
What is most specific test for pernicious anaemia?
Intrinsic factor Ab
128
What is the best test to identify B12 deficiency?
Holo-transcobalamin II -> active form
129
What is the best test to identify folate deficiency?
Red cell folate
130
What are the elements of a haemolysis screen?
```
Blood film (polychromasia, red cell morphology)
LDH
Haptoglobin (low)
LDH
Bilirubin
```
131
What is role of haptoglobin?
Where is it produced?
Binds to free Hb in haemolysis
Made in liver, low in chronic liver disease
132
What is the classic lab finding which distinguishes INTRAvascular haemolysis from EXTRAvascular?
Urinary haemosiderin will be positive in intravascular
133
3 causes of INTRAvascular haemolysis?
Red cell fragmentation (MAHA, mechanical)
PNH
Paroxysmal cold haemoglobinuria
134
What is the acquired genetic mutation in Paroxysmal nocturnal haemoglobinuria?
Mutation in PIG-A gene.
| This is essential for complement activation
135
What is a common vascular complication of PNH?
Highly thrombogenic condition
Large vessel thrombosis e.g. portal vein
136
What does a lack of cell surface proteins CD55 and CD59 indicate?
PNH
137
What is the gold standard diagnostic test for PNH?
Flow cytometry, looking for CD55 / CD59 cell surface markers
138
What is the key medication for management of PNH?
Eculizumab - anti-C5 mab
139
Classic finding on blood film of Warm AIHA?
Spherocytes (smaller without central pallor)
140
What type of ab usually found in warm AIHA?
IgG
141
What type of ab usually found in cold agglutinins?
IgM
142
3 classic associations with Warm AIHA?
CLL
SLE + other autoimmune conditions
Drugs
143
What is Evan's Syndrome?
TTP + warm AIHA, associated with CLL
144
Key management principles of warm AIHA?
Prednisolone + immunosuppression
| Folate
145
What does 'thermal amplitude' of cold agglutinins refer to?
The temperature threshold at which haemolysis occurs
146
3 classic associations with cold AIHA?
Low grade lymphoma
Mycoplasma
EBV
147
DAT finding in cold AIHA?
C3d. There will be no IgG (is usually IgM)
148
What is the DAT finding in PNH?
Negative (complement mediated)
149
What is the most common of the inherited RBC membrane defects?
Mode of inheritance?
Hereditary spherocytosis
Autosomal dominant
150
What is gold standard diagnosis for Hereditary spherocytosis?
What is the finding of DAT?
Flow cytometry
Negative DAT
151
Thorny apple cells on blood film?
Pyruvate kinase deficiency
152
What is role of G6PD in
What is mode of inheritance of deficiency?
Involved in glutathione ?recycling
X-linked
153
Classic finding on blood film in haemolytic crisis of G6PD deficiency?
Bite / blister cells
154
What is HbA made up of?
Chains -> Alpha 2, Beta 2
155
What is HbA2 made up of?
Chains -> Alpha 2, delta 2
156
Which Hb lines are affected in beta thal?
HbA (only one with beta chains)
157
Which Hb lines are affected in alpha thal?
HbA, HbA2, HbF
158
What is phenotype of alpha thal trait?
Mildly low Hb
Low MCV
Normal iron studies
159
How is alpha thal trait diagnosed?
Genetic studies
Will not be picked up on Hb electrophoresis
160
HbH disease phenotype?
Significant anaemia
Chronic haemolysis with mild splenomegaly
Iron overload
May or may not be transfusion-dependant
161
Hb Barts / Hydrops foetalis phenotype?
Fatal in utero
| Increased maternal morbidity / mortality
162
Beta thal findings on Hb electrophoresis?
Increased HbA2, and HbF
163
What time of life does Beta Thal major manifest?
3-6 months of life, when body is switching from foetal Hb to adult forms
164
Main cause of death in Beta thal major?
Cardiac failure, due to iron overload
165
Genetic change leading to HbS (sickle cell)?
Point mutation in beta globin gene
166
Most cause of death in sickle cell disease after puberty?
Acute chest syndrome
167
What is a key benefit of hydroxyurea in sickle cell?
Increased HbF production, which directly inhibits sickling
168
What is Crizanlizumab?
What is its potential role?
P-selectin mAb
Prevents pain crises in sickle cell disease
169
What is significance of Flt3 mutation in AML?
What is the new therapeutic option for this?
Actiavtes TK activity, driving proliferation
Negative prognostic marker
Midostaurin -> targets Flt3 mutation
170
What are 3 "good risk" cytogenetics in AML?
t(15, 17) - APML
t(8,21)
inv(16)
171
Key management of APML?
Complication of this?
ATRA (all trans retinoic acid)
Helps promyelocytes to differentiate
ATRA syndrome - hyperleukocytosis, ARDS.
Mx - steroids, ventilatory support, may need to interrupt therapy
172
What is significance of 5q deletion mutation in MDS?
What is key therapeutic used?
More favourable prognosis
Lenolidamide
173
CML classic genetics?
Philadelphia chromosome -> t(9:22), BCR-ABL
174
Key management of CML?
TKIs
1st gen - Imatinib
2nd gen - dasatinib, nilotinib
175
Classic SEs of TKIs for CML?
Oedema, pleural effusions, GI SEs
176
High WCC with basophilia/eosinophilia -> DDx?
CML, MPN
177
Choice of cytoreductive agent in pregnancy?
Interferon
178
EPO level in PCV?
Differentiating feature from reactive polycythaemia?
Low EPO
Can also have thrombocytosis / leukocytosis
179
Leukoerythroblastic blood film
PMF
180
3 classic mutations in MPNs?
JAK2
CALR
MPL
181
Implications of CALR mutation in essential thrombocythaemia
Better prognosis
| Lower thrombosis risk
182
Causes of polycythaemia with high EPO?
Cardio / lung disease
Testosterone use
High altitude
183
What are high risk features of essential thrombocythaemia? (3)
Age >60
Plts >1000
Hx thrombosis
184
What is the key treatment in high-risk MDS to decrease progression to AML?
Azacitidine - hypomethylating agent
185
What would be a classic cause of bleeding tendency in essential thrombocythaemia?
Acquired vWD
186
Classic flow cytometry finding in T cell lymphoma?
CD30 positive
187
Match genetics with lymphoma
t(14;18):
t(8;14):
t(11;14):
Burkitt's lymphoma
Mantle cell lymphoma
Follicular lymphoma
t(14, 18) -> follicular
t(8,14) -> Burkitt’s
t(11,14) -> mantle cell
188
Name 3 high grade NHLs
DLBCL
Burkitts
Mantle cell lymphoma
189
Name 3 low grade NHLs
Follicular
SLL/CLL
Marginal zone
190
Match lymphomas to virus associations
Burkitts, Hodgkins, PTLD
T cell lymphoma / leukaemia
Primary effusion lymphoma
Splenic marginal zone lymphoma
EBV
HTLV-1
HCV
HHV-8
EBV - Burkitts, Hodgkins, PTLD
HTLV-1 - T cell lymphoma / leukaemia
HHV 8 - primary effusion lympoho
HCV - splenic marginal zone lymphoma
191
Why is Rituximab not used in multiple myeloma?
Anti-CD20 -> b cell marker
Not expressed on plasma cells
192
Usual chemo regime for DLBCL?
R-CHOP
193
What are Reed-Sternberg cells found in?
What are the cell surface markers typically expressed?
Hodgkin's lymphoma
CD 15 / CD30
194
What is usual chemo regime for Hodgkin's ?
ABVD = doxorubicin, bleomycin, vinblastine, dacarbazine
195
What is Brentuximab vedotin?
Role ?
Anti-CD30 ab
New option for relapsed Hodgkin's
196
What is the most common adult leukaemia?
CLL
197
What are classic cell markers expressed in CLL?
CD5, CD19
198
What is Richter's transformation?
A low grade lymphoma transforming to high grade
199
Indications for treating CLL?
Lymphocyte doubling time (NOT absolute count)
Symptomatic
Stage 3-4 disease
200
What is prognostic implication of IVgH unmutated status in CLL?
Poor prognosis
201
What is prognostic implication of Deletion 17p or tp53 mutation in CLL or multiple myeloma?
Poor prognosis
202
What is obinutuzumab?
CD20 mAb, new version of rituximab with higher binding affinity
Used in CLL with del(17p) or tp53 mutant
203
What is venetoclax?
BH3 mimetic -> inhibits function of BCL2 (which is anti-apoptotic)
Thus restores apoptosis
Associated with TLS
204
What is treatment of choice in del(17p) or tp53 mutation CLL?
Ibrutinib OR Venetoclax + Obinutuzumab
205
What parameters define a shift from MGUS to smouldering myeloma?
>30g / L
| Plasma cells in BM >10%
206
What is the main benefit of lenalidomide compared to thalidomide re: SEs?
Less peripheral neuropathy
207
Which agents increase risk of VTE in MM?
Thalidomide, lenalidomide (particularly in combo with dex)
208
2 main purposes of conditioning for SCT?
1. To provide adequate immunosuppression to prevent rejection of the transplanted graft
2. To eradicate the disease for which the transplant is being performed
209
Engraftment usually occurs when?
Day 15-30
210
Main indications for autologous hSCT?
MM
| NH / Hodgkin's Lymphoma
211
Main cause of death following autologous hSCT?
Disease relapse
212
Main indications for allogeneic hSCT?
AML
| ALL
213
Most important factor determining GVHD post hSCT?
HLA matching
214
What time frame defines 'chronic' GVHD?
Beyond day 100 post SCT
215
DDx for new cytopaenias post SCT? (3)
Relapse
Drugs
Viruses (CMV, adenovirus)
