Haematology Flashcards
1
Q
Which haematological condition is budd chiari associated with?
A
Polycythemia vera
2
Q
Mutation associated with Polycythemia Vera
A
jAK2 V617F somatic mutation
3
Q
What is erythromelalgia
A
tenderness or painful burning and/or redness of fingers, palms, heels, or toes
4
Q
Symptoms of primary myelofibrosis
A
Anaemia, hepatosplenomegaly
5
Q
BMAT findings in myelofibrosis
A
fibrosis + atypical megakaryocytic hyperplasia and thickening +distortion of the bony trabeculae (osteosclerosis)
6
Q
MOA of Tranexamic acid
A
synthetic analogue of the amino acid lysine. It serves as an anti-fibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen. This reduces conversion of
plasminogen to plasmin, preventing fibrin degradation
7
Q
Test which indicates pure red cell aplasia
A
LOW Reticulocyte count
8
Q
Most common cause for ABO incompatibility
A
Wrong patient identified
9
Q
Hb is 190. What test is required to diagnose Polycythemia Vera
A
Jak2 V61F mutation
10
Q
MOA of Warfarin
A
Anti-thrombotic effect: Factor II inhibitor - 3 day half life.
Anti-coagulant effect: Factor VII, IV, X - 12 hour half life.
Inhibition of Protein C - Pro-coagulant effect - warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C
11
Q
Cause of Warfarin necrosis
A
Inhibition of Protein C - Pro-coagulant effect - warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C
12
Q
Chemotherapy neutrophil nadir
A
10-14 days
13
Q
Short term management of bleeding in Von Willibrands disease
A
DDAVP
vWF concentrates
14
Q
CML mutation
A
Philadelphia chromosome t( 9,22) BCR-ABL translocation.
15
Q
CML first line treatment
A
TKI - Imatinib.
Others - Nilotinib, Dasatinib
16
Q
What is factor V leiden?
A
Factor 5a is a procoagulant that has a positive feedback loop with thrombin. Thrombin activates Protein C which negatively feeds back to factor 5.
Factor V leiden is where Factor 5 is resistant to Protein C - leads to procoagulant state.
17
Q
What is protein S ?
A
Protein S is a co-factor of protein C. It breaks down factor 8a and 5a.
18
Q
Treatment of ITP
A
High dose glucocorticoids or IVIG - treat only if high bleeding risk or plt <20,000.
19
Q
Type of inheritance of Von Willebrands disease
A
Autosomal dominant
20
Q
Management of Haemophillia perioperatively?
A
Give factor 8
21
Q
Cause of High Hepcidin
A
Chronic inflammation
22
Q
Low Hepcidin
A
Haemachromatosis
23
Q
Drug which prolongs survival in MDS
A
Azacitidine
24
Q
Mechanism of action of antiplatelets
A
inhibits the P2Y12 subtype of ADP receptor, which is important in activation of platelets and eventual cross-linking by the protein fibrin.
25
Warfarin MOA
Vit K epoxide reductase inhibitor
26
Heparin MOA
binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation.
Inhibits Xa and thrombin.
27
Cause of TTP
ADAMTS13 deficiency ( <10%)- usually cleaves large Von Willibrand factor multimers
28
Pathophys of complement mediated TMA (previously called aHUS)
hereditary deficiency of regulatory proteins that
restrict activation of the alternative pathway of complement or mutation of proteins that accelerate this
pathway. leads to uncontrolled activation of complement on cell
membranes.
29
Warfarin reversal
1. Vitamin K
2. Prothrombin X (4 factor) - (DO NOT use activated prothrombin)
3. Tranexamic acid
4. PRBC
30
Thrombosis secondary prevention in pregnancy
Clexane
31
4 causes of impaired Haematological cell production
1. Congenital aplastic anaemia
2. Acquired aplasic anaemia
3. Bone marrow infiltration
4. MDS
32
Cause of acquired aplastic anaemia
Auto-immune due to IL 17
33
Treatment of aplastic anaemia
Cell count > 50 - triple immunosuppresion - Cyclosporin + Methyl pred + Anti-thymoglobulin.
Cell count < 50 - HSCT
34
4 features of Fanconi's anaemia
1. FANC genes
2. Cafe au lait spots
3. Microcephaly
4. Haematological malignancies
35
GATA 2 mutation effects
Increased mycobacterial infections
| MDS/ AML
36
Findings in hairy cell leukemia
1. splenomegaly
2. pancytopenia
3. dry BMAT
4. CD103, CD25, CD11, CD20
37
Pathophys of Paroxysmal nocturnal haemaglobinuria
Lack of GPI anchor on blood cells, therefore no CD55 or CD59. Causes complement mediated cell destruction.
38
Pathyophys of Haemophagocytic Lymphohistiocytosis (HLH)
Loss of destruction of activated immune cells.
| Macrophages phagocytose red cells.
39
Signs/Symptoms of Haemophagocytic Lymphohistiocytosis (HLH)
1. Fever
2. Splenomegaly
3. Cytopenias
4. High triglycerides and low fibrin
5. Hemophagocytosis on biopsy
6. Decreased or absent NK cell activity
7. High ferritin
8. Elevated CD25
40
MGUS criteria
1. M protein <30
2. BM clonal plasma cells <10%
3. No MM defining events
41
Smouldering myeloma criteria
1. M protein > 30
2. BM clonal plasma cells 10-60%
3. No MM defining events
42
Multiple Myeloma criteria
1. BM clonal plasma cells > 10% OR has plasmacytoma
| 2. MM defining event (CRAB, FLC>100, clonal plasma cells >60%, >1 bone lesion)
43
Hyperviscosity findings on fundoscopy
Flame haemorrhages
44
Multiple Myeloma genes
t(4,14) t(14,16), del(17p)
45
Causes of renal failure in multiple myeloma
1. Myeloma Cast nephropathy
2. Light chain deposition disease
3. Amyloidosis
46
Myeloma treatement
Bortezomib, Thalidomide, Daratumumab
| +/- BMAT
47
AML gene mutations
- FLT3 (Mx with Midastaurin)
- NPM1 mutation is protective
- t(8;21)
- t(16;16)
- t(15;17) - APML
48
AML treatment
Cytarabine + Anthracycline (rubicin)
49
APML treatment
```
Medical emergency
Vit A (ATRA) + Arsenic
```
Good prognosis
50
APML histology and flow cytometry
Granulation + Auer rods
| Flow cytometry - CD13, CD33, CD45, CD117, MPO. (CD34 and HLA negative)
51
APML gene mutaion and presentation.
t (15,17) - creates fusion of PML and RARA. - Leads to cessation of differentiation and abnormal retinoic metabolism.
Haemorrhage from DIC
52
Management of Waldenstroms Macroglobulinemia
Rituximab + Bendamustine
Dexamethasone + Cyclophosphamide
Ibrutinib.
53
Management of DLBCL
R-CHOP
54
What is Rasburicase
To prevent hyperuricaemia in Tumor lysis syndrome.
| Is a urate oxidising agent.
55
CLL blood film finding
smudge cells.
56
CLL surface proteins
CD5, CD19, CD23, CD200
57
Target for Clopidogrel
P2Y12
58
Von Willibrand Factor function
Platelet adhesion + Binds factor 8
59
Management of Haemophilia A
- 3 weekly injections of clotting factor concentrate.
| - If antibodies present - Factor 7
60
How long do NOACs need to be withheld pre-surgery?
24hrs if normal renal fn.
61
Dabigatran reversal agent
Idarucizumab
If Idarucizumab is not available - use Activated Prothrombin concentrate (aPCC/ FEIBA)
If within 2 hours of last dose - use activated charcoal
62
Apixaban reversal agent
Andexanet
63
Hepcidin role
Decreases serum iron. Regulates iron transport.
64
What causes HbE
Single base substitution.
| Only causes symptoms when in combination with b-Thalassemia.
65
Management of a-Thalassemia
transfuse >100 to prevent EPO production.
| Iron chelation
66
Types of haemolytic anaemia
Cold agglutinin disease
Warm AIHA
Microangiopathic Haemolytic anaemia (MAHA)
67
TTP Pentad of symptoms
1. Anaemia
2. Neurological symptoms.
3. Renal failure
4. Fever
5. Thrombocytopenia
68
Universal plasma donor
Type AB
69
TPO receptor agonists
Romiplostim
| Eltrombopag
70
Aplastic anaemia has overlap with which other disease?
Paroxysmal Nocturnal Haemoglobinuria.
71
BMAT findings in MDS
1. Increased blasts <20%
2. Granulocytic precursor myeloid cells
3. small mononuclear megakaryocytes.
72
Allergies, anaphylactic symptoms + high tryptase = what diagnosis
Systemic mastocytosis. Requires BMAT
73
Lymphoma's associated with EBV
1. Burkitts
2. NK cell lymphoma
3. T cell lymphoma.
74
Lymphoma associated with Hep C
Marginal cell lymphoma
75
Lymphoma associated with Helicobacter Pylori
MALT lymphoma
76
Salmonella Osteomyelitis is associated with which condition
Sickle cell disease
77
Auto-immune gene linked to pernicious anaemia
AIRE gene (auto-immune regulator)
- AIRE mutation also leads to candidiasis, alopecia, hypoparathyroidism and adrenal insufficiency.
- usually have interferon autoantibodies
78
What is Glanzmann's thrombasthenia caused by?
Glycoprotein 2b3a deficiency
79
Cause of hereditary spherocytosis
defect of ankyrin protein
80
What is Feltys syndrome
```
Splenomegaly
Anaemia
Neutropenia
Thrombocytopenia
Arthritis (RA)
```
- Santa wears a felt belt
81
Treatment of 5q del (MDS)
Lenalidomide
82
Most common cause of renal failure in Multiple myeloma
Cast nephropathy
83
Cause of death in Beta thalassemia major
Cardiomyopathy from iron overload
84
When to use FFP
- reversal of anticoagulation
| - for massive transfusion protocols
85
When to use platelets
Stable non-bleeding - use if plt <10
Stable non-bleeding febrile - use if plt <20
Pre- major surgery - use of plt <50
Pre- neuro or eye surgery - use if plt <100
Do not use in ITP/TTP/HITTS - will worsen thrombosis
86
Highest risk of infection for blood products
platelets
87
When to use cryoprecipitate
When there is low factor 8 or fibrinogen.
| After massive haemorrhage
88
Site of coagulation factor activation
surface of activated platelets
89
MOA of venetoclax
inhibits BCL2
90
complication of ABO incompatible bone marrow transplant
Red cell aplasia
91
Poor chemo response gene in CLL
del17p
92
Good chemo response gene in CLL
del13q - IVGH
93
Predictors of improved survival in ALL with ASCT
1. transplantation in first complete remission
2. Short time between diagnosis and SCT
3. HLA matched at DRB1
4. CMV negative
5. Philadelphia chromosome negative
94
Best type of donor in ASCT
Relapse rates are higher after syngeneic or T cell-depleted grafts compared with unmanipulated sibling grafts.
Best grafts are HLA matched siblings.
95
Highest cause of death in ALL post SCT
relapse of disease
96
Binding site of Von-Willebrand factor
glycoprotein Ib-IX-V
| Von Willibrand work 9-5
97
Management of sickle cell disease
Hydroxyurea
Folic acid
avoid iron supplements
Regular Opthalmology for - proliferative sickle retinopathy
98
Management of Antiphospholipid syndrome (anticoagulation choice)
WARFARIN.
Target 2-3.
Warfarin has greater efficacy than DOACs in trials.
99
What is Emicizumab used for
Binds factor 9+10 together to make a surrogate factor 8 --> used in congenital haemophilia prophylaxis only.
100
Mutations associated with Essential thrombocytosis (ET)
1. JAK2
2. CALR (Calreticulin) - lower risk of thrombosis
3. MPL
101
SE of Arsenic
Differentiation syndrome - give dex (serositis, effusions, hepatic dysfn, renal dysfn)
Electrolyte disturbance
Torsades de pointes
102
Mx of aHUS
Eculizumab
103
Diagnostic criteria for antiphospholipid syndrome
least one of the following clinical criteria AND at least one of the following laboratory criteria:
Clinical criteria
1. Deep Vascular thrombosis – One or more episodes of venous. Superficial venous thrombosis does not satisfy the criteria.
1. Pregnancy morbidity – One or more unexplained deaths of a morphologically normal fetus at ≥10 weeks gestation, or one or more premature births of a morphologically normal neonate before 34 weeks gestation because of eclampsia, preeclampsia, or placental insufficiency, or three or more consecutive spontaneous pregnancy losses at <10 weeks gestation, unexplained by chromosomal abnormalities or by maternal anatomic or hormonal causes.
Laboratory criteria – The presence of one or more antibodies (aPL) on two or more occasions at least 12 weeks apart:
* IgG and/or IgM anticardiolipin antibodies (aCL)
* IgG and/or IgM anti-beta2-glycoprotein (GP)
* Lupus anticoagulant (LA) activity detected according to published guidelines.
104
Von Willibrands disease subtypes
●Type 1, an autosomal dominant disease, is the most common, accounting for approximately 75 percent of patients. It represents a partial quantitative deficiency of VWF.
●Type 2, which is usually an autosomal dominant disease, is characterized by several qualitative abnormalities of VWF. Four subtypes have been identified: 2A, 2B, 2M, and 2N.
●Type 3, a total deficiency of VWF, is an autosomal recessive disorder that leads to severe disease with undetectable levels of VWF.
105
Hepatosplenomegaly + femoral bone deformity
Gaucher disease
lysosomal storage disease. Imaging shows Erlenmeyer flask deformity.
Associated with Parkinsons disease.
106
What is Gaucher disease
lysosomal storage disease - error of metabolism that affects the recycling of cellular glycolipids. components accumulate within the lysosomes of cells (macrophages)
107
What is Sweet syndrome
(acute febrile neutrophilic dermatosis) is an inflammatory disorder
characterized by the presence of inflammatory papules, plaques, or nodules on the skin,
systemic symptoms, and neutrophilic infiltration of the skin.
108
Sweet syndrome histology
Neutrophilic infiltration
109
Causes of Sweet syndrome
Classical - idiopathic
Malignancy related - AML
Drug related - GCSF
110
Treatment of Sweet syndrome
Steroids
111
Clexane/Heparin reversal agent
Protamine (fish sperm)
| Adexanet (clexane only)
112
Reversal for NOACs
1. Adexanet
2. Prothrombin X
3. Activated charcoal if within 6 hours.
113
Massive transfusion blood products and amounts
improved survival when the ratio of transfused Fresh Frozen Plasma (FFP, in units) to platelets (in units) to red blood cells (RBCs, in units) approaches 1:1:1
114
Complication of massive transfusion
Large amounts of citrate are given with massive blood transfusion, since blood is anticoagulated with sodium citrate and citric acid. Metabolic alkalosis and a decline in the plasma free calcium concentration are the two potential complications.
Therefore should give calcium gluconate with infusion.
115
CD200 can be used to differentiate which 2 conditions
CD200: a useful marker for differentiation between CLL (positive) and MCL mantle cell lymphoma (negative)
116
CD23+ CD5+ CD200+
CLL
117
CD23-, CD5+, CD200-
Mantle cell
118
Venetoclax SE and MOA
SE: Tumor lysis syndrome, Oedema
MOA: BCL-2 mediates tumor cell survival and has been associated with chemotherapy resistance. Venetoclax binds directly to the BCL-2 protein, restoring the apoptotic process.
119
Ibrutinib MOA and SE
irreversible inhibitor of Bruton's tyrosine kinase (BTK), an integral component of the B-cell receptor (BCR) and cytokine receptor pathways.
SE: Infection, anaemia, HTN, bleeding, arrhythmias.
120
Platelet transfusion is contraindicated in which type of bleeding
Intracerebral haemorrhage - increases death and dependence
121
Drug to prevent aplastic anaemia in haemolysis
folate
122
Marker for ALL
TDT - found only in immature lymphoid cells (lymphoblasts)
123
Indications for AUTOLOGOUS BM transplant
Multiple myeloma - autologous is gold standard
relapsed lymphoma
Some auto-immune
124
Indications for ALLOGENEIC BM transplant
```
AML/ALL/MDS - post initial therapy
Aplastic anaemia
SCID
NHL
Haematological disease - eg sickle cell
```
125
How long does immune reconstitution take after allogeneic transplant
12-18m
126
Biggest factor in post transplant survival for allogeneic transplant
GVHD
| Pre-transplant disease severity
127
Biggest cancer increase after bone marrow transplant compared to population risk
oesophageal/ oropharyngeal
128
Name of hepatic complication post bone marrow transplant
sinusoidal obstruction syndrome
129
Features of DIC
- acute precipitant
- oozing from wound sites
- thrombocytopenia
- coagulopathy
130
Management of MDS
- EPO, antithymocyte, azacitadine. BM transplant.
| - Lenalidomide if 5Q mutation.
131
Management of MF
Ruxolitinib (JAK2)
| or hydroxyurea.
132
Hydroxyurea MOA
Hydroxyurea is an antimetabolite that selectively inhibits ribonucleoside diphosphate reductase, preventing the conversion of ribonucleotides to deoxyribonucleotides, halting the cell cycle at the G1/S phase and therefore has radiation sensitizing activity by maintaining cells in the G1 phase and interfering with DNA repair. In sickle cell anemia, hydroxyurea increases red blood cell (RBC) hemoglobin F levels
133
What do lymphocytes attack in transfusion related GVHD
recipients bone marrow
134
How to prevent transfusion related GVHD
Irradiation (as opposed to leukodepletion in febrile non-haemolytic reactions)
135
Treatment of CML
BCR-ABL inhibitors (TKI) - imatinib
136
Mechanism of relapse after CAR-T therapy and immunotherapy
Antigenic escape
137
Abdo pain + weakness + psych changes
Acute intermittent porphyria
138
Blistering to sun exposed skin
Porphyria cutanea tarda
139
Target of Daratumumab in multiple myeloma
CD38 - expressed more on MM cells than normal lymphocytes.
140
Multiple Myeloma high risk genes
- t(4;14)
- t(14;16)
- Del17p
- Del13
- 1q21 amplification
141
Management CLL
If high grade then can treat with Ibrutinib and Venetoclax
Traditional therapy - Fludrabine, clyclophosphamide, Rituximab (FCR)
Can watch and wait if indolent
142
High risk mutations in CLL and best treatment.
un-mutated IGHV
TP53 aberration
chromosome 11q deletion.
Treatment - good response to Ibrutinib + Venetoclax
143
Type of immunoglobulin in Warm auto immune haemolysis
IgG
144
Type of immunoglobulin in Cold auto immune haemolysis
IgM
145
Treatment for FLT3 mutation
Midastaurin
146
1st line treatment for Philadelphia positive malignancy
Imatinib
147
Treatment for T3151 positive malignancy
Ponatinib
