Haematology Flashcards
1
Q
What are the causes of a microcytic anaemia?
A
Fe deficiency
Thalassaemia
Chronic disease
2
Q
What are the FBC/hematinic findings suggestive of Fe deficiency anaemia?
A
FBC - Hb low, MCV low, MCH low
Haem - Fe low, Ferritin low, transferrin high
3
Q
How is Thalassaemia classified?
A
Alpha
Beta
4
Q
What is Thalassaemia?
A
Gene disorder causing decreased/absent synthesis of a/b globin chains
5
Q
What are the subtypes of alpha thalassaemia?
A
Vary depending on how many genes deleted
1 - minima
2 - minor
3 - HbH
4 - Bart’s
6
Q
Describe alpha thalassaemia minima
A
aa/a-
Low Hb/MCV
Normal RDW
Asymptomatic
7
Q
Describe alpha thalassaemia minor
A
aa/– OR a-/a-
cis deletions more common in asians –> risk hydrops
Low Hb/MCV
Raised RDW
Asymptomatic
8
Q
Describe alpha thalassaemia HbH
A
a-/–
VERY low Hb/MCV
VERY raised RDW
Haemolytic anaemia after birth
9
Q
How is thalassaemia diagnosed?
A
HPLC/electrophoresis
10
Q
How is alpha thalassaemia HbH managed?
A
Fe transfusion
Splenectomy (splenomegaly)
11
Q
Describe alpha thalassaemia Bart’s
A
–/–
severe intrauterine haemolytic anaemia
fetal hydrops
fatal in utero
12
Q
What is the inheritance pattern of thalassaemia?
A
Autosomal recessive
2x alpha genes on Chr 16
1x beta gene on Chr 11
13
Q
What are the subtypes of beta thalassaemia?
A
Minor/trait
Intermedia
Major
14
Q
Describe beta thalassaemia trait
A
B2/-
Low Hb/MCV/MCH
Target cells
Clinically asymptomatic
15
Q
Describe beta thalassaemia intermedia
A
B0/B2 OR B+/B-
High HbF
Low Hb
VERY low MCV/MCH
Splenomegaly, bone changes
Variable transfusion dependency
16
Q
Describe beta thalassaemia major
A
B0/B0
17
Q
Describe beta thalassaemia major
A
B0/B0
HbF >90%
VERY low MCV/MCH
Severe haemolytic anaemia
-chronic transfusion dependency
Hepatosplenomegaly, bone changes
18
Q
How should beta thalassaemia be treated?
A
Folate supplementation
Chronic transfusion w/ desferroxamine chelation
Ascorbate (removes Fe in urine)
GH Tx for endocrine complications
Bone marrow transplant (curative)
19
Q
Why is excess Fe problematic in thalassaemia?
A
Causes endocrinopathy
-diabetes
-thyroid/adrenal/pituitary problems
20
Q
What are the major complications of thalassaemia?
A
Aplastic crises if Parvovirus B19 infection
Osteopenia
21
Q
What causes anaemia of chronic disease?
A
Chronic inflammation –>
Fe sequestration in macrophage stores –>
Reduced erthyropoiesis
22
Q
What are the FBC/hematinic findings suggestive of anaemia of chronic disease?
A
Can be micro (late) OR normocytic (initial)
LOW transferrin
23
Q
How is anaemia of chronic disease treated?
A
Treat underlying cause
Exogenous EPO (cancer, CKD)
IV Fe (not PO)
24
Q
What are the causes of a macrocytic anaemia?
A
Folate deficiency
B12 deficiency
EtoH
Hypothyroidism
Drug-induced
Myelodyplastic syndromes
25
What are the causes of Folate deficiency?
Poor diet (folate in foliage)
Increased demand (pregnancy, dialysis, liver disease)
Inhibited (antifolates)
Malabsorption (resection, coeliac)
26
What commonly prescribed drugs are antifolates?
MTX
Phenytoin
(EtoH)
27
What are the FBC/hematinic findings suggestive of Folate deficiency?
Megaloblastic anaemia
Folate low
B12 normal
Hypersegmented neutrophils on blood film
28
How is Folate deficiency treated?
Folate replacement w/ B12
29
What is the potential complication of folate replacement alone?
Precipitation of subacute combined degeneration of cord if B12 drops too low
30
In which patients should prophylactic folate replacement be considered?
Pregnancy
Long term MTX usage
31
What are the causes of B12 deficiency?
Pure vegan diet
Defect in processing pathway/malabsorption
-pernicious anaemia
-gastric bypass
-terminal ileitis (Chron's)
-pancreatic insufficiency
32
What is Pernicious anaemia?
Autoimmune destruction of parietal cells
Associated autoimmune disease (vitilligo, Hashimoto's)
Increased risk of gastric ca
33
How can B12 deficiency present clinically?
Glossitis + angular stomatitis
Sensory polyneuropathy
Cognitive impairment
Optic atrophy (nutritional)
SACD
Osteoporosis
34
What are the FBC/hematinic findings suggestive of B12 deficiency?
Megaloblastic anaemia
Folate normal
B12 low
Hypersegmented neutrophils
35
How should B12 deficiency be treated?
B12 img IM inj for life
36
What are the causes of a normocytic anaemia?
Haemolysis
Underproduction
37
How can haemolytic anaemias be distinguished from underproductive anaemias?
Corrected reticulocyte count <3% = underproduction
-would be elevated in haemolysis
38
What are the two types of haemolysis?
Intravascular
-RBCs broken down w/i vessels
Extravascular
-RBCs destroyed by reticuloendothelial system (macrophages liver/spleen/LN)
39
What is a major complication of intravascular haemolysis?
Tubular necrosis 2o haemosiderin
40
What is Hereditary Spherocytosis?
Autosomal dominant condition causing spherocytosis of RBC
-prone to haemolysis
41
Describe the presentation, ix, tx and cx of hereditary spherocytosis
Mild haemolytic anaemia, high unconjungated bilirubin
Ix - SDS-PAGE (electrophoresis)
Tx - Folate, splenectomy
Cx - B19 crisis
42
What is Sickle Cell disease?
Autosomal recessive mutations of B-chain Hb
43
What are the two types of Sickle cell disease?
SC trait
Sickle cell disease/anaemia
44
Describe Sickle Cell Trait
Heterozygous mutation
Generally asymptomatic
Protective against malaria
45
Describe Sickle Cell Anaemia
Homozygous mutation (can co-exist w/ B-thal)
Fragile cells --> haemolysis (both intra/extra)
46
How does Sickle Cell Anaemia present?
Facial/cranial bone abrormalities
Hepatomegaly
Autoinfarction of spleen
Aplastic crises (B19 risk)
Vaso-occlusive crisis
47
What is a Sickle Cell crisis?
Vaso-occlusion in microcirculation caused by extensive sickling
Precipitated by:
-hypoxia
-cold
-dehydration
-infection
48
How can sickle cell crises present?
Dactylitis
Avascular necrosis
Acute chest syndrome
Renal papillary necrosis
Pain
CNS infarct --> stroke/seizures
Priapism
49
How is priapism treated in sickle cell crises?
A-agonist OR blood aspiration OR saline irrigation
50
What is the acute chest syndrome in sickle cell crisis?
Vaso-occlusion in pulmonary microcirculation w/ 2o infiltrates
Presents with:
-fever
-cx pain
-SOB
-wheeze
-cough
-tachypnoea
-pain
51
What are the complications of acute chest syndrome in sickle cell crisis?
Acute - ventilation, death (MCC)
Chronic - fibrosis --> Pulm HTN --> cor pulmonale
52
How should an acute chest syndrome in sickle cell crisis be managed?
Bronchodilators
Abx
Transfusion
Ventilation
Exchange transfusion
53
What are the chronic complications of Sickle Cell Anaemia?
Auto-splenectomy/infarction
-increased risk of infection w/ encapsulated organisms
Sickle cell retinopathy
-non-proliferative OR proliferative
54
How is Sickle cell Retinopathy managed?
Non-proliferative - Hydroxyurea
Proliferative - anti-VEGF, lasers, surgery
55
What is a sequestration crisis?
Pooling of blood in spleen +/- liver --> severe anaemia + shock
-mainly occurs in children
-requires uregent transfusion
56
What are the FBC/hematinic findings suggestive of B12 deficiency?
Normocytic anaemia
Sickle cells w/ target cells on film
Howell-Jolly bodies on film
Bili high
57
How should Sickle Cell anaemia be ix?
HPLC/electrophoresis
PCR
58
How is Sickle cell anaemia treated?
Hydroxyurea (reduces f of crisis)
Immunization/PPx abx
Folate supplement
Transfusions
Bone marrow transplant CURATIVE
59
What is G6PD deficiency?
XLR deficiency of G6PD
Causes haemolytic crises
60
What are the precipitants for a G6PD crisis?
Drugs (aspirin, sulphonamides, quinine, dapstone)
Fava beans
Henna tattoo
Infections
61
How does G6PD present?
Sudden haemolytic crises
-anaemia
-jaundice
-flank pain (Hb nephrotoxic)
62
How should G6PD be ix?
Blood film - Heinz bodies, bite cells
Enzyme assay
63
How is G6PD managed?
Self limiting
Transfusion if severe
64
What is autoimmune haemolytic anaemia?
Ig directed RBC destruction
-mediated by macrophages
IgG or IGM disease
65
How should autoimmune haemolytic anaemia be ix?
DIRECT coomb's test + agglutination
-warm = IgG
-cold = IgM
66
Describe IgG autoimmune haemolytic anaemia
WARM agglutinin
Extravascular, central body
Associated w/ autoimmune disease/drugs
67
How should IgG autoimmune haemolytic anaemia be managed?
Treat underyling cause
Steroids
IVIG
Splenectomy
68
Describe IgM autoimmune haemolytic anaemia
COLD agglutinin
Intravascular, peripheries
Associated w/ EBV, HBV, mycoplasma
69
What is Porphyria?
Inherited metabolic disorders caused by abnormal heam synthesis
70
How dose acute intermittent porphyria present?
20-40ys
Painful abdomen
Polyneuropathy
Port-wine urine on sunlight exposure
Psych disturbances
PPT by drugs (P450 inducers, EtOh, starvation)
71
How is acute intermittent porphyria treated?
Glucose
Heme
72
How does porphyria cutanea tarda present?
Photosensitive blistering milla
-slow to heal
-hyperpigmentation
73
How should porphyria cutanea tarda be ix and rx?
Ix - uroporphyinogen (deficient), pink fluorescence of urine, ferritin
Rx - Chloroquine, venesection
74
What are the potential reactions to a blood product transfusion?
Non-immune mediated (hypoCa, CCf, infection, hyper K)
Acute
-febrile reaction
-minor allergic
-anaphylaxis
-acute haemolysis
-TACO
-TRALI (ARDS)
Chronic (delayed haemolysis)
GVHD (ciclosporin)
75
What are the common myeloproliferative disorders?
Chronic Myeloid Leukaemia
Polycythaemia Vera
Myelofibrosis
Essential thrombocytopenia
76
What gene abnormality is high risk for CML?
Philadelphia t9:22
77
How does CML present?
Fatigue
Wt loss
Night sweats
Priapism
Tinnitus
Maturing granulocytes
78
How should CML be investigated?
FISH/karyotype/PCR
FBC
-WBC 50-400
-Plt normal/high
-Hb low
Film - <10% blasts
BM hypercellular
79
What is the treatment for CML?
Imatinib (tyrosine kinase inhibitor)
Hydroxycarbamide
80
What is the progression of CML?
Chronic --> accelerated --> blast crisis (ALL/AML)
81
How does PV present?
Viscosity headache
Dizziness
CVA
Pruritis
Ruddy complexion
VTE
Bleeding
Hepatosplenomegaly
Gouty arthritis
Peptic ulcers
81
What gene mutation is high risk for PV?
JAK2 (95%)
82
What are the 2o causes of PV?
High altitude
RCC
Von Hippel-Lindau
PKD
COPD
Heart disease
83
What is the progression of PV?
15% progress to MF
84
How should PV be investigated?
Flow cytometry
FBC
-high Hb
-high platelets
-low neutrophils
Low EPO
85
How is PV treated?
Venesction
Low dose aspirin
Hydroxycarbamide
86
How does MF present?
Lethargy
Wt loss
Night sweats
Fever
Pallor
Hepatosplenomegaly
High urate
87
How should MF be investigated?
FBC
-high platelets
-high WCC
BM biopsy
-fibrosis
-dry tap
Teardrop cells on film
High urate/LDH
88
How is MF treated?
Hydroxycarbamide
Thalidomide
89
How does ET present?
Thrombosis/bleeding
-digital ischaemia
-CVA
-budd-chiari
90
How should ET be investigated?
Screen for JAK2 (50%)
High platelets (>500)
Calreticulin (20%)
91
How should ET be treated?
a-interferon (avoided in pregnancy)
Hydroxycarbamide
Low dose aspirin
Anagrelide
92
What are the common types of Leukaemia?
Acute Myeloid Leukaemia
Acute Lymphoblastic Leukaemia
Chronic Lymphocytic Leukaemia
Myelodysplastic Syndromes
93
What is a Leukaemoid reaction?
Leukocytosis 2o stress/infection/haemolysis as opposed to Leukaemia
94
How can a Leukaemoid reaction be distinguished from Leukaemia?
Clinical context
High Leukocyte Alanine Phosphatase
Dohle bodies
LEFT shift
95
What are the risk factors for AML?
Down's
Radiation
Benzene exposure (smoking, paints/solvents, gasoline)
Mutations
-t(15;17) - good prognosis
-trisomies - poor prognosis
96
How is AML classified?
FAB classification (M0-M7)
-M3 = Acute promyelocytic
-M7 = Acute megakaryoblastic
97
What are the key features of Acute promyelocytic leukaemia?
10% of AML
t(15;17)
can cause DIC
treated w/ retinoids
good prognosis
98
How does AML present?
Older patients
Bone marrow failure
Pallor
Fatigue
Exertional SOB
Recurrent infection
Bleeding
Gum infiltrates (M5)
99
How should AML be investigated?
Platelets (low)
Blood film
-Blasts >20%
-auer rods
Immunophenotyping
100
How is AML treated?
CTX (80% remission)
Platelet/RBC tranfusion
Bone marrow transplant
101
What are the two main subtypes of ALL?
Bcell-ALL (most common)
Tcell-ALL
102
How does ALL present?
2-4yrs
Weakness
Bruising
Otitis media
Bone pain
Enlarged LN
Headache
103
What factors are suggestive of poor prognosis in ALL?
FAB L3 type
T/B cell surface marker
Philadelphia t(9;22)
Age <2 or >10
Male
CNS involvement
Initial WBC >100
Non-caucasian
104
What factors are suggestive of good prognosis in ALL?
FAB L1 type
Low initial WBC
del9p
t(12;21)
t(1;19)
105
How is ALL treated?
4 phase CTX
106
How does CLL present?
>50 y/o
ASYMPTOMATIC
Constitutional sx
Immune thrombocytopenia (bleed)
Warm autoimmune haemolytic anaemia (10%)
Hypogammaglobulinaemia (infections)
Red cell aplasia
Angioedema
107
What is Richter's transformation?
Transformation of CLL into more aggressive large cell lymphoma
-3% of cases
108
Which cell-line is most commonly implicated in CLL?
>95% B-cell clonal
109
What factors suggest a poor prognosis in CLL?
Male
>70 y/o
Lymphocyte >50
Prolymphocyte >12
Doubling of lymphocytes <12mo
Raised LDH
CD38, TP52, del17p
110
What factors suggest a good prognosis in CLL?
Del13q
-most common mutation in CLL (50%)
111
What findings suggestive of CLL can be seen on a blood film?
Lymphocytes +++
Smear/smudge cells
112
How should CLL be treated?
Watch and wait
High WCC NOT an indication to treat
Treat when other cell lines start to fall
-Fludarabine
-Ciclosporin
-Rituzimab
-Ibrutinib
113
What is Hairy Cell Leukaemia?
Subtype of CLL
114
How does Hairy Cell Leukaemia present?
Pancytopenia
Splenomegaly
Skin vasculitis
115
How should Hairy Cell Leukaemia be investigated?
Bone marrow biopsy
-dry tap
TRAP stain +ve
116
How should Hairy Cell Leukaemia be treated?
CTX
Immunotherapy
117
What is Myelodysplasia?
Dysplasia in 2 or more cell lines
118
How does Myelodysplasia present?
Elderly
Anaemia
30% progress to AML
119
How should Myelodysplasia be treated?
Supportive
CTX not effective
120
When should an enlarged LN be investigated?
If LN >1cm present for >6/52 needs excision biopsy
121
What staging system is used for lymphoma?
Ann-Arbor
1 - (single group)
2 - 2+ regions on one side of diaphragm
3 - Both sides of diaphragm
4 - Extralymphatic manifestations
122
What are the two main types of Lymphoma?
Hodgkin's (rarer)
Non-Hodgkin's
123
At what ages does Hodgkin's lymphoma present?
Bimodal distribution
-15-35
->60
124
What are the main histological subtypes of Hodgkin's lymphoma?
Nodular sclerosing (70%, women)
Mixed cellularity (20%)
Lymphocyte predominant (5%)
Lymphocyte depleted (rare)
125
What factors suggest a poor prognosis in Hodgkin's lymphoma?
B sx
Age >45
Stage IV
Hb <10.5
Male
Albumin <40
WBC >15
126
How should Hodgkin's lymphoma be treated?
External beam radiation therapy
Brentuximab
ABVD chemo
127
What are the common subtypes of Non-Hodgkin's lymphoma?
Waldenstrom macroglobulinaemia
Follicular
Mantle cell
Marginal zone
Diffuse large B-cell
Burkitt
128
How does Walendstrom macroglobulinaemia present?
>50
Headache
Hepatosplenomegaly
Visual disturbance
Cold AIHA
Hyperviscosity
Raynauld
129
How should waldenstrom macroglobulinaemia be treated?
Exchange therapy
Ciclosporin
130
What are the key features of mantle cell lymphoma?
Presents >60 y/o
Widespread (LN/liver/GI)
Aggressive w/ poor prognosis
131
What are the key features of marginal zone lymphoma?
Extranodal
-gastric MALT
-thyroid
-salivary nodes
-lungs
-spleen
132
What are the key features of B-cell lymphoma?
V. common (40%)
Fast/high grade
B-sx
Spreads to GI/testis/bone
Can require surgical removal of masses
133
What is Paraproteinaemia?
Group of related diseases characterized by excess proliferation of Ig secreting cells
Spectrum from MGUS to myeloma
134
How does myeloma present?
CRAB sx
-hypercalcaemia
-renal failure
-anaemia (bone marrow failure, other penias)
-bone pain (lumbar spine)
Amyloidosis
135
What are the sx of Amyloidosis?
Peripheral neuropathy
Macroglossia
Cardiomegaly
Carpal tunnel syndrome
Hyperviscosity
Encapsulated bacteria infection
136
How should suspected myeloma be investigated?
Film - Roleaux formation, anaemia (norm/norm)
Raised ESR, hyperCa, AKI
SPEP (M-spike)
UPEP (10% no M-spike, Bence-Jones)
Serum free light chain
Bx/radiology
137
How should myeloma be managed?
HyperCa - IVI, bisphosphonates
Anaemia - EPO
Plasma exchange, dialysis
Chemo/radiotherapy
Autograft stem cell therapy
138
Which clotting factors affect APPT?
12, 11, 9, 8, 10 5, 2, 1 (intrinsic)
139
Which clotting factors affect PT?
7, 10, 5, 2, 1 (extrinsic)
140
What can prolong the Thrombin time?
Heparin
Fibrinogen deficiency
141
What clotting factor does LMWH work against?
Factor Xa
142
What are the common causes of thrombocytopenia?
Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Haemolytic Uraemic Syndrome
Heparin-induced thrombocytopenia
DIC
143
What are the causes of ITP?
1o - IgG antibodies
2o - SLE, leukaemia, quinine, heparin, HIV, hep C, antiphospholipid syndrome
144
What is Evans Syndrome?
Autoimmune condition causing ITP + AIHA
145
How does ITP present?
Acute form (children)
-self-limiting post viral infection
Chronic form (adults)
-women of childbearing age
-purpura, epistaxis, menorrhagia
146
How is ITP investigated?
Dx of exclusion
(low platelet and normal clotting)
147
How is ITP treated?
Steroids
IVIg
Splenectomy
Rituximab (if refractory)
NOT platelet transfusion
148
What is thrombotic thrombocytopenia purpura?
Congenital lack of VWF cleaving protein (ADAMTS13)
Leads to platelet microthrombi that shear RBC --> microangiopathic haemolytic anaemia
149
How does TTP present?
Microangiopathic haemolytic anaemia
Thrombocytopenia
Neurological abnormalities
Fever
Renal dysfunction
150
How is TTP treated?
Steroids
Plasma exchange
Rituximab
AVOID platelet transfusion
151
What is Haemolytic Uraemic Syndrome?
Vasculitis common in children
-90% post E.coli (0157:H7 infection)
-10% atypical
Most common cause of AKI in paeds
152
How does HUS present?
Profuse diarrhoea --> bloody stools 1-3/7 later
Abdo pain
Vomiting
Fever
Rash
153
How is HUS treated?
Supportive therapy +/- dialysis
154
What is DIC?
Consumptive coagulopathy
Microthrombi and bleeds
155
How is DIC treated?
Platelet replacement
Cryoprecipitate (fibrinogen + factors 8, 13, VWF)
FFP
RBC
156
How does thrombophilia present?
Thrombosis
-DVT
-CVA
-VST
-PE
-Budd-Chiari
-MI
157
What are the inherited causes of thrombophilia?
Factor V LEiden
Prothrombin 20210A gene mutation
Protein C or S deficiency
Antithrombin III deficiency
158
What are the acquired causes of thrombophilia?
Tamoxifen
Olanzapine
HRT
OCP
159
What is Von-Willebrand's disease?
AD inherited deficiency of VWF
160
What are the subtypes of VWD?
Type 1 (80%) - partial deficiency
Type 2 - abnormal form
Type 3 - total lack of factor (AR)
161
How does VWD present?
Mild mucosal/skin bleeding
162
How should VWD be investigated?
APTT (high) but PT normal
Bleeding time increased
Ristocetin test
163
How is VWD treated?
Desompressin (increases VWF release)
164
What is the action of Von-Willebrand factor?
Promotes platelet adhesion to damaged endothelium
Stabilizes FVIII
165
What is haemophilia?
X-linked deficiency of clotting factors
166
What are the two main types of haemophilia?
A - lack of factor 8
B - lack of factor 9
167
How does haemophilia present?
DEEP TISSUE BLEEDING
Haemarthroses
Haematomas
168
How should haemophilia be investigated?
Prolonged APTT ONLY
169
How should haemophilia be treated?
Minor - elevation, pressure, TXA
Severe - recombinant FVIII/FIX
170
How does unfractionated heparin work?
Unfractionated - Inhibits Xa + IIa
LMWH - binds ATIII Xa
171
What reversal agent is available for heparin?
Protamine sulphate
-UFH full reversal
-LMWH partial reversal
-Fondaparinux no reversal
172
What are the s/e of heparin?
HIT (not Fondaparinux)
Osteoporosis
HyperK
173
What are the indications for DOACs?
Non-valvular AF
VTE
174
How are DOACs eliminated?
Dabigatran (renal)
Rivaroxaban (liver)
Apixaban (faecal)
175
What drugs commonly interact w/ DOACs?
Antiepileptics
Anti-retrovirals
Anti-fungals
Rifampicin
176
How do DOACs work?
Dabigatran - inhibits thrombin
Others - inhibit Xa
177
What reversal agent is available for DOACs?
Beriplex (PCC)
Dabigatran - Idarucizumab
178
How does Warfarin work?
Vit K antagonist
Reduces II, VII, IX, X, protein C
179
What are the s/e of Warfarin?
Haemorrhage
Teratogenic (can be used in breastfeeding)
Skin necrosis
Purple toes
180
What factors can cause a high INR in warfarin pts?
Change in diet
Liver disease
ODEVICES
-omeprazole
-disulfiram
-erythromycin
-valproate
-isoniazide
-cipro/cimetidine
-acute EtoH
-sulphonamide
PCBRAS inducers
Cranberry juice
NSAIDs
Foods high in Vit K (leafy greens)
181
What reversal agents are available for Warfarin?
Vit K
4 factor prothrombin complex
182
When should Warfarin be used instead of a DOAC, and vice-versa?
Warfarin - CrCl <30, extracranial bleeding, poor compliance, wt >120kg, arterial thrombosis
DOAC - non valvular AF, VTE, prev. ICH, polypharmacy, good control
