Haematology Flashcards
(130 cards)
1
Q
Components of blood?
A
Plasma (clotting factors, albumin and Igs)
Cells (RBCs, WBCs and platelets)
2
Q
Granulocytes vs agranulocytes?
A
Granulocytes = neutrophils, eosinophils, basophils
Agranulocytes = monocytes, lymphocytes
3
Q
Main types of lymphocyte?
A
B cell
T cell
NK cell
4
Q
Main types of differentiated T cell, CD expressed and MHC they present to?
A
T helper (CD4+) cell
→ presents to MHC class II
Cytotoxic (CD8+) cell
→ presents to MHC class I
5
Q
What does CD stand for and represent?
A
Cluster of differentiation
Specific set of antigens on a cell’s surface
6
Q
CD used to calculate total T cell count and why?
A
CD3
Present on all mature T cells
7
Q
Average lifespan of RBCs, platelets and neutrophils?
A
RBCs = 90-120 days
Platelets = 10 days
Neutrophils = 4 days
8
Q
Cell morphology associated with IDA, thalassaemia, hyposplenism, G6PD deficiency, myelofibrosis, haemolysis?
A
IDA = target cells, “pencil” pokilocytes
Thalassaemia = target cells, basophilic stippling
Hyposplenism = target cells, howell-jolly bodies
G6PD deficiency = heinz bodies, bite cells
Myelofibrosis = leukoerythroblastosis, “tear drop” poikilocytes
Haemolysis = schistocytes
9
Q
Adult haemoglobin composition and globin chain structures?
A
96% HbA = 2 α and 2 β chains
2% HbA2 = 2 α and 2 δ chains
2% HbF = 2 α and 2 γ chains
10
Q
Clinical relevance of Hb, Hct, MCV, MCH, MCHC, retic count, haptoglobin, ferritin, transferrin, TIBC, transferrin saturation?
A
Hb = amount of Hb in blood
Hct = % of blood that is RBCs
MCV = average RBC size
MCH = amount of Hb per RBC
MCHC = conc. of Hb in a given volume
Retic count = number of immature RBCs, indicator of bone marrow activity
Haptoglobin = decreased if free Hb
Ferritin = amount of iron stores
Transferrin = amount of iron transporters
TIBC = amount of transferrin available to bind iron
Transferrin saturation = % of transferrin bound to iron
11
Q
Features of anaemia?
A
Fatigue
SOB
Pallor
Angina
Palpitations
Koilonychia
Atrophic glossitis
Angular stomatitis
12
Q
Causes of microcytic anaemia (MCV < 80fL)?
A
Iron deficiency anaemia (IDA)
Thalassaemia
Sideroblastic anaemia
13
Q
Where is iron absorbed vs stored?
A
Absorbed = duodenum and proximal jejunum
Stored = RBC (2/3rds), ferritin and haemosiderin (1/3rd)
14
Q
Blood test features of IDA?
A
Low iron
Low ferritin
High TIBC
High transferrin
Low transferrin saturation
15
Q
New iron deficiency in an adult without a clear cause?
A
Refer for OGD and colonoscopy
16
Q
Management options for IDA?
A
Increase dietary iron
Oral ferrous sulfate
IV iron infusion
Blood transfusion
17
Q
How much should iron rise during treatment?
A
10 grams/litre/week
18
Q
Genetic inheritance of thalassaemias?
A
Autosomal recessive
19
Q
Features of thalassaemia?
A
Anaemia symptoms
Haemolysis e.g. jaundice
Hepatosplenomegaly
Bone deformities
Failure to thrive (kids)
20
Q
Outline the genetics of α-globin chains?
A
- 2 genes on chromosome 16 code for α-globin
- 2 copies of chromosome 16 in each diploid cell means 4 α-globin alleles (e.g. αα/αα)
21
Q
α thalassaemia mutations and their clinical name?
A
1 deleted allele = silent carrier
2 deleted alleles = α thalassaemia trait
3 deleted alleles = HbH disease
4 deleted alleles = Hb Barts
22
Q
What is HbH disease?
A
Lack of α-globin production causes excessive amounts of β-globin
β-globins bind together to form HbH
23
Q
Outline the genetics of β-globin chains?
A
- 1 gene on chromosome 11 codes for β-globin
- 2 copies of chromosome 11 in each diploid cell means 2 β-globin alleles (e.g. ββ)
24
Q
Types of β-globin mutation?
A
β+ = reduced chain synthesis
β0 = no chain synthesis
25
β thalassaemia mutations and their clinical name?
β0β or β+β = thalassamia minor
β+β+ or β+β0 = thalassaemia intermedia
β0β0 = thalassaemia major
26
Investigation for thalassaemia and feature of β?
Hb electrophoresis
β thalassaemia = increased HbA2
27
Management of thalassaemia?
Blood transfusions (if symptomatic)
Iron chelation e.g. desferrioxamine (if iron overload)
Splenectomy (if severe haemolysis)
Bone marrow transplantation
28
Outline the pathophysiology of sideroblastic anemia?
- Defect in heme synthesis within RBC mitochondria
- Iron unable to be incorporated so low Hb
- Iron accumulates within mitochondria
29
Sub-types and causes of macrocytic anaemia (MCV > 100fL)?
Megaloblastic
→ B12 deficiency, folate deficiency
Normoblastic (non-megaloblastic)
→ alcohol, liver disease, hypothyroidism, pregnancy, myelodysplasia, reticulocytosis
30
Where is B12 vs folate absorbed?
B12 = terminal ileum
Folate = duodenum and jejunum
31
Most common cause of B12 deficiency?
Pernicious anaemia
32
Features of B12 deficiency?
Anaemia symptoms
Atrophic glossitis
Angular stomatitis
Mood changes
Peripheral neuropathy
Loss of vibration or proprioception
33
Management of B12 deficiency?
IM hydroxocobalamin
→ 3 times a week for 2 weeks
→ then once every 3 months
34
Management of folate deficiency?
PO folate
→ once every day for 3 months
35
Advice for treating mixed B12 and folate deficiency?
Treat B12 deficiency first!
Starting with folic acid can cause subacute combined degeneration of the spinal cord
36
Causes of normocytic anaemia (MCV 80-100 fL)?
Anaemia of chronic disease
Chronic kidney disease
Aplastic anaemia
Haemolytic anaemia
Acute blood loss
37
Spurious (false) normocytic anaemia cause?
Fluid overload e.g. heart failure, CKD
(Increased plasma volume dilutes RBCs)
38
Outline the pathophysiology of anaemia of chronic disease?
- High levels of inflammatory cytokines
- IL-6 causes hepcidin release from the liver
- Hepcidin decreases ferroportin activity
- Less iron is absorbed so less Hb produced
39
Outline the pathophysiology of aplastic anaemia?
- Immune destruction of bone marrow or premature death of haematopoietic stem cells
- Causes pancytopaenia and hypocellular marrow
40
Triggers of aplastic anaemia?
Infection e.g. parvovirus
Drugs e.g. carbamazepine
Autoimmune disease
Radiation/chemical exposure
41
Features of haemolysis?
Anaemia symptoms
Jaundice
Gallstones
Hepatosplenomegaly
42
Pathophysiology of intravascular haemolysis and causes?
RBCs destroyed within vessels
→ ABO mismatched blood transfusion
→ cold-agglutinin disease (IgM)
→ red cell fragmentation e.g. DIC, TTP, HUS, prosthetic heart valve
→ paroxysmal nocturnal haemoglobinruria
→ G6PD deficiency
43
Blood test feature of intravascular haemolysis?
Low haptoglobin
44
Pathophysiology of extravascular haemolysis and causes?
RBCs destroyed in the spleen
→ haemoglobinopathies e.g. sickle cell
→ warm-agglutinin disease (IgG)
→ hereditary spherocytosis
→ haemolytic disease of the newborn
45
Outline the pathophysiology of Disseminated Intravascular Coagulation (DIC)?
- Trigger e.g. infection causes mass release of procoagulants
- Widespread formation of thrombi
- Thrombi damage RBCs causing haemolysis
- Clotting factors diminish causing bleeding
46
Blood test features of Disseminated Intravascular Coagulation (DIC)?
Prolonged PT/APTT
Thrombocytopenia
Low fibrinogen
Fibrinolysis products (e.g. D-dimer)
47
Outline the pathophysiology of Thrombotic Thrombocytopenic Purpura (TTP)?
- Deficiency of metalloprotease (ADAMTS13) which cleaves vWF multimers
- Large vWF multimers cause platelets to clump within vessels and form thrombi
- Thrombi damage circulating RBCs causing haemolysis
- Platelets diminish causing thrombocytopenia
48
AIHA vs non-AIHA examples and test to differentiate?
AIHI = warm-agglutinin and cold-agglutinin disease
Non-AIHI = all other haemolytic anaemias
Investigation = direct Coomb's test
49
Management options for warm (IgG) AIHI?
1st line = steroids
2nd line = rituximab
3rd line = splenectomy
50
Management options for cold (IgM) AIHI?
1st line = supportive e.g. avoid cold
2nd line = rituximab
51
Patient with VTE and dark urine in the morning? Investigation of choice?
Paroxysmal nocturnal haemoglobinuria
Investigation = flow cytometry
52
Male baby with jaundice and anaemia? Investigation of choice?
G6PD deficiency
Investigation = G6PD enzyme assay
53
Triggers of G6PD crisis?
Infection
Fava beans
Anti-malarials
Ciprofloxacin
Sulph-group drugs
54
Patient with haemolysis and raised MHCH? Investigation of choice?
Hereditary spherocytosis
Investigation = mostly clinical if family history + blood film evidence, EMA binding test if unsure
55
Genetic inheritance of sickle cell?
Autosomal recessive
56
Sickle cell mutations and their clinical name?
HbAS = sickle cell trait
HbSS = sickle cell disease
57
Outline the pathophysiology of sickle cell anaemia?
- Glutamate (polar) is substituted for valine (non-polar) in the β chains
- Deoxy-Hb becomes less water soluble
- HbS molecules polymerise to form sickle shape
- Sickle cells are fragile and haemolyse easily
58
Sickle cell investigation and management?
Investigation = Hb electrophoresis
Management = hydroxyurea/hydroxycarbamide
59
Types of sickle cell crises and cause?
Vaso-occlusive = infarct
Acute chest syndrome = infarct +/- infection
Aplastic crisis = parvovirus infection
Sequestration crisis = pooling of blood in spleen
Severe infection = encapsulated bacteria
60
Sickle cell crisis management?
Analgesia
IV fluids +/- antibiotics
High-flow oxygen
Exchange transfusion
61
Threshold and target for blood transfusion in non-ACS vs ACS?
Patient without ACS:
→ Hb < 70g/L threshold
→ 70-90g/L target
Patient with ACS:
→ Hb < 80g/L
→ 80-100g/L target
62
Threshold for platelet transfusion in active vs non-active bleeding?
Active = < 30 (moderate bleed) or < 100 (severe bleed)
Non-active = ≤ 10
63
Universal RBC donor vs plasma donor?
RBC = O-
Plasma = AB+
64
When to use FFP vs cryoprecipitate vs prothrombin complex?
FFP = patients with prolonged PT/APTT
Cryoprecipitate = patients with low fibrinogen
Prothrombin complex = major haemorrhage
65
What is cryoprecipitate and components?
Concentrated FFP:
→ factor VIII
→ factor XIII
→ fibrinogen
→ vWF
66
Features of non-haemolytic transfusion reaction and management?
Fever, chills
Management = slow/stop transfusion, paracetamol
67
Features of transfusion-associated allergic reaction and management?
Pruritis, urticaria
Mangement = stop transfusion, antihistamine
68
Features of transfusion-associated anaphylaxis and management?
Hypotension, angioedema, wheezing
Management = stop transfusion, IM adrenaline, ABCDE
69
Features of acute haemolytic reaction and management?
Hypotension, abdominal pain, fever
Management = stop transfusion, IV fluids
70
Features of TACO and management?
Hypertension, pulmonary oedema
Management = stop transfusion, IV loop diuretic, oxygen
71
Features of TRALI and management?
Hypotension, hypoxia, pulmonary infiltrate on CXR
Management = stop transfusion, oxygen
72
Primary vs secondary haemostasis?
Primary = formation of the platelet plug
Secondary = intrinsic or extrinsic pathway leading to conversion of fibrinogen to fibrin
73
Outline primary haemostasis?
- Damaged endothelium exposes collagen
- Endothelial cells release vWF which binds to collagen
- Platelets bind to vWF and release platelet activating factors (e.g. TXA2, vWF)
- More platelets arrive at injury site and clump together
74
Factors involved in the extrinsic vs intrinsic vs common pathway?
Extrinsic = XII, XI, IX, XIII (12, 11, 9, 8)
Intrinsic = III, VIII (3, 7)
Common = X, V, II, I (10, 5, 2, 1)
75
Factor names for tissue factor, prothrombin, thrombin, fibrinogen and fibrin?
Tissue factor = III
Prothrombin = II
Thrombin = IIa
Fibrinogen = I
Fibrin = Ia
76
Factor with the shortest half life?
VII
77
Vitamin K dependent clotting factors?
II, VII, IX, X (2, 7, 9, 10)
78
Laboratory measurements of the intrinsic vs extrinsic pathway?
Intrinsic = PTT
→ play table tennis (inside)
Extrinsic = PT
→ play tennis (outside)
79
Outline the pathophysiology of ITP?
- Antibodies against glycoprotein IIa/IIIb or Ib-V-IX
- Platelet destruction causes isolated thrombocytopenia
80
Management options for ITP?
Prednisolone
Splenectomy
IV immunoglobulins
Immunosuppressants
81
Most common cause of thrombophilia?
Factor V Leiden (activated protein C resistance)
82
Outline the pathophysiology of Factor V Leiden?
- Normal factor V broken down by protein C
- Factor V Leiden is a mutated form of factor V
- Degraded 10 x more slowly by protein C leading to increased VTE risk
83
Features of VWD?
Easy bruising
Menorrhagia
Epistaxis
GI bleeds
Prolonged bleeding
84
Types of VWD and cause?
Type 1 = reduction in vWF quantity
Type 2 = reduction in vWF quality
Type 3 = absence of vWF
85
Coagulation screen features of VWD?
Prolonged APTT
Normal PT
Prolonged bleeding time
86
Management options for VWD?
Tranexamic acid
DDAVP (desmopressin)
Factor VIII concentrate
87
Tranexamic acid mechanism of action?
Bind to lysine receptors on plasminogen and plasmin to prevent plasmin breaking down fibrin
88
Inheritance of haemophilia?
X-linked recessive
89
Factor affected in haemophilia A vs B?
A = factor VIII
B = factor IX
90
Features of haemophilia?
Severe bleeds
Haemarthroses
Haematomas
91
Coagulation screen features of haemophilia?
Prolonged APTT
Normal PT
Normal bleeding time
92
Management options for haemophilia A vs B?
A = DDAVP (acute) and recombinant factor VIII (long-term)
B = recombinant factor IX
93
Cells produced from myeloid vs lymphoid progenitors?
Myeloid = neutrophils, eosinophils, basophils, monocytes, RBCs, platelets and mast cells
Lymphoid = B cells, T cells, NK cells
94
What is myeloproliferative disease and give examples?
Bone marrow makes too much of a myeloid cell
→ polycythaemia vera (RBCs)
→ essential thrombocytosis (platelets)
→ myelofibrosis (myeloid cells)
95
Blood test features of high cell turnover?
High LDH
High urate
High retic count
96
Features and management of polycythaemia vera?
Pruritis (after hot bath)
Thrombosis
Erythromelalgia
Red complexion
Splenomegaly
Management = aspirin + venesection
97
Blood test features of polycythaemia vera?
JAK2 mutation
High Hb
High Hct
98
Complication of polycythaemia vera?
Progression to myelodysplastic syndrome
Progression to acute myeloid leukemia
99
Feature of myelodysplastic syndrome?
Complete bone marrow failure (pancytopaenia)
100
Features and management of essential thrombocytosis?
Thrombosis
Erythromelalgia
Splenomegaly
Livedo reticularis
Management = aspirin + hydroxurea
101
Blood test features of essential thrombocytosis?
JAK2 mutation
High platelet count (> 600)
102
Features of myelofibrosis?
Anaemia symptoms
Massive splenomegaly
Weight loss, night sweats, fever
103
Bone marrow biopsy features of myelofibrosis?
Unsuccessful "dry" tap (due to bone marrow fibrosis)
Trephine biopsy required
104
Leukemia vs lymphoma?
Both are malignancies of haematopoetic stem cells
Leukemia = originates in the bone marrow, can affect myeloid OR lymphoid cells, classified as acute or chronic
Lymphoma = originates in the lymph nodes, only affects lymphoid cells, classified as Hodgkin or non-Hodkin
105
Main types of leukemia?
Classified by how fast they develop and whether they affect myeloid or lymphoid cells
→ acute myeloid leukemia (AML)
→ chronic myeloid leukemia (CML)
→ acute lymphoblastic leukemia (ALL)
→ chronic lymphocytic leukemia (CLL)
106
Outline the pathophysiology of leukemia?
- Proliferation of a single type of abnormal WBC (usually B cells)
- Excess of one cell type suppresses all others leading to pancytopaenia
107
Features of leukemia?
Anaemia symptoms
Petechiae
Easy bruising
Frequent infection
Lymphadenopathy
Hepatosplenomegaly
108
Most common cancer in children?
ALL
109
Key blood film feature of AML?
Auer rods
110
Key blood film feature of CLL?
Smear/smudge cells
111
Leukemia linked to the ABL mutation?
CML
112
Leukemias linked to the Philadelphia chromosome t(9;22)?
ALL and CML
113
Stages of CML?
Chronic phase
Accelerated phase
Blast phase (20% of bone marrow is blasts)
114
Management of leukemia?
Chemotherapy regime
Imatinib if philadelphia +ve
115
Features of lymphoma?
Lymphadenopathy
Hepatosplenomegaly
B symptoms (weight loss, fever, night sweats)
116
Types of Hodgkin lymphoma?
Nodular sclerosing (most common)
Mixed-cellularity
Lymphocyte-predominant
Lymphocyte-depleted
117
Blood film feature of Hodgkin lymphoma?
Reed-Sternberg cells
118
Main CD markers for Hodgkin lymphoma?
CD15 and CD30
119
Ann Arbour staging of lymphoma?
Stage I = single node
Stage II = ≥ 2 nodes on same side of diaphragm
Stage III = nodes on both sides of diaphragm
Stage IV = spread beyond nodes
A or B depending on presence of B symptoms
120
Management of Hodgkin lymphoma?
Chemotherapy regime
Usually ABVD (doxorubicin, bleomycin, vincristine, dacarbazine)
121
Examples of non-Hodgkin lymphoma?
Burkitt's lymphoma
Diffuse large B cell lymphoma
MALT lymphoma
Mantle cell lymphoma
Follicular lymphoma
Waldenstrom's macroglobinaemia
122
Lymphoma linked to BCL-2?
Follicular lymphoma
123
Lymphoma linked to c-MYC translocation t(8;14)?
Burkitt's lymphoma
124
Blood film feature of Burkitt's lymphoma?
"Starry sky" appearance
125
Which cell is affected in multiple myeloma?
Plasma cells
126
Features of multiple myeloma?
CRABBI:
Calcium (hypercalcaemia)
Renal impairment
Anaemia
Bleeding
Bone lesions
Infection
127
Imaging for multiple myeloma?
Whole body MRI
128
Blood film feature of multiple myeloma?
Rouleux formation
129
Bence Jones proteins?
Monoclonal immunoglobulin light chains
Classified as kappa or lambda
130
Asymptomatic paraproteinaemia?
MGUS
