Haematology Flashcards
1
Q
Where is EPO secreted?
A
Type 1 glomus cells in the kidney (as well as in renal fibroblasts)
2
Q
Where are haematopoietic stem cells found?
A
Yellow bone marrow
3
Q
Outline the normal process of red cell breakdown
A
Cells >120 days old –> elevated methaemoglobin levels are reduced deformability –> trapped in splenic capillaries –> splenic macrophages lyse RBCs –> iron is removed –> remainder (biliverdin - green) is converted to uncojugated bilirubin (by being converted by biliverdin reductase and albumin added) –> travels to liver for conjugation etc.
4
Q
Where is iron absorbed?
A
Enterocytes in the duodenum
5
Q
What factors enhance the absorption of iron?
A
Haem form, Fe2+ form, acidic pH (aids release of iron from transferrin), pregnancy, hypoxia, iron-deficiency
6
Q
What factors inhibit the absorption of iron?
A
Non-haem form, Fe3+ iron, alkali pH (e.g. with PPIs –> reduced release from transferrin), inflammatory disorders of small intestine, iron overload
7
Q
Besides iron-deficiency, what else may cause a microcytic anaemia?
A
Thalassaemia or anaemia of chronic disease
8
Q
What is the main cause of macrocytic anaemia?
A
Vitamin B12/folate deficiency (pernicious anaemia)
9
Q
Describe how vitamin B12 is absorbed
A
Vitamin B12 is originally bound to proteins in food; this bond is broken by stomach acid –> free B12 then binds to intrinsic factor (produced by gastric parietal cells) and is then absorbed by enterocytes in the ileum
10
Q
Where are vitamin B12 and folate absorbed?
A
Vitamin B12 = ileum
Folate = duodenum and jejunum
11
Q
Where is intrinsic factor produced?
A
Parietal cells of the gastric mucosa
12
Q
Where is vitamin B12 mainly found?
A
The liver
13
Q
What is the function of vitamin B12 and folate?
A
They are required for the synthesis of DNA (converting homocysteine –> methionine), in their absence the cell fails to divide post-replication, leading to the production of one larger RBC
14
Q
Why does vitamin B12/folate deficiency lead to macrocytic anaemia?
A
Impairs DNA synthesis (can’t convert homocysteine into methionine) so there is failure to divide into 2 new cells, so instead the cell remains as one larger cells
15
Q
What conditions may cause a normocytic anaemia?
A
Sickle cell, anaemia of chronic disease (reduced production of RBCs), haemolysis, uncompensated increased plasma volume, vitamin B2/B6 deficiency
16
Q
How can chronic disease lead to the development of anaemia?
A
Reduced life-span of RBCs due to infection/cancer/inflammation, but there is also reduced production due to bone marrow having a poor response to EPO or reduced EPO production due to inflammatory cytokines interring with this process (IL-1, TNFa)
17
Q
Outline the mechanism of metabolism in red blood cells
A
Anaerobic: produce ATP via glycolysis and lactic acid fermentation of the produced pyruvate as well as using the pentose phosphate pathway
18
Q
Outline the acquired causes of haemolytic anaemia
A
Autoimmune haemolytic anaemia (warm and cold), microangiopathic haemolytic anaemia (mechanical damage to RBCs) and infection (malaria
19
Q
Outline the hereditary causes of haemolytic anaemia
A
Enzyme defects (G6PD deficiency, pyruvate kinase deficiency), haemolobinopathies (sickle cell, thalassaemia), membrane defects (hereditary spherocytosis and elliptocytosis)
20
Q
Describe warm autoimmune haemolytic anaemia
A
IgG mediated (cold is IgM) causes extravascular haemolysis and spherocytosis Cause = CLL, lymphoma, idiopathic Treatment = steroids and immunosuppression
21
Q
Describe cold autoimmune haemolytic anaemia
A
IgM-mediated, causes extravascular haemolysis and spherocytosis
Cause = may follow infection EBV, mycoplasma
Treatment = keep warm
22
Q
Describe G6PD deficiency
A
X-linked condition (affects boys mainly)
GP6D usually produces gluthionine to prolong RBC life-span
Presentation: asymptomatic until trigger (java beans, infection)
Blood film: bite and blister cells
23
Q
Describe pyruvate kinase deficiency
A
Autosomal recessive
Reduced ATP production –> reduced RBC survival
24
Q
Describe hereditary spherocytosis and elliptocytosis
A
Autosomal dominant
Extravascular haemolysis due to becoming trapped in the spleen
> Elliptocytosis can be protective against malaria
Treatment: folate
25
Describe microangiopathic haemolytic anaemia
Mechanical damage to RBCs causes intravascular haemolysis
| Causes: HUS, ITP, DIC, prosthetic valve (pre)-eclampsia
26
How do signs of haemolytic anaemia differ from those of normal anaemia?
There is usually jaundice, organomegaly, gallstones (can be pigmented due to increased bilirubin from haemolysis), and leg ulcers in addition to the normal presentation
27
What is meant by 'extravascular haemolysis'?
Breakdown is outside of the blood vessels e.g. spleen
28
What is meant by 'intravascular haemolysis'?
Where RBC breakdown occurs within the blood vessels e.g. due to ABO mismatched transfusions, snake bites and infections
29
What common drugs may induce haemolytic anaemia?
Cephalosporins, levodopa, methyldopa, nitrofurantoin, NSAIDs
30
What are the signs of severe/complicated malaria?
```
Impaired consciousness/seizures
AKI
Shock
Hypoglycaemia
Pulmonary oedema
Hb <80g/L
Spontaneous bleeding/DIC
pH <7.3
```
31
What's the most common bacterium implicated in malaria?
Plasmodium falciparum, second is plasmodium viva
32
Explain sickle cell disease
Autosomal recessive; single amino acid substitution (GAG-->GTG) causes valine to present instead of glutamic acid at codon 6 of B-globin chain --> produces abnormal haemoglobin S that distorts RBCs into a crescent shape at low oxygen levels
33
What mode of inheritance does sickle cell disease have?
Autosomal recessive
34
What is alpha thalassaemia, generally?
Where one or more of the alpha genes on chromosome 16 are deleted/faulty
35
Which chromosome is implicated in alpha thalassaemia?
Chromosome 16
36
Which chromosome is implicated in beta thalassaemia?
Chromosome 11
37
What is alpha thalassaemia minima?
1/4 of the alpha genes on chromosome 16 are defective --> no clinical symptom
38
What is alpha thalassaemia minor?
2/4 of the alpha genes on chromosome 16 are defective --> normal production of RBCs with mild microcytic, hypochromic anaemia
39
What is alpha thalassamia major (Haemoglobin H disease)?
3/4 of the alpha genes on chromosome 16 are defective --> very little HbA can be produced --> high levels of unstable Hb Barts (4 gamma units) or Hb H (4 beta units) --> which have greater O2 affinity --> more difficult to transfer oxygen to the tissues.
Clear microcytic, hypochromic anaemia
40
What is hydrops fetalis?
Where 4/4 of the alpha genes on chromosome 16 are defective --> the only Hb present is Hb Barts (4 gamma units) which is incompatible with life
41
What is beta thalassaemia, generally?
Where there is a point mutation in the B-globin region on chromosome 11
42
How is sickle cell disease diagnosed at newborn screening?
Haemoglobin isoelectric focusing (IEF) shows elevated HbF at first, later in life there is higher HbS and no presence of HbA
43
How does beta thalassaemia trait differ from beta thalassamia major?
Trait = microcytic anaemia that is compensated (slightly increased levels of HbA2, 2x alpha and 2x delta globin chains) with normal HbA and HbF.
Major = severe microcytic anaemia with absent HbA and increase HbA2 and HbF
44
How is sickle cell disease managed?
Hydroxycarbamide - if they have frequent crises (to increase HbF)
45
What are the three different types of sickle cell crisis?
Vaso-occlusive - microvascular occlusion --> ischaemia
Aplastic - due to parvovirus B19 --> sudden reduction in RBC production by bone marrow
Sequestration - pooling of blood in spleen/liver
46
What is a vaso-occlusive sickle cell crisis?
Painful crisis due to microvascular occlusion. It's triggered by cold, dehydration, infection or hypoxia.
47
What is a aplastic sickle cell crisis?
Due to parvovirus B19 --> sudden reduction in RBC production by the bone marrow. Usually self-limiting
48
What is a sequestration sickle cell crisis?
Pooling of blood in the spleen and/or liver, presenting with organomegaly, severe anaemia and shock. Urgent transfusion is required.
Doesn't tend to occur in adults as the spleen becomes atrophic in sickle cell disease.
49
Why are those with sickle cell disease more vulnerable to infection?
Microvascular occlusion usually causes splenic infarction before the age of two, reducing the immune system of the individual and increasing their susceptibility to infection
50
What are the causes of polycythaemia (increased numbers of RBCs)?
Relative
Absolute: primary = polycythaemia vera, secondary = hypoxia (high altitude, lung disease, cyanotic heart disease, heavy smoking) or inappropriate EPO production (renal or hepatocellular carcinoma)
51
What is polycythaemia vera?
Malignant proliferation of haematopoietic stem cells in the bone marrow due to a mutation in JAK2 (95% cases) --> hyper viscosity and thrombosis
52
What is the role of neutrophils?
First response to bacterial and fungal infection
53
What increases and decreases the number of neutrophils?
```
Increases = bacterial infection, inflammation, trauma, burns
Decreases = viral infection, cytotoxic/chemotherapy drugs, severe sepsis, neutrophil antibodies (SLE, haemolytic anaemia), hypersplenism
```
54
What is the role of lymphocytes?
Cell-mediated immunity and antibody production
55
What increases and decreases the numbers of lymphocytes?
```
Increase = acute viral infection, chronic infection, leukaemia/lymphoma
Decrease = steroids, HIV, chemo/cytotoxic therapy,
```
56
What is the role of eosinophils?
Mediate allergic reactions and defend against parasites
57
What increases and decreases the numbers of eosinophils?
Increase = allergies, parasitic infection (Helminths), skin disease (eczema, psoriasis)
58
What is the role of monocytes?
Act as tissue macrophages (engulf pathogens to present them)
59
What increases and decreases the numbers of monocytes?
Increase = aftermath of radio/chemotherapy, chronic infection, malignant disease
60
What is the role of basophils?
Response to IgE-mediated hypersensitivity to release histamine
61
What increases and decreases the numbers of basophils?
Increase = myeloproliferative disease, viral infection, IgE mediated hypersensitivity (asthma, hay fever, hives/urticaria), inflammatory disorders (UC, RA)
62
What type of cells stem from the common myeloid progenitor?
Megakaryocytes, mast cells, myeloblasts (which then forms granulocytes)
63
What type of cells stem from the common lymphoid progenitor?
Natural killer cells, T and B lymphocytes (and then antibodies)
64
How do you handle a patient on a ward who has neutropenia?
Full barrier nursing in side room
Avoid IM injections (danger of infected haematoma)
Keep the patient as clean as possible
65
What is meant by the two-hit model of leukaemia?
Loss of function of transcription factors needed for differentiation of cells
Gain of function mutations fo tyrosine kinase to enhance proliferation
66
Name some examples of myeloproliferative disorders
CML, polycythaemia vera, essential thrombocytosis, primary/idiopathic myelofibrosis
67
What is petechiae?
Red speckles on the skin due to superficial bleeding (can be related to thrombocytopenia)
68
What are the common causes of thrombocytopenia?
Reduced production: leukaemia, liver failure, sepsis, vitamin B12/folate deficiency
Increased destruction: ITP, TTP, HUS, DIC, SLE, Zika and Dengue
69
Give examples of 5 drugs that can inhibit platelet function
Valproic acid - prevents epilepsy
Methotrexate - immunosuppressant (IBD)
Carboplatin - alkylating chemotherapy agent
Interferon - treatment of cancer or Hep C
PPI - treatment of GORD
70
Explain how balance is maintained between clot production and degradation.
t-PA is released into the blood very slowly by damaged endothelium of the blood vessels, such that when the bleeding has stopped (several days later) the clot is broken down
71
Which substances are involved in the breakdown of clots?
Tissue plasminogen activator (t-PA) and urokinase work to convert plasminogen --> plasmin --> breaks down the fibrin mesh in clots
72
What factor is deficient in haemophilia A?
Factor 8
73
What factor is deficient in haemophilia B?
Factor 9
74
What is the mode of inheritance of haemophilia?
X-linked recessive
75
What clotting screen aspect would be increased in both haemophilia and vWF disease?
Increased APTT (intrinsic pathway affected)
76
What are the two main inherited bleeding disorders?
Haemophilia and vW disease
77
Which clotting factors does vitamin K deficiency affect?
10, 9, 7, 2 (1972)
78
What are the potential causes of vitamin K deficiency?
Haemorrhagic disease of the newborn (no bacterial gut synthesis of vitamin K)
Biliary obstruction (malabsorption of vitamin K)
Liver disease (ineffective use of vitamin K)
Use of warfarin (vitamin K antagonist)
79
What is haemorrhage disease of the newborn?
Where the newborn has no bacterial gut synthesis of vitamin K so requires vitamin K supplementation at birth
80
How can kidney disease lead to impaired platelet function?
Reduced clearance of toxins by the kidney leads to increased levels of urea --> uraemia --> inhibits platelet function
81
What is diffuse intravascular coagulation (DIC)?
Widespread intravascular deposition of fibrin --> using up all of the clotting factors and platelets --> bleeding due to depletion of coagulation proteins and platelets
Causes: infection, malignancy, liver disease, ABO mismatch post-transfusion, shock
82
What are the causes of DIC?
Causes: infection, malignancy, liver disease, ABO mismatch post-transfusion, shock
83
What's the mechanism of action of LMWH, fondaparinux and DOACs?
Inactivates factor Xa
84
What's the mechanism of action of unfractionated heparin (UFH)?
Binds to antithrombin
85
What's the mechanism of action of warfarin?
Inhibits reductase enzyme responsible for regenerating vitamin K --> deficiency in 10, 9, 7 and 2 clotting factors
86
What's the mechanism of action of tranexamic acid?
Competitively inhibits the conversion of plasminogen to plasmin (so prevents clot breakdown)
87
Why may desmopressin be prescribed to a patient with haemophilia A?
Works to stimulate the production of clotting factor 8
88
What is meant by 'Virchow's triad'?
A triad associated with increased risk of developing VTE:
1) Endothelial damage (smoking/HTN, surgery, trauma)
2) Hyper-coagulability (Factor V Leiden, cancer, pregnancy, HRT, obesity, chemotherapy)
3) Stasis (immobility, polycythaemia)
89
Are all UK blood products leukocyte deplete?
Yes - to reduce the incidence of any complications
90
Outline the potential complications from blood transfusion
Acute haemolyrtic reaction (due to ABO incompatibility) - STOP transfusion, keep IV line open with saline
Anaphylaxis - STOP transfusion, maintain airway and give oxygen, contact anaesthetist
Bacterial contamination - STOP transfusion and start broad-spectrum antibiotics
TRALI (transfusion-related acute lung injury) - STOP transfusion, start 100% oxygen and remove donor from donor panel
Non-haemolytic febrile transfusion reaction - stop/slow transfusion and give paracetamol
Allergic reaction - slow/stop transfusion and give antihistamine
Fluid overload - stop transfusion
91
How would an acute haemolytic reaction to blood transfusion present and how would you manage it?
(Due to ABO incompatibility)
Signs = agitation, rapid temperature spike, low BP, flushing, abdo/chest pain
Mx = stop transfusion, send off all cultures, keep IV line open with saline and treat DIC if present
92
How would an anaphylaxis to blood transfusion present and how would you manage it?
```
Signs = bronchospasm, cyanosis, low BP
Mx = stop transfusion, maintain airway
```
93
How would an acute bacterial contamination blood transfusion present and how would you manage it?
```
Signs = rapid temperature spike, low BP and rigors
Mx = stop transfusion and start broad spectrum antibiotics
```
94
How would a non-haemolytic febrile transfusion reaction to blood transfusion present and how would you manage it?
```
Signs = shivering and fever 30mins-1hr after starting transfusion
Mx = slow/stop transfusion, give paracetamol and monitor
```
95
How would an allergic reaction to blood transfusion present and how would you manage it?
```
Signs = urticaria and itch
Mx = slow/stop transfusion, give antihistamine and monitor
```
96
How would a transfusion-related acute lung injury present and how would you manage it?
```
Signs = dyspnoea, cough, CXR shows white out
Mx = stop transfusion, give 100% oxygen and remove donor from donor panel
```
97
When is the adminstration of clotting factor concentrate contraindicated?
In the presence of DIC
98
When might you administer packed red cells?
Anaemia (Hb 70-80) and blood loss
99
When might you administer platelet concentrate?
If there is continuous bleeding or a platelet count <20
100
When might you administer fresh frozen plasma?
Clotting defects e.g. DIC, warfarin overdose, liver disease, TTP
101
When might you administer cryoprecipitate?
Haemophilia (when clotting concentrate isn't available)
102
When might you administer human albumin solution?
To replace protein in liver disease or nephrosis (usually as a treatment for ascites)
103
When might you administer clotting factor concentrate?
Haemophilia
104
Where is IgA found and what's it's function?
Found in mucus, saliva, tears and breast milk. Protects against pathogens
105
Where is IgD found and what's it's function?
Part of the B cell receptor, it activates basophils and mast cells
106
Where is IgE found and what's it's function?
Protects against parasitic worms and is responsible for allergic reactions
107
Where is IgG found and what's it's function?
Secreted by plasma cells in the blood and is able to cross the placenta to the foetus
108
Where is IgM found and what's it's function?
May be attached to the surface of a B cell or secreted directly into the blood. This antibody is responsible for the early stages of immunity
109
What is meant by 'paraproteinaemia'?
The presence of excessive amounts of paraprotein in the blood, usually due to an underlying immunoproliferative disorder e.g. multiple myeloma
110
Describe acute lymphoblastic leukaemia (ALL)
Most common childhood cancer
Involved immature lymphoblasts
Hyperdiploidy is common (twice the normal amount of chromosomes)
Normocytic anaemia, low platelets and high WCC
Presence of philadelphia chromosome gives a worse disease prognosis
111
Describe acute myeloid leukaemia (AML)
Involves myeloid precursor cells
| Bloods: macrocytic anaemia, low platelets, high leukocytes, AUER RODS (ELONGATED STRUCTURES OF GRANULES)
112
Describe chronic lymphocytic leukaemia (CLL)
Involves mature B cells
Presentation: 65-70 year olds
Bloods: normocytic anaemia, low platelets, high WCC, mild neutropenia
113
Describe chronic myeloid leukaemia (CML)
Associated with philadelphia chromosome
Phases: chronic (3-5 years), accelerated (3-6 months), blast crisis (3 months then death)
Blood: normocytic anaemia, high platelets, high WCC, agranulocytosis
Treatment: imatinib (bcr-abl inhibitor)
114
What are myelodysplastic syndromes?
Conditions that cause abnormal production of cells in the bone marrow
115
Describe myeloma
Tumour of plasma cell proliferation
Presents with PARAPROTEINAEMIA, back pain, high calcium, recurrent bacterial infection, renal impairment (light chain deposition)
Blood: normocytic anaemia, ROULEAUX CELLS
116
Who often presents with myeloma?
70+ Black Males
117
Describe lymphoma
Malignant proliferation of lymphocytes (90% are B cells)
| Lymph node pain when drinking alcohol, non-tender lymph node enlargement
118
What's the difference between leukaemia and lymphoma?
In lymphoma malignant cells begin in the lymph nodes, in leukaemia they are in the bone marrow.
119
What is the Philadelphia Chromosome?
Recipricol translocation of chromosome 9:22 causing the fusion of bcr-abl --> uncontrolled tyrosine kinase activity --> uncontrolled cell proliferation
Mainly implicated in CML
120
What symptom is characteristic of lymphoma
Lymph node pain induced by drinking alcohol
