Haematology Peer Teaching Flashcards
1
Q
how much of blood is plasma and how much is cellular
A
55% is plasma
45% is cellular
2
Q
what is eryptosis and where does it occur
A
it is the apoptosis of RBCs and occurs in the spleen, liver and bone marrow
3
Q
which white blood cells are granulocytes
A
neutrophils
basophils
eosinophils
4
Q
what are platelets derived from?
A
they are derived from megakaryocytes
5
Q
what are the functions of thrombin
A
- convert fibrinogen to fibrin (major component of a clot)
- activates factors
- V
- VIII
- XI
- this causes positive feedback on more thrombin production
6
Q
which clotting factors are vitamin k dependent
A
2
7
9
10
7
Q
what are the two reasons that the liver is important for clotting
A
produces bile salts which are important for vitamin K absorption
the liver synthesises clotting factors
8
Q
draw the clotting cascade
A
9
Q
5 things included in an FBC
A
red blood cell volume
white blood cell volume
platelet volume
Hb concentration
mean corpuscular volume
10
Q
what is the reticulocyte count and what can it tell you
A
- the reticulocyte count is a blood test that enables you to see how quickly the bone marrow is producing new RBCs
- low RC:
- something is preventing RBCs from being produced
- e.g. haematinic deficiency
- high RC:
- indicates that rbcs are being lost or destroyed so more RBCs are being made to compensate
- e.g. bleeding/haemolytic anaemia
11
Q
what is haematinic defiiciency
A
it is anaemia that is caused by deficiency in the constituents of blood cells
12
Q
what is serum ferritin and what does it mean if it’s high or low
A
ferritin is the major iron storage protein in the body
it can be used to indirectly measure iron levels in the body
it’s also an acute phase protein so can be raised in inflammation and malignancy
13
Q
why would you choose a THICK blood film
A
this allows the examination of a large amount of blood for the presence of parasites
14
Q
why would you choose a THIN blood film
A
this allows observation of RBC morphology, inclusions and intracellular and extracellular parasites
15
Q
how much O2 can each haemoglobin carry
A
there are two alpha chains and two beta chains
each can carry a molecule of O2
so overall, each molecule of haemoglobin can carry 4O2
16
Q
what is anaemia
A
it is a decrease in haemoglobin below reference range
17
Q
when is it microcytic, normocytic or macrocytic
A
microcytic - MCV <80
normocytic - MCV 80-100
macrocytic - MCV >100
18
Q
nearly all anaemia presents with the same 5 symptoms
what are they
A
- Fatigue
- Lethargy
- Dyspnoea
- Palpitations
- Headache
19
Q
nearly all anaemia presents with the same 3 signs
what are they
A
- Pale skin
- Pale mucous membranes
- Tachycardia
20
Q
what are the 3 main causes of microcytic anaemia
A
thalassaemia
iron deficiency anaemia
anaemia of chronic disease
21
Q
where in the digestive system is iron absorbed
A
in the duodenum
22
Q
what are 4 signs specific to iron deficiency anaemia
A
- brittle hair and nails
- kolionychia - spoon shaped nails
- atrophic glossitis - inflamed tongue with depapillation
- angular stomatitis - inflammation of corners of mouth
23
Q
name 5 things that can cause iron deficiency anaemia
A
low iron diet
blood loss
breastfeeding
malabsorption
hookworm
24
Q
what does hypochromic mean
A
that red blood cells are paler than usual due to a deficiency of Hb
25
Ix for iron deficiency anaemia and what you will find
* FBC: hypochromic microcytic anaemia
* serum ferritin: low
* reticulocyte count: low
* endoscopy: possible GI bleed
26
treatment for iron deficiency anaemia and 5 SEs
* Ferrous Sulphate or Ferrous Fumarate
* SEs:
* black stools
* constipation
* diarrhoea
* nausea
* epigastric abdo pain
27
3 main causes of normocytic anaemia
acute blood loss
combined haematinic deficiency (iron and B12)
anaemia of chronic disease
28
4 conditions that can cause anaemia of chronic disease
* any that causes a shortening of red blood cell like or reduces red blood cell proliferation
* CKD
* Rheumatoid Arthritis
* Lupus
* Cancer
29
what are the three main causes of macrocytic anaemia
B12 deficiency (pernicious anaemia)
Folate deficiency
Alcohol excess
30
what is megaloblastic anaemia
this is what B12 and folate deficiency anaemia are sometimes called
it means that there has been an inhibition of DNA synthesis
the red blood cell continues to grow without mitosis causing macrocytosis
31
where is folate absorbed
it is absorbed in the jejunum
32
what are the main causes of folate deficiency
poor folate diet
malabsorption
pregnancy
anti-folate drugs (methotrexate)
33
investigation for folate deficiency anaemia
blood film: macrocytic anaemia
erythrocyte folate level: indicates reduced body stores
34
what is the treatment for folate deficiency anaemia
the treatment is folic acid supplementation and treatment of the underlying cause
consider prophylactic supplementation in pregnancy
35
what is the dietary source of folate
leafy greens and spinach
36
where is vitamin B12 absorbed
in the terminal ileum
37
what is pernicious anaemia
it is when there is no intrinsic factor commonly due to autoimmune destruction of parietal cells that produce it or against IF itself
intrinsic factor is required for vitamin B12 to bind and be absorbed
this leads to a B12 deficiency that causes anaemia
38
4 causes of pernicious anaemia
atrophic gastritis
gastrectomy
crohns
coeliac
these all either affect the production of intrinsic factor or absorption in the ileum
39
investigations for pernicious anaemia
blood film: macrocytic red cells
autoantibody screen: there may be IF antibodies
40
treatments for pernicious anaemia
vitamin B12 (Hydroxycobalm) injections
41
complications of pernicious anaemia
heart failure
angina
neuropathy
42
how are red blood cells removed from the circulation
after ~120 days they are removed by macrophages present in the red pulp of the spleen
43
what is haemolytic anaemia
this is when rbcs are destroyed before their 120 day lifespan is up
44
draw the rbc breakdown diagram
45
How does haemolytic anaemia present
* normal anaemia presentation
* jaundice (from excess bilirubin)
* gallstones (from excess bilirubin)
* signs of underlying disease (SLE Malar rash)
* leg ulcers
* splenomegaly
46
what are the two broad categories of causes of haemolytic anaemia
inherited
acquired
47
three inherited auses of haemolytic anaemia
membranopathies
enzymopathies
haemoglobinopathies
48
three acquired causes of haemolytic anaemia
autoimmune
infections
secondary to systemic disease
49
what is the treatment of haemolytic anaemia
treatment of the underlying cause
folate and iron supplementation
immunosuppressives if autoimmune
splenectomy if severe
50
what are the investigations for haemolytic anaemia
* FBC: reduced haemoglobin
* Reticulocyte count: increased
* Blood film: presence of schistocytes
51
what is bone marrow failure
this is where a reduction in the number of pluripotent stem cells causes a lack of haemopoiesis
the reduced number of new RBCs replacing the old ones causes anaemia
52
4 causes of bone marrow failure
congenital
acquired: i.e. aplastic anaemia
cytotoxic drugs/radiation
infections
malignant infiltration
53
what are some causes of aplastic anaemia
radiation
chemotherapy
infection
54
specific signs and symptoms of bone marrow failure
increased susceptibility to infection
increased bruising
increased bleeding (from nose and gums especially)
55
investigations for aplastic anaemia
1. FBC: pancytopaenia
2. Reticulocyte count: low
3. Bone marrow biopsy: increased fat spaces where stem cells were
56
treatment for aplastic anaemia
removal of causative agent
blood/platelet transfusion
bone marrow transplant
immunosuppressive therapy
57
what is the definition of polycythaemia
it is an increase in haemoglobin, PCV and RBCs
58
primary causes of polycythaemia
* these are causes that increase the sensitivity of bone marrow to EPO
* Polycythaemia rubra vera
* mutation in JAK2 gene
* Primary familial congenital polycythaemia
* mutation in EPOR gene
59
secondary causes of polycythaemia
* these are causes where there are more RBCs due to incresed circulating EPO
* chronic hypoxia
* poor oxygen delivery (e.g. high altitude)
* abnormal RBC structure
* tumours that release EPO
60
symptoms of polycythaemia
may be asymptomatic
may present with easy bleeding/bruising, fatigue, dizziness, headaches
61
what are the Ix for polycythaemia
* FBC: increased PCV, RBC and Hb
* Genetic testing for JAK2 and EPOR gene
62
treatments for polycythaemia
primary: blood letting and aspirin
secondary: treat the underlying cause
63
risk factors for a DVT or embolism
* age
* obesity
* varicose veins
* long haul travelling
* immobility/bed rest
* plasminogen deficiency
* thrombophilia
* pregnancy
64
what is Virchow's triad
Virchow's triad of hypercoagulability, venous stasis, and injury to the vessel wallprovides a model for understanding many of the risk factors that lead to the formation of thrombosis
65
symptoms of DVT
calf pain and swelling
ankle oedema
calf warmth
pitting oedema
66
DVT Ix
D-Dimer test for EXCLUSION ONLY
Coagulation screen
FBC including platelets
US doppler
WELL'S SCORE
67
differential diagnosis for DVT
cellulitis
68
treatment for DVT
start LMWH and Warfarin immediately
stop LMWH when INR is 2-3
then either continue on warfarin or swap to a NOAC like rivaroxaban
69
how does LMWH work?
it inactivates factor Xa
70
how does warfarin work
it antagonises vitamin K dependent clotting factors
these are 2, 7, 9 and 10
71
what is the prevention of DVT
stockings
mobilisation
hydration
leg elevation
72
name 5 things on the well's score and what the threshold is for likely vs unlikely DVT
73
three categories of red cell disorder and an example of each
* haemoglobinopathy
* sickle cell disease
* thalassaemia
* membranopathy
* spherocytosis
* enzymopathy
* glucose-6-phosphate deficiency
74
what is the inheritance pattern of sickle cell disease
autosomal recessive
commoner in afrocarribean populations
75
what is the mutation in sickle cell disease
it is apoint mutation of the B globin gene with valine changed to a glutamine
this produces HS variant
76
what happens in sickle cell disease
under stress, i.e. cold, infection, dehydration, the RBCs become deoxygenated which causes HS to polymerise
this makes the RBCs rigid and sickled
77
carriers of sickle cell trait are protected from what
falciparum malaria
78
acute and chronic complications of sickle cell disease
* acute
* painful crisis
* sickle cell chest crisis
* haemolytic crisis
* mesenteric ischaemia
* chronic
* renal impairment
* pulmonary hypertension
* joint damage
79
Ix for sickle cell disease
* screen neonates: blood/heel prick test
* FBC: Hb and reticulocyte count
* Blood film: sickled erythrocytes
* Hb electropharesis for Dx shows HbSS to be present
80
management of sickle cell disease
* supportive
* agressive analgesia (i.e. opiates)
* treat underlying cause of crisis (Abx)
* fluids
* folic acid
* transfusion if falling Hb
* stem cell transplant
* if hyposplenic
* prophylactic Abx
* pneumococcal and meningococcal vaccination
81
what is the inheritance pattern of thalassaemia
autosomal recessive
82
what is hyposplenism
it is when there is reduced spleen functuion and you get increased risk of serious infections
it can occur in sickle cell anaemia as well as coeliac
83
what populations in thalassaemia most common in
mediterranean, middle eastern and asian
84
what is the normal makeup of HbA (adult haemoglobin)
2 alpha and 2 beta chains
85
how many genes produce alpha chain and beta chain of Hb
4 genes produce alpha
2 genes produce beta
86
what is thalassaemia
thalassaemia is the decreased production of one or more globin chain in red cell precursors or mature red cells
alpha thalassaemia: decreased alpha chain synthesis
beta thalassaemia: decreased beta chain synthesis
87
what happens in thalassaemia
* precipitation of globin chains in red cell precursors inhibits erythropoiesis
* there is reduced production of red cells
* precipitation of globin chains in mature red cells causes haemolysis
so overall you get faulty production and premature destruction of RBCs
88
what happens in alpha thalassaemia
* 4 genes control alpha chain production and symptoms vary depending on the number of mutations
* all 4 affected: invariably fatal in utero
* 3 affected: commmon in parts of asia. patients have severe haemolytic anaemia and splenomegaly. they're sometimes dependent on transfusions
* 2 deletions: asymptomatic with possible mild anaemia
* 1 deletion: blood picture is normal
CARRIERS ARE PROTECTED FROM FALCIPARUM MALARIA
89
What is HbA
it is made up of two alpha and two beta chains
90
what is HbA2
it is made up of two alpha chains and two delta chains
91
what is HbF
it is made up of 2 alpha and 2 gamma chains
92
what are the clinical syndromes of B thalassaemia
beta thalassaemia minor
beta thalassaemia intermediate
beta thalassaemia major
93
what is the beta thalassaemia minor like
it is an asymptomatic heterozygous carrier state
there is mild or absent anaemia (low MCV and MCH)
iron stores and ferritin are normal
94
what is the presentation of beta thalassaemia intermediate
it is moderate anaemia
doesn't require transfusions
there is often splenomegaly, bone abnormalities and recurrent leg ulcers and gallstones
95
what happens in beta thalassaemia major
aka cooley's anaemia
presents in first year of life with severe anaemia, failure to thrive and chronic infections
there may be bony abnormalities like skull bossing and thalassaemic facies
they may have hepatosplenomegaly
96
investigations for beta thalassaemia
* FBC and blood film will show hypochromic microcytic anaemia
* there will be irregular and pale RBCs
* there are increased reticulocytes and nucleated RBCs
* diagnosis is by Hb electrophoresis
97
treatment of beta thalassaemia
* regular blood transfusions are the mainstay of treatment
* risk of iron overload and deposition in major organs like liver, spleen, pancreas and heart
* iron chelation needed (desferrioxamine reduces iron overload)
* ascorbic acid increases urinary excretion of iron
* promote fitness and healthy diet
98
what is the aetilogy of membranopathy and what are the two types
this is an autosomal dominant condition that leads to a deficiency in a protein for the RBC membrane
deformed cells get trapped in the spleen
spherocytosis is where they have vertical deformity
elliptocytosis is where they have a horizontal deformity
99
symptoms of membranopathy
neonatal jaundice and haemolytic anaemia
this is exacerbated during infection
there's excess bilirubin which can cause gallstones
100
investigation for membranopathy
FBC and reticulocyte count
Blood film: osmotic fragility tests (RBCs show fragility in hypotonic solutions)
101
treatment for membranopathy
folic acid and splenectomy
102
what is the inheritance pattern of glucose-6-phosphate deficiency
it is x linked but can affect women
103
who does glucose-6-phosphate deficiency mainly affect
mainly affects men from mediterranean, africa, and middle east
104
what are the symptoms of glucose-6-phosphate deficiency
* it is rarely symptomatic!
* there can be oxidative crisis
* precipitated by drugs (nitrofurantoin) or illness
* Henna is also a precipitant
* rapid haemolysis --\> jaundice --\> anemia
105
Ix of glucose-6-phosphate deficiency
blood film: bite and blister cells
diagnosis is by enzyme assay
106
management of glucose-6-phosphate deficiency
avoid precipitants e.g. henna
transfuse if severe
107
what are two ways to assess someone's coagulation
APTT (Activated partial thromboplastin time) tests the intrinsic pathway
PTT (prothrombin time) tests the extrinsic pathway
108
what is DIC
* disseminated intravascular crisis
* generation of fibrin within blood vessels and also consumption of platelets/coagulation factors causing secondary activation of fibrinolysis
* this means there will be initial thrombosis followed by bleeding tendancy
* this is rare but life threatening
109
causes of DIC
* malignancy
* septicaemia
* obstetric causes
* trauma
* infections
* haemolytic transfusion reactions
* liver disease
110
treatment for DIC
treat underlying cause
maintain blood volume and tissue perfusion
may require transfusions
give activated protein C
111
what is thrombocytopenia? what are the two types and which is more common
thrombocytopenia is low platelet count
it can be immune thrombocytopenic purpura (ITP) which is more common or thrombotic thrombocytopenic puprura (TTP) which is less common
112
three general causes of thrombocytopenia
reduced platelet production in the bone marrow
excessive peripheral destruction of platelets
problems associated with an enlarged spleen
113
ITP physiology
* immune thrombocytopenic purpura
* often triggered by a viral infection or malignancy
* there is antibody mediated destruction of platelets
* may be associated with other autoimmune conditions
* acute: in kids 2 weeks after infection
* chronic: mainly in women with fluctuating course
114
ITP clinical features
easy bruising
purpura
epistaxis/menorrhagia
115
investigation of ITP
reduced platelets so normal/increased megakaryocytes
may be able to detect platelet autoantibodies
116
what is TTP and what is the pathology
* thrombotic thrombocytopenic purpura
* deficiency in ADAMTS13 protease which usually cleaves von willebrand factor multimers
* large vwf multimers cause platelet aggregation and fibrin deposition in small vessels
* this is a haematological emergency due to multi-system thrombotic microangiopathy
117
treatments for ITP
corticosteroids like prednisolone
splenectomy
118
what are the clinical features of TTP
aki
neurological symptoms e.g headache, palsies, seizure
fever
microangiopathic haemolytic anaemia
119
Ix for TTP
reduced platelets so normal/increased megakaryocytes
ADAMTS13 activity
120
what is the treatment for TTP
plasma exchange flushes away antibodies and replaces ADAMTS13 protease
corticosteroids like prednisolone
consider retuximab for non-responders r
121
what are the two main types of Haemophilia and what are the causes
also which is more common
* haemophilia A: factor 8 deficiency (more common)
* haemophilia B: factor 9 deficiency
122
what is the inheritance patterns of haemophilia A and B
both are x linked recessive so females are rarely affected
123
will haemophila A and B affect the APTT or the PTT
the PPT will be normal but the APTT will be prolonged
this is because factor 8 and 9 are part of the intrinsic pathway not the extrinsic
PTT = extrinsic
APTT = intrinsic
124
who usually gets AML
usually older people - there is better survival in young people
125
who usually gets ALL
this is the commonest malignancy in childhood and has very good survival
126
investigation for AML and ALL
FBC
Blood film
BM aspiration
127
AML and ALL treatment
* supportive
* blood
* platelets
* fluids
* abx
* chemo to induce remission
* bone marrow transplant
* steroids to maintain and manage GVHD
128
who gets CLL
incidence increases with age
M\>F
white\>black
usually with a FH of ALL or CLL
129
what is the cell type affected by CLL
it is a malignancy of B cells
130
what is the presentation of CLL
* 50% cases are incidental findings from something unusual on a FBC
* symptomatic disease is generally associated with later stage disease
* lymphadenopathy
* infections
* hepatosplenomegaly
131
treatment of CLL
usually watchful waiting
maube chemo or radio to shrink lymphadenopathy
its chronic and incurabl - patients die with rather than from
132
who gets CML
middle aged people
philadelphia chromosome
133
what is the philadelphia chromosome and what is the treatment associated with it
* translocation that produces BCR-ABL1 fusion protein
* this is a constitutively active tyrosine kinase
* causes cell proliferation
* seen in CML
* treatment is imatinib which is a TK inhibitor
134
what is the age incidence of hodgkin's lymphoma
bimodal - young and old
135
what histology is hodgkin's lymophoma associated with
reed sternberg cells
136
what disease is associated with auer rods
AML
137
what is the system used to stage lymphoma
ann arbour system
138
stages 1 - 4 of ann arbor system
which diseases does it apply to
* Stage 1: involvement of single lymph node region
* stage 2: involvement of two or more lymph node regions on same side of diaphragm
* stage 3: involvement of lymph node regions on both sides of the diaphragm
* stage 4: diffuse extralymphatic disease (e.g. in liver or bone marrow)
A and B refers to presence or absense of B symptoms
ann arbor is for both hodgkin and non-hodgkin lymphomas
139
what are B symptoms
fever
night sweats
weight loss
140
what is the difference between low grade and high grade lymphoma
low grade you won't cure and median survival is 3-10 years
high grade is more severe but there's a 30% cure rate
141
what is myeloma
it is malignancy of one clone of plasma cells in the bone marrow
there is monoclonal Ig so repeat infections cause no other Ig
bence jones protein (it's an Ig protein) found in urine
142
does Myeloma affect men or women more
men
143
clinical features of myeloma
cancer symptoms
confusion (maybe due to hyperviscosity and hypercalcaemia)
hypercalcaemia symptoms
repeat infections
pathological fractures
bone pain
renal impairment
144
diagnosis of myeloma
monoclonal Ig band seen on electrophoresis
BM aspiration shows excess plasma cells
X-Ray: pepper pot skull
145
treatment for myeloma
chemo
supportive care including bisphosphonates
watchful waiting
146
what is tumour lysis syndrome and how can you prevent it
this is where chemo is given and cells die and lyse releasign their contents
this leads to hyperkalaemia and release of nucleic acids
this can produce crystals which get deposited in the kidney impairing function
to prevent this give allopurinol
to treat give IV fluid and correct electrolytes
147
what type of organism is responsible for malaria
protozoa called Plasmodia falciparim normally
sometimes it's P. ovale or P. vivax
148
what organism transmits malaria
female anopheles mosquito
149
what are the three stages of malaria
exo-erythrocytic
endo-erythrocytic
dormant stage (P.ovale and P.vivax)
150
signs and symptoms of malaria
* fever + exotic travel = malaria until proven otherwise
* chills
* sweats
* anemia
* hepatosplenomegaly
* fatigue
* black urine
151
pathogenesis of malaria
* paracite matures in RBC
* knobs form in RBC surface
* infected cells bind to eachother and this is called rosetting
* they also bind to receptors on endothelial cell walls
* this causes microvascular obstruction which may lead to tissue hypoxia
152
investigations for suspected malaria
* thick and thin blood film
* rapid diagnostic test (RDT) detects plasmodium antigens in blood
* RULE OUT MENINGITIS
153
Treatment for malaria
quinine and doxycycline
154
what is neutropenic sepsis and what is the management
it is temperature \>38 and absolute neutrophil count of \<0.5 x 10 9/L
Give Abx immediately
155
management for acute sickle cell crisis
fluids and pain relief
