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MBBS - Year 2 > Haematology - Anaemia, red cell metabolism and transfusion > Flashcards

Haematology - Anaemia, red cell metabolism and transfusion Flashcards

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1
Q

Amount of iron in avg man

A

4g total

30-45% less in avg woman

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2
Q

What % of iron is stored as Hb

A

65%

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3
Q

What % of iron is stored as ferritin

A

20-30%

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4
Q

What is iron stored as excluding Hb and ferritin

A

Myoglobin
Catalase
Various enzymes

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5
Q

What is iron status regulated by

A

Absorption

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6
Q

Iron requirements for men and women

A

Male: 0.5 - 1.0 mg/d
Menstruating female: +0.5 - 1.0mg/d
Pregannacy: +1 - 2mg/d
Growing children: +0.6 - 1.0mg/d

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7
Q

Key players in iron metabolism

A 
DMT 1 
Ferritin 
Transferrrin and transferrin receptors
Haemosiderin 
Ferroportin 
Hepcidin 
HFE
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8
Q

Function of DMT 1

A

Take up Fe2+ from gut into gut wall

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9
Q

When is DMT1 upregulated

A

Fe deficiency

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10
Q

What is ferritin

A

Intracellular storage form of iron in the liver

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11
Q

What is ferritin upregulated by

A

Fe excess

Infl

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12
Q

Role of transferrin

A

Carries iron around body to transferrin receptors allowing uptake into cells

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13
Q

When is transferrin upregulated

A

Fe deficiency

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14
Q

Role of ferroportin

A

Transfer iron for enterocyte into plasma

Opposite to DMT - 1

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15
Q

Haemosiderin

A

Partial degradation of haemoferritin

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16
Q

Role of hepicidin

A

Acute phase protein - feedback signal
Controls absorption by binding to ferroportin
Affected in anaemia of c/c disease

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17
Q

Can we actively excrete iron

A

No

Only passive loss through gut, skin, faeces

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18
Q

Haematinics

A

What is needed for blood cell formation

Iron - incorporated into haem
AA - make globin chain
Bone marrow blasts - DNA synthesis forms dividing cells to package the O2

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19
Q

Anaemia of c/c disease and hepcidin

A

C/c disease causes release of IL6 which upregulates hepcidin
Hepcidin is a competitive inhibitor of iron on ferroportin —> decreased uptake of Fe

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20
Q

Factors increasing the absorption of iron

A 
Increased Fe2+ and haem iron 
Acids and ascorbate in diet 
Pregnancy 
Solubilising agents - sugars, AA
Increased erythropoiesis 
Haemochromatosis 
Increased DMT-1 and ferroportin
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21
Q

Hameochromatosis

A

Genetic disorder causing body to absorb excessive amount of iron from diet
Iron accumulates over time and causes damage to several organs incl liver

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22
Q

Factors decreasing the absorption of Fe

A 
Increased Fe3+ and non-organic iron 
Alkali
Phytate (tea) and phosphates 
Tetracycline 
High iron diet 
Infections - hepcidin 
High body iron stores
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23
Q

Ix and mx of IDA algorithm

A

Confirm IDA
Determine cause
Treat anaemia
Treat underlying cause

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24
Q

IDA

A

Iron deficiency Anaemia

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25
Microytic anaemias
``` Thalassaemia trait Anaemia of c/c disease IDA Lead poisoning Sideroblastic anaemia ```
26
Labs for IDA
Low MCV Low serum Fe Low ferritin Increased transferrin
27
Labs of ACD
Low MCV Low serum Fe Low transferrin
28
Labs for thalassaemia
Low MCV
29
Sideroblastic anaemia
Problem of haem ring
30
Labs for sideroblastic anaemia
Low MCV
31
Newer metrics for measuring anaemia
Ret-Hb % of hypochromic red cells Measuring functional iron delivery to the bone marrow
32
Using Ret-Hb to measure anaemia
Reticulocyte-Hb | Low is abnormal
33
Using % of hypochromic red cells to measure anaemia
Low is abnormal
34
Measuring functional iron delivery to the bone marrow to measure anaemia
Shorter term changes than Hb or MCV | Abnormal in IDA, ACD and thalassaemia
35
Causes of iron deficiency
Inadequate diet Increased requirements Malabsorption Blood loss
36
Examples of increased requirements causing iron deficiency
Pregnancy | Growth
37
Examples of blood loss causing iron deficiency
Menstrual GI Urinary Lung
38
Determining cause of IDA
Hx and examination In UK, dietary deficiency alone is unusual - take diet hx Menstrual hx - duration, clots, tampons, flooding GI ix Othe rcxauses usually obvious - pulm haemorrhage, PMH, urinary hameosiderin
39
Who gets GI ix for IDA
All men and all post-menopausal women Symptomatic women Women 45+ (or 50) check Fhx of colon cancer
40
GI ix for IDA
``` Hx Faecal Hb - FIT Tissue transglutaminase antibody (tTG) Image upper and lower GI tracts The above are usually sufficient, if not test stool for parasites ```
41
What is important in GI hx for IDA
Drugs - NSAIDs, aspirin, bisphophonates
42
Imaging upper and lower GI tract for IDA ix
Gastroscopy (duodenal bx) and colonoscopy | Gastroscopy plus CT colonography
43
GI causes of IDA
``` Hookworm infections Coeliac disease Crohn's disease Gatritis/ oesphagitis Peptic ulceration Gastrectomy Colon cancer - esp R sided Large polyps Haemorrhoids Diverticular bleeding ```
44
Iron replacement drug therapy
Oral ferrous sulphate for 3/12 post Hb-normalisation - 60mg Fe/ 200mg Ferrous gluconate - 37mg/ 300mg Sodium ironedetate - 27.5mg/ 5ml Feric maltose - probably better tolerated (20mg)
45
What should be avoided in iron replacement therapy
Slow-release preparations
46
Parenteral iron for IDA
Rarely required | Modern total dose replenishment in 1-2 doses of ferric caboxymaltose/ derisomaltose
47
Benefits of parenteral iron
Hb responds equivalent Replensishes stores faster May be able to overcome some ACD Low risk of allergic reactions, hypophosphataemia
48
When should parenteral iron for IDA be considered
If absorption is impaired
49
When do you switch to parental iron if oral fails
Relatively early (2/52 to 4/52)
50
What is folic acid synthesised by
Bacteria
51
Where is folic acid found
Green vegetable, offal
52
What is folic acid biologically active as
Polyglutamates
53
What is required for biological activity of folic acid
B12
54
Store of folic acid vs vit B12
Relatively small store vs large store
55
What is vit B12 synthesised by
Microorganisms, not by humans
56
Kay players in B12 metabolism
``` R binders Gasttric parietal cell Gastric acid Intrinsic factor * Pancreatic secretion Ileal receptor Transcobalamin- I/ II/ III ```
57
Which cells are affected by B12 and folate deficiency
All cells | Rapidly dividing cells most vulnerable e.g. bone marrow precursors, gut epithelium
58
Spp symptoms of B12 deficiency
Neuropathy and optic atrophy
59
Ix and mx of megaloblastic anaemia algorithm
Confirm haematological dx Provide replacement therapy Determine underlying cause Clinically significant B12 deficiency can occur w/ out haematological effects
60
Confirming haematological dx of megaloblastic anaemia
Blod film B12 and red cell folate levels Condiser other causes of macrocytosis Bone marrow
61
Can clinically significant B12 deficiency occur w/ out haematological effects
Yes
62
What can microcytic anaemia be divided into
Megaloblastic and non-megaloblastic
63
Causes of megaloblastic microcytic anaemia
B12/ folate deficiency or combined Abnormal folate metabolism - MTX Abnormal DNA synthesis Myelodysplasia
64
Abnormal DNA synthesis causing megaloblastic macrocytic anaemia
Orotic acuduria Azathioprine Zidovudine
65
Orotic aciduria
Disease caused by enzyme deficiency resulting in decreased ability to synthesise pyrimidines
66
Causes of non-megaloblastic macrocytic anaemia
``` Pregnancy Liver disease Alcoholism Retiuclocytosis Hypothyroidism Drugs Marrow infiltration Sideroblastic anaemia Cold agglutinins ```
67
B12 replacement therapy
Parenteral hydroxycobalamin 3 monthly replacements Oral replacement if absorption intact
68
When is B12 given as prophylaxis
After total gastrectomy or ileal resection
69
Folate replacement therapy
Oral folic acid 4/12 or continuously | Folicinic acid for DHF-reductase inhibition - MTX
70
Why is folate given after B12 in combined deficiency
Initial folate may exacerbate neuropathy
71
When is folate given as prophylaxis
Pregnancy and preconception - neural tube defects normal risk vs high risk Haemolysis MTX therapy
72
Causes of folate deficiency
``` Diet Increased utilisation Malabsorption Urinary loss Drugs ```
73
Diet causing folate deficiency
Anorexia Children Elderly Alcoholics
74
Increased utilisation causing folate deficiency
Physiological - pregnancy, growth | Pathological - haemolytic, cancers, infl
75
Malabsorption causing folate deficiency
Diffuse small bowel diseases
76
Urinary loss causing folate deficiency
Haemodialysis
77
Drugs causing folate deficiency
Phenytoin - anti-seizure Primidone - anti-epileptic SSZ & related drugs MTX
78
Causes of B12 deficiency
``` Diet Gastric disease Ileal disease Infections Pancreatic disease Transcobalamin-II deficiency B12 destruction ```
79
Diet causing B12 deficiency
Vegan
80
Gastric disease casing B12 deficiency
Autoimmune gastritis | Major gastrectomy
81
Ileal disease causing B12 deficiency
Resection | Infl
82
Infections causing B12 deficiency
``` Small bowel bacterial overgrowth Fish tapeworm (D latum) ```
83
B12 destruction causing B12 deficiency
Nitrous oxide
84
B12 absorption tests
57/58Co labelled B12 +/- intrinsic factor Urinary excretion or whole body counting
85
Ix for causes of B12 deficiency
``` Dietary hx Autoantibodies - anti-parietal cells, anti-intrinsic factor (pernicious anaemia) B12 absorption tests Small bowel FT and bx Gastric bx Gastric and pancreatic function tests ```
86
Ix for causes of folate deficiency
Dietary hx Autoantibodies - anti-gliadin, anti-0endomysela Duodenal bx Consider systemic diseases
87
Nutrients essential for normal RBC formation
``` Iron Folate Vit B12 Vit B6 Vit C Vit E Copper Protein ```
88
Out of the nutrients essential for normal RBC function, which are we most likely to have deficiencies in
Iron Folate Vit B12
89
Symptoms seen in anaemia
V non-spp ``` Tiredness Weakness Pale skin Tachycardia SOB Chest pain Dizziness Numbness or coldness in extremities FTT and growth retardation in children ```
90
Epidemiology of IDA
Most widespread nutritional problem WW Caused debilitated health of 500 million women, >60,000 deaths during childbirth Increased morbidity and mortality, decreased productivity
91
Most vulnerable groups of IDA
Women of child-bearing age - menstrual blood loss and pregnancies Children - increased requirements for Fe to meet growth (muscles, tissues, menarche)
92
What does iron bioavilabity reopen on
Physiological factors | Dietary factors
93
Risk factors that can lead to IDA
Long-term use of PPIs Blood loss Pregnancy H. pylori infection
94
Dietary factors that explain ID in industrialised countries
Low bioavailability Sedentary lifestyle Lower micronutrient density - processed foods
95
Dietary sources of B12
Products of animal origin e.g. meat (esp liver), poultry, fish, milk, eggs Fortified breakfast cereals Fermented foods e.g. sauerkraut
96
Is folic acid naturally present in food
No - it is used to fortify foods
97
Folate vs folic acid absorption
Folic acid is highly bioavailable (85%) and folate are less absorbed (50%) and partially destroyed on cooking Alcohol consumption in creases requirements
98
Dietary sources of folate
``` Liver Yeast extract Green, leafy vegetables Legumes (beans, lentils) Orange juice Fortified cereals ```
99
Vulnerable group for nutritional anaemias
``` Infants and children (Fe) Vegans (Fe and B12) Pregnant women (Fe and folate) Elderly (all 3) Low income Ethnic minorities ```
100
Why is iron deficiency v rare in infants <4-6/12
Foetal Hb has sufficient stores Late (i.e 2. mins delay) cord clamping is important High efficiency of absorption from breast milk; cows filk formulas are fortified
101
Why is iron deficiency in infants more common after 6/12
Inappropriate weaning Poor wt gain Frequent infections Developmental delay Behavioural disorders
102
Iron and B12 deficiency in children
Prolonged bottle/ breast feeding may lead to ID If weaning foods have a low Fe content --> ID Vein children may require Vit B12 supplements
103
How do physiological adaptations in pregnancy affect | iron absorption
Fe absorption increases by ~50% in 2nd trimester and 4x in 3rd trimester Despite this, the iron deficit is 400-500mg
104
Why are pregnant women at a higher risk of folate deficiency
Higher physiological requirements (DNA synthesis and other 1-C transfer reactions)
105
What is the significance of women w/ MTHFR mutation and pregnancy
They require addn folate to reduce their increased risk of NTDs
106
Anaemia in the elderly
``` Higher risk of nutritional deficiencies Impaired absorption Poor quality meals in institutions Lower socio-economic status Mental problems ```
107
Preventive action of anaemia in the elderly
Increase the micronutrient density of the diet
108
Dietary assessment for anaemia
Growth in children (percentile charts) Detailed diet hx - meal patterns and food group Changes in appetite and food intake Medical hx
109
Nice pre-conception advice and nutritional deficiencies
Assess couple's risk of NTD | Thos at high risk should take folic acid 5mg daily until 12th week and those at normal risk 400micrograms
110
Lymph nodes in the head & neck
``` Submental Sublingual Submandibular Parotid Anterior cervical chain Posterior superficial cervical chain Supraclavicular Occiptal Postauricular ```
111
Border of axillary lymph nodes
Medial wall (chest wall) Lateral (humerus) Anterior (pectoralis major) Posterior (lat dorsi)
112
Groups in inguinal lymph nodes/ groin nodes
Horizontal | Vertical
113
Infectious causes of lymphadenopathy
Viral/ bacteria/ parasitic (generalised) | In areas drained by lymph nodes or involving lymph nodes
114
Malignant causes of lymphadenopathy
Haematological - lymphoma, CLL, ALL | Non-haematological - metastatic
115
Miscellaneous causes of lymphadenopathy
SLE Sarcoidosis Drugs
116
How many segments is the abdomen divided into
9
117
Segments of the abdomen
``` RH/ LH - Right/ left hypochondriac E - epigastrium RF/ LF - right/ left flank U - umbilical region RIF/ LIF - right/ left iliac fossa SP - suprapubic ```
118
How does the liver expand in hepatomegaly
Downwards | Towards RIF
119
How does the spleen expand in splenomegaly
Diagonally | Towards RIF
120
Types of causes of splenomegaly
Infection Infl Congestion Infiltration
121
Infective causes of splenomegaly
EBV Malaria Leishmaniasis TB
122
Infl causes of splenomegaly
RhA | SLE
123
Congestive causes of splenomegaly
Cirrhosis (portal HTN) | Haemolysis
124
Infiltrative causes of splenomegaly
``` Gaucher's Metastatic cancers Lymphoma CLL Myeloproliferative neoplasms (PV/ MF/ CML) ```
125
PV
Polycythemia vera
126
MF
Myelofibrosis
127
What do RBCs need to function
``` Efficient production (synthesis) To be pliable (get through small vessels) Hb on which to carry O2 Ensymes for metabolism Removal of defective cells ```
128
Erthryopoiesis
Synthesis of RBC in bone marrow | Erythroblast --> nucleated RBC --> reticulocyte --> mature red cells
129
Requirements for erythropoiesis
``` Normal stem cell Normal maturation Healthy bone marrow microenvironment Growth factors Essential components ```
130
Growth factors needed ion erythropoiesis
Erythropoietin | GM-CSF
131
Addn essential components for erythropoiesis
Fe Vit B12 Folate AA
132
What are RBC membrane's held together by
Proteins - some intrinsic (Band 3 which forms vertical scaffold) and horizontal scaffold formed by spectrin
133
Hb structure
Tetramer - 2 pairs of globin chains Haem molecules bound to each globin Iron within centre of haem
134
Phases of Hb production
Embryonic Foetal Adult
135
Does embryonic Hb have clinical implications
No
136
When does disease caused by defect in beta chain manifest
3/12 - 6/12 after birth
137
What chromosome codes for alpha chain
16
138
Where are alpha chains in Hb found
In all Hb from foetal to adult
139
What chromosome codes for beta-like chains in Hb
11
140
How many more alpha chains do we have compared to beta chains in Hb
2x as many alpha
141
Beta-like chains in different Hb
Beta in HbA (adult) (2:2 ratio for alpha) Gamma in HbF (foetal) Delta in HbA2 - v low levels from week 30 gestation
142
Why do RBC need enzymes for metabolism
Mature RBC has no nucleus or mitochondria so require enzymes for response to oxidative stress e.g. G6PD and ATP production
143
What happens if there are defects in the enzymes RBCs use for metabolism
Portion of RBCs that are susceptible to oxidative stress and die early due to ATP depletion
144
Normal RBC lifespan
120 days
145
How are old RBC removed
Macrophages - phagocytosis
146
Where are macrophages that remove old RBCs found
Spleen Liver Marrow - prevent damaged cells from entering circulation (protective mechanism)
147
What is anaemia
Reduced g of Hb/L blood below the age/ sex adjusted normal range q
148
What may anaemia occur as a result of
Too few RBCs Too little Hb An abnormally low haematocrit
149
Haematocrit
Ratio of RBC:plasma - aka packed cell volume | Reduced if increased plasma or decreased RBC
150
A/c vs c/c symptoms of anaemia
A/c - symtoms more marked | C/c - symptoms less severe; time for body to compensate
151
Less common symptoms of anaemia
Muscle cramps | Angina/ heart failure - anaemia exacerbates these condns
152
Signs of anaemia
Pallor - look in conjuctiva in darker skinned individuals Tachypnoea Tachycardia Hypotension
153
Causes of normocytic anaemia
``` ACD A/c blood loss A/c renal failure Bone marrow disorders Mixed B12/ folate and iron deficiency ```
154
How can we classify causes of anaemia aside from MCV
Reduced RBC production | Increased RBC destruction (haemolysis) or loss
155
Causes of reduced RBC production leading to anaemia
``` Defective stem cells Defective maturation Unhealthy microenvironment Absence of stimulation by growth factors Lack of components for RBC formation ```
156
Reduced RBC production as a result of defective stem cells
Inherited e.g. Diamond-Blackfan anaemia (rare) | Acquired - drugs, infections, immune (aplastic anaemia)
157
Aplastic anaemia
Bone marrow does not produce new blood cells | Empty bone marrow on bx
158
Defective maturation leading to reduced RBC production
Lack of nutrients e.g B12 deficiency | Myelodysplasia
159
Unhealthy microenvironment leading to RBC production
Damaged e.g. radiation, infections | Lack fo space due to fibrosis, haematological malignancy, non-haematological malignancy
160
Reduced RBC product as a result of absence of stimulation by growth factors
Decreased erythropoietin - renal failure
161
Lab findings for reduced RBC production leading to anaemia
Usually normocytic and normochromic - unless deficiency Fe, B12 or folate Reticulocytes not raised
162
Myelodysplasia
Failure to produce normal RBC
163
What causes ACD
Ineffective iron utilisation due to raised hepcidin
164
What is ACD seen in
C/c infl e.g. RhA, IBD C/c infection e..g pneumonia, TB Malignant disease
165
Haemolysis
Immature breakdown of RBCs
166
What does hameolysis lead to
Erythropoietic hyperplasia | Reticulocytosis
167
Erythropoietic hyperplasia
Marrow produces 6-8x normal rate
168
Signs of haemolysis
Due to formation of bilirubin Jaundice Dark urine Gallstones - (RBC pigment) +/- anaemia
169
Blood results in haemolysis
``` Anaemia - normocytic or microcytic (reticulocytosis) Raised reticulocyte count Raised bilirubin Raised LDH Low haptoglobin - binds to free Hb ```
170
How can the causes of haemolysis be divided
Abnormality within cell - intrinsic | Abnormality outside cell - extrinsic
171
Types of cell abnormalities causing haemolysis
Membrane - membranopathies Metabolism (enzymes) - enzymopathies Hb - haemoglobinopathies
172
Examples of inherited RBC membranopathies
RBC can't maintain biconcave shape ``` Hereditary spherocytosis (HS) Hereditary elliptocytosis (HE) Hereditary stomatocytosis ```
173
Consequences of RBC membranopathies
RBC more easily damaged | Macrophage removal - shortened RBC life
174
Inheritance pattern of inherited RBC membranopathies
Usually autosomal dominant (occasionally recessive or sporadic)
175
What may inherited RBC membranopathies cause in neonates
Prolonged neonatal jaundice and mild anaemia presenting at any age
176
Are RBC membranopathies jaundice fluctuant
Yes - worse in infections
177
What may aplastic crises be precipitated by
Parvo virus (B19)
178
Lab findings for inherited RBC membranopathies
``` Anemia - usually mild Reticulocytosis Raised bilirubin Raised LDH Blood film shows abnormally shaped RBC** Direct antibody test -ve (not autoimmune) ```
179
Ic for inherited RBC membranopathies
Fhx Blood film Haemolysis screen Special tests
180
Mx for inherited RBC membranopathies
Folic acid supplementation | Splenectomy (HS)
181
Most common RBC enzymopathy
Deficiency in G6PD - susceptible to oxidative stress
182
Inheritance pattern of G6PD deficiency
X linked recessive | M > F
183
Where is inherited G6PD deficiency most common
Africa and Mediterranean
184
What can oxidant stress cause in a pt w/ G6PD deficiency
A/c episodes of haemolysis | Oxidants may be drugs, infections, moth balls, fava beans
185
Hb production
Alpha globin chain made from foetus onwards (4 genes, 2 each chromosome) pair w/ beta-like globin chains (2 genes, 1 each chromosome) Adult ratio alpha: beta ~ 1:1 (2:2 of each chain)
186
Thalassemia
Reduced alpha/ beta globin chain synthesis
187
Where is thalassaemia most common WW
Asia Africa South Mediterranean
188
Consequences of thalassaemia
Chain imbalance Excess alphas or beta chains ppt Precipitated chains damage RBC membrane Damaged cells destroy prematurely by macrophages
189
Thalassaemia classification
``` Alpha thalassaemia Beta thalassaemia Thalassaemia major Thalassaemia trait Thalassaemia intermediate ```
190
Chains in alpha thalassaemia
Too few alpha chains
191
Chains in beta thalassaemia
Too few beta chains
192
Number of chains in thalassaemia major
No alpha/ beta chains
193
Chains in thalassaemia trait
Reduced alpha/ beta chains so no transfusions required
194
Thalassaemia intermediate
Mixed clinical picture | Not as affected
195
Clinical features of beta thalassaemia major
Severe anaemia from 3/12 to 6/12 - beta gene mutations as opposed to deletions Enlargement of liver and spleen Expansion of bone marrow
196
How is beta thalassaemia detected
New-form screening - treat w/ transfusions
197
Clinical features of alpha thalassaemia
Usually caused by alpha deletions, not mutations Fatal in utero (hydrops fetalis) People born w/ 1/4 alpha genes have HBH disease
198
HBH disease
Tetramer of 4 beta chains | Variable phenotype - intermediate
199
Clinical features of thalassaemia trait
Mild microcytic anaemia Asymptomatic 'Carrier' - can pass gene onto child B thalassaemia trait (1 of 2 genes affected) Alphas thalassaemia trait (1-2 pf the 4 genes affected)
200
Alpha thalassaemia - genetic counselling
Important to know whether 2 genes deleted from same chromosome Antenatal screening to identify the type of alpha thalassaemia
201
Alpha-0 vs alpha-plus thalassaemia
Alpha-0 is when 2 genes are deleted from same chromosome | Alpha-plus is when 2 genes are deleted from different chromosomes
202
Thalassaemia dx
Hypochromic microcytic anamia (excl Fe deficiency) Hb electrophoresis or HPLC Genetic analysis
203
Hb electrophoresis in thalassaemia
Beta thalassaemia trait - increased HbA2 Beta thalassameia major - absence HbA Cannot pick up alpha trait
204
Thalassaemia major mx
Lifelong transfusions every 3/52 - 4/52 to keep Hb > 100g/L Splenectomy - reduce blood requirements Allogeneic bone marrow transplantation
205
Success rate of allogeneic bone marrow transplantation in thalassaemia major
>80% - curative
206
Allogeneic transplantation vs autologous
Allogeneic stem cels come from a donor | Autologous stem cell come from pt
207
Mx of thalassaemia trait
Avoid Fe unless Fe deficient | Genetic counselling
208
SCD
Sickle cell disease
209
Genetics in SCD
Point mutation leads to single AA substitution valine ---> glutamate at position 6 beta chain - forms HbS Homozygous HbS = disease but heterozygous = trait
210
What does HbS form
Crystals when exposed to low oxygen levels - causes 'sickling' of RBC
211
Sickle cell trait
Benign condn - no/mild anaemia, normal appearance of RBC
212
What % of total Hb is HbS in sickle cell trait
25-45%
213
When should sickle cell trait patients take care
During anaesthesia (and high altitude)
214
Is genetic counselling required for sickle cell trait
Yes
215
Clinical features for sickle cell disease
C/c haemolytic anaemia from 3/12 - 6/12 old (when HbF ---> HbA)
216
When is the rate of haemolysis in SCD increased
During crisis
217
Usual Hb amount in SCD
60-90g/ L | Symptoms of anaemia often mild - HbS oxygen dissociation curve shifted to R
218
Sickle cell complications
Occlude vessel | Damage to skin on legs may cause c/c ulceration and sickly in lungs may ppt chest pain
219
Vessel occlusion in SCD
Can cause symptoms e.g. Pain (esp bones) Organ damage Splenic infarction from age 2 - auto splenectomy Organ engorgement with blood can occur (sequestration - spleen, liver)
220
Blood film in SCD
Sickle cells Target cells Nucleated red cells Howell-Jolly bodies (splenic atrophy)
221
SCD lab findings
Spp cells on blood film Sickle solubility screen +ve - HbS less soluble when reduced O2 Hb electrophoresis/ HPLC shows HbS, no HbA, variable amounts HbF
222
What does mx of SCD focus on
Preventing crises and infections associated w/ hyposplenism | May requires stem cell transplantation
223
Prophylactic mx of SCD
Avoid opting factors Folic acid supplementation Pneumococcal vaccine; regular oral penicillin Hydroxycarbamide
224
Hydroxycarbamide for SCD
For recurrent crises | Increases amount of HbF, reducing sickling
225
Mx for SCD crises
Analgesia (opiates), rest, rehydration, oxygen +/- abx | Blood transfusion/ exchange transfusion - if severe
226
Can SCD and beta thalassaemia co-exist
Yes
227
Abnormalities outside the cell (extrinsic) that can cause haemolysis
Antibody attack Mechanical trauma Infection Chemical and physical agents
228
Antibody attack causing haemolysis
Antibodies primed to only attack foreign cells Occasional antibodies attack own cells = autoimmune Autoimmune atacking RBC = AIHA
229
AIHA
Autoimmune haemolytic anaemia
230
How can AIHA be detected
Using Direct Antiglobulin Test (Coombs) Warm: antibody reacts w/ RBC at 37 degrees (IgG) Cold: antibody reacts w/ RBC below 37 degrees (IgM)
231
AIHA causes - warm IgG
Idiopathic | Secondary - autoimmune condn, disordered immune system, drugs
232
Disordered immune system causing AIHA (warm IgG)
CLL | Low grade lymphoma
233
Drugs causing AIHA (warm - IgG coated)
Drug: RBC membrane complex - penicillin | Ig against RBC membrane - methyldopa
234
AIHA causes - cold (IgM - coated)
Idiopathic | Secondary - lymphoma , infections, paroxysmal cold haemoglobinuria - RARE - syphilia
235
Infections causing AIHA - cold IgM
Mycoplasma pneumonia | EBV
236
AIHA lab findings
Haemolysis ``` Anaemia Reticulocytosis Raised LDH Raised unconjugated bilirubin +ve DAT (Coombs) Blood film - spherocyte IgG; agglutination IgM ```
237
AIHA mx
``` Remove or treat underlying cause e.g. drugs/lymphoma Keep pt warm if IgM (cold-reacting) Folic acid supplementation Transfusion Immune suppression Splenectomy ```
238
Immune suppression as mx of AIHA
Corticosteroids (warm) | Rituximab (cold and relapsed warm)
239
When will a splenectomy be performed for AIHA
Resistant cases - less helpful if IgM
240
Mechanical trauma as an extrinsic cause of haemolysis
Microangiopathic haemolytic anaemia Faulty mechanical heart valve March haemoglobinuria
241
Microangiopathic haemolytic anaemia
TTP DIC HUS
242
TTP
Thrombotic thrombocytopenic purpura
243
HUS
Haemolytic uraemic syndrome
244
March haemoglobinuria
Repeat capillary faults in the feet
245
DAT (Coombs) when mechanical trauma is causing haemolysis
-ve (not immune)
246
Why would urine be +ve for Hb when mechanical trauma is causing hameolysis
Hameolysis is hapenning in blood vessels not spleen/ liver
247
Infections causing haemolysis
Malaria
248
Chemicals and physical agents causing haemolysis
Drugs - dapsone (oxidative haemolysis) Copper - Wilsons disease Lead burns Snake and spider bites
249
PNH
Paroxysmal nocturnal haemoglobinuria | Small print cause of intravascular haemolysis
250
Key blood tests before a blood transfusion
``` FBC U&Es LFTs Coag screen Group and antibody screen - identifies blood group ```
251
How long is a serum sample saved for in case of transfusion
7/7 to be used for cross-matching
252
How does antigen and antibody expression on RBCs vary with age
Foetus and newborns have relatively low levels of Ag on surface which protects them from incompatibility with mother's blood group
253
Antigens and antibodies in blood group A
"A' antigen of red cell surface | Anti-B antibodies in plasma
254
Antigens and antibodies in blood group B
"B' antigens on red cell surface | Anti-A antibodies in plasma
255
Antigens and antibodies in blood group AB
"A" + "B' antigens on red dell surface | No antibodies in plasma
256
Antigens and antibodies in blood group O
Small 'H' antigens on red cell surface | Anti-A and Anti-B antibodies in plasma
257
Determining the pts ABO and Rh D status
Use the pt's red cells and monoclonal IgM anti-A, anti-B, anti-D - and once agglutinated cannot fall into gel Use pt's serum and donor A and B to ensure correct antibodies are present
258
Improving transfusion safety
Second sample required if no previous blood group Compare results w/ previous blood bank results Only accepts correctly labelled samples Use barcodes - a 'closed system' in lab Use electronic pt identification
259
For avg wt pts, how much will 1 unit RBC rise Hb
10g/L
260
How should red cell support be given if bleeding rapidly
20 - 30 minutes
261
How should red cell support be given if stable
Given over 2-4hrs
262
Does ABO and RhD need to be identical for platelet transfusion
No just compatible
263
How long should platelet support be given over
20 mins
264
Which pts might need platelets
Thrombocytopneia due to failure of marrow production e.g. after chemo Functional platelet disorder w/ bleeding e..g inherited platt disorder 'Dilutional' thrombocytopenia e.g massive bleeding Thrombocytopenia which is multifactorial and associated w/ bleeding e.g. liver
265
Which clotting factors does FFP contain
All of them
266
What can FFP be refined to
Cryroprecipitate - high in factor VIII and fibrinogen
267
When is FFP used
``` DIC w/ bleeding Massive transfusion (check clotting) Plasma exchange in TTP Liver disease w/ abnormal clotting Some factor deficiencies where factor concentrate bis not available ```
268
Problems w/ future transfusions
Possible antibody formation to other red cell antigens Pt can no longer be blood donor Increased risk of transfusion reactions
269
How can antibodies other than anti-A or anti-B be acquired
During pregnancy or transfusion
270
When is an alloantibody likely to be formed to a red cell antigen
The more blood a pt receives
271
What is the timing of G&S sample the basis of
the 72-hr rule - a new antibody may be forming
272
What are pts w/ red cell antigen allaoantibodies at risk of
Delayed haemolytic transfusion reactions - need blood cross-matched to ensure compatibility May form other antibodies
273
What grade are most transfusion reaction
Mild
274
Examples of severe transfusion reactions
Anaphylaxis Bacterial contamination A/c and delayed haemolysis
275
Greatest risk to pts getting a blood transfusion
Getting the incorrect blood component as ABO incompatibility can be rapidly fatal
276
Alternatives to blood products when treating anaemia
Treatment of underlying cause | Iron tablets, IV iron, Vit B12 and folic acid, erythropoietin
277
Alternatives to blood products to treat thrombocytopenia
Platelets only if unavoidable, corticosteroids, TXA, maximise clotting - avoid aspirin, NSAIDs
278
Porphyria
Group of disorders caused by build up of natural chemical that produce porphyrins Porphyrins are essential for Hb function
279
Symptoms in a/c attacks of porphyria
``` Unexplained abdominal pain Nausea and vomiting Constipation Neuropsychiatric symptoms +/- hyponatraemia ```
280
Haematinic
Nutrient needed for formation of blood cells
281
Unconjugated vs conjugated bilirubin
Unconjugated bilirubin is fat soluble | Conjugated bilirubin is water soluble
282
Where does conjugated bilirubin appear
Urine | Faeces
283
Bilirubin metabolism
Unconjugated bilirubin is found in blood stream | Taken into canaliculus and conjugated
284
How does haemolytic jaundice affect the production of bilirubin
Increases it More bilirubin is conjugated and excreted than normal, but the conjugation mechanism is overwhelmed --> large amount of unconjugated bilirubin in blood
285
What might cause decreased bilirubin uptake by liver cells
Inability of the hepatocytes to take up bilirubin from blood ---> unconjugated bilirubin accumulates
286
How does impaired bilirubin conjugation affect unconjugated bilirubin
Causes it to be retained by the body
287
What is defective secretion of conjugated bilirubin from liver cells associated w/
The inability of the hepatocytes to secrete conjugated bilirubin after it has been formed Conjugated bilirubin returns to the blood
288
How do the blood levels of conjugated bilirubin change in an obstruction of biliary network (intrahepatic or extrahepatic)
Increase | Biliary calculi causes backup and reabsorption of conjugated bilirubin
289
Beware painless jaundice
Slowly evolving Continuous increase in bilirubin No colic type systems Pancreatic cancer
290
Urine colour in obstructive liver disease
Dark
291
Faeces colour in obstructive liver disease
Pale
292
Bilirubin levels in obstructive liver disease
Elevated (conjugated)
293
Bilirubin levels in haemolytic liver disease
Elevated (unconjugated)
294
Urobilinogen in obstructive liver disease
-ve
295
Urobilinogen in haemolytic liver disease
Elevated
296
Causes of neutropenia
``` Congenital (Fanconi's anaemia) Immune mediated (SLE, Feltys) Infection (sepsis, HIV, influenza) Bone marrow failure Chemo, drugs Radiation ```
297
Bacterial causes of neutropenic sepsis
``` Staph A Coagulase -ve staph Viridian strep Enterococcus E. coli, enterobacter Psedomonas Klebsiella Listeria ```
298
Fungal causes of neutropenic fever
``` Aspergillus Pneumocystitis jiroveci (PCP) Fusraium Zygomycosis Candidasis ```
299
Viral causes of neutropenic fever
``` Herpes simples CMV VZV RSV Parainfluenza viruses 1-4 Influenza viruses A & B Adenoviruses ```
300
Primary prevention of infection
Prevent or reduce exposure | Immunisation
301
Secondary prevention of infection
Chemoprophylaxis (abx, antivirals)
302
Tertiary prevention of infection
Effective treatment | Phsyio
303
Possible causes of splenectomy
Surgery (trauma, RTA) Immunologic - ITP Hypersplenism (function asplenia) - thalassaemia, portal HTN Malignancy - Hodgkin lymphoma, ovarian cancer
304
Functional asplenia
Splenic tissue is present but does not function well vs anatomical asplenia, where the spleen is not present
305
Causes of functional hyposplenism
``` Autoimmune disorders - SLE Haematological diseases - SCD, haemophilia Lymphoproliferative disease (NHL, CLL) Infiltrative disease Intestinal disorders ```
306
Functional hyposplenism
Splenic activity is diminished or absent in an anatomically present spleen
307
Infiltrative diseases causing functional hyposplenism
Sarcoidosis | Amyloidosis
308
Intestinal disorders causing functional hyposplenism
Crohns and Whipple's disease
309
Most common pathogen causing post-splenectomy sepsis
Strep. pneumonia followed by H. influenza
310
Preventing infections in absent/ dysfunctional spleen
``` Pneumococcal vaccine H. influenza vaccine Meningoccoal vaccine (B,. C, ACWY) Infelunze vaccine Pt education, info and documentation Abx prophylaxis ```
311
When should the pneumococcal vaccine be administered to prevent infections in absent spleen
2/52 prior to splenectomy | Re-immunisation necessary
312
Abx prophylaxis to prevent infections in absnet/ dysfunctional spleen
Penicillin V/ amoxicillin (first 2 years)
313
What does the monospot test look for
EBV virus
314
Crossmatching blood
Test donor blood against pt for transfusion
315
Standard admin time for red cell transfusion
2-3 hrs
316
Standard admin time for platelet transfusion
30 mins
317
Standard admin time for FFP transfusion
30 mins
318
Standard admin time for cryoprecipitate transfusion
20 mins
319
Key things before transfusion of blood components
Check - you have right pt Check - you have right blood component Monitor - the pt before, during and after for adverse events incl reactions Seek - clinical or transfusion lab advice if concerned/ in doubt
320
Complications w/ haematinic replacement
Transfusion: allergic reactions, fever, a/c immune haemolytic anaemia Fe replacement: headaches, vomiting
321
When do we see anisocytosis on a blood film
Myelodysplasia
322
When do we see target cells on a blood film
IDA | Post splenectomy
323
When do we see Howell-Jolly bodies on a blood film
Severe anaemia | Post splenectomy
324
When do we see Heinz bodies on a blood film
G6PD deficiencies | Alpha Thalassaemia
325
When do we see reticulocytes (if raised) on a blood film
Haemolytic anaemia
326
When do we see spherocytes on a blood film
HS | AIHA
327
When do we see schistiocytes on a blood film
Haemolytic anaemia
328
When do we see smudge cells on a blood film
CLL
329
When do we see sideroblasts on a blood film
Myelodysplastic syndrome
330
Reticulocytes vs RBC
Reticulocytes are immature so still have RNA and are larger than RBCs
331
What does it mean if reticulocytes are raised by pt is NOT anaemic
Impaired bone marrow function | Lack of epo stimulus
332
MAHA
Micronagiopathic Haemolytic Anaemia
333
What is Micronagiopathic Haemolytic Anaemia
Intravascular destruction of red cells in presence of abnormal microcirculation/ structural abnormalities in small blood vessels
334
What is haemolytic uraemic syndrome
Condn characterised by triad of MAHA, AKI and thrombocytopenia Most cases occur in children and are diarrhoea related (E. coli)
335
What is disseminated intravasc coagulation
Acquired syndrome characterised by activation of coagulation pathways --> intravasc thrombi and depletion of platelets and clotting factors
336
What is paroxysmal nocturnal haemoglobinuria
Acquired disorder characterised by intravasc haemolysis and thrombophilia Small print cause of MAHA
337
What type of bilirubin is found in blood in a jaundiced pt
Uncojugated
338
Why is there dark urine in jaundiced pts
Urobiliogen - haemoglobinuria
339
What should LNs be assessed for
``` Size Position Shape Consistency Mobility Tenderness Isolated LN or several coalesce? ```
340
Glossitis
Enlarged tongue due to infl | Seen in IDA
341
Examination findings of splenomegaly
Spleen palpated >2cm below costal margin
342
Ferritin in ACD
Normal or raised
343
LDH in CLL
Raised
344
When would you see pencil cells on a blood film
IDA
345
How might platelets change in IDA
Can increase
346
Polychromosia
Stained reticulocytes - RNA is bluish
347
What is every blood donation tested for
``` ABO Rh Hep B, C, E Syphilis HTLA ```
348
Risk of anaphylaxis w/ blood transfusions
Low in general but generally high risk in plasma based components
349
Can granulocytes be given as a transfusion
Yes but is very rare - must be discussed w/ haem consultant | Indications incl sepsis w/ reversible BM failure
350
What extra blood producst can be transfused
PCC Anti D - prevents haemolytic disease of newborn, given to any pregnant women in hosp (sensitising event) Fibrinogen concentrate
351
Transfusion in Rhesus D pts
D -ve can receive +ve blood, but may develop anti-D antibodies D-ve pts of child-bearing age should never receive +ve blood - risk of haemolytic disease of newborn
352
Alloantibodies
Antibody produced in pregnancy, transfusion or transplantation against an antigen not presents on person's RBC
353
What are blood group O universal donors for
RBC only | Never FFP
354
Why is iron given through IV infusion in an active infection
Oral iron is contraindicated | Part of immune response
355
GVHD
Graft vs host disease | Graft cells recognises recipients cells as foreign and attacks them
356
What type of blood component must HL pts receive
Irradiated | Pts are given a card to show hospitals
357
Possible reactions to transfusions
``` Febrile A/c haemolytic reaction Anaphylaxis TACO TRALI Delayed haemolytic reaction ```
358
How do you respond to a febrile reaction during a blood transfusion
Discontinue transfusion or continue at a reduced rate
359
What would cause an a/c haemolytic reaction after a transfusion
Incompatible blood reaction
360
What is seen in an a/c haemolytic reaction to transfusion
Pt goes into shock, a/c renal failure or DIC
361
Symptoms of an a/c haemolytic reaction to a transfusion
``` Pyrexia Chills Rigours Hyper/ hypotension Flushing Rashes Pain SOB Generally feeling unwell Reduced urine output (late sign) ```
362
TACO
Transfusion Associated Circulatory Overload
363
What is seen in a TACO
A/c or worsening pulmonary oedema within 6 hrs of a blood transfusion
364
Symptoms of a TACO
A/c resp distress Tachycardia HTN +ve fluid balance
365
How is a TACO treated
Stopping transfusion | Giving diuretics
366
TRALI
Transfusion-related a/c lung injury
367
What is a TRALI
An infl reaction caused by antibodies of donor cells in blood transfusion Infl cells cause leakage in lungs Occurs within 2-6 hrs
368
Symptoms seen in TRALI
``` Pink stained, frothy sputum Bilateral pulmonary oedema - CXR Hypotension Fever Rigors ```
369
Treatment of a TRALI
Oxygen and ventilation | Recovery in 1-3 days
370
Delayed haemolytic reactions to blood transfusions
Secondary immune response (24hrs to 14 days) | Pt is already alloimmunised to red cell antigens
371
Whats sites should be avoided for venepuncture
``` Infection/ infl Brusing AV fistula Side of mastectomy/ node dissection Side of hemiparesis - stroke ```
372
Order of draw of blood bottles
``` Blue (Red) Yellow Green Lavender Pink Grey ```
373
What is sampled for in blue blood bottles
Coagulation studies
374
What is sampled for in yellow blood bottles
Biochem
375
What is sampled for in green blood bottles
Cardiac enzymes
376
What is sampled for in lavender blood bottles
FBC
377
What is sampled for in pink blood bottles
G&S | Crossmatch
378
What is sampled for in grey blood bottles
Glucose Lactate Ethanol
379
Indications for blood cultures
``` Pyrexia Focal signs of infection Low BP Raised RR Abnormal WCC New or worsening confusional state - sepsis ```
380
What are taken first, blood culture samples or other bloods
Blood culture samples
381
Order of draw for blood culture samples
Blue bottle for aerobic organisms | Red for anaerobic
382
At which platelet count is it safe to anticoagulate
50
383
Types of bleeding in low platelets vs low clotting factors
Low platelet is mucosal bleeds | Clotting factors is bleeding into joints
384
Post-transplant lymphoproliferative disorder
Occurs of solid organ transplants | Immune suppression can cause lymphocytosis (may be 2' to EBV) --> lymphoma
385
Features of neutropenic sepsis
Can be seen in a/c leukaemia - after treatment w/ chemo | Fever >37.5 and neutropenia <1
386
Treatment of neutropenic sepsis
Tazobactam (tazocin) and gentamicin | May give G-CSF
387
Why might haemolysis cause MCV to increase
Presence of reticulocytosis
388
Blood film for B12/ folate deficicny
Hypersegmented neutrophils | Poikilocytes
389
Blood film for alcoholic liver disease
Target cells | Acanthocytes
390
Why might platelets decrease in alcoholic liver disease
Liver produces tpo | Alcohol is toxic to BM
391
Why is LDH raised in haemolysis
Due to increased cell turnover
392
Lab features of DIC
Low platelets Prolonged clotting time Low fibrinogen
393
Causes of AKI
Hypoperfusion Sepsis Dehydration Medication
394
What does it mean if blood culture results show a growth from Hickman line but not peripheral blood
Bacteria introduced into lumen of line, not widespread
395
Drugs causing secondary erythrocytosis
Anabolic steroids | epo
396
What kind of tumours can cause 2' erythrocytosis
Tumours secreting epo (liver, kidney, thyroid, fibroid)
397
What does a pt ned to know before giving consent for a transfusion
``` Indication Risks vs benefits What the process entails Any spp needs for the pts Any alternatives They can no longer be blood donors ```
398
Risk factors in TACO
``` Age > 70 Cardiac failure Renal failure Low albumin Existing fluid overload ```
399
Post transfusion care
Check Hb to make sure it was successful | If discharged, make sure pt is aware of who to contact if any issues arise
400
What needs to be included in a discharge summary post transfusion
Indication fro transfusion Any adverse events Pt no longer eligible to be blood donor

MBBS - Year 2 (20 decks)

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