Haematology Flashcards
1
Q
Why might pregnant women get anaemia?
A
Raised plasma volume
2
Q
What does MCV stand for?
A
Mean cell volume
3
Q
Why might someone with anaemia be asymptomatic?
A
Due to a rise in BPG causing the oxygen dissociation curve to shift to the R
4
Q
What are some symptoms of anaemia?
A
‘Tired all the time’ (fatigue + lethargy/malaise), headaches, faintness, SOB, Angina
5
Q
What are some signs of anaemia>
A
Pallor (+ conjunctival pallor), tachycardia, compensatory heart failure
6
Q
What does MCH stand for? What is it an indication of?
A
Mean corpuscular haemoglobin - amount of Hb per RBC
7
Q
What is MCHC?
A
Mean cell Hb concentration - amount of Hb relative to the size of the cell
8
Q
How do you look at RBCs and determine their MCV, MCH, MCHC?
A
Blood film
9
Q
Give an example of a disease where the cell types/sizes on a blood film are dimorphic
A
Coeliac disease
10
Q
What cell size will you see in coeliac disease?
A
2 cell types/sizes: macrocytic (due to B12/folate malabsorption) and microcytic (iron malabsorption)
11
Q
How do you evaluate bone marrow?
A
Aspirate from the iliac crest OR use trephine
12
Q
Where is iron stored?
A
Bone marrow
13
Q
Give 3 causes of microcytic anaemia
A
Fe deficiency, chronic disease and thalassaemia
14
Q
Give 3 causes of normocytic anaemia
A
Acute blood loss, anaemia of chronic disease, combined haematinic deficiency
15
Q
Give 4 causes of macrocytic anaemia
A
Acute blood loss, liver failure + alcohol excess, hypothyroidism
16
Q
What type of anaemia (MCV) does haematological causes (BM failure, BM infiltration, haemolytic anaemia, anti-metabolite therapy) causes?
A
Macrocytic anaemia
17
Q
What haemolytic anaemia doesn’t cause macrocytic anaemia? What type of anaemia is it?
A
Thalassaemia - microcytic anaemia
18
Q
What type anaemia is haemolytic anaemia?
A
Macrocytic (Except thalassaemia)
19
Q
What plasma protein transports iron in the blood? Where does it transport iron to?
A
Plasma transferrin - to the bone marrow for storage
20
Q
What is the most common cause of anaemia world-wide?
A
Iron deficiency
21
Q
What proportion of menstruating women have iron deficiency anaemia?
A
14%
22
Q
What are the causes of iron deficiency anaemia?
A
Blood loss (Chronic), menstruation, Hook worm (blood loss), malabsorption, poor dietary intake
23
Q
What disease might cause malabsorption of iron?
A
Coeliac disease
24
Q
What iatrogenic cause may cause malabsorption of iron?
A
Gastrectomy
25
What symptoms might you get with iron deficiency anaemia?
Fatigue, headaches, faint, SOB, palpitations, dyspnoea (Severe SOB)
26
Why might someone get angina as a symptom of anaemia?
Because they have pre-existing coronary artery disease (IHD) which has gone unnoticed until now as there is supply demand mismatch (less O2 carrying capacity) to meet the demands of the heart muscle
27
What are some signs of iron deficiency anaemia?
Koilonycia (spoon shaped nails), brittle hair + nails, smooth tongue (atrophy of tongue papillae), angular somatitis, glositis (red tongue)
28
What should you ask in a Hx of anaemia to determine the cause?
Dietary intake, self medication (GI bleeding), blood in faeces, woman (duration + heaviness of periods), other diseases/symptoms (E.g. coeliac symptoms)?
29
What 4 tests might you do to determine whether the person has iron deficiency anaemia?
Blood count + blood film, serum iron, serum ferritin, total iron binding capacity
30
What would you see on a blood film of iron deficiency anaemia?
MCV low (microcytic), MCH low (hypochromic)
31
What results would you get for serum iron and serum ferritin in iron deficiency anaemia?
Both will be low (ferritin may be high)
32
Why is serum ferritin not a reliable diagnostic tool for iron deficiency anaemia (why do you need to do serum iron + TIBC)?
because it is an acute phase protein and therefore rises in inflammation, infection...etc
33
What does serum ferritin reflect?
Iron stores
34
What tests might you do to determine the cause of the iron deficiency?
Pt Hx, serology (for coeliac), GI tract bleeding exam??
35
What treatments should you give a patient with iron deficiency anaemia?
Oral iron (ferrous sulfate) and treat the cause
36
What are the side effects of oral iron tablets?
GI upset (nausea, constipation, abdo pain...etc)
37
What compound is used in oral iron?
Ferrous sulfate
38
What result would total iron binding capacity give for iron deficiency anaemia?
High (don't get confused)
39
If someone is in renal failure, what causes their anaemia? What treatment should they be given?
Reduced production of EPO - give recombinant EPO therapy
40
What MCV is seen in normocytic anaemia?
Normal (but low Hb conc.)
41
What is needed for vitamin B12 absorption? What produces it?
Intrinsic factor from parietal cells
42
What is the role of vitamin B12?
Normal NS functioning + formation of RBCs
43
What are the 2 main causes of vitamin B12 malabsorption?
Pernicious anaemia and malabsorption
44
What causes malabsorption of vitamin B12?
(Pernicious anaemia), diet deficiency, gastrectomy, iliectomy, coeliac, metformin
45
What groups of people are at risk of vitamin B12 diet deficiency?
Vegans
46
What is pernicious aneamia?
An autoimmune disease that causes vitamin B12 deficiency
47
What auto-antibodies are found in pernicious anaemia? Which is more common?
Antibodies against parietal cells (90%) and intrinsic factor antibodies (50%)
48
What other autoimmune diseases are associated with pernicious anaemia?
Addison's disease, thyroid disease (Hashimoto's), ...
49
What is the main cause of vitamin B12 deficiency?
Pernicious anaemia
50
What is the pathology of pernicious anaemia?
Auto-antibodies --> atrophic gatritis w/ loss of parietal cells in gastric mucosa --> Intrinsic factor not produced --> vitamin B12 malabsorption
51
What is the classic symptom of pernicious anaemia? (EXAM)
Progressively increasing anaemia symptoms
52
What are the signs of pernicious anaemia and vitamin B12 deficiency?
Glositis, angular stomatitis, neurological features (polyneuropathy [periphera neuropathy], prgressive weakness, ataxia, paraplegia if untreated, dementia)
53
What cancer risk are those with pernicious anaemia at increased risk of getting
Gastric carcinoma
54
Why might a person have mild jaundice in pernicious anaemia?
It is a cause of megaloblastic anaemia (large cells) --> ^ Hb breakdown into bilirubin
55
What tests might you do if you suspect pernicious anaemia (or vitamin B12 def. anaemia)?
Blood film, blood count, serum vitamin B12, LDH, serum bilirubin, serology
56
What would you see on serology for non-autoimmune causes of anaemia?
Normal
57
Why do you carry out a serum bilirubin in vitamin B12 def. anaemia?
Because the patient may present with jaundice
58
Why might serum bilirubin be raised in vitamin B12 deficiency anaemia?
Megaloblastic anaemia (large cells) --> ^ Hb breakdown into bilirubin
59
What does a blood film show in pernicious + vit. B12 deficiency anaemia?
Megaloblastic anaemia
60
What is test shows that the person is vit B12 deficient?
Serum vitamin B12
61
What does LDH stand for? What value does in have in pernicious anaemia?
Lactic dehydrogenase + raised
62
When would you carry out a BM examination if someone has anaemia?
When the cause isn't straightforward
63
What would you see on serology for pernicious anaemia?
Auto-antibodies to parietal cells and intrinsic factor
64
What test might you do to distinguish between pernicious anaemia and other causes of vitamin B12 deficiency?
Duodenal biopsy for coeliac
65
What treatment should you give someone if the cuase of their anaemia is untreatable malabsorption (such as pernicious anaemia)?
IM hydroxocobalamin
66
What treatment should you give to treat dietary vitamin B12 insufficiency?
Oral vitamin B12
67
What foods is folate found?
Green vegetables, liver, kidney
68
What might occur if a pregnant woman is folate deficient?
Spina bifida
69
Where is folate absorbed?
duodenum and jejunum
70
What is folate used for?
DNA synthesis (RBC development)
71
What is the main cause of folate deficiency?
Poor dietary intake
72
What are some causes of folate deficiency?
Poor dietary intake, alcohol, drugs, excessive utilisation (to make more RBC) e.g. pregnancy or chronic haemolytic anaemia
73
Give an example of a drug that causes folate deficiency?
Methotrexate
74
What is the differences in presentation between vitamin B12 def. anaemia and folate def. anaemia?
In folate def. anaemia there isn't neuropathy
75
What two investigations can you do to measure the pt's folate levels?
Serum folate and red cell folate
76
Which Ix gives a better indication of tissue folate levels: serum or red cell folate?
Red cell folate
77
What does BM analysis show in B12 and folate def. anaemia?
Megaloblastic haematopoiesis (activity)
78
What is the treatment for folate deficiency?
Treat the cause + oral folic acid
79
What must you give pregnant women during their pregnancy?
Prophylactic folic acid to ensure neural tube closure
80
What is a cause of macrocytic normochromic anaemia?
Alcohol excess (biggest cause), liver disease, pregnancy..
81
What type of anaemia does BM failure show?
Macrocytic anaemia
82
What are the two primary causes of anaemia due to BM failure?
Idiopathic (most common) and inherited (Fanconi's anaemia)
83
What drugs can cause BM failure?
Cytotoxic drugs
84
What infections can cause BM failure?
Hepatitis, TB, HIV
85
What is pancytopaenia
Reduction in all cell lines: RBCs, WBCs and platelets)
86
What causes pancytopaenia?
BM failure (leukaemia, primary: aplastic anaemia), hypersplenism (^ peripheral destruction)
87
What occurs in BM failure?
Reduction in pluripotent stem cells (can be only one cell line)
88
What are the clinical features of BM failure?
^ Infections (reduced WBCs), anaemia (reduction in RBCs), bleeding + brusing (platelet reduction)
89
What signs might occur in BM failure?
Hepatosplenomegaly + lymphadenopathy
90
What will you see in a blood count of someone with BM failure?
Pancytopaenia (Reduction in all cell lines)
91
What is needed for diagnosis of BM failure?
BM examination/biopsy (aspirate from iliac crest)
92
What must your Ix's also do to determine whether the cause of pancytopaenia is BM failure? How will you
Distinguish from other causes of pancytopaenia. Do a BM examination
93
What does BM examination show for someone with BM failure?
hypocellular marrow w/ ^ fat spaces
94
What is the treatment for BM failure?
Remove the causative agent (E.g. drugs, radiation...)
95
How do you treat the anaemia and bleeding of BM failure?
Red cell transfusion therapy + platelet transfusion
96
How do you treat the neutropaenia in BM failure?
Naeutropenic regimen (Abx?)
97
How do you treat BM failure if Red cell + platelet transfusion doesn't work?
Bone marrow Tx w/ immunosuppression (ciclosporin)
98
What Haemolytic anaemia is not macrocytic?
Thalassaemia
99
What are the two broad causes of Haemolytic anaemia?
Acquired and hereditary (genetic)
100
What are the 3 types of hereditary causes of haemolytic anaemia?
RBC membrane defects, Haemoglobin abnormalities, Metabolic (enzyme) defects
101
Give an example of a RBC membrane defect that cause haemolytic anaemia
Hereditary spherocytosis
102
Give 2 examples of Hb abnormalities that cause haemolytic anaemia
Sickle cell disease and Thalassaemia
103
Give two examples of metabolic (Enzyme) defects that cause Haemolytic anaemia
GP6D deficiency and pyruvate kinase deficiency
104
What are the two acquired causes of haemolytic anaemia
Immune and non-immune
105
Give 3 examples of non-immune acquired causes of haemolytic anaemia
Paroxysmal nocturnal haemoglobulinuria, infections (malaria), hypersplenism
106
In paroxysmal nocturnal haemoglobulinuria, what happens to RBCs and why?
Lysed by activating complement (CDC) due to abnormal RBC surface markers
107
What do you treat paroxysmal nocturnal haemoglobulinuria with?
Anti-coagulation + eculizumab
108
Why do you treat paroxysmal nocturnal haemoglobulinuria with anti-coagulation?
Predisposition to clotting
109
Why is malaria sometimes called black water fever?
Causes haemoglobulinuria (looks black)
110
How does the bone marrow compensate for haemolytic anaemia (increased destruction of RBCs)? So what would you see on a blood count?
Increased reticulocytes
111
What molecule might you see an increase of in haemolytic anaemia?
Bilirubin
112
What molecule might you see an increase of in haemolytic anaemia in the urine?
Urobilinogen
113
What genetic pattern does hereditary spherocytosis show?
Autosomal dominant
114
What is the pathophysiology in hereditary spherocytosis?
deficiency of RBC membrane proteins --> ^ Na+ permeability --> rigid + large --> gets trapped in capillaries of spleen --> broken down by spleen (reticuloendothelial system)
115
What is the most common membranopathy?
hereditary spherocytosis
116
What group of people does hereditary spherocytosis occur in?
N. Europeans
117
What is the commonest membrane protein that is deficient in hereditary spherocytosis?
Spectrin
118
What does parvovirus cause in children? How does it affect hereditary spherocytosis?
slapped cheek syndrome. In hereditary spherocytosis it causes BM failure
119
in general what is needed in BM failure?
Blood transfusion (RBCs, platelets...)
120
What is seen on a blood film of a patient with hereditary spherocytosis?
^ reticulocytes + ^ spherocytes
121
What is the management for hereditary spherocytosis?
Splenectomy
122
What are the two conditions characterised Hb abnormality and haemolytic anaemia?
Thalassaemia and sickle cell disease
123
What chains are seen in Foetal Hb?
2alpha and 2gamma globin chains
124
What is the group of people affected by thalassaemia?
Spanish (irish)
125
What is the pathophysiology behind thalassaemia
Reduced production of either alpha or beta globin chains
126
What are the two types of thalassaemia?
Alpha thalassaemia and beta thalassaemia
127
What type of anaemia is seen in thalassaemia?
Microcytic anaemia
128
What type of mutation is mainly scene in alpha thalassaemia?
Deletions (genes)
129
What type of mutation is mainly scene in beta thalassaemia?
point mutations
130
What is the pathophysiology behind beta thalassaemia?
Point mutations --> highly unstable beta chains that can't be used + excess alpha chains --> haemolysis
131
What are the 3 clinical classifications of beta thalassaemia?
Thalassaemia minor, thalassaemia intermedia, thalassaemia major
132
What is beta thalassaemia minor? How do they present? And what is the clinical presentation?
Heterozygous carrier for beta thalassaemia - asymptomatic
133
How do you distinguish Thalassaemia from iron deficiency anaemia?
Do a serum ferritin, TIBC, serum iron
134
What is thalassaemia intermdia and how does it present symptoms wise?
Combo of beta and alpha thalassaemia - symptoms: mild anaemia, ^ infections...etc
135
What are the signs of thalassaemia intermedia?
recurrent ulcers, gallstones, splenomegaly and bone deformities
136
What is the beta thalassaemia major? How does it present?
Heterozygous beta thalassaemia - severe anaemia symptoms
137
Why does Beta thalassaemia major present at 6-12 months following gestation?
Because at 6-12 months is when all the HbF is replaced by HbA (HbF starts to replace HbA at 13 weeks following gestation) - HbF is unaffected by beta thalassaemia as it doesn't contain beta globin chains
138
Why is Foetal haemoglobin unaffected by beta thalassaemia but is by alpha thalassaemia? What does this mean in terms of presentation of each thalassaemia?
It has alpha chains but no beta chains. Therefore alpha thalassaemia presents at birth whilst beta thalassaemia presents later on (when HbF is replaced by HbA)
139
What are the symptoms of beta thalassaemia major?
Failure to thrive, failure to feed, crying, severe anaemia symptoms, pale, classical facial features
140
What can be seen on a skull XR of beta thalassaemia major?
Classic 'hair on end appearance'
141
What blood Ix's would you carry out on someone with thalassaemia?
Blood film (MCH, MCV), serum ferritin/iron
142
Why do you carry out a serum ferritin for thalassaemia?
Both cause microcytic anaemia (shown by the blood film) therefore it is to rule out Fe deficiency as a cause of microcytic anaemia
143
What results to you see in beta thalassaemia?
blood film MCV + MCH (low), normal ferritin/iron
144
What is the treatment for beta thalassaemia?
Regular blood transfusion, splenectomy
145
What is the prblem with regular blood transfusion?
Iron overload: can leads to hepatic fibrosis + cirrhosis, DM, cardiac arrhythmias, hypothyroidism, HF and death
146
How do you prevent iron overload from regular blood transfusion?
Iron chelation using either Desferrioxamine ascorbic acid (vitamin C) or Deferiprone
147
How does thalassaemia present and why do the presentations vary?
Mild to severe - depends on how many genes are deleted (mutated) for the alpha chains
148
How many alpha globin chain genes are found on a haploid chromosome 16?
4
149
How many alpha globin chain genes in alpha thalassaemia need to be deleted for a clinical presentation?
2 (because if only one is deleted then there are still 3 other genes to produce a sufficient quantity of Hb alpha chains to prevent anaemia)
150
What is the name of the condition when 4 alpha globin chain genes are deleted? What is it characterised by?
Hydrops fetalis - incompatible with life (stillborn)
151
In the UK, what is the 1st and 2nd commonest genetic conditions?
1st: CF and 2nd: sickle cell disease
152
Which group of people are affected by sickle cell disease?
Black people + Africans
153
What globin chain does Sickle cell disease affect and when does it therefore present/manifest?
Beta globin chains and manifests at 6months (HbF --> HbS)
154
Which malaria causing organism do sickle cell carriers have protection from?
Plasmodium falciparum
155
What occurs to a HbS molecule when it desaturates from oxygen?
It sickles and become insoluble (polymerises and crystalises) --> causing RBC deformity/rigidity
156
What is the commonest form of sickle cell?
HbSS
157
What is the homozygous (carrier) and heterozygous state called for sickle cell disease?
HbAS and HbSS
158
How does sickling/dehydration occur in sickle cell disease?
k+ leaves the cell by Gados channels
159
Is sickling reversible?
Yes but after so many repeats of sickling it is irreversible
160
What does sickling cause in sickle cell disease?
Haemolysis (reduced RBC life) and impaired passage of cells through smaller vessels leading to tissue infarction
161
Despite being anaemia, why might a sickle cell disease pt feel well?
HbS releases oxygen more readily than HbA AND there is constant Hb range (until acute fall in sickle cell crisis)
162
What precipitates RBC sickling?
Hypoxia, infection, dehydration, cold, acidosis
163
What does sickling mean in terms of flexibility?
Less flexibility + rigid (can't change shape like normal RBCs)
164
When does sickle cell disease manifest in terms of clinical presentation?
6 months
165
Is there variation in clinical presentation for someone with sickle cell disease?
Yes: some pts have few symptoms while others have recurrent sickle cell crisis (+ reduced life expectancy)
166
What causes anaemia in patients with sickle cell disease? What type of anaemia is it?
Chronic haemolysis - macrocytic anaemia
167
What can cause a huge fall in Hb in patients with sickle cell disease?
Splenic sequestration, BM aplasia, further haemolysis (due to other causes)
168
What is sickle cell crisis characterised by?
Vaso-occlusion causing ishcaemia + pain
169
What occurs in sickle cell crisis?
PAIN in hands + feet (dactylitis), severe pain in bones, fever, SOB (sickle chest syndrome - infarcts)
170
What are some chronic complications of sickle cell disease?
Avascular necrosis (femur head), pulmonary hypertension, joint damage (avascular necrosis), pigment gall stones, hepatomegaly, background retinopathy
171
What are the chronic and acute (crisis) respiratory complications of sickle cell disease?
Chronic: pulmonary hypertension
| Acute (sickle cell crisis): acute chest syndrome (infarcts)
172
What causes sickle cell crisis (acute complications)?
Vaso-occlusion
173
What other complications can sickle cell crisis (vaso-occlusion) lead to?
Leg ulcers, spontaneous abortion/foetal death, stroke, MI, seizures...etc
174
What tests would you carry out to diagnose sickle cell disease?
Blood count, blood films, sickle solubility test, Hb electrophoresis
175
What must you do before surgery if a patient is from an ethnic group?
Firstly a sickle solubility test and then sickle cell disease screening
176
What do blood counts and blood films show in sickle cell disease?
Blood counts show high reticulocyte count
| Blood film shows high reticulocytes and sickling of RBCs
177
What does sickle solubility test show in sickle cell disease? What must you do if the test is positive?
HbS precipitates in the reducing solution (because it desaturates)
178
What test confirms the diagnosis of sickle cell disease? What does it show?
Hb electrophoresis (shows no HbA only HbS)
179
What is the conservative management of sickle cell disease?
Avoid precipitating factors (hypoxia, infection, cold..), pneumococcal + influenza vaccination, folic acid, councelling (psychosocial issues, pregnancy and drugs)
180
What is the drug treatment for chronic sickle cell disease (not acute crisis)?
Penicillin (daily), manage painful crisis with NSAIDs + paracetamol, hydroxycarbamide
181
When should BM Tx be offered in sickle cell disease?
If they have severe, + recurrent crisis
182
When should blood transfusions be offered in sickle cell disease?
TIA, stroke, acute chest syndrome, pregnancy, splenic sequestration crisis, before surgery
183
If a painful crisis can't be managed by NSAIDs + paracetamol, what should be the next stage in treatment?
Hospital admission
184
If a sickle cell disease pt is admitted to hospital for a severe painful crisis, what analgesia should be given?
morphine or diamorphine + adjuvant non-opioid
185
What does PCA stand for?
Patient controlled analgesia
186
If a sickle cell disease pt is admitted to hospital for a severe painful crisis, what else should be given apart from analgesia?
Oxygen, laxatives (lactulose), anti-emetic, anti-pruritics (hydroxyzine), rehydration (IV saline or oral fluids)
187
How does Hydroxycarbamide work in sickle cell disease?
Increases the amount of HbF
188
What causes acute chest syndrome in sickle cell disease?
Infarcts to the lung
189
Give two metabolic (enzyme) RBC disorders that causes haemolytic anaemia?
G6PD deficiency and pyruvate kinase deficiency
190
What does G6PD stand for?
Glucose-6-phosphate dehydrogenase
191
Is G6PD deficiency common?
Yes
192
What type of genetic disease is G6PD deficiency?
X linked
193
What is the role of G6PD?
It is involved in the hexose monophosphate shunt forming NADPH
194
What is the role of NADPH in a red blood cell if red blood cells have no mitochondria? What does this mean in terms of the role of G6PD in a RBC?
Protection of the RBC from oxidative damage - therefore, G6PD provides protection of the RBC from damage and haemolysis by oxidants
195
Why does G6PD deficiency cause haemolysis?
Less NADPH is produced so there is oxidative damage
196
What are the clinical presentations of G6PD deficiency?
mostly asymptomatic, anaemia, jaundice, hemoglobinuria, ^ infections
197
What is the triad of symptoms in G6PD deficiency CRISIS?
Jaundice, anaemia, haemoglobinuria
198
What causes the triad of symptoms in G6PD deficiency CRISIS?
Rapid intravascular haemolysis
199
What causes rapid intravascular haemolysis and G6PD deficiency crisis?
Favism (broad beans [VICIA FAVA]), henna, infection, drugs (quinolones, quinine, sulphonamides, nitrofurantoin)
200
What is the common presentation of G6PD deficiency?
ASYMPTOMATIC (unless crisis precipitated by broad beans, drugs, henna causing RAPID haemolysis)
201
What is G6PD deficiency crisis characterised by?
Anaemia, jaundice, haemoglobinuria
202
What does a blood film show in G6PD deficiency between acute attacks (crisis)?
Normal cells
203
What does a blood film show in G6PD deficiency during an acute attack (crisis)?
Bite and blister cells, reticulocytes ^, Heinz bodies
204
What is the diagnostic Ix for GP6D deficiency?
Enzyme assay showing G6PD deficiency
205
What is the treatment for G6PD deficiency?
Avoid precipitants (henna, drugs, broad beans), treat infection, blood transfusion in acute crisis
206
What is the function of pyruvate kinase?
Involved in the last step of glycolysis
207
What occurs in pyruvate kinase deficiency?
Reduced ATP production --> reduced RBC survival --> haemolysis
208
What types of anaemia do pyruvate kinase and G6PD def. display?
Macrocytic/haemolytic
209
What is the presentation of pyruvate kinase def.?
Anaemia
210
How do you diagnose pyruvate kinase def?
blood film (distorted prickle cells + reticulocytosis) and enzyme assay
211
What is the difference between pyruvate kinase def. and G6PD def. in terms of treatment?
Splenectomy in pyruvate kinase def.
212
Why does chronic haemolytic anaemia lead to folate deficiency?
folate is needed to make RBCs and therefore in haemolytic anaemia there is ^ demand to make more RBCs (depleting folate stores)
