Aani Haem: Anaemia Flashcards
1
Q
What are causes of microcytic anaemia?
A
Iron deficiency
Thalassaemia
ACD
Sideroblastic anaemia
2
Q
What is sideroblastic anaemia?
A
When body cannot incorporate iron into haemoglobin - ineffective erythropoeisis
3
Q
What do sideroblasts look like?
A
Nuceleated erythroblasts - they have iron granules around the nucleus to form ‘rings’ = Ring Sideroblasts
4
Q
Where are sideroblasts normally found?
A
In the Bone Marrow
5
Q
What will the TIBC be in iron deficiency anaemia (IDA)?
A
High because there is free transferrin because not enough iron to bind to it
6
Q
What will the ferritin levels be in IDA?
A
LOW because it is a storage of iron. Not enough iron to form storage tins
7
Q
Causes of IDA?
A
- Lack of absorption e.g. gastic surgery, coeliac.
- Too much excretion e.g. MAHA
- Little intake e.g. Babies/Old people
- Blood loss e.g. peptic ulcers, hookworm, HMB
- Higher demand e.g. kids and pregnancy
8
Q
Where in sideroblasts is the iron stored?
A
In mitochondria around the nucleus
9
Q
Which stain is used to see sideroblasts?
A
Prussian Blue Stain
10
Q
Causes of sideroblastic anaemia?
A
- MDS
- Lead excess
- Chemo
- Alcohol excess
11
Q
Treatment of sideroblastic anaemia?
A
Pyridoxine (Vit B6- promotes RBC synthesis)
12
Q
What will the ferritin levels be in ACD?
A
High because the iron is sequestered to prevent bacteria from getting it
13
Q
What will serum iron levels be in ACD?
A
Low, it all been sequestered
14
Q
What will TIBC be in ACD?
A
Low
15
Q
What is TIBC an indirect measure of?
A
Transferrin
16
Q
When is TIBC low?
A
When the iron stores are full e.g. ACD, sideroblastic anaemia
17
Q
When is TIBC high?
A
When the iron stores are low and empty so we need more iron e.g. IDC
18
Q
How do inflammatory markers cause ACD?
A
IL1 and TNF reduce the EPO receptor so less EPO synthesis
IL6 and LPS make hepcidin which reduces Iron absorption from the gut by reducing Transferrin
19
Q
When is Ferritin high?
A
It is an acute phase protein and high during infection/inflammation/ malignancy
20
Q
Causes of macrocytic anaemia?
A
M FAT RBC Myelodysplastic Disorders Foetus Antifolates (phenytoin) /Alcohol Thyroid (hypothyroid) Reticulocytosis B12 deficiency/Folate deficiency Cirrhosis
21
Q
What causes megaloblastic anaemia?
A
b12 and folate deficiency
22
Q
What does megaloblastic film look like?
A
Hypersegmented neutrophils
Leukopaenia
Macrocytosis of RBCs
Anaemia
23
Q
Why does B12 deficiency take less time to occur than folate deficiency?
A
because we have B12 stores in our liver
24
Q
Where does B12 come from?
A
Meat & dairy
25
Where is B12 absorbed?
Stomach, then terminal ilium
26
Which cells make Intrinsic factor?
Gastric parietal cells
27
Which condition prevents absorption of B12?
Pernicious Anaemia (Abs against IF and parietal cells)
28
Which tests can test for Pernicious anaemia?
- Schillings (outdated)
- Parietal cell ABS
- Intrinsic Factor Abs
29
Treatment of B12 deficiency?
Replenish B12 with IM hydroxocobalamin
30
Where is folate absorbed?
Jejenum
31
Where does folate come from?
Green vegetables, nuts, yeast
32
Symptoms of B12/folate deficiency?
Glossitis
| Angular Cheilosis
33
What does free plasma Hb bind to? N.B. Free plasma Hb is ABNORMAL. Hb should be contained within RBCs.
Haptoglobins
34
When haptoglobins run out, what happens to excess free Hb?
Filtered by glomerulus --> Haemoglobinuria (dark red/coca cola urine)
35
At what level of Hb do haptoglobins run out?
150 g/l
36
What are the consequences of free Hb?
AKI - nephrotoxic!
| Haemosiderinuria
37
Consequences of haemolysis?
Anaemia
Excess bilirubin --> gall stones
Susceptible to parvovirus B19
Iron overload
38
What is the purpose of the DAT test?
Identify whether haemolytic anaemia is autoimmune or not.
39
Do you get free plasma Hb in extravascular haemolysis?
No. It occurs within macrophages
40
What is missing in paroxysmal nocturnal haemoglobinuria (PNH)?
GPI anchor that protects RBC against complement mediated destruction
41
Causes of extravascular haemolysis?
Autoimmune & Hereditary Spherocytosis
42
What is LDH?
Lactate Dehydrogenase
43
When is LDH released: intra or extra vascular haemolysis?
Intravascular only (it is released from cells)
44
Biological features of extravasc haemolysis?
- Splenomegaly
- Rise in unconj bilirubin
- Rise in urobilinogen
- High reticulocytes
- Pigmented gallstones
45
Biological features of intravasc haemolysis?
Same as extravas except no splenomegaly.
| Plus Rise in LDH, Fewer haptoglobins and Cocacola urine
46
Which membrane proteins can be affected in Hereditary Spherocytosis?
SPECTRIN
ANKYRIN
BAND 3
47
3 drug triggers for G6PD deficiency?
Primaquin
Sulphonamides
Aspirin
'Prim took a Selphie of her As'
48
4 Non-drug triggers for G6PD deficiency?
- Fava beans/broad beans
- Naphthalene Moth balls
- Acute stress
- Acute infection
49
Which haemolytic anaemia protects against malaria?
G6PD deficiency (enzyme defect)
South East Asian Ovalocytosis
and
Thalassaemia
50
Mnemonic to remember Inherited Haemolytic Anaemias?
MEH (Membrane, Enzyme, Haemoglobinopathy)
Horrid Henry Gave Peter Some Trouble
Hereditary Spherocyt, hereditary eliptocyte, G6PD, PK, Sickle, Thallassaemia
51
What will the pearl stain show?
Increased iron in kuppfer cells
52
When is pearl stain used?
In Pyruvake Kinase deficiency HA
53
Why does sickle cell not present until 3-6 months?
the defect is on the Beta chain. Foetal Hb is a-a. So it only manifests when b chains come into effect
54
Which codon is the defect that causes sickle cell and what is the defect?
Glutamic acid --> Valine on Codon 6 of B chain
55
What is aplastic crisis?
Temporary cessation in RBC production
56
Which infection is most commonly associated with aplastic crisis in sickle cell disease?
Parvovirus B19
57
What are the consequences of haemolysis in Sickle Cell?
```
FGS AA
Folate Deficiency
Gallstones
Splenomegaly
Anaemia
Aplastic Crisis
```
58
What are the consequences of infarction in Sickle Cell?
```
SICKLED Penis
Stroke
Infections (CKD, hyposplenism)
Crises (splenic, chest pain etc)
Kidney (nephrotic syndrome)
Liver (gall stones)
Eyes (retionopathy)
Dactilitis
```
Penis constantly erect (Priapism)
59
What is Beta thalassaemia?
Missing Beta chains
60
When does beta thal manifest?
A few months age (3-6 months) after foetal haemoglobin runs out. Foetal haemoglobin is alpha alpha gamma gamma
61
How many chains should everyone have?
4: in adults - 2 alpha, 2 beta
62
What is HbA?
Normal: alpha alpha beta beta
63
What is HbA2?
alpha alpha delta delta
64
What is HbF?
Foetal haemoglobin: alpha alpha gamma gamma
65
What type of Gene defect leads to beta Thal? + which chromosome?
MUTATION- Cr 11
66
What type of Gene defect leads to alpha Thal? + which chromosome?
DELETION- Cr 16
67
Which test is done for Paroxsysmal Nocturnal Haemoglobinuria?
Ham's test - looks for in vitro acid induced lysis
68
When can you get iron-overload in Thalassaemia pts?
Transfusion-induced
69
What do you give to prevent iron overload in pts?
Desferrioxamine
70
What happens in iron overload (haemochromatosis)?
Tissue damage due to iron deposition, especially in the pancreas, gonads, pituitary, liver, and heart.
71
What is the difference between haemosiderosis and haemochromatosis?
Hemosiderosis is focal deposition of iron that does not cause tissue damage.
Hemochromatosis (iron overload) is a typically systemic process in which iron deposition can cause tissue damage.
72
Why is parvovirus B19 extra dangerous in B thalassaemia?
Parvovirus shuts down your RBC precursors, this cant be tolerated in B thal because already not enough RBCs
73
Why do you get skull deformity in B thal?
Because of low Hb, you get erythroid hyperplasia and so haematopoiesis in the marrow of other bones and it causes bone marrow to expand so that's why you get the deformities
74
Are B thal Intermedia homo or heterozygous?
Hetero- it is only different to B thal minor based on clinical differences, not genetic
75
How many copies of the alpha chain do we each have?
4 - 2 from each parent. 2 chains coded foe=r on each gene
76
What are the acquired haemolytic anaemias?
'Cold/Warm Prime Minister'
Immune; Warm/cold (coombs +)
Non immune (coombs -):
- PNH
- MAHA
77
What type of Abs are the Warm-Antibody Immune Haemolytic Anaemias (WAIHA)?
IgG
78
What type of Abs are the Cold Agglutinin Disease?
IgM
79
Tx for Cold agglutinin disease?
Treat cause + Avoid cold +/or Chlorambucil (Chemo)
80
Tx for WAIHA? (warm immune HA)
Steroids
Splenectomy
Immunosuppression
81
What is the defect in NPH?
Absent GPI on RBCs and Platelets
82
Why is GPI needed?
GPI is needed to make DAF. DAF protects cells from complement mediated lysis
83
Mnemonic to remember what Ham's test is for?
Please No Ham
PNH
Paroxysmal Nocturnal Haemoglobinuria
84
Coombs test negative acquired haemolytic anaemias?
PNH
| MAHA (TTP and HUS)
85
Which drug prevents complement from binding to RBCs in PNH?
Eculizumab
86
What is Budd-Chiari Syndrome?
Occlusion of hepatic vein that drains liver (do not confuse with central vein).
Classical triad of abdominal pain, ascites, and liver enlargement.
87
How does MAHA occur? (explain why RBCS break)
Intravascular haemolysis when RBCs are forced through fibrin mesh in damaged vessels.
88
What cells do you get in MAHA?
Schistocytes (red cell fragments)
89
Treatment of MAHA?
Plasma exchange
90
What are 2 causes of MAHA?
TTP and HUS
91
What is the genetic defect that causes TTP and explain?
ADAMTS13 defect (Adam Toy Story 13). It usually cuts VWF in half but without it, you have hypercoaguability.
92
What happens in TTP?
Platelet activation with large VWB factor --> coagulation. Leads to pentad of symotoms:
MAHA, Fever, Renal impairment, Neuro abnormalities, Thrombocytopaenia
Think: Maha has fever, kidneys, brain and bleeding
93
What happens in HUS?
E.Coli damages endothelium. You get platelet aggregation and fibrin mesh --> RBC damage
94
Which organisms cause HUS?
E.Coli
95
What will the BM look like in Aplastic Anaemia?
Hypocellular BM
96
Clinical features of Aplastic Aneamia?
Low RBC leads to tiredness/breathlessness
Low neutrophils leads to infections
Low platelets leads to bleeding
97
What percentage of Aplastic Anaemias are inherited?
10%
98
How do you categorise Aplastic Anaemia?
Primary: idiopathic (70%) and inherited (10%)
| Secondary
99
What are some secondary causes of Aplastic Anaemia?
```
Malignant infiltration
Radiation
Drugs
Chemo
Viruses
Autoimmune e.g. SLE
```
100
Name some inherited causes of primary Aplastic Anaemia? (Bone Marrow Failure Syndrome)
Fanconi Anaemia
Dyskeratosis Congenita
Schwachman-Diamond Syndrome
Diamond-Blackfan Syndrome
101
How to diagnose Aplastic Anaemia?
```
Hypocellular BM (<20%)
AND 1 of:
1. <1% reticulocytes
2. <0.5 neutrophils
3. <20 platelets
```
102
Mnemonic to remember the Inherited causes of Aplastic Anaemia?
```
Fat Swans Don't Die
Fanconi Anaemia
Schwachman-Diamond Syndrome
Dyskeratosis Congenita
Diamond-Blackfan Syndrome
```
103
What blood abnormalities do you get in Faconi Anamia?
Pancytopaenia
104
What is the genetic inheritance of Faconia Anaemia?
X linked
105
What are the clinical features of Faconia Anaemia?
Cafe au lait spots
Skeletal abnornalities
Short stature
Renal malformations
106
What is the risk of Faconi Anaemia becoming AML?
10%
107
What is the triad of symptoms in Dyskeratosis Congenita?
BM failure plus triad:
- Skin pigmentation
- Nail dystrophy
- Oral Leukoplakia
108
Which cells are mostly affected in Schwachman Diamond Syndrome?
Neutrophils (neutrophillia)
109
What is the genetic inheritance of Dyskeratosis Congenita?
X linked - telomere shortening
110
Which cells are mostly affected in Diamond Blackfan Syndrome?
Erythrocytes missing!
| But platelets and neurophils normal
111
How do you treat Diamond Blackfan Syndrome?
TPO agonists
112
Management of Aplastic Anaemia?
Transfusions with iron chelation
Antibiotics
Marrow recovery drugs e.g. oxymethalone
SCT
