Anaemia and Thrombocytopenia Flashcards
(81 cards)
1
Q
What haematinic deficiencies can lead to anaemia?
A
o Iron
o Vitamin B12
o Folate
2
Q
Common causes of anaemia:
A
- Blood loss
- Haematinic deficiencies
- Secondary to chronic disease
- Haemolysis
- Alcohol, drugs, toxins
- Renal impairment – EPO
- Primary haematological/ marrow disease e.g. malignant, Hb disorders (sickle etc), congenital, aplasia
3
Q
What is pernicious anaemia?
A
Inability to absorb B12 and iron (e.g. in atrophic gastritis) leading to anaemia
4
Q
What is the MCV?
A
Mean cell volume i.e. how big your red cells are
5
Q
What is the term for an elevated MCV?
A
Macrocytic: when the MCV value is increased, the RBCs are abnormally large.
6
Q
What is macrocytic MCV typically seen in?
A
o B12, folate deficiencies (megaloblastic anemias)
o Metabolic e.g. thyroid/liver disease
o Marrow damage (alcohol, drugs, marrow disease)
o Haemolysis
7
Q
How can haemolytic anaemia lead to a macrocytic MCV?
A
RBCs are broken down quickly and young red cells (called reticulocytes) are released into the blood by the marrow to compensate.
Reticulocytes are larger than normal RBCs.
8
Q
What is the term for anaemia with a normal MCV?
A
Normocytic
9
Q
What is normocytic MCV seen in?
A
o Anaemia of chronic disease
o Inflammatory
o Acute blood loss
10
Q
What is the term for an reduced MCV?
A
Microcytic
11
Q
What is microcytic MCV typically seen in?
A
o Iron deficiency
o Haemoglobin disorders
o Sometimes chronic disease
12
Q
What is the most common cause of microcytic anaemia?
A
Iron deficiency
13
Q
Potential causes of iron deficiency in;
a) children
b) young women
c) older
A
a) diet, growth, malabsorption
b) menstrual loss/problems, pregnancy (don’t underestimate long-term impact of pregnancy on iron levels), diet
c) bleeding, GI problems (ulcer, aspirin, gastritis)
14
Q
Why is it very easy to become iron deficient?
A
Body only absorbs a limited amount of iron (7% TDI) due to having no excretory mechanism. Most iron is thus recycled.
15
Q
Where is iron absorbed?
A
Absorbed in the duodenum (less in jejunum)
16
Q
What is iron transported by?
A
Transferrin
17
Q
Where is iron stored?
A
ferritin/haemosiderin
18
Q
How should you approach an iron deficiency?
A
- Establish that there is a low iron
- Find cause
- Treat iron and cause
19
Q
What is the initial investigation in iron deficiency?
A
FBC, indices, film
20
Q
Describe the RBC indices in iron deficiency?
A
MCV will be low in iron deficiency
21
Q
What is the most important diagnostic test in iron deficiency?
A
Ferritin
22
Q
What is ferritin?
A
Ferritin is a blood protein that contains iron.
23
Q
If a ferritin test reveals that your blood ferritin level is lower than normal, what does this indicate?
A
low ferritin = iron deficiency
24
Q
What are hypochromic cells?
A
Hypochromia means that the red blood cells have less color than normal when examined under a microscope
25
What does a higher % of hypochromic cells indicate?
iron deficiency
26
What is the MCH?
The mean corpuscular hemoglobin , or "mean cell hemoglobin"
27
Describe the MCH value in hypochromic anaemias?
MCH value is diminished in hypochromic anemias.
28
4 main investigations in iron deficiency?
1. FBC, indices, film
2. Ferritin
3. %hypochromic cells
4. Serum iron/TIBC
29
What are the 3 types of iron therapy?
o Oral iron: often unreliable, unpleasant, not good compliance
o IM iron: painful, out of date
o IV iron: increasingly used.
30
What is megaloblastic anaemia?
Refers to description of appearance of abnormally large RBCs
* Proper term is the characteristic cell morphology caused by impaired DNA synthesis
* Used to describe raised MCV due to B12/folate deficiency
* RBCs are larger with high MCV
31
What is the most common cause of megaloblastic anaemia?
B12 and/or folic acid deficiency
32
How can B12 and/or folic acid deficiency lead to megaloblastic anaemia?
DNA has purine/pyrimidine bases which require folate for the synthesis.
B12 is essential for cell folate generation. Low folate or B12 starves DNA of bases.
33
Other causes of megaloblastic change?
* Alcohol
* Drugs: cytotoxics, folate antagonists, N2
* Haematological malignancy
* Congenital rarities: transcobalamin deficiency, orotic aciduris
34
Where is vitamin B12 found?
Only present in animal sources, but many other foods are fortified
35
How is vitamin B12 absorbed?
Absorbed very easily and stored for a long time (unlike iron).
1. Gastric parietal cells produce intrinsic factor
2. Intrinsic factor – binds to B12 in diet and enters ileum
3. Receptors in terminal ileum absorb intrinsic factor-B12 complex
36
What are 3 causes of B12 deficiency?
1. Nutritional – vegans (rare)
2. Gastric problems; lack of intrinsic factor
3. Small bowel problems; problem with terminal ileum
37
What is pernicious anaemia? How does it lead to B12 deficiency?
Pernicious anaemia causes autoimmune destruction of gastric parietal cells so no intrinsic factor is released --> unable to absorb B12.
38
How can a gastrectomy lead to B12 deficiency?
Gastrectomy is the removal of part or all of the stomach --> removal of parietal cells that produce intrinsic factor.
39
What small bowel problems can cause B12 deficiency?
Terminal ileum resection / Crohns
Stagnant loops/jejunal diverticulosis
Tropical sprue/Fish tapeworm
40
Where is folic acid found?
* Mainly in green vegetables, beans, peas, nut, liver
| * Required intake needs decent daily diet as don't store folic acid very well
41
Where is folic acid absorbed?
Upper small bowel
42
Potential causes of folic acid deficiency?
o Mainly dietary/malnutrition (easy to become malnourished)
o Malabsorption/small bowel disease
o Increased usage; Pregnancy, Haemolysis, Inflammatory disorders
o Drugs/alcohol/ITU
43
Size of RBCs in folic acid deficiency?
Megaloblastic
44
Clinical features of B12/folate deficiency?
If severe, can lead to damaged bone marrow which can cause:
* Can have pancytopenia if more severe (can be fatal)
* Mild jaundice (from constant breakdown of abnormal RBCs)
* Glossitis/angular stomatitis
* Anorexia/ weight loss
* Sterility
45
Describe MCV in B12/folate deficiency?
Raised - macrocytic
46
Lab investigations in B12/folate deficiency?
o Blood count and film, sometimes marrow
o Bilirubin and LDH for haemolysis
o B12 and folate levels
o Antibodies
o B12 absorption tests +/- intrinsic factor
o GI investigations; Crohn's, malabsorption, blind loop
47
Atrophic gastritis can also lead to pernicious anaemia. What is this?
Chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular (parietal) cells and their eventual replacement by intestinal and fibrous tissues.
48
What is SACDC?
Subacute combined degeneration of the cord; neurological disease caused by SEVERE B12 deficiency
N.B. anaemia is not an absolute requirement
49
What does SACDC cause?
* Demyelination of dorsal and lateral columns
| * Peripheral nerve damage
50
How does SACDC present?
o Peripheral neuropathy/ paraesthesia
o Numbness and distal weakness
o Unsteady walking
o Dementia
51
Treatment of B12/folate defiecieny?
B12 is given intramuscularly x5 then usually 3x month for life
Folic acid 5mg daily to build stores
Sometimes need potassium and iron initially due to frequent B12/folate injections.
52
How can frequent B12 injections affect potassium levels?
In some patients potassium levels can drop (hypokalemia) with frequent B12 injections.
53
What is haemolysis?
Shortened RBC life, less than 120 days
i.e. something causes RBCs to live less long
54
But put simply, causes are:
1. Things wrong inside the red cell
2. Things wrong with the red cell membrane
3. Things wrong external to the red cell
What are the causes of haemolysis inside the RBC?
- Haemoglobinopathy (sickle cell, thalassaemia)
| - Enzyme defects (G6PD)
55
What are the causes of haemolysis due to the red cell membrane?
Hereditary spherocytosis – red cells look very round and are broken down /elliptocytosis
56
What are the causes of haemolysis external to the red cell?
- Antibodies (warm/cold) – autoimmune haemolytic anaemia
- Drugs, toxins
- Heart valves
- Vascular / vasculitis / microangiopathy
57
Why can mild haemolysis not always cause anaemia?
Bone marrow may compensate
58
Tests for haemolysis?
o Anaemia (can be compensated by bone marrow)
o High MCV, macrocytic due to high reticulocytes (young red cells)
o Blood film (fragments, spherocytes, sickle cell, reticulocytes)
o Raised bilirubin, LDH (lactate dehydrogenase) of RBCs
o Low haptoglobins
o Urinary haemosiderin
59
Why is there raised bilirubin and LDH in haemolysis?
Due to break down products of RBCs
60
What are haptoglobins?
In blood plasma, haptoglobin binds to free haemoglobin
61
Treatment of haemolysis?
Depends on the cause:
o Autoimmune: steroids/immunosuppression (transfusion can be difficult due to difficulty cross-matching)
o Can transfuse
62
What is anaemia of chronic disease seen in?
A common general medical issue seen in;
- Malignant / inflammatory / infectious
- Multiple medical diseases (DM, autoimune etc)
63
What is the MCV like in anaemia of chronic disease?
Typically, normal MCV
64
What causes the reduced red cell production in anaemia of chronic disease?
o Abnormal iron metabolism
o Leads to poor supply of iron for erythropoiesis
o Poor erythropoietin response
o Blunted marrow response
These effects are mediated by cytokines and hepcidin.
65
How do cytokines play a role in anaemia of chronic disease?
Cytokines, such as interleukins (IL-1 and IL-6), and tumor necrosis factor (TNF-alpha), are believed to cause the destruction of RBC precursors and decrease the number of EPO receptors on progenitor cells.
66
What is the key hormone involved in anaemia of chronic disease?
Hepcidin
67
What is hepcidin?
Hepcidin is a regulator of iron absorption and release from macrophages.
Increased hepcidin = decreased iron
68
Describe levels of hepcidin in inflammation?
Hepcidin levels rise, decreasing iron absorption from gut and stops iron release from iron stores.
69
Features of anaemia of chronic disease?
- No other causes of anaemia
- A suitable medical history
- Usually mild anaemia, normal MCV
- Often raised inflammatory markers; ESR, CRP, PV etc
- Normal/high ferritin + low serum iron
- Normal % Saturation transferrin
70
Common causes of thrombocytopenia:
* Drugs, alcohol, toxins
* ITP (sometimes associated with lymphoma/CLL/HIV) – autoimmune thrombocytopenia, along with other autoimmune disorders
* Liver disease and/or hypersplenism
* Pregnancy (physiological and a range of complications)
* Haematological/ marrow disease
* Infections acute or otherwise e.g. acute sepsis/HIV/EBV/ others
* Disseminated intravascular coagulation (DIC)
* Range of congenital conditions
71
What is immune thrombocytopenic purpura (ITP)?
A blood disorder characterised by a decrease in the number of platelets in the blood. Common immune disorder. Behaves differently in adults and children.
72
How does ITP present in;
a) children
b) adults
a) severe, sudden, preceded by a viral illness, self-limiting without treatment given to adults
b) can be as severe but not as bad, doesn’t get better on its own and is not preceded by a viral infection, can become chronic
73
ITP can also occur in association with which other diseases?
o Other autoimmune diseases
o Lymphoma/ CLL
o HIV
74
Presentation of ITP?
```
o Bruising or petechiae or bleeding
o Platelet count can be anything:
<10 urgent, probably bleeding
<20 concerning
<30 needs treatment
o Must exclude other causes
```
75
What is first line of treatment in ITP?
Steroids
76
Function of steroids in treating ITP?
These work by stopping your immune system from destroying your platelets, by reducing the level of antibodies in your bloodstream. Only short course needed.
77
IV immunoglobulin can also be used in the treatment of ITP.
How does it function?
IVIG contains antibodies that bind to the cells in the spleen, which keeps these cells from destroying the platelets. More platelets stay in the blood.
78
What is thrombotic thrombocytopenic purpura (TTP)?
A blood disorder that results in blood clots forming in small blood vessels throughout the body. This results in a low platelet count, low red blood cells due to their breakdown.
Rare but urgent diagnosis.
79
Most TTPs are autoimmune. What are the antibodies targeted towards?
ADAMTS-13/VwF:
1. When vwF is abnormal (due to antibody), it will trigger chronic mild coagulopathy and endothelial damage.
2. Platelets are recruited and the platelet count will be depleted
3. Widespread activated clotting (then DIC due to consumption of platelets)
80
What is ADAMTS-13?
Primarily synthesised in the liver, and its main function is to cleave von Willebrand factor (VWF).
81
When should TTP be suspected?
Suspect if thrombocytopenia and;
o Fever
o Neurological symptoms
o Haemolysis (retics, LDH)
