(45) Anaemia and thrombocytopenia Flashcards
1
Q
What are the causes of anaemia? (other than blood loss)
A
- haematinic deficiencies
- secondary to chronic disease
- haemolysis
- alcohol, drugs, toxins
- renal impairment (EPO)
- primary haematological/marrow disease
2
Q
What are the categories of primary haematological/marrow disease?
A
- malignant
- haemoglobin disorders (sickle etc)
- aplasia
- congenital
3
Q
EPO is an abbreviation for what?
A
Erythropoietin
4
Q
What is a haematinic agent?
A
An agent that stimulates the production of red blood cells or increases the amount of haemoglobin in the blood
5
Q
Name 3 different types of anaemia
A
- macrocytic
- normocytic
- microcytic
6
Q
What is MCV?
A
Mean corpuscular volume/mean cell volume
Measure of average volume of a red blood cell
7
Q
What is used to classify anaemia as macrocytic/normocytic/microcytic?
A
MCV (mean corpuscular volume)
8
Q
Define the different classes of anaemia according to MCV?
A
Microcytic = MCV below normal range
Normocytic = MCV within normal range
Macrocytic = MCV above normal range
9
Q
Why does normocytic anaemia occur?
A
The bone marrow has not yet responded with a change in cell volume
Occurs in acute conditions eg. blood loss and haemolysis
10
Q
Why is macrocytic anaemia a type of anaemia?
A
Larger red cells are associated with insufficient numbers of cells and insufficient haemoglobin per cell
- results in total blood haemoglobin concentration that is less than normal (i.e., anaemia)
11
Q
What are the causes of macrocytic anaemia?
A
- B12, folate, metabolic (thyroid/liver disease)
- marrow damage (alcohol, drugs, marrow disease)
- haemolysis (due to reticulocytosis)
12
Q
What are the causes of normocytic anaemia?
A
Anaemia of chronic disease/inflammatory
13
Q
What are the causes of microcytic anaemia?
A
- iron deficiency
- haemoglobin disorders
- (sometimes chronic disease)
14
Q
What is reticulocytosis?
A
Increase in reticulocytes, immature red blood cell
Commonly seen in anaemia
15
Q
Why is reticulocytosis seen in anaemia?
A
Bone marrow is highly active in an attempt to replace red blood cell loss
16
Q
Describe how iron balance is maintained
A
- no excretion
- limited absorption (7% TDI)
- most iron is recycled
17
Q
Where is iron balance controlled?
A
At the level of the gut mucosa
18
Q
Where is iron absorbed?
A
Absorbed in the duodenum (less in jejunum)
19
Q
What is iron transported by?
A
Transferrin
20
Q
What is iron stored in?
A
Ferritin/haemosiderin
21
Q
What is ferritin?
A
Intracellular protein that stores iron and releases it in a controlled fashion
22
Q
What is haemosiderin?
A
Iron-storage complex. It is only found within cells (as opposed to circulating in blood) and appears to be a complex of ferritin, denatured ferritin and other material. The iron within deposits of hemosiderin is very poorly available to supply iron when needed.
23
Q
Which foods have a high iron content?
A
- red meat
- chicken
- baked beans
- boiled eggs
- oily fish
- cereals with added vitamins
- green leafy veg
- dried fruit
- wholemeal bread
- lentils, beans, peas, nuts
24
Q
Describe the approach to the disorder (iron deficiency)
A
- establish that there is low iron
- establish the cause
- treat the iron and the cause
25
What are the lab tests to establish low iron?
- FBC, indices and film
- ferritin
- % hypo chromic cells
- serum iron/TIBC
- marrow
26
What is TIBC?
Total iron binding capacity - blood test to test ability of transferrin to transport iron in blood
27
What is hypochromic anaemia?
Any type of anemia in which the erythrocytes are paler than normal.
Area of central pallor is increased
28
What is MCH?
Mean corpuscular haemoglobin
Average mass of haemoglobin per red blood cell - reported as part of standard complete blood count.
MCH diminished in hypochromic anaemias
29
What are the main causes of iron deficiency?
- blood loss (gut, PV, PU, resp tract etc)
- increased demand (pregnancy, growth)
- reduced intake (diet, malabsorption)
30
What are the main causes of iron deficiency in children?
- diet
- growth
- malabsorption
31
What are the main causes of iron deficiency in young women?
- menstrual loss/problems
- pregnancy (causes long term deficiency afterwards)
- diet
32
What are the main causes of iron deficiency in older people?
- bleeding
| - GI problems (ulcer, gastritis, aspirin, malignancy, diverticulitis, GI surgery etc)
33
What are the 3 different types of iron therapy?
- oral iron
- IM iron
- IV iron
34
State the main features of each type of iron therapy
- oral iron = unreliable
- IM iron = painful and out of date
- IV iron = increasingly used
35
What is megaloblastic anaemia?
Anaemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production - characteristic cell morphology caused by impaired DNA synthesis
36
What are the typical peripheral blood changes in megaloblastic anaemia?
Big red cells (high MCV)
37
What are the causes of megaloblastic change?
- B12 and/or folic acid deficiency
- alcohol
- drugs
- haematological malignancy
- congenital rarities
38
What kinds of drugs can cause megaloblastic change?
- cytotoxics
- folate antagonists
- n2o
39
What types of congenital disorders can cause megaloblastic change?
- transcobalamin deficiency
| - orotic aciduria
40
What is transcobalamin?
Glycoprotein produced by the salivary glands - serves to protect cobalamin (Vitamin B12) from acid degradation in the stomach by producing a Haptocorrin-Vitamin B12 complex
41
How do B12 and folate cause anaemia?
- DNA consists of purine/pyrimidine bases
- folate required for their synthesis
- B12 essential for cell folate generation
- low folate or low B12 starves DNA of bases
42
How do we get vitamin B12?
Loads in most diets compared to needs but only from animal sources
Stores sufficient for some years
43
What is involved in vitamin B12 absorption?
- gastric parietal cells
- intrinsic factor
- receptors in terminal ileum
44
What causes vitamin B12 deficiency?
- nutritional (vegans)
- gastric problems
- small bowel problems
45
What type of gastric problems cause B12 deficient?
- pernicious anaemia (autoimmune)
| - gastrectomy
46
What type of small bowel problems cause B12 deficiency?
- terminal ileal resection/Crohn's
- stagnant loops/jejunal diverticulosis
- tropical sprue/fish tapeworm
47
What foods contain folic acid?
- green veg
- beans
- peas
- nuts
- liver
Required intake needs decent daily diet
48
Where is folic acid absorbed?
Upper small bowel
49
How much folic acid does the body store?
4 months body store
50
What are the causes of folic acid deficiency?
- mainly dietary/malnutrition
- malabsorption/small bowel disease
- increased usage
- drugs/alcohol/ITU
51
Increased usage may cause folic acid deficiency. Give examples
- pregnancy
- haemolysis
- inflammatory disorders
52
What are the features that are common to B12 or folate deficiency?
- megaloblastic anaemia
- can have pancytopenia if more severe
- mild jaundice
- glossitis/angular stomatitis
- anorexia/weight loss
- sterility
53
What is pancytopenia?
Deficiency of all three cellular components of the blood (red cells, white cells, and platelets)
54
What is glossitis?
Inflammation of the tongue
55
What is angular stomatitis?
Inflammation of one, or more commonly both, of the corners of the mouth
56
What are the lab tests for B12 + folate deficiency?
- blood count and blood film (marrow sometimes)
- bilirubin and LDH 'haemolysis'
- B12 and folate levels
- antibodies
- B12 absorption tests +/- IF
- GI investigations (Crohn's, malabsorption, blind loop etc)
57
What is blind loop syndrome?
When digested food slows or stops moving through part of the intestines. This causes an overgrowth of bacteria in the intestines. It also leads to problems absorbing nutrients
58
What is the classic cause of B12 deficiency?
Pernicious anaemia
59
What causes pernicious anaemia?
Antibodies to parietal cells/intrinsic factor (so unable to absorb B12)
Autoimmune associations
60
What is pernicious anaemia also related to?
- atrophic gastritis
- achlorhydria
- increased risk of stomach cancer
61
Who first described pernicious anaemia?
Thomas Addison
62
What does SACDC stand for?
Subacute combined degeneration of the cord
63
What happens in SACDC?
- demyelination of the dorsal and lateral columns of the spinal cord
- peripheral nerve damage
64
What causes SACDC?
Severe B12 deficiency
Usually associated with pernicious anaemia but anaemia not an absolute requirement
65
How does SACDC present?
- peripheral neuropathy/paraesthesiae
- numbness and distal weakness
- unsteady walking
- dementia
66
What is the treatment for SACDC?
- B12 + folate until B12 deficiency excluded
- B12 x5 then 3 monthly for life for PA
- folic acid 5mg daily to build stores
- need for potassium and iron initially
67
What are the key messages concerning iron, B12 and folate?
- all common problems
- multiple causes and links to consider
- reasonably easy to diagnose and treat
- attend to the underlying causes
68
Put simply, what are the causes of haemolysis (shortened red cell life)?
- things wrong inside red cell
- things wrong with red cell membrane
- things wrong external to red cell
69
What are the causes of haemolysis inside the cell?
- haemoglobinopathy (Sickle cell)
| - enzyme defects (G6PD)
70
What are the causes of haemolysis related to the membrane?
- hereditary spherocytosis/elliptocytosis
71
What are the causes of haemolysis external to the red cell?
- antibodies (warm/cold)
- drugs, toxins
- heart valves
- vascular/vasculitis/microangiopathy
72
What are the tests for the presence of haemolysis?
- anaemia (or not - compensated)
- high MCV, macrocytic
- high reticulocytes
- blood film (fragments, spherocytes)
- raised bilirubin, LDH
- low haptoglobins
- urinary haemosiderin
73
What are reticulocytes?
Immature red blood cells without a nucleus, having a granular or reticulated appearance when suitably stained
74
What is LDH and why is it a marker of haemolysis?
Lactate dehydrogenase - often used as a marker of tissue breakdown as LDH is abundant in red blood cells and can function as a marker for haemolysis
75
What are haptoglobins?
The bind free hemoglobin (Hb) and so are low in haemolysis as they get used up
76
How is the cause of haemolysis identified?
- history + exam
- drug history (alcohol/toxins/work)
- positive DCT (evidence of antibody)
- blood film
- abnormal haemoglobins (eg. sickle)
- membrane studies
- enzyme studies
ect
77
What is a DCT?
Direct Coomb's Test
Used to detect IgG antibodies that bind to antigens on the RBC surface membrane, leading to RBC destruction
Tests for autoimmune haemolytic anaemia
78
What is the general approach to diagnosis of haemolysis?
- demonstrate that haemolysis is present
- think about the causes
- history + exam
- work through the necessary tests
79
What is AIHA?
Autoimmune haemolytic anaemia
80
How is AIHA managed?
With steroids/immunosuppression
81
Can you transfuse in haemolysis?
Can be tricky in AIHA (hard to cross match)
82
What is anaemia of chronic disease?
A form of anemia seen in chronic infection and inflammation, chronic immune activation, and malignancy eg. DM, autoimmune etc
83
What is the MCV in anaemia of chronic disease?
Typically normal MCV
84
In anaemia of chronic disease, there is reduced red cell production due to what?
- abnormal iron metabolism
- poor erythropoetin response
- blunted marrow response
85
Which inflammatory cytokines are involved in anaemia of chronic disease?
- IL1
- IL6
- TNF-alpha
86
What is hepcidin?
A key regulator of iron absorption and release from macrophages
87
What happens when hepcidin levels are high such as in inflammation?
Serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red cells.
88
What are the main features of anaemia of chronic disease (ACD)?
- no other causes of anaemia
- a suitable medical history
- usually mild anaemia, normal MCV
- often raised inflammatory markers
- normal/high ferritin + low serum iron
- normal % saturation transferrin
89
Which inflammatory markers are often raised in ACD?
- ESR
- CRP
- PV
etc
90
The effects of ACD are mediated by what?
- cytokines
| - hepcidin
91
What are transferrins?
Iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. Bind iron tightly, but reversibly
92
What is the treatment for ACD?
- treat the cause if possible
- erythropoetin/iron/IV
- transfusion?
- careful symptom assessment first
93
What is thrombocytopenia?
Deficiency of platelets in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury
94
What are the common causes of thrombocytopenia?
- drugs, alcohol, toxins
- ITP
- autoimmune diseases
- liver disease or hypersplenism
- pregnancy
- haematological and marrow diseases
- infections
- DIC
- congenital conditions
95
What is ITP?
Immune thrombocytopenic purpura - isolated low platelet count with normal bone marrow and the absence of other causes of thrombocytopenia
96
What is hypersplenism? (cause of thromboyctopenia)
Condition in which the spleen becomes increasingly active and then rapidly removes the blood cells. It can result from any splenomegaly
97
What types of infections can cause thrombocytopenia?
- acute sepsis
- HIV
- other viral infections eg. EBV etc
98
What does DIC stand for? (cause of thrombocytopenia)
Disseminated intravascular coagulation
99
Give 3 different classifications of ITP
- acute
- chronic
- relapsing
100
ITP is a common immune disorder that can occur on its own or part of what?
- other autoimmune disease
- lymphomas/CLL
- HIV
101
How does thrombocytopenia/ITP present?
- bruising or petechiae or bleeding
| - low platelet count
102
What platelet count is urgent?
under 10 = urgent
under 20 = a worry
under 30 = needs treatment
otherwise observe
103
What is the first line treatment for thrombocytopenia/ITP?
Steroids
104
Other that steroids, what are the other therapy types for thrombocytopenia/ITP?
- IV immunoglobin
- immunosuppressives or splenectomy
- thrombo-mimetics
105
What are thrombo-mimetics and give 2 examples
Have thrombopoetin-like properties
- eltrombopag
- romiplostin
106
What is thrombopoetin?
A glycoprotein hormone produced by the liver and kidney which regulates the production of platelets.
- also known as megakaryocyte growth and development factor (MGDF)
107
What is the outcome of treatment for ITP?
- usually rapid responses
- can relapse after therapy
- rarely life-threatening
- but commonly recurrent
- some difficult refractory cases
108
What is TTP (thrombotic thrombocytopenia purpura)?
A rare and urgent disorder of the blood-coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the bod
109
Most cases of TTP are what?
Immune (AMAMTS-13/VWD)
110
Suspect TTP if thrombocytopenia and what else?
- fever
- neurological symptoms
- haemolysis (retics, LDH)
111
In TTP, you should seek evidence of what type of angiopathy?
Microangiopathy (blood film fragments)
112
Urgent therapy for TTP includes what?
- plasma exchange with FFP/plasma
- steroids
- (vincristine)
- (rituximab)
Outcomes vary - can see relapses
113
What must you monitor in TTP?
ADAMTS-13
