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8. CP - Core Haematology > (45) Anaemia and thrombocytopenia > Flashcards

(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
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2
Q

What are the categories of primary haematological/marrow disease?

A
  • malignant
  • haemoglobin disorders (sickle etc)
  • aplasia
  • congenital
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3
Q

EPO is an abbreviation for what?

A

Erythropoietin

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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

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5
Q

Name 3 different types of anaemia

A
  • macrocytic
  • normocytic
  • microcytic
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6
Q

What is MCV?

A

Mean corpuscular volume/mean cell volume

Measure of average volume of a red blood cell

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7
Q

What is used to classify anaemia as macrocytic/normocytic/microcytic?

A

MCV (mean corpuscular volume)

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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

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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

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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)
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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)
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12
Q

What are the causes of normocytic anaemia?

A

Anaemia of chronic disease/inflammatory

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13
Q

What are the causes of microcytic anaemia?

A
  • iron deficiency
  • haemoglobin disorders
  • (sometimes chronic disease)
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14
Q

What is reticulocytosis?

A

Increase in reticulocytes, immature red blood cell

Commonly seen in anaemia

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15
Q

Why is reticulocytosis seen in anaemia?

A

Bone marrow is highly active in an attempt to replace red blood cell loss

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16
Q

Describe how iron balance is maintained

A
  • no excretion
  • limited absorption (7% TDI)
  • most iron is recycled
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17
Q

Where is iron balance controlled?

A

At the level of the gut mucosa

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18
Q

Where is iron absorbed?

A

Absorbed in the duodenum (less in jejunum)

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19
Q

What is iron transported by?

A

Transferrin

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20
Q

What is iron stored in?

A

Ferritin/haemosiderin

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21
Q

What is ferritin?

A

Intracellular protein that stores iron and releases it in a controlled fashion

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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.

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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
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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
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25
Q

What are the lab tests to establish low iron?

A
  • FBC, indices and film
  • ferritin
  • % hypo chromic cells
  • serum iron/TIBC
  • marrow
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26
Q

What is TIBC?

A

Total iron binding capacity - blood test to test ability of transferrin to transport iron in blood

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27
Q

What is hypochromic anaemia?

A

Any type of anemia in which the erythrocytes are paler than normal.

Area of central pallor is increased

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28
Q

What is MCH?

A

Mean corpuscular haemoglobin

Average mass of haemoglobin per red blood cell - reported as part of standard complete blood count.

MCH diminished in hypochromic anaemias

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29
Q

What are the main causes of iron deficiency?

A
  • blood loss (gut, PV, PU, resp tract etc)
  • increased demand (pregnancy, growth)
  • reduced intake (diet, malabsorption)
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30
Q

What are the main causes of iron deficiency in children?

A
  • diet
  • growth
  • malabsorption
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31
Q

What are the main causes of iron deficiency in young women?

A
  • menstrual loss/problems
  • pregnancy (causes long term deficiency afterwards)
  • diet
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32
Q

What are the main causes of iron deficiency in older people?

A
  • bleeding

- GI problems (ulcer, gastritis, aspirin, malignancy, diverticulitis, GI surgery etc)

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33
Q

What are the 3 different types of iron therapy?

A
  • oral iron
  • IM iron
  • IV iron
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34
Q

State the main features of each type of iron therapy

A
  • oral iron = unreliable
  • IM iron = painful and out of date
  • IV iron = increasingly used
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35
Q

What is megaloblastic anaemia?

A

Anaemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production - characteristic cell morphology caused by impaired DNA synthesis

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36
Q

What are the typical peripheral blood changes in megaloblastic anaemia?

A

Big red cells (high MCV)

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37
Q

What are the causes of megaloblastic change?

A
  • B12 and/or folic acid deficiency
  • alcohol
  • drugs
  • haematological malignancy
  • congenital rarities
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38
Q

What kinds of drugs can cause megaloblastic change?

A
  • cytotoxics
  • folate antagonists
  • n2o
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39
Q

What types of congenital disorders can cause megaloblastic change?

A
  • transcobalamin deficiency

- orotic aciduria

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40
Q

What is transcobalamin?

A

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

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41
Q

How do B12 and folate cause anaemia?

A
  • 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
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42
Q

How do we get vitamin B12?

A

Loads in most diets compared to needs but only from animal sources

Stores sufficient for some years

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43
Q

What is involved in vitamin B12 absorption?

A
  • gastric parietal cells
  • intrinsic factor
  • receptors in terminal ileum
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44
Q

What causes vitamin B12 deficiency?

A
  • nutritional (vegans)
  • gastric problems
  • small bowel problems
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45
Q

What type of gastric problems cause B12 deficient?

A
  • pernicious anaemia (autoimmune)

- gastrectomy

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46
Q

What type of small bowel problems cause B12 deficiency?

A
  • terminal ileal resection/Crohn’s
  • stagnant loops/jejunal diverticulosis
  • tropical sprue/fish tapeworm
47
Q

What foods contain folic acid?

A
  • green veg
  • beans
  • peas
  • nuts
  • liver

Required intake needs decent daily diet

48
Q

Where is folic acid absorbed?

A

Upper small bowel

49
Q

How much folic acid does the body store?

A

4 months body store

50
Q

What are the causes of folic acid deficiency?

A
  • mainly dietary/malnutrition
  • malabsorption/small bowel disease
  • increased usage
  • drugs/alcohol/ITU
51
Q

Increased usage may cause folic acid deficiency. Give examples

A
  • pregnancy
  • haemolysis
  • inflammatory disorders
52
Q

What are the features that are common to B12 or folate deficiency?

A
  • megaloblastic anaemia
  • can have pancytopenia if more severe
  • mild jaundice
  • glossitis/angular stomatitis
  • anorexia/weight loss
  • sterility
53
Q

What is pancytopenia?

A

Deficiency of all three cellular components of the blood (red cells, white cells, and platelets)

54
Q

What is glossitis?

A

Inflammation of the tongue

55
Q

What is angular stomatitis?

A

Inflammation of one, or more commonly both, of the corners of the mouth

56
Q

What are the lab tests for B12 + folate deficiency?

A
  • 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
Q

What is blind loop syndrome?

A

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
Q

What is the classic cause of B12 deficiency?

A

Pernicious anaemia

59
Q

What causes pernicious anaemia?

A

Antibodies to parietal cells/intrinsic factor (so unable to absorb B12)

Autoimmune associations

60
Q

What is pernicious anaemia also related to?

A
  • atrophic gastritis
  • achlorhydria
  • increased risk of stomach cancer
61
Q

Who first described pernicious anaemia?

A

Thomas Addison

62
Q

What does SACDC stand for?

A

Subacute combined degeneration of the cord

63
Q

What happens in SACDC?

A
  • demyelination of the dorsal and lateral columns of the spinal cord
  • peripheral nerve damage
64
Q

What causes SACDC?

A

Severe B12 deficiency

Usually associated with pernicious anaemia but anaemia not an absolute requirement

65
Q

How does SACDC present?

A
  • peripheral neuropathy/paraesthesiae
  • numbness and distal weakness
  • unsteady walking
  • dementia
66
Q

What is the treatment for SACDC?

A
  • 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
Q

What are the key messages concerning iron, B12 and folate?

A
  • all common problems
  • multiple causes and links to consider
  • reasonably easy to diagnose and treat
  • attend to the underlying causes
68
Q

Put simply, what are the causes of haemolysis (shortened red cell life)?

A
  • things wrong inside red cell
  • things wrong with red cell membrane
  • things wrong external to red cell
69
Q

What are the causes of haemolysis inside the cell?

A
  • haemoglobinopathy (Sickle cell)

- enzyme defects (G6PD)

70
Q

What are the causes of haemolysis related to the membrane?

A
  • hereditary spherocytosis/elliptocytosis
71
Q

What are the causes of haemolysis external to the red cell?

A
  • antibodies (warm/cold)
  • drugs, toxins
  • heart valves
  • vascular/vasculitis/microangiopathy
72
Q

What are the tests for the presence of haemolysis?

A
  • anaemia (or not - compensated)
  • high MCV, macrocytic
  • high reticulocytes
  • blood film (fragments, spherocytes)
  • raised bilirubin, LDH
  • low haptoglobins
  • urinary haemosiderin
73
Q

What are reticulocytes?

A

Immature red blood cells without a nucleus, having a granular or reticulated appearance when suitably stained

74
Q

What is LDH and why is it a marker of haemolysis?

A

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
Q

What are haptoglobins?

A

The bind free hemoglobin (Hb) and so are low in haemolysis as they get used up

76
Q

How is the cause of haemolysis identified?

A
  • history + exam
  • drug history (alcohol/toxins/work)
  • positive DCT (evidence of antibody)
  • blood film
  • abnormal haemoglobins (eg. sickle)
  • membrane studies
  • enzyme studies
    ect
77
Q

What is a DCT?

A

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
Q

What is the general approach to diagnosis of haemolysis?

A
  • demonstrate that haemolysis is present
  • think about the causes
  • history + exam
  • work through the necessary tests
79
Q

What is AIHA?

A

Autoimmune haemolytic anaemia

80
Q

How is AIHA managed?

A

With steroids/immunosuppression

81
Q

Can you transfuse in haemolysis?

A

Can be tricky in AIHA (hard to cross match)

82
Q

What is anaemia of chronic disease?

A

A form of anemia seen in chronic infection and inflammation, chronic immune activation, and malignancy eg. DM, autoimmune etc

83
Q

What is the MCV in anaemia of chronic disease?

A

Typically normal MCV

84
Q

In anaemia of chronic disease, there is reduced red cell production due to what?

A
  • abnormal iron metabolism
  • poor erythropoetin response
  • blunted marrow response
85
Q

Which inflammatory cytokines are involved in anaemia of chronic disease?

A
  • IL1
  • IL6
  • TNF-alpha
86
Q

What is hepcidin?

A

A key regulator of iron absorption and release from macrophages

87
Q

What happens when hepcidin levels are high such as in inflammation?

A

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
Q

What are the main features of anaemia of chronic disease (ACD)?

A
  • 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
Q

Which inflammatory markers are often raised in ACD?

A
  • ESR
  • CRP
  • PV
    etc
90
Q

The effects of ACD are mediated by what?

A
  • cytokines

- hepcidin

91
Q

What are transferrins?

A

Iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. Bind iron tightly, but reversibly

92
Q

What is the treatment for ACD?

A
  • treat the cause if possible
  • erythropoetin/iron/IV
  • transfusion?
  • careful symptom assessment first
93
Q

What is thrombocytopenia?

A

Deficiency of platelets in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury

94
Q

What are the common causes of thrombocytopenia?

A
  • drugs, alcohol, toxins
  • ITP
  • autoimmune diseases
  • liver disease or hypersplenism
  • pregnancy
  • haematological and marrow diseases
  • infections
  • DIC
  • congenital conditions
95
Q

What is ITP?

A

Immune thrombocytopenic purpura - isolated low platelet count with normal bone marrow and the absence of other causes of thrombocytopenia

96
Q

What is hypersplenism? (cause of thromboyctopenia)

A

Condition in which the spleen becomes increasingly active and then rapidly removes the blood cells. It can result from any splenomegaly

97
Q

What types of infections can cause thrombocytopenia?

A
  • acute sepsis
  • HIV
  • other viral infections eg. EBV etc
98
Q

What does DIC stand for? (cause of thrombocytopenia)

A

Disseminated intravascular coagulation

99
Q

Give 3 different classifications of ITP

A
  • acute
  • chronic
  • relapsing
100
Q

ITP is a common immune disorder that can occur on its own or part of what?

A
  • other autoimmune disease
  • lymphomas/CLL
  • HIV
101
Q

How does thrombocytopenia/ITP present?

A
  • bruising or petechiae or bleeding

- low platelet count

102
Q

What platelet count is urgent?

A

under 10 = urgent
under 20 = a worry
under 30 = needs treatment
otherwise observe

103
Q

What is the first line treatment for thrombocytopenia/ITP?

A

Steroids

104
Q

Other that steroids, what are the other therapy types for thrombocytopenia/ITP?

A
  • IV immunoglobin
  • immunosuppressives or splenectomy
  • thrombo-mimetics
105
Q

What are thrombo-mimetics and give 2 examples

A

Have thrombopoetin-like properties

  • eltrombopag
  • romiplostin
106
Q

What is thrombopoetin?

A

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
Q

What is the outcome of treatment for ITP?

A
  • usually rapid responses
  • can relapse after therapy
  • rarely life-threatening
  • but commonly recurrent
  • some difficult refractory cases
108
Q

What is TTP (thrombotic thrombocytopenia purpura)?

A

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
Q

Most cases of TTP are what?

A

Immune (AMAMTS-13/VWD)

110
Q

Suspect TTP if thrombocytopenia and what else?

A
  • fever
  • neurological symptoms
  • haemolysis (retics, LDH)
111
Q

In TTP, you should seek evidence of what type of angiopathy?

A

Microangiopathy (blood film fragments)

112
Q

Urgent therapy for TTP includes what?

A
  • plasma exchange with FFP/plasma
  • steroids
  • (vincristine)
  • (rituximab)

Outcomes vary - can see relapses

113
Q

What must you monitor in TTP?

A

ADAMTS-13

8. CP - Core Haematology (11 decks)

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