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Y2 Clinical Pathology > Anaemia & Thrombocytopenia > Flashcards

Anaemia & Thrombocytopenia Flashcards

1
Q

What are some 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
  • malignant
  • haemoglobin disorders
  • aplasia
  • congenital
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2
Q

What is a hematinic?

A

a nutrient required for the formation of blood cells in the process of haematopoiesis

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3
Q

What is the MCV?

What does it measure and how is it calculated?

A

mean corpuscular volume

it measures the size and volume of a red blood cell

it can be used to determine the eitology of anaemia

it is calculated by multiplying the percentage haematocrit by ten and then dividing by the erythrocyte count

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4
Q

What are the 3 categories of anaemia depending on the MCV?

A

macrocytic:

  • B12, folate, metabolic (e.g. thyroid / liver disease)
  • marrow damage (alcohol, drugs, marrow disease)
  • haemolysis (due to reticulocytosis)

normocytic:

  • anaemia of chronic disease / inflammatory

microcytic:

  • iron deficiency
  • haemoglobin disorders
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5
Q

What is a very common cause of anaemia?

A

iron deficiency

the cause may matter more than the treatment

causes vary with age and sex

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6
Q

What is involved in iron balance?

How is it transported / stored?

Where is it absorbed?

A

it has no excretion and limited absorption

this is controlled at the level of the gut mucosa and most iron is recycled

it is absorbed in the duodenum and less so in the jejunum

it is transported by transferrin and stored in ferritin / haemosiderin

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7
Q

What is involved in the approach to treating iron deficiency anaemia?

A
  • establish that there is an iron deficiency
  • establish the cause of deficiency
  • treat the low iron and the cause
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8
Q

What lab tests are used to establish iron deficiency?

A
  • full blood count, indices and film
  • ferritin
  • % of hypochromic cells
  • serum iron / TIBC
  • marrow
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9
Q

What do the cells look like in anaemia caused by iron deficiency?

A

there are small pale red cells

there is low MCV and low MCH

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10
Q

What is MCV and MCH?

A

mean corpuscular volume:

  • measures the size and volume of a red blood cell
  • use in determining the etiology of anaemia

mean corpuscular haemoglobin:

  • average amount of haemoglobin found in the red blood cells in the body
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11
Q

What are the main causes of iron-deficiency anaemia?

A
  • blood loss from anywhere in the body
  • increased demand e.g. pregnancy, growth
  • reduced intake e.g. diet, malabsorption
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12
Q

What are the causes of iron deficiency anaemia in children?

A
  • diet
  • growth
  • malabsorption
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13
Q

What are common causes of iron deficiency anaemia in young women?

A
  • menstrual loss / problems
  • pregnancy
  • diet
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14
Q

What are the common causes of iron deficiency anaemia in older people?

A
  • bleeding
  • GI problems:
    • ulcer / gastritis / aspirin
  • malignancy
  • diverticulitis
  • GI surgery of various types
  • others
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15
Q

What are the 3 different types of iron therapy?

A
  • oral iron is often unreliable
  • IM iron is painful
  • IV iron is increasingly used
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16
Q

What is megaloblastic anaemia?

A

a characteristic cell morphology caused by impaired DNA synthesis

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17
Q

What do blood cells look like in megaloblastic anaemia?

A

large red blood cells with high MCV

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18
Q

What causes megaloblastic anaemia?

A

anaemia that results from inhibition of DNA synthesis during red blood cell production

when DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage

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19
Q

What are the causes of megaloblastic anaemia?

A
  • B12 and/or folic acid deficiency
  • alcohol
  • drugs - cytotoxics, folate antagonists, N2O
  • haematological malignancy
  • congenital rarities
  • transcobalamin deficiency
  • orotic aciduria
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20
Q

How do vitamin B12 and folate cause anaemia?

A
  • DNA consists of purine / pyramidine bases
  • folate is required for their synthesis
  • B12 is essential for cell folate generation
  • low folate or B12 starves DNA of bases
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21
Q

What is involved in vitamin B12 absorption?

Where does it come from?

A

absorption involves:

  • gastric parietal cells
  • intrinsic factor
  • receptors in terminal ileum
  • there is lots of B12 in most diets compared to needs, but only from animal sources
  • stores are sufficient for some years
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22
Q

In what conditions and circumstances is B12 deficiency seen?

A
  • nutritional - vegans
  • gastric problems
  • pernicious anaemia (autoimmune)
  • gastrectomy
  • small bowel problems
  • terminal ileum resection / Crohns
  • stagnant loops / jejunal diverticulosis
  • tropical sprue / fish tapeworm
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23
Q

Where is folic acid found?

How long do stores last for?

A

it is mainly in green vegetables, beans, peas, nuts and liver

the required intake needs a decent daily diet

it is absorbed in the upper small bowel and the body stores last for 4 months

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24
Q

What are the causes of folic acid deficiency?

A
  • mainly dietary / malnutrition
  • malabsorption / small bowel disease
  • increased usage
  • pregnancy
  • haemolysis
  • inflammatory disorders
  • drugs / alcohol / ICU
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25
Q

What are features common to B12 or folate deficiency?

A
  • megaloblastic anaemia
  • pancytopenia in more severe cases
  • mild jaundice
  • glossitis / angular stomatitis
  • anorexia / weight loss
  • sterility
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26
Q

What is pancytopenia?

A

a deficiency of all three cellular components of the blood

(red cells, white cells and platelets)

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27
Q

What is glossitis?

A

inflammation of the tongue

it causes the tongue to swell in size, change in colour and develop a different appearance on the surface

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28
Q

What are the lab features of B12 and folate deficiency?

A
  • blood count and film (sometimes marrow)
  • bilirubin and LDH - ‘haemolysis’
  • B12 and folate levels
  • antibodies
  • B12 absorption tests +/- IF
  • GI investigations for Crohn’s, malabsorption, blind loop etc.
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29
Q

What is the classic cause of B12 deficiency?

A

pernicious anaemia

30
Q

What is pernicious anaemia?

What causes it?

A

a deficiency in red blood cells caused by lack of vitamin B12 in the blood

vitamin B12 deficiency results from impaired uptake of vitamin B12 due to a lack of intrinsic factor produced by the stomach lining

31
Q

What is pernicious anaemia associated with?

A
  • antibodies to parietal cells / intrinsic factor
  • autoimmune associations
  • atrophic gastritis with achlorhydria
  • incidence of stomach cancer
32
Q

What is SACDC?

A

subacute combined degeneration of the cord

any cause of severe B12 deficiency

anaemia is not an absolute requirement

involves demyelination of dorsal + lateral columns and peripheral nerve damage

33
Q

How does SACDC present?

A
  • peripheral neuropathy / paraesthesiae
  • numbness and distal weakness
  • unsteady walking
  • dementia
34
Q
A
35
Q

What is meant by paraesthesia?

A

an abnormal sensation, typically tingling or prickling (‘pins and needles’) caused mainly by pressure on or damage to peripheral nerves

36
Q

What is shown here?

A

SACDC

subacute combined degeneration of the cord

37
Q

What is the treatment for SACDC?

A
  • B12 + folate until B12 deficiency is excluded
  • B12 is given x5 and then given every 3 monthly for life
  • folic acid is given 5mg daily to build stores
  • there may be a need for potassium and iron initially
38
Q

How is the response to treatment for SACDC monitored?

A
  • retics by day 7
  • blood count / MCV
  • neuropathy
39
Q

What is meant by ‘retics’?

A

reticulocyte count

this measures the levels of reticulocytes in the blood

it determines whether the bone marrow is producing enough red blood cells

40
Q

What are reticulocytes and where do they originate from?

A

immature red blood cells

in the process of erythropoiesis, reticulocytes develop and mature in the bone marrow

they circulate for about a day in the bloodstream before they develop into mature red blood cells

41
Q

What is haemolysis?

A

the rupture or destruction of red blood cells

this leads to a shortened red cell life

42
Q

What are the 3 broad categories of causes of haemolysis?

A
  • things wrong inside the red cell
  • things wrong with the red cell membrane
  • things wrong external to the red cell
43
Q

What are the common causes of haemolysis in each of the 3 categories?

A

inside the cell:

  • haemoglobinopathy (sickle cell)
  • enzyme defects (G6PD)

membrane:

  • hereditary spherocytosis / elliptocytosis

external to the cell:

  • antibodies (warm / cold)
  • drugs / toxins
  • heart valves
  • vascular / vasculitis / microangiopathy
44
Q

What is the main enzyme defect that causes haemolysis?

A

glucose - 6 - phosphate dehydrogenase (G6PD) deficiency

this is a genetic disorder that most often affects males

G6PD protects red blood cells from damage and premature destruction

45
Q

What is hereditary spherocytosis / elliptocytosis?

A

hereditary spherocytosis:

  • mutations in genes relating to membrane proteins
  • the erythrocytes change shape and become sphere-shaped

hereditary elliptocytosis:

  • an abnormally large number of red blood cells are ellipitical rather than the typical biconcave disc shape
46
Q

What is meant by “hot” and “cold” antibodies?

A

any red cell antibody that binds its target antigen best at levels below body temperature (37 C) is a “cold antibody”

“warm antibodies” react best at or near body temperature

47
Q

What tests are used to determine the presence of haemolysis?

A
  • anaemic
  • high MCV, macrocytic
  • high reticulocytes
  • blood film showing fragments / spherocytes
  • raised bilirubin & LDH
  • low haptoglobins
  • urinary haemosiderin
48
Q

What is haptoglobin?

What is its function?

A

it binds to free haemoglobin released from erythrocytes, inhibiting its oxidative activity

it forms a complex that is rapidly removed from the circulation by the liver, and the iron is recycled

49
Q

What does a low level of haptoglobin suggest?

A

a level below 45 mg / dl means that the red blood cells are being destroyed more quickly than they are being made

this is suggestive of haemolysis / anaemia

50
Q

What does urinary haemosiderin measure?

A

urinary haemosiderin reflects haemoglobinuria and suggests severe or intravascular haemolysis

urinary haemoglobin is reabsorbed by renal tubular cells and is processed to haemosiderin

51
Q

What tests are used to identify the cause of haemolysis?

A
  • history + exam
  • drug history incl alcohol, toxins, work
  • positive DCT (evidence of antibody)
  • blood film
  • abnormal haemoglobins
  • membrane studies
  • enzyme studies
52
Q

What is meant by a positive DCT?

What is an alternative name for this test?

A

Coombs’ test

it detects antibodies that act against the surface of red blood cells

the presence of these antibodies (postive test) indicated haemolytic anaemia

the blood does not contain enough red blood cells as they are destroyed prematurely

53
Q

What is the treatment for autoimmune haemolytic anaemia?

A

it is managed with steroids and immunosuppression

transfusion in haemolysis can be difficult as it is hard to cross match

54
Q

What is meant by anaemia of chronic disease?

A

a common general medical issue

can be malignant, inflammatory, infectious

present in multiple medical diseases including diabetes and autoimmune conditions

55
Q

What features are typically seen in anaemia of chronic disease?

Why is there reduced red cell production?

A

typically there is a normal MCV

reduced red cell production is due to:

  • abnormal iron metabolism
  • poor erythropoietin response
  • blunted marrow response
56
Q

What is hepcidin?

What is its role?

A

it is a regulator of iron metabolism

it inhibits iron transport by binding to the iron export channel (ferroportin)

this is located on the basolateral surface of gut erythrocytes and the plasma membrane of reticuloendothelial cells (macrophages)

57
Q

What are the effects of anaemia of chronic disease mediated by?

A

release of inflammatory cytokines:

  • IL1, IL6, TNF-alpha

Hepcidin:

  • regulator of iron absorption and release from macrophages
58
Q

What are the features of anaemia of chronic disease?

How is ferritin, iron and transferrin usually affected?

A
  • a suitable medical history and no other causes of anaemia
  • anaemia is usually mild with normal MCV
  • often raised inflammatory markers - ESR, CRP, PV
  • normal / high ferritin and low serum iron
  • normal % saturation of transferrin
59
Q

What are the treatment options for anaemia of chronic disease?

A
  • identify the cause if possible by a careful symptom assessment
  • erythropoietin / iron IV
  • potential transfusion
60
Q

What are common causes of thrombocytopenia?

A
  • drugs / alcohol / toxins
  • ITP
  • autoimmune diseases
  • liver disease and / or hypersplenism
  • pregnancy
  • haematological / marrow diseases
  • infections
  • disseminated intravascular coagulation (DIC)
  • range of congenital conditions
61
Q

What is ITP?

What is it associated with?

A

immune thrombocytopenic purpura

a bleeding disorder in which the immune system destroys platelets

associated with lymphoma / CLL / HIV

62
Q
A
63
Q

What are the different types of immune thrombocytopenic purpura (ITP)?

A

a common immune disorder that occurs on its own or as part of:

  • HIV
  • lymphomas / CLL
  • other autoimmune disease

it can be acute, chronic or relapsing

64
Q

What is the presentaion of immune thrombocytopenic purpura like?

A

present with bruising or petechiae or bleeding

platelet count can be anything

65
Q

What platelet counts should be looked for in immune thrombocytopenic purpura?

A

< 10 - urgent - query bleeding

<20 - concerning

< 30 - needs treatment

otherwise, platelet counts should be observed

66
Q

What are the different therapies used in immune thrombocytopenic purpura?

A
  • steroids are first line therapy
  • IV immunoglobulin
  • other immunosuppressives or splenectomy
  • thrombo-mimetics
67
Q

What are thrombomimetics?

What are the ones used in treatment for ITP?

A

they are newer drugs that have thrombopoeitin-like properties

eltrombopag and romiplostin are commonly used

68
Q

What is the outcome like for most cases of ITP?

A
  • usually rapid responses but can relapse after therapy
  • rarely life-threatening
  • commonly recurrent
69
Q

What is thrombotic thrombocytopenia purpura?

A

a rare blood disorder characterised by clotting in small blood vessels (thromboses)

this results in a low platelet count

most cases are immune and it requires an urgent diagnosis

70
Q

When should TTP be suspected?

What evidence should be looked for?

A

TTP should be expected if there is thrombocytopenia and:

  1. fever
  2. neurological symptoms
  3. haemolysis (retics / LDH)

seek evidence of microangiopathy from blood film fragments

71
Q

What is involved in the urgent therapy used to treat thrombotic thrombocytopenia purpura (TTP)?

A
  • plasma exchange with FFP/plasma
  • steroids
  • vincristine
  • rituximab
  • outcomes vary as there may be relapses so ADAMTS-13 is monitored
72
Q

What is the function of ADAMTS13?

A

it is a von-Willebrand factor-cleaving protease

it cleaves vWF, a large protein involved in blood clotting

Y2 Clinical Pathology (76 decks)

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