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Y2 MCD > Haematology > Flashcards

Haematology Flashcards

1
Q

Where are all blood cells derived from?

A
  • pluripotent haematopoietic stem cells in the bone marrow
  • these cells in turn came from lymphoid stem cells
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2
Q

What are the two brances of stem cell differentiation?

A
  • Multipotent Myeloid Stem Cells/Precursors -> granulocyte-monocytes, erythroid, megakaryocyte
  • Lymphoid Stem Cells -> T cells, B cells, NK cells
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3
Q

Describe normal erythrocyte maturation.

A
  • proerythroblasts have something in common: they have LARGE nuclei and small amounts of cytoplasm
  • as the red cells differentiate, the colour of the cytoplasm goes from dark blue to a more pink colour -> a mature red cell is completely pink
  • the process of producing red blood cells is called erythropoiesis
  • normal erythropoiesis requires the presence of erythropoietin which is synthesised mainly in the kidneys, in response to hypoxia but also partly made in the liver -> erythopeietin triggers bone marrow activity
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4
Q

What are the major triggers in erythropoiesis?

A

o Hypoxia is detected by the kidneys

o This leads to an increase in erythropoietin synthesis

o This increases bone marrow activity

o This leads to an increase in red cell production

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5
Q

What is the process of producing red blood cells called?

A
  • erythropoiesis
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6
Q

Where is erythropoietin produced?

A
  • mainly in the juxta-tubular interstitial cells of the kidney
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7
Q

What is RBCs adaptaion to not having a nucleus?

A
  • an extensive cytoskeleton
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8
Q

Describe the destruction of RBCs?

A
  • a cells get older they become less flexible and therefore less able to squeeze through the wall so they get held up in the spleen and destroyed
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9
Q

What does Anisocytosis mean?

A
  • RBCs that show more variation in SIZE than normal
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10
Q

What does Poikilocytosis mean?

A
  • RBCs that show more variation in SHAPE than normal
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11
Q

What terms are given to cells depending on their size?

A
  • smaller than normal = microcytic
  • normal = normocytic
  • larger than normal = macrocytic
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12
Q

Define hypochromia

A
  • RBCs that have a larger area of central pallor than normal
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13
Q

What is the usual cause of hypochromia?

A
  • a low haemoglobin content and conc. causing a flatter cell
  • consequently hypochromia often goes along with microcytosis
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14
Q

How do hypochromic cells appear under a microscope?

A
  • a rim of red around the cell is visible but its mainly pale
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15
Q

Define hyperchromia.

A
  • RBCs that lack a central pallar
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16
Q

What are the two important types of hyperchromatic cells?

A
  • spherocytes
  • irregularly contracted cells
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17
Q

Describe spherocytes

A
  • RBCs that are approximately spherical in shape
  • they have a round regular outline and lack central pallor
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18
Q

How do spherocytes develop

A
  • result from loss of cell membrane without the loss of an equivalent amount of cytoplasm -> cell is forced into a spherical form over time via intermediate shapes
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19
Q

Name a disease that cause the formation of spherocytes.

A
  • hereditary spherocytosis
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20
Q

Why is it difficult to diagnosis spherocytes by looking through a microscope?

A
  • not all the RBCs will be spherical
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21
Q

Describe irregularly contracted cells.

A
  • irregular in outline and smaller than normal cells
  • they have also lost their central pallor
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22
Q

Name a disease that is linked with irregularly contracted cells.

A
  • sepsis
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23
Q

How do irregularly contracted cells usually develop?

A
  • result from oxidant damage to cell membranes and haemoglobin
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24
Q

What is polychromasia?

A
  • an increased blue tinge to the cytoplasm of a red cell
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25
Q

What causes polychromasia?

A
  • as red cells mature they go from being dark blue to pink
  • the blue tinge to the cells in polychromasia indicates that the cells are young
  • reticulocytes are RBCs that are slightly younger than the proper mature cells -> these can be stained with methylene blue
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26
Q

What is the normal range of blue tinged RBCs when stained with methylene blue?

A
  • 1-2%
  • anymore suggests major blood loss
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27
Q

State six examples of polikilocytosis

A
  • spherocytes
  • irregularly contracted cells
  • sickle cells
  • target cells
  • elliptocytes
  • fragments
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28
Q

What are target cells?

A
  • cells with an accumulation of haemoglobin in the middle of the central pallor -> hence they look like a target
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29
Q

When do target cells occur?

A
  • OBSTRUCTIVE JAUNDICE – main cause
  • liver disease
  • haemoglobinopathies
  • hyposplenism
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30
Q

What are elliptocytes?

A
  • RBCs that are elliptical in shape
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31
Q

When do elliptocytes occur?

A
  • hereditary elliptocytes
  • iron deficiency
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32
Q

How is it possible to differentiate between hereditary elliptocytosis and iron deficiency anaemia?

A
  • in anaemia the cells are elliptical and hypochromic
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33
Q

What causes sickle cell formation?

A
  • polymerisation of haemoglobin S in a high concentration
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34
Q

What are RBC fragments (schistocytes)?

A
  • small pieces of RBCs that can cause turbulent flow
  • tend to have the RBC colour and sometimes even the central pallor - its just the shape that is different/obviously not a full cell
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35
Q

What is Rouleaux?

A
  • stacks of RBC, resembling piles of coins
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36
Q

What causes Rouleaux?

A
  • alteration in plasma proteins pushes the cells together
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37
Q

What are Agglutinates?

A
  • irregular clumps of RBC resulting from antibodies sticking them together
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38
Q

What are Howell-Jolly Bodies?

A
  • nuclear remnants remaining in RBCs
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39
Q

What is the most common cause of Howell-Jolly Body?

A
  • lack of splenic function -> spleen is falling to remove the tiny remaining parts of nuclear material
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40
Q

Describe Neutrophils.

A
  • main function is defence against infection via phagocytoses of micro-organisms
  • bi/mulit-lobed nucleus
  • survives for 7-10 hours in circulation
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41
Q

Describe Eosinophils.

A
  • main function is defence against Parasitic infection
  • bi-lobed nucleus
  • lasts a few hours in circulation
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42
Q

Describe Basophils.

A
  • role in allergic responses
  • granulated nucleus
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43
Q

Describe Monocytes.

A
  • develop into macrophages which have specialised phagocytic function
  • macrophages also store and release iron from digested haemoglobin
  • large cells with kidney shaped nucleus
  • can survive several days in circulation
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44
Q

Describe Platelets.

A
  • cells derived from megakaryocytes
  • role in primary haemostasis -> forms a platelet plug (aspirin inhibits this)
  • can survive for up to 10 days in circulation
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45
Q

Describe Lymphocytes.

A
  • lymphoid stem cell gives rise to B cells, T cells and NK cells
  • recirculate to the lymph nodes and other tissues and then back to the blood stream
  • intravascular life span of lymphocytes is very variable
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46
Q

Define leucocytosis.

A
  • too many WBCs
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47
Q

Define leucopenia.

A
  • too few WBCs
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48
Q

Define neutrophilia

A
  • too many neutrophils
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49
Q

Define neutropenia.

A
  • too few neutrophils
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50
Q

Define lymphocytosis.

A
  • too many lymphocytes
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51
Q

Define eosinophilia.

A
  • too many eosinophils
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52
Q

Define Thrombocytosis.

A
  • too many platelets
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53
Q

Define Thrombocytopenia.

A
  • too few platelets
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54
Q

Define Erythrocytosis.

A
  • lots of RBCs
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55
Q

Define Reticulocytosis.

A
  • lots of reticulocytes
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56
Q

Define Lymphopenia.

A
  • decrease in the number of lymphocytes
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57
Q

In terms of haematology, what is left shift?

A
  • an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood
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58
Q

What is toxic granulation?

A
  • heavy granulation of neutrophils resulting from infection, inflammation and tissue necrosis
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59
Q
A
  • yes, large space between the cells
  • arrowed is a macrocyte
  • neutrophil is hypersegmented.
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60
Q
A
  • hyperchromic - irregularly contracted cells
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61
Q
A
  • Howell-Jolly Body
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62
Q
A
  • target cell, fragment, Howell-Jolly Body
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63
Q

What does left shift suggest?

A
  • fighting of an infection -> shows that the bone marrow is chucking out lots of lymphocytes
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64
Q

When toxic granulation expected to be seen?

A
  • in a normal pregnancy
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65
Q

What are hypersegmented neutrophil?

A
  • an increase in the average number of neutrophil lobes or segments
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66
Q

When does hypersegmentation of neutrophils occur?

A
  • when there is a lack of Vitamin B12 or folic acid
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67
Q
A
  • sickle cell
  • cells starting to sickle
  • Howell-Jolly Body (indicates hyposplenism)
  • hyposplenic patient with sickle cell anaemia
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68
Q
A
  • all of them
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69
Q
A
  • tear drop cell
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70
Q
A
  • high
  • EDIT THIS
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71
Q
A
  • high WBC count. Neutrophils. Monocytes. They have an infection. Agglutinates. Polychromatic
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72
Q
A
  • its a spherocyte -> loss of membrane
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73
Q

How do you interpret a blood count?

A

1) is there leucocytosis or leucopenia?
- if so, why?
- which cell line is abnormal?
- are there any clues in the clinical history?
2) is there anaemia?
- if so, are there any clues in the blood count?
- are the cells large or small?
- are there any clues in the clinical history?
3) is there thrombocytosis or thrombocytopenia?
- if so, are there any clues in the blood count?
- are there any clues in the clinical history?

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74
Q

What is the difference between pseudo and true polycythaemia?

A
  • pseudo = reduced plasma volume
  • true = increase in total volume of red cells in the circulation
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75
Q

What is anaemia?

A
  • a reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender
  • RBC and HCT are usually also reduced
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76
Q

Besides from anaemia what is another cause of low haemoglobin concentration?

A
  • increased plasma volume
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77
Q

What are the 4 mechanisms of anaemia?

A
  • reduced production of red blood cells/haemoglobin in the bone marrow
  • loss of blood from the body (haemorrhage)
  • reduced survival of red blood cells in the circulation (haemolytic)
  • pooling of red blood cells in a very large spleen (splenomegaly)
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78
Q

Is microcytic anaemia usually hypochromic, normochromic or hyperchromic?

A
  • usually hypochromic
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79
Q

Is noromocytic anaemia usually hypochromic, normochromic or hyperchromic?

A
  • usually normochromic
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80
Q

Is macrocytic anaemia usually hypochromic, normochromic or hyperchromic?

A
  • usually normochromic
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81
Q

What are the common causes of microcytic anaemia?

A

o Defect in HAEM synthesis

  • iron deficiency -> mainly due to diet but can be lack of iron to compensate for blood loss
  • anaemia of chronic disease -> chronic inflammation (rheumatoid arthritis)

o Defect in GLOBIN synthesis (THALASSAEMIA)

  • defect in ALPHA chain synthesis (alpha thalassaemia)
  • defect in BETA chain synthesis (BETA thalassemia)
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82
Q

What is a megaloblast?

A
  • an abnormal bone marrow erythroblast
  • are larger than normal
  • shows nucleo-cytoplasmic dissociation
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83
Q

What cause megaloblast formation?

A
  • in the megaloblasts, the nuclear development is not matching the cytoplasmic development
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84
Q

HOw is it possible to determine between macrocytic and megaloblastic anaemia?

A
  • bone marrow must be sampled to be sure
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85
Q

What are the common causes of macrocytic anaemia?

A
  • megablastic anaemia as a result of laco of Vitamin B12 or Folic Acid
  • drugs that interfere with DNA synthesis -> chemo
  • liver disease and ethanol toxicity
  • recent major blood loss
  • haemolytic anaemia
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86
Q

What are the common mechanisms for normocytic, normochromic anaemia?

A
  • recent blood loss
  • failure of production of RBCs
  • pooling of RBC in the spleen
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87
Q

Name some causes of blood loss.

A
  • trauma
  • oesophageal varices
  • peptic ulcer
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88
Q

Name some causes of failure of production of RBCs.

A
  • early stages of iron deficiency
  • anaemia of chronic disease
  • bone marrow failure/suppression
  • bone marrow infiltration
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89
Q

Name a cause of hypersplenism.

A
  • portal cirrhosis
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90
Q

Define haemolytic anaemia

A
  • anaemia resulting from shortened survival of RBCs in the circulation
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91
Q

Name three ways in which haemolytic anaemia is classified

A

o intrinsic and extrinsic

  • intrinsic = abnormality of RBC
  • extrinsic = factor that acts on normal cells

o inherited and acquired

  • inherited = results from abnormalities of cell membranes, haemoglobin or enzymes within the RBC
  • acquired = extrinsic factors such as micro-organisms, chemicals or drugs

o intravascular and extravascular

  • intra = very acute damage to RBC (haemoglobin in urine)
  • extra = defective RBC removal by the spleen
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92
Q

Name the important deficiencies when talking about Haemolytic Anaemia?

A

o glucose-6-phosphate dehydrogenase deficiency

  • produce less ATP therefore cells are prone to burst in states of oxidative stress

o pyruvate kinase deficiency

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93
Q

When would you suspect haemolytic anaemia?

A

o evidence of morphologically abnormal RBCs

o evidence of increased RBC breakdown

o evidence of increased bone marrow activity

o JAUNDICE

o GALLSTONES

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94
Q

Name an inherited haemolytic anaemia with a membrane defect.

A
  • hereditary sphereocytosis
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95
Q

Name an inherited haemolytic anaemia with a haemoglobin defect.

A
  • sickle cell anaemia
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96
Q

Name an inherited haemolytic anaemia with a glycolytic pathway defect.

A
  • pyruvate kinase deficiency
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97
Q

Name an inherited haemolytic anaemia with a pentose shunt defect.

A
  • glucose-6-phosphate dehydrogenase deficiency
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98
Q

Name an acquired haemolytic anaemia with a membrane defect.

A
  • autoimmune haemolytic anaemia
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99
Q

Name an acquired haemolytic anaemia with a whole cell, mechanical defect.

A
  • microangiopathic haemolytic anaemia
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100
Q

Name an acquired haemolytic anaemia with a whole cell, oxidant defect.

A
  • drugs and chemicals
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101
Q

Name an acquired haemolytic anaemia with a whole cell, microbiological defect.

A
  • malaria
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102
Q

What is hereditary spherocytosis?

A

o a chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell membrane

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103
Q

Give some diagnoses for high Hb, high RBC and high HCT.

A

o decrese in plasma volume -> pseudopolycythaemia or apparent polycythaemia

o increase in number of circulating cells -> true polycythaemia

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104
Q

How is microangiopathic haemolytic anaemia treated?

A

o removing the cause, e.g. treating severe hypertension or stopping a causative drug

o plasma exchange when it is caused by an antibody

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105
Q

What are causes of polycythaemia?

A

o blood doping

o too much erythropoietin - can be appropriately elevated at high altitude

o erythropoietin can be inappropriately administered to normal subjects (doping)

o tumour - a renal, liver or other tumour can secrete inappropriate levels of EPO

o abnormal function of the bone marrow - polycythaemia can result from

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106
Q

Name a problem that polycythaemia can lead to.

A

o hyperviscosity of the blood -> vascular obstruction

  • if no physiological reason for a high haemoglobin, or if hyperviscosity is extreme, blood can be removed to thin the blood (venesection)
  • if there is an intrinsic bone marrow disease, drugs can be used to reduce the production of red blood cells by the bone marrow
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107
Q
A

o Iron Deficiency

  • B12 and folate deficiency you would expect it to be macrocytic
  • haemolysis and blood loss are normocytic
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108
Q
A

o Renal Carcinoma

  • haemolysis will give you dark urine because there is lots of bilirubin
  • chronic renal failure and haemolysis do NOT cause polycythaemia (haemolysis causes anaemia)
  • other three options can cause polycythaemia but the only one where you could get blood in the urine is renal carcinoma
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109
Q

What is the Betas?

A
  • point mutation at codon 6 of the gene for BETA GLOBIN
  • glutamic acid is replaced by valine
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110
Q

What chains are present in Sickle Haemoglobin?

A
  • TWO NORMAL ALPHA CHAINS and TWO VARIANT BETA CHAINS
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111
Q

What is the problem with glutamic acid replacing valine in the beta chain?

A

o Glutamic Acid

  • polar
  • soluble

o Valine

  • non-polar
  • insoluble
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112
Q

How does the distortion of RBC shape occur in SCD?

A
  • HbS polymerises to form fibres called tactoids
  • deoxyhaemoglobin can form intertetrameric contacts to stabilise the structure -> long polymers form within the red cell -> causes the distortion and damage to the red cells
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113
Q

What changes occur to membranes of RBCs in SCD?

A
  • membrane expresses a different profile of adhesion molecules which makes the red cells stick to the vascular endothelium
  • cells appear to have little projections in the cell membrane though they seem to maintain their biconcave shape
  • t is probably caused by short chains of polymers projecting through the inner surface of the cell membrane
  • this polymerisation eventually gives rise to the sickle shape
  • THIS MECHANISM IS NOT FULLY UNDERSTOOD
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114
Q

What are the 3 key differences between SCD cells and normal RBCs?

A

SCD RBCs are

  • more rigid
  • more adherent
  • dehydrated
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115
Q

What does Sickle Cell Disease mean?

A
  • a generic term that encompasses sickle cell anaemia and all other conditions that can lead to a disease syndromes due to sickling
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116
Q

What is the most common SCD?

A
  • Sickle Cell Anaemia (homozygous - SS)
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117
Q

Summarise the pathogenesis of Sickle Cells.

A
  • whenever red cells distort, due to age or disease, they are removed from the body
  • normal red blood cells have a life span of 120 days but sickled cells only last for up to 20 days
  • this reduction in the life span of red cells leads to increased haemolysis
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118
Q

What are the consequences of the increased haemolysis

A
  • anaemia
  • gallstones
  • aplastic crisis (parvovirus B19)
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119
Q

Explain how increased haemolysis is linked with anaemia?

A
  • anaemia is partly due to a reduced erythropoietic drive as haemoglobin S has a low affinity for oxygen, so it delivers oxygen more effectively to tissues
  • hypoxia doesn’t stimulate the erythropoietin release from the kidneys as much
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120
Q

Describe how increased haemolysis causes gallstones.

A
  • increased haemolysis -> increase in the release of bilirubin and other red cell breakdown products -> excreted through the gallbladder and risks causing gallstones
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121
Q

Describe how aplastic crisis can occur in patients with SCD.

A
  • parvovirus B19 is a common respiratory virus which doesn’t normally produce any significant haematological sequelae but can cause aplastic crisis in people with SCD
  • parvovirus B19 infects the developing RBCs in the bone marrow and blocks their production for up to 10 days
  • normal RBCs have a life span of 120 days, so if parvovirus switches off red cell production for a few days until the virus clears, it won’t have any big effects
  • but because the life span of sickled RBCs is so low, a parvovirus infection in people with SCD can lead to a steep drop in haemoglobin (ANAEMIA)
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122
Q

What is the problems associated with blockage of microvascular circulation (vaso-occlusion)?

A
  • tissue damage and necrosis -> INFARCTION
  • PAIN
  • DYSFUNCTION
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123
Q

What is the vital problem with tissue infarction?

A
  • spleen -> leads to vunerabitility to capsulated bacteria (particularly pneumococcal)
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124
Q

What is the most site of tissue infarction?

A
  • bones and joints
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125
Q

How does infarction to bones and joints usually present and what longer consequences are?

A
  • presents with DACTYLITIS (inflammation of a finger or toe caused by bone infection) - this is painful
  • over time, chronic ischaemic damage can lead to avascular necrosis (death of bone tissue due to lack of blood supply)
  • also susceptible to osteomyelitis (inflammation of the bone due to infection)
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126
Q

What is the commonest cause of death in adults with SCD?

A
  • acute chest syndrome -> a vaso-occlusive crisis of the pulmonary vasculature
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127
Q

What are the long-term effects of SCD in on the lungs?

A
  • pulmonary hypertension
  • chronic sickle cell lung disease
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128
Q

What are the effects of SCD on the urinary tract?

A
  • haematuria (from papillary necrosis)
  • hypostheuria
  • renal failure
  • priapism -> persistent and usually painful erection of the penis that requires urgent decompression (sometimes it may not be painful and so isn’t as urgent)
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129
Q

What are the consequences of SCD on the brain?

A
  • stroke
  • cognitive impairment
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130
Q

How can the eyes be damaged due to SCD?

A
  • proliferative retinopathy
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131
Q

Which group of patients, of whom have SCD, are most likely to be effected by a stroke?

A
  • 2-9 year olds
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132
Q

How do strokes occur in patients suffering from SCD?

A
  • involves major cerebral vessels (middle cerebral and intra-cranial internal carotid arteries)
  • NOT MICROVASCULAR LIKE OTHER LINKED VASCULAR PROBLEMS
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133
Q

What is the earliest in life you would expect to see symptoms of SCD?

A
  • 3-6 months -> when you get a switch from foetal to adult haemoglobin
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134
Q

What are the early manifestations of SCD?

A
  • dactylitis
  • splenic sequestration - acute condition of intra-splenic pooling of large amounts of blood -> causes rapid enlargement of the spleen
  • infection
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135
Q

What are the triggers of painful crises?

A

o Infection

o Exertion

o Dehydration

o Hypoxia

o Psychological Stress

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136
Q

What are the median survival times for males and females with SCD?

A
  • males = 42 years
  • females = 48 years
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137
Q

What are the general mesurements taken in the management of SCD?

A

o Folic Acid Supplementation -> suffers have a high production of red blood cells so they need to have adequate folate levels

o Penicillin -> started aged 3 months to reduce the risk of life-threatening pneumococcal infection

o Vaccination -> against organisms that individuals with hyposplenism are susceptible to

o Monitoring of Spleen Size -> splenic sequestration is a potential cause of death in young people (parents are taught how to monitor spleen size)

o Blood transfusion for acute anaemia events, acute chest syndrome and stroke

o Pregnancy care

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138
Q

NAme the prevention against early mortality from SCD.

A

o prophylaxis against pneumococcal infection

o monitoring for acute splenic sequestration

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139
Q

Describe the what management occurs in a painful crisis.

A

o pain relief (opioids)

o hydration

o keep warm

o oxygen if hypoxic

  • blood and urine cultures
  • chest x-rays
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140
Q

In what scenarios is exchange transfusions carried out on patients suffering from SCA?

A

o Stroke -> risk of recurrent stroke in children with sickle cell anaemia is very high so they should keep having regular transfusions

o Acute chest syndrome (fever, cough, chest pain, tachypnoea)

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141
Q

What SCD patients are offered Haematopoietic Stem Cell Transplantation?

Also state the treatments effectiveness.

A
  • children <16 with severe disease
  • 85-90% curative
  • 90-95% survival
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142
Q

What are the problems with Haematopoietic Stem Cell Transplantation?

A
  • few children have perfectly matched donors -> treatment only available to a small subset
  • infertility
  • pubertal failure
  • chronic GvHD (Graft vs Host Disease)
  • organ toxicity
  • secondary malignancies
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143
Q

How does hydroxyurea work as a treatment for SCD?

A
  • is cytotoxic - it is a ribonucleotide reductase inhibitor
  • induces the production of RBCs in the bone marrow that mainly contain HbF -> over time there is an increase in the number of red cells that are UNABLE to sickle
  • other effects such as reducing the adhesion to the vascular endothelium
  • significantly reduces the frequency of crises
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144
Q

Name and describe a non-definitive diagnostic test for Sickle Cell Anaemia?

A
  • SOLUBILITY TEST
  • -n the presence of a reducing agent, oxyhaemoglobin is converted to deoxyhaemoglobin -> solubility decreases -> solution becomes turbid
  • does NOT differentiate between AS and SS
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145
Q

Name a definitive diagnostic test for Sickle Cell Anaemia?

A
  • ELECTROPHORESIS
  • HIGH-ERFORMANCE LIQUID CHROMATOGRAPHY
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146
Q

What are the laboratory features of SCD?

A
  • low Hb (6-8g/dL)
  • high reticulocytes
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147
Q

Describe SC trait.

A
  • genotype: HbAS
  • normal life expectancy
  • normal blood count
  • usually asymptomatic
  • rarely painless haematuria -> due to papillary necrosis
  • under conditions of hypoxia they may have some complications due to sickling of red blood cells e.g. anaesthesia, high altitude, extreme exertion
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148
Q

True or False. Sickle Cell Anaemia includes both HbSS and HbAA

A

False -> only HbSS is SCA

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149
Q

True or False. Sickling is due to a change in the alpha globin chain.

A

False -> its the beta chain

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150
Q

True or False. The molecular alteration is a deletion which protects against malaria.

A

False - it is a missense not a deletion

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151
Q

True or False. Sickle Hb makes RBCs less deformable

A

True

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152
Q

True or False. Clinical manifestations may start in utero.

A

False -> there isnt any beta-globin in fetal Hb

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153
Q

True or False. Osteomyeltis is the name given to inflammation of a digit.

A

False -> it is Dactylitis

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154
Q

True or False. Women with HbSS have a normal life expectancy.

A

False

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155
Q

True or False. Chest crises maybe fatal.

A

True

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156
Q

True or False. Solubility tests are used to confirm SCA if screening tests are positive.

A

False -> simply show presence of mutated gene (could be carrier)

  • electrophoresis is used
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157
Q

True or False. If a lady with HbAS has a partner with HbSS she should be offered genetic counselling.

A

True

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158
Q

What is the normal range of RBC count?

A

3.5-5x1012/L

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159
Q

What is the normal concentration of Hb in adults?

A

120-165g/L

  • each Nh contains 3.4mg of Fe
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160
Q

How much Hb is produced and destroyed each day?

A
  • 90mg/kg
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161
Q

Where are the components of Hb synthesised?

A
  • haem = mitochondria
  • globin = ribosomes
162
Q

Describe the structure of Hb.

A
  • combination of protoporphyrin ring with central iron atom (ferroprotoporphyrin)
  • iron usually in ferrous form (Fe2+)
163
Q

Which enzyme regulates haem synthesis?

A
  • ALAS
164
Q

Describe the globin structure in Hb.

A

o Primary

  • α = 141 aa
  • non-α = 146 aa

o Secondary

  • 75% α and b chains-helical arrangement

o Tertiary

  • approximate sphere with hydrophilic surface (charged polar side chains) and hydrophobic core
  • haem pocket
165
Q

What is the name of the phenomenon that leads to the sigmoid shape of oxy-Hb dissociation curves?

A
  • co-operative binding -> when one binds it becomes easier for others to bind and so on
166
Q

What is the P50 in adult Hb?

A

26.6mmHg

167
Q

What factors shift the curve to the right?

A

o High 2,3-DPG

o High H+

o High CO2

o HbS

168
Q

What factors shift the curve to the left?

A

o Low 2,3-DPG

o HbF

169
Q

What are the two classes of Haemoglobinpathies?

A
  • structural variants of haemoglobin
  • defects in globin chain synthesis (thalassaemia)
170
Q

What is beta-thalassaemia?

A
  • a deletion or mutation in beta globin gene causing a reduced or absent production of beta globin chains
171
Q

What is the difference between betao and beta + thalassaemia?

A
  • betao = no beta globin is produced
  • beta+ = some mutated beta globin is produced
172
Q

How is thalassaemia diagnosed in a lab?

A

o FBC = microcytic hypochromic indices and increased RBCs relative to Hb

o Film = target cells, poikilocytosis but no anisocytosis

o Hb EPS/HPLC = a-thal -> normal HbA2 & HbF, +/- HbH

b-thal -> raised HbA2 & raised HbF

o Globin Chain synthesis/DNA studies = gnetic analysis for β-thalassaemia mutations and XmnI polymorphism (in β-thalassaemias) and α-thalassaemia genotype (in all cases)

173
Q

What is the major complication of beta thalassaemia major and when does it present?

A

o severe anaemia -> incompatible with life without regular blood transfusions

o clinical presentation usually after 4-6 months of life when beta chains start to take over

174
Q

What are the clinical presentations of thal-major?

A
  • severe anaemia usually presenting after 4 months
  • hepatosplenomegaly
  • blood film shows gross hypochromia, poikilocytosis and many NRBCs
  • bone marrow -> erythroid hyperplasia
  • extra-medullary haematopoiesis
  • chronic fatigue
  • failure to thrive
  • jaundice
  • delay in growth and puberty
  • skeletal deformity
  • iron overload
175
Q

What complications occur with thal-major?

A
  • cholelithiasis and biliary sepsis
  • cardiac failure
  • endocrinopathies
  • liver failure
176
Q

What is the prominent cause of death in beta-thal-major?

A
  • cardiac disease -> due to iron overload
177
Q

What are the treatments for thal-major?

A
  • regular blood transfusions
  • iron chelation therapy
  • splenectomy
  • supportive medical care
  • hormone therapy
  • hydroxyurea to boost HbF
  • bone marrow transplant -> curative
178
Q

Describe transfusions as a treatment for thal.

A
  • phenotyped red cells
  • aim for pre-transfusion Hb 95-100g/L
  • regular transfusion 2-4 weekly
  • if high requirement, consider splenectomy
179
Q

When is iron chelation therapy started in thalassemia?

A
  • after 10-2 transfusions or when serum ferritin >1000mcg/l
180
Q

What are the three iron chelators currently available?

A
  • DFO
  • deferiprone
  • deferazirox
181
Q

What is the dose of deferasirox?

A
  • 20-40mg/kg orally
  • once a day
182
Q

What are the side effects of deferasirox?

A
  • rashes
  • Gi symptoms
  • hepatitis
  • renal impairment
183
Q

What is the dose for desferrioxamine?

A
  • 20-50mg/kg/day IV
  • 8-12 hours for 5-7 days a week
184
Q

What is the dose for deferiprone?

A
  • 5-100mg/kg/day orally
  • 3 times a day
185
Q

What is deferiprone particularly effective at?

A
  • reducing myocardial iron
186
Q

Name some side effects of deferiprone.

A
  • GI disturbance
  • hepatic impairment
  • neutropenia
  • agranulocytosis
  • arthropathy
187
Q

What is alpha thalassaemia?

A
  • deletion or mutation in alpha globin gene leading to a reduced or absent production of a globin chains
  • affects both foetus and adult
  • excess b and g chains form tetramers of HbH and Hb Barts respectively
  • severity depends on number of a globin genes affected (4 from 4 results in embryonic death)
188
Q

What are the preventative measures against thalassaemia?

A
  • screening
189
Q

Define Lymphoid.

A
  • relating to or denoting the tissue responsible for producing lymphocytes
190
Q

What factors regulate cell numbers?

A
  • cytokines
  • chemokines
  • hormones
191
Q

Define Leukaemia.

A

o a malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leukocytes. This leads to suppression of the production of other blood cells such as erythrocytes, granulocytes and platelets.

192
Q

Define Lymphoma.

A

o any group of blood cell tumours that develop from lymphatic cells. If the disease is mainly in the lymphatic tissue then it is lymphoma, if it is mainly in the blood it is leukaemia

193
Q

Define Myeloma.

A

o a malignant disease of the bone marrow characterised by two or more of the following criteria:

  • presence of an excess of abnormal malignant plasma cells in the bone marrow
  • typical lytic deposits in the bones on X-ray, giving the appearance of holes
  • presence in the serum of an abnormal gammaglobulin, usually IgG
194
Q

What are the causes of increased WBCC?

A

o increased cell production

  • reactive -> infection, inflammation
  • malignant -> leukaemia, myeloproliferative

o cell survival

  • failure of apoptosis
195
Q

What are the causes of decreased WBCC?

A

o cell production

  • B12 or folate deficiency
  • bone marrow failure -> aplastic anaemia, post-chemo, metastatic cancer, haematological cancer

o cell survival

  • immune breakdown
196
Q

How to investigate a raised WCC?

A
  • history and examination
  • haemoglobin and platelet count
  • automated differential
  • examination of blood film
  • abnormality in the white cells only or is it in all THREE lineages? (red cells, platelets, white cells)
  • if white cell count is raised, is only 1 cell type raised or all the lineages?
197
Q

What should be suspected if immature cells appear in the blood film?

A
  • leukaemia
198
Q

What is the difference in blood films between infection and leukaemia?

A
  • both have high WCC
  • infection = granular neutrophils, leukaemia = neutrophils without granules
  • leukaemia also has myelocytes and metamyelocytes
199
Q

What should be suspected if only immature cells with low Hb and platelets appear in the film?

A
  • acute leukaemia
200
Q

Name some causes of neutrophilia.

A

o INFECTION

o tissue Inflammation (e.g. colitis, pancreatitis)

o physical Stress

o adrenaline

o corticosteroids

o underlying neoplasia (e.g. lung cancer)

o malignant neutrophilia

  • myeloproliferative disorders
  • chronic myeloid leukaemia
201
Q

What can be deduced if the neutrophil count is low but there are other features of infection?

A
  • viral infection -> brucella, typhoid
202
Q

What are some causes of eosinophilia?

A

o Reactive -> parasitic infection, allergic diseases (asthma, rheumatoid, polyarteritis, pulmonary eosinophylia), neoplasms (Hodgkin’s, Non-hodgkin’s lymphoma), hypereosinophilic syndrome

o Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene)

203
Q

What are the markers of Hodgkin’s Disease?

A

o increased mediastinal mass on the chest X-ray

o secretion of interleukin 5 which stimulates a reactive eosinophilia

o a mutation in the GM-CFC eosinophilia which then expands the eosinophils

204
Q

Name some causes of monocytosis.

A
  • TB, brucella, typhoid
  • CMV (cytomegalovirus), varicella zoster
  • sarcoidosis
  • chronic myelomonocytic leukaemia (MDS - myelodysplastic syndrome)
205
Q

Differentiate between the right and the left blood films.

A
  • LEFT:

o The cells are very similar to each other

o They have the typical appearance of a mature lymphocyte with a BIG NUCLEUS with little cytoplasm

o This is typical of chronic lymphocytic leukaemia (CLL)

o If you have an oligoclonal expansion then all the cells will look alike

o The lymphocytosis with cells looking like those in the left image can also be achieved in the case of autoimmune or inflammatory conditions

  • RIGHT:

o The immature lymphoblasts are much LARGER than the mature lymphocytes

o Within the large nucleus you can see the nucleolus which shows that the cell is immature

o This is acute lymphoblastic leukaemia

206
Q

Name a cause of primary lymphocytosis.

A

o monoclonal lymphoid proliferation -> all cells will look the same because it is a mutated cell that is expanding and making clones of itself

o CHRONIC LYMPHOCYTIC LEUKAEMIA

207
Q

Name the response of secondary lymphocytosis.

A

o POLYCLONAL -> responses to infection, chronic inflammation or underlying malignancy

208
Q

If cells are mature in lymphocytosis, it is in response to what?

A
  • reaction to infection
  • primary disorder
209
Q

If cells are immature in lymphocytosis, it is in response to what?

A
  • primary disorder -> leukaemia/lymphoma
210
Q

What are the causes of reactive lymphocytosis?

A
  • Infection

o EBV, CMV, toxoplasma (a parasite spore-forming protozoa)

o infectious hepatitis, rubella, herpes infections

  • Autoimmune disorders
  • Neoplasia
  • Sarcoidosis
211
Q

What is mononucleosis syndrome, aka Glandular Fever?

A
  • EBV infection of B lymphocytes via the CD21 receptor
  • infected B cell proliferates and expresses EBV associated antigens
  • there is a cytotoxic T-lymphocyte response
  • acute infection is resolved resulting in lifelong sub-clinical infection

o more common in the young

o results in lymphocytosis

212
Q

How is it possible to evaluate lymphocytosis via light chain?

A
  • polyclonal expansion of B cells = 50:50 divide of kappa and lambda
  • monoclonal expansion of B cells = only kappa OR lambda
213
Q

How can gene rearrangement be used to evaluate lymphocytosis?

A
  • in primary monoclonal proliferation, ALL daughter cells carry identical configuration of Ig, or TCR gene -> detectable by southern blot analysis
214
Q
A

o PARASITIC INFESTATION -> most common is schistosomiasis

  • could be due to underlying lymphoma or allergic autoimmune disorder
215
Q
A
  • cells are mature but nucleoli cannot be seen and the cells are all very similar to each other
  • this could be -> Reactive (viral infection, TB) or Primary/monoclonal (CLL)
216
Q
A
  • monoclonal expansion because there is kappa restriction (82%)
  • to distinguish further you will need to test light chain restriction or test for T cell receptor rearrangement
  • as there is kappa restriction, this is most likely to be Chronic Lymphocytic Leukaemia
217
Q
A
  • cells are immature as they have an irregular cell and the nucleoli are visible
  • shouldn’t be able to see such cells in a normal blood film or in the blood film of someone with an infection so this is acute lymphoblastic leukaemia
218
Q
A
  • can see some of the neutrophils and some of precursors to the neutrophils, furthest to the right is a myelocyte
  • precursors should NOT be in a blood film
  • toxic granules aren’t visible in the neutrophils, which would normally be seen in neutrophilia caused by infection
  • also a basophil on the left which are not normally seen
  • expansion of the myeloid cells so this is Chronic Myeloid Leukaemia (CML)
219
Q

Define Haemostasis.

A
  • the cellular and biochemical processes that enables both the specific and regulated cessation of bleeding in response to vascular insult
220
Q

Describe Haemostatic Plug Formation due to dmage to the endothelium.

A
221
Q

What is the primary initiator of the co-agulation cascade?

A
  • tissue factor
222
Q

Where are platelets derived from?

A
  • megakaryocytes in the bone marrow
223
Q

Where do platelets exit megakaryocytes?

A
  • out of protrusions into blood vessels within the bone marrow
224
Q

Describe the ultrastructure of platelets.

A
  • NO nucleus but it is still a pretty active cell
  • storage granules include granules containing ADP (very important for platelet function)
  • have another type of storage granule called alpha granules with contain proteins including Factor V and von Willebrand factor -> released when the platelt is activated
  • important glycoprotein receptors (includes thrombin receptor) on the platelet surface which interact in the formation of a platelet plug
225
Q

Name platelets roles.

A
  • haemostasis
  • thrombosis
  • cancer
  • atherosclerosis
  • infection
  • inflammation
226
Q

Describe platelet plug formation.

A

o when the endothelial monolayer is damaged, the subendothelial structures get exposed, including collagen

o platelets can bind to the collagen in TWO ways:

  • von Willebrand factor can bind to the collagen at the site of damage and unravels so that it can capture the platelets via glycoprotein 1b receptors
  • platelets can bind directly to the collagen via glycoprotein 1a receptors in low sheer conditions

o adhesive reactions are passive - it is a mechanism of recruiting the platelet to the site of damage but the platelet itself has NOT been activated

o once the platelets have been recruited and the receptors have been engaged (activated) - receptors signal inside the cell to release the ADP from the storage granules and to synthesise thromboxane

  • these agents are released they bind to receptors on the surface of the platelets and activate them - making them change shape and release its storage granules -> platelets aggregate and form a haemostatic plug
  • once platelets are activated, glycoprotein 2b/3a receptors become available which can bind to fibrinogen and helps the platelets clump together -> glycoprotein 2b/3a receptors are important therapeutic targets
  • aggregation takes place once the platelet has been activated and additional receptors become available on the surface of the platelets
  • platelets can also be activated by THROMBIN which is generated in coagulation
227
Q

At what levels of platelets do we start to get bleeding with trauma and also spontaneous bleeding?

A
  • bleeding with trauma = <100x109/L
  • spontaneous bleeding = <40x109/L
  • severe spontaneous bleeding = <109/L -> associated with treating leukaemia
228
Q

Where are plasma clotting factors produced?

A
  • liver -> mainly
  • endothelial cells -> VWF, TM, TFPI
  • megakaryocytes -> VWF, FV
229
Q

What is Gla Domain proteins formation dependent on?

A
  • Vitamin K
230
Q

What is the the significance of the Gla Domain?

A
  • enables platelets/proteins to bind to the negatively charged phospholipids

-

231
Q

What is the process which allows Gla Domains to bind to phospholipids?

A
  • Ca2+ binding which causes a structural transition
232
Q

What is Warafirin’s mode of action?

A
  • clotting factors have clusters of GLUTAMIC ACID which are converted in a post-translational modification in the presence of VITAMIN K to Gamma Carboxyglutamic Acid, in the liver -> (an extra carboxyl group is added)
  • this enables calcium to facilitate the binding of the gamma carboxyglutamic acid to the activated platelet membrane phospholipid
  • warfarin inhibits Vitamin K -> STOPS THE GAMMA CARBOXYLATION taking place -> stops the ability of the clotting factors to bind to the surface of the platelets -> reduces the production of thrombin
233
Q

Explain the co-agulation cascade.

A
  • FXa is inefficient in producing Thrombin and therefore thrombin catalyses FXVIIIa and FVa which enhances the rate of production of thrombin 1000s of times
234
Q

What is deficient in Haemophilia A and B?

A
  • haemophilia A (FVIII deficiency)
  • haemophilia B (FIX deficiency)

o X-linked

235
Q

What are the 3 natural anti-coagulant pathways?

A
  • TFPI (tissue factor pathway inhibitor)
  • protein S
  • anti-thrombin
236
Q

How does TFPI work?

A
  • binds/inactivates TF-FVIIa active site
237
Q

How easily is TFPI overwhelmed?

A
  • very easily as it is only present in very low concentration
238
Q

What is the mechanism of Protein C?

A
  • protein C is activated by thrombin-TM complex on EC
  • activated protein C (APC) inhibits thrombin generation by proteolytically inactivating procoagulant cofactors FVa and FVIIIa
239
Q

How does anti-thrombin function?

A
  • is a serine protease inhibitor (SERPIN)
  • inactivates many activated coagulation serine proteases (FXa, thrombin, FIXa, FXIa)
  • “mops up” and free serine proteases that escape the site of vessel damage.
240
Q

What is the mechanism of action of Heparin?

A
  • heparin POTENTIATES the action of anti-thrombin - makes anti-thrombin work more efficiently at directly inhibiting these clotting enzymes
  • is used for immediate anti-coagulation in venous thrombosis and pulmonary embolism (warfarin takes more time to build up in the circulation)
241
Q

Describe fibrinolysis.

A
  • plasma protein, plasminogen, and endothelial cells produce tissue plasminogen activator (tPA)
  • normally there is no interaction between these two
  • however, when a fibrin clot forms, these two proteins assemble on the surface of the clot and the plasminogen is converted to PLASMIN by tPA -> plasmin breaks down the clot
242
Q

How can fibrinolysis by clincal exploited?

A
  • tPA and bacterial activator streptokinase are used in therapeutic thrombolysis of MI
  • thrombolytic agents aren’t used often because there are bleeding problems associated with their use
  • normally, more direct mechanical intervention is used e.g. angioplasty
243
Q

Name three anti-coagulants.

A
  • heparin
  • warfarin
  • DOACs
244
Q

Name two anti-platelet agents.

A
  • aspirin
  • P2Y12 blockers
245
Q

Name 3 laboratory tests for blood coagulation.

A
  • Activated Partial Thromboplastin Time (APTT)
  • Prothrombin Time (PT)
  • Thrombin Clotting Time (TCT)
  • d-dimer
246
Q

What is thrombocytopenia?

A
  • low number of platelets
  • is a primary haemostasis disorder
247
Q

Name some causes of thrombocytopenia.

A
  • bone marrow failure (megakaryocytes) -> leukaemia, B12 deficiency
  • accelerated clearance -> autoimmune thrombocytopenia, disseminated intravascular coagulation
  • hypersplenism
248
Q

What is autoimmune thrombocytopenia?

A
  • antibodies that develop against the platelets and binding of these antibodies means that they are cleared rapidly by the macrophages
249
Q

Name 3 hereditary platelet defects.

A
  • Glanzann’s Thrombasthenia
  • Bernard Soulier Syndrome
  • Storage Pool Disease
250
Q

What is Glanzann’s Thrombasthenia?

A
  • the absense of glycoprotein 2b/3a -> lack of platelet aggregation
251
Q

What is Bernard Soulier Syndrome?

A
  • lack of glycoprotein 1b -> platelets can’t bind to VWF
252
Q

What is Storage Pool Disease?

A
  • a problem with the storage granules -> they are not able to release adequately
253
Q

Name the causes of impaired platelet function?

A
  • hereditary absense of glycoproteins or storage granules
  • acquire -> drugs (aspirin, NSAIDs etc)
254
Q

State the causes of primary haemostasis disorder due to VWF.

A

o hereditary decrease in quantity +/ function (COMMON)

o acquired due to antibody (rare)

255
Q

State the differences between Type 1, 2 and 3 von Willebrand Disease (VWD).

A
  • Type 1 = deficiency of VWF but it functions normally
  • Type 2 = VWF is made but it does NOT function normally
  • Type 3 = VWF is not made AT ALL
256
Q

Name disorders of the vessel wall leading to primary haemostasis.

A

o Inherited (rare)

  • hereditary haemorrhagic telangiectasia
  • Ehlers-Danlos syndrome
  • other conective tissue disorders

o Acquired

  • scurvy
  • steroid therapy

o Atrophy of the supporting tissues of blood vessels results in the vessels being very fragile

  • ageing (senile purpura)
  • vasculitis
257
Q

What are the main three elements, which if damaged cause primary haemostasis disorders?

A
  • platelets
  • VWF
  • vessel wall
258
Q

Why does bleeding occur in primary haemostasis disorders?

A
  • the platelet plug isn’t strong enough to stop bleeding
259
Q

What is typical primary haemostasis disorder bleeding?

A

o Immediate

o Prolonged bleeding from cuts

o Epistaxes

o Gum bleeding

o Menorrhagia

o Easy bruising

o Prolonged bleeding after trauma or surgery

260
Q

What is unique about thrombocytopenia?

A
  • petechiae
261
Q

Why do you get haemophilia type bleeding with severe VWD?

A
  • if VWF is at very low levels then factor 8 will also be LOW
262
Q

What tests can be ran for disorders of primary haemostasis?

A
  • platelet count
  • bleeding time (PFA100 in lab)

o incision on patient’s arm - measure the time taken to stop bleeding

  • assays of VWF
  • clinical observation
  • platelt morphology
263
Q

Describe the graphs produced from a thrombogram of normal and haemophilia patients.

A
  • thrombin is on the y-axis
264
Q

In terms of bleeding, describe haemophilia?

A
  • spontaneous joint and muscle bleeding
  • severe but compatible with life
265
Q

What happens if you are deficient in prothrombin (FII)?

A
  • its lethal -> will die as an embryo/foetus
266
Q

In terms of bleeding, what is the consequence of FXI deficiency?

A
  • bleed after trauma but not spontaneously
267
Q

What bleeding issues occur with FXII deficiency?

A
  • no excess bleeding
  • has a role against thrombosis
268
Q

What are the acquired causes of disorders of coagulation?

A
  • liver disease
  • dilution
  • anti-coagulant drugs -> warfirin etc
269
Q

Why does liver disease cause acquired coagulation disorders?

A
  • most coagulants are produced in the liver
270
Q

What are the causes of dilution of the bloods coagulation factors?

A
  • haemorrhage
  • transfusions -> major transfusions require plasma and well as RBCs and platelets
271
Q

What is Disseminated Intravascular Coagulation (DIC)?

A

o generalised activation of coagulation -> tissue factor

  • associated with sepsis, major tissue damage, inflammation
  • tissue factor is exposed and causes the activation of the clotting cascade -> consumes and depletes coagulation factors and platelets -> activation of fibrinolysis depletes fibrinogen -> deposition of fibrin in vessels causes organ failure

o will continue until the underlying cause is treated

272
Q

Summarise the bleeding patterns in coagulation disorders.

A
  • superficial cuts do NOT bleed (platelets are working fine)
  • bruising is common
  • nosebleeds are rare
  • pontaneous bleeding is deep, into muscles and joints
  • bleeding after trauma may be delayed and is prolonged
  • frequently restarts after stopping
273
Q

What is the hallmark of haemophilia?

A
  • haemarthrosis -> patients can become very disabled by this
274
Q

What should be avoided in haemophilia patients and why?

A
  • intramuscular injections -> can cause deep bleeding patterns
275
Q

Name some tests for coagulation disorders.

A

o Screenings tests

  • Prothrombin Time (PT) (give someone tissue factor and see how long until fibrin forms)
  • Activated partial thromboplastin time (APTT)
  • Platelet count

o Factor assays (FVIII etc)

o Tests for inhibitors

276
Q

Name diseases not detected by routine clotting tests.

A

· Mild factor deficiencies

· Von Willebrand disease

· Factor 8 deficiency (cross-linking)

· Platelet disorders

· Excessive fibrinolysis

· Vessel wall disorders

· Metabolic disorders (e.g. uraemia)

· (thrombotic disorders)

277
Q

Name a hereditary cause of fibrinolysis disorders.

A
  • anti-plasmin deficiency
278
Q

State acquired causes of fibrinolysis disorders.

A

o Drugs such as tissue plasminogen activator (tPA)

o Disseminated intravascular coagulation (because everything has been used up)

279
Q

What is the pattern of inheritance for haemophilia?

A
  • X-linked recessive
280
Q

What is the pattern of inheritance for VWD?

A
  • Type 1 = autosomal dominant
  • Type 2 = autosomal dominant
  • Type 3 = autosomal recessive
281
Q

What is the pattern of inheritance for the vast majority of bleeding disorders?

A
  • autosomal recessive
282
Q

What are the treatments for abnormal haemostasis?

A

o Failure of Production

  • replace missing factor/platelets -> prophylactic or therapeutic
  • stop drugs

o Immune Destruction

  • immunosuppression (e.g. prednisolone)
  • splenectomy for autoimmune thrombocytopenia

o Increased Consumption

  • treat cause
  • replace as necessary
283
Q

What are the treatments for haemostatic disorders causing bleeding?

A

o Factor Replacement Therapy

  • plasma -> contains ALL coagulation factors
  • cryoprecipitate -> rich in fibrinogen, FVIII, VWF, FXIII
  • factor concentrates -> available for all apart from FV

o Platelet Replacement Therapy

NOTE: patients will develop inhibitors in replacement therapy

o Gene Therapy

  • for haemophilia

o Novel approaches -> in development

  • bispecific antibody
  • anti- TFPI antibody
  • anti-thrombin RNAi
284
Q

What other less direct treatments are available for haemostatic disease?

A
  • DDAVP (desmopressin) -> vasopressin analogue which makes the endothelial cells release their own VWF that is stored

o good for people with milder Von Willebrand Disease

  • Tranexemic Acid -> inhibits fibrinolysis

o widely distributed - crosses the placenta and is in low concentration in breast milk

  • Fibrin Glue/Spray
285
Q
A
  • C
286
Q
A
  • B
287
Q
A
  • A
288
Q
A
  • E
289
Q
A
  • 12.5%
  • 25%
  • 50%
290
Q
A
  • Oral Contraceptive Pill
  • intermediate purity VWF/FVIII concentrates
  • prothrombin complex concentrates
  • DDAVP
  • tranexamic acid
291
Q

What proteins contains iron?

A
  • haemoglobin - MOST
  • myoglobin
  • catalase
  • cytochrome P450
  • ribonucleotide reductase
  • cyclo-oxygenase
  • succinate dehydrogenase
  • cytochrome a,b,c
292
Q

How long do RBCs live for?

A
  • 120 days
293
Q

How much iron is required by the body daily?

A
  • 20mg per day
  • fortunately it is recycled so men only need 1mg and women 2mg per day through diet -> easily achieved as on average 12-15mg/day is achieved
294
Q

Why is the form of iron ingested important?

A
  • MOST iron that is eaten is NOT absorbed
  • the body CANNOT absorb iron in the ferric (Fe3+) form
  • the body can only absorb ferrous iron (Fe2+)
295
Q

What factors affect iron absorption?

A
  • diet -> increase in ferrous iron
  • iron deficient -> increased absorption
  • pregnancy
296
Q

How does the gut alter iron absorption?

A
  • iron passes into the epithelial cells but at the basement membrane, you need ferroportin to transport the iron into the blood
  • if hepcidin is HIGH (as it is when your iron levels are high), it blocks the ferroportin and stops the absorptionof iron and visa versa

o iron is part of the complex that switches on hepcidin transcription

297
Q

What different forms of iron are present in the body?

A
  • elemental iron, from the diet, gets taken into the cell
  • a protein shell normally forms in cells to form ferritin micelles

iron in plasma is linked to transferrin which transports the iron around the body

298
Q

What is the usually saturation of transferrin with iron?

A
  • 20-40%
299
Q

What is the clincial relevance of transferrin?

A
  • its saturation and levels can be measured in labs
300
Q

What is erythropoietin?

A
  • hormone produced in the kidneys that affects red cell production and development
301
Q

What is the relevance of erythropoietin in anaemia?

A
  • if you are hypoxic (as considered by the kidneys in anaemia) then there is an increase in erythropoietin secretion and hence and increase in red blood cell precursors
  • the red cell precursors will survive longer and the EPO will make them grow and differentiate to produce more progeny
302
Q

What is anaemia of chronic disease?

A

Definition: anaemia that is seen in patients with chronic disease e.g. chronic infection, chronic immune activation or malignancy

o patient will:

  • NOT be bleeding
  • NOT have any bone marrow infiltration
  • NOT be iron/B12 or folate deficient

o NO obvious cause for their anaemia EXCEPT that the patient is ILL

303
Q

What are the laboratory markers that suggest that someone is ill with a chronic disease?

A
  • raised C-reactive protein
  • increased erythrocyte sedimentation rate (ESR)
  • rise in ferritin, FVIII, fibrinoge, immunoglobulins -> acute phase responses
304
Q

Name some conditions associated with ACD.

A

· Chronic Infections - eg TB/HIV

· Chronic Inflammation eg rheumatoid arthritis/systemic lupus erythematosus

· Malignancy

· Miscellaneous - eg cardiac failure

305
Q

What is the cause of ACD?

A
  • cytokine release -> prevent flow of iron from duodenum to the RBCs therefore blocking RBC utilisation of iron
  • cytokine also:

o stop erythropoietin from increasing

o stop iron flowing out of cells

o increase production of ferritin

o increase death of red cells

  • consequently fewer RBCs are made, more RBCs die and there is a lower iron availability
306
Q

Name some causes of iron defiency.

A
  • Bleeding - e.g. menstrual/GI tract
  • physiological/increased use - e.g. growth/pregnancy
  • dietary deficiency - e.g. vegetarian
  • malabsorption - e.g. coeliac disease
307
Q

On what groups of people are full GI investigations performed if iron deficient and anaemic?

A

· Male

· Women over 40

· Post-menopausal women

· Women with scanty menstrual loss

308
Q

What is involved in full GI investigations?

A
  • upper GI endoscopy (oesophagus, stomach and duodenum)
  • duodenal biopsy
  • colonoscopy

o if nothing was found a small meal should be followed through the tract

309
Q

What laboratory parameters can be measured to help diagnosis anaemia?

A
  • MCV
  • Serum Iron
  • Ferritin
  • Transferrin (= total iron binding capacity (TIBC))
  • Transferrin Saturation
310
Q

If someone has low MCV and Hb are they iron deficient?

A
  • no necessarily -> could be iron deficiency, thalaessemia trait or ACD
311
Q

Can you confirm a iron deficiency diagnosis if Hb, MCV and serum iron are all low?

A
  • NO

o Iron Deficiency - LOW serum iron

o Anaemia of Chronic Disease - LOW serum iron

o Thalassemia - NORMAL serum iron

  • could still be either iron deficiency or ACD
312
Q

What are the levels of ferritin in patients with iron deficiency and ACD?

A

· LOW - iron deficiency

· HIGH - ACD

  • ferritin isn’t definitive because if the patient has both lack of iron and ACD it will be normal
313
Q

What clues indicate that ferritin might not be a good measure?

A

o Raised CRP

o Raised ESR

  • shows that there is some acute condition that is causing a rise in all the acute phase proteins and hence ferritin can not be relied upon
314
Q

What are the levels of transferrin in patients with iron deficiency and ACD?

A
  • iron deficiency = increase
  • ACD = normal or decrease
315
Q

What are the levels of transferrin saturation in patients with iron deficiency and ACD?

A

o Iron Deficiency - LOW saturation -> there is more transferrin and less iron

o ACD - NORMAL saturation -> iron and transferrin have both gone down so the saturation is normal

316
Q

What are the classic parameters for iron deficiency?

A
317
Q

What are the classic parameters for ACD?

A
318
Q

What are the parameters for thalassaemia trait?

A
319
Q

What is the tell tail sign of iron deficiency on a blood film?

A
  • pencil cells
320
Q

What is Vitamin B12 required for?

A
  • DNA synthesis
  • integrity of the nervous system
321
Q

What is Folic Acid required for?

A
  • DNA synthesis
  • homocysteeine metabolism
322
Q

Why are folate and B12 important in DNA synthesis?

A
  • both needed for the synthesis of deoxythymidine (dTMP), which is a crucial building block in DNA synthesis
  • folate is converted to methyl tetrahydrofolate (Methyl-THF) as it is absorbed into the luminal cells
  • B12 acts as a co-factor for methionine synthetase for the conversion of homocysteine to methionine
  • the reaction releases methyl groups that go on to methylate the building blocks of DNA -> if you can’t methylate these building blocks then you can’t synthesise DNA
323
Q

What are the clincal features of B12 and/or folate deficiency?

A
  • anaemia -> weak, tired, short of breath
  • jaundice -> ineffective erythropoiesis
  • glossitis - red, raw, inflammed tongue that is quite painful
  • angular cheilosis - soreness in the corner of your mouth
  • weight loss, change of bowel habit
  • sterility

o effects cells that divide rapidly

324
Q

What are the size of RBCs in iron deficient anaemia?

A
  • microcytic
325
Q

What are the size of RBCs in folate or B12 deficient anaemia?

A
  • macrocytic
326
Q

What are the causes of macrocytic anaemia?

A

o Vitamin B12/folate deficiency

o Liver Disease or Alcohol

o Hypothyroidism

o Haematological Disorders - myelodysplasia, aplastic anaemia, reticulocytosis

o Drugs that interfere with DNA synthesis - azathioprine, zidovudine, hydroxycarbamide, methotrexate

o Prolonged nitrous oxide anaesthesia

327
Q

Define myelodysplasia.

A
  • a group of disorders in which the production of any one or all types of blood cells by the bone marrow is disrupted. Look for hypo-granular neutrophils and/or monocytosis
328
Q

Define aplastic anaemia.

A
  • characterised by a failure of blood cell production resulting in pancytopenia and reduced bone marrow cellularity
329
Q

What is reticulocytosis?

A
  • haemolytic anaemia or bleeding -> happens when bone marrow is trying to catch up with the demand for RBCs -> reticulocytes are bigger than mature RBCs so the MCV increases
330
Q

Define megaloblastic.

A
  • describes a morphological change in the red cell precursors within the BONE MARROW
331
Q

Describe normal RBC maturation.

A

o Erythroblast = RBC precursor -> if normoblastic, you can see loads of different forms from early, intermediate to late

  • nucleus of a proerythroblast has a lot of space in it - this is chromatin which looks very open in the proerythroblast, as cell becomes more mature, it becomes tighter and just before the red cell is about to spit out its nucleus, the nucleus appears very dark

o Reticulocyte = young red cell, no nucleus -> cell gets smaller and more pink (from blue) as they mature as more haemoglobin is present compared to DNA

332
Q

How can you determine whether the lineage of cells is normal?

A

o The chromatin and how open it is

o Colour of the cytoplasm and how blue it is

333
Q

Define megaloblastic anaemia.

A
  • asynchronous maturation of the nucleus and cytoplasm in the erythroid series -> nucleus doesn’t mature but the cytoplasm does
334
Q

What is the mechanism of megaloblastic anaemia?

A
  • delay in DNA synthesis

o Red Cells and Red Cell Precursors

  • increase in the size of red cell precursors at all stages of maturation
  • increase in the activity of the bone marrow because haemopoiesis is ineffective (dysplastic)

o White Cells and White Cell Precursors

  • in bone marrow you will find GIANT metamyelocytes -> neutrophils will become hyper-segmented
335
Q

State the appearance of RBCs in the peripheral blood in patients with megaloblastic anaemia.

A
  • Anisocytosis
  • Large red cells
  • Hypersegmented neutrophils
  • Giant metamyelocytes
336
Q

True or False. Folate is required for DNA synthesis.

A
  • true
337
Q

True or False. Thyroid disease can be a cause of megaloblastic RBCs.

A
  • false
338
Q

True or False. B12 deficiecny is a cause of microcytic RBCs.

A
  • false - its macrocytic
339
Q

True or False. Patients with megaloblastic anaemia may be sterile.

A
  • true
340
Q

True or False. Patients with megaloblastic anaemia may develop jaundice.

A
  • true
341
Q

What is abnormal about this blood film?

Name two possible underlying clinical disorders.

A
  • macrocytic, hyper-segmented neutrophils, anisocytosis
  • B12 or folate deficiency
342
Q

Give some examples of blood tests that could be carried out on someone with suspected macrocytosis.

A
  • blood film
  • B12 level
  • folate level
  • liver function
  • reticulocytes
  • thyroid function
343
Q

Who are most at risk to decreased folate deficiency?

A
  • elderly
  • sick
  • those with eating disrorders
  • alcoholics
344
Q

What are the causes of folate deficiency?

A

· Not enough folate in the diet

· Not absorbing folate enough

· Increased demand for folate

345
Q

Name some causes of increased folate demand.

A
  • Physiological (rapid increase in growth)

o pregnancy

o adolescence

o premature babies

  • Pathological (rapid cell turnover)

o malignancy

o erythroderma - whole body skin rash

o haemolytic anaemia

346
Q

Why might folate absorption be decreased?

A

· Combined with iron deficiency in COELIAC DISEASE

· Surgery or inflammatory bowel disease interferes with normal absorption

· Drugs

347
Q

What is the test to diagnose folate dificiency?

A
  • blood folate level
348
Q

What is the best way to access the cause of a foltae deficiency?

A
  • History -> diet, alcohol intake, haemolytic anaemia, pregnancy, drugs
  • Examination -> skin disease (e.g. erythroderma), alcoholic liver disease
349
Q

Name the consequences of folate deficiency.

A
  • Macrocytic, Megaloblastic Anaemia
  • Neural Tube Defects -> spina bifida, anencephaly (absence of a major portion of the brain, skull, and scalp) -> affected by folate intake before and during pregnancy
  • Increased Risk of Venous Thromboembolism
350
Q

What is the link between folic acid and homocysteine?

A
  • folate is used to convert homocysteine to methionine
  • if folate deficient homocysteine builds up in cells
351
Q

Why is homocysteine builds up an issue?

A
  • Very HIGH homocysteine levels are independently associated with: atherosclerosis and premature vascular disease
  • Mildly elevated homocysteine levels are associated with: cardiovascular disease, probably arterial thrombosis and probably venous thrombosis
352
Q

What are the causes of B12 deficiency?

A

· Not enough B12 in the diet

· Not absorbing enough B12

353
Q

Although unlikely in the general population, what group of people have increased risk of dietary deficiency of B12?

A
  • vegans and vegetarians - particularly vegans as no food of animal origin
354
Q

What factors could decrease B12 absorption?

A
  • autoimmune disease
  • surgery- > post gastrectomy
  • inflammatory bowel disease
355
Q

Name some consequences of B12 deficiency.

A
  • Macrocytic and Megaloblastic Anaemia - REVERSIBLE with treatment
  • Neurological problems due to DEMYELINATION - NOT always reversible with treatment

o Subacute combined degeneration of the spinal cord

o Neuropathy of cranial and peripheral nerves

o Cognitive impairment due to loss of white matter in the central nervous system

o Optic atrophy

356
Q

What are the symptoms of B12 deficiency?

A
  • weak, tired, lethargic
  • symmetrical numbness
  • muscle weakness
  • difficulty walking/loss of balance
  • visual impairment
  • memory impairment
  • psychiatric disturbance
357
Q

What are the signs of B12 deficiency?

A
  • jaundice
  • loss of vibration and joint position sense
  • absent reflexes
358
Q

What factors are vital for B12 absorption?

A
  • intact stomach -> produces intrinsic factor
  • functioning small intestine
359
Q

What test is ran if B12 deficiency is suspected?

A
  • serum B12 level
360
Q

Define pernicious anaemia.

A
  • autoimmune atrophic gastritis with loss of intrinsic factor due to atrophy of the gastric parietal cells which are responsible for producing acid and intrinsic factor
  • results in macrocytic/megaloblastic anaemia +/- neurological damage
361
Q

What is the cause of pernicious anaemia?

A
  • lack of B12 -> can’t be treated with tablets as there is a lack of intrinsic factor
362
Q

What does pernicious anaemia increase the chance of?

A
  • stomach cancer - especiallly in males
363
Q

How do you diagnose pernicious anaemia?

A
  • Intrinsic Factor Antibodies -> occasionally found in other conditions -> 40-60% of adults with PA will have +ve anti-intrinsic factor antibodies
  • Parietal Cell Antibodies -> 80-90% of adults with PA and 10-16% of normal females over the age of 60

o Screen people for pernicious anaemia with gastric parietal cell antibodies then confirm it with intrinsic factor antibodies -> very rarely will you have someone with PA who tests negative for both those tests

364
Q

What tests are ran to determine the cause of B12 deficiecny?

A
  • antibodies to parietal cells and intrinsic factor
  • anitbodies for coeliac disease
  • breath test for bacterial overgrowth
  • stool for H Pylori
  • test for Giardia
365
Q

What is the treatment for B12 deficiency?

A
  • Injections of B12, 3 times a week for 2 weeks -> afterwards every 3 months
  • IF NEUROLOGICAL INVOLVMENT B12 injections on alternating days until no further improvement for up to 3 weeks -> then every 2 months
366
Q

A 49-year old man with grey hair and blue eyes presents with anaemia. His blood count is as follows:

  • Hb: 90g/l
  • WBC: 4x109/l
  • Platelets: 160x109/l
  • MCV: 110fl

Which would be the most appropriate set of investigations?

A. Blood film, liver function, Shilling test

B. Folate, B12, thyroid function, liver function

C. Thyroid function, B12 and anti-intrinsic factor antibodies

D. Ferritin, shilling test, folate

E. Blood film, thyroid antibodies, anti-parietal cell antibodies

A

B

367
Q

Where does the donated blood come from?

A
  • HUMANS -> no synthetic forms have been created yet
  • Scarce resource:

o 1 donor can only give 1-pint (unit) maximum every 4 months

o 9000 units of blood are needed per day in the UK

o You cannot stockpile blood because it has a shelf-life of 5 weeks

368
Q

When are blood transfusions used?

A
  • massive haemorrhage and plain fluids are not sufficient
  • if anaemic and iron/folate/B12 are not appropriate
369
Q

Describe the differences between ABO blood groups.

A
  • ALL of us have a common H stem
  • blood group O - common stem and there are no A or B antigens
  • blood group A - common H stem and the A antigen
  • blood group B - common H stem and the B antigen
  • blood group AB - common H stem and A and B antigens
370
Q

What determines ABO blood groups?

A
  • antigens are determined by corresponding genes
  • A gene codes for the enzyme that adds N-acetyl galactosamine onto the common glycoprotein and fructose stem
  • B gene codes for an enzyme that adds galactose
  • A and B genes are CODOMINANT whereas O gene is recessive
371
Q

Why is not possible to give someone a blood group which they are not?

A
  • people have antibodies against antigens that is NOT present on their own red cells
  • antibodies are naturally occurring (from a few months) and are in the class IgM
  • an ABO incompatible transfusion then the antibody/antigen interaction is often FATAL via cytokine storm, lysis, cardiovascular collapse and death
372
Q

What tests can be ran to determine ABO blood groups?

A
  • tests with known anti-A and anti-B reagents
  • patients serum is mixed with donor RBCs -> if it doesnt rwcat then they are compatible
373
Q

What are the RhD groups?

A
  • either RhD positive (you have the D antigen) or RhD negative (lack the D antigen) -> D codes for D antigen on the red cell membrane and d codes for no antigen and is recessive

o 85% = RhD POSITIVE

o 15% = RhD negative

374
Q

What is significant about O negative blood?

A
  • it is safe for everyone -> is given in an emergency
375
Q

What can RhD negative people do when exposed to RhD antigen?

A
  • they lack the RhD antigen so can make anti-D antibodies after exposure -> could be by transfusion or pregnancy to a RhD positive feotus
  • anti-D antibodies are IgG
376
Q

What are the implications of anti-D antibodies?

A
  • Future Transfusions

o patient must have RhD negative blood otherwise, anti-D antibodies would react with the RhD positive blood and cause a delayed haemolytic transfusion reaction resulting in anaemia, high bilirubin, jaundice etc.

  • Haemolytic Disease of the Newborn (HDN)

o if a RhD negative mother has anti-D antibodies and in the next pregnancy the foetus is RhD positive - the mother’s IgG anti-D antibodies can cross the placenta and causes haemolysis of the foetal red blood cells -> can cause hydrops fetalis and death

377
Q

Define hydrops fetails.

A
  • the accumulation of fluid in foetal tissues or body cavities. In its most severe form, excessive fluid collects in the peritoneal cavity (ascites), the pleural and pericardial cavities and the soft tissues (oedema)
378
Q

A woman is O positive; her partner is AB positive. Which of these cannot be a child of theirs?

Donald - B+

Theresa - AB+

Angela - A+

Emmanuel - O+

A
  • Theresa and Emmanuel
379
Q

A patient is B positive. Which of the following blood could kill them?

  • A positive
  • O positive
  • B negative
A
  • A positive
380
Q

Why is whole blood not used anymore?

A
  • waste of blood
  • can cause heart failure is too much liquid is giving to boost RBC numbers
381
Q

How is plasma seperated

A
  • freezing plasma within 6 hours of donation preserves all the coagulation factors - this is FRESH FROZEN PLASMA
  • taking FFP and thawing it overnight in a 4 degrees celsius fridge, will separate out into CRYOPRECIPITATE at the bottom and some supernatant on top
  • cryoprecipitate is a very concentrated form of fibrinogen, factor 8, VWF, factor 13, fibronectin
  • not doing either of those two things, then we can pool the plasma of several thousand donors and stick it in a fractionating column and pull off different fractions
  • we can pull off things like albumin, anti-D antibodies and haemophilia factors
  • plasma for fractionation is NOT done in the UK
382
Q

How long do RBCs last after being donated?

A
  • red blood cells can be stored in a 4-degree fridge for 5 weeks
  • don’t normally tend to freeze blood because it’s inefficient - if you freeze and thaw blood then you lose red cells however, rare groups/antibodies you will need to freeze the red blood cells (national frozen bank)
383
Q

How is FFP stored?

A
  • at -30 degrees celsius (within 6 hours of donation) for up to 2 years
384
Q

How must FFP be thawed?

A
  • at room temperature for 20-30 mins before use
  • ideally you want to use it within an hour because the coagulation factors will start to degenerate at room temperature
385
Q

What is the dose of FFP?

A
  • 12-15ml/kg = usually 3 units
386
Q

When is FFP used?

A
  • If bleeding and abnormal coagulation test results (PT, APTT)
  • Reversal of warfarin - for urgent surgery -> because warfarin inhibits factor 2, 7, 9 and 10 but better things are available
  • NEVER to bulk up blood volume
387
Q

What is contained within cryoprecipitate?

A
  • fibrinogen and FVIII in concentrated form
  • standard dose comes from 10 donors
388
Q

When is cryoprecipitate used?

A

o massive haemorrhage and fibrinogen is very low

o hypofibrinogenaemia (rarely)

389
Q

What is the standard adult dose of platelets?

A
  • 1 pool from 4 donors
  • alternative one donor by apheresis
390
Q

How are platelets stored?

A
  • room temperature (22 degrees)
  • must be constantly agitated to prevent them from aggregating
  • shelf life is only 5-7 DAYS (because of risk of bacterial infection)
391
Q

Is there a need for cross-matching with platelets?

A
  • no need to cross-match but must be same blood group because platelets have low levels of ABO so the wrong group platelets would be destroyed very quickly
  • platelets have to be suspended in plasma when they are given because if all the plasma is removed, the platelets would just clump together
  • should cross-match if as replacement for chemo as they must last longer than for surgery
392
Q

When are platelets used?

A
  • mostly patients with bone marrow failure
  • massive Bleeding
  • DIC -> widespread activation of the coagulation cascade and you get little thrombi forming everywhere and it depletes the amount of platelets you have
  • very low platelets and the patient needs surgery
  • if cardiac bypass is needed and the patient is on anti-platelet drugs
393
Q
A

A. He needs FFP because his PT and APTT are both prolonged suggesting that there are problems in the extrinsic and intrinsic pathway so more than one factor is missing

B. He needs FFP AND Cryoprecipitate - cryoprecipitate only has fibrinogen and factor 8 so this will solve the low fibrinogen problem and the FFP will supplement the other coagulation factors

394
Q

What are the fractionated products of blood?

A
  • Factor 8 and Factor 9 -> for haemophilia, FVIII for von Willebrand’s disease -> recombinant factor 8 and 9 alternatively are increasingly used, but expensive
  • Immunoglobulins -> IM: specific - tetanus; anti-D; rabies, IM: normal globulin - broad mix in population (e.g. HAV), IVIg: pre-op in patients with ITP (idiopathic thrombocytopenic purpura) and AIHA (autoimmune haemolytic anaemia)
  • Albumin -> 4.5%: useful in burns, plasma exchanges and 20%: certain severe liver and kidney conditions only (this is when they lose masses of proteins)
395
Q

Describe gene expression in the development of feotus and into early life.

A
  • during the early part of embryogenesis, the production of red cells is mainly in the yolk sac, later on the main sites of production are the liver and the spleen -> switches to bone marrow occurs shortly after birth
  • during embryonic life, the zeta and epsilon chains are produced until 6-8 weeks, after which there is a switch to alpha globin chains
  • gamma globin chain production persists until 3-6 months in life, after which beta globin chains take over
396
Q

Describe the primary structure of globin chains.

A
  • α-globin chains = 141 amino acids
  • non-α-globin chains = 146 amino acids
397
Q

Describe the secondary structure of globin chains.

A
  • 75% α and β chains form a helical arrangement
398
Q

Describe the teritary structure of globin chains.

A
  • approximate sphere with a hydrophilic surface (charged polar side chains)
  • hydrophobic core
  • haem pocket
399
Q

What is HbH disease?

A

i impaired production of 3 or 4 alpha globins, coded by genes HBA1 and HBA2

  • has a haemolytic element with microcytosis, anisocytosis, poikilocytosis and puddling of Hb in RBCs
400
Q

How does sickle cell disease cause pulmonary hypertension?

A
  • the free plasma haemoglobin resulting from intravascular haemolysis scavenges NO -> vasoconstriction

Y2 MCD (5 decks)

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