haematology Flashcards

1
Q

types of haematologists

A

benign
blood transfusion
malignant
haemostasis + thrombosis

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2
Q

definition of anaemia

A

haemoglobin conc below normal range
male <125g/l
female <115g/l
due to either low red cell mass or increased plasma volume (preg)

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3
Q

symptoms of anaemia

A
fatigue
reduced exercise tolerance
SOB
post hypotension
dizziness
angina
palps
hf - SOB, peripheral oedema
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4
Q

signs of anaemia

A
pallor + conjunctiva
tachycardic
heart murmurs
koilonychia - iron deficiency
angular stomatitis
glosssitis - B12/folate
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5
Q

classes of anaemia

A

microcytic - iron deficient, thalassaemia, anaemia of chronic disease, sideroblastic

macrocytic - vit B12 deficient, folate deficient, without anaemia = liver disease, hypothyroid,

normocytic - acute bleeding, haemolysis, chronic disease, haemolytic anaemia, primary marrow problem, pregnancy, renal failure

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6
Q

myelodysplasia

A

found in elderly

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7
Q

what doses of oral ferrous sulphate would you prescribe for iron deficient anaemia

A

200mg OD

BNF says TDS but recently been found OD works just as good but with less s/e

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8
Q

most common preventable error with blood transfusions

A

incorrect blood product

- most couldve been prevented with the final identification check

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9
Q

what antibodies would someone produce if they had type 0 blood

A

anti-A

anti-B

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10
Q

what antibodies would someone produce if they had type AB blood

A

none

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11
Q

what antibodies would someone produce if they had type B blood

A

anti-A

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12
Q

what antibodies would someone produce if they had type A blood

A

anti-B

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13
Q

what happens if you transfuse the wrong blood to someone

A

triggers massive immune response leading to shock and DIC

Individuals may die from circulatory collapse, severe bleeding or renal failure, often within minutes or hours.

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14
Q

which blood type can be safely given to anyone and why

A

blood group O

as there are no A or B antigens for the recipient’s antibodies to react with

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15
Q

what antigen do people who are rhesus positive create

A

D-antigen

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16
Q

talk through the steps in the decision to transfuse

A
  1. is the patient at risk of transfusion associated circulatory overload - low body weight, >70, pre-existing conditions eg cardiac/renal failure
  2. use of single unit recommended in non bleeding adult
  3. signed consent isnt a legal requirement in UK and Ireland - but patient should be informed in a timely manner for indication/risks/benefits
  4. record of this discussion documented in notes
  5. The patient should have the opportunity to raise any concerns and discuss alternative therapies, e.g. oral iron therapy (BSH 2017) have stated that a record of the administration of each blood component is essential (i.e., reason for transfusion, number of units prescribed and outcome)
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17
Q

what needs to be included to reach the minimum patient identification data set when requesting blood

A
full name
dob
unique identifier eg NHS number
adress
gender
middle name
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18
Q

what information is required to request blood in someone who cannot be identified

A

the assigned unique hospital identification number e.g. ED number / Major Incident Number and gender are required as a minimum

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19
Q

who is responsible for checking for previous transfusion history/ specific requirements?

A

the person making the request

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20
Q

what information is needed when requesting a pre-transfusion test or blood component

A

minimum patient identification data set
the reason for the request, the pre-transfusion test or number and type of component required, urgency of request, location of patient, blood group antibodies (if known), previous transfusion history and/or transfusion in the past three months, any special requirements, the date and time required

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21
Q

what specific blood should be requested for neonates up to 28 days post expected date of delivery

A

cytomegalovirus negative blood

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22
Q

what specific blood should be requested for patients who are immunocompromised and why

A

irradiated blood

Is used to destroy any T lymphocytes remaining in the blood donation, which may cause graft-versus-host disease in vulnerable patients. If an immunocompromised patient receives blood components that are not irradiated, the donors T cells can cause tissue and organ damage leading to death.

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23
Q

worried about potassium overload - what blood should be requested

A

blood of specified age

For example, blood of less than 5/7/10 days is required because of concerns of the potassium content in older units.

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24
Q

what blood is used for transfusion in children

A

paedipacks
One adult unit divided between 4 - 8 aliquots. Several aliquots are allocated to one child to allow sequential transfusions from the same donor, reducing donor exposure.

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25
Q

what is the difference between the group and save and crossmatch tests

A

group and save
- is the sample processing that determines the patient blood group (ABO and RhD) and screens for any atypical antibodies.
The process takes around 40 minutes and no blood is issued

crossmatch
- is the final step of pretransfusion compatibility testing, to request blood from the laboratory.
Crossmatching involves physically mixing of patient’s blood with the donor’s blood, in order to see if any immune reaction occurs
After ensuring that donnor blood is compatible, the donor blood is issued and can be transfused to the patient.
This process takes around 40 minutes, in addition to the 40 minutes required to G&S the blood.

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26
Q

what blood do you prescribe in an emergency setting when not knowing the patients blood type

A

type O D negative

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27
Q

how long can a pre-transfusion testing sample be used for repeat cross-matching purposes

A

7 days

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28
Q

sampling procedure for pre-transfusion testing

A

1 - identify patient
2 - complete minimum indentification requiements on blood form
3- Take the blood sample and immediately after hand-write on the tube unless using a computer prepared label generated by an electronic bar-coding system. If electronic systems are used the bar-coded label must be printed at the bedside from the patients ID band. Re-check that the details on the sample tube and request form match before putting them in the transport bag

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29
Q

who is responsible for ensuring that the patient identification details on the sample tube and request form match when taking for blood transfusion

A

the person taking the sample

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30
Q

what must be included on the sample tube when taking blood for transfusion

A

date
time
signature

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31
Q

blood availability - timescales

A

OD negative - emergency immediate 5 mins

group compatible blood - 10-15 mins

fully crossmatched blood - 30-40 mins (maybe hours if antibody found)

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32
Q

if someone has no history of transfusions what may also be required as a pre-transfusion test?

A

a secondary confirmatory blood group sample - as long as it doesn’t impede on delivery of urgent blood components

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33
Q

red cells storage

  • time
  • temp
  • if removed
A

35 days
2-6 degrees
alarmed fridge
transfused within 4 hours of removal from fridge
if removed and not transfused sent back to lab with the length of time it was out to see if it can be reused

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34
Q

platelets storage

  • time
  • temp
  • if removed
A

20-24 degrees
not in fridge as they aggregate
5-7days
if removed and not used returned to lab

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35
Q

FFP + cryoprecipitate

  • time
  • temp
  • if removed
A

-25 degrees
- 3 years
transfused as soon as possible
if unused return to lab

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36
Q

collection steps before transfusion

A

ensure patient has identification band in situ
check minimum patient identification data set
ensure informed consent
IV access?
pre-tranfusion obs taken within 60 mins of the transfusion
only collect one unit at a time
only pass over the blood to the person who requested it
Clinical staff are required to check the correct component is received upon delivery, and to sign and time receipt.

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37
Q

what do you need to do if you use group O cells in an emergency

A

inform the lab so they can replace it

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38
Q

blood transfusion bedside checklist

A
  • blood integrity eg no clots, leaks, damage, discoloration, expirary etc
  • informed consent documented
  • positive patient identification
  • check unit tag against unit label, prescription, patient ID band and PPID
  • perform obs - temp, pulse, resp, bp
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39
Q

what venous access is required for transfusions

A

central line normally

when using this the blood should be warmed through a blood warming device

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40
Q

venous access for blood transfusions big no no’s or do do’s

A

must be a CE-marked tranfusion set with an integral mesh filter to remove microaggregates
do not prime with 0.9 saline
do not administer meds or other IV fluids through the access for the tranfusion as there is a risk of incompatibility (e.g. dextrose & calcium containing solutions can cause haemolysis or lead to clotting of the transfusion components
the administration set should be changed every 12 hours
never use the same admin set for platelets as red cells as will cause aggregation

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41
Q

administration of blood components steps

A
  • full patient identification data set with patient and on the laboratory generated label attached to the blood component against the patient’s identity band
  • check the laboratory generated label attached to the blood component against the label affixed to the unit to ensure all the following is the same:
  • donation number
  • patients blood group
  • component type
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42
Q

methods for patient identification for transfusion best practise points

A

NO WRISTBAND NO TRANSFUSION
in the unconscious/compromised patient (e.g. neonates or paediatric practice or confused patients) it is imperative that greater vigilance should be taken to identify these patients,

unidentified patients in A&E should use unique identification number and gender

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43
Q

documenting a transfusion

A

sign the transfusion documentation
record the donation number
complete traceability documentation

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44
Q

treatment of choice for emergency reversal of warfarin

A

prothrombin comples concentrate

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45
Q

signs and symptoms of a transfusion reaction

A

patients should be transfused in an area where they can observed

  • advise pt on signs symps to look out for
  • stop transfusion immediately following any sign
  • check the blood component against the wrist band
  • antipyretic or antihistamine may be required
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46
Q

can you restart a transfusion if they have only had mild reaction to the first component?

A

yes after 30 mins if the patient has responded to symptomatic treatment

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47
Q

management of a severe transfusion reaction?

A
  • stop transfusion
  • check compatibility of unit
  • assess patient - ABCDE
    -Replace the administration set and preserve IV access with normal saline to maintain systolic BP
    Check urine for signs of haemoglobinuria
    Commence appropriate treatment
    Maintain airway and give high flow Oxygen.
    If appropriate administer adrenaline and/or diuretic and resuscitate if/as required.
    Reassess patient and treat appropriately - Seek expert advice if patient’s condition continues to deteriorate
    document it as adverse event
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48
Q

delayed haemolytic transfusion reaction
-what is it?
signs/symps

A

rare
usually seen in patients who have developed red cell antibodies in the past from transfusion or pregnancy. A combination of the features occurs days after the transfusion, suggesting that the red cells are being destroyed abnormally quickly

signs/sympts

  • fever
  • falling haemoglobin or a rise less than expected
  • jaundice
  • haemoglobinuria
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49
Q

what should be measured 15 mintues after starting a transfusion

A

temp
bp
hr
rr

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50
Q

alternatives to a donor blood transfusion

A

sometimes can have autologous transfusion - recycling your own blood

allogenic - drug therapies eg oral or IV iron, erythropoietin and tranexamic acid

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51
Q

when should you crossmatch blood?

A

only when a transfusion is likely to be required

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52
Q

what is the universal donor for plasma?

A

group AB

has no anti-A or anti-B antibodies in it

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53
Q

what percent of the population are rhesus positive or resus neg

A

85% rhesus pos

15% neg

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54
Q

how much blood can someone donate in blood per year

A

470mLs of whole blood three times a year

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55
Q

what is a bag of red blood cells?

A

red cells in additive solution - contains up to 20 mLs of plasma
leucocyte-depleted
haematocrit typically 0.55
stored for up to 5 weeks at 4 degrees +/- 2 degrees
can be irradiated +/or CMV neg

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56
Q

when would you prescribe transfusion of red cells?

A

improve oxygenation to tissues by increasing circulating red cell mass

main indications =

  • bleeding
  • anaemia
  • haemoglobin disorders
  • loss of 30-40% volume
  • if hb is below 70g/L in fit pt
  • if below 80-90 g/L in pt with CVS
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57
Q

transfusing red cells will give a rise of haemoglobin to what ratio?

A

for 4mL/kg of red cells = rise of 10g/L of Hb

this works for people with body weights of 70-80kg if very low then use smaller volumes

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58
Q

define apheresis donation

A

a single donor

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59
Q

pooled donation

A

whole blood derived - 4 donations

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60
Q

adult therapeutic dose

A

one pack

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61
Q

one adult therapeutic dose of platelets should increase the platelet count by what?

A

20x10(9)/L

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62
Q

when will platelets be tranfused?

A

to prevent bleeding not stop it
when platelet count drops below 10x10(9)

for example in:

  • Reversible bone marrow failure including allogeneic stem cell transplant and critical illness
  • Chronic bone marrow failure if patient is receiving intensive treatment or to prevent persistent bleeding
  • to prevent bleeding prior to a procedure
  • thrombocytopenia

dont have to cross match but preferre

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63
Q

do you need to match the group when tranfusing fresh frozen plasma

A

yes as a first choice

fine tho as long as its ‘low-titre’ and another group

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64
Q

when is fresh frozen plasma given?

A

inherited coagulation factor deficiency where no suitable factor concentrate is available, e.g. Factor V deficiency
Acute disseminated intravascular coagulation (with evidence of bleeding)
Thrombotic thrombocytopenic purpura (TTP)
Major haemorrhage*
Prophylaxis before surgery (or another invasive procedure) if abnormal coagulation test results AND one or more additional risk factors for bleeding:
i) Personal or family history of abnormal bleeding
ii) Procedure associated with major blood loss
iii) Procedure involves critical tissues such as eye, brain or spinal cord
iv) Concurrent thrombocytopenia.

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65
Q

dose of fresh frozen plasma for:

  • prophylaxis for surgical or invasive procedure
  • major haemorrhage
A
  • proph - 15ml/kg

- major - 15-20ml/kg

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66
Q

when should FFP not be used

A

As a plasma expander to correct hypovolaemia.
For the reversal of warfarin anticoagulation, treatment of bleeding in this circumstance is vitamin K, with or without prothrombin complex concentrate.
To non-bleeding patients with liver disease*
To critically ill patients with prolonged PT or APPT in the absence of bleeding.
For patients with liver disease: there is no evidence that prophylactic FFP reduces the risk of bleeding from percutaneous liver biopsy or variceal haemorrhage.

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67
Q

how much cryoprecipitate should be used to increase fibrinogen levels by approx 1g/l in non-bleeding average-sized adult of 70kg

A

2 x 5-donor pools

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68
Q

which blood component is the most likely to cause an allergic or serious reaction

A

FFP

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69
Q

define major haemorrhage

A
  • loss of one blood volume within a 24 hour period
  • 50% blood volume loss within 3 hours
  • rate of loss of 150mLs/min

Bleeding which leads to a heart rate of >110 bpm and/ or a systolic BP < 90 mm Hg is a useful indicator of major blood loss of 1000 mL or more in an adult.

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70
Q

commonest causes of major haemorrhage

A

GI haemorrhage]trauma
ruptured AA
obstetric haemorrhage

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71
Q

management of major haemorrhage in adults

A

Activate major haemorrhage protocol
Administer high flow oxygen
Insert 2 wide bore peripheral cannulae and provide fluid resuscitation.
Contact key personnel, including experts to treat bleeding cause.
Arrest bleeding and treat underlying cause as soon as possible.
Request laboratory investigations and perform Point of Care Tests where available, including blood gas analysis and viscoelastic tests (ROTEM/ TEG).
Transfuse red cells to maintain a haemoglobin level of 70-90 g/L
Administer tranexamic acid within 3 hours of onset of haemorrhage unless complicated by disseminated intravascular coagulation
Transfuse FFP empirically if estimated blood loss greater than 20% blood volume or if microvascular bleeding
Anticipate the need for additional blood components (including red cells, FFP, platelets and cryoprecipitate)
Use cell salvage where available and appropriate
When bleeding is under control additional doses of FFP should be based on results

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72
Q

procedure to maintain Hb between 70-90g/L

A

Give group O D negative uncrossmatched red cells in cases of life-threatening bleeding, until patient’s ABO group and D status is known. The clinical assessment of the urgency of the transfusion needs of the patient is key to ensure blood availability specifically meets the needs of patient
Cross-matched red cells can be transfused if already prepared for patient concerned
Group specific red cells should be requested on the group and screen sample, since a full cross match will take time for serological testing.
A blood warmer with rapid infusion facility should be used to reduce the risk of hypothermia.
Consider use of cell salvage , where available, to reduce requirement for allogenic red cells
The patient’s haemoglobin level should be checked regularly (minimum of hourly intervals during active bleeding) to monitor transfusion therapy and to avoid excessive red cell transfusion. A blood gas analyser or other point of care test eg haemocue may be used. Similarly coagulation tests/ POCT should be regularly repeated.
Administer 10% calcium gluconate if ionised calcium less than 1.13 mmol/l to optimise coagulation.

73
Q

complications of major haemorrhage

A
thrombocytopenia
hypothermia
hypocalcaemia
hyperkalaemia
adult resp distress syndrome 
coagulopathy
74
Q

what is included in plasma albumin solution

A

95% albumin and electrolytes but no clotting factirs or BG antibodies - so crossmatching not required

75
Q

how much does concentrated 20% human albumin solution expand the circulation by?

A

3-4

76
Q

what are the two concs that albumin comes in and the volumes and infusion rates for them

A

4.5-5% - 400mLs 5-15mLs/min

20-25% - 100mLs 1-2 mLs/min

77
Q

why would conc 20-25% albumin solution be needed?

A

restore plasma volume in pts with interstitial oedema
acute lung injury with severe resp failure
promote diuresis in patients with severe hypoalbuminaemia eg hepatic cirrhosis

vital signs should be closely monitored due to risk of circ overload

78
Q

what is prothrombin complex concentrate and when is it used

A

conc of three or four inactivated clotting factors - II, IX, X or II, VII, IX, X and Protein S and C anticoagulant factors

treats - bleeding, peri-op proph of bleeding

79
Q

common s/e of IV IG

A

fever
muscle pain
headaches

these can be resolved by slowing rate of infusion and administering paracetamol

80
Q

toxicity with IV IG

A

The total dose per course must not exceed 2g / kg body weight, usually administered over 2-5 days.

81
Q

define acute transfusion reaction

A

are adverse reactions occurring at any time up to 24 hours after a transfusion of blood or blood components

82
Q

what is a delayed transfusion reaction + examples

A

defined as a fever and other signs of haemolysis more than 24 hours after
confirmed by
- fall in Hb or failure of increment
- raise in bilirubin and LDH
- incompatible crossmatch not detectable pre-transfusion
- iron overload

83
Q

name 4 myeloproliferative disorders

A

polycythaemia rubra vera - red cell proliferation

chronic myeloid leukaemia - white cell proliferation

essential thrombocythaemia - platelet proliferation

myelofibrosis - marrow stroma proliferation

84
Q

what level of platelets will cause spont bleeding or haemostasis

A

spont bleeding <20

haemostatic >80

85
Q

causes of thrombocytopenia

A

Failure of platelet production

  • Vitamin B12 or folate deficiency
  • Bone marrow infiltration (leukaemia or metastases)
  • Radiation, cytotoxic therapy

Increased consumption of platelets

  • Immune thrombocytopenia (ITP)
  • Disseminated intravascular coagulation (DIC)
  • HIV infection

Hypersplenism

86
Q

causes of thrombocytosis

A

Secondary

Bleeding, Infection, Inflammation, malignancy

Primary: Essential Thrombocythaemia

  • Uncontrolled malignant proliferation of megakaryocytes
  • Platelets >600 persistently
  • Arterial and venous thrombosis
  • Bleeding with very high counts eg >1500
  • Treatment with aspirin, hydroxycarbamide, anagrelide, interferon
87
Q

normal haemostasis pathophys

A

Localized vasoconstriction at the site of injury

Adhesion of platelets to damaged vessel wall and
formation of a platelet aggregate or plug

Activation of the coagulation cascade leading to fibrin
formation, reinforcing the platelet plug

Activation of the fibrinolytic system which digests the
haemostatic plug, re-establishing vascular patency

88
Q

two types of thrombosis and their differences/treatment

A

arterial circ - MI/stroke, platelet rich, antiplatelet

venous circ - DVT/PE, fibrin rich, anticoags

89
Q

RF for venous // arterial thrombosis

A
venous 
Acquired
Age, previous VTE
Surgery/trauma, immobility, obesity
Cancer, serious illness
Pregnancy, contraceptive pill, HRT
Inherited (Thrombophilia)
ARTERIAL 
Smoking
Obesity
Hypertension
Diabetes mellitus
Older age
Not inherited thrombophilia
90
Q

DOACs vs Warfarin

A

Advantages of DOACs
Rapid onset of action
Fixed oral dosing with predictable anticoagulant effect
Low potential for food or alcohol interactions
Low potential for drug interactions
No need for blood monitoring

Disadvantages of DOACs
Renal elimination
No specific antidotes for the Xa inhibitors
Licensed for only specific indications

91
Q

severe anaemia classification and waht it causes

A

<8g/dl

causes signs of hyperdynamic circulation:

  • tachycardia
  • flow murmur
  • cardiac enlargement
  • increased cardiac output
92
Q

approach to normocytic anaemia to find differential

A
  1. check reticulocyte count
    - > increased -> haemolysis? yes = haemolytic anaemia, no = recent bleed
  • > decreased or normal -> any evidence of renal or endocrine failure or chronic inflam? then = anaemia of renal, endocrine or chronic disease
  • > if not then consider a primary bone marrow problem (pure red cell aplasia, MDS, MM, infiltration) -> bone marrow ix
93
Q

where is absorption of iron folate and B12 take place

A

iron = duo/jejunum

folate = jejunum

b12 = ileum

94
Q

what is iron transported as and stored as

A

trans = transferrin

stored = ferritin, haemosiderin

95
Q
iron deficiency anaemia
pres
causes
ix
differentials
mgmt
A
pres
Fatigue
Pallor
Pica
Nail changes - koilonychia (spoon nails), brittleness
Hair loss
Mouth changes - angular stomatitis, atrophic glossitis (burning)
Faintness
Dyspnoea

causes
Inadequate intake - poor diet, poverty
Poor absorption - poor acid production, gastric surgery, coeliac
Excessive loss - GI bleeding (unknown loc), peptic ulcer, diverticulosis, neoplasm, menorrhagia
Excessive iron requirement - infancy, preg, hookworm

ix
Hb and haematocrit
<13g/dL (men), <12g/dL (women)
MCV
<80fL = microcytic
MCHC
Low = hypochromic
Peripheral blood smear
- Hypochromic
- Microcytic
- Anisocytosis (different size)
- Poikilocytosis (different shape, pencil)
Iron studies (FITT)
- Serum iron - low
- Serum ferritin - low (<12ng/mL is diagnostic, but dont forget its an acute phase protein so raised in any infection, inflam, malignancy)
- Total Iron Binding Capacity - increased
- Transferrin saturation - low
Investigations for cause
- Coeliac serology, H. pylori/urease breath test, UGI/LGI endoscopy (rule out malignancy)

ddx
chronic disease - 20%
sideroblastic

mgmt
oral iron replacement - ferrous sulphate 2-3mg/kg/day in 4 doses, for 3-6 months SE = constipation, black stools, vomiting
diet - dark-leafy green veg, meat, iron-fortified bread

consider transfusion - if symptomatic at rest or hb <70 or <80 with cardiac illness, old etc

96
Q
sideroblastic anaemia
when to suspect
define sideroblast
mechanism
causes
ix
mgmt
haemosiderosis
A

when to suspect
microcytic hypochromic anaemia not responding to iron

sideroblast = Atypical abnormally nucleated erythroblast with perinuclear iron accumulation

mech
Ineffective erythropoeisis. Increased
iron absorption but can’t incorporate
to haemoglobin

causes
Congenital - inherited XLSA (x-linked)
Acquired - MDS (myelodysplastic syndrome), myeloma, PRV, pyridoxine (B6) deficiency, alc, anti-TB meds

ix
Hb and haematocrit
<13g/dL (men), <12g/dL (women)
MCV
<80fL = microcytic
MCHC
- Low = hypochromic
Peripheral blood smear - Dimorphic population of normal and hypochromic red blood cells
Iron studies (FITT)
- Serum iron - high
- Serum ferritin - high
- TIBC - low
Marrow aspirate - Perinuclear ring of iron granules with Prussian Blue
mgmt
mainly supportive
iron chelation = desferrioxamine
repeat transfusion - if sympt at rest
avoid alc + vit c as these increase iron absorption
if hereditary consider pyridoxine (B6) 

haemosiderosis = iron deposition at liver kidney and heart

97
Q

thalassaemia haemoglobin

A

normal - 2x alpha 2x beta chains

HbF = 2 x alpha 2 x gamma

HbA2 = 2xa 2x delta

98
Q
beta thalassaemia
what is it 
patho
epi
TYPES
investigations
mgmt
comps
A
what is it 
Inherited microcytic anaemia caused by mutation in beta-globin gene.
autosomal recessive
chromosome 11
β0 - complete absence
β+ - some beta-globin

epi
med, africa, south east asia

patho
Decreased/absent synthesis of beta-globin leads to excess alpha production + membrane damage/cell destruction
Ineffective erythropoeisis
cells cant survive - 1. anaemia
2. erythroid hyperplasia - bony changes in skull (flat bones, air space sinus, vertebral bodies)
skull bossing + Extramedullary hematopoiesis - hepatosplenomegaly

TYPES

  1. silent carrier -> normal haem
  2. minor/trait -> B/B+ or B/B0, usually asymp, mild anaemia (confused with IDA)
  3. intermedia -> β+/β+ or β0/β+, similar pres as maj but as toddler
  4. major (aka cooleys anaemia) β0/β0, Complete absence HbA, presents at months with progressive pallor and abdo distension + skull bossing (or chipmunk face) + failure to thrive

ix
FBC- microcytic anaemia
Peripheral blood smear:
- Microcytic
- Target cells
- Nucleated red cells
Reticulocyte count- Elevated (haemolytic)
Haemoglobin analysis (electrophoresis)
- Major: No HbA, elevated HbF and HbA2
- Intermedia: Decreased HbA, elevated HbF and HbA2
- Minor/Trait: Mostly HbA, elevated HbF and HbA2
LFT - Elevated total and unconjugated bilirubin (haemolytic)
XRay skull - Hair on end sign, widening of diploeic space
AUSS - Hepatosplenomegaly

mgmt
minor - genetic counselling + iron advice
inter - genetic counselling + transfusion at symptomatic anaemia (infection, perioperative) + iron monitoring with chelation (desferrioxamine)
3. maj - Genetic counselling + regular transfusion to >10g/dL + iron monitoring with chelation
+/- splenectomy
+/- assessment for haematopoeitic stem cell transplant

comps
1. Thrombotic
2. Complications of iron overload
a - Arthropathy (MSK)
b - Pigmentation and bronzing
c - Arrhythmias and contractile dysfunction -> congestive heart failure
d - Endocrine
anterior pituitary -> slow growth, delayed sexual maturation
pancreatic islet cells -> impaired insulin secretion (T1DM)
3. Transfusion reactions + transmission acquired infections (HIV, HBV, HCV)
4. Splenectomy complications

99
Q

causes of splenomegaly

A

Splenomegaly results from multiple transfusions, iron deposition and extramedullary erythropoeisis and can lead to hypersplenism.
This leads to an increased transfusion requirement and a decreased red cell survival as well as leukopenia and thrombocytopenia.

100
Q
alpha thalassaemia
what is it
patho
epi
types
pres
ix
mgmt
A

what is it
Inherited microcytic anaemia caused by mutation in alpha-globin genes.
autosomal recessive
chromosome:
16
Different mutations:
α0 (–/) - both alpha genes on same chromosome deleted
α+ (α-/) - one of two alpha globin genes is deleted on same chromosome

patho

  1. Decreased/absent synthesis of alpha-globin leads to excess beta production
  2. There are 2 copies/alleles of the alpha globin gene on each chromosome 16 (α1 and α2)
  3. Ineffective erythropoeisis - anaemia and haemolysis

epi
Corresponds to malaria distribution -
sub-saharan africa + middle east + south east asia

TYPES

  1. silent carrier - 1 of 4 alpha globin genes affected - asymptomatic
  2. trait - 2 of 4 alpha globin genes affected - heterozygous (α0/α) or (α+/α+) - mild anaemia (hypochromic, microcytic) or normal Hb, confused IDA
  3. HbH disease - 3 deletions (α0/α+) - leads to beta tetramers - detected on electrophoresis - anaemia + splenomeg
  4. major or bart hydrops fetalis - Homozygous (α0,α0), all 4 alleles affected death in utero

pres
RF - fh, malaria, geo
Symptoms of anaemia - fatigue, dizziness, SOB
Splenomegaly
Presentation in childhood - more severe, growth retardation
Symptoms of gallstones - bloating, abdo pain, gallstones common in HbH

ix
FBC - Microcytic anaemia (MCV low, MCHC low)
Peripheral blood smear:
- Microcytic/hypochromia
- Target cells
- Basophilic stippling in HbH
Reticulocyte percentage- Elevated (haemolytic)
Haemoglobin analysis (electrophoresis):
- Presence of HbH, Hb Bart, will not detect silent carrier or trait
Iron studies:
- Serum iron - normal or elevated
- Serum ferritin - normal or elevated

mgmt
genetic counselling + iron advice (avoid unless deficient)
HbH - + folic acid (1mg, PO) + education + regular transfusion to >10g/dL + iron monitoring with chelation
+/- splenectomy
+/- assessment for haematopoeitic stem cell transplant
crisis - identify cause + monitor + folic acid +/- red cell transfusion

101
Q

haemolytic anaemias
what is it
when can it happen

A

Haemolysis is the premature destruction of RBC. It can happen in two places:
1. Within circulation/Intravascular:
a. Trauma e.g. mechanical heart valve
b. Complement mediated lysis
Reticuloendothelial system/Extravascular:
a. Macrophages of liver
b. Spleen
c. Accelerated red cell destruction due to immune targeting by antibodies

102
Q
haemolytic anaemia
causes
accquired explained
pres
ix
mgmt
A

causes
1. Hereditary:
a - Enzyme defects - Glucose 6 phosphate dehydrogenase deficiency
b - Membrane defects - Hereditary spherocytosis, elliptocytosis
c - Abnormal Hb production - Sickle cell anaemia, thalassaemia

  1. Acquired:
    a - Immune mediated
    b - Non-immune mediated

ACCQUIRED
Immune mediated:
- Caused by autoantibodies and direct antiglobulin +ve (Coombs’ positive)
- Often part of other AI cond (SLE/reactive arthritis/scleroderma)
- Divide into 2 subtypes depending on temperature at which antibody binds to RBC:
1. Warm
IgG mediated - Rx: steroids
2. Cold
IgM mediated - Rx: keep warm

Non-immune mediated:
- Direct antiglobulin -ve
- Infection (e.g. malaria), trauma, microangiopathic haemolytic anaemia (DIC, TTP, HUS, HELLP), hypersplenism, liver disease
- Paroxysmal nocturnal haemoglobinuria:
a - Rare membrane defect
b - Haemoglobinuria, marrow failure + thrombophilia, Dx: urinary haemosiderin

pres
anaemia symps
jaundice
splenomeg
episodic dark urine
presence of RF - AI disorders, prosthetic heart valve, family origin Med or middle east, 
family history haemoglobinopathy or RBC membrane defect, PND, 
Cephalosporins, fava beans

ix
FBC + MCHC + reticulocyte count:
- Low Hb
- Increased MCHC suggestive of spherocytes and reticulocytes
- Reticulocyte count >2%
Unconjugated bilirubin - Mildly elevated
Urinalysis - Haemoglobinuria
LDH and Haptoglobin: (this will bind free haemoglobin in intravascular causes)
High and Low, n.b. High LDH and low haptoglobin is 90% sensitive for haemolytic anaemia
Peripheral blood film:
- Sickle cells
- Spherocytes
- Elliptocytes
- Heinz bodies: bite and blister cells - G6PDD
- Hypochromic - thalassaemia
Coombs test - blood cells washed and incubated with Coombs’ reagent - look for agglutination, Positive for immune mediated
Other tests - creatanine/urea (raised in TTP or HUS), LFT (elevated in liver disease), Donald-Landsteiner antibody in cold-immune disease

mgmt
coombs posi - Treat underlying + support (packed RBC transfusion, if symps + folic acid for RBC prod)

combs neg:

  • valve - cardiology eval
  • TTP - plasma exchange
  • Paroxysmal Nocturnal Haemoglobinuria - corticosteroids + anticoag
  • hypersplenism - splenectomy

membrane disorder - splenectomy + support

G6PDD - avoid triggers + support

haemoglobinopathies - support + disease specific

103
Q

in haemolytic anaemias what does the… cause:
increased breakdown?
increased production?
extravascular or intravascular?

A

Increased breakdown?
- Increased bilirubin, increased urobilinogen, increased LDH

Increased production?
- Increased MCV by increased reticulocytes, marrow hyperplasia

Extravascular or intravascular?

  • Intravascular - increased free plasma Hb and decreased haptoglobin, increased haemoglobinuria (no blood cells)
  • Extravascular - splenomegaly
104
Q
G6PDD
what is it 
patho
pres
triggers
ix
mgmt
A

what is it
An inherited X-linked recessive (G6PD gene) enzyme deficiency common among parts where malaria (protective) is common: Mediterranean, sub-Saharan Africa, Asia

patho
G6PD catalyses step one of pentose phosphate pathway (similar glycolysis) which generates NADPH (important for red cells to protect from oxidative stress)

pres
prolonged neonatal jaundice or haemolytic anaemia
pallor
dark urine -  suggests intravascular haemolysis
nausea
vom
dehydration
AKI - haemoglobin precip

triggers:
infection
broad beans
drugs that cause oxidative stress - sulphonamides, cephalosporins

ix
See haemolytic anaemia investigations
Peripheral blood smear:
- Blister/bite cells - suggestive of oxidative stress as cause of haemolysis
- Heinz bodies - fragments of denatured haemoglobin
Genetic testing for G6PD variants

mgmt
treat as acute haemolysis:
- Maintain fluid intake
- Folic acid 5mg orally (for RBC production)
- Blood transfusion if severe anaemia (<7g/dL)
- Renal support if renal impairment by haemoglobinuria (EPO)

105
Q
anaemia of chronic disease
characteristic features
why?
ix
patho
causes
mgmt
A

characteristic
anaemia and evidence of immune system activation

due to
Inflammation mediated reaction and decreased RBC production + decreased survival

ix
Normocytic normochromic/microcytic hypochromic hb
Low reticulocyte count as of underproduction by marrow (typical in ACD) due to EPO
Low serum iron
Low TIBC
Low transferrin saturation
Elevated ferritin

patho
Release of pro-inflammatory cytokines by infection, neoplasm, autoimmune, trauma (VITAMIN CDEF)
Cascade leads to fall in serum iron and decreased RBC survival

IL-1 and IL-6:
1. upregulate hepcidin synthesis
Hepcidin is a regulator of iron metabolism produced by the liver
2. Down regulates ferroportin (which exports iron from enterocyte)
Less free iron for erythropoeisis (and micro-organism growth) and cytokine induced shortening of RBC life

causes - VITAMIN CDE
Vascular
Infective/inflammatory - Chronic: TB, fungal, hepatitis, HIV, Acute: pneumonia, pyelonephritis, endocarditis, cellulitis
Traumatic
Autoimmune - RA, SLE, dermatomyositis, PMR, scleroderma
Metabolic
Iatrogenic
Neoplastic - lymphoma, carcinoma
Congenital
Degenerative - CKD, CHF, chronic lung disease
Endocrine - DM

mgmt
treat underlying disease
RBC trans if symptomatic

106
Q
aplastic anaemia
def
pres
causes
assocs
pathophys
ix
mgmt
A

def
TRIAD:
Pancytopenia (BM failure) with hypocellular bone marrow and no abnormal cells (aka On BM biopsy
Hypocellularity with no dysplasia or blasts)

pres:
1. neutropenia - infections (<1.5) (lymphocytes are typically spared)
2. normochronic, normocytic anaemia - fatigue, pallor, dyspnoea, faintness (<100)
3. thrombocytopenia - bleeding, bruising (<50)
30 yrs old

causes
acquired:
- Idiopathic (50%)
- Drug or toxin exposure -> NSAIDs, penicillamine, gold, chloramphenicol, phenytoin
- Post virus (especially hepatitis + parvovirus)
inherited:
- Fanconi anaemia (AR)
- Shwachman-Diamond syndrome (AR)

assocs
PNH, pregnancy, coeliac, SLE

patho
autoimmune attack on hematopoietic
system
DNA damage repair mechanisms

ix
FBC - At least 2 cytopenias
Reticulocyte count - <1%
Bone marrow biopsy - Hypocellular marrow with no abnormal cell population

mgmt
If asymptomatic:
- Give neutropenic regimen (MASSC risk assessment if NP< 0.5, Full barrier nursing, Avoid IM injections, Look for infection, Check bloods and cultures, Vitals 4 hourly)

If severe:
- Matched related allogeneic BM transplant (If BM cellularity < 25% can be curative
Worry about Graft vs host disease (GVHD)) + RBC and Pt transfusion + ABX (Antibiotics and antifungals to local guidelines)

107
Q
neutropenia
when immunocomp/severe?
causes
sepsis triad
mgmt
A

when immunocomp = 0.5-1.0

severe = <0.5

causes
Aplastic anaemia, immunosuppression, chemotherapy, HIV, BM infiltration,
Neoplastic disease, infections…… (think decreased prod and increased destruct)

sepsis triad
T > 38.5 or 2 readings >38.0 (an hour apart) + NP < 0.5 x 10^9/L + hypotension

mgmt
Sepsis work up (FBC, BC, CRP, ESR etc) + Sepsis 6 with tazocin (tazobactam [beta lactamase inhib] + piperacillin) +fluid challenge + G-CSF (Given S/C to stimulate NP production)

108
Q

where does the bone marrow do haemopoiesis?

where would you get a sample

A

axial skeleton - vertebrae, sternum, ribs, skull
long bones
biopsy taken from iliac crest

109
Q
sickle cell anaemia
what is it
patho
epi
types
precipitants
symps
crisis pres
ix
mgmt + crisis gen management
comps
A

what is it
Disease of RBC caused by AR single gene defect in beta chain of Hb (HbA) (valine replaces glutamine in sixth amino acid) resulting in sickle cell haemoglobin (HbS)

patho
crescent shaped haemoglobin = disrupted blood flow + break (haemolysis), cause varying degrees anaemia, obstruction of small blood caps = painful crises, organ damage, increased vulnerability to infection
HbS will polymerise at periods of hypoxia + acidosis

epi
very common in sub-saharan africa

types

  1. sickle cell trait = HbSA - protective falciparum malaria, disability @ hypoxia. Venous occlusion may occur at operation therefore require testing before if black.
  2. sickle cell disease = HbSS
  3. haemoglobin SC disease = HbSC - sickle gene from one parent and haemoglobin C (lysine for glutamine at 6) from other. Make no HbA.
  4. sickle cell beta thal
precipitated by CHIDS
Cold
Hypoxia
Infection
Dehydration
Stress
symps
parents have it
jaundice
pallor
lethargy
tachycardia
vaso-occlusion - Dactylitis, visual floaters (retinal arterioles), persistent pain in skeleton, chest and abdomen, chronic renal failure, CNS infarct

crisis pres

  1. Acute chest syndrome: pneumonia like syndrome (due to sickling in pulmonary vasculature) - chest pain, fever, dyspnoea, tachypnoea, ?collapse
  2. painful, ischaemia - bone/ abdo - Bone infarction and avascular necrosis femoral head, mesenteric ischaemia
  3. aplastic - temp bone marrow failure - severe anaemia - trig = PARVOVIRUS B19
  4. splenic sequestration - life threatening sudden enlargement of the spleen leading to hypovolaemia
  5. cerebrovascular
  6. priaprism - nocturnal + risk of long-term impotence

ix
Hb- low
Reticulocytes - High (10-20%)
Bilirubin - high
Peripheral blood film - Sickled cells and Howell-Jolly bodies. Target cells at HbSC
Sickle solubility test - Doesn’t distinguish HbSS from HbSA - turbid appearance, normal Hb is clear
GOLD - Hb electrophoresis - To diagnose variant
Iron studies - Normal
Other - LFTs, Renal function, LuFT at diagnosis for baseline
SHOULD BE DIAGNOSED AT NEWBORN BLOOD SPOT

mgmt
Give pneumococcal vaccine 5 yrly and penicillin prophylactically for pneumococcus + genetic counselling + parental education
*Sequestration prevents blood from leaving spleen -> acute splenic engorgement
trigger avoidance
manage daily pain
Hydroxyurea (with monthly blood tests) - Increases production of fetal haemoglobin - reduces painful crises
Repeat blood transfusion to maintain HbS below 30% and Hb > 10g/dL
CRISIS GEN MGMT PRINCIPLES:
1. hydration - IV fluids
2. oxygenation
3. pain relied
4. abx as indicated by local guidelines
5. consider exchange transfusion

comps
Anaemia
Liver complications - jaundice, hepatomegaly and gallstones
Iron overload from chronic transfusion
Dactylitis
Leg ulcers
Priapism - requires urgent urological aspiration if >4 hours
CV - hyperdynamic precordium, flow murmur, cardiomegaly. Treat for heart failure and HTN

110
Q

megaloblastic anaemia
what is it
causes
symps

A

what is it
Unusually large, structurally abnormal RBCs
Defective DNA synthesis which also leads to leukopenia and thrombocytopenia
macrocytic anaemia

causes
B12/folate deficiency + drugs (hydroxyurea)

symps
Tend to be asymptomatic as slow onset of decreased Hb due to fall in B12 and folate allowing the body to adjust

111
Q
folate deficiency 
what is it 
what is folate used for
present in?
absorbed in?
causes
pres
ix
mgmt
A

what is it
A type of macrocytic anaemia with absence of neurological signs

what is folate used for
DNA synthesis + repair (@pregnancy = NT defects)

present in
Green vegetables, nuts and liver

absorbed in
prox jejunum + duodenum

caused by

  1. poor diet - pov, alc, elderly
  2. increased demand - preg, renal disease/dialysis, chronic haemolytic anaemia
  3. malabsorption - coeliac, tropical sprue
  4. drugs, alc, methotrexate - inhibits synthesis folic acid

symps
Pallor, fatigue, dyspnoea, faintness, tachycardia, heart murmur
headache - hallmark sign of megaloblastic anaemia
GI - loss of apetite/ weight loss (from increased energy demand of ineffective erythropoeisis) - hallmark sign of megaloblastic anaemia. Diarrhoea if coeliac.
skin/mouth - exfoliative dermatitis, glossitis, painful swallowing (inflamed oral mucosa)

ix
FBC - low haem, raised MCV + MCH, thrombocytopenia, neutropenia
reticulocyte count - low
peripheral blood smear - macrocytic RBCs and hypersegmented neutrophils
serum folate - low
RBC folate - low
serum B12 - normal
LFT - ?alc liver disease

mgmt
macrocytosis without anaemia - oral folic acid 1-5mg + treat disorder
macrocytosis + pancytopenia - oral folic + treat disorder + packed RBC transfusion
folic acid for 4 months +/- B12

112
Q
B12 deficiency 
aka
what is it
B12 used for
present in
absorbed in/how
causes
pres
ix
mgmt
A

aka
cobalamin

what is it
A type of macrocytic anaemia with peripheral neuropathy and neuropsych complaints

used for: DNA synth, myelination of nerves and red blood cells (without = megaloblastic anaemia + neuropathy)

present in - meat, fish, dairy

absorbed in - ileum (combined with intrinsic factor)
how - 1. B12 released from food in stomach by peptic acid
2. Parietal cells at gastric fundus produce intrinsic factor (IF)
3. IF binds B12 to form an IF-B12 complex
4. Complex travels to terminal ileum
5. Endocytosis occurs and complex binds to transcobalamin which is released into the blood stream

caused by -

  1. poor diet - vegan, vege, old age
  2. decreased gastric breakdown - hx of gastric surg, atrophic gastritis
  3. malabsorption - pernicious anaemia, crohns, coeliac
  4. drugs - metformin (decreases absorption), PPI, H2 antagonists

pres
pallor
fatigue
dyspnoea
faintness
mild jaundice
haemolysis
NEURO - Paresthesias, ataxia + loss vibration (posterior column degeneration), peripheral neuropathy, dementia, psychosis
SUBACUTE DEGENERATION SPINAL CORD - upgoing plantars, loss knee jerk, loss ankle jerk
GI - chronic GI illness, surgery
mouth signs - glossitis, angular chelitis

ix
FBC - Elevated MCV, low haematocrit, 25% do not have anaemia, if severe = pancytopenia
Serum B12 - Low
Peripheral blood smear - Megalocytes (RBC precursor) and hypersegmented neutrophils -> megaloblastic anaemia
Reticulocyte count - Low (decreased production)
IF antibody
+ve if cause is pernicious anaemia

mgmt
Symptomatic + severe i.e. pancytopenia + anaemia + neurological = IM hydroxycobalamin 1mg (daily) + refer to
neuro/haem + oral folic acid (1mg PO OD) will correct Hb
not neuro + admit and blood transfusion

mod + no neuro involve -
IM hydroxycobalamin 1mg 3x/week for 2 weeks then
once every 3 months
Need for lifelong therapy

113
Q
pernicious anaemia 
what is it 
associated with
risk of 
pres
specific test
mgmt
A

what is it
Autoimmune atrophic gastritis -> Atrophy of gastric mucosa with failure of IF and acid production due to autoantibodies to IF
leads to B12 deficiency
pernicious = causing harm, especially in a gradual or subtle way

assoc with other AI diseases ->
Thyroid (25%)
Vitiligo
T1DM
Addisons
group A blood
Women > men x 1.6

risk of GASTRIC CANCER

pres
anaemia features:
lethargy, pallor, dyspnoea
neurological features:
peripheral neuropathy: ‘pins and needles’, numbness. Typically symmetrical legs > arms
subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia
neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy
other features
mild jaundice: combined with pallor results in a ‘lemon tinge’
glossitis → sore tongue

specific tests:
FBC + vit b12 + folate
1. IF antibody
2. Antiparietal cell antibody:
- 90% sensitive (not specific - elevated in atrophic gastritis)
3. Serum gastrin (fasting)
4. Schilling test (NO LONGER DONE) (radiolabeled B12)
- Oral radiolabelled B12 with IM unlabelled B12 @1 hour later
- Collect urine over 24 hours
- Normal result shows 10% of radiolabelled B12 in urine, if = impaired absorption there will be less
- If impaired absorption give oral radiolabelled B12 with IF
- If urinary radiolabelled B12 is high = pernicious anaemia, if low = malabsorption

mgmt
B12 replacement as in B12
folic acid supplements

114
Q

two main types of haematological malignancies

A
  1. bone marrow - myeloid (haematopoietic stem cells - blood forming system)
  2. lymphatic - lymphoid (can be B/T cell)
115
Q

what is leukaemia

A

Excess of abnormal white cells in peripheral blood - myeloid or lymphoid

116
Q

what is lymphoma

A

Tumour presentation with local or scattered lumps in lymphatic system

117
Q

what is myeloproliferative disorders

A

Involve BM, liver and spleen with peripheral blood features

118
Q

for haematological malignancies what are the differentials for Acute onset with rapid
progression -> life-threatening
in weeks/months

A

myeloid - AML

lymphoid - ALL (T or B cell origin). high grade lymphoma (DLBCL)

119
Q
for haematological malignancies what are the differentials for 
Slowly progressive disorders
with usual interval of years
between presentation and
clinically relevant condition
A

myeloid - CML myeloproliferative neoplasm (polycythaemia rubra
vera, myelodysplastic syndrome)

Lymphoid - CLL, low grade lymphoma (follicular, marginal
zone), myeloma

120
Q

acute leukaemia

pres

A

pres
tumour - bone pain, fever, lethargy, fatigue, night sweats, weight loss
bone marrow failure - anaemia (pallor, SOB, fatigue), thrombocytopenia (petechial rash, bleeding, bruising), neutropenia (freq/recurrent infections) eg candida
circ cell related - hyperviscocity (headache, neurology eg cranial nerves), infiltration (tissues, organs), skin/gums @ monoblastic AML, hepatosplenomeg, lymphadenopathy, testicular enlargement

121
Q

DIAGNOSE:
A 58-year-old man presents to his primary care physician with increasing tiredness, accompanied by bruising on his legs. He also complains of aching bones. He has no previous illnesses. On examination, he is pyrexial and pale, has bony tenderness over the sternum and tibia, and has petechiae on his legs. There are no palpable lymph nodes. He has crepitations at the left base. The liver and spleen are not palpable.

A

AML

122
Q
AML 
what is it 
diagnostic feature
epi
assocs
ix
ddx
mgmt
prog
A

what is it
Clonal expansion of myeloid blasts in bone marrow, peripheral blood or extramedullary tissue, unable to differentiate into neutrophils

diagnostic feature
Bone marrow blasts > 20% or peripheral blood

epi
most common ADULT leukaemia (>65) - can be comp of chemo

assoc
Myelodysplastic syndrome, Down’s syndrome, bone marrow failure syndromes (e.g. Fanconi, Diamon-Blackfan, aplastic anaemia), smoking

ix
FBC - Leukocytosis (increase in WCC) with neutropenia, thrombocytopenia, anaemia
Peripheral blood film - Blasts + Auer rods (crystallised granules in myeloid blasts)
Coagulation panel- As baseline: PT and PTT may be prolonged with normal fibrinogen and D-dimer
U+E, LFT, renal function- For baseline
Bone marrow biopsy/aspirate (for definitive diagnosis) + immunophenotyping:
- Hypercellularity, blasts > 20%, Auer rods
- Flow cytometry immunophenotyping/FISH
CXR - Pulmonary infiltrates

ddx
ALL - clinically indistinguishable, requires BM biopsy + immunophenotyping
myelodysplastic syndrome - based on number of blasts (blood film >10%, bone marrow <20%)
aplastic anaemia - hypocellular bone marrow

mgmt
Supportive care:
Hydration - electrolyte abnormalities
Allopurinol - for acute tumour lysis syndrome (increased urate)
Leukoreduction - hydroxycarbamide/leukapheresis
Transfusions - RBC + platelets
Treat infections (complication)
INDUCTION CHEMO:
Cytarabine and daunorubicin (interferes with all stages of cell cycle)
+/- STEM CELL TRANSPKANT AT FIRST REMISSION - allogenic

prog
5 yr survival 25%
poor prog factors - > 60 years
> 20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7
123
Q

what is tumour lysis syndrome

A

Electrolyte and metabolic disturbance due to breakdown of large number leukaemic cells (hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia,
renal impairment)

124
Q

diagnose
A 4-year-old girl presents with lethargy, dyspnoea, fever, and bruising. On examination she has hepatosplenomegaly. CXR shows a mediastinal mass and pleural effusion.

A

ALL

125
Q

acute promyelocytic leukaemia M3

A

associated with t(15;17)
fusion of PML and RAR-alpha genes
presents younger than other types of AML (average = 25 years old)
Auer rods (seen with myeloperoxidase stain)
DIC or thrombocytopenia often at presentation
good prognosis

126
Q
ALL
what is it 
diagnostic
epi
assocs
chromosomes
classification
extra pres
types
ix
mgmt
comps
prog + poor factors
A

what is it
Malignancy of lymphoid cells (B or T). Undergoes somatic change and undergoes uncontrolled proliferation. Lymphoid cells replace hematopoietic cells.

diagnostic
Bone marrow blasts > 20%, blood smear leukaemic lymphoblasts

epi
Rare in adults. Most common childhood leukaemia (75% < 6), girls > boys

assoc
Down’s syndrome, ionising radiation, Kleinefelter’s, Fanconi anaemia, smoking

chromosome
Most common cytogenetic abnormality in adults is Philadelphia chromosome - translocation (9,22). BCR-ABL fusion oncogene = poor prognosis

CLASSIFICATIONS
1. FAB (french american british):
L1 - small homogenous blasts (children)
L2 - large heterogenous blasts (adults)
L3 - Burkitt large basophilic B cells with vacuoles
  1. Immunological - uses surface markers
  2. Cytogenetic - chromosomal analysis, Ph chromosome is a poor prognosis

extra pres
CNS involvement - CNS infiltration by leukaemoid cells presents as papilloedema, nuchal rigidity and meningismus
May also have a focal neurology (CN 3, 4, 6, 7)
TESTICULAR SWELLING!

TYPES
from most to least common:
Pre B CD10 phenotype
Pre T
T
B

ix
FBC - Leukocytosis (increase in WCC) with lymphopenia, thrombocytopenia, anaemia
Peripheral blood film - Leukaemic lymphoblasts
Coagulation panel (for bleeding/petechiae)
U+E, LFT, renal function - For baseline
Bone marrow biopsy/aspirate (for definitive diagnosis) + immunophenotyping - Hypercellularity, lymphoblasts > 20-25% + Flow cytometry immunophenotyping/FISH/ PCR for t(9,22)
CXR + LP + pleural tap - Mediastinal widening (T), leukaemic lymphoblasts, leukaemic lymphoblasts

mgmt
Supportive care:
- Hydration - electrolyte abnormalities
- Allopurinol - for acute tumour lysis syndrome (increased urate)
- Prophylactic antimicrobials (aciclovir + fluconazole + ciprofloxacin + co-trimoxazole - pneumocystis pneumonia)
- Transfusions - RBC + platelets (if pt<10 x 10^9)
- Beware neutropenic sepsis
Induction chemotherapy (kill leukaemic cells):
- Prednisolone, vincristine, daunorubicin (anthracycline) +- tyrosine kinase inhibitor (imatinib)
- Intrathecal methotrexate (for CNS disease)
Consolidate remission (weeks)
Maintain remission (years) - mercaptopurine (daily), methotrexate (weekly), vincristine + pred (monthly)

comps
Tumour lysis syndrome
Neutropenic sepsis
Pancytopenia
Chemotherapy side effects

prog
Complete remission 90% at < 30
worst prog: male, <2 >10, WCC > 20, T or B type, philly, black

127
Q
CML 
what is it
pres
diagnosis
pathophys
course
epi
ix
mgmt
A

what is it
Uncontrolled proliferation of myeloid cells in bone marrow

pres
1/3 may be asymp
typical early: 
Malaise
Fever
Wt loss
Abdominal discomfort due to splenomegaly (elevated WBC count)
Night sweats
Arthralgia - increased uric acid from cell turnover

diagnosis
Presence of Philadelphia chromosome/ BCR-ABL fusion gene

patho

  1. Philadelphia chromosome t(9,22) produces BCR-ABL fusion oncogene (chromosome 22)
  2. Produces p210 BCR-ABL protein (p190 @ ALL)
  3. Expresses constitutionally active tyrosine kinase on surface of myeloid cells
  4. Unregulated cell division

course
Chronic phase may transform to accelerated (symptomatic) or blast phase (AML) in 10%

epi
15 - 20% of adult leukaemias. Median age 50

ix
FBC - Leukocytosis (increase in WCC), anaemia, normal platelets, thrombocytosis (chronic/accel), thrombocytopenia (accel/blast crisis)
Peripheral blood film:
- Almost all WBCs are mature myeloid cells (NP, basophil, eosinophil)
- Blasts > 10% - accelerated + basophils > 20%
- Blasts > 20% - blast phase
Metabolic profile - Raised potassium, LDH, uric acid due to cell turnover
Bone marrow biopsy/aspirate
- Granulocytic hyperplasia
Cytogenetics (FISH)
- Philadelphia chromosome

mgmt
FIRST LINE- Tyrosine kinase inhibitor (imatinib - muscle cramps/heart failure or dasatinib - pleural effusion) +- allogeneic haematopoeitic stem cell transplant + high-dose induction chemotherapy
- Blast crisis (see AML) -> leads to pancytopenia
- Presence of philadelphia chromosome is GOOD prognosis - event free survival 95%, able to use tyrosine kinase inhibitor for older people who may not tolerate chemotherapy

128
Q
CLL
what is it
epi
triggers
ix
ddx
criteria/staging
mgmt
comps
A

what is it
A malignant disorder of B lymphocytes that escape cell death (apoptosis) involving bone marrow and peripheral blood. Leukaemic cells may infiltrate lymphatic tissue and haemopoietic organs (liver, spleen, bone marrow)

epi
most common leukaemia

triggers
pneumonia,
increasing age

ix
FBC - Lymphocytosis (marked), low Hb, low pt
Peripheral blood film:
- Smudge and smear cells (damage to lymphocytes in slide prep)
- Flow cytometry: CD5, CD19, CD23 positive
CT scan - Hepatosplenomegaly, retroperitoneal, mediastinal lymph node

ddx
leukaemic phase of lymphoma

criteria/staging
BINET:
A - < 3 lymphadenopathy + normal Hb and Pt,
B - >=3 lymphadenopathy + normal Hb and Pt
C - anaemia or thrombocytopenia with any lymphadenopathy

mgmt
A + B + asymptomatic - watch and wait. Monitor with FBC, flow cytometry every 3 months
C - chemotherapy: rituximab + cyclophosphamide + fludarabide +- stem cell transplant

comps

  1. Hypogammaglobulinaemia - lymphocytes are dysfunctional and can’t produce antibodies. Pt deficient in IgG, IgA, IgM therefore increased infection risk (can give monthly IVIG)
  2. Autoimmune haemolytic anaemia - dysfunctional antibodies directed towards RBCs. Give prednisolone
  3. transformation to high grade lymphoma - richters transformation (become very unwell very suddenly)
129
Q

diagnose
A 55-year-old male farmer presents with worsening shortness of breath, night sweats, fevers, bilateral axillary lymphadenopathy, and a 7.7 kg (12%) total body weight loss over 3 months. Recently, he has not been able to work because of fatigue. Physical examination reveals a 3.5 cm left axillary mass; enlarged cervical, axillary, and inguinal lymph nodes; splenomegaly; and no hepatomegaly.

A

non-hodgkin’s lymphoma

130
Q
Non-hodgkin's lymphoma
what is it
most common
epi/rf
subtypes
assoc 
pres
ix
ddx
staging
mgmt
comps
prog
A

what is it
basically all the ones that aren’t hodgkins
Lymphomas are solid, leukaemias are circulating

most common
Most common is diffuse large B-cell lymphoma (mainly from B cell lines) -May produce immunoglobulins. T cells can travel to extranodal sites e.g. skin and CNS

epi
5x more common than hodgkins
older, caucasians, hx of chemo/radio, fh, recent viral infection, AI, immunodeficient

subtypes

  1. Diffuse large B-cell lymphoma (30%) - aggressive/high grade
  2. Follicular lymphoma (20%) - indolent/low grade
  3. Burkitt’s (HG) (1%) - EBV - characteristic jaw lymphadenopathy (child)
  4. Primary CNS lymphoma (1%) - EBV with AIDS
  5. MALT (LG) (gastric mucosa associated lymphoid tissue) - H.pylori
  6. Marginal zone - massive splenomegaly
  7. T cell

assoc
AI disorders - sjogren’s, RA, SLE, coeliac
immunodeficiency

pres
nodal - painless lymphadenopathy, asymmetrical (can be rapid)
extranodal (MUCH more common than in hodgkins):
1. Bone marrow - pancytopenia (fatigue, dyspnoea), bone pain
2. Splenomegaly (massive in marginal zone) + hepatomegaly
3. Dry cough - mediastinal mass/pneumonia
4. Skin (T cell)
5. Gut: diarrhoea, vomiting, abdo pain (MALT)
6. Bone pain
7. CNS - nerve palsies
B symptoms ( less so than in hodgkins)

ix
FBC + blood film - Thrombocytopenia (liver or BM), or pancytopenia (BM)
Lymph node core biopsy/skin biopsy/bone marrow biopsy (for flow cytometry - tumour surface markers and cytogenetics) +ve
LDH: Elevated - proliferative rate of lymphoma
ESR
CT scan/MRI - For staging
Other - LP, LFT (mets), HIV test

ddx

  1. Hodgkin’s lymphoma (bimodal 20s and 60s, pruritus and alcohol pain) - Reed Steenberg cells
  2. ALL (acute onset, purpura, bleeding, infection) - blast cells
  3. Infectious mononucleosis - with pharyngitis and rash
staging 
ANN ARBOR
1 - Single lymph node group
2- Multiple on same side diaphragm
3 - Multiple on opposite side diaphragm
4 - Multiple extranodal sites or lymph nodes and extranodal disease
E - extranodal extension
B - weight loss > 10%, fever, drenching night sweats
A - no B symptoms (B symps = worst prog

mgmt
for diffuse large b cell lymphoma or stage 3-4 follicular lymphoma
R-CHOP-21 (6-8 cycles)
+/- CNA proph - intrathecal methotrexate
+/- growth factor - G-CSF - filgastim
+/- antimicrobial proph - cipro + acic + fluconazole

prog
DLBCL - S1/2 - 80% cure rate, S3/4 - 40% cure rate
FL - incurable

comps
Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
Superior vena cava obstruction
Metastasis
Spinal cord compression
Complications related to treatment e.g. Side effects of chemotherapy

131
Q

philidelphia chromosome

A

It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of norma

132
Q
hodgkins lymphoma
what is it
pres
diagnostic
epi
most common type
causes
patho
key RF
staging
ix
mgmt
A

what is it
malignant proliferation of lymphocytes
arises from mature B cells

pres
cervical or supraclavicular lymphadenopathy (painless)
Risk factors
B symptoms (25%) - pel ebstein fever
Pruritus (10%)
Alcohol induced pain
Symptoms of mediastinal adenopathy - Dry cough, Dyspnoea, Chest pain, Superior vena cava syndrome (facial and upper limb oedema, dilated vessels)

diagnostic
Presence of Reed-Sternberg cells (large, multinucleated, mirror image nuclei, may contain EBV)

epi
bimodal @ 25 + 50

most common type
nodular sclerosing - 70%
others - mixed cellularity
lymphocyte rich/ depleted

causes
Primary immunodeficiency - ataxia-telangiectasia, Wiscott-Aldrich
Secondary immunodeficiency - HIV/transplants
Infection - EBV
Autoimmune disorders - SLE

patho
Impaired immunosurveillance of EBV infected cells. B cells escape regulation and proliferate

RF
EBV
Positive hamily history
Young adult from higher socioeconomic class

staging - ann arbor

ix
FBC - low hb, pt, WCC high or low
ESR - raised is poor prog
excisional lymph node biopsy 
CXR - mediastinal mass
PET-CT - staging
PCR - EBV
baseline liver/renal function

mgmt
Chemotherapy (ABVD) + Radiotherapy (mainly for the chest) (80% curative)
Doxorubicin
Bleomycin
Vincristine
Dacarbizine
Be aware of the side effects of chemotherapy and radiotherapy

133
Q
multiple myeloma
what is it
pres
diagnosis
3 main assocs
epi
classification
ix
criteria
comps + rx
when to transplant
A

what is it
Plasma dyscrasia: Clonal proliferation of plasma cells in the bone marrow associated with monoclonal element (Ig or Ig fragment) in serum or urine
It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells

pres
chronic relapse/remit
Bone pain (esp back pain!) - osteolytic lesions + fractures, vertebral collapse (high osteoclast activity)
Anaemia
Fatigue
recurrent bact Infections
Hypercalcaemia - bone break down babes
Renal impairment - due to light chain deposition and precipitation of light chains with Tamm-Horsfall protein in ascending loop of Henle
Bleeding -bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising

diagnosis
serum and urine protein electrophoresis

3 main assocs

  1. Osteolytic bone disease + hypercalcaemia
  2. Anaemia - by accumulation plasma cells in BM
  3. Renal disease

epi
Most common haematological malignancy
Mean age is 60/70

classification
spectrum: m-protein is monoclonal component
1. MGUS - monoclonal gammopathy of unknown significance (may progress): M-protein < 30g/L, bone marrow clonal cells <10%
2. SMOULDERING myeloma - asymp: M-protein > 30g/L OR bone marrow clonal cells >10%, No related organ or tissue involvement (including bone lesions)
3. ACTIVE myeloma - symps -
A - M-protein > 30g/L OR bone marrow clonal cells >30% (10% = minor, 30% = major) 1 major + 1 minor
B - CRAB (tissue/organ involvement):
Calcium elevation (>2.75mmol/L)
Renal insufficiency (Cr > 173mmol/L)
Anaemia (Hb < 10g/dL or 2g/dL below normal)
Bone disease - lytic or osteopenic

ix
REMEMBER EVIDENCE OF END ORGAN DAMAGE
1. serum electrophoresis - GOLD (Paraprotein spike IgG > 30g/L, IgA > 20g/L, light chain urinary excretion >1g/day Bence Jones, hypogammaglobulinaemia)
2. skeletal survey, whole body MRI - Osteopenia, osteolytic lesions (e.g. pepper pot/raindrop skull), pathological fractures
3. BM aspirate + trephine biopsy - Plasma cell infiltrate >10% (minor) or >30% major
4. blood film - rouleaux formation
5. serum ca -> raised
6. FBC - anaemia
7. creatinine/urea - raised
8. ESR - raised with increased viscosity

mgmt
must begin immediately
TREAT COMPS
Bone disease: Hypercalcaemia + pain - bisphosphonates + analgesics
Anaemia - blood transfusion/EPO
Spinal cord compression - dexamethasone
Hyperviscosity (reduced cognition/blurred vision) - plasmapheresis
AKI - rehydration/ preserve good hydration
Infection - antibiotics + pneumonia/flu vaccine, IVIG
VTE proph
MGUS - Monitor closely with urine/serum electrophoresis 6 monthly

considering transplant (younger/healthier): (bortezomib) based induction + dexamethasone + DVT prophylaxis (aspirin 75mg OD) + autologous/allogeneic stem cell transplant

no transplant:
Thalidomide + an Alkylating agent + Dexamethasone

completion of treatment - monitor every 3 months- bloods, electropheresis

relapse - bortezombin monotherapy

134
Q

explain assoc of osteolytic bone disease and multiple myeloma

A

Rapid growth of myeloma cells (in BM) inhibits formation of osteoprogenitor cells and osteoblasts
Production of macrophage inflammatory protein 1 alpha (MIP1a) stimulates osteoclastogenesis and Dkk-1 inhbits osteoblasts
Imbalance leads to hypercalceamia and hypercalciuria

135
Q

50 with back pain

A

serum electrophoresis and ESR

136
Q

major and minor criteria in MM

A

Criteria: req 1 major and 1 minor

Major
Plasmacytoma on BM biopsy
BM plasmacytosis > 30%
Monoclonal spike as 1a.

Minor
Plasmacytosis 10-30%
Smaller monoclonal spike
Lytic lesions

137
Q

diagnose
A 55-year-old man has had routine physical examinations for several years and has always been healthy, does not smoke, and has no history of pulmonary disease. His primary care physician has noted a gradually increasing haemoglobin level over the past few years (to a current level of 195 g/L [19.5 g/dL]), mild leukocytosis, and mild thrombocytosis. He has frequent episodes of facial flushing that are associated with slight headaches and a feeling of fullness in his head and neck. He has noted intermittent burning, stinging, and tingling sensations in his fingertips. He has recurrent, often severe, pruritus that is exacerbated by taking a hot bath. On examination, he has a red face and neck and the spleen is mildly enlarged.

A

polycythaemia vera

138
Q
polycythaemia vera
what is it/patho
causes
pres
ix
diagnosis
mgmt
comp
A

what is it
Polycythaemia is increased proportion of haemoglobin in the blood either by:
Relative - decreased plasma volume:
1. Acute - dehydration, alcohol, diuretics
2. Chronic - smoking, obesity
Absolute - increased red cell numbers:
1. Primary - polycythaemia rubra vera
2. Secondary - high altitude, chronic lung disease (hypoxia), or increased EPO due to renal carcinoma

Polycythaemia rubra vera = is a myeloproliferative (overactive BM) disorder of predominantly red cells (but also WBC and Pt)
DEFINITION: Clonal hematopoietic disorder with erythrocytosis, thrombocytosis, leukocytosis and splenomegaly

aetiology
95% JAK2 V617F somatic mutation n.b. Ph chromosome -ve (differentiates from CML)

symps
hyperviscosity = Headache, tinnitus, dizziness, visual disturbance, plethoric appearance (red and full)
thrombosis/bleeding = Stroke, MI, PE, thrombophlebitis, DVT, haemorrhage
bath = Pruritus after hot bath, erythromelalgia (pain) + redness of fingers, palms, heels toes

ix
FBC/film - Raised haemoglobin, raised haematocrit, raised WBC, raised Pt
LFT for Budd-Chiari syndrome (raised)
JAK2 gene mutation screen (e.g. PCR)
serum ferritin
U+E
low ESR
BM biopsy- Hypercellular with trilineage growth
Chromium studies - Elevated RBC mass
EPO- Low with high Hb -> PV
MCV - Low MCV with normal Hb -> PV with IDA

diagnosis
>0.52 men >0.48 women haematocrit OR raised red cell mass >25% above predicted
mutation in JAK2

mgmt
aim - to keep low haematocrit + reduce risk of thrombosis
1. Phlebotomy/venesection (for low risk, ie. <60 and no thrombosis)
2. Cytoreduction (for high risk) - hydroxycarbamide
3. Low dose aspirin (75mg)
4. Management of CV risk factors (DM, hyperlipidaemia, HTN, smoking)

comp
10-15% transform to AML

139
Q

PV vs CML

A

PV has no philadelphia chromosome

Neutrophil alkaline phosphatase is raised in PV but decreased in CML

140
Q
myelodysplastic syndrome 
what is it
characteristics
patho
causes
epi
pres
ddx
diagnosis
mgmt
comps
A

what is it
group of malignant haematopoietic disorders

characteristics

  1. dysplastic changes in one or more cell lineages
  2. ineffective hematopoiesis
  3. predilection to develop AML
patho
bone marrow becomes hyper/hypocellular 
peripheral blood cytopenias
affects different cell lines:
- myeloid WBC
- erythroid RBC
- megakaryocyte platelet

aetiology
primary - 90%
secondayr - worst prog - due to radio/cancer

epi
>70
male
smoker

pres

  1. anaemia -> Unexplained macrocytic anaemia: fatigue, exertional dyspnoea, worsening of angina, CCF
  2. neutropenia -> If granulocyte depletion - recurrent infections/sepsis
  3. thrombocytopenia -> Decreased platelets: BLEEDING, petechia, bruising, nosebleeds, bleeding gums, ecchymosis (discolouration from bleeding)
ddx
macrocytic anaemia -> B12/folate def
neutropenia -> viral infection, drugs
thrombocytopenia -> ITP, drugs
all of above -> CML, BM failure, aplastic anaemia

diagnosis
of EXCLUSION + dysplastic cell morphology
-> FBC + blood film:
Anaemia (normo/macrocytic)
Neutropenia, thrombocytopenia, neutrophilia, thrombocytosis
Dimorphic red cells, Pappenheimer bodies, anisocytosis, poikilocytosis
-> ferritin + B12 - normal
-> renal func, LFT, CXR, ECG - co-morbs
BM asp/biopsy + cytogenetics - hypercellular with blasts

mgmt
Supportive blood and platelet transfusions + monitoring iron status (ferritin)
EPO + granulocyte colony-stimulating factor (G-CSF)
If sepsis - broad spectrum ABX
If recurrent infections - G-CSF
High-intensity chemotherapy

comps
anaemia, thrombocytpenia, neutro
transfusion related iron overload -Chronic fatigue, Joint pain, Abdominal pain, Liver disease (cirrhosis), Irregular heart rhythm/heart failure, Bronze/ashen grey skin –> desferrioxamine
transform to AML
bone marrow failure - leading cause of death
median survival - 2 yrs

141
Q

fanconi anaemia
what is it
pres

A

what is it
Mainly AR inherited bone marrow failure syndrome
Cells derived are sensitive to DNA cross-linking

pres

  1. Congenital dysmorphic features;
    - Triangular faces
    - Cafe au lait + hyperpigmented skin
    - Cardiac and renal malformations
    - Abnormal thumbs
    - Short
  2. Pancytopenic bone marrow failure
  3. Susceptibility to cancer (AML, solid tumours - head and neck squamous cell carcinoma, gynaecological cancers <50)
142
Q

thrombocytopenia causes

A

decreased production:

  1. BM infiltration - leukaemia, lymphoma, myeloma, myleofibrosis
  2. liver disease - reduction of TPO
  3. decreased BM production - low B12/folate, aplastic anaemia, infection
  4. dysfunctional prod - myelodysplasia

increased destruction

  1. autoimmune - ITP
  2. hypersplenism
  3. drug related - heparin
  4. consumption of platelets - DIC, TTP, HUS, haemorrhage
143
Q
Idiopathic thrombocytopenic purpura
what is it
typically occurs in
symptoms
important ddx
ix
mgmt
A
what is it
isolated thrombocytopenia (<100) thought to be due to autoimmune phenomenon and antiplatelet autoantibodies leading to rapid clearance in spleen

typically occurs in:
children with a preceding viral illness or middle aged women

pres
bleeding - petechiae on skin or mucosal membrane, haemorrhagic bullae in oral cavity/tongue, gum/mucocutaneous bleeding, menorrhagia

ddx
must ddx from delayed visceral bleed of coag disorders
1. Pseudothrombocytopenia
2. Thrombocytopenia due to liver disease or alcohol - raised GGT, alk phos
3. TTP - may have neurological changes or fever + anaemia
4. DIC - prolonged PT and aPTT
5. Drug induced
6. Splenomegaly

ix
FBC - pt count <100
peripheral smear - rules out pseudothrombocytopenia due to clumping/poor counting
bone marrow biopsy - increased megakaryocytes, no evidence of malignancy
causes of secondary ITP - HIV serology, H.pylori, hep B/C serology, SLE, drug induced (eg quinine)

mgmt
severe active bleeding - immunosuppression:
IVIG + pred + pt transfusion (works in 1-5 days for 4 weeks)
chronic? give rituximab (anti-b cell ie antibody) + splenectomy
if <2 consider wiskott-aldrich
IN CHILDREN - usually self-limiting -2 weeks

144
Q
thrombotic thrombocytopenic purpura
what is it
pres
patho
RFs
CAUSES
ix
mgmt
A

what is it
MEDICAL EMERGENCY - 95% fatality
clinical syndrome with microangiopathic haemolytic anaemia and thrombocytic purpura

pres
PENTAD:
1. fever
2. renal failure - raised urea + creat
3. haemolytic anaemia - pallor jaundice
4. thrombocytopenia -> purpura, ecchymosis, menorrhagia
5. neurological change - coma, focal neurology, seizure, headache, confusion
\+ GI - N+V/d

patho

  1. Absence of VWF cleaving protein (ADAMTS-13)
  2. Leads to large VW multimers
  3. Spontaneous platelet aggregation in microvasculature (brain, kidney, heart)
  4. Red cells passing clots subjected to shear force and rupture -> haemolytic anaemia
RF
black
fat
female
preg
causes
post infection
pref
drugs - ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
SLE 
HIV
ix
FBC - decreased pt, hb <80
reticulocyte count - high
LDH + bilirubin - raised
peripheral blood smear - microangiopathic blood film with schistocytes - RBC fragments
U+E - raised
urinalysis - proteinuria

mgmt
urgent plasma exchange + pred (immunosup) + antiplatelet agent (aspirin)
long-term aspirin to decrease platelet aggregation
DO NOT GIVE PLATELETS
rituximab - easy method for targeting antibody production

145
Q
DIC
suspect if
pres
how?
whats decreased?
whats increased?
mgmt
A

suspect if
CRITICALLY ILL
1. Severe sepsis or obstetric or malignancy
2. Shock
3. Extensive tissue damage - trauma and burns

pres
shock - oliguria, hypotensive, tachy
bleeding - brusing, purpura, haemorrhage, petechiae, oozing, haematuria
GEN BLEEDING from 3 unrelated sites = DIC

how
coag pathways activated
diffuse fibrin deposition at microvascular circ
consumption of coag factors and platelets

dereased:

  1. platelet count
  2. fibrinogen
  3. factor v/8
increased:
 PT (extrinsic pathway)
aPTT (intrinsic pathway - activated partial thromboplastin time)
D-dimer
fibrin degradation products
mgmt
treat cause eg sepsis
to intensive care
supportive care -stop bleeding:
- FFP - replace coagulation factors
- cryoprecipitates - second line but dont require ABO match
- platelet transfusion <20
146
Q

haemophilia
pres in who
inheritance
bleeding pattern

A

toddlers

x-linked recessive so only little boys

bleed into muscles and joints

147
Q

VWD
pres in who
inheritance
bleeding pattern

A

teenagers

AD on chromosome 12

bleed into mucus membranes and skin

148
Q
haemophilia
inheritance
types
factor 8
mgmt
A

inheritance
x-linked recessive - skip a gen

types
A = F8 deficient
B = F9 deficient (christmas disease)

F8
< 1% = severe - spontaneous bleeding to muscles/joints crippling arthritis
1-5% = mod - bleed post minor trauma
>5% = minor - bleed post surgery

mgmt
Treat with recombinant F8 or F9 concentrate (IV at bleed)
+ avoid IM injections, aspirin and NSAIDS
if mild haemophilia A - give desmopressin IV DDAVP -> stimulates endogenous release F8 + VWF

149
Q

VWD
what is it
ckinically
mgmt

A

AD chromosome 12 - defective production of VWF = defective platelet plug formation and F8 deficiency
Clinically: bruising, prolonged bleeding, mucosal bleeds, epistaxis, menorrhagia
Management is severity dependent
Type 1 = DDAVP
Severe give additional recombinant F8

150
Q
osler-weber-rendu syndrome
aka
characteristics
inheritance
diagnosis requirements
pres
mgmt
A

aka
HHT - hereditary haemorrhagic telangiectasia

characteristics
vascular dysplasia -> telangiectasia

inheritance
AD

diagnosis 
3 of:
- epistaxis (recurrent)
- telangiectasia
- visceral lesions
- family hist

pres
sharply demarcated mucocutaneous lesions

mgmt
treat severe haemorrhage with blood transfusions

151
Q

what is vit k needed for
what is it
when deficient
mgmt

A

synthesis of 1972
fat soluable vitamin
deficient in malabsorption especially obstructive jaundice

mgmt - IV vit K

152
Q

coag cascade - v basic

A

Series of proteolytic enzymes that circulate in inactive state which are sequentially activated
Generate thrombin that cleaves fibrinogen creating fibrin = clot

153
Q

platelet physiology

A

Endothelium damaged
Platelets adhere via collagen and VWF and GP1b
Binding of collagen stimulates cytoskeleton shape change
Activation causes degranulation
Alpha - PDGF, TGF-beta
Delta - ADP + ATP (amplification) + Ca2+
Aggregation: cross linking of platelets by fibrin
Activated platelet allows binding of coag factors

154
Q

what do aspirin + clopidogrel work on

A

platelet function

155
Q

what do hep and warfarin work on

A

coagulation cascade

156
Q

antiplatelets + how they work

A

aspirin
Irreversibly inhibits COX1 and prevents production of thromboxane A2. TXA2 induces platelet aggregation and vasoconstriction (75-300mg od) for arterial thrombosis

clopidogrel
Irreversible P2Y12 antagonist. P2Y12 is activated by ADP and amplifies platelet activation by activating glycoprotein Gp2b3a. Inhibits ADP induced platelet aggregation.

157
Q
anticoagulant: heparin
what is it
how does it owrk
comp
lmwh
A

works on intrinsic pathway - aPTT- measures all factors except F13 (fibrin) + F7 (tissue factor)

Heparin is a glycoaminoglycan

Binds to antithrombin and increases activity, inactivates thrombin and FXa

comp - heparin induced thrombocytopenia

LMWH - dalt is smaller and therefore renally excreted, mech inactivates FXa

158
Q

anticoag warfarin:
pathway
how it works
INR range

A

extrinsic pathway WEPT 1972 uses PT - measures F7 + 1,2,5,10

Prevents synthesis of FII, VII, IX, X
It is a vitamin K antagonist with a long half life
It prolongs the PT
It is monitored with INR (international normalised ratio derived from prothrombin time)
Aim 2-3

159
Q
DOACs
examples
work on
indications
problem
A

FXa inhibitors - apixaban, rivaroxiban

Thrombin inhibitors (FIIa) - dabigatran

Indicated for DVT/PE and AF

require no monitoring

The problem is they are NOT easily reversible

160
Q

thrombosis
what is it
arterial
venous

A

Thrombosis is blood coagulation within a vessel

May occur in arterial circulation - high pressure, platelet rich (atherosclerosis + RF)

Venous circulation: low pressure, fibrin rich (DVT + PE)

161
Q

hypercoagulable states

A
Antiphospholipid syndrome
Cancer
Slow flow - sickle cell, PRV
Nephrotic syndrome
Obesity
Pregnancy
162
Q

Blood transfusion complications

A
  1. INFECTION
    HBV
    HCV
    HIV
  2. ACUTE - non infectious
    Acute haemolytic reaction - ABO incompat
    Febrile, non-haemolytic reaction - hypersensitivity to allergens in plasma (IgE)
    Allergic/anaphylactic reaction - Result of granulocyte activation in pulmonary vasculature - increased permeability
    Transfusion-associated circulatory overload
    Transfusion-related acute lung injury (TRALI)

DELAYED non infectious
Iron overload
Delayed haemolytic reaction - Non-preventable - non-ABO aB/antigen incompatability
Transfusion-associated graft vs host disease - In immunodeficient patients, transfused white cells react recipient antigens
Post-transfusion purpura - Immune thrombocytopenia occurring post transplant
of Pt containing component. Recipient prior sensitised to foreign platelet antigen. (preg)

163
Q

which blood transfusion comp would pres like this

Fever, chest/abdo/flank pain, pain @ infusion site

A

acute haemo

discontinue blood + fluid resus

164
Q

which blood transfusion comp would pres like this

Flushing + dyspnoea + pruritus + urticaria (mins), hypotension (anaphylaxis)

A

alllergic transfusion

discontinue blood + adrenaline + secure airway (intubate) + salbutamol ± antihistamine

165
Q

which blood transfusion comp would pres like this

fever

A

febrile non haemolytic

stop blood + para

166
Q

which blood transfusion comp would pres like this

Fever, dyspnoea (hours) + rales

A

TRALI

O2 +/- ventilation
IV furose

167
Q

which blood transfusion comp would pres like this

Fever + jaundice

A

Delayed haemolytic transfusion reactions

supportive

168
Q

Transfusion-associated Graft Vs Host Disease pres

A

fever

supportive

169
Q

post transfusion purpura mgmt

A

IVIG

170
Q

pres of splenomeg

A

LUQ mass, moves with respiration, enlarges towards RIF, cannot feel above, dull to percuss.

171
Q

causes of hypersplenism

A

CHINA - MMM
Congestion - p HTN, portal vein thrombosis, budd-chiari, HF
Haematological - anamia, thalassaemia, sickle cell, leukaemia
Infection - malaria, EBV, CMV, HIV, TB, glandular fever
Neoplasm - CML, myelofibrosis, lymphoma
Autoimmune/connective tissue - RA, sarcoidosis, amyloidosis, SLE,
Chronic Myeloid Leukaemia
Myelofibrosis
Malaria

172
Q
splenectomy
types
indications
comps
mgmt
A
types
1. Planned
2. Traumatic
3. Autosplenectomy/hyposplenism (physiological loss of function) e.g. sickle cell (splenic infarct) or coeliac -> this leads to an increased risk of infection from encapsulated bacteria (Will see Howell-Jolly bodies (basophilic) in RBC - healthy spleen would normally filter these out
Might see Pappenheimer bodies (iron) )

indications

  1. Spontaneous rupture at massive splenomegaly (infectious mononucleosis) precipitated by trauma
  2. Hypersplenism: ITP, hereditary spherocytosis
  3. Neoplasia: lymphoma or leukaemic infiltration
  4. Splenic cyst or abscess

comps
Thrombocytosis - platelet count peaks at 7-10 days (? prophylactic aspirin)
*Overwhelming infection:
Encapsulated bacteria - s.pneumoniae, h. Influenza, n.meningitidis
4% if no prophylaxis
Mortality of 50% for first 2 years

mgmt
Prophylactic ABX + vaccines
Oral phenoxymethylpenicillin + or macrolides (azithromycin/clarithromycin)
Pneumococcal vaccine and influenza vaccine
Carry health alert card

173
Q

Haemopoietic stem cell transplant

how

A

Before transplant give chemo/radiotherapy
Ablative or reduced intensity
Harvest
BM removed from pelvis under GA
Peripheral blood stem cells: from blood via apheresis
Give BM IV as inpatient
Engraftment

174
Q

autologous BM transplant

A

Stem cells harvested from own BM
Pt undergoes ablative or reduced treatment

(+) rapid immunity, less chance infx, reduced risk rejection
(-) not suitable for AML (high relapse)

175
Q

allogeneic BM transplant

A

Healthy donor and patient
Must match HLA to patient HLA at 3 Loci
Donor normally sibling or relative or identified match

176
Q

BM transplant comps

A

Infection - decreased leukocytes and immunosuppression post procedure

Veno-occlusive disease - chemotherapy damages hepatic venous epithelium

Mucositis - mouth and throat

GvHD - @allogeneic, graft recognises host as non-self and begins immune response against recipients tissues. Typically @<3 months. Skin, intestine and liver commonly affected (maculopapular rash, nausea/vom, cholestatic jaundice)

Gv tumour effect - beneficial. Response of donor T lymphocytes against diseased lymphocytes of recipient lead to reduced likelihood of cancer return

177
Q

when would JAK-2 be positive?

A

in myeloproliferative disorders

178
Q

what is the difference between PT and APTT

A

PT on extrinsic factors
APTT on intrinsic factors

1972 WEPT - warfarin acts on extrinsic pathway and is measured by PT.

179
Q

explain when you would expect the diffeent immunoglobulins to be raised

A

Immunoglobulin A (IgA), which is found in high concentrations in the mucous membranes, particularly those lining the respiratory passages and gastrointestinal tract, as well as in saliva and tears.

Immunoglobulin G (IgG), the most abundant type of antibody, is found in all body fluids and protects against bacterial and viral infections.

Immunoglobulin M (IgM), which is found mainly in the blood and lymph fluid, is the first antibody to be made by the body to fight a new infection.

Immunoglobulin E (IgE), which is associated mainly with allergic reactions (when the immune system overreacts to environmental antigens such as pollen or pet dander). It is found in the lungs, skin, and mucous membranes.

Immunoglobulin D (IgD), which exists in small amounts in the blood, is the least understood antibody.