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* year 2 Clinical Pathology > core haematology > Flashcards

core haematology Flashcards

1
Q

what is haemopoiesis?

A

the physiological development process that gives rise to the cellular components of blood

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2
Q

what is the name of the cell which can divide and differentiate to form different cell lineages that will populate the blood?

A

multipotent haemopoietic stem cell

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3
Q

what is the difference between symmetric and asymmetric self-renewal of a haemopoietic stem cell?

A

symmetric: stem cell divides to create 2 more stem cells
asymmetric: stem cell divides to create 1 stem cell and 1 (more specialised) progenitor cell

(nb can also have ‘lack of self renewal’ when one stem cell divides to create 2 progenitor cells)

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4
Q

which blood cells are in the lymphoid lineage and which are in the myeloid lineage?

A

everything is from the myeloid lineage, EXCEPT:

  • B-lymphocytes
  • T-lymphocytes
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5
Q

what is the difference between monocytes and neutrophils?

A

monocytes

  • become macrophages when get into tissue (circulate blood as monocytes)
  • long lived
  • antigen-presenting

neutrophils

  • short lived
  • not antigen-presenting
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6
Q

what is the lifespan of a RBC?

A

3 months/ 120 days

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7
Q

in the EARLY developing embryo, where does haemopoiesis occur?

A

(originally slightly in yolk sac)

but mainly in EMBRYONIC PLATE (between amniotic sac + yolk sac)

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8
Q

where does haemopoiesis occur in the developing foetus?

A

Aorto-gonado-mesonephros (AGM)

at day 40, the haemopoietic stem cells migrate, via the aorta, to the foetal liver (which become the subsequent site of haemopoiesis

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9
Q

what is the name given when there are too many RBCs?

A

polycythaemia

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10
Q

what is relative polycythaemia?

A

when plasma volume is REDUCED (but no. of RBCs doesn’t change)

  • therefore there is a higher concentration of RBCs in the blood
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11
Q

what are the three main groups of leukocytes?

A
  • lymphocytes
  • monocytes
  • granulocytes
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12
Q

what are the three types of granulocytes?

A
  • neutrophils
  • eosinophils
  • basophils
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13
Q

what is the name given when there are more neutrophils than normal in the blood?

what might cause this? 3

A

neutrophilia

  • bacterial infection
  • inflammation
  • use of steroids (flush neutrophils out of tissues into blood??)
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14
Q

what is the name given when there are fewer neutrophils than normal in the blood?

what might cause this?

A

neutropenia

side effects of certain drugs, eg:

  • co-trimoxazole (an Abx)
  • chemo drugs
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15
Q

what is it called when there are more eosinophils in the blood than normal?

what might cause this? 2

A

eosinophilia

  • parastic infection (eg schistomiasis)
  • allergies
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16
Q

what is it called when there are more basophils in the blood than normal?

what normally causes this?

A

basophilia

myeloma proliferative neoplasms
- especially: chronic myeloid leukaemia

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17
Q

what are the name for the macrophages in the:

  • liver?
  • skin?
  • brain?
A

liver: kupffer cells
skin: langerhans cells
brain: microglia

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18
Q

what is it called when there are more monocytes in the blood than normal?

when might this occur?

A

monocytosis

tuberculosis

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19
Q

what is it called when there are more lymphocytes in the blood than normal?

when might this occur?

A

lymphocytosis

  • eg in chronic lymphocytic leukaemia (CLL)

also in glandular fever (infectious mononucleosis) you get lots of ATYPICAL lymphocytes (which look like monocytes, hence the name!)

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20
Q

what is it called when there are fewer lymphocytes in the blood than normal?

when might this occur?

A

lymphopenia

  • post bone marrow transplant
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21
Q

which lymphocyte produces cell-mediated-immunity and which produces humoral immunity?

A

cell mediated = t cells

humoral = b cells (via soluble antibodies they produce)

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22
Q

what is adaptive immunity and what is innate immunity?

A

adaptive = t + b lymphocytes

innate = all other white blood cells (ie myeloid lineage)

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23
Q

what is an increased number of plasma b cells called?

what might cause this?

A

plasmacytosis

benign
- eg response to infection

myeloma

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24
Q

what is the name of the cell which platelets are derived from?

A

megakaryocytes

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25
Q

what are the 4 main subspecialties of haematology?

A
  • coagulation
  • malignant
  • non-malignant
  • transfusion
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26
Q

what are the constituents tested for in a Full Blood Count (FBC) blood test?

A

Hb concentration

Red cell parameters:

  • MCV (mean cell volume)
  • MCH (mean cell Hb)

white cell count (WCC)

platelet count

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27
Q

what are the RBCs called when they have:

  • too little Hb?
  • too much Hb?
A

too little: hypochromate (pale)

too much: hyperchromate (dark)

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28
Q

how do coagulation screens test coagulation function?

what are the main three specific tests used? and what are they used for?

A

by measuring the time taken for a clot to form when plasma (from patient) is mixed with specified reagents

prothrombin time
- used for warfarin monitoring

activated partial thromboplastin time
- used for unfractioned heparin monitoring

thrombin time
- used for diagnosing specific clotting deficiencies

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29
Q

how are diagnostic bone marrow tests carried out?

A

under local anaesthetic, liquid marrow is aspirated from POSTERIOR ILLIAC CREST of pelvis and a trephine core biopsy is then taken with a hollow needle

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30
Q

when taking blood what things should you make sure to do? 5

A
  • appropriate sample from patient (eg fasting or not etc)
  • blood should be filled to line on tube
  • mix blood well (a few inversions is fine)
  • labble bottle correctly
  • keep bottle with request form
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31
Q

what is the definition of a reference range?

A

the set of values for a given test that incorporates 95% of the normal population

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32
Q

what is the definition of sensitivity?

A

the proportion of abnormal results correctly classified by the test

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33
Q

what is the formula for calculating sensitivity?

A

no. true positives / (no. true positives + no. false negatives)

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34
Q

what is the definition of specificity?

A

the proportion of normal results correctly classified by the test

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35
Q

what is the formula for calculating specificity?

A

no. true negatives / (no. true negatives + no. false positives)

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36
Q

what might cause mild lymphocytosis? (but be completely harmless)

A

post-splenectomy mild lmphocytosis

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37
Q

what might cause lymphopenia? (but not be pathological)

A

3 months post-bone marrow transplant lymphopenia

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38
Q

what conditions cause microcytic anaemia? 5

A
  • iron deficiency
  • thalassaemia
  • lead poisoning
  • anaemia of chronic disease (some)
  • sideroblastic anaemia (some)
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39
Q

what conditions cause normocytic anaemia? 6

A
  • after acute blood loss
  • renal disease
  • bone marrow failure (eg post chemo, infiltration by carcinoma etc)
  • mixed deficiencies
  • many haemolytic anaemias
  • anaemia of chronic disease (some)
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40
Q

what conditions cause macrocytic anaemia? 6

A

megaloblastic:

  • vit B12 deficiency
  • folate deficiency

non-megaloblastic

  • alcohol
  • liver disease
  • myelodysplasia
  • aplastic anaemia
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41
Q

what is the main symptom of a sickle cell crisis?

A

excruciating bone pain

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42
Q

what are megaloblastic cells (present in some forms of macrocytic anaemia)?

A

a type of immature progenitor RBC which didn’t divide like it should and so just kept getting bigger
(called megaloblastic erythropoiesis)

  • B12 + folate deficiency
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43
Q

what are three main types of macrocytic anaemia?

what causes them?

A

megaloblastic anaemia (ie with megaloblastic erythropoiesis)

  • vit B12/folic acid deficiency
  • myelodysplastic syndrome

macrocytic anaemia with normoblastic erythropoiesis
- eg liver disease, alcohol, hypothyroidism, myelodysplastic syndrome

‘stress’ haemopoiesis
- eg haemolytic anaemia, recovery from blood loss (macrocytosis reflects high reticulocyte, immature RBC, count)

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44
Q

what are myelodysplastic syndromes (MDS)?

what are the two clinical manifestations of these conditions?

A

a group of cancers in which immature blood cells in the bone marrow do not mature and become healthy blood cells. Early on there are typically no symptoms. Later symptoms may include feeling tired, shortness of breath, easy bleeding, or frequent infections.

  • chronic anaemia with survival for several years
  • aggressive disease terminating in ACUTE MYELOID LEUKAEMIA
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45
Q

what is an iatrogenic cause of myelodysplastic syndrome?

A
  • complication of treatment with chemotherapy or radiotherapy
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46
Q

who is most likely to be affected by myelodysplastic syndromes?

A

typially mid-life to older people

occasionally in younger people

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47
Q

why do myelodysplastic syndromes cause anaemia?

A

because: a mutated stem cell produces a clone of abnormal cells that replaces normal haemopoiesis

abnormal cells:

  • show abnormal maturation morphologically
  • often die before leaving the bone marrow
  • –> peripheral blood cytopenias

so basically the right amount of cells are still made in the bone marrow but, because they’re mutated, they often die before leaving the bone marrow so there aren’t enough cells in the blood

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48
Q

what are the THREE typical abnormalities seen in BLOOD TESTS of patients with myelodysplastic syndrome (MDS)?

what symptoms do each of these abnormalities produce?

A

anaemia

  • fatigue
  • dyspnoea (SOB)

neutropenia
- lots of infections

thrombocytopenia

  • bruising
  • bleeding
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49
Q

what are 3 types of myelodysplastic syndrome (MDS)?

A
  • refractory anaemia
  • refractory anaemia with excess blasts
  • MDS 5Q- syndrome
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50
Q

what are the ACTIVE treatments for myelodysplastic syndrome? 4

who is suitable for each one?

A

lenalidomide
(for 5Q syndrome)

azacytidine
(for patients who aren’t well enough to have a bone marrow transplant)

chemotherapy

bone marrow transplant

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51
Q

what are the SUPPORTIVE treatments for myelodysplastic syndromes? 3

A
  • RBC transfusions
  • erythropoietin
  • platelet transfusions
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52
Q

what treatment would you give to someone who had too much iron in their body? (side effect of RBC transfusions)

A

give iron chelation to treat iron overload

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53
Q

what is the process which isolates RBCs from donors blood called?

A

leucodepletion

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54
Q

how long can RBCs be stored?

how long does it usually take to transfuse 1 unit of RBCs?

A

up to 35 days

1.3-3 hours

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55
Q

what is the definition of a transfusion threshold (trigger)?

A

the lowest concentration of Hb that is not associated with symptoms of anaemia

(once you go below that threshold, you should transfuse the patient)

(this threshold varys hugely between patients)

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56
Q

what are the body’s mechanisms of adapting to anaemia? 6

what occurs after these methods have been exhausted (or if the body hasn’t had enough time to respond to the anaemia)?

A
  • increase cardiac output
  • increase cardiac artery blood flow
  • increase oxygen extraction
  • increase of RBC 2,3 DPG (diphosphoglycerate)
  • increase production of erythropoitin (from kidneys)
  • increase erythropoiesis

–> tissue hypoxia –> symptoms of anaemia

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57
Q

what FOUR things could cause a patient’s transfusion threshold to be lower?

A

basically if their body has a reduced capacity to react to anaemia due to less effective:

  • cardiac output
  • arterial blood flow
  • O2 saturation
  • Hb

eg in:

  • cardiovascular disease
  • respiratory disease
  • haemoglobinopathies
  • increased age
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58
Q

what are alternative treatments for anaemia? (ie not RBC transfusions) 5

A

correction of treatable causes of anaemia:

  • iron tablets (for iron deficiency)
  • B12 injections (for B12/folate deficiencies)
  • erythropoietin treatment (for patients with renal disease)

correction of coagulopathy:

  • discontinuation of antplatelet agents
  • administration of anti-fibrinolytic agents
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59
Q

how much blood does a person have to loose (in an acute setting) in order for a transfusion to be necessary?

A

about 1.5 litres

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60
Q

why are patients with inherited anaemias (eg thalassaemia) given regular blood transfusions?

what is a possible adverse event of these?

A

to suppress endogenous erythropoiesis (which produces the abnormal RBCs)

iron overload

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61
Q

what is the ‘shelf life’ of platelet donations?

what is the usual transfusion for one unit of platelets?

A

5 days from collection

30 mins/unit

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62
Q

why transfuse platelets? 3

A

treatment of bleeding due to:

  • severe thrombocytopenia (low platelets)
  • platelet dysfunction

prevention of bleeding

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63
Q

what are the two main contraindications of platelet transfusion?

A
  • heparin induced thrombocytopenia + thrombosis

- thrombotic thrombocytopenic purpura

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64
Q

how is fresh frozen plasma (FFP) stored?

A

frozen for up to 2 years

- thawed immediately before use

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65
Q

when should fresh frozen plasma be transfused? 3

when shouldn’t it be transfused? 2

A
  • coagulopathy (problems w clotting factors) with bleeding/surgery
  • massive haemorrhage
  • thrombotic thrombocytopenic purpura

do not transfuse:

  • for warfarin reversal
  • for replacement of single factor deficiency
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66
Q

what is the treatment for patients who are bleeding due to too much warfarin?

A

prothrombin complex concentrate (PCC)

basically a lot of plasma-derived Vit K dependent factors - factors 2, 7, 9 + 10

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67
Q

what is a ‘group and screen’ blood test for?

A
  • determination of patient’s ABO + Rh group
  • patient’s plasma ‘screened’ for antibodies against other clinically significant blood group antigens

so that blood can be transfused safely (esp in an emergency) wwith a lower probability of adverse events

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68
Q

what is ‘crossmatching’?

A

donor red cells of the correct ABO and Rh group are selected from the blood bank
(avoid any other groups the patient has antibodies against - detected in screen)

‘crossmatching’ = patient’s plasma is mixed with aliquots of donor red cells to see if a reaction (agglutination or haemolysis) occurs

if no reaction: RBC units compatible!

if reaction: RBC units INcompatible, risk of acute haemolysis

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69
Q

what is the difference between an acute transfusion reaction and a delayed one?

A

acute reactions present: <24hr after transfusion

delayed reactions present: >24hr after transfusion

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70
Q

what are the possible acute transfusion reactions (to a blood transfusion)? 6

A

immunological:

  • acute haemolytic transfusion reaction (ABO incompatibility)
  • allergic/anaphylactic reaction
  • TRALI (transfusion-related acute lung injury)

non-immunological:

  • bacterial contamination
  • TACO (transfusion associated circulatory overload)
  • febrile non-haemolytic transfusion reaction
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71
Q

what are the possible delayed transfusion reactions (to a blood transfusion)? 4

A

immunological:

  • transfusion-associated graft-versus-host disease (TA-GvHD)
  • post transfusion purpura

non-immunological:

  • transfusion transmitted infection (TTI) - viral/prion
  • iron overload
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72
Q

what is the pathological process of an acute haemolytic reaction (ABO incompatibility)?

A
  • haemolysis of RBCs
  • > release of free Hb
  • > deposition of Hb in the distal renal failure
  • > stimulation of coagulation
  • > microvascular thrombosis
  • > stimulation of cytokine storm
  • > scavenges NO resulting in generalised vasoconstriction
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73
Q

what are the signs and symptoms of an acute haemolytic reaction? 7

when do these symptoms occur?

A
  • fever + chills
  • back pain
  • infusion pain
  • chest pain
  • hypotension/shock
  • haemoglobinuria (may be 1st sign in anesthetised patients)
  • increased bleeding (DIC)
  • sense of ‘impending death’

severe reactions may occur early in the transfusion (within first 15 mins)
(milder reactions may occur later but usually before the end of the transfusion)

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74
Q

What is a delayed haemolytic reaction?

what are the clinical signs/symptoms of this? 3

what are the laboratory findings? 4

A

onset 3-14 days following RBC transfusion

  • delayed haemolytic reaction is due to immune IgG antibodies against RBC antigens other than ABO
  • the antibodies are formed AFTER the transfusion

clinical features:

  • fatigue
  • jaundice
  • fever

laboratory findings:

  • drob in Hb
  • increased LDH (lactate dehydrogenase)
  • increased indirect bilirubin
  • positive antiglobulin test
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75
Q

what is the Coomb’s test?

what is it also known as?

A

rabbit antibodies to human IgG
(called: anti-human globulin (AHG))

they are used to detect IgG antibodies on RBCs

  • so see if RBCs are being attacked by immune system (as in a post-transfusion haemolytic reaction)=
  • get visible agglutination if there are IgG on RBCs when AHG is added

aka:

  • anti-human globulin test (AHG)
  • direct anti-globulin test (DAT)
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76
Q

what does TRALI stand for?

why does it occur?

what is the mechanism of the condition?

A

transfusion related acute lung injury

  • DONOR has antibodies to RECIPIENT’S LEUCOCYTES
    (nb almost always complicates transfusion of plasma rich components - ie platelets or fresh frozen plasma)

donor antibodies attack recipients leucocytes

  • > activated leucocytes lodge in pulmonary capillaries
  • > release substances that cause endothelial damage and capillary leak
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77
Q

when does TRALI occur?

what are the clinical signs of it?

A

sudden onset of ‘acute lung injury’ occuring within 6 hours of a transfusion

  • hypoxia
  • new bilateral chest x-ray infiltrates (consolidation)
  • no evidence of volume overload (eg heart size is normal)
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78
Q

how do you confirm a diagnosis of TRALI?

A
  • donor’s blood is tested for HLA and granulocyte antibodies
  • recipient’s blood is tested for expression of neutrophil antigens

confirmation of diagnosis if:
- donor has antibodies against antigens that are expressed on recipient’s granulocytes

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79
Q

what is the treatment for TRALI?

A

if mild:
- supplementary oxygen therapy

if severe:
- mechanical ventilation and ICU support

nb there is no role for diuretics or corticosteroids

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80
Q

what does TACO stand for?

what are the:

  • symptoms? 5
  • signs? 2
A

transfusion-associated circulatory overload

symptoms:

  • sudden dyspnoea (SOB)
  • orthopnoea
  • tachycardia
  • hypertension
  • hypoxaemia

signs:

  • raised BP
  • elevated jugular venous pulse
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81
Q

what are the risk factors for TACO? 5

A
  • elderly
  • small children
  • patients with compromised left ventricular function
  • increased volume of transfusion
  • increased rate of transfusion

nb this is hugely unreported/unrecognised by clinicians (if you suspect it, hold transfusion, if just to check that it’s not bacterial infection or another more serious adverse effect)

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82
Q

what are the differences between the presentation and treatment of TACO + TRALI?

  • type of blood component transfusion which causes it?
  • affect on BP?
  • affect on temp?
  • do diuretics worsen or improve it?
  • does fluid loading worsen or improve it?
A

Type of blood component transfused:

  • TRALI: usually plasma
  • TACO: any

BP:

  • TRALI: often reduced
  • TACO: often raised

temp:

  • TRALI: often raised
  • TACO: normal

diuretics:

  • TRALI: worsens
  • TACO: improves

fluid loading:

  • TRALI: improves
  • TACO: worsens
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83
Q

what are the two different types of allergic reaction to a blood transfusion?

how do they present?

A

urticarial rash (+/- wheeze)

  • often not severe
  • hypersensitivity to a ‘random’ protein (in donor’s blood)

anaphylaxis

  • severe, life-threatening reaction soon after transfusion started
  • wheeze/asthma
  • increased pulse
  • decreased BP (shock)
  • laryngeal/facial oedema
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84
Q

what is a febrile non-haemolytic reaction (FNHTR)?

why does it occur?

how should it be managed?

A

during (or soon after) transfusion:

  • fever, rise in temp >1degree (+/- shakes/rigors)
  • +/- increased pulse
  • unpleasant but not life threatening (it is self-limiting)

FNHTR are due to cytokines (or other biologically active molecules) that accumulate during storage of blood components

  • discontinue transfusion until you exclude ‘wrong blood’ or bacterial infection
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85
Q

what are the primary and secondary aspects of haemostatic plug formation?

A

primary
= aggregation
—platelet aggregation -> clotting

secondary
= coagulation cascade
-> thrombin -> fibrin

both together –> haemostatic clot

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86
Q

how do platelets become activated?

A

normal platelets in flowing blood (w receptors on their surface)

  • if blood contacts collagen then a protein in blood (von willebrands factor) binds to the collagen and to the platelets, creating a connection
  • platelets are therefore adhered to damaged endothelium and undergo ACTIVATION

–> aggregation of platelets into a thrombus (due to fibrinogen acting as a bridge between platelets)

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87
Q

what activates:

  • the intrinsic clotting pathway?
  • the extrinsic clotting pathway?
A

intrinsic:
- when blood exposed to COLLAGEN (from damaged surfaces)

extrinsic:
- when blood exposed to TISSUE FACTOR (released from tissues when endothelium is damaged)

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88
Q

what part of the coagulation cascade do these times measure:

  • activated partial thromboplastin time?
  • prothrombin time?
  • thrombin clotting time?
A

activated partial thromboplastin time:
- intrinsic pathway

prothrombin time:
- extrinsic pathway

thrombin clotting time:
- common pathway

“intrinsic pathway is activated by contact with collagen, which is a bit like PLASTIC, thromboPLASTIN”

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89
Q

what factors are vitamin K dependent:

  • clotting? 5
  • anti-clotting? 2
A

clotting:

  • factor 2
  • factor 7
  • factor 9
  • factor 10
  • prothrombin

anticlotting:

  • protein c
  • protein s
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90
Q

what are the procoagulant (2) and anti-coagulant (4) components found in the blood?

A

procoagulant:

  • platelets
  • clotting factors

coagulant:

  • protein C
  • protein S
  • anti-thrombin III
  • fibrinolytic system
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91
Q

what sort of bleeding do these types of bleeding disorders tend to cause:

  • platelet/vessel wall defect?
  • coagulation defect?
A

platelet/vessel wall defect:
- mucosal + skin bleeding

coagulation defect:

  • deep muscular + joint bleeds
  • bleeding following trauma
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92
Q

what is the general role of alpha and dense granules in platelets

A

contain chemicals which are released of platelet activation

these chemicals stimulate the activation and aggregation of other platelets

so a positive feedback loop

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93
Q

what does aspirin inhibit the synthesis of?

A

inhibits the synthesis of thromboxane (via inhibition of COX enzyme)

thromoxane is a hormone that is released from blood platelets, which induces platelet aggregation and arterial constriction

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94
Q

where is tissue factor (TF) found?

A

TF is a transmembrane receptor expressed by cells surrounding blood vessels

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95
Q

what does tissue factor activate?

A

factor 7 -> factor 7a

extrinsic pathway

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96
Q

which is faster: extrinsic or intrinsic pathway?

A

extrinsic (fewer steps)

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97
Q

what does factor 12 deficiency cause?

A
  • prolonged clotting time in vitro

- but very rarely causes clinical symptoms

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98
Q

what bleeding disorders are caused by:

  • factor 8 deficiency?
  • factor 9 deficiency?
A

factor 8 = haemophillia A

factor 9 = haemophillia B

“A is earlier in the alphabet than B”

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99
Q

what is the end product of the fibrinolytic cascade?

what does this do?

A

plasmin (produced from plasminogen, which is converted by t-pa)

(t-pa = tissue plasminogen activator)

plasmin breaks down fibrin clot

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100
Q

what are the 4 broad different types of platelet/vessel wall defects which all give rise to a prolonged bleeding time? (each with an example)

A

1) reduced no. of platelets (thrombocytopenia)
- many causes (eg viruses, chemo)

2) abnormal platelet function
- eg aspirin/other drugs

3) abnormal vessel wall (rarer)
- eg ehlers danlos syndrome

4) abnormal intercation between platelets + vessel wall
- eg von willebrand diseas

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101
Q

what is an example of an acquired condition which causes abnormal vessel walls?

A

scurvy

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102
Q

what are petechiae?

A

red or purple spots on the skin, caused by a minor bleed from broken capillary blood vessels

they are NON-BLANCHING

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103
Q

what is the classical presentation of vascular/platelet defects?

A
  • petechiae + superficial bruises
  • affects skin + mucosal membranes
  • spontaneous
  • bleeding immediate, prolonged + NON-recurrent
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104
Q

what is the classical presentation of coagulation defects?

A
  • deep spreading haematomas
  • haemarthrosis
  • retroperitoneal bleeding
  • bleeding preolonged and often RECUURENT
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105
Q

what is haemarthrosis?

A

bleeding into joints

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106
Q

what is the scientific name for nose bleeds

A

epistaxis

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107
Q

what is the most common inherited bleeding disorder?

A

von Willebrand disease

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108
Q

what are the 2 functions of von willebrand factor?

A
  • to bind platelets to wound site (esp collagen)

- to act as a carrier of factor 8

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109
Q

what are the 3 types of von willebrand disease?

A

type 1

  • vWF is normal but there’s not enough of it
  • less severe
  • most common (75%)

type 2

  • vWF is abnormal (not as effective) but there is enough of it
  • less severe
  • about 20% of cases

type 3

  • there is very little vWF in blood
  • severe
  • very rare
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110
Q

what other condition can vWD present similar to? why?

A

mild haemophillia

as vWF carries factor 8 in the blood plasma so if there is less vWF then this can lead to low levels iof factor 8

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111
Q

what is the inheritance pattern of von Willebrand disease?

A

mainly autosomal dominant

nb penetrance is very variable though, even within families

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112
Q

what part of haemostasis is affected in von willebrands disease?

A

defective primary haemostasis

ie platelets/cell walls NOT coagulation

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113
Q

what other things (except vWD) can affect a person’s level of vWF?

increase? 3
decrease? 1

A

increase:

  • illness
  • stress
  • exercise

decrease
- being blood group O

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114
Q

what are women with vWD given to reduce their menorrhagia?

A

combined oral contraceptive pill (COCP)

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115
Q

when are treatments normally given for von Willebrand disease?

A
  • when symptoms occur
  • before surgery
  • during pregnancy
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116
Q

what anti-fibrinolytic treatment is given to treat vWD?

how does it work?

A

tranexamic acid

bind to plasminogen or plasmin. This prevents plasmin from binding to and degrading fibrin and preserves the framework of fibrin’s matrix structure

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117
Q

what other treatment is occasionally given to patients with vWD? (esp type 1)

what does it do?

A

desmopresin (aka DDAVP)

(it is an analogue of endogenous vasopressin)

  • one of its actions is to release stores of vWF in endothelial cells
  • only works temporarily
  • side effect is water retension
  • efficacy reduces after repeated uses
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118
Q

what vaccinations are people with vWD given? why?

A

hepatitis

because they are sometimes given (donated) plasma-derived concentrates containing vWF + so at higher risk from infected blood donors

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119
Q

what are the two most common hereditary COAGULATION deficiencies?

A

Haemophilia A + B

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120
Q

which coagulation screening test is elongated in haemophilia? why?

A

activated partial thromboplastin time (APTT)

as this measures the INTRINSIC pathway - where factor 8 + 9 are

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121
Q

what is the function of factor 13?

what does deficiency present as?

what do coagulation screening tests show?

A

to crosslink fibrin, stabilises clots

Bleeding tendencies similar to hemophiliacs develop, such as hemarthroses and deep tissue bleeding.

ALL NORMAL (APTT, PT, TCT)
- as these measure formation of fibrin clots whereas factor 13 is to do with stabilisation of clots
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122
Q

why might some female carriers of haemophilia be more symptomatic than others?

A

due to random X-inactivation (lyonisation)

- if more X with normal gene is inactivated then factor 8 levels will be lower than 50% so mild symptoms may occur

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123
Q

what is the inheritance pattern of haemophilia A + B?

A

X-linked recessive

nb severity levels vary BUT are consistent between family members

about 30% of haemophilia cases are new mutations

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124
Q

what are the definitions of the three degrees of haemophilia severity?

A

factor 8 or 9 levels:

  • mild = 6-50%
  • moderate = 1-5%
  • severe = <1%

nb mild haemophiliacs will only bleed during truma and surgery, whereas severe haemophiliacs will have lots of spontaneous bleeds

the more severe the condition, the earlier in life patients will present

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125
Q

what types of bleed do haemophiliacs tend to get? 5

A
  • spontaneous/post traumatic
  • haemarthrosis (joint bleeding)
  • muscle haemorrhage
  • soft tissue bleeds
  • life threatening bleeds
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126
Q

what is haemophilic arthropathy?

what can reduce risk?

A

permanent joint disease occurring in haemophilia sufferers as a long-term consequence of repeated haemarthrosis

factor injections every other day, reduce number of joint bleeds so likelihood of permanent joint damage

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127
Q

what is the main treatment for haemophilia?

A

injections (every other day) of RECOMBINANT factor 8 or 9

nb factors from donated blood products no longer used

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128
Q

what are the 2 main complications of haemophilia treatment?

A

transfusion transmitted infections

  • many adults got these before use of recombinant factors was used
  • eg hepatitis, HIV, parvovirus

inhibitor development

  • sometimes body can produce antibodies to injected factors
  • more common in haemophilia A (25% of patients)
  • means normal treatment is not effective
  • more commonly temporary but can be permanent
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129
Q

what are the 6 most common causes of acquired bleeding disorders?

A
  • vit K deficiency
  • liver disease
  • massive transfusion syndrome
  • disseminated intravascular coagulation (DIC)
  • iatrogenic causes
  • acquired inhibitors (of coagulation)
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130
Q

what are the most important questions to ask when assessing someone with a possible bleeding disorder?

A
  • date of onset/previous bleeding episodes?
  • responses to ‘challenges’ (ie did surgery/dental extraction cause lots of bleeding) (nb in infants use things like bleeding from umbilical stump, vaccinations, circumcision)
  • have they ever needed medical/surgical intervention to stop bleeding?
  • any systemic illness? (eg liver problems)
  • drug history?
  • family history?
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131
Q

if the APPT (activated partial thromboplastin time) is prolonged, how can you tell if this is due to a deficiency of a factor or an inhibitor of the factor?

A

repeat test but mix patient’s plasma with plasma which you know has correct factors in, if:

  • correction of APPT then: deficiency in patient’s plasma
  • no correction of APPT then: presence of inhibitorin patient’s plasma
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132
Q

In liver disease, what results will be seen in these tests:

  • platelet count?
  • prothrombin time?
  • APPT (activated partial thromboplastin time)?
  • thrombin time?
A

platelet count:
- low

prothrombin time:
- prolonged

APPT:
- prolonged

thrombin time:
- normal

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133
Q

in DIC, what results will be seen in these tests:

  • platelet count?
  • prothrombin time?
  • APPT (activated partial thromboplastin time)?
  • thrombin time?
A

platelet count:
- low

prothrombin time:
- prolonged

APPT:
- prolonged

thrombin time:
- grosssly prolonged

“basically everything is shit, DIC is shit!”

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134
Q

in Massive transfusion syndrome, what results will be seen in these tests:

  • platelet count?
  • prothrombin time?
  • APPT (activated partial thromboplastin time)?
  • thrombin time?
A

platelet count:
- low

prothrombin time:
- prolonged

APPT:
- prolonged

thrombin time:
- normal

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135
Q

in oral anticoagulants (eg warfarin), what results will be seen in these tests:

  • platelet count?
  • prothrombin time?
  • APPT (activated partial thromboplastin time)?
  • thrombin time?

what other condition can cause these results?

A

platelet count:
- normal

prothrombin time:
- grossly prolonged

APPT:
- prolonged

thrombin time:
- normal

vit K deficiency

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136
Q

why do you get low platelet count in liver disease?

A

because liver problems often cause portal hypertension which backs into spleen, so platelets get trapped and clogged up in spleen, so have lower levels circulating (ie due to hypersplenism)

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137
Q

what is the action of warfarin?

A

warfarin is a vitamin K reductase inhibitor
- it stops vit k being recycled

vit K is needed in the activation of some coagulation factors

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138
Q

what are the 4 main causes of vit K deficiency? (not including warfarin treatment)

what are the mechanisms?

A

obstructive jaundice
- need bile to breakdown + absorb fat, vit K is a fat soluble vitamin -> deficiency

PROLONGED nutritional deficiency
- less fat for vit K to be absorbed in

broad spectrum antibiotics

  • kill off gut flora
  • a lot of out vit k is synthesised by gut flora

neonates (classic 1-7 days)
- all babies are given a vit k injection at birth to prevent this (aka haemorrhagic disease of the newborn)

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139
Q

why might patients on ICU be at higher risk of becoming vit K deficient?

A

have prolonged nutritional deficiency AND often lots of antibiotics

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140
Q

what coagulation factors are synthesised in the liver?

A

all except factor 8

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141
Q

what is a major cause of mortality in patients with liver disease?

A

cirrhotic coagulopathy

  • complex reduction in coagulation factors, anti-coagulation factors + platelets leads to reduction in haemostatic abilities
  • less likely to get spontaneous bleeds but highly likely to bleed a lot during surgery etc
  • very hard to treat effectively
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142
Q

what is the definition of a ‘massive transfusion’

A

transfusion of a volume of blood equal to:

  • patient’s total blood volume in <24hrs

OR

  • 50% of patient’s blood volume within 3 hours
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143
Q

why do you get coagulation deficits with massive transfusions? (massive transfusion syndrome)

A
  • due to RELATIVE (/dilutional) depletion of platelets + coagulation factors (as only RBC’s are transfused)

nb give fresh frozen plasma (FFP) as well to prevent this

also, less commonly, due to:

  • DIC
  • underlying disease (eg liver/renal drug treatment or surgery)
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144
Q

what are the main causes of ACUTE DIC? 5

what is this more likely to present as?

A
  • sepsis (most common)
  • obstetric complications
  • trauma/tissue necrosis
  • acute intravascular haemolysis (eg ABO incompatibilty blood transfusion)
  • fulminant (aka acute) liver disease

bleeding as main symptom

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145
Q

what are the main causes of CHRONIC DIC? 4

what is this more likely to present as?

A
  • malignancy
  • end stage liver disease
  • severe localised intravascular coagulation
  • obstetric: retained dead foetus

end organ damage (due to microvascular clots) is main symptom

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146
Q

what is the management of DIC?

A

treat underlying cause
- eg antibiotics, obstetric intervention, chemo for cancer

supportive treatment:

  • maintain tissue perfusion
  • folic acid + vit k to support recovery esp if illness is prolonged
147
Q

what is the INR (international normalised ratio)?

A

used to monitor warfarin use

a ratio: patient’s prothrombin time/mena normal prothrombin time

148
Q

what types of drugs can increase the effect of warfarin? 3

A
  • some antibiotics
  • NSAIDs
  • corticosteroids
149
Q

what are the treatments for overtreatment of warfarin?

A

depends on severity!

  • if mild, just withold warfarin
  • if moderate, do above + administer vit K

if severe, do above AND give four factor concentrate (PCC)

150
Q

what is the antidote used in cases of over treatment with un-fractioned heparin?

A

protamine

nb effects of protamine on low molecular weight heparin are less predictable and more complex

151
Q

what are the three commonest myeloproliferative disorders?

what % of these transform into acute leukaemia?

A
  • polycythaemia vera
  • essential thrombocytosis
  • idiopathic myelofibrosis

10%

152
Q

what is polycythaemia vera?

A
  • increased RBCs (+/- neutrophils, +/- platelets)

basically bone marrow makes too many mature RBCs

(nb distinguish from secondary polycythaemias + reactive polycythaemia)

153
Q

what is essential thrombocythaemia?

A

increased platelets (overproduction in bone marrow)

(nb distinguish from reactive thrombocytosis)

aka essential thrombocytosis

154
Q

what is myelofibrosis?

A

proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis (the replacement of the marrow with scar tissue)

leading to severe anemia, weakness, fatigue and often an enlarged spleen

(varied cytopenias with a large spleen)

(nb distinguish from other causes of splenomegaly)

155
Q

what is a condition that is secondary to many myeloproliferative disorders? how does this transformation present clinically?

A

myelofibrosis

clinically the blood cell count will be very high (due to the primary condition) but will then suddenly drop due to fibrosis in the bone marrow

156
Q

what are the symptoms of polycythaemia vera? 8

A
  • itching (aquagenic - stimulated by eg hot baths)
  • plethoric face (ie red)
  • headache/muzziness
  • general malaise
  • tinnitus
  • peptic ulcer
  • gout (due to uric acid released by increased cell turnover)
  • gangrene of the toes

nb can present very insidiously

157
Q

what are the signs of polycythaemia vera? 4

A

look flushed (red)

engorged (‘sausage-like’) retinal veins

splenomegaly

persistent haematocrit of over 50% (0.5)

158
Q

at what age are people most likely to get polycythaemia vera?

A

50-70years

159
Q

what are the 5 first line blood tests you would carry out on someone you suspect to have polycythaemia vera?

A
  • FBC
  • ferritin
  • epo level
  • U+Es
  • LFTs
160
Q

what conditions can cause secondary polycythaemia?

A

central hypoxic process:

  • chronic lung disease
  • right-to-left shunts heart disease
  • carbon monoxide poisoning
  • smoker
  • high altitude

drug associated

  • treatment with androgen preparations
  • post-renal transplant erythrocytosis

congenital

  • high oxygen affinity Hb
  • erythropoetin receptor-mediated
  • renal disease
  • EPO production tumours (type of kidney tumour)
161
Q

what 2nd line tests for polycythaemia vera would you use if:

  • epo was elevated? 3
  • epo was normal or low? 3
A

elevated epo

  • chest x-ray
  • arterial blood gas
  • abdominal ultrasound

normal or low epo

  • test for JAK2 mutation
  • test for EXON12 mutation
  • bone marrow examination
162
Q

what does a high haematocrit indicate?

what may cause a relatively high haematocrit?

A

polycythaemia (primary or secondary)

dehydration (as reduced level of plasma means haematocrit rises but no RBCs hasn’t actually risen)

163
Q

what is thrombopoietin?

aka tpo

A

similar to erythropoietin (but for platelets instead of RBCs)

stimulate production of megakaryocytes/platelets

164
Q

what is the genetic mutation that occurs in most myeloproliferative disorders?

why does it encourage the overproduction of blood cells?

A

JAK2 mutation

means that the epo (or tpo) receptors in the cell membranes of the bone marrow cells are permanently switched on so bone marrow cells think there is a higher amount of epo/tpo than there actually is –> more blood cells!

165
Q

what is the treatment for polycythaemia vera?

A
  • venesections (taking blood out, ie opposite of traansfusion)
  • aspirin daily (prevent platelet clots)
166
Q

what are the two conditions which polycythaemia vera most commonly develops into?

A

acute myeloid leukaemia

myelofibrosis

167
Q

what things can cause reactive thrombocytosis? 9

A
  • surgery
  • drug induced
  • infection
  • inflammation
  • iron deficiency
  • hyposlenism
  • haemolysis
  • malignancy
  • rebound post chemo
168
Q

what 2 types of drugs can result in drug-induced reactive thrombocytosis?

A
  • steroids

- adrenaline

169
Q

if, after doing first line tests to rule out reactive thrombocytosis, there is no known primary cause, what tests would you do?

A
  • look for JAK2 mutation
  • look for CALR mutation (similar effect to JAK2)

if those negative then do bone marrow biopsy

170
Q

what is the treatment for essential thrombocytosis?

A
  • daily aspirin

- assess thrombotic risk factors, if at high risk of clot then do CYTOREDUCTION

171
Q

what types of cytoreduction are used for patients with essential thrombocytosis who are at high risk of clots? 4

A

hydroxycarbamide
- suppresses the bone marrow (but affect all bone marrow cells, so will cause anaemia)

interferon
- unknown mechanism but works, however bad side effects

anagrelide
- just targets megakaryocytes but increased risk of myelofibrosis

  • P32
172
Q

how does myelofibrosis present? 3

A
  • pancytopenia (ie all blood cells are low)
  • B symptoms
  • massive splenomegaly
173
Q

what are B symptoms? 3

A
  • weight loss
  • fever
  • night sweats (so drenched you have to change clothes)

“B symptoms are associated with Blood malignancies”

174
Q

what tests would you do to diagnose myelofibrosis? 4

what would these show?

A

blood film

  • tear drop shaped RBCs
  • ertyhroblasts outside bone marrow

bone marrow biopsy
- lots of fibrous bands

JAK2 mutation
- in 50% f cases

CALR2 mutation
- in 30% of cases

175
Q

what are the common causes of splenomegaly?

what is the acronym to remember these?

A

CHICAGO

C - cancer

H - haematological (myelofibrosis, CML)

I - Infection (schistomiasis, malaria)

C - Congestion (liver disease/portal hypertension)

A - autoimmune (haemolysis)

G - glycogen storage disorders

O - Other (amyloid etc)

176
Q

what is the treatment for myelofibrosis? 3

A
  • JAK2 inhibitors
  • bone marrow transplant
  • supportive care (transfusions, symptom management etc)
177
Q

what is the prognosis for:

  • polycythaemia vera?
  • esssential thrombocytosis?
  • myelofibrosis?
A

polycythaemia vera
= good, 15 years

essential thrombocytosis
= good, 20 years

myelofibrosis
= poor, 5 years

178
Q

what is the median age of diagnosis of chronic myeloid leukaemia?

A

55-60 years

179
Q

what are the signs/histological results of chronic myeloid leukaemia (CML)? 4

A
  • leucocytosis
  • leucoerythroblastic blood picture (should be in bone marrow)
  • anaemia
  • splenomegaly
180
Q

what are the symptoms of CML? 5

why do these occur?

A

abdominal discomfort
- splenomegaly

abdominal pain
- splenic infarction

fatigue

  • anaemia
  • catabolic state

venous occlusion (eg retinal vein, DVT, priapism)

gout
- hyperuricaemia

nb about half are asymptomatic and present following an incidental blood test finding

181
Q

what is priapism?

A

priapism is an involuntary, prolonged erection unrelated to sexual stimulation and unrelieved by ejaculation

182
Q

what is the genetic mutation seen in CML?

A

translocation from C22 (philadelphia chromosome) to C9

  • puts together BCR and ABL gene to make BCR-ABL oncogene which makes tyrosine kinase
183
Q

what is the most effective treatment for CML?

how does it work?

what was the standard treatment before this?

A

gleevec (imatinib)

a tyrosine kinase inhibitor
-this stops the cell cycle in cancerous cells but, very specific, does not affect healthy cells

interferon was standard treatment before imatinib

184
Q

what is the main problem with imatinib?

A

malignant cells can develop resistance to it

185
Q

in polycythaemia vera, would epo levels be low or high?

A

low!!

if high, then polycythaemia is secondary to something else

186
Q

if you have acute gout, what will show up in the blood tests? why?

A

low uric acid

  • as all uric acid has condensed into gout so lower levels in blood
187
Q

where is gout classically found?

A

on first metatarsal joint (bottom of big toe)

188
Q

what is more common: b cell lyphomas or t cell lymphomas?

A

b cell lymphomas

189
Q

what do scientists use to work out the differentiation level of different b-cell malignancies?

A
  • presence or absence of certain antigens on the b cell clones indicate what level of maturity/differentiation the clonal cells are at!
190
Q

which pathway is almost always mutated in lymphoma?

A

NF-kB pathway (plasma cell differentiation pathway)

191
Q

what are the 2 different types of light chains on immunoglobulins (aka antibodies)?

A

kappa

lamda

“sound like names of american sororities - the people in these sororities are often very skinny = light”

192
Q

what are the 5 different types of heavy chains on immunoglobulins (aka antibodies)?

A

IgA

  • 2 antibodies
  • found in mucous, saliva, tears + breast milk
  • protects against pathogens
  • “Archiologists, always need to work in pairs as work is so boring, do a lot of outdoor work”

IgD

  • 1 antibody
  • part of the B-cell receptor
  • activates basophils + mast cells
  • “Dentistry, no one really knows what they do all day, few of them”

IgE

  • 1 antibody
  • protects against parasites
  • responisble for allergic reactions
  • very few norm in body
  • “economics, likely to rile against really parasites (eg donald trump) but fake ones too (eg poor people), rarely see them”
IgG
- 1 antibody
- secreted by plasma cells in blood
- only Ig able to cross placenta
- most numerous
"Geography, they are everywhere, able to use a map to get to the placenta"

IgM

  • 5 antibodies
  • responsible for early stages of immunity
  • may be attached to surface of B cell or secreted in blood
  • “Medics, always the first to the scene, so keen! hang around in groups”
193
Q

what is a paraprotein?

what are they indicative of?

A

a monoclonal immunoglobulin or light chain present in the blood or urine; it is produced by a clonal population of mature B cells, most commonly plasma cells

ie identical Igs (fully formed or not) which are produced by malignant b cell clones

multiple myeloma

194
Q

how are paraproteins picked up in the blood?

A

protein electrophoresis (ie looking at the protein content of the blood)

should have lots of albumin (+ other non-Ig proteins) and then a variety of different Igs, but if malignancy then lots of one specific Ig (and fewer other Igs)

195
Q

multiple myeloma:

  • median age at presentation?
  • ethnic variation?
  • preceeded by?
A

median age: 70 years

higher incidence in afro-caribbean groups (lower in caucasians)

asymptomatic MGUS

196
Q

what does multiple myeloma progress to?

A

plasma cell leukaemia (PCL)

basically myeloma but spread more into blood (not just bone marrow)

197
Q

what is the diagnostic criteria for myeloma?

A
  • clonal bone marrow plasma cells >10% (of plasma cells in bone marrow)
  • OR plasmacytoma present

AND one or more of:

  • CRAB features
  • MDEs (myeloma defining events)
198
Q

what is a plasmacytoma?

what are the 2 different types?

A

A plasmacytoma is a discrete, solitary mass of neoplastic monoclonal plasma cells in either bone or soft tissue

types:
- Soft-tissue = extramedullary plasmacytoma (EMP)
- bone = Solitary bone plasmacytoma (SBP)

199
Q

what are the ‘CRAB’ features of myeloma?

A

C - hyperCalcaemia

R - Renal insufficiency

A - Anaemia

B - Bone lesions (seen on imaging)

200
Q

what are ‘myeloma defining events’ (MDEs)? 3

A

> 60% clonal plasma cells on bone marrow biopsy

SFLC ratio is over certain threshold (and no. light chains is high)

more than 1 focal lesion on MRI measuring >5mm

201
Q

what is SFLC ratio?

A

serum free light chain ratio

measures ratio between kappa and lamda light chains in blood

  • should be equal as about same amount produced by healthy cells but if lots of one type being produced by clonal cancer cells then this will skew ratio

also no. of light chains will increase in myeloma as cancer cells don’t bother making whole antibodies

202
Q

what % of patients with myeloma will have renal insufficiency at some point during the disease course?

A

50%

203
Q

what are the 9 main reasons why myeloma is likely to cause renal insufficiency?

A
  • renal vein thrombosis (myeloma is prothrombotic)
  • hyperviscosity of blood
  • cryoglobulinaemia (Igs in blood clump + become insoluble)
  • hypercalcaemia
  • bisphosphonates (used to treat hypercalcaemia)
  • dehydration (occurs w myeloma)
  • CT contrast
  • NSAIDs
  • ACEi

nb also:

  • increased age of patients
  • often have comorbidities which require treatment w nephrotoxic drugs
204
Q

what are the common clinical symptoms of myeloma? 3

A
  • fatigue + malaise
  • bone pain (particularly back + rib pain)
  • infective episodes (particularly pneumococcal chest infections secondary to failure of production of normal Igs)
205
Q

what are the symptoms of hypercalcaemia? 4

A
  • anorexia
  • confusion
  • constipation
  • polyuria
206
Q

what are the symptoms of renal impariment? 2

A
  • confusion

- oligouria/anuria

207
Q

what is MGUS?

what are the diagnostic criteria?

A

monoclonal gammopath of uncertain significance

basically ‘pre-myeloma’
- is asymptomatic

  • serum paraproteins lower than certain point
  • <10% clonal plasma cells in the bone marrow
  • absence of end-organ damage (CRAB) or myeloma-related events (MREs)
208
Q

what is the risk of progression from MGUS to myeloma?

A

approx 1% a year progress

nb majority progress to myeloma but can also progress to other lymphocyte disorders

209
Q

what 3 things makes a patient with MGUS more likely to progress to myeloma?

A

higher paraprotein levels

if have IgA/IgM paraproteins (IgG less likely to progress)

abnormal SFLC ratio

210
Q

what is AL amyloidosis?

what organs can it affect?

what is the prognosis?

A

Amyloid Light chain amyloidosis

light chains are abnormally produced, they fold and aggregate in organs -> organ damage

  • kidney (nephrotic syndrome)
  • liver (hepatomegaly)
  • neuropathy (nerves)
  • heart (heart failure)

very poor prognosis (but rare

211
Q

what is the difference between nephrotic syndrome and nephritic syndrome?

A

nephrotic syndrome

  • proteinuria
  • hypoalbuminaemia (as albumin is peed out)
  • oedema (due to low albumin)
  • hyperlipidaemia (liver compensates low albumin by increaasing production, side effect is more lipid production)

“there’s an O in nephrOtic and in prOtein”

nephritic:

  • haematuria
  • proteinuria (small amount)
  • oligouria

nb nephritic is more serious condition as blood cells are bigger than protein so if that’s coming through then kidneys are more damaged

212
Q

what is the treatment for AL amyloidosis?

A

same as for myeloma:
- aim to ‘switch off’ production of light chains by the plasma cells

  • very difficult to remove the proteins which have already deposited -> significant morbidity + mortality
213
Q

what are the two different groups of non-hodgkin B lymphomas? give some examples of each

A

high-grade

  • burkitt lymphoma
  • diffuse large b-cell lymphoma

low-grade

  • follicular lymphoma
  • marginal zone lymphoma
  • hairy cell leukaemia
  • mantle cell lymphoma
214
Q

what are the differences between high-grade and low-grade lymphomas? 5

A

onset

  • high-grade = sub-acute onset (weeks/couple of months)
  • low-grade = months/years

lymph nodes (LN):

  • high-grade = lots of LN involved at presentation
  • low-grade = only a few LN sites involved at presentation

symptoms:

  • high-grade = systemic symptoms (weight loss, night sweats, fatigue)
  • low-grade = clinically well

bloods

  • high-grade = often abnormal
  • low-grade = often normal

prognosis:

  • high-grade = curative (very chemoresponsive as high cell turnover), but poor prognosis if relapse
  • low-grade = non-curative but relapsing/remitting course over years
215
Q

what are the possible causes of a neck mass:

  • malignant? 3
  • non-malignant? 5
A

malignant:

  • lymphoma
  • chronic lymphocytic leukaemia (CLL)
  • metastatic cancer of lung/breast/cervix

non-malignant:

  • infective (bacterial, viral, mycobacterial)
  • inflammatory (sarcoidosis)
  • lipoma
  • fibroma
  • haemangioma
216
Q

what do you see on lymph node biopsies if lots of B cells are proliferating (norm clonally)?

A

lots of follicles

217
Q

what is follicular lymphoma?

what genetic mutation is seen?

A
  • a type of low-grade non-hodgkin lymphoma
  • neoplastic disorder of lymphoid tissue
  • translocation from C14 to C18
  • “from the ages of 14-18 people tend to be very cliquey and live in their own little bubbles = follicles”
218
Q

what is hodgkin lymphoma?

what age does it occur?

A
  • neoplastic lymphocytes characterised by Hodgkin Reed-Sternberg (HRS) cells SURROUNDED BY a lot of non-malignant inflammatory cells (eg eosinophils)

nb HRS cells are large + look like popcorn

nb often present with B symptoms!

can occur at any age!!

219
Q

what are LDH tests used for?

A

lactate dehydrogenase tests

  • present in all cells of body, if high in blood means there is lots of cellular damage and/or high cell turnover

used to measure progression of:

  • some cancers
  • kidney problems
  • liver disease

(nb used to be used for heart attacks but not anymore)

220
Q

what is the treatment for hodgkin lympohoma?

A
  • chemotherapy (ABVD)
  • —- “like ABCD but get rid of the C for cancer”
  • radiotherapy
221
Q

what is the prognosis for hodgkin lymphoma?

A

very good

however there are long term effects due to treatments and chance of relapse

222
Q

what is a pet ct scan?

A

using pet AND ct scan to find areas of high cell turnover

223
Q

what does a typical lymph node biopsy of a patient with hodgkin’s lymphoma look like?

A

big popcorn (hodgkins cells) with lots of inflammatory cells

224
Q

what is chronic lymphocytic leukaemia (CLL)?

whao is it predominately seen in?

A
  • malignant disorder of MATURE B-cells
  • low-grade non-hodgkins lymphoma
  • most common type of leukaemia
  • seen in older people
225
Q

what does presenation of CLL vary between?

A

incidental finding of lymphocytosis

to..

widespread lymphadenopathy, splenomegaly, bone marrow failure + systemic symptoms

226
Q

what is the system used to stage CLL?

what 3 factors does it use?

A

binet system

  • Hb level (low is bad)
  • platelet level (low is bad)
  • no. of areas of lympadenopathy (more is bad)
227
Q

what is a rare, but serious , complication of CLL?

A

transformation to a high-grade lymphoma

  • acute onset of severe symptoms
  • rapidly enlarging lyph nodes
  • poor prognosis (less than a year, even with chemo)
228
Q

what is the treatment for any weakness of the bone (also used for hypercalcaemia)?

A

biphosphates

229
Q

what are 6 cancers which commonly metastasise to bone? (and so often cause pathological fractures)

A
  • myeloma
  • breast cancer
  • lung cancer
  • prostate cancer
  • renal cancer
  • thyroid cancer
230
Q

what is a bence jones protein?

where is it found?

if found, what does it indicate?

A

monoclonal immunoglobulin light chain

found in the urine

multiple myeloma

231
Q

what is myeloma?

A

Myeloma is a malignant disorder of plasma cells whereby neoplastic plasma cells
proliferate in the bone marrow and secrete monoclonal immunoglobulin.

232
Q

what are the 6 most common clinical presentations of myeloma (aka multiple myeloma)?

A
  • anaemia
  • fatigue
  • weight loss
  • BONE PAIN
  • hypercalcaemia
  • renal impairment

nb these are a result of:

  • bone marrow infiltration
  • infiltration into organs
  • kidney damage secondary to serum free light chain deposition
233
Q

name 10 causes of macrocytic anaemia

A
  • B12 deficiency
  • folate deficiency
  • alcohol excess
  • liver disease
  • smoking
  • hypothyroidism
  • pregnancy
  • haemolysis (causing a reticulocytosis)
  • myeloproliferative neioplasm
  • myelodysplastic syndrome
234
Q

what is the IPSS-R scoring sytem used for?

A

to work out prognosis of patients with myelodysplatic syndrome (and likelihood of progression to AML)

based on:

  • blood count parameters
  • blast count
  • cytogenetic abnormalities
235
Q

what are the main sites of haematopoiesis at:

  • 1 month gestation
  • 5 months gestation
  • birth
  • adult
A

1 month = yolk sac

5 months = liver (+ spleen)

birth = bone marrow (in femur + tibia)

adult = 
- vertebrae
- pelvis 
- sternum
(- ribs)
(- lymph nodes)
236
Q

what is the % of foetal Hb at birth?

A

55-65%

237
Q

what are the main differences between new born blood and adult blood?

A
  • foetal Hb is larger than adult Hb
  • therefore RBCs are also larger
  • therefore haematocrit is also higher
238
Q

what chains make up:

  • foetal Hb
  • adult Hb
  • adult 2 Hb
A

foetal Hb = a2y2

adult Hb = a2B2

adult 2 Hb = a2d2

(d = delta, y = gamma)

239
Q

which antibodies can be transfered from mother to baby via:

  • the placenta?
  • breast milk?
A

placenta
- IgG ONLY

breast milk
- ALL (IgA, IgD, IgE, IgG, IgM)

240
Q

at what age to babies start to produce their own antibodies?

at what age can they make a satisfactory immune response?

A

antibodies = 2-3 months old

satisfactory immune response = 6 months

241
Q

how to white cell counts differ between newborns and adults?

A
  • similar numbers

but babies have higher lymphocyte counts

242
Q

how are infant’s and adult’s platelets different?

A

functionally different, infant’s are:

  • hyporesponsive to certain agonists
  • hyperresponsive to vWF

so babies are hyperresponsive to blood vessel tears (as vWF lives in endothelial cells)

balances out (ie babies have about the same functionality of platelets as adults)

243
Q

coagulation factors:

  • which cross the placenta?
  • which are present (at normal levels) at birth?
  • at what age does the infant have adult levels?
A

NONE cross the placenta
- to prevent clot forming in umbilical cord in the womb

at birth:

  • factors 5, 8 and 13
  • “5+8 = 13”

normal levels at 6 months

244
Q

what is the difference between haemorrhagic disease of the newborn and haemolytic disease of the newborn?

A

haemorrhagic
= haemorrhages in baby due to vit K deficiency
(nb all babies are slightly vit K deficient)

haemolytic
= anti-rhesus antibodies from Rh- mother attack Rh+ baby’s RBCs

245
Q

how is haemorrhagic disease of the newborn prevented?

A

all babies are given a vit K injection at birth

246
Q

what drugs, taken by the mother, will increase the risk of haemorrhagic disease of the newborn in the baby?

A
  • warfarin

- anti-convulsants (aka anti-epileptic drugs)

247
Q

what are congenital causes of anaemia in childhood? 5

A

haemoglobin synthesis problem (ie haemoglobinopathy)
- eg sickle cell, thalassaemia

bone marrow failure syndromes

bone marrow infiltration (ie cancer)

peripheral destruction (you are making something but it’s being destroyed)

blood loss

248
Q

what are the causes of peripheral destruction (leading to congenital anaemia)? 4

ie causes of haemolytic anaemia

A

Rh/ABO or other incompatibility

membrane defect
- eg hereditary spherocytosis

enzyme defect:

  • G6PD deficiency
  • Pyruvate Kinase (PK) deficiency

infection

249
Q

what is hereditary spherocytosis?

why does it result in haemolytic anaemia?

how do the cells look on a blood screen?

A

spherical RBCs, not flexible, will break at the slightest insult

(so much shorter lifespan than normal RBCs)

(nb normal RBCs bend to fit through capillaries, spherical RBCs can’t do this so break)

RBCs don’t have the normal central palor on blood screen

250
Q

what is G6PD deficiency?

A

deficiency of enzyme Glucose 6 Phosphate Dehydrogenase

causes haemolytic anaemia in presence of:

  • fava beans (and other foods)
  • infection
  • some drugs
251
Q

what are two causes of congenital blood loss?

A
  • twin to twin transfusion (nb twin with extra blood is also not healthy as blood is too thick, hard to get through capillaries)
  • fetomaternal haemorrhage
252
Q

What is a common cause of acquired anaemia in children?

A
  • iron deficiency

nb B12 + folate deficiencies in children are rare - unless mum is vegan

253
Q

what are three congenital causes of bleeding/bruising?

A
  • platelet problem
  • clotting factor problem
  • connective tissue disorder
254
Q

what is the function of the globin part of the haemoglobin molecule? 3

A
  • protects haem from oxidation
  • renders the molecule soluble
  • permits variation in oxygen affinity (resulting in sigmoid dissociation curve)
255
Q

what are the % of HbA, HbA2 + HbF in normal adult blood?

A

HbA = >95%

HbA2 = <3.5%

HbF = <1%

256
Q

what are thalassaemias (alpha or beta)?

A

change in globin gene expression (none or reduced rate) leads to reduced rate of synthesis of NORMAL globin chains. Pathology is due to imbalance of alpha and beta chain production (free globin chains damage red cell membrane)

(nb sickle cell disease produces correct amount of globin proteins, they are just abnormal!)

257
Q

what physiological changes occur in the blood during pregnancy? 8

A
  • plasma volume expands by 50% (therefore lower haematocrit) - called HAEMODILUTION
  • RBC mass expands by 25%
  • increased requirement for iron (often become iron deficient)
  • leucocytosis (mainly a neutrophilia)
  • left shift (outflow of some blasts into blood)
  • thrombocytopenia (normal but rule out other causes too!)
  • increase in coagulation factors + thrombin generation
  • reduction in anti-coagulant factors + fibrinolysis

nb pregnancy (+ 2 months following birth) is a pro-thrombotic state -> ^risk of clots

258
Q

what do RBCs look like in thalassaemias?

A

small, pale and red

ie microcytic anaemia

(resembles iron deficient anaemia)

259
Q

sickle cell anaemia:

  • what is the NORMAL genetic cause?
  • why does it cause RBCs to ‘sickle’?
A

valine substituted for glutamine at position 6 of the B globin gene

Sickle Hb polymerises at low oxygen saturations to form long fibrils (tactoids) which distort RBC membrane –> sickel shape

260
Q

what is the average lifespan of:

  • sickle cell?
  • normal RBC?
A

sickle = 10-20 days

normal RBC = 120 days

261
Q

what can reduce the levels of polymerisation of sickle Hb?

A

if other Hb is present, eg foetal Hb

262
Q

apart from the direct effects of sickling caused by sickle cell disease, what secondary effects does this cause?

A

inflammatory response due to haemolysis of sickle cells, confusing, don’t need to know detail

263
Q

what are the acute complications of sickle cell disease?

A
  • vaso-occlusive crisis (aka sickle cell crisis, accounts for 80% of hosp admissions)
  • septicaemia
  • aplastic crisis (temporary cessation of RBC production)
  • sequestration crisis (spleen, liver)
264
Q

what are reticulocytes?

A

Reticulocytes are immature red blood cells, typically composing about 1% of the red blood cells in the human body. In the process of erythropoiesis, reticulocytes develop and mature in the bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells

so if you have a high reticulocyte count then likely to have a haemolytic anaemia so your boduy is producing more RBCs

265
Q

where in the body do sickle cell crises normally occur?

A
  • hands and feet (dactylitis)
  • chest syndrome
  • mesenteries (abdo pain)
  • bones (long bones, ribs, spine)
  • brain
  • penis (priapism)
266
Q

what is a sequestration crisis?

A

Splenic sequestration crises are acute, painful enlargements of the spleen, caused by intrasplenic trapping of red cells and resulting in a precipitous fall in haemoglobin levels with the potential for hypovolemic shock.

267
Q

which acute complication is the highest cause of mortality in sickle cell patients?

A

chest syndrome

nb opiate painkillers given for painful crisis decrease resp drive + so may be a contributing factor to chest syndrome

268
Q

what are four chronic complications of sickle cell disease? 9

A

hyposplenism
- due to infarction + atrophy of spleen

renal disease

avascular necrosis (AVN) of femoral/humeral heads
- due to poor collateral circulation, if clot, no blood can get there

leg ulcers

osteomyelitis

gall stones

retinopathy

cardiac problems

resp problems

269
Q

what is osteomyelitis?

A

infection in the bone

270
Q

what treatment do sickle cell disease sufferers recieve from age 6 months?

A

penicilin

as prophylaxis

271
Q

what treatment is given in a vaso-occlusive (sickle cell) crisis?

A
  • analgesia (norm opiates)
  • hydration
  • treatment of precipants

(nb no evidence that transfusions help in crises!)

272
Q

what treatment is given to sickle cell patients who have a lot of vaso-occlusive crises?

how does it work?

A

hydroxycarbamide

  • increases Foetal Hb
    (thus reducing polymerisation)

(also acts as an anti-inflammatory, reduces inflammatory response to crisis, recover quicker!)

273
Q

when would you give a blood transfusion (or exchange) to a sickle cell patient? 5

A
  • splenic sequestration
  • aplastic crisis
  • acute chest crisis
  • acute stroke
  • pre-operative
274
Q

what treatment is given to sickle cell patients to reduce burden of chronic complications? 5

A

transcranial doppler
- monitors blood flow in brain, likelihood of stroke

MRI

  • for monitoring of avascular necrosis of bone ends
  • may need joint replacement

cholecystectomy
- for symptomatic bilary disease

monitoring of renal function via blood tests

opthalmic review (annually)

nb can be cured by bone marrow transplant!

275
Q

what is it called if you are:

  • heterozygous carrier of a thalassaemia?
  • homozygous for a thalassaemia?
A

heterozygous = thalassaemia minor (clinically normal)

homozygous = thalassaemia major

nb thalassaemia is a very heterogeneous condition! many mutations cause it and all have slightly different phenotypes, also have thalassaemia intermedia!

276
Q

what complications can occur due to thalassaemias?

A
  • pulmonary hypertension
  • extramedullary haemaopoiesis (start making blood in liver + spleen)
  • bone changes + osteoprosis
  • endocrine + fertility problems
  • leg ulcers

nb lots of problems are caused by iron overload as body brings in more iron from guts as wants more Hb but RBCs are also breaking down releasing more Hb/iron and body has no way of excreting iron!

277
Q

what is the pathophysiology of B-thalassaemia major?

A

alpha chain excess

  • > ineffective erythropoiesis (RBCs die in marrow)
  • > shortened RBC lifespan (haemolysis)
  • —> anaemia

increased marrow activity

  • > skeletal deformity, stunted growth
  • > increased iron absorption from gut + organ damage (exacerbated by blood transfusion)
  • > protein malnutrition

enlarged + overactive spleen (+liver)

  • > pooling of RBCs (increased anaemia)
  • > increased transfusion requirement
  • > extramedullary haemopoiesis
278
Q

what head bone abnormalities can occur in thalassaemias? why?

A
  • frontal bossing
  • maxillary hypertrophy
  • -> abnormal dentition

all due to expanded bone marrow

279
Q

what is the treatment for B-thalassaemia major?

A

monthly transfusions

  • suppress marrow RBC production
  • prevents skeletal deformity
  • prevents liver/spleen enlargement

iron chelation therapy
- to prevent iron overload

(bone marrow transplant)
- nb only successfukl if early in life + before iron overload occurs

280
Q

what different types of iron chelation therapy are there?

how is iron level monitored?

A
  • long subcutaneous injection (via overnight syringe pump) of DESFERRIOXAMINE (older treatment)
  • new oral iron chelators (inlcude DEFERIPRONE + DEFERASIROX)

“the longer drug name takes the longer time to give”

measuring ferritin levels in the blood

(nb ferritin is a carrier of iron in the blood)

281
Q

what comlications can be seen in B-thalassaemia major?

A

increased rate of infections

  • eg line infections (as loose peripheral access)
  • eg transfusion transmitted infection

endocrine complications

  • eg can get diabetes
  • eg hypothyroidism + hypoparathyroidism

liver disease
- cancer can develop secondary to cirrhosis + iron overload

bone problems
- give bisphosphates, don’t over-chelate

fertility

  • issues due to hypogonadism
  • norm need IVF to stimulate ovaries
  • need low iron + perfect health before get pregnant
282
Q

what organs are affected by iron overload? what happens?

A

gonads/hypothalamus
- failure of puberty, growth failure

pancreas
- diabetes

heart
- dilated cardiomyopathy + heart failure

liver
- cirrhosis

283
Q

what are the three corners of virchovs triangle?

A
  • blood flow
  • blood composition
  • vascular endothelium

factors which affect risk of arterial or venous clots

284
Q

which parts of virchovs triangle are normally abnormal in formation of:

  • arterial clots?
  • venous clots?
A

arterial clots:
- vascular endothelium (atheromatous plaques)

venous clots:

  • blood flow (stasis)
  • blood composition (hypercoaguable state)
285
Q

what are the main components of:

  • arterial clots?
  • venous clots?
A

arterial:
- mainly platelets

venous
- mainly fibrin

286
Q

what % of DVTs are clinically silent?

A

80%

287
Q

what are the risk factors for venous thromboembolism (VTE)? 16

A
  • oestrogen containing contraceptive
  • pregnancy + post-natal period
  • hormone replacement therapy
  • active cancer (or cancer treatment)
  • critical care admission
  • surgery
  • major trauma
  • immobility
  • one or more significant medical comorbidities
  • varicose veins with phlebitis
  • known thrombophilias
  • personal history of VTE
  • first degree relative with VTE
  • age over 60
  • obesity
  • dehydration
288
Q

what are 3 bits of general advice of how patient risk of VTE can be easily reduced?

A
  • don’t allow patients to become dehydrated (unless clinically indicated)
  • encourage patients to mobilise as much as possible
  • do not regard aspirin (or other antiplatelets as adequate prophylaxis for VTE)
289
Q

what are the two type of prophylaxis for VTE?

A
  • TED stockings

- low-dose anticoagulant (normally low-dose lmwh)

290
Q

who can’t use TED stockings?

A

patients who have:

  • peripheral neuropathy
  • peripheral blood problems
  • skin problems
291
Q

what’s the difference between unfractionated heparin and lmwh?

A

both enhance the effect of antithrombin!

unfractionated:

  • acts on thrombin AND factor 10a
  • also acts on other molecules
  • less reliable effect

lmwh:

  • only acts on factor 10a
  • more reliable effect
292
Q

if a patient has a suspected VTE, what tests should you do?

A

calculate likelihood of risk using WELLS SCORE

if wells

293
Q

what is the gold standard test for:

  • DVT?
  • PE?
A

DVT = ultrasound

PE = multislice CT with contrast

294
Q

if a patient with a suspected PE cannot have a multislice CT with contrast, what scan can they have instead?

how does this work?

who would this be used for?

A

VQ scan

  • inhaled radioisotope is administered to look for ventilation
  • injected radioisotope is administered to look for perfusion
  • then compare images to see if any mismatches

useful for:

  • pregnancy (no x-rays)
  • renal insufficiency (contrast is nephrotoxic)
295
Q

what is the normal treatment for confirmed VTE?

A
  • high dose lmwh

- – then start and gradually shift over to warfarin (heparin is faster acting)

296
Q

what is the newer alternative treatment for VTE?

A

NOACs

eg rivaroxaban + apixaban

  • they work as DIRECT factor 10a inhibitors (heparin + warfarin work via anti-thrombin)
  • they can be used as one drug (ie not like lmwh then warfarin)
  • can be taken orally
  • predictable effect, less dose monitoring
  • however there is no antidote!

“apiXAban = inhibits Xa, ie 10a”

297
Q

name 6 heritable thrombophilias

A
  • antithrombin deficiency
  • protein C deficiency
  • protein S deficiency
  • Factor V leiden (aka activated protein C resistance)
  • dysfibrinogenaemia
  • prothrombin 20210A
298
Q

name an acquired thrombophilia

A

antiphospholipid syndrome

an autoimmune condition

  • get autoantibodies against negatively charged phospholipids
  • confusing but main effect is that it increases risk of arterial and venous thrombosis

nb can occur secondary to lupus (SLE)

299
Q

what is factor V leiden

A

aka activated protein C resistance

basically, normally protein C cleeves activated factor 5 to break up clots
- however, in factor V leiden, the protein C can’t bind to the factor 5a (as it’s mutated) and so cannot deactivate it!

leading to a prothrombotic effect

nb most common european familial thrombophilia (can be heterozygous or homozygous)

nb interacts with other VTE risk factors, unlikely to cause a clot on its own but has an additive effect

300
Q

what is prothrombin 20210A?

A
  • point mutation in enhancer region of prothrombin gene

leads to INCREASED prothrombin levels
–> increased likelihood of clots

a weak risk factor for VTE on its own, interacts with other risk factors to have an additive effect

301
Q

in haematology, what is MCV?

A

mean cell volume

used to differentiate between macrocytic, normocytic + microcytic anaemia

302
Q

what are 7 causes of macrocytic anaemia?

A
  • B12 deficiency
  • folate deficiency
  • alcohol
  • liver damage
  • drugs (cytotoxics/folate antagonists/N2O)
  • haematological malignancy (or other bone marrow problems)
  • haemolysis (due to increased production of reticulocyte, which are bigger than mature RBCs)
303
Q

what are 2 causes of normocytic anaemia?

A
  • anaemia of chronic disease

- blood loss

304
Q

what are 3 causes of microcytic anaemia?

A
  • iron deficiency
  • haemoglobin disorders (sickle cell, thalassaemia)

( - sometimes anaemia of chronic disease)

305
Q

in the body, what molecules is iron:

  • transported by?
  • stored in?

where in GI tract is iron absorbed?

can iron be excreted?

A

transported by transferrin

stored in ferritin

absorbed in duodenum (+ bit in jejunum)

no!

306
Q

what lab test is most commonly used to diagnose iron-deficient anaemia?

A

ferritin

there is no other known cause of low ferritin apart from iron deficiency

307
Q

what type of RBCs are present in iron-deficient anaemia?

A

microcytic (low MCV)

AND

hypochromic (low MCH)

MCH = mean cell Hb

308
Q

what are the main causes of iron deficient anaemia? 3

A

blood loss from anywhere (sub-acute/chronic)

increased demand
- pregnancy/growth

reduced intake
- diet/malabsorption (eg coeliac)

309
Q

what are the most likely causes of iron-deficient anaemia in:

  • children? 3
  • young women? 3
  • old people?
A

children:

  • diet
  • growth
  • malabsorption

young women:

  • menstrual loss/problems
  • pregnancy (even long after)
  • diet

old people:

  • bleeding
  • GI problems (malignancy, ulcer, gastritis, diverticulitis, GI surgery etc)

nb in elderly rule out bleeding + canceer first as these most severe

310
Q

what is the treatment for iron deficient anaemia?

A
  • iron tablets (but can be poorly tolerated due to GI side effects)
  • IV iron, better tolerated
311
Q

how does B12/folate deficiency cause anaemia?

A
  • DNA consists of purine/pyramidine bases
  • folates are required for their synthesis
  • B12 is essential for cell folate generation
  • so low folate OR B12 starves DNA of bases

so they are clinically indistinguishable

312
Q

problems with what things cause B12 deficiency?

A
  • gastric parietal cells (produces intrinsic factor)
  • intrinsic factor (binds to B12 to allow absorption)
  • receptors in terminal illeum (where intrinsic factor/B12 complex absorbed)

nb low dietary B12 causing B12 deficiency is very rare! as only need a small amount and is stored for long periods of time (years)

nb also get a lower level in pregnancy but this is normal doesn’t need treatment

313
Q

what are 2 diseases affecting the stomach can cause B12 deficiency?

A

pernicious anaemia
- autoimmune antibodies against intrinsic factor/parietal cells

gastrectomy

314
Q

give 6 example of diseases of the small bowel which can cause B12 deficiency

A
  • terminal illeum resection
  • crohns
  • stagnant loops
  • jejunal diverticulosis
  • tropical sprue
  • fish tapeworm
315
Q

what are the causes of folate deficiency?

A
  • mainly dietary/malnutrition cause
  • also malabsorption/small bowel disease

also if increased usage:

  • pregnancy
  • haemolysis
  • inflammatory disorders
  • drugs/alcohol/ITU
316
Q

what are the signs + symptoms of B12/folate deficiency? 6

A

megaloblastic anaemia
- can have pancytopenia if more severe (esp in advanced B12 deficiency)

mild jaundice

glossitis (inflammation of tongue)

angular stomatitis (inflammation of lips)

anorexia/weight loss

sterility

317
Q

what is a severe complication of B12 deficiency? (normally of pernicious anaemia)

what happens?

how can this present? 4

A

subacute combined degeneration of the cord (SACDC)

  • demyelination of dorsal + lateral columns
  • peripheral nerve damage

presents as:

  • peripheral neuropathy/paraesthesiae
  • numbness + distal weakness
  • unsteady walking
  • dementia

nb may get this before anaemia presents

always think about B12 deficiency when a patient has neuro symptoms

318
Q

what is the treatment for:

  • folate deficiency?
  • B12 deficiency?
A

folate:
- folic acid pills daily

B12:
- 3 monthsly IM injection of B12
(- can have oral B12 if know it’s not pernicious anaemia)

319
Q

causes of haemolytic anaemia:

  • things that are wrong inside RBC? 2
  • things that are wrong with RBC membrane? 1
  • things that are wrong external to RBC? 4
A

inside cell:

  • haemoglobinopathies (sickle cell, thalassaemias)
  • enzyme defects (G6PD)

membrane:
- hereditary conditions (eg hereditary spherocytosis)

external:

  • antibodies to RBC membranes
  • drugs/toxins
  • faulty heart valves
  • vascular/vasculitis/microangiopathy
320
Q

what are the 4 main things to test for in the blood if you suspect haemolysis?

A
  • high MCV (body compensating)
  • high reticulocytes (body compensating)
  • raised bilirubin
  • raised LDH

nb also look at blood film for fragments/spherocytes/etc

321
Q

what test do you use to test if there are antibodies attacking RBCs?

A

DCT/DAT

direct coombes test/direct anti-globulin test

tests to see if there are any anti-RBC antibodies in blood

322
Q

what is the treatment for autoimmune haemolytic anaemia (AIHA)?

A

managed with steroids/immunosuppression

if severe: transfusion (but hard to reliable crossmatch!)

323
Q

with what sort of conditions do you normally see ‘anaemia of chronic disease’?

why?

A
  • malignant
  • inflammatory
  • chronic infectious
  • multiple medical diseases
  • etc

reduced RBC production due to:

  • abnormal iron metabolism
  • poor erythropoetin production
  • poor erythropoetin response
  • blunted marrow response

it’s basically an inflammatory effect on bone marrow - often have raised inflammatory markers

nb this is a diagnosis of exclusion, exclude any other causes of anaemia first

324
Q

how do you treat ‘anaemia of chronic disease’?

A

if underlying disease is treated anaemia normally resolves
- but this is often hard

  • give erythropoietin and/or iron if they are symptomatic

(can do transfusions if nothing else works)

325
Q

what sort of things can cause thrombocytopenia? 9

A
  • ITP
  • other autoimmune disorders
  • drugs/alcohol/toxins
  • liver disease and/or hypersplenism
  • pregnancy (physiological + complications, eg ITP, preeclampsia)
  • haematological/marrow diseases
  • infections (eg acute sepsis, HIV, other viral)
  • DIC
  • range of congenital conditions

nb there are many more

326
Q

what is ITP?

what conditions can it be associated with? 4

A

immune (formerly idiopathic) thrombocytopenic purpura

autoimmune condition against antigens on platelets

can be: acute/chronic/relapsing

associated with:

  • lymphoma
  • CLL
  • HIV
  • other autoimmune disease

nb kids often have a preceding illness (prodrome) whereas adults tend not to

“12 year old pregnant diver in House had this”

327
Q

how does ITP present?

A

bruising, petechiae and/or bleeding

low platelet count (but can vary hugely)

nb this is a diagnosis of exclusion! no definitive test

328
Q

what is the treatment for ITP? 4

A

steroids (first line)

IV immunoglobulin (2nd line)

other immunosuppressives or splenectomy (3rd line)

newer thrombo-mimetics (eltrombopag, romiplostin)
- stimulate platelet production (mimic thrombopoetin)

nb usually rapid response to treatmetn but can relaps + commonly recurrent (though rarely life-threatening)

329
Q

why do you give someone IV immunoglobulins if they are suffering from ITP/how do they work?

A

if you saturate spleens (and other lymphatics) with exogenous Igs then spleen ‘chews up’ them instead of platelets (so fewer platelets destroyed)

  • however this is a temporary solution as, once Igs are ‘chewed up’, spleen wil go back to destroying platelets instead
330
Q

what is TTP?

why does it occur?

what are the signs/symptoms?5

A

thrombotic thrombocytopenia purpura (TTP)

extensive microclots throughout circulation (damaging organs, incl kidneys, heart + brain)

autoimmune anitbodies against enzyme ADAMTS-13 (this normally reduces the action of vWF) increasing potency of vWF so any slight endothelial injury results in lots of clots
- so basically have too much vwf

signs/symptoms:

  • thrombocytopenia (all used up in clots)
  • fever
  • neurological symptoms
  • haemolysis (retics/LDH)
  • bleeding

nb this is a lot rarer than ITP but is a lot more serious

331
Q

what is the treatment for TTP?

A
  • plasma exchange with FFP/plasma
  • steroids

(monitor ADAMTS-13 level in case of relapse)

332
Q

what is acute leukaemia?

what are the 2 main subgroups?

A

result of accumulation of early myeloid or lymphoid precursors in the bone marrow, blood and other tissues

may arise de novo or be the terminal event of a pre-existing blood disorder

  • acute myeloid leukaemia (AML)
  • acute lymphoblastic leukaemia (ALL)
333
Q

what histological feature do blast cells have that mature ones do not?

A

nucleoli

  • appear a small white circles in the nucleus
334
Q

what are the main symptoms of acute leukaemia? 3

which organs may leukaemia cells infiltrate? 5

A
  • anaemia
  • infections
  • easy bruising + haemorrhage
  • spleen
  • liver
  • meninges
  • testes
  • skin
335
Q

which type of leukaemia is most likely to infiltrate the meninges?

why is this important?

A

acute lymphoblastic leukaemias (ALL)

because of the blood-brain barrier, once the cancer has spread to CNS it’s harder to get drugs to the cancer cells via normal route (eg IV) so have to do spinal injections which are higher risk

336
Q

name 3 examples of common infections in leukaemia patients.

what type of leukaemias are most likely to lead to each one?

A

staphylococcus aureus infection of the orbit (around eye)
- AML

mixed perianal infection with strep faecalis + E. coli
- AML

oral candida
- ALL

337
Q

what are haemorrhagic ecchymoses?

how are they different from purpura?

in what type of leukaemia do you tend to get this? why?

A

a sub-cutaneous spot of bleeding not caused by trauma but by underlying cell pathology (ie clotting problems)

same as purpura, but larger

AML
- as platelets are derived from the myeloid lineage

338
Q

at what level of platelet count do you get spontaneous bruising and bleeding?

A

platelet count below 10

339
Q

what specific type of leukaemia often causes gum infections and hypertrophy?

A

monocytic leukaemia

- a type of AML

340
Q

what tests are done to confirm a leukaemia diagnosis? 4

A
  • blood smeer (morphology of cells)
  • immunological markers
  • cytogenetics, FISH
  • molecular techniques (PCR - polymerase chain reaction)
341
Q

what was the ‘old’ and what is the ‘new’ classification of AMLs?

A

old: FAB classification = ‘morphological’
new: WHO classification = ‘risk adapted’

ie new one is about working out the likely prognosis of the cancer and using that to guide appropriate treatment decisions

342
Q

what is the normal process of myeloid cell maturation (to a neutrophil)?

(ie what are the 6 intermediate cell types)

A

myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> band -> neutrophil

nb shape of nuclei:

  • metamyelocyte = kidney
  • band = horseshoe
  • neutrophil = lobed
343
Q

what feature is typically of promyelocytic leukaemia?

what is the treatment?
- how does it work?

A

when you give chemo:
- get DIC

because cellular contents are very procoagulant so when the cells are broken down (due to chemo) these are released -> DIC (+ related clotting problems)

treatment:
- give chemo AND all trans retinoic acid (ATRA)

ATRA makes premyelocytes mature to neutrophils (fewer procoagulant contents) so when chemo breaks cells down, DIC doesn’t occur!

344
Q

what histological findings are often present in the blast cells found in AML?

A

auer rods

small linear red lines (of crystalised granules)

345
Q

what is the philadephia translocation?

in which leukaemias is this found?

A

exchange of material between C22 + C9

(9 becomes longer, 22 shorter)

BCR-ABL fusion gene created on C22 –> tyrosine kinase

  • CML - 95%
  • ALL - 25%
    (- AML - occasionally)
346
Q

what is the treatment for AML in:

  • favourable risk groups?
  • intermediate risk groups?
  • poor risk groups?
A

give chemo to all first

favourable risk groups
- chemo

intermediate risk groups
- depends

poor risk groups (or younger patients)
- bone marrow transplant

347
Q

what are poor prognostic risk factors in ALL? (2 major, 4 minor)

A

major risk factors:

  • increasing age (kids do very well)
  • high white cell count (at presentation)

minor risk factors:

  • male
  • certain cytogenetic abnormalities
  • poor response to treatment
  • T-ALL and null-ALL (ie if B-cell then best prognosis)
348
Q

what is the treatment for ALL? 3

A

all patients:

  • intensive chemo
  • intrathecal methotrexate (prophylaxis of meningeal leukaemia)
  • cranial irradiation (prophylaxis of meningeal leukaemia)

then:

  • good risk patients = maintenance chemo
  • bad risk patients = bone marrow transplant
349
Q

what is the main complication of treatment of acute leukaemia?

what is the treatment?

A

neutropenic sepsis

all patients w acute leukaemia will become neutropenic during treatment

puts at high risk of BACTERIAL infection -> sepsis

treatment:
- IMMEDIATE broad-spectrum antibiotics (within an hour) - eg tazocin + gentamicin

nb given before get results of cultures, then can make treatment more specific

350
Q

what is done to prevent neutropenic sepsis? (incl drug names) 5

A
  • protective isolation (sterile hospital room)
  • prophylactic antibiotics (LEVOFLOXACIN)
  • use of granulocyte colony stimulating factors
  • strict hand hygiene
  • patient education
351
Q

what are the large cells characteristic of hodgkins lymphoma called?

A

reed sternberg cells

“popcorn cells”

inflammatory cells almost always found with them

“hodgkins sounds like a hedge, and both hedges and reeds are plants, so with hodgkins you get reed sternberg cells”

352
Q

name a NOAC which is a direct thrombin inhibitor

A

dabigatran

353
Q

what is the most common type of non-hodgkins low-grade lymphoma?

A

follicular lymphoma

called because the abnormal b lymphocytes cluster in lymph nodes to form, what are called, follicles

354
Q

what is the suffix of lmwh’s?

give an example

A

-parin

“like hePARIN”

enoxaparin

355
Q

a transfusion related lung injury (TRALI) is a reaction against which cells?

A

leucocytes

356
Q

what are the two main functions of vwf?

A
  • to transport factor 8 in the blood (factor 8 degrades rapidly when not bound)
  • it binds to exposed collagen (ie when endothelium is damaged) and then binds to platelets
    (effectively forming a bridge between damaged endothelial wall and platelets) + activating the platelets in the process

-> degranulation of platelets

platelets secrete:

  • more vwf
  • fibrinogen
  • serotonin -> vasocomstriction
  • ADP -> activates platelets
  • Ca2+ -> secondary haemostasis
  • thromboxane -> vasoconstriction, activates platelets + causes activation
357
Q

where is vwf produced/stored? 2

A
  • in granules in platelets

- in granules in endothelial cells

358
Q

why does aspirin have an anti- platelet effect?

A

becuase it is a COX inhibitor

COX is the enzyme which (among other things) synthesises thromboxane in platelets

so without thromboxane, have less vasocnstriction, activation + aggregation of platelets

359
Q

what is the mechanism of clopidogrel (another anti-platelet)?

A

interferes with ADP receptor

another way that platelets are activated

360
Q

what clotting time is used to monitor anticoagulation with warfarin? aka? why?

A

prothrombin time

INR

because this measures the EXTRINSIC pathway which is the one in whick the vit K dependent factors are in

“1972”

361
Q

what is the sickle cell mutation?

A

when the 6th amino acid is mutated from glu -> val

362
Q

what ethnic group are thalassaemias particularly common in?

A

greeks

esp greek cypriots

363
Q

what globin chains do you have an excess of in:

  • alpha thalassaemia?
  • beta thalassaemia?
A

alpha thalassaemia:
- excess of beta chains

beta thalassaemia:
- excess of alpha chains

364
Q

why do thalassaemias lead to skeletal deformities?

A

because increased activity in bone marrow to compensate for the haemolytic anaemia

so messes up structure of bone thus changing the morphology and reducing the strength

* year 2 Clinical Pathology (11 decks)

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