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Haematology Flashcards

1
Q

Describe the changes to the FBC in pregnancy

A

Mild anaemia (dilutional)
Neutrophilic leucocytosis
Thrombocytopenia with increase in size

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2
Q

What is the recommended pregnancy Fe and folate intake?

A

Folate: 400ug/day
Fe: 30mg/day

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3
Q

Describe several reasons for platelet levels falling in pregnancy

A

Gestational thrombocytopenia: normal, not well understood. Increases in the days following delivery

Pre-eclampsia: increased platelet activation and consumption due to inflammation. Associated with DIC. Improves after delivery

Immune thrombocytopenic purpura: may precede pregnancy, or pregnancy can uncover. Very low levels.

Microangiopathic syndromes: eg HELLP, SLE, APS, HUS. Deposits of 0latelet rich thrombi and fragmented RBCs, causing organ damage.

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4
Q

Describe the management of ITP in pregnancy

A

Management includes IV Ig, steroids and azathioprine.

May affect the fetus, so important to check cord blood and monitor for falling platelets.

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5
Q

Describe the changes to the maternal clotting pathways in pregnancy

A

Increased clotting factors (vWF, FVIII, fibrinogen)
Decreased fibrinolytic factors (protein S)
Placenta produces PAI 1 and 2, which are hypofibrinolytic

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6
Q

T/F. D dimer remains unchanged in pregnancy.

A

False. Ddimer is increased and therefore should not be used to assess for VTE

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7
Q

What is antiphospholipid syndrome? What are the indications for testing?

A

APS: recurrent miscarriages or mid trimester loss and persistence of antibodies
Indications:
-3+ consecutive miscarriages before 10 weeks
-1+ mid trimester loss of normal fetus
-1+ preterm birth with abnormal placenta

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8
Q

Describe some haematological conditions that affect the fetus

A
  • Twin-twin transfusion syndrome/TAPS: polycythaemia in one, anaemia in the other twin. Due to imbalance of AV anastomoses
  • Parvovirus infection: anaemia/hydrops
  • Rhesus disease: anaemia/hydrops
  • Polycythaemia due to placental insufficiency
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9
Q

Which disorder is associated with congenital leukemia? Describe this condition.

A

Downs syndrome.

Transient disease, often remits in several months but may relapse after several years

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10
Q

Which chromosomes contain the globin genes?

A

Chromosome 11: beta cluster

Chromosome 16: alpha cluster

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11
Q

What are the types of haemoglobin? When are they present?

A

Foetal Hbs: 1st trimester
HbF (2 alpha, 2 gamma): during most of fetal life, and first few months of life
HbA (2 alpha, 2 beta): increases during 1st year of life. Main adult Hb
HbA2 (2 alpha, 2 delta): develops during 1st year of life. Makes up <3.5% of adult Hb

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12
Q

Describe the spectrum of sickle cell disease

A

Sickle cell disease: describes a spectrum of AR conditions including sickle cell anaemia + other heterozygous states

  • SCA: HbSS. Homozygous for HbS
  • HbSC: heterozygous for HbS and HbC (similar)
  • Sickle beta thalassaemia: heterozygous for HbS and beta thalassaemia
  • Sickle cell trait: HbAS. Heterozygous for HbS
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13
Q

What is the cause of sickle cell anaemia?

A

Point mutation of GAG -> GUG on codon 6 of beta globin
Causes amino acid switch from glutamine -> valine
Results in abnormal polymerisation of Hb when deoxygenated
Sickling of RBCs

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14
Q

Describe the complications of sickle cell anaemia

A 
SICKLED
Splenomegaly + sequestration crises -> hyposplenism
Infarction: stroke, splenic 
Crises: painful, acute chest, aplastic
Kidney disease
Liver + lung disease
Erections (priapism)
Dactylitis

+gallstones

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15
Q

Describe the blood results of a person with sickle cell anaemia

A
  • FBC: low, microcytic
  • Film: sickle cells, boat cells, Howell-Jolly bodies (hyposplenism)
  • Sickle solubility test
  • Hb electrophoresis/HPLC: low HbA, higher HbA2
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16
Q

Which complications of sickle cell anaemia are specific to children?

A
  • Splenic sequestration
  • Hand-foot syndrome (painful crises)
  • Increased susceptibility to infections
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17
Q

Strokes in children should make you think of ___

A

Sickle cell anaemia

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18
Q

Describe the pathophysiology of beta thalassaemia

A
  • Defect in the beta globin gene on Chromosome 11
  • Low levels of HbA, increased HbA2. Presents in infancy
  • Trait: asymp/mild anaemia mimics Fe deficiency
  • Intermedia: mild-mod anaemia
  • Major: severe anaemia, extramedullary haematopoiesis, requires transfusions and chelation with desferrioxamine
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19
Q

Name some consequences of blood transfusion for beta thalassaemia

A

Iron overload causing:

  • Cardiomyopathy
  • Diabetes
  • Hyperpigmentation
  • Infertility
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20
Q

Describe the pathophysiology of alpha thalassaemia

A
  • Defect in the alpha globin gene on Chr 16
  • Low/absent HbF, HbA, HbA2
  • Trait: only 2-3 functioning genes
  • HbH: only 1 functioning gene
  • HbBarts: no functioning genes. Incompatible with life. Severe hydrops.
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21
Q

Name some causes of haemolysis in neonates

A
  • Haemolytic disease of the newborn: eg Rh disease
  • ABO incompatibility
  • Hereditary spherocytosis
  • G6PD deficiency
  • Pyruvate kinase deficiency
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22
Q

Describe the presentation (clinical and biochemical) of haemolytic anaemia

A

-Anaemia: conjunctival pallor, fatigue, SOB
-Jaundice
-Splenomegaly
-Low Hb
-Film: schistocytes, spherocytes, etc.
-High unconjugated bilirubin and urobilinogen (+ dark urine)
-High reticulocyte count (polychromasia)
-High LDH
-Low haptoglobins
+/- DAT test

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23
Q

What are some types of acquired haemolytic disease?

A
  • Autoimmune haemolytic anaemia
  • MAHA: HUS, DIC, TTP
  • Malaria
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24
Q

What are some characteristics of AIHA?

A

Spherocytes, DAT +ve

Can be associated with infections (eg hepatitis, mycoplasma), malignancy, connective tissue D (RA, SLE)

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25
Q

What is HUS?

A

Haemolytic uraemic syndrome:

  • Microangiopathic haemolytic anaemia
  • AKI
  • Thrombocytopenia
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26
Q

What is the pathophysiology of haemophilia? How does it present?

A

Deficiency in FVIII (A) or FIX (B). A > B incidence

  • > abnormal secondary haemostasis
  • Bleeding, bruising, haemarthrosis
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27
Q

Define anaemia + ranges

A

Low RBCs or haemoglobin in the blood.
Men: <135 g/L
Women: <115 g/L

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28
Q

Name some broad mechanisms of anaemia

A

Reduced production of RBCs: aplastic anaemia
Increased breakdown of RBCs: haemolytic anaemia
Decreased haemoglobin: Fe/B12/folate deficiency
Increased plasma volume: pregnancy

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29
Q

What are the different types of anaemia? What are some causes of each

A

Microcytic: Fe deficiency, anaemia of chronic disease, sideroblastic anaemia, thalassaemia
Normocytic: blood loss, pregnancy, anaemia of chronic disease, bone marrow failure, haemolysis, renal disease
Macrocytic: B12/folate deficiency, alcoholism/liver disease, hypothyroidism, reticulocytosis

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30
Q

Name some signs/symptoms of anaemia

A

Pallor, SOB, dizziness, fatigue, palpitations, headache

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31
Q

Name some signs/symptoms of iron deficiency. What is the syndrome associated with iron deficiency and what are the features?

A

-General anaemia: pallor, SOB, dizziness, fatigue
-Koilonychia
-Atrophic glossitis
-Angular cheilosis
-Brittle hair and nails
Plummer Vinson syndrome: oesophageal webs, iron deficiency anaemia, dysphagia

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32
Q

Describe the FBC + blood film in iron deficiency anaemia

A
  • Anaemia (low Hb)
  • Microcytic (low MCV)
  • Hypochromic
  • Anisocytosis, poikilocytosis
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33
Q

What are some causes of iron deficiency anaemia? What are some red flags?

A
  • Chronic blood loss: GI (ulcers, cancer), HMB, urine
  • Increased use: growth/pregnancy/lactation
  • Decreased intake: poor diet, malabsorption

**Worried if male, post-menopausal, weight loss -> ?malignancy

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34
Q

How is iron deficiency anaemia treated?

A

Treat cause
Conservative:
-Diet modification

Medical:

  • Ferrous sulphate 200mg PO BD
  • > ferrous fumarate
  • > IV
  • Co-prescribe with laxatives, warn about GI upset
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35
Q

Describe the pathophysiology of anaemia of chronic disease. What are some common causes?

A

Cytokines cause inhibition of RBC production thru affecting EPO synthesis and iron metabolism

  • Inflammatory conditons eg. IBD, RA
  • Chronic infection eg. TB
  • Malignancy
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36
Q

Describe the haem picture in ACD

A
  • Anaemia
  • Micro/normocytic
  • High ferritin
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37
Q

What is sideroblastic anaemia? What are some causes?

A

A condition of ineffective erythropoiesis causing iron loading in the bone marrow -> ringed sideroblasts
-Myelodysplastic disorders, chemorad, alcohol, anti-TB drugs, porphyrias

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38
Q

Describe the iron studies in iron deficiency anaemia

A

LOW iron
HIGH total iron binding capacity
LOW ferritin

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39
Q

Describe the iron studies in ACD

A

LOW iron
LOW TIBC
HIGH ferritin

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40
Q

Describe the iron studies in chronic haemolysis

A

HIGH iron
LOW TIBC
HIGH ferritin

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41
Q

What is ferritin? What is it affected by?

A

Ferritin is an acute phase protein that stores iron in cells.
It can be increased in inflammation, infection, malignancy -> always do a CRP with ferritin

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42
Q

If a patient has an inflammatory condition, what is the best way to estimate iron?

A

Transferrin saturation (serum iron/TIBC)

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43
Q

Name some causes of macrocytosis

A
  • Megaloblastic: B12 deficiency, folate deficiency
  • Non-megaloblastic: alcohol, reticulocytosis (from haemolysis), liver disease, hypothyroidism, pregnancy
  • Other: myelodysplasia, myeloma, etc
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44
Q

What are 4 characteristics of a megaloblastic blood film?

A
  • Macrocytic anaemia: nucleated RBCs, Howell-Jolly bodies
  • Leukopenia
  • Thrombocytopenia
  • Hypersegmented neutrophils
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45
Q

What are some causes of B12 deficiency? How can it present?

A

-Dietary insufficiency eg. vegan
-Malabsorption: pernicious anaemia, Crohn’s, infestation
Presents with peripheral neuropathy (tingling, numbness), glossitis, angular cheilosis, neuropsych (irritable, depression, dementia)

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46
Q

Describe the pathophysiology of pernicious anaemia

A
  • Antibodies to gastric parietal cells + intrinsic factor

- Decreased absorption of B12

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47
Q

What is the treatment for B12 deficiency?

A

IM hydroxycobalamin

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48
Q

Where is folate found? What are some causes of deficiency?

A
  • Leafy greens, nuts, yeast
  • Causes: poor diet, pregnancy, increased cell turnover (malignancy, haemolysis), malabsorption, alcohol, anti-epileptics, methotrexate
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49
Q

How is folate deficiency treated? What is the important caution?

A
  • Give folate supplements

- Be careful not to give randomly as can exacerbate B12 neuropathy

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50
Q

What are the haem features of haemolytic anaemia?

A
  • Low Hb, normocytic or macrocytic if reticulocytosis
  • High reticulocytes, polychromasia
  • High LDH
  • High bilirubin (unconjugated)
  • Low haptoglobins
  • Blood film: specific depending on type eg spherocytes, Heinz bodies, bite cells, schistocytes
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51
Q

Describe the classification of haemolytic anaemia and name some causes

A
  • Inherited (hereditary spherocytosis, SCA, G6PD deficiency)

- Acquired can be immune (AIHA, HDFN) vs non-immune (MAHA, malaria, ADENOCARCINOMA)

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52
Q

Describe the pathophysiology of hereditary spherocytosis and elliptocytosis

A

HS: AD mutation in the B spectrin, ankyrin, band 3

HE: usually AD mutation in A/B spectrin
-Leads to membrane structure changes -> haemolysis in the spleen

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53
Q

A 35 year old man comes to A&E with severe breathlessness and extreme fatigue for the past 2 days after developing a mild cold. He has a PMH of hereditary spherocytosis. What investigation will indicate the most likely diagnosis?

A

Reticulocyte count- this man may have parvovirus B19 infection that has caused aplastic crisis. Therefore, a reticulocyte count would be low.

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54
Q

Which stain shows iron deposition in the liver? What is the name for this state?

A

Perl’s stain. Hepatic siderosis

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55
Q

Which tests are diagnostic for hereditary spherocytosis?

A

Osmotic fragility and dye binding tests

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56
Q

What is the pathology in paroxysmal nocturnal haemoglobinuria

A

Mutation in GPI protein (on outside of membrane), important for preventing immune-mediated destruction

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57
Q

What is the pathophysiology of G6PD deficiency?

A
  • X linked mutation causing decreased G6PD enzyme activity
  • Protects against oxidative damage thru glutathione
  • When ox. damage occurs -> intravascular haemolysis
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58
Q

Describe the haematological features of G6PD deficiency

A
  • Haemolytic anaemia picture (low Hb, high reticulocytes, high bilirubin, high LDH etc)
  • Blood film: bite cells, Heinz bodies, abnormally contracted cells
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59
Q

Name some triggers of haemolysis in G6PD deficiency

A
  • Fava beans
  • Moth balls
  • Infection
  • Drugs: sulfonamides, primaquine
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60
Q

What are the classic cells seen in pyruvate kinase deficiency?

A

Echinocytes - spiky cells

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61
Q

What are the types of autoimmune haemolytic anaemia? Describe.

A
  • Warm AIHA: IgG. Associated with blood cancers, SLE

- Cold agglutinin disease: IgM. Assoc with EBV, mycoplasma

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62
Q

What is Ham’s test used for?

A

To diagnosis paroxysmal nocturnal haemolgobinuria

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63
Q

Name some types of MAHA.

A
  • HUS
  • TTP
  • HELLP
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64
Q

What are the features of HUS? TTP?

A

HUS: MAHA, AKI, thrombocytopenia
TTP: MAHA, AKI, thrombocytopenia, fever, neurological dysfunction

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65
Q

Describe the pathophysiology of TTP

A

ADAMTS13 antibodies -> abnormal vWF that cause RBC destruction

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66
Q

Heinz bodies suggest ____

A

Oxidative damage eg. G6PD deficiency

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67
Q

Describe the principles of haemostasis

A
  • Primary haemostasis: formation of the platelet plug. Involves platelet activation and recruitment, binding.
  • Secondary haemostasis: formation of a fibrin clot. Involves clotting cascade forming crosslinking fibrin
  • Fibrinolysis
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68
Q

Describe the clotting cascade

A
  • Intrinsic pathway: includes FXII -> FXI - FIX - FVIII - FX
  • Extrinsic pathway: involves TF activating FVII
  • Common pathway: FV - Prothrombin - Fibrin
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69
Q

What is the role of FVIII in the clotting cascade?

A

Supports the conversion of FIX to FX

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70
Q

How is clotting assessed?

A
  • APTT: intrinsic pathway
  • PT: extrinsic pathway
  • TT: common pathway
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71
Q

What is Virchow’s triad? Name some factors that affect each.

A
  • Vessel wall injury: atherosclerosis, infection, malignancy, vasculitis
  • Hypercoagulability: pregnancy, COCP, dehydration, multiple myeloma
  • Stasis: flights, surgery, casts, bed rest
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72
Q

Describe the process of primary haemostasis

A
  • Vessel wall injury causes exposure of collagen + vWF to the blood
  • Attracts platelets -> binding directly or via vWF with Glp1 -> release CKs/thromboxane
  • Platelet activation + recruitment -> crosslinking with GlpII and fibrinogen
73
Q

What is the mechanism of action of aspirin? Other NSAIDs?

A

Aspirin is an irreversible inhibitor of COX1 enzymes -> inhibits production of thromboxane A2 -> decreased platelet aggregation

NSAIDs are reversible inhibitors.

74
Q

What is the function of thrombin?

A
  • Activates platelets
  • Activates the clotting cascade
  • Converts fibrinogen -> fibrin
75
Q

What is the complex that is needed to activate thrombin the most efficiently?

A
  • FXa
  • FVa
  • Ca
76
Q

Why is vitamin K needed?

A

Important in the activation of factors:

-2, 7, 9, 10

77
Q

Describe the process of fibrinolysis

A
  • Tissue plasminogen activator activates plasminogen to plasmin
  • Plasmin cuts fibrin into fibrin degradation products
78
Q

What are the physiological anticoagulants? How do they work?

A
  • Protein C and S: protein S supports activation of protein C to inactivate FV and FVIII
  • Antithrombin: binds to thrombin, allows excretion
79
Q

What is the pathophysiology of FV Leiden?

A

Resistant to breakdown by protein C -> leads to hypercoagulable state

80
Q

What is the mechanism of action of heparin? Warfarin? How are they monitored?

A

Heparin: potentiates the action of antithrombin. Measured with APTT
Warfarin: Vit K antagonist, prevents activation of Factors 2,7,9,10. Monitored with INR/PT. Narrow therapeutic window

81
Q

What is the mechanism of action of DOACs? What are their advantages?

A
  • Anti Xa: rivaroxaban, apixaban
  • Anti IIa: dabigatran
  • Better bc less risk of bleeding
82
Q

Name some causes of bleeding disorders

A
  • Inherited: platelet disorders, haemophilias, vWD

- Acquired: liver disease, Vit K deficiency, thrombocytopenias (ITP, TTP, pre-eclampsia, HUS), DIC

83
Q

Describe the pattern of bleeding in platelet disorders and clotting factor deficiencies

A
  • Platelet: superficial bleeding, petechiae/purpura, mucous membrane bleeding, prolonged bleeding
  • Clotting factors: deep bruising, haemarthrosis, delayed bleeding
84
Q

When is treatment required for thrombocytopenia?

A

When Plt <30 X 10^9. Risk of spontaneous haemorrhage

85
Q

What are the treatment options for ITP?

A
  • Steroids

- IVIG (to bind antibodies and prevent destruction)

86
Q

What are some causes of thrombocytopenia?

A
  • Immune: MAHA, HUS, ITP, SLE, RA

- Non-immune: B12 deficiency, bone marrow failure, DIC

87
Q

What are the types of haemophilia? What is the treatment?

A

A: FVIII deficiency
B: FIX deficiency
Haem: prolonged APTT, normal PT, low FVIII/IX
Management: transfusion of factor VIII/IX concentrate when bleeding occurs, may need prophylactic transfusions

88
Q

What are the types of vWD? What is the haematological/clotting picture?

A

Type 1: partial decreased vWF
Type 2: poor vWF function
Type 3: no vWF -> low FVIII. Similar to haemophilia
-Prolonged APTT and bleeding time, normal PT, normal Plts, low/normal vWF antigen, low vWF function

89
Q

What are some causes of DIC?

A
  • Sepsis
  • Burns
  • Trauma
  • Malignancy
90
Q

Describe the pathophysiology of DIC

A

Activation of coagulation pathways:

1) Deposition of fibrin clots in small vessels -> organ damage
2) Consumption of clotting factors, Plts -> bleeding

91
Q

A 78 year old man with urosepsis is in ICU due to DIC. What do you expect to see on the clotting screen?

A
  • Prolonged APTT
  • Prolonged PT
  • Low Plts
  • Low fibrinogen
  • High FDPs
  • +/- haemolytic anaemia
92
Q

Why is liver disease associated with increased bleeding?

A

Decreased synthesis of clotting factors: 2, 7, 9, 10, 11, fibrinogen

93
Q

What is the therapeutic window for warfarin? How is warfarin OD managed?

A

Around 2.0-3.0

-Depending on the INR and bleeding, may hold next dose/give PO Vit K/give Vit K infusion/give FFP or PCC

94
Q

How is heparin OD managed? What are the complications of heparin use?

A

Protamine

Bleeding, heparin induced thrombocytopenia, osteoporosis

95
Q

Name some ways in which cancer can cause anaemia

A
  • Chronic blood loss-> Fe deficiency (colon)
  • Anaemia of chronic disease
  • Haemolytic anaemia (thru immune + non-immune)
  • Infiltration of bone marrow
96
Q

What is leucoerythroblastic anaemia?

A

Red and white cell precursor anaemia. Occurs due to bone marrow infiltration eg. mets, lymphoma, myelofibrosis.
Findings include: teardrop RBCs, nucleated RBCs, immature myeloid cells

97
Q

What do nucleated RBCs indicate?

A

Bone marrow stress - eg. infiltration by malignancy, myelofibrosis

98
Q

What do spherocytes in the blood film indicate?

A

Hereditary spherocytosis, autoimmune haemolytic anaemia

99
Q

Define polycythaemia. Name some causes

A

Polycythaemia: increase in Hb and haematocrit
Relative: due to decreased plasma eg alcohol, obesity
1˚: polycythaemia rubra vera (increased JAK2)
2˚: high altitude, chronic hypoxia, renal cancer

100
Q

What are immature white cells in the blood film called? What do they suggest?

A

Blasts eg. myeloblasts, lymphoblasts.

Bone marrow problem eg leukemia

101
Q

Name some causes of neutrophilia. What do you look for on a film?

A

Neutrophilia: infection (bacterial), inflammation, leukemia, steroids
Film can show if they are reactive (eg. toxic granulation) in infection/inflammation or malignant (eg. presence of blasts)

102
Q

What can cause eosinophilia?

A

Parasitic infection, allergic disease, malignancy (Hodgkins)

103
Q

What are some causes of lymphocytosis and lymphopenia? How do you interpret a lymphocytosis?

A

Lymphocytosis: viral infection (EBV), malignancy (CLL)
-Reactive will have polyclonal expansion, malignant will have monoclonal
-Film: atypical lymphocytes in infection eg. mono, smear cells in CLL, immature in ALL
Lymphopenia: HIV, autoimmune disease

104
Q

What is immunophenotyping used for?

A

Determining the stages of maturation

Determining clonality eg. light chain restriction

105
Q

Describe the clinical features of acute leukemias. What are the distinguishing features?

A

Rapidly worsening

  • Anaemia: fatigue, pallor, SOB, dizziness
  • Thrombocytopenia: petechiae, bruising, mucosal bleeding
  • Neutropenia: infections
  • Weight loss, fever, night sweats, hepatosplenomegaly

Specific to AML: gum hypertrophy, skin infiltration, hyperviscosity and retinal haemorrhages

Specific to ALL: lymphadenopathy, CNS involvement, testicular and thymic enlargement

106
Q

Which groups are primarily affected by acute leukemias? What are some risk factors?

A

ALL: children. Down’s.
AML: older adults + infants. RFs: radiation, chemo, smoking, trisomy

107
Q

Describe the pathogenesis of AML

A

Genetic changes: duplications esp Chr 8 and 21, t15;17 translocation to form the APML gene, deletion of 5/5q or 7/7q, changes to core binding factor (CBF) action
-> inability to mature -> proliferation of immature myeloblasts

108
Q

What is APML?

A

Acute promyelocytic leukemia. A form of AML caused by the formation of a fusion gene at t15;17 -> PML-RARA
-Characteristically causes haemorrhage and DIC

109
Q

What is the classic finding on blood film in AML?

A

Auer rods

110
Q

What investigations are used for diagnosing AML and ALL? What will they show? What is the importance of each?

A
  • FBC: low Hb, low Plt, high WCC (suggests malignancy)
  • Film: blasts, Auer rods (diagnostic of leukemia)
  • Cytochemistry: for AML- myeloperoxidase, Sudan black
  • Immunophenotyping: MPO, different CDs (diagnostic for type: AML, B-ALL, T-ALL)
  • Cytogenetics: very important. (aids in treatment decision-making)
111
Q

Describe the treatment of acute leukemias

A

Chemotherapy is mainstay. 6 mos AML, 2 yrs F/3 yr M in ALL
1) Induce remission -> 2) consolidation -> 3) maintenance
+ Intrathecal chemo in ALL
Also important to give allopurinol, antibiotics, etc
Last line: BMT

112
Q

Describe the pathogenesis of ALL

A

Genetic changes in the B/T cell lineages: translocations, duplications etc. Usually first hit happens in utero
-> oncogene dysregulation and proliferation of blasts

113
Q

What percentage of blasts in peripheral blood is normal? What level is too high?

A

Normal is <5%
5-19% suggests myelodysplasia
>20% suggests AML

114
Q

What type of mutations typically leads to cell proliferation in haem malignancies?

A

Tyrosine kinase mutations -> increased mature cells

115
Q

What is a myeloproliferative disorder? What does this include? What are the common mutations associated with these?

A

Increase in myeloid cells with normal differentiation. Includes PV, CML, essential thrombocytopenia, PMF
Common mutations: JAK2, philadelphia chr (9:22), calreticulin

116
Q

What are some signs and symptoms of PV, management

A
  • Hyperviscosity: thrombosis, plethoric, retinal haemorrhage, blurred vision, headache,
  • Splenomegaly
  • Aquagenic pruritus
  • Erythromelalgia

Mx:

  • Aspirin
  • Venesection (remove RBCs)
  • Hydroxycarbamide
117
Q

What is primary myelofibrosis? What are the signs/symptoms? How is it diagnosed? What is the prognosis?

A

A type of MPD, caused by replacement of BM with collagen (reactive fibrosis) and extramedullary haematopoeisis.
-Anaemia, thrombocytopenia
-Massive splenomegaly + hepatomegaly (EMHP)
-Hypermetabolic state
Dx: clinical, BM biopsy is key (dry tap)
Very poor prognosis

118
Q

What are the haem findings in PV, PMF, ET?

A
  • PV: high Hb/Hct/RCV, high Plt
  • PMF: low Hb, low Plt (leucoerythroblastic anaemia). Tear drop RBCs, nucleated RBCs, circulating megakaryocytes
  • ET: very high Plts
119
Q

What is essential thrombocytosis? How does it present?

A

Increase in platelets (abnormal functioning)

  • Can have either increased thrombus formation OR bleeding
  • Erythromelalgia
  • Splenomegaly, headache, dizziness, blurred vision
120
Q

What is the classic genetic mutation in CML? What is the presentation?

A 
Philadelphia chromosome (9:22 translocation, formation of the fusion protein BCR-ABL, abnormally active tyrosine kinase) detected with FISH/PCR
Hypermetabolism, MASSIVE hepatosplenomegaly, bleeding/bruising
121
Q

Describe the haem findings in CML

A
  • N/High Hb, Plts
  • Massively high WCC (neutrophils, basophils)
  • Ph +ve on FISH
122
Q

What is the course of CML? What is the treatment?

A
  1. Chronic phase: asymptomatic, slow increase in WCC. Increased proliferation but normal differentiation
  2. Accelerated phase: increase in WCC + symptoms
  3. Blast phase: increase in blasts, becomes like AML with hypermetabolic symptoms
    - During the chronic phase, can use Imatinib/newer
123
Q

What is lymphoma? Describe the classification

A

Lymphoma is a malignant tumour of lymphoid cells. Can occur in the lymph nodes, spleen, skin, gut- any organ with lymphoid tissue.
Many types!!!
-Hodgkins (20%)
-Non-Hodgkins (80%): B cell, T cell

124
Q

How does the physiology of lymphocyte production create the environment for lymphoma?

A
  • Recombination means genetic instability: VDJ recom, class switching, somatic hypermutation contribute
  • Reliance on apoptosis to regulate -> if mutated, prolif
  • Rapid proliferation -> increased error
125
Q

What are some risk factors for lymphoma?

A
  • Constant antigen stimulation eg. inflammation -> H pylori and gastric MALT, coeliac and EATL
  • Infection: HTLV1 and ATLL, EBV
  • Loss of T cell function: HIV (fails to stop EBV lymphomas eg Burkitts, Hodgkins)
126
Q

Describe the anatomy of the lymph nodes

A

B cell follicles surrounded by T cell zones
Centre is the medulla where B cells end up
Within the B cell follicles: mantle zone -> germinal centre where the naive cells undergo maturation when meeting presented Ag

127
Q

Name the common CD markers that differentiate lymphocytes

A

CD20: B cells, not plasma B cells (differentiated)
CD19: B cells
CD10: germinal centre B cells
CD 3, 4, 5: T cells

128
Q

Describe the different investigations used in diagnosis of lymphoma

A
  • Cytology and histology: eg follicular, diffuse
  • Immunophenotyping: clonality, CD markers, etc
  • Molecular tools: FISH/PCR for chromosomal translocations etc
129
Q

Name some types of NH B cell lymphoma and briefly describe

A
  • Follicular: lymphadenopathy in older adults. Low grade, 14;18 translocation of bcl-2 gene. Germinal centre.
  • Marginal zone/MALT: post-GC memory B cells. Usually extranodal eg. GI, thyroid. Chronic Ag stimulation. May reverse with removal of stimulus in early stage
  • Diffuse large B cell: sheets of large cells, destroy node structure. Aggressive.
  • Burkitts: presents as jaw/abdo mass, rapidly growing. Assoc w/ EBV, HIV. c-myc oncogene. Starry sky appearance. Germinal centre cells.
  • Mantle cell: pre-GC cells. CD5 and cyclin D1. 11;14 translocation. Aggressive.
130
Q

Name some types of NH T cell lymphoma and briefly describe

A
  • Anaplastic large cell: young. Large cells. Alk-1 protein.
  • Adult T cell leukemia/lymphoma (ATLL): HTLV1 infection. Caribbean and Japan.
  • EATL: assoc w/ coeliac
131
Q

What are the main differences between Hodgkins and non-Hodgkins lymphoma?

A

Hodgkins: spreads contiguously to nearby nodes, more localised, germinal/post-germinal B cells only

132
Q

What are the types of Hodgkins lymphoma? Briefly describe

A

Classical- nodular sclerosing/lymphocyte rich or depleted/mixed: single nodal group. Young + middle aged. Large cells w/ pink nucleoli- owl’s eyes, Reed Sternberg cells, eosinophils. CD30+ 15+ 20-.

Non-classical/lymphocyte predominant: B cell rich nodules, no eosinophils, CD 30/15 -ve, CD 20+ve.

133
Q

How does Hodgkins lymphoma present? How is it staged?

A

Presents with painless enlarging LNs +/- obstructive symptoms, B symptoms
Staged with Ann Arbor staging:
1: 1 group of nodes affected (spleen counts)
2: multiple groups affected, same side of diaphragm
3: multiple groups affected, two sides of diaphragm
4: other sites eg. liver, BM
A/B: if B symptoms present eg. fever >38, night sweats, weight loss (>10% in <6 mos).

134
Q

Describe the management of Hodgkins lymphoma. What is the prognosis?

A

Intensive chemotherapy ABVD: adriamycin, bleomycin, vinblastine, dacarbazine
+/- radiotherapy: if bulky area
Stem cell transplant
Prognosis is very good!! Treatment is balance of risk of recurrence and risk of chemo-related complications (2˚ malignancy, etc)

135
Q

How are lymphomas staged/graded?

A
  • Biopsy: cytology, histology, immunophenotyping, cytogenetics, molecular genetics
  • Imaging: PET-CT, MRI
  • Bloods: kidney function, LDH, BBVs, albumin
136
Q

What is the standard treatment for NHL? What is the prognosis?

A 
For DLBC: chemotherapy with R-CHOP
-Rituximab
-Cyclophosphamide
-Doxorubicin
-Vincristine
-Prednisolone
For indolent eg. follicular: watch and wait
The higher the grade (based on histological subtype), the better the outcome eg. DLBCL better, follicular worse
137
Q

Which group is CLL commonly found? What are the signs/symptoms?

A

Old white people. Most common leukemia in West

  • Usually asymp/picked up on routine testing
  • Anaemia, thrombocytopenia, neutropenia
  • Smear cells on blood film
138
Q

Which cells are affected in CLL? What are the CD markers?

A
  • Mature B cells

- Express CD-19 (normal for B cells) but also abnormally express CD 5 (normal for T cells)

139
Q

What is Richter transformation?

A

Transformation of CLL into a high grade leukemia (ALL) or aggressive large cell lymphoma

140
Q

What is the treatment for CLL?

A

Usually watch and wait due to indolent course

Can use new agents eg Ibrutinib (BCR kinase inhibitor), Venetoclax or CAR-T cell therapy

141
Q

What is multiple myeloma? Describe the pathophysiology and precursor syndrome. Which type is most common?

A

Malignancy of plasma cells. Lead to proliferation of monoclonal B cells that produce immunoglobulins (paraproteins). IgG most common
-Preceded by monoclonal gammopathy of uncertain significance (MGUS)

142
Q

Describe the clinical features of multiple myeloma

A

Signs/symptoms due to BM infiltration and Ig secretion
Calcium high (>2.75)
Renal failure: raised Cr (>177) or GFR (<40)
Anaemia (<100)
Bone pain, osteoporosis
-Infections due to low range of Igs
-Monoclonal paraprotein, Bence Jones proteins in urine
-High ESR

143
Q

What CD markers are found on myeloma plasma cells?

A

CD 138, CD 38, CD 56. NO CD 19/20

144
Q

Describe the diagnostic tests for multiple myeloma

A
  • FBC and film: low Hb, lots of plasma cells, rouleaux
  • U+Es: renal failure
  • Bone profile: high Ca
  • BM biopsy: high blasts (>10%), Immunohistochemistry
  • Serum protein electrophoresis: monoclonal gammopathy, high M spike (>30g/l). IgG/A
  • 24 hr urine collection/urine protein electrophoresis: Bence Jones proteins
145
Q

What is Waldenstrom’s macroglobinaemia?

A

A type of low grade NHL, producing monoclonal IgM. Similar to MM

146
Q

Describe the management of multiple myeloma

A
  • Symptomatic: bisphosphonates
    1. Chemo: melphalan, cyclophosphamide
    2. Steroids: dex/pred
    3. Proteasome inhibitors: Bortezumib
    4. Immunomodulatory drugs: Lenalidomide, thalidomide
  • Stem cell transplant
147
Q

What are myelodysplastic syndromes? How do they present?

A

A group of disorders of myeloid stem cells characterised by ineffective proliferation and differentiation
-Present with signs of pancytopenia in the elderly with defective cells (on film/BM biopsy)

148
Q

Name some different types of MDS

A

-Refractory anaemia (RA): anaemia no blasts.
-Refractory anaemia with ringed sideroblasts (RARS):
-Refractory cytopenia with multilineage dysplasia (RCMD): cytopenia, dysplasia in BM
-RCMD + RS:
etc etc

149
Q

Name some cells/findings in blood film and BM biopsy in MDS

A
  • Hypercellular and dysplastic BM with peripheral cytopenias
  • Ringed sideroblasts
  • Hypogranulated white cells, bilobed neutrophils (Pelger-Huet)
  • Small platelets
  • <20% blasts
150
Q

Describe the treatment of MDS

A
  • Supportive: eg transfusions, antibiotics/vaccines
  • Modifiers: azacytidine, lenalidomide
  • Chemo
  • Stem cell transplant
151
Q

Name some causes of BM failure

A

1˚: Fanconi anaemia, Diamond-Blackfan anaemia, Kostmanns

2˚: mets, haem malignancy, drugs, radiation, autoimmune, infection

152
Q

What is aplastic anaemia? What are some causes?

A

AA is the inability of BM to produce blood cells. Usually refers to RBCs but can be all cells

  • Idiopathic (80%)
  • Inherited: Fanconi (all cells), dyskeratosis congenita
  • Infection: parvovirus
  • Infiltration (all cells)
153
Q

How is aplastic anaemia assessed?

A

Camitta criteria

154
Q

Describe the differences between aplastic anaemia, MDS, and MPD.

A
  • AA: hypocellular BM and cytopenias
  • MDS: hypercellular BM and cytopenias, blasts in BM
  • MPD: fibrotic/hypercellular BM, cythaemias
155
Q

What type of reaction occurs if someone is transfused with the wrong blood group (ABO)? What about the wrong blood group (Rh)?

A
  • ABO incompatibility: immediate massive intravascular haemolysis (IgM mediated)
  • Rh incompatibility: delayed haemolytic transfusion reaction (IgG mediated)
156
Q

What are some RBC antigens that can cause transfusion reactions?

A
  • ABO
  • Rh C, D, E
  • Duffy
  • Kell
  • Kidd
157
Q

What is a group and screen and how is it done?

A

Checks for reaction between patient plasma and donor RBCs. Detects significant ABs in patient plasma
-Isolate recipient plasma, add donor blood -> add Coombs antibodies -> reaction occurs if Coombs ABs cause linking of the RBCs -> clumping

158
Q

What is a full crossmatch and how is it done? When is it needed?

A
  • Incubate recipient plasma with donor RBCs for 30-40 mins
  • Or can be electronic CM system without testing. But needs a valid G&S
  • If there are antibodies found on G&S, ALWAYS do a crossmatch
159
Q

When is a RBC transfusion reasonable? Platelets? FFP?

A
  • RBC: If symptomatic <80 or asymp <70
  • Plts: <10 or <20 in sepsis. <50 before surgery. In DIC only if actively bleeding
  • FFP: if patient bleeding/before surgery, severe liver disease
160
Q

How are RBCs stored and how should they be used? Platelets? FFP? Which need to be crossmatched?

A

-RBCs: 4˚ for 35 days. Use within 4 hours. Transfuse over 2-3 hours.
-Plts: 22˚ for 7 days. Transfuse over 20-30 mins
-FFP: transfuse over 20-30 mins.
RBCs and plasma must be crossmatched (recipient plasma may interact) eg. give O blood or AB plasma to anyone. Platelets should be D compatible.

161
Q

What blood should be given to immunosuppressed patients?

A

Irradiated (gets rid of donor lymphocytes)

162
Q

Name some immediate transfusion reactions

A
  • Acute haemolytic reaction: ABO incompatibility, IgM mediated
  • Febrile non-haemolytic: cytokine release
  • Allergy: anaphylaxis, itching
  • Bacterial contamination: esp platelet transfusion
  • Circulatory overload (TACO)
  • Acute lung injury (TRALI)
163
Q

How does ABO incompatibility present? How should it be managed?

A
  • Immediate (mins-hours)
  • Chest pain, fever, vomiting, flushing, collapse
  • STOP transfusion. Check blood products. Do blood tests: FBC, U+Es, LFTs, CM, DAT
164
Q

How does febrile non-haemolytic transfusion reaction present? How should it be managed?

A
  • During/soon after transfusion
  • Increase in temp <1, chills, rigors
  • Stop or slow transfusion
  • Paracetamol
165
Q

How does transfusion related allergy present? How should it be managed?

A
  • Itching, wheezing +/- anaphylaxis (BP, HR)
  • Stop/slow infusion
  • Give antihistamines or IM adrenaline etc
166
Q

How does bacterial contamination of blood products present?

A

Very similarly to ABO incompability. But more common with platelets (ABO rare).

167
Q

How does transfusion associated circulatory overload present? How is it managed?

A
  • Presents within 6 hours
  • Pulmonary oedema/fluid overload, heart failure, raised JVP
  • Responsive to diuretics
168
Q

How does transfusion related acute lung injury present? How is it managed?

A
  • Similar to TACO but less common. Due to anti-WBC antibodies in donor blood
  • eg SOB, low sats, increased HR
  • NO response to diuretics
169
Q

Name some types of delayed transfusion reactions.

A
  • Delayed haemolytic transfusion reaction: extravascular haemolysis-IgG mediated. Due to other ABs eg. Kell Usually occurs in patients with multiple transfusions
  • Infections: HIV, HCV (rare). CMV, parvovirus.
  • Transfusion associated graft-vs-host disease: fatal but rare. Lymphocytes in donor blood evade host defence and destroy host tissues. If immunosuppressed.
  • Iron overload: if lots of tranfusions. Chelators.
170
Q

Describe the process of bone marrow transplantation

A
  • Remove bone marrow cells -> isolate CD 34+ve (stem cells) -> freeze
  • Eradicate BM with chemo
  • Reinfuse stem cells -> find way to BM and multiply
171
Q

Name some indications for BM transplant

A
  • Haem malignancy eg. MM, leukemia

- Haemoglobinopathy eg. SCA, B thal major

172
Q

What are the different types of BM transplant?

A

Autologous: patient-patient
Allogeneic: donor-patient

173
Q

How are BM transplant donors identified?

A

HLA matching. Best are siblings/parents

174
Q

Name some complications of BM transplantation

A
  • Infection
  • Graft failure
  • Graft vs host disease: donor lymphocytes attack patient causing multiorgan system damage -> give immunosuppression.
  • Relapse
175
Q

What causes basophilic stippling?

A

Beta-thal trait
Lead poisoning
Alcoholism
Sideroblastic anaemia

176
Q

What causes target cells?

A

Iron deficiency
Thalassaemia
Hyposplenism
Liver disease

177
Q

Describe the management of sickle cell crises

A

A to E approach

  • Analgesia!! Opioids
  • Hydration, warmth
  • High flow O2

Septic screen + treat

178
Q

What is subacute combined degeneration of the spinal cord?

A

Irreversible complication of B12 deficiency (usually pernicious an.)

  • Combined symmetrical dorsal column sensory loss + corticospinal loss
  • > distal sensory loss (esp proprioception + vibration) + ataxia + UMN/LMN signs

Pathology (6 decks)

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