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Flashcards in Haematology (finished) Deck (263):
1

What are acanthocytes and what might they suggest?

  • RBCs with lots of spicules/spur/spike cells (Ah! It's a SCYTHE)
  • Abetalipoproteinaemia, liver disease, hyposplenism (spiking into your organs)

2

What does basophilic RBC stippling look like and what might it suggest?

  • Accelerated erythropoiesis, or defective Hb synthesis - see small dots at the periphery (rRNA)
  • Suggests: lead poisoning, megaloblastic anaemia, myelodysplasia, liver disease, haemoglobinopathy e.g. thalassaemia

3

What do Burr cells look like and what do they suggest?

  • Irregularly shaped (like a burr...)
  • Could be: uraemia, GI bleeding, stomach carcinoma (if you swallowed a burr you'd get GIT problems)

4

What are Heinz bodies and what do they suggest?

  • Inclusions within RBCs of denatured Hb (like how ketchup is a poor imitation of tomatoes)
  • Suggests: glucose-6-phosphate dehydrogenase deficiency, chronic liver disease

5

What are Howell Jolly bodies and what do they suggest?

  • Basophilic (purple spot) nuclear remnants in RBCs
  • Suggests: post-splenectomy of hyposplenism (e.g. sickle cell, coeliac, congenital, UC/Crohn's, myeloproliferative disease, aylod), also megaloblastic anaemia, hereditary spherocytosis
  • HOWell-Jolly bodies - HOW'S your spleen?

6

What does leucoerythroblastic anaemia on a blood film and what does it tell you?

  • Marrow infiltration - nucleated RBCs and primitive WBCs in peripheral blood; could be myelofibrosis, malignancy

7

What do Pelger Huet cells look like and what causes it?

  • Hypo segmented neutrophil (PELger - the lobes would rather be PALS and stay together)
  • Causes: congenital (lamin B receptor mutation - like laminating the lobes together so they can't segment), or acquired (myelogenous leukaemia and myelodysplastic syndromes)

8

What does polychromasia look like and what does it tell you is happening?

  • RBCs of multiple colours, especially grey-blue, due to differing amounts of Hb in RBCs.
  • Tells you there is premature/inappropriate release from bone marrow

9

What do reticulocytes look like/how do you stain for them? When are they increased and when are they decreased?

  • Immature RBCs - their mesh like network of ribosomal RNA becomes visible with certain stains e.g. new methylene blue.
  • Increased: haemolytic anaemias.
  • Decreased: aplastic anaemia, chemo

10

What is 'right shift' and what does it suggest?

  • Hypermature WBCs - hypersegmented polymorphs (>5 loves to nucleus)
  • Really old/MATURE people are really RIGHT wing
  • Suggests: megaloblastic anaemia, uraemia, liver disease

11

What is a rouleaux and what does it suggest?

  • Red cells stacked up
  • Could be due to chronic inflammation, paraproteinaemia, myeloma

12

What do schistocytes look like and what could be the underlying condition?

  • Fragmented parts of RBCs - irregularly shaped, jagged, asymmetry
  • SCHIsTocytes - oh SHIT the red cell's fragmented
  • Could be:
    • Microangiopathic anaemia e.g. DIC, HUS
    • TTP
    • Pre eclampsia

13

What do spherocytes look like and what might be the underlying condition?

  • Sphere shaped RBC
  • HEreditary spherocytosis, autoimmune haemolytic anaemia

14

What do stomatocytes look like and what might be the underlying condition?

  • Central pallor is straight or curved rod-like shape
  • 'Smiling face' or 'fish mouth'
  • Suggests: hereditary spherocytosis, high alcohol intake, liver disease

15

What do target cells look like and what might be the underlying condition?

  • Bull's eye appearance in central pallor
  • Could be: liver disease, hyposplenism, thalassaemia, IDA

16

What's the definition of anaemia?

Men: Hb <135 g/L (13.5g/dL)

Women: <115 g/L (11.5g/dL)

17

What are the 3 main mechanisms of anaemia?

  1. Reduced production of RBCs
  2. Increased loss of RBCs (haemolytic anaemias)
  3. Increased plasma volume (pregnancy)

18

What are the possible symptoms of anaemia?

  • Fatigue
  • Faintness
  • Headache
  • Anorexia
  • Dyspnoa
  • Palpitations
  • Tinnitus

19

What are the signs of anaemia?

Pallor, if severe (Hb <80) can get hyperdynamic circulation (tachycardia, flow murmurs = ejection systolic over apex, heart failure)

20

What are the causes of microcytic anaemia?

  • FAST
  • Fe-deficiency anaemia
  • Anaemia of chronic disease
  • Sideroblastic anaemia
  • Thalassaemia (in the absence of anaemia)

21

What are the causes of normocytic anaemia?

  • Acute blood loss
  • Anaemia of chronic disease
  • Bone marrow failure
  • Renal failure
  • Hypothyroidism
  • Haemolysis
  • Pregnancy

22

What are the causes of macrocytic anaemia?

FAT RBC

  • Fetus (pregnancy)
  • Antifolates e.g. phenytoin
  • Thyroid (hypothyroidism)
  • Reticulocytosis (Release of larger immature cells e.g. with haemolysis)
  • B12 or folate deficiency
  • Cirrhosis (alcohol excess or liver disease)
  • Myelodysplastic syndromes

23

What are the signs of iron deficiency anaemia?

  • Koilonychia
  • Post-cricoid webs (Plummer Vinson syndrome)
  • Atrophic glossitis
  • Brittle hair and nails
  • Angular cheilosis

24

What would you see on a blood film for iron deficiency anaemia?

  • Microcytic
  • Hypochromic
  • Anisocytosis (varying size)
  • Poikilocytosis (shape)
  • Pencil cells

25

What are the side effects of oral iron?

  • Nausea
  • Abdominal discomfort
  • Diarrhoea/constipation
  • Black stools

26

What is the pathophysiology in anaemia of chronic disease?

Inflammatory markers (IFNs, TNF, IL1) reduce EPO receptor production, and therefore EPO synthesis, by the kidneys.  Iron metabolism gets dysregulated.

 

IL6 and LPS stimulate the liver to make hepcidin, which decreases iron absorption from the gut (by inhibiting transferrin) but also causes iron accumulation in macrophages.

27

What are some common causes of anaemia of chronic disease?

  • Chronic infection e.g. TB, osteomyelitis
  • Vasculitis
  • Rheumatoid arthritis
  • Malignancy

28

What happens to ferritin in anaemia of chronic disease?

  • Ferritin is high!  Ferret of chronic disease
  • Intracellular protein, iron store
  • Fe sequestered in macrophage sso invading bacteria can't have it (unless patient has co existing IDA)

29

What is the pathophysiology of anaemia in renal failure?

Not cytokine driven like other chronic diseases - due to EPO deficiency

30

What is the pathophysiology in sideroblastic anaemia?

Iron loading (bone marrow) causing haemosiderosis (endocrine, liver and cardiac damage due to iron deposition)

31

How is a diagnosis of sideroblastic anaemia made?

Ring sideroblasts seen in the marrow (erythroid precurosrs with iron deposited in mitochondria in a ring around the nucleus)

32

What are the causes of sideroblastic anaemia?

  • Myelodysplastic disorders
  • Following chemotherapy
  • IRradiation
  • Alcohol excess 
  • Lead excess
  • Anti TB drugs
  • Myeloproliferative disease

33

How do you treat sideroblastic anaemia?

Remove cause + Pyridoxine (vitamin B6 promotes RBC production)

34

What is the iron, TIBC and ferritin in the following conditions?

  • Iron deficiency
  • Anaemia of chronic disease
  • Chronic haemolysis
  • Haemochromatosis
  • Pregnancy
  • Sideroblastic anaemia

  • Iron deficiency - low iron, high TIBC, low ferritin
  • Anaemia of chronic disease - low iron, low TIBC, high ferritin
  • Chronic haemolysis - high iron, low TIBC, high ferritin
  • Haemochromatosis - high iron, low or normal TIBC, high ferritin
  • Pregnancy - high iron, high TIBC, normal ferritin
  • Sideroblastic anaemia - high iron, normal TIBC, high ferritin

35

What is ferritin?

An acute phase protein - do a CRP with every ferritin you send

36

What are the features of a megaloblastic blood film?

  • Hypersegmented polymorphs
  • Leukopenia
  • Macrocytosis
  • Anaemia
  • Thrombocytopenia

37

What are the megaloblastic causes of macrocytosis?

  • B12 deficiency
  • Folate deficiency
  • Cytotoxic drugs

 

Thing of a MEGALOmanic depriving people of things

38

What are the non-megaloblastic causes of macrocytic anaemia?

  • Alcohol (most common cause of macrocytosis without anaemia)
  • Reticulocytosis (e.g. in haemolysis)
  • Liver disease
  • Hypothyroidism
  • Pregnancy

MacRocytosis - like a Scottish person - think of things that happen to Scottish people (drinking lots, liver disease)

 

39

Which haematological diseases cause macrocytosis?

  • Myelodysplasia
  • Myeloma
  • Myeloproliferative disorders
  • Aplastic anaemia

40

What are the causes of B12 deficiency?

  • Diet e.g. vegans
  • Malabsoprtion
    • Stomach - lack of intrinsic factor (= pernicious anaemia), portgastrectomy
    • Terminal ileum - ileal resection, Crohn's disease, bacterial overgrowth, tropical sprue and tapeworms

41

What are the features of B12 deficiency?

  • Mouth: glossitis, angular cheilosis
  • Neuropsychiatric: irritability, depression, psychosis, dementia
  • Neurological: parasthesiae, peripheral neuropahty (loss of vibration and proprioception first, absent ankle reflex, spastic paraparesis, SACD of spinal cord)

42

What is the pathophysiology of pernicious anaemia and how do you test for it?

  • Autoimmune atrophic gastritis -> achlorhydria and lack of gastric IF
  • Most common cause of macrocytic anaemia in the West, usually >40 years
  • Specific tests:
    • Parietal cell antibodies 90%
    • Intrinsic factor antibodies 50%
    • Schilling test outdated

43

How do you treat B12 deficiency?

Replace stores with IM hydroxocobalamin (B12)

44

Where do you get folate from?

Diet: green vegetables, nuts, yeast and liver

Synthesised by gut bacteria (low body sotres, cannot produce de novo)

45

What are the causes of folate deficiency?

  • Poor diet
  • Increased demand: pregnancy of increased cell turnover (haemolysis, malignancy, inflammatory disease or renal dialysis)
  • Malabsorption: coeliac disease, tropical sprue
  • Drugs: alcohol, anti epileptics (phenytoin), methotrexate, trimethoprim

46

What's the treatment for folate deficiency and what should you be careful of?

Oral folic acid

Don't do it if you don't know the cause of anaemia becuase it exacerbates neuropathy of B12 deficiency

 

47

What is the normal RBC life span?

120 days

48

What are the biochemical features of all haemolytic anaemias?

  • High bilirubin (unconjugated)
  • High urobilinogen
  • High LDH
  • Reticulocytosis (high MCV and polychromasia)
  • May have pigmented gallstones

49

What are the features of intravascular haemolytic anaemia in particular?

  • High free plasma Hb
  • Low haptoglobin (binds free Hb)
  • Haemoglobinuria (dark red urine)
  • Methaemalbuminaemia (haem and albumin in blood)

50

What's the key feature indicating extravascular haemolytic anaemia?

Splenomegaly

51

What are the inherited causes of haemolytic anaemia?

  • Membrane defects
    • Hereditary spherocytosis
    • Hereditary elliptocytosis
  • Enzyme defect
    • G6PD deficiency
    • Pyruvate kinase deficiency
  • Haemoglobinopathies
    • Sickle cell disease
    • Thalassaemias

52

What are the acquired causes of haemolytic anaemia?

  • Immune
    • Autoimmune - warm or cold
    • Alloimmune - haemolytic transfusion reactions
  • Non immune
    • Mechanical e.g. metal valves, trauma
    • PNH
    • MAHA
    • Infections i.e. malaria
    • Drugs

53

How is hereditary spherocytosis inhertied?

Autosomal dominant - 25% are recessive or de novo

54

What is the pathophysiology of hereditary spherocytosis

Spectrin or ankyrin deficiency (membrane proteins).  Susceptible to parvovirus B19 and develop gallstones.

Extravascular haemolysis - splenomegaly

55

What makes up a diagnosis of hereditary spherocytosis?

  • Spherocytes
  • Increased osmotic fragility (lysis in hypotonic solutions)
  • Flow cytometry
  • Negative DAT as not autoimmune Ab mediated

56

How do you treat hereditary spherocytosis?

Splenectomy, folic acid

57

What are the features of hereditary elliptocytosis?

  • Almost all are autosomal dominent - spectrin mutations
    • Except for herditary pyropoikilocytosis - erythrocytes are abnormally sensitive to heat - autosomal recessive
  • Severity ranges from hydrops foetalis to asymptomatic
  • Erythrocytes are elliptical in shape

58

What is South East Asian Ovalocytosis?

Inherited haemolytic anaemia.  Recessive - heterozygous +/- malaria protection

59

What is the commonest RBC enzyme defect?

G6PD deficiency

60

How is G6PDD inherited and where is it commonest?

X linked

Prevalent in areas of malarial endemicity i.e. Africa, Mediterranean, Middle East

61

What are the clinical features of G6PD deficiency?

  • Attacks of rapid anaemia and jaundice with bite cells and Heinz bodies (blue deposits - oxidised Hb)
  • Precipitated by oxidants as G6PD helps RBCs make glutathione which protects them from oxidant damage

62

What are the precipitants in G6PD deficiency?

  • Drugs - usually 2-3 days after starting, primaquine, sulfonamides, aspirin
  • Broad beans within 1 day of eating
  • Acute stressors
  • Moth balls
  • Acute infection

63

How do you diagnose G6PD deficiency?

Enzyme assay 2-3 months after a crisis (young RBCs may hav esufficienct enzyme so results appear normal).

In intravascular haemolysis they will have dark urine.

64

How do you treat G6PD deficiency?

  • Avoid precipitants
  • Transuse if severe
  • Genetic screening - rare subtypes give chronic haemolysis for which splenectomy is a good treatment

65

What are the features of pyruviate kinase deficiency?

  • Autosomal recessive (but autosomal dominant has been observed)
  • Clinical features include:
    • Severe neonatal jaundice
    • Splenomegaly
    • Haemolytic anaemia
  • Most don't need treatment but can have a blood transfusion or splenectomy

66

What is the mutation in sickle cell?

Glutamine changed to valine at codon 6 of beta chain = HbS instead of HbA

67

What are the forms of sickle cell disease?

  • Sickle cell anaemia = HbSS - severe
  • Sickle cell trait = HbAS - usually asymptomatic
  • Sickle-haemoglobin C = HbSC - HbC is another defective beta chain
  • Sickle beta thalassaemia = HbS/beta - one beta thal gene inherited as well (Similar in severity to HbSS)

68

When does sickle cell anaemia manifest?

3-6 months coinciding with decreasing foetal Hb

69

How does sickling occur in sickle cell disease?

Low O2 tension -> HbS polymerisation -> sickling

70

What are the haemolytic features in sickle cell disease?

  • Anaemia 60-80 g/L
  • Splenomegaly
  • Folate deficiency
  • Gallstones
  • Aplastic crises (parvovirus B19)

71

What are the vaso-occlusive/infarction features of sickle cell disease?

SICKLED:

  • Stroke
  • Infections (hyposplenism, CKD)
  • Crises (splenic, seequestration, pain)
  • Kidney (papillary necrosis, nephrotic syndrome)
  • Liver (gallstones)
  • Eyes (retinopathy)
  • Dactylitis (impaired growth)

 

+ Mesenteric ischaemia + priaprism

72

What are the features seen in sickle cell disease in children, teens and adults?

  • Child: strokes, splenomegaly, splenic crises, dactylitis
  • Teens: impaired growth, gallstones, psych, priaprism
  • Adult: hyposplenism, CKD, retinopathy, pulmonary hypertension

73

How do you diagnose sickle cell disease?

  • Sickle cells and target cells on blood film
  • Sickle solubility test
  • Hb electrophoresis
  • Guthrie test (birth) to aid prompt pneumococcal prophylaxis (and family history!)

74

What's the treatment for sickle cell disease?

  • Analgesia for painful crises
  • Penicillin V
  • Hydroxycarbamide
  • Folic acid
  • Pneumovax and Hib vaccine
  • Carotid doppler monitoring in early childhood with prophylactic exchange transfusion if turbulent carotid flow

75

What is the pathophysiology in thalassaemia?

Unbalanced Hb synthesis -> unmatched globins precipitate -> haemolysis and ineffective erythropoiesis

76

What is the pathophysiology of beta thalassaemia?

Point mutations - low beta chain synthesis (spectru of disease), excess alpha chains.  High HbA2 and HbF.

77

What are the clinical features of beta thalassaemia?

  • Skull bossing
  • Maxillary hypertrophy
  • Hairs on end skull X-ray
  • Hepatosplenomegaly

78

What are the types of beta thalassaemia?

  • Beta thal minor (heterozygous) - asymptomatic carrier, mild anaemia
  • Beta thal intermedia - moderate anaemia, splenomegaly, bone deformity, gallstones
  • Beta thal major (homozygous) - 3-6 months severe anaemia, FTT, hepatosplenomegaly (extramedullary erythropoiesis), bony deformity, severe anaemia, and heart failure

79

How do you diagnose thalassaemia?

Hb electrophoresis (Guthrie at birth)

80

How do you treat beta thal?

Blood transfusions

Desferrioxamine to stop iron overload

Folic acid

81

What are the types of alpha thalassaemia and what causes it?

  • Deletions cause reduced alpha chain synthesis and excess beta chains
  • 4 alpha chains and severity depends on number deleted:
    • Alpha thal trait (1 or 2 deleted) - asymptomatic, mild anaemia
    • HbH disease (3 deleted) - moderate anaemia, splenomegaly
    • Hydrops foetalis (4 deleted) - incompatible with life

82

What is the Coombs test result for autoimmune acquired haemolytic anaemias?

Positive

83

What are the features of warm autoimmune haemolytic anaemia?

  • 37 degrees
  • IgG (Greece is warm!)
  • Blood film shows spherocytes

84

What are the features of cold autoimmune haemolytic anaemia?

  • <37 degrees
  • IgM (Munich is cold!)
  • Positive Coombs test
  • Often with Raynuad's

85

What are the causes of warm autoimmune haemolytic anaemia?

  • Mainly primary idiopathic
  • Lymphoma, CLL, SLE, methyldopa

86

What are the causes of cold autoimmune haemolytic anaemia?

  • PRimary idiopathic
  • Lymphoma, infections: EBV, mycoplasma

87

How do you manage warm autoimmune haemolytic anaemia?

  • Steroids
  • Splenectomy
  • Immunosuppression

88

How do you manage cold autoimmune haemolytic anaemia?

  • Treat underlying condition
  • Avoid the cold
  • Chlorambucil (chemo)

89

What is paroxysmal cold haemoglobinuria and what are the features?

  • Haemoglobin in the urine usually caused by a viral infection e.g. measles, syphilis, VZV
  • Donath-Landsteiner antibodies
    • Stick to RBCs in cold -> complement mediated haemolysis on rewarming (self limiting as IgG so dissociate at a higher temperature than IgM)

90

What is the pathophysiology and clinical presentation of paroxysmal nocturnal haemoglobin?

  • Acquired loss of protective surface GPI markers on RBCs (platelets and neutrophils) -> complement mediated lysis -> chronic intravascular haemolysis especially at night
  • Morning haemoglobinuria, thrombosis (+ Bud dChiari syndrome - hepatic venous thrombosis)

91

How do you diagnose paroxysmal nocturnal haemoglobunuria?

Immunophenotype shows altered GPI or Ham's test (in vitro acid-induced lysis)

92

How do you treat paroxysmal nocturnal haemoglobinuria?

  • Iron/folate supplements
  • Prophylactic vaccines/antibiotics
  • Expensive monoclonal antibodies (eculizumbab) that prevents complement from binding RBCs

93

What's the pathophysiology in microangiopathic haemolytic anaemia?

Mechanical RBC destruction (forced through fibrin/plt mesh in damaged vessels) -> schistocytes

94

What causes microangiopathic haemolytic anaemia?

  • TTP: thrombotic thrombocytopenic purpura
    • Autoimmune - platelet activation
    • MAHA, fever, renal impairment, neuro abnormliaties, thrombocytopenia (classic pentad of symptoms)
  • HUS: haemolytic uraemic syndrome
    • Caused by E coli -> toxin damages endothelial cells -> fibrin mesh and RBC damage -> impaired renal function and MAHA
    • Diarrhoea, renal failure, no neuro problems, children and elderly

95

How do you treat microangiopathic haemolytic anaemia?

Usually plasma exchange

96

DON'T FORGET

LOOK AT THE CLOTTING CASCADE NOW

97

What are the phases of the coagulation cascade?

Initiation -> amplification -> propagation and thrombin burst -> stable clot

98

What are the inhibitors of the coagulation cascade?

  • Tissue factor pathway inhibitor (TFPI)
  • Protein C
  • Protein S
  • Antithrombin III

99

What are the tests of the coagulation cascade and what do they tell you?

  • Intrinsic pathway: APTT
    • Activated partial thromboplastin time
    • Monitor heparin therapy
  • Extrinsic pathway (PT)
    • PRothrombin time
    • Monitor warfarin therapy
  • Common pathway: TT
    • Thrombin time

100

What kinds of bleeding disorders are there?

  • Vascular defects - easy bruising
  • Platelet disorders - low or abnormal function
  • Coagulation disorders - factor deficiency
  • Mixed - DIC

101

What features indicate a vascular defect or platelet disorder?

  • Superficial bleeding into skin, mucosal membranes
  • Bleeding immediate after injury

102

What features indicate a coagulation disorder?

  • Bleeding into deep tissues, muscles, joints
  • Delayed but severe bleeding after injury
  • Bleeding often prolonged

103

What are the congenital and acquired causes of vascular defect bleeding disorders?

  • Congenital
    • Osler Weber Rendu syndrome
    • Connective tissue disease e.g. Ehlers-Danlos
  • Acquired
    • Senile purpura
    • Infection e.g.
      • Meningococcal
      • Measles
      • Dengue
    • Steroids
    • Scurvy - perifollicular haemorrhages

104

What are the causes of decreased platelet function?

  • Acquired
    • Aspirin
    • Cardiopulmonary bypass
    • Uraemia
  • Congenital
    • Storage pool disease
    • Thrombasthenia (glycoprotein deficiency)

105

What is a normal platelet count?

150-400x10^9 g/L

106

What are the causes of thrombocytopenia?

  • Low production - bone marrow failure
  • Increased destruction
    • Autoimmune thrombocytopenic purpura (AITP) - formerly idiopathic (ITP)
    • Drugs e.g. heparin, DIC, HUS, TTP

107

What are the characteristics of acute ITP?

  • Children 2-6 years
  • F:M 1:1
  • Commonly have preceding infection
  • Abrupt onset of symptoms
  • Platelet count at presentation <20,000
  • 2-6 weeks duration
  • Commonly remit spontaneously, usually self limiting

108

What are the characteristics of chronic ITP?

  • Adults
  • F:M 3:1
  • Rare to have preceding infection
  • Abrupt or indolent onset
  • <50,000 platelet count at presentation
  • Long term - associated with autoimmune disease, CLL, HIV
  • Uncommon for it to remit spontaneously; treat with IVIG, steroids, splenectomy

109

What is the pathophysiology of haemophilia A?

Factor 8 deficiency.  X-linked recessive affecting 1/10,000 males.  SEverity depends on factor level - severe <1%, mod 1-5%, mild 5-25%

110

What are the clinical features of haemophilia A?

  • PResents often early in life or wtih prolonged bleeding after surgery/trauma
  • Diagnosis: increased APTT, normal PT and low factor 8 assay

111

How is haemophilia A managed?

  • Avoid NSAIDs and IM injections
  • Desmopressin (increases vWF release which is an 8 carrier)
  • Factor 8 concentrates as replacement

112

What are teh features of haemophilia B?

  • Factor 9 deficiency
  • X linked recessive - 1/50,000 males
  • Clinically like haemophilia
  • Management is with factor 9 concentrates

113

What is the pathophysiology/inheritence of von Willebrand's disease?

  • Several types: quantitative (deficiency) vs qualitative
  • Decreased platelet function and decreased factor 8 (vWF carriers factor 8 in circulation)
  • Mostly autosomal dominant affecting 1/10,000

114

How does vWF disease present and how is it diagnosed?

  • Often bleeding indicative of platelet disorder (i.e. mucocutaneous)
  • Can include bleeding indicative of coagulation disorders
  • Diagnosis: high APTT, high bleeding time, low factor 8, low vWF Ag, normal INR and platelets

115

How is vWF disease managed?

  • Desmopressin
  • vWF + factor 8 concentrates

116

What is DIC?

Widespread activation of coagulation.

Clotting factors and platelets are consumed -> increased risk of bleeding

117

What are the causes of DIC?

  • Malignancy
  • Sepsis
  • Trauma
  • Obstetric complications
  • Toxins
  • Low platelets
  • Low fibrinogen
  • High FDP/D dimer
  • Long PT/INR

118

How do you treat DIC?

Treat the cause

Give transfusions, FFP, platelets, cryo etc

119

What coagulation disorders are present in liver disease?

  • Low synthesis of factors 2, 5, 7, 9, 10, 11 and fibrinogen
  • Low absorption of vitamin K
  • Abnormalities of platelet function

120

What coagulation disorders does vitamin K deficiency cause?

Low factors 2, 7, 9, 10 and protein C/S

121

What are the causes of vitamin K deficiency?

  • Warfarin 
  • Vitamin K malabsorption/malnutrition
  • Abx therapy
  • Biliary obstruction

122

How do you treat vitamin K deficiency?

IV vitamin K, or FFP for acute haemorrhage

123

Heparin:

  • INR
  • APTT
  • Thrombin time
  • Platelet count
  • Bleeding time

Heparin:

  • INR - high
  • APTT - v high
  • Thrombin time - v high
  • Platelet count - normal
  • Bleeding time - normal

124

DIC:

  • INR
  • APTT
  • Thrombin time
  • Platelet count
  • Bleeding time

DIC:

  • INR - v high
  • APTT - v high 
  • Thrombin time - v high
  • Platelet count - low
  • Bleeding time - high
  • And high D dimer

125

Liver disease:

  • INR
  • APTT
  • Thrombin time
  • Platelet count
  • Bleeding time

Liver disease:

  • INR - high
  • APTT - high 
  • Thrombin time - normal or high
  • Platelet count - normal or high
  • Bleeding time - normal or high
  • High AST

126

Platelet defect:

  • INR
  • APTT
  • Thrombin time
  • Platelet count
  • Bleeding time

Platelet defect:

  • INR - normal
  • APTT - normal
  • Thrombin time - normal
  • Platelet count - normal
  • Bleeding time - high

127

Vitamin K deficiency:

  • INR
  • APTT
  • Thrombin time
  • Platelet count
  • Bleeding time

Vitamin K deficiency:

  • INR - v high
  • APTT - high 
  • Thrombin time - normal
  • Platelet count - normal
  • Bleeding time - normal

128

Haemophilia:

  • INR
  • APTT
  • Thrombin time
  • Platelet count
  • Bleeding time

Haemophilia:

  • INR - normal
  • APTT - v high
  • Thrombin time - normal
  • Platelet count - normal
  • Bleeding time - normal

129

Von Willebrand's disease:

  • INR
  • APTT
  • Thrombin time
  • Platelet count
  • Bleeding time

Von Willebrand's disease:

  • INR - normal
  • APTT - v high
  • Thrombin time - normal
  • Platelet count - normal
  • Bleeding time - high

130

What's Virchow's triad of venous thrombosis?

Vessel wall

Blood

Flow

131

What are the inherited causes of venous thrombosis?

  • Antithrombin deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Factor V leiden - 5% Caucasian population (= resistance to protein C)
  • Prothrombin G20218A
  • Lupus anticoagulant
  • Coagulation excess: Factor 8 (10%), factor 2 (2%), fibrinogen

132

What are the acquired causes of venous thrombosis?

  • Age, obesity
  • Previous DVT or PE
  • Immobilisation
  • Major surgery - especially ortho, >30 mins or plaster cast immobilisation
  • Long distance travel
  • Malignancy - especially pancreatic, 10% idiopathic VTE due to Ca
  • PRegnancy, COCP, HRT
  • Antiphospholipid syndrome
  • Polycythaemia
  • Thrombocythaemia

133

What should patients have for DVT prophylaxis?

Daily subcutaneous LMWH, TED stockings

134

How is DVT/PE treated?

  • LMWH (175 units/kg) and Warfarin (some NOACs e.g. rivaroxaban)
    • LMWH stopped once INR in therapeutic range (2.5)
    • 1st VTE with known cause - 3 months warfarin
    • Cancer VTE - 3-6 months LMWH
    • 1st VTE unkown cause - 3-6 months warfarin, possibly lifelong
    • 1st VTE in thrombophilic patient - 3 months warfarin, ?lifelong
    • Recurrent VTE - lifelong warfarin
  • TEDS to prevent post phlebitic syndrome

135

What does heparin do?  How is it given and  does it need monitoring?

Potentiates antithrombin III which inactivates thrombin and factors 9, 10, 11.  

LMWH given subcut once daily. Doesn't need to be monitored except in late pregnancy and renal failure.

Unfractionated heparin is given IV as a loading dose then an infusion.  Monitor APTT.

136

What's the antidote to heparin?

Protamine sulphate

137

What are the side effects of heparin?

  • Bleeding
  • Heparin induced thrombocytopenia (HIT) and osteoporosis with long term use (more so with UFH)

138

What does warfarin do?

Inhibits the reductase enzyme responsible for regenerating the active form of vitamin K.

Therefore, inhibits the synthesis of factors 2, 7, 9, 10 + proteins C, S and Z

139

WHow do you reverse warfarin?

IV vitamin K/factor concentrates

140

What is the target INR on warfarin?

  • 2.5 if:
    • 1st episode DVT or PE, atrial fibrillation (2-3)
    • Cardiomyopathy, symptomatic inherited thrombophilia, mural thrombosis, cardioversion
  • 3.5 if:
    • Recurrent DVT or PE, mechanical prosthetic valve (2.5-3.5)
    • Coronary artery graft thrombosis, antiphospholipid syndrome

141

What should you do if someone's INR is 5-8 and they're not bleeding?

Withhold a few doses, reduce maintenance, restart when INR <5

142

What should you do if someone's INR is 5-8 and they have minor bleeding?

Stop warfarin.  Vit K slow IV.  Restart when INR <5

143

What should you do if someone's INR is >8 and they're not bleeding/have minor bleeding?

  • Stop warfarin
  • Vitamin K (oral/IV) if no bleeding or if risk factors for bleeding, or minor bleeding
  • Check INR daily

144

What should you do if someone's on warfarin has major bleeding (including intracranial haemorrhage)?

  • Stop warfarin
  • Give prothrombin complex concentrate
  • If unavailable give FFP
  • Also give vitamin K IV

145

What are the features of acute leukaemia?

  • NEoplastic process of bone marrow and blood
  • Acute - rapidly progressing and fatal
  • Immature blasts >20% of bone marrow
  • Features of bone marrow production failure:
    • Anaemia
    • Thrombocytopenia - bleeding
    • Neutropenia - infection
  • Organ infiltration: hepatomegaly, splenomegaly, lymphadenopathy, bone pain, CNS, skin, gum hypertrophy

146

What are the aetiological factors in acute leukaemia?

  • Many unknown
  • Ionising radiation (radiotherapy)
  • Cytotoxic drugs (chemotherapy)
  • Benzene
  • Pre-leukaemic disorders: myelodysplastic syndromes, myeloproliferative disorders
  • Downs: increased risk of AML and ALL
  • NEonates: 30% develop transient abnormal myelopoiesis; resembles AML but resolves spontaneously and completely after a few weeks

147

How do you diagnose acute leukaemia (and haem malignancies in general)?

  • Morphology +/- cytochemistry (stains)
  • Immunophenotyping (lineage, differentiation)
  • Cytogenetics (chromosomal translocations)
  • Molecular genetics (PCR, point mutations etc)

148

Who gets acute lymphoblastic leukaemia?

Children (children get it ALL)

149

What are the clinical features of  acute lymphoblastic leukaemia?

  • General leukaemia features +
  • Lots of lymphadenopathy
  • Lots of CNS involvement
  • Testicular enlargement
  • Thymic enlargement (mediastinum)

150

What do you see in the blood in acute lymphoblastic leukaemia?

High WCC and lots of lymphocytes or precursors

151

How is acute lymphoblastic leukaemia treated?

  • Remission induction - chemo agents often given with steroids
  • Consolidation: high dose multi drug chemotherapy
  • CNS treatment
  • MAintenance: 2 years in girls and adults, 3 years in boys
  • Consider allo stem cell transplant
  • Supportive treatment: blood products, Abx, allopurinol, fluid, electrolytes - to prevent tumour lysis syndrome

152

Who gets acute myeloid leukaemia?

Adults (risk increases with age) and undre 2s (infant peak)

153

What are the clinical features of acute myeloid leukaemia?

  • As general acute leukaemia
  • Lymphadenopathy less common
  • M3: acute promyelocytic leukaemia - prone to DIC
  • M4+M5: monoblasts/monocytes; skin/gum infiltration and hypokalaemia

154

What would you see in the blood in acute myeloid leukaemia?

  • High WCC
  • Auer rods and granules
  • Myeloperoxidase and Sudan black B stains

155

How is acute myeloid leukaemia treated?

  • Chemotherapy: similar to ALL but
  • No CNS prophylaxis/maintenance herapy needed
  • Consider allo SCT in the young
  • Specific: ATRA for M3 (acute promyelocytic leukaemia)
  • Supportive: similar principles to ALL
  • Prognosis worse with age

156

Who gets chronic myeloid leukaemia and what's the prognosis?

Middle aged (40-60); often diagnosed on routeine bloods (large number of differentiated neutrophils).

Meadian survival 3-5 years.

157

What is seen on examination in chronic myeloid leukaemia?

Massive splenomegaly

158

What investigations are done in chronic myeloid leukaemia and what are the findings?

  • Philadelphia chromosome in 80% - 9;22 translocation
  • PCR for BCR-ABLE (Philadelphia Chr fusion gene)
  • Monitor disease and therapeutic response
  • WBC, neutrophils 50-500
  • Hypercellular bone marrow with spectrum of immature (e.g. myelocytes) and mature granulocytic cells in blood

159

What defines the chronic phase of chronic myeloid leukaemia and how is it treated?

  • <5% blasts in BM/blood, WBCs slowly increase over years (indolent)
  • Rx: oral hydroxyurea/interferon to suppress WBC
    • Imatinib - BCR-ABLE tyrosine kinase inhibitor
    • Dasatinib/nilotinib for resistance - extremely effective
    • BMT potentially curative

160

What defines the accelerated phase of chronic myeloid leukaemia and how is it treated?

  • >10% blasts in bone marrow/blood
  • Increasing manifestatinos such as splenomegaly, lasting up to a year
  • Less responsive to therapy

161

What defines the blast phase of chronic myeloid leukaemia and how is it treated?

  • >20% blasts in blood
  • Resembles acute leukaemia; timeframe is months (+/- weight loss, lethargy, night sweats)
  • Treatment similar to AML, possibly with allogeneic SCT for young patients

162

What is chronic lymphocytic leukaemia/small lymphocytic leukaemia?

Both lymphoproliferative diseases.  Basically the same, but CLL is primarily seen in BM, and SLL in lymph nodes

163

Who gets chronic lymphocytic leukaemia?

M>F, elderly (median 65-70)

164

What are teh clinical feautres of  chronic lymphocytic leukaemia?

  • MAy be asymptomatic; often diagnosed on routein bloods (80%)
  • Symmetrical painless lymphadenopathy
  • BM failure: anaemia and thrombocytopenia symptoms, recurrent infections (50% deaths)
  • Weight loss, low grade fever, night sweats
  • Hepatomegaly and splenomegaly (less prominent)
  • Associated with autoimmunity (Evans syndrome): AIHA, ITP
  • Can progress to a form of lymphoma (DLBC) - Richter's transformation

165

What are the investigation findings in  chronic lymphocytic leukaemia?

  • High WBC with lymphocytosis >5 (high % of WBC composed of lymphocytes, small mature)
  • Low serum Ig
  • Smear cells (Smear CLLs) seen on blood film
  • Abnormal BM - lymphocytic replacement

166

What are the prognostic factors in  chronic lymphocytic leukaemia?

  • LDH raised, CD38+ positive, 11q23 deletion - bad
  • HYpermutated Ig gene, low ZAP-70 expression, 13q14 deletion - good
  • Binet staging: A, B, C (Rai staging 1-4 can also be used):
    • Stage A: high WBC, <3 groups of enlarged lymph nodes, usually no treatment required
    • Stage B: >3 groups of enlarged lymph nodes
    • Stage C: anaemia or thrombocytopenia

167

How is  chronic lymphocytic leukaemia treated?

  • Commenced as patient becomes more symptomatic - 1st line is chlorambucil
  • Can also use fludarabine (purine analogue), alemtuzumab (anti-CD52) and steroids
  • SCT considered in young, fit patients

168

What is polycythaemia?

Raised red cell mass, Hb, red cell count and packed cell volume

169

What is relative (pseudo) polycythaemia and what causes it?

Red cell mass normal but plasma volume reduced.  Seen in dehydration, burns, vomiting, diarrhoea, cigarette smoking

170

What is polycythaemia rubra vera and what causes it?

MPD where erythroid precursors dominate the BM.  Incidence rises with age.  Point mutations (JAK2/V617F).  Independent of normal mechanisms of regulation.

171

What are the clinical features of polycythaemia rubra vera?

  • Hyperviscosity/hypervolaemia/hypermetabolism
  • Blurred vision, headache
  • Plethoric ('red nose'), gout, thrombosis and stroke, retinal vein engorgement, erythromelagia
  • Splenomegaly
  • Histamine release -> aquagenic prutritus (contact with water) and peptic ulcers

172

What are the investigation findings in polycythaemia rubra vera?

  • Raised Hb, HCT, 
  • Also possibly raised platelets, WCC (neutrophils and basophils)
  • Low serum EPO

173

What is the treatment for polycythaemia rubra vera?

  • Venesection
  • Hydroxycarbamide (maintenance)
  • Aspirin

174

What characterises the myeloproliferative disorders?

CLonal proliferation of one or more haemopoietic component i.e. increased production of mature cells

175

Which myeloproliferative disorders are Philadelphia chromosome positive?

Chronic myeloid leukaemia

176

Which myeloproliferative disorders are Philadelphia chromosome negative?

  • Polycythaemia vera
  • Myelofibrosis
  • Essential thrombocytosis 

177

What mutations are Philadelphia chromosome negative myeloproliferative disorders associated with?

JAK2 mutations

178

What are the inherited aplastic anaemia/bone marrow failure syndromes?

  • Fanconi anaemia
  • Dyskeratosis congenita
  • Schwachman-Diamond syndrome
  • Diamond-Blackfan syndrome

179

Whta are the features of fanconi anaemia?

  • Autosomal recessive
  • Pancytopenia
  • Presents at 5-10 years
  • Skeletal abnormalities (radii, thumbs), renal malformations, microophthalmia short stature, skin pigmentation
  • MDS (~30%), AML risk (10% progress)

180

What are the features of dyskeratosis congenita?

  • X linked
  • Chromosome instability (telomere shortening)
  • Skin pigmentation, nail dystrophy, oral leukoplakia (triad) and BM failure

181

What are the features of Schwachman-Diamond syndrome?

  • Autosomal recessive
  • Primarily neutrophilia +/- others
  • Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature
  • AML risk

182

What are the features of Diamond-Blackfan syndrome?

  • Pure red cell aplasia
  • Normal WCC and platelets
  • Presents at one year/neonatal
  • Dysmorphology

183

What are the features of aplastic anaemia?

Bone marrow can't produce adequate blood cells:

  • Haemopoeitic stem cell numbers are reduced in BM trephines (hypocellular BM)
  • Typically refers to anaemia (RBCs) but pateints can have pancytopenia as well
  • Symptoms/signs related to each cytopenia
  • Patients typically present with bleeding problems and can affect any age

184

What is aplastic anaemia closely linked to?

Leukaemia and paroxysmal nocturnal haemoglobinuria

185

How is aplastic anaemia classified?

  • Primary:
    • Idiopathic (70%)
    • Inherited (10%)
  • Secondary (10-15%)
    • Due to malignant infiltration, radiation, drugs including chemo, viruses, autoimmune e.g. SLE

186

How is aplastic anaemia managed?

  • Supportive: transfusions, Abx, iron chelation
  • Drugs: to promote marrow recovery, growth factors and oxymethalone (androgen)
  • Immunosuppressnats - idiopathic AA
  • SCT

187

What are the blood and bone marrow features of refractory anaemia?

Blood: Anaemia, no blasts

Bone marrow: erythroid dysplasia with <5% blasts

188

What are the blood and bone marrow features of refractory anaemia with ringed sideroblasts?

Blood: anaemia, no blasts

Bone marrow: erythroid dysplasia with >15% ringed sideroblasts

189

What are the blood and bone marrow features of refractory cytopaenia with multilineage dysplasia?

Blood: cytopaenia in ≥2 cell lines

Bone marrow: dysplasia in >10% of cells in ≥2 cell lines

190

What are the blood and bone marrow features of refractory cytopaenia with multilineage dysplasia and ringed sideroblasts?

Blood: cytopenia in ≥2 cell lines

Bone marrow: Dysplasia in >10% of cells in ≥2 cell lines and >15% ringed sideroblasts

191

What are the blood and bone marrow features of refractory anaemia with excess blasts - I (RAEB I)?

Blood: cytopenias, <5% blasts, no Auer rods

Bone marrow: dysplasias, 5-9% blasts

192

What are the blood and bone marrow features of refractory anaemia with excess blasts - II (RAEB II)?

Blood: Cytopenias or 5-19% blasts or Auer rods

Bone marrow: dysplasias, 10-19% blasts or Auer rods

193

What are the blood and bone marrow features of MDS with 5q deletion?

Blood: anaemia, normal or increased platelets

Bone marrow: megakaryocytes with hypolobulated nuclei and <5% blasts

194

What are the blood and bone marrow features of myelodysplasia syndrome unclassified?

Blood: complex - cytopenias, no blasts, no Auer rods

Bone marrow: complex - myeloid or megakaryocytic dysplasia, <5% Blasts

195

What do you call it if there are 21-30% myeloblasts in the marrow in refractory anaemia?

AML (used to be refractory anaemia with excess blasts in transformation - RAEB-T)

196

What are the myelodysplastic syndromes?

Group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells

197

What characterises myelodysplastic syndromes?

  • Peripheral cytopenia
  • Qualitative abnormalities of cell maturation
  • Risk of AML transformatoin
  • Typically seen in the elderly and symptoms develop over weeks/months
  • By definition they have <20% blasts, because if there were more it would be acute leukaemia

198

What are the clinical features of myelodysplastic syndromes?

  • BM failure and cytopenias - infection, bleeding, fatigue
  • Hypercellular BM
  • Defective cells:
    • RBCs e.g. ring sideroblasts (abnormal nucleated blast surrounded by iron granule ring)
    • WBCs: hypogranulation, pseudo-Pelger-Huet anomaly (hyposegmented neutrophil)
    • Platelets: micromegakaryocytes, hypolobulated nuclei

199

How are myelodysplastic syndromes treated?

  • Supportive: transfusions, EPO, G-CSF, Abx
  • Biological modifiers: immunosuppressive drugs, lenalidomide, azacytidine
  • Chemo: similar to AML
  • Allogeneic SCT

200

What's the prognosis in myelodysplastic syndromes?

  • Depends on International PRognostic SCoring System (IPSS)
    • BM blast %
    • Karyotype
    • Degree of cytopenia
  • Mortality rule of 1/3
    • 1/3 die from infection
    • 1/3 die from bleeding
    • 1/3 die from acute leukaemia

201

What is the pathology in multiple myeloma?

  • Neoplasia of plasma cells (effector B cells -> antibodies) of BM
  • Production of monoclonal immunoglobulin (paraprotein); IgG most common

202

Who gets multiple myeloma?

Middle aged to elderly, more common in Afro-Caribbeans

203

What are the clinical features of multiple myeloma?

  • CRAB:
  • Calcium high - thirst, moans, groans, stones, bones
  • Renal failure (plus amyloidosis and nephrotic syndrome)
  • Anaemia (and pancytopenia)
  • Bones - pain, osteoporosis, osteolytic lesions, fractures e.g. wedge compression, pepper pot skull
  • And hyperviscosity syndrome

204

What are the investigation findings in multiple myeloma?

  • Dense narrow band on serum electrophoresis (compared with broad band in polyclonal)
  • Rouleaux on blood film (RBC stacking)
  • Bence Jones protein in urine
  • ESR very high
  • >10% plasma cells in BM

205

How is multiple myeloma staged?

Durie-Salmon staging system

206

What's the treatment for multiple myeloma?

  • Supportive for CRAB symptoms including bisphosphonates
  • Chemo combinations:
    • Melphalam
    • Bortezomib (proteosome inhibitor)
    • Lenalidomide
    • Thalidomide
    • +/- auto SCT or uncommonly allo SCT
  • Steroids: dex or pred

207

What are the features of monoclonal gammaglobinopathy of unknown significance (MGUS)?

  • <10% plasma cells in marrow
  • 30g/L monoclonal paraprotein
  • No CRAB etc
  • Incidental finding; progresses to multiple myeloma at rate of 1-2% per year

208

What are the features of smouldering myeloma?

  • >10% plasma cells (+>30g/L) in BM
  • No CRAB/organ/tissue involvement
  • For this + MGUS: no Rx at this stage but monitor for transformation

209

What are the features of Waldenstrom's macroglobulinaemia (lymphoplasmacytoid lymphoma) and how is it treated?

  • Elderly man
  • Low grade NHL - lymphoplasmacytoid cells produce monoclonal serum IgM that infiltrates the LNs/BM
  • Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness)
  • Treatment:
    • Plasmapharesis for hyperviscosity
    • Chlorambucil
    • Cyclophosphamide and other chemo

210

What are the features of systemic amyloidosis and how is it treated?

  • Ig light chains = paraprotein -> deposition of abnormal proteinaceous substance in tissues
  • Diagnosed via congo red stain -> apple green birefringence
  • Presents with:
    • Macroglossia
    • Carpal tunnel syndrome
    • Peripheral neuropathy
    • Heart failure
    • Renal failure
  • Treatment - chemo or auto SCT

211

What are the features general to all kinds of Burkitt's lymphoma?

  • B cell lymphoma
  • All aggressive and fast growing
  • t(8;14) translocation
  • C-myc oncogene overexpression
  • Rapidly responsive to treatment
  • Starry sky appearance

212

How do you treat Burkitt's lymphoma?

  • Chemotherapy - rituximab, anti CD20, found on B cells
  • Leukaemia protocol or SCT

213

What are the features specific to endemic Burkitt's lymphoma?

  • Most common malignancy in equatorial Africa
  • EBV associated
  • Characteristic jaw involvement and abdominal masses

214

What are the features specific to sporadic Burkitt's lymphoma?

  • Found outside Africa
  • EBV associated
  • Jaw less commonly involved

215

What are the features specific to immunodeficiency Burkitt's lymphoma?

  • Not EBV associated
  • HIV/post transplant patients

216

What are the clinical features and histology in Diffuse Large B Cell Lymphoma (DLBC)?

  • Middle aged and elderly
  • Aggressive
  • Richter's transformatoin
  • Other lymphomas occur secondary to DLBC
  • Histology: sheet sof large lymphoid cells

217

What are the clinical features and histology in Mantle Cell Lymphoma?

  • Middle aged, M>F
  • Aggressive
  • Disseminated at presentation
  • Median survival 3-5 years
  • t(11;14) translocation
  • Cyclin D1 dysregulation
  • Histology: angular nuclei

218

What are the clinical features and histology in Follicular Lymphoma?

  • B cell lymphoma
  • Indolent
  • Mostly incurable - median survival 12-15 years
  • t(14;18) translocation
  • Histology: follicular pattern, nodular appearance

219

What are the clinical features and types of MALT lymphoma?

  • Marginal zone NHL, middle aged
  • Chronic antigen stimulation:
    • H pylori -> gastric MALT lymphoma
    • Sjogrens -> parotid lymphoma

220

How is diffuse large B cell lymphoma treated?

  • Rituximab-CHOP
  • Auto SCT for relapse

221

How is mantle cell lymphoma treated?

  • Rituximab-CHOP
  • Auto SCT for relapse

222

How is follicular lymphoma treated?

  • Watch and wait
  • Rituximab CVP

223

How is MALT lymphoma treated?

  • Remove antigenic stimulus e.g. H pylori triple therapy
  • Chemotherapy

224

What are the characteristic features of anaplastic large cell lymphoma?

  • T cell lymphoma
  • Children and young adults
  • Aggressive
  • Large 'epithelioid' lymphocytes
  • t(2;5), Alk-1 protein expression

225

What are the characteristic features of peripheral T-cell lymphoma?

  • Middle aged and elderly
  • Aggressive 
  • Large T cells

226

What are the characteristic features of adult T-clel leukaemia/lymphoma?

  • Caribbean and Japanese
  • HTLV-1 infection
  • Aggressive

227

Which lymphoma is associated with long standing coeliac disease?

Enteropathy-associated T cell lymphoma (EATL)

228

Which lymphoma is associated with mycosis fungoides?

Cutaneous T cell lymphoma

229

Which mab can you use to treat T cell lymphoma?

Alemtuzumab (anti CD52)

230

How is non-Hodgkin's lymphoma classified?

  • Mature or immature
  • Histology:
    • High grade:
      • Very aggressive: Burkitt's
      • Aggressive: diffuse large B cell, mantle cell
    • Low garde
      • Indolent: follicular, marginal zone, small lymphocytic
  • Lineage: B or T cell

231

How does non-Hodgkin's lymphoma present?

  • Painless lymphadenopathy
  • Often involves multiple sites
  • Constitutional symptoms
  • No pain after alcohol

232

Where are stem cells harvested from for stem cell transplants?

  • Peripheral blood (following stimulation by G-CSF)
  • Bone marrow
  • Umbilical cord blood

233

In which conditions are stem clel transplants used?

Leukaemia, lymphoma, multiple myeloma, aplastic anaemia, MDS, sickle cell anaemia, thalassaemia major

234

How does autologous SCT work?  What's it good for?

  • Patient's own SCs harvested and frozen, then reintroduced into patient after high dose chemo +/- radiotherapy to eradicate malignant cells at the cost of partial or complete bone marrow ablation
  • Used more in multiple myeloma, lymphoma, particularly with relapse
  • Less used in leukaemia
  • No GVHD, lower risk of infection

235

How does allogeneic SCT work?  What's it good for?

  • HLA-matched donor SCs are harvested
  • Patient's own BM completed eradicated by high dose chemo +/- radiotherapy
  • Donor SCs are introduced and 'colonise' empty BM
  • Used more in leukaemia
  • GVHD risk, risk of opportunistic infections, infertility and secondary malignancies

236

Who gets Hodgkin's lymphoma?

M>F, bimodal age incidence - 20-29 year olds and>60 years.  EBV associated

237

What are the clinical features of Hodgkin's lymphoma?

  • Spreads contiguously to adjacent LNs; often involves a single LN group
  • Asymmetrical painless lymphadenopathy +/- obstructive/mass symptoms
  • +/- constitutional symptoms (B symptoms): weight loss, low grade fever, night sweats, pruritus, fatigue
  • Pel-Ebstein fever (cyclical 1-2 weeks) seen in a minority
  • Pain in affected nodes after alcohol

238

What are the investigation findings in Hodgkin's lymphoma?

  • CT/PET for staging
  • Tissue diagnosis: LN or BM biopsy - cells stain with CD15 and CD30
  • Reed-Sternberg cell: binucleate/multinucealte ('owl eyed') cell on a background of lymphocytes and reactive cells

239

What are the subtypes of Hodgkin's lymphoma?

  • Nodular sclerosing (most common)
  • Mixed cellularity
  • Lymphocyte rich
  • Lymphocyte depleted
  • Nodular lymphocyte predominant (not classical HL)

240

What are the stages of Hodgkin's lymphoma?

  • Stage 1 - one LN region (LN region can include spleen)
  • Stage 2 - 2 or more LN regions on the same side of the diaphragm
  • Stage 3 - 2 or more LN regions on opposite sides of the diaphragm
  • Stage 4 - extranodal sites (liver, BM)
  • A: no constitutional symptoms
  • B: constitutional symptoms

241

How do you treat Hodgkin's lymphoma and what's the prognosis?

Prognosis is excellent especiall yin the young.

  • Combination chemotherapy:
    • USed in most cases
    • ABVD: adriamycin, bleomycin, vinblastine, dacarbazine
    • 2-4 cycles in stage 1/2, 6-8 cycles in stage 3-4
  • Radiotherapy
    • Often used alongside chemo in bulky areas
  • Intensive chemo in autologous SCT
    • Relapsed patients

242

What are the general characteristics of lymphoma?

  • Neoplastic tumour of lymphoid tissues
  • Often lymph nodes, + BM +/- spill out to blood
  • Sometimes other lymphoid tissues: spleen, MALT
  • Rarely 'anywhere' - skin (often T cell), CNS, testes, breast
  • Hodgkin's 20%
  • Non Hodgkin's 80%

243

Blood transfusions:

What are the possible adverse reactions if it is immediate and immune related?

  • Wrong blood: ABO
  • Febrile non-haemolytic
  • Allergic/anaphylaxis
  • Transfusion related acute lung injury (TRALI)

244

Blood transfusions:

What are the possible adverse reactions if it is delayed and immune related?

  • Delayed haemolytic transfusion reaction (DHTR)
  • Post-transfusion purpura
  • Transplant associated GVHD

245

Blood transfusions:

What are the possible adverse reactions if it is immediate and non-immune related?

  • Bacterial infection
  • Transfusion associated cardiac overload (TACO)

246

Blood transfusions:

What are the possible adverse reactions if it is delayed and non-immune related?

  • Viral infections
  • Iron overload

247

What is the adverse transfusion reaction if it only involves a mild fever?

Febrile non-haemolytic transfusion reaction

248

What is the adverse transfusion reaction if it only involves an urticarial rash?

Mild allergic reaction

249

What is the adverse transfusion reaction if there are significant changes in observations with collapse/shock, bleeding, and dark urine?

ABO incompatibility

250

What is the adverse transfusion reaction if it involves a significant change in observations with collapse/shock, swelling and wheeze?

Severe allergic reaction

251

What is the adverse transfusion reaction if it involves a significant change in observations with collapse/shock, and high fever/rigors?

Bacterial infection of unit

252

What is the adverse transfusion reaction if it involves a significant change in observations with collapse/shock, no significant fever but there is significant breathlessness?

  • Raised CVP - TACO (fluid overload)
  • Normal CVP - TRALI

253

How does haemolytic disease of the newborn happen?

  • Person can form red cell Abs thorugh blood transfusion or if foetal cells enter the mother's circulation during pregnancy or delivery
  • If maternal Ab is high, it can destroy foetal red cells if they have corresponding red cell Ag -> foetal anaemia and jaundice

254

Which Ig can cross the placenta?

IgG

255

How can you prevent haemolytic disease of the newborn?

Ab most responsible is anti-D, so always transfuse RhD negative blood to RhD negative women of child bearing age.

 

In women who are RhD negative:

  • Give mother im anti-D Ig when she is at high risk of foeto-maternal haemorrhage
  • Routine antenatal prophylaxis at 28 and 34 weeks
  • During prenancy give anti D if sensitising event occurs (Abortion, miscarriage, abdo trauma, ECV, amniocentesis)
  • At delivery if baby is RhD positive

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What is essential thrombocythaemia and what's it associated with?

MPD where megakaryocytes dominate the BM.  50% associated with JAK2

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What are the clinical features of essential thrombocythaemia?

  • Incidental finding in 50%
  • Venous and arterial thrombosis (stroke and MI), gangrene and haemorrhage
  • Erythromelalgia
  • SPlenomegaly, dizziness, headache, visual disturbances

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What are the investigation findings in essential thrombocythaemia?

  • Platelet count >600 x 10^9
  • Blood film: large platelets and megakaryocyte fragments
  • Increased BM megakaryocytes (not reactive)

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How do you treat essential thrombocythaemia?

  • Aspirin
  • Anagrelide: reduce formation of platelets from megakaryocytes 
  • Hydroxycarbamide

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What is myelofibrosis and what are the 2 types?

MPD where myeloproliferation -> fibrosis of BM or replacement with collagenous tissue

Can be primary (idiopathic) or secondary (following PRV, ET, leukaemia etc)

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What are the clinical features of myelofibrosis?

  • Usually elderly
  • Pancytopenia related symptoms
  • Extramedullary haematopoiesis - hepatomegaly, massive splenomegaly, WL, fever
  • Can present with Budd-Chiari syndrome

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What are the investigation findings in myelofibrosis?

  • Blood film: tear drop poikilocytes (dacrocyte), leukoerythroblasts (primitive cells)
  • BM: fibrosis, 'dry tap'

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How do you treat myelofibrosis?

  • Support with blood products, in some cases splenectomy
  • Hydroxycarbamide, thalidomide, steroids and SCT