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Year 5 Pathology > Haem > Flashcards

Haem Flashcards

1
Q

Which protein is deficient in haemophilia A?

A

Factor VIII deficiency

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2
Q

Which protein deficiency leads to pro-thrombotic disease?

A

Protein C deficiency

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3
Q

What blood disorders result due to the excess in the following:

a) erythrocytes,
b) granulocytes,
c) lymphocytes,
d) platelets?

A

a) polycythaemia
b) leukaemia (CML) or reactive eosinophilia
c) leukaemia (CLL)
d) essential thrombocythemia

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4
Q

What blood disorders result due to deficiency in the following:

a) erythrocyte,
b) lymphocyte,
c) platelets?

A

a) anaemia
b) lymphopenia (HIV)
c) idiopathic thrombocytopenic purpura (ITP)

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5
Q

Causes of high neutrophils

A 
Corticosteroids (due to demargination)
Underlying neoplasia
Tissue inflammation
Myeloproliferative/leukaemia disorder
Pyogenic infection
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6
Q

Causes of reactive eosinophilia

A 
Parasitic infection
Allergic diseases (asthma, RA)
Underlying neoplasms (Hodgkin's, T cell lymphoma)
Drug reaction (erythema multiforme)
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7
Q

Mutations in what lead to the following:

a) increase cellular proliferation,
b) impair/block cellular differentiation,
c) prolong cell survival (anti-apoptosis)?

A

a) tyrosine kinase signal-inducing genes
b) nuclear transcription factors (e.g. retinoic acid receptor alpha)
c) apoptosis genes, leads to lymphomas

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8
Q

Many spicules seen on blood film

What is observed and what may be causing this?

A

Acanthocytes (spur/spike cells)

Liver disease, hypersplenism, abetalipoproteinemia

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9
Q

Small dot on the peripheries of RBC seen

What is observed and what may be causing this?

A

Basophilic RBC stippling; accelerated erythropoiesis/defective Hb synthesis

Lead poisoning, megaloblastic
anaemia, myelodysplasia, liver
disease, haemoglobinopathy e.g.
thalassaemia

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10
Q

Cell looks like sea urchin with regular spicules

What is observed and what may be causing this?

A

Burr cells (echinocyte)

Often artefact cell if blood sat in EDTA prior to film being made

Uraemia, GI bleed, stomach carcinoma

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11
Q

Inclusions on very edge of RBCs due to denatured Hb

What is observed and what may be causing this?

A

Heinz bodies

Glucose-6-phosphate dehydrogenase deficiency, chronic liver disease

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12
Q

Basophilic (purple spot) nuclear remnants in RBCs

What is observed and what may be causing this?

A

Howell-Jolly bodies; note much bigger purple spots in nucleated RBCs

Post-splenectomy or hyposplenism
(e.g. sickle cell disease, coeliac 
disease, congenital, UC/Crohn's, 
myeloproliferative disease, amyloid) 
Megaloblastic anaemia, hereditary 
spherocytosis
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13
Q

Hyposegmented neutrophil with 2 lobes like a dumbell

What is observed and what may be causing this?

A

Pelger Huet Cells

Congenital (lamin B Receptor 
mutation)
Acquired (myelogenous leukaemia 
and myelodysplastic syndromes
[pseudo-pelger in MDS])
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14
Q

Red cells stacked on each other

What is observed and what may be causing this?

A

Rouleaux formation

Chronic inflammation, paraproteinaemia, myeloma

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15
Q

Fragmented parts of RBCs, irregularly shaped with sharp edges and no central pallor

What is observed and what may be causing this?

A

Schistocytes

Microangiopathic anaemia, e.g.
DIC, haemolytic uraemic syndrome,
thrombotic thrombocytopenic
purpura, pre-eclampsia

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16
Q

Smaller, sphere shaped RBC

What is observed and what may be causing this?

A

Spherocytes

Hereditary spherocytosis,
Autoimmune Haemolytic Anaemia

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17
Q

Central pallor straight/curved rod-like shape, RBCs look like ‘smiling faces’ or ‘fish mouths’

What is observed and what may be causing this?

A

Stomatocytes

Artefacts during slide preparations

Hereditary stomatocytosis, high alcohol intake, liver disease

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18
Q

Bull’s eye appearance in central pallor of RBC

What is observed and what may be causing this?

A

Target cells (codocyte)

Liver disease, hyposlepnism, thalassamia, IDA

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19
Q

Hb in anaemia

A

Men
<135 g/L / 13.5 g/dL

Women
<115 g/L / 11/5 g/dL

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20
Q

Signs and sx in anaemia

A

Sx
- fatigue, dyspnoea, faint, palpitations, headache, tinnitus, anorexia

Signs
- pallor, tachycardia

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21
Q

Causes of microcytic anaemia

A

Iron deficiency
Anaemia of chronic disease
Sideroblastic
Thalassaemia

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22
Q

Causes of normocytic anaemia

A 
Acute blood loss
Anaemia of chronic disease
Bone marrow failure
Renal failure
Hypothyroidism
Haemolysis
Pregnancy
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23
Q

Causes of iron deficiency anaemia

A

Blood loss
- GI loss, colon cancer, peptic ulcers, menorrhagia

Increased use
- pregnancy, growing children

Decreased intake
- veggies/vegans, elderly suboptimal diet

Decreased absorption
- coeliac, post-gastro surgery

Intravascular haemolysis
- microangiopathic, haemolytic anaemia, PNH

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24
Q

Mx plan if no clear cause for iron deficiency anaemia?

A

OGD + colonoscopy, urine dip, coeliac investigations

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25
Q

Mechanism of anaemia of chronic disease

A

Ferritin increases in inflammatory state, holds in iron

Additionally inflammatory markers reduce EPO receptor production thus EPO synthesis

Also inflammatory markers stimulate hepcidin production, decreasing iron absorption from the gut + increasing iron accumulation in macrophages

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26
Q

What is sideroblastic anaemia?

A

Result of ineffective erythropoiesis
- iron loading in bone marrow causing iron deposition to endocrine, liver, and cardiac systems

Ring sideroblasts seen in marrow (iron deposited in mitochondria in ring around nucleus)

Caused by myelodysplastic/myeloproliferative disorders, following chemo, irradiation, alcohol excess, lead excess, anti-TB drugs

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27
Q

How do you treat sideroblastic anaemia?

A

Remove cause

Pyridoxine (vitamin B6 promotes RBC production)

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28
Q

Which plasma iron study is more useful if the pt is in an inflammatory state?

A

Transferrin saturations > ferritin

Ferritin is an acute phase protein that increases with inflammation so check CRP with every ferritin to confirm accuracy

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29
Q

What would the plasma iron studies be for the following:

a) iron deficiency,
b) anaemia of chronic disease,
c) chronic haemolysis,
d) haemochromatosis,
e) pregnancy,
f) sideroblastic anaemia?

A

Order: Iron // TIBC // Ferritin

a) low // high // low
b) low // low // high
c) high // low // high
d) high // low-normal // high
e) high // high // normal
f) high // normal // high

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30
Q

What investigations should you do in the case of pancytopenia?

A

B12/folate/iron

Abdominal exam to assess spleen
- ?myelofibrosis

Reticulocyte count
- ?aplastic anaemia

Blood film

  • ?leukaemia
  • ?myelodysplasia

Myeloma screen

Parovirus blood PCR
- immunocompromised pts

Review medications

Bone marrow biopsy if no clear cause indicated

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31
Q

Megaloblastic causes of macrocytic anaemia

A

B12 deficiency
Folate deficiency
Cytotoxic drugs

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32
Q

Non-megaloblastic causes of macrocytic anaemia

A 
Alcohol (seen without anaemia also)
Reticulocytosis (in haemolysis)
Liver disease
Hypothyroidism
Pregnancy
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33
Q

Other causes of macrocytosis of RBCs

A

Myelodysplasia
Myeloma
Myeloproliferative disorders
Aplastic anaemia

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34
Q

What would you see on a megaloblastic blood film?

A 
Hypersegmented polymorphs
Leucopenia
Macrocytosis
Anaemia
Thrombocytopenia with megalobalsts
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35
Q

Clinical features of B12 deficiency

A

Glossitis, angular cheilosis

Irritable, depression, psychosis, dementia

Paraesthesia, peripheral neuropathy (loss of vibration and proprioception first, absent ankle reflex, spastic paraperesis, subacute combined degeneration of spinal cord)

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36
Q

What is pernicious anaemia?

A

Autoimmune atrophic gastritis
- achlorhydria, lack of gastric intrinsic factor

Testing

  • parietal cell antibodies (90%)
  • intrinsic factor antibodies (50%)

Treat
- replenish stores with IM hydroxocobalamin (B12)

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37
Q

Causes of B12/folate deficiencies

A

Poor diet
- vegan

Malabsorption

  • post gastrectomy, coeliac disease, tropical sprue, crohn’s
  • pernicious anaemia (B12)

Drugs (folate)
- alcohol, anti-epileptics (phenytoin), methotrexate, trimethoprim

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38
Q

What is the normal life span of a RBC?

A

120 days

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39
Q

What changes do you see in all haemolytic anaemias?

A 
Increased unconjugated bilirubin
Increased urobilinogen 
Increased LDH 
Reticulocytosis (increased MCV and polychromasia)
May have pigmented gallstones
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40
Q

What changes do you see in intravascular haemolytic anaemia?

A

Increased free plasma Hb
Decreased haptoglobin (binds free Hb)
Haemoglobinuria (dark red piss)
Methaemalbuminaemia (haem + albumin in blood)

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41
Q

What changes do you see in extravascular haemolytic anaemia?

A

Splenomegaly

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42
Q

What do you expect to happen to the reticulocyte count in haemolytic anaemia?

A

Increased/high

If pt acutely anaemia, you would expect bone marrow to respond thus pump out reticulocytes to make up for the lost RBCs

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43
Q

What complications are associated with an erythroid hyperplasic state?

A

Susceptible to parvovirus B19 (aplastic crisis)
Risk of iron overload
Risk of osteoporosis

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44
Q

When would you see a low reticulocyte count in a haemolytic anaemia pt?

A

Parvovirus B19 infection

  • virus infects developing erythroid progenitor cells in bone marrow
  • production of RBCs switched off
  • low reticulocyte count
  • results in aplastic crisis in pts with shortened RBC survival
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45
Q

Name causes of inherited haemolytic anaemias

A

Membrane defect

  • hereditary spherocytosis
  • hereditary elliptocytosis

Enzyme defect

  • G6PD deficiency
  • pyruvate kinase deficiency

Haemoglobinopathies

  • sickle cell disease
  • thalassaemias
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46
Q

Name causes of acquired haemolytic anaemias

A

Immune

  • autoimmune (warm or cold)
  • alloimmune (haemolytic transfusion reactions)

Non-immune

  • mechanical (e.g. metal valves, trauma)
  • paroxysmal nocturnal haemoglobinuria
  • microangiopathic haemolytic anaemia (e.g. HUS, TTP)
  • infections (i.e. malaria), drugs
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47
Q

Name an inherited haemolytic anaemia due to a membrane defect that leads to malaria protection

A

South East Asian Ovalocytosis

  • autosomal recessive incompatible with life
  • heterozygotes typically asx and malaria protection
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48
Q

Mutations in which membrane proteins lead to:

a) hereditary spherocytosis
b) hereditary elliptocytosis

A

a) autosomal dominant, spectrin or ankyrin deficiency

b) autosomal dominant, spectrin mutation

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49
Q

Which hereditary elliptocytosis is autosomal recessive?

A

Hereditary pyropoikilocytosis

- abnormally sensitive to heat

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50
Q

How is hereditary spherocytosis diagnosed?

A

Spherocytes seen on blood film
Lysis in hypotonic solutions (increased osmotic fragility)
-ve DAT Coombs
Flow cytometry (dye binding test)

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51
Q

Tx for hereditary spherocytosis

A

Splenectomy

Folic acid

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52
Q

What are pts with hereditary spherocytosis at increased risk of?

A

Parvovirus B19 -> aplastic crisis
Gallstones due to increased unconjugated bilirubin
Sepsis if had splenectomy

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53
Q

What dye is used in flow cytometry to diagnose hereditary spheroctysois?

A

Eosin-5-malemide

- reduced binding to surface of RBCs in those with h spherocytosis compared to unaffected person

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54
Q

Blood film in hereditary spherocytosis

A

No central pallor
Microcytic
Densely stained (hyperchromic)
Polychromasia

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55
Q

Blood film of G6PD deficiency during acute haemolysis

A

Contracted cells
Nucleated red cells
Bite cells (evidence a Heinz body has been formed and removed by spleen)
Hemighosts (Hb retracted to one side of cell)

*in steady state, blood film is normal

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56
Q

How is G6PD deficiency acquired?

A

X-linked leading to RBC enzyme defect

  • hemizygous males
  • homozygous females
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57
Q

Clinical features of G6PD deficiency

A

Neonatal jaundice (can lead to kernicterus)
Acute haemolysis
Chronic haemolytic anaemia

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58
Q

What type of haemolytic anaemia do you see in G6PD deficiency?

A

Intravascular haemolysis (dark urine)

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59
Q

Name triggers of acute haemolysis in those with G6PD deficiency

A 
Oxidant drugs 
- antimalarials, antibiotics, dapsone, vitamin K
Infections
Fava beans (ingestion/inhalation both)
Naphthalene mothballs (potent oxidant)
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60
Q

When is it anaemia during pregnancy?

A

Hb < 110 g/l 1st trimester

Hb < 105 g/l 2nd and 3rd trimester

Hb < 100 g/l postpartum

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61
Q

What haem factors are increased in pregnancy?

A 
Plasma volume
Red cell mass
MCV
WCC
Factors VII, VIII, IX, X, XII
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62
Q

What haem factors are decreased in pregnancy?

A 
Hb
Haematocrit
Platelets
Factor XI
Protein S
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63
Q

What is HELLP syndrome?

A

Haemolysis, elevated liver enzyes, low platelets

  • life-threatening complication of pre-eclampsia
  • type of MAHA (increased AST, ALT, low plts, normal APTT, PT)

Mx: supportive, delivery of fetus

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64
Q

What is haemolytic disease of the newborn (HDN)?

A

When maternal Ab level is high that it destroys fetal red cells if they have corresponding red cell Ag, it leads to fetal anaemia and jaundice (HDN)

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65
Q

Which Ig can cross the placenta?

A

IgG

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66
Q

How do we prevent haemolytic disease of the newborn?

A

Anti-D prophylaxis for RhD -ve women

  • routine: 28 and 34 weeks
  • sensitising event occurs: abortion, miscarriage, abdo trauma, ECV, amniocentesis
  • delivery: if baby is RhD +ve
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67
Q

When do you see Heinz bodies?

A

Formed from denatured Hb due to oxidative haemeolysis

Seen transiently because cells containing Heinz bodies are quickly removed by the spleen

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68
Q

G6PD tx

A 
Avoid precipitants
Transfuse if severe
Genetic screening (rare subtypes give chronic haemolysis for which splenectomy is good treatment)
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69
Q

How may pyruvate kinase deficiency present?

A

Severe neonatal jaundice
Splenomegaly
Haemolytic anaemia

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70
Q

What is PKD?

A

Pyruvate kinase deficiency

  • autosomal recessive
  • most common defect in the glycolytic pathway
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71
Q

Which mutation leads to sickle cell disease?

A

Autosomal recessive

Single base mutation: GAG -> GTG / Glu -> Val

Codon 6 of beta chain leads to HbS instead of HbA

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72
Q

What type of sickle cell disease are the following?

a) HbSS
b) HbAS
c) HbSC
d) HbS/B

A

HbSS - severe, sickle cell anaemia

HbAS - sickle cell trait, asx except under stress

HbSC - sickle-Hb C disease, one inherited from each parent

HbS/B - sickle beta thalassaemia, one inherited from each parent

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73
Q

When does sickle cell disease manifest?

A

3-6 months when fetal HbF decreases

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74
Q

What features of sickling may you see in sickle cell disease?

A

Vaso-occlusion + infarction

  • stroke
  • infections (hyposplenism, CKD)
  • crises (splenic, sequestration, chest and pain)
  • kidney (papillary necrosis, nephrotic)
  • liver (gallstones)
  • eyes (retinopathy)
  • dactylitis (impaired growth)
  • mesenteric ischaemia
  • priapism
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75
Q

Clinical features of haemolytic anaemia

A 
Pallor
Jaundice
Splenomegaly
Pigmenturia (dark urine)
FHx
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76
Q

Laboratory findings of haemolytic anaemia

A 
Anaemia
Increased reticulocytes 
Polychromasia 
Hyperbilirubinaemia 
Increased plasma LDH (intravascular haemolysis)
Reduced/absent haptoglobins (intravascular haemolysis)
Haemoglobinuria
Haemosiderinuria
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77
Q

What features of sickle cell disease would you expect to see in a child?

A

Strokes
Splenomegaly + splenic crises
Dactylitis

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78
Q

What features of sickle cell disease would you expect to see in a teenager?

A

Impaired growth
Gallstones
Psych issues
Priapism

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79
Q

What features of sickle cell disease would you expect to see in an adult?

A

Hyposplenism
CKD
Retinopathy
Pulmonary hypertension

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80
Q

Diagnosis of sickle cell disease

A

Blood film
- sickle cell, target cells

Sickle solubility test

Hb electrophoresis

Guthrie test (birth)

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81
Q

Tx of acute sickle cell disease

A 
Opioid analgesia 
Blood transfusion (exchange transfusion)
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82
Q

Tx of chronic sickle cell disease

A

Pencillin V, pneumovax, HIB vaccine
Folic acid
Hydroxycarbamide
Regular exchange transfusions
Carotid doppler in early childhood to detect turbulent flow
Crizanlizumab (new drug being trialled)
Allogeneic stem cell transplant (other countries do this)

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83
Q

What mutation leads to beta thalassaemia?

A

Point mutations leading to decreased B-chain synthesis (spectrum of disease) and excess alpha-chains

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84
Q

What phenotypes of beta thalassaemia are there?

A

B0 - no expression of gene
B+ - some expression of gene
B - normal gene

B-thalassaemia minor (B+/B+ or B0/B+)

B-thalassaemia intermediate (B+/B or B0/B)

B-thalassaemia major (B0/B0)

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85
Q

How does B-thalassaemia minor present?

A

Asx carrier

Mild anaemia

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86
Q

How does B-thalassaemia intermediate present?

A

Moderate anaemia
Splenomegaly
Bony deformity
Gallstones

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87
Q

How does B-thalassaemia major present?

A 
3-6 months severe anaemia
Failure to thrive 
Hepatosplenomegaly (extramedullary erythropoiesis)
Bony deformity
Severe anaemia + heart failure
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88
Q

Diagnosis of beta thalassaemia

A

Guthrie test at birth -> Hb electrophoresis

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89
Q

Tx for beta thalassaemia

A

Major form

  • blood transfusions with iron chelation to stop iron overload
  • folic acid
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90
Q

What mutation leads to alpha-thalassaemia?

A

Deletions leading to reduce alpha-chain synthesis and excess beta-chains

4 alpha genes

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91
Q

What types of alpha-thalassaemia are there?

A

a-thalassaemia trait (1/2 genes deleted)
- asx, mild anaemia

HbH disease (3 genes deleted)
- moderate anaemia, splenomegaly
Hydrops foetalis (4 deleted)
- incompatible with lie
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92
Q

Name autoimmune (Coombs +ve) causes of acquired haemolytic anaemias

A

Warm (WAIHA)

  • idiopathic
  • lymphoma, CLL, SLE, methyldopa

Cold agglutinin disease

  • idiopathic
  • lymphoma, infections (EBV, mycoplasma)

Paroxysmal cold haemoglobinuria
- viral infection (measles, syphilis, VZV)

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93
Q

Features of warm autoimmune haemolytic anaemia

A

+ve Coombs test
37oC
IgG-mediated
Spherocytes

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94
Q

Features of cold agglutinin disease

A

+ve Coombs test
< 37oC
IgM-mediated
Often with Raynaud’s

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95
Q

Tx for warm autoimmune haemolytic anaemia

A

Steroids
Splenectomy
Immunosuppression

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96
Q

Tx for cold agglutinin disease

A

Treat underlying condition
Avoid the cold
Chemotherapy if lymphoma

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97
Q

Why is paroxysmal cold haemoglobinuria self-limiting?

A

Donath-Landsteiner antibodies stick to RBCs in cold, resulting in complement-mediated haemolysis in rewarming

IgG-mediated and these dissociate at higher temperatures than IgM thus self-limiting

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98
Q

Name nonimmune (Coombs -ve) causes of acquired haemolytic anaemias

A

Paroxysmal nocturnal haemoglobinuria

Microangiopathic haemolytic anaemia (MAHA)
- HUS, TTP, DIC, pre-eclampsia, eclampsia

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99
Q

What causes paroxysmal nocturnal haemoglobinuria?

A

Acquired loss of protective surface GPI markers on RBCs

Leads to complement-mediated lysis and chronic intravascular haemolysis, especially at night

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100
Q

Features of paroxysmal nocturnal haemoglobinuria

A

Morning haemoglobinuria

Thrombosis
- Budd-Chiari syndrome

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101
Q

Diagnosis of paroxysmal nocturnal haemoglobinuria

A

Immunophenotype shows altered GPI

Ham’s test (in vitro acid-induced lysis)

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102
Q

Tx of paroxysmal nocturnal haemoglobinuria

A

Iron/folate supplements

Prophylactic vaccines/abx

Eculizumab (spenny) prevents complement from binding RBCs

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103
Q

What is MAHA?

A

Mechanical RBC destruction due to forced RBCs through fibrin/platelet mesh in damaged vessels

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104
Q

What would you see in a blood film for MAHA?

A

Schistocytes

105
Q

What is TTP?

A

Thrombotic thrombocytopenic purpura

  • haematological emergency requiring emergency plasma exchange
  • type of MAHA
106
Q

What sx do you see in TTP?

A

Pentad

  1. MAHA
  2. Fever
  3. Renal impairment (less pronounced than HUS)
  4. Neuro abnormalities
  5. Thrombocytopenia
107
Q

What causes TTP?

A

Antibodies against ADAMTS13 lead to long strands of VWF

These act like cheese wire in blood vessels and cut up RBCs -> MAHA

108
Q

What is HUS?

A

Haemolytic uraemic syndrome

  • E. coli toxin damages endothelial cells -> fibrin mesh -> damages RBCs
  • often seen in children & elderly
109
Q

What sx do you see in HUS?

A

MAHA
Diarrhoea
Renal failure
No neuro problems

110
Q

What responses do vessel injury stimulate?

A
  1. Blood vessel vasoconstriction
  2. Platelet activation
  3. Activation of coagulation cascade
111
Q

Life span of a platelet

A

7-10 days

112
Q

How can platelets adhere to exposed sub-endothelial structures?

A

Direct via Glp-Ia that binds to collagen in exposed wall

Indirectly via Glp-Ib that binds to vWF in exposed wall (most common and important one)

113
Q

How do platelets attach to each other?

A

Via GlIb/IIIa (fibrinogen receptor)

114
Q

What do platelets release when they bind to exposed wall?

A

Release ADP and thromboxane A2 which promote platelet aggregation

115
Q

Effects of thrombin

A

Activates fibrinogen
Activates platelets
Activates procofactors (5, 8)
Activate zymogens (7, 11, 13)

116
Q

Describe the intrinsic pathway

A 
Factors all converted into a version which sets off next factor:
12
11
9 (8 co factor)
10 (common pathway, 5 co factor)

This usually happens in vitro during clotting studies

117
Q

Describe the extrinsic pathway

A

Tissue factor activation results in
7
10 (common pathway, 5 co factor)

More important pathway in body that sets off coagulation cascade

118
Q

Describe the common pathway

A

10 (5 co-factor)
Prothrombin -> thrombin
Fibrinogen -> fibrin

Stable fibrin clot made

119
Q

What does APTT measure?

A

Activated partial thromboplastin time

  • intrinsic pathway
  • monitor heparin therapy
120
Q

What does PT measure?

A

Prothrombin time

  • extrinsic pathway
  • monitor warfarin therapy (INR)
121
Q

Which coagulation factors are vit K-dependent?

A

2, 7, 9, 10
Protein C
Protein S

122
Q

How does the body breakdown fibrin clots?

A

Tissue plasminogen activator (tPA) converts plasminogen to plasmin

Plasmin breaks down fibrin into degradation products

123
Q

What is an important inhibitor of fibrin breakdown?

A

Thrombin-activatable fibrinolysis inhibitor (TAFI)

124
Q

Role of protein C and S

A

Inactivate factors 5 and 8 to stop thrombin generation

125
Q

Classifications of aplastic anaemia

A

IDIOPATHIC: Vast majority (70-80%)

INHERITED (rare):

  • Dyskeratosis congenita (DC)
  • Fanconi anaemia (FA)
  • Shwachman-Diamond syndrome

SECONDARY:

  • Radiation: Predictable
  • Drugs: Predictable: (cytotoxic agents)
  • Idiosyncratic: chloramphenicol, NSAIDS
  • Viruses (idiosyncratic): Hepatitis viruses
  • Immune: SLE
126
Q

What is aplastic anaemia linked with?

A

Leukaemia

Paroxysmal nocturnal haemoglobinuria

127
Q

Inherited pancytopenia conditions

A

Fanconi Anaemia (FA)
Dyskeratosis congenita (DC)
Shwachman-Diamond Syndrome (SDS)
Familial aplastic anaemia (autosomal and X-linked forms)
Myelodysplasia
Non-haematological syndromes (Down’s, Dubowitz’s)

128
Q

Clinical Presentation of Bone Marrow Failure

A

Triad of Bone Marrow Failure Findings

  1. Anaemia: fatigue, breathlessness
  2. Leukopenia: infections
  3. Thrombocytopaenia: bleeding/bruising
129
Q

DDx of pancytopenia and hypocellular marrow

A 
Hypoplastic MDS/AML
Hypocellular ALL
Hairy cell leukaemia
Mycobacterial (usually atypical) infection
Anorexia nervosa
Idiopathic thrombocytopenic purpura
130
Q

Mx of aplastic anaemia

A 
Supportive
- transfusions, abx, iron chelation 
Drugs
- promote recovery: growth factors and oxymethalone (androgen) 
Immunsuppresants
- idiopathic AA
Stem cell transplant
131
Q

Features of Fanconi Anaemia

A 
Autosomal recessive 
Pancytopenia 
Presents 5-10 yrs 
Skeletal abnormalities, renal malformations, microophathalmia, short stature, skin pigmentation 
Myelodysplastic syndrome (30%)
AML risk (10% progress)
132
Q

Features of Dyskeratosis Congenita

A

X-linked, chromosome instability due to telomere shortening
Skin pigmentation, nail dystrophy, oral leukoplakia
BM failure

133
Q

Features of Schwachman-Diamond syndrome

A

Autosomal recessive
Primarily neutrophilia
Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature
AML risk

134
Q

Features of Diamond-Blackfan syndrome

A

Pure red-cell aplasia: normal WCC and platelets
Presents at 1 yr/neonatal
Dysmorphology

135
Q

Inherited single cytopaenia conditions

A 
Diamond-Blackfan syndrome
Kostmann’s syndrome
Shwachman-Diamond Syndrome (SDS)
Reticular dysgenesis
Amegakaryocytic thrombocytopenia with absent radii (TAR)
136
Q

Clinical features of multiple myeloma

A

CRAB

Calcium high
- groans, moans, stones, bones

Renal failure
- amyloidosis, necrotic syndrome

Anaemia
- pancytopenia

Bones
- pain, osteoprosis, osteolytic lesions, freactures

+ Hyperviscosity syndrome

137
Q

Describe what multiple myeloma is

A

Neoplasia of plasma cells (effector B cell antibodies) of bone marrow

Leads to production of monoclonal immunoglobulin - the paraprotein - namely IgG

138
Q

Bence Jones proteins

Dx?

A

Multiple myeloma

  • present in urine
  • monoclonal globulin protein/immunoglobulin light chain
139
Q

Ix findings for multiple myeloma

A

Dense narrow band on serum electrophoresis

Rouleaux on blood film (RBC stacking)

CRAB sx

Bence Jones protein in urine

ESR elevated

> 10% plasma cells in bone marrow

140
Q

Staging system for multiple myeloma

A

Durie-Salmon staging system

141
Q

Emergency presentations of multiple myeloma patients

A

Cord compression
Hypercalcaemia
Renal failure

142
Q

Tx for multiple myeloma

A

Treat CRAB sx (i.e. bisphosphonates)

Induce remission of autologous stem cell transplant to prolong remission as NOT CURABLE (5-7 yr survival) using:

  • immunomodulatory drugs
  • steroids
143
Q

Timeline of disease to multiple myeloma

A

Monoclonal gammopathy of uncertain significance (MGUS)

  • <30g/l M-spike
  • < 10% clonal plasma cells

Smouldering myeloma

  • > 30g/l M-spike
  • > 10% clonal plasma cells

Multiple myeloma

  • loads plasma cells and M-spike + CRAB sx + organ damage
  • remitting-relapsing
144
Q

How may systemic amyloidosis present?

A 
Macroglossia
Carpal tunnel syndrome
Peripheral neuropathy
Heart failure
Renal failure
145
Q

What is Waldenstrom’s macroglobinaemia?

A

Lymphoplasmacytoid lymphoma (LPL)

  • non-Hodgkin’s lymphoma that produces monoclonal serum IgM infiltrating lymph nodes and bone marrow
  • systemic sx, hyperviscosity syndrome
146
Q

Which +ve expressions do you get for myeloma cells?

A

CD138
CD38
Monotypic cytoplasmic immunoglobulin
Light chain restriction

147
Q

Characteristics of myelodysplastic syndromes

A

Peripheral cytopenia
Qualitative abnormalities of cell maturation
Risk of AML transformation
Seen in the elderly and develops over weeks/months

BY DEFINITION PTS HAVE < 20% BLASTS

148
Q

Clinical features of myelodysplastic syndromes

A

BM failure and cytopenias
- infection, bleeding, fatigue

Hypercellular BM

Defective cells

149
Q

What could be seen in a blood film of a pt with myelodysplastic syndrome?

A

RBC
- ring sideroblasts

WBC

  • hypogranulation
  • Pseudo-Pelger-huet anomaly (hyposegmented neutro)

Platelets

  • micromegakaryocytes
  • hypolobated nuclei
150
Q

Tx for myelodysplastic syndrome

A

Supportive
- transfusions, EPO, G-CSF, abx

Biological modifiers
- immunosuppressive drugs, lenalidomide, azacytidine

Chemotherapy
- similar to AML

Allogeneic SCT

151
Q

Prognosis of myelodysplastic syndroe

A

Depends on International Prognostic Scoring System

  • BM blast %
  • Karyotype
  • Degree of cytopenia

Mortality rule of 1/3

  • 1/3 die from infection
  • 1/3 bleeding
  • 1/3 acute leukaemia
152
Q

Define lymphoma

A

Tumour of lymphoid cells

153
Q

Define myeloma

A

Tumour of plasma cells

154
Q

Name the different leukaemias

A

Acute lymphoblastic leukaemia (ALL)

Acute myeloid leukaemia (AML)

Chronic lymphocytic leukaemia (CLL)

Chronic myeloid leukaemia (CML)

155
Q

Main clinical feature of leukaemia

A

Bone marrow function failure

  • anaemia
  • thrombocytopenia = bleeding
  • neutropenia = infection
156
Q

AML subtype M3 is prone to

A

*Acute promyelocytic leukaemia
DIC
Haemorrhage

157
Q

AML subtype M4 & 5 are prone to

A

Monoblasts/monocytes infiltrating skin & gums

Hypokalaemia

158
Q

Which flow cytometry markers are useful for ALL?

A

CD34 = precursor/stem cells
CD3, 4, 8 = T lymphocytes
CD19, 23 = B lymphocytes

159
Q

Which flow cytometry markers are useful for AML?

A

CD34 = precursor/stem cells

CD33, 13, MPO = myeloid cells

160
Q

Compare blood films in ALL vs AML

A

ALL

  • high WCC (blasts)
  • often tails/blebs of cytoplasm tails

AML

  • High WCC (blasts)
  • AUER RODS
161
Q

Targeted tx in ALL

A

T-lymphocytes

  • nelarabine
  • CAR-T cells

B-lymphocytes

  • blinatumumab
  • imatinib (9;22 translocation)
162
Q

Targeted rx in AML

A

ATRA
- acute promyelocytic leukaemia

Midostaurin
- FLT3 mutation

Gemtuzumab
- CD33 immunotherapy

Enasidenib
- IDH mutations

163
Q

How CML is commonly diagnosed

A

Incidental finding on routine bloods
- large number of differentiated cells
OR
Present with malaise, wt loss, infections & bruising

164
Q

Tx for CML

A

Imatinib (95% remission rate)

165
Q

Positive findings in CML

A

+ve Philadelphia chromosome

  • 9;22
  • PCR for BCR-ABL fusion gene

High WCC
- neutrophils, basophils

Hypercellular BM
- myelocytes and mature granulocytic cells

166
Q

Phases of CML

A
  1. Chronic phase
    - < 5% blasts, WBC increases over years
    - imatinib response very high
  2. Accelerated phase
    - > 10% blasts, splenomegaly
    - less responsive to therapy
  3. Blast phase
    - > 20% blasts, resembles ALL
    - tx similar to ALL
167
Q

Diagnostic finding for CLL on blood film

A

Smear cells

- smear CLLS get it

168
Q

Monoclonal population seen in CLL

A

CD5+

CD23+

169
Q

Bad prognostic factors in CLL

A

LDH raised
CD38 +ve
11q23 deletion

170
Q

Good prognostic factors in CLL

A

Hypermutated Ig gene
Low ZAP-70 expression
13q14 deletion

171
Q

One way CLL is staged

A

Binet Staging

A = high WBC, < 3 groups of enlarged lymph nodes, no tx required

B = > 3 groups enlarged lymph nodes

C = anaemia or thrombocytopenia

172
Q

Tx for CLL

A

Watchful waiting
Supportive (infection, transfusions)

1st line if p53 deletion
- alemtuzumab
ibrutinib
idalasisib + transplant

173
Q

Summary of lymphoma types

A

Hodgkin’s (20%)

Non-Hodgkin’s (80%)

  • B cell
  • T cell
174
Q

B cell lymphomas

A

Non-Hodgkin types

  • Burkitt’s
  • Diffuse Large B-cell (DLBC)
  • Mantle cell
  • Follicular
  • Mucosal associated lymphoid tissue (MALT)
175
Q

T cell lymphomas

A

Non-Hodgkin type

  • anaplastic large cell lymphoma
  • peripheral T-cell lymphoma
  • adult T cell leukaemia/lymphoma
  • enteropathy-associated T cell lymphoma (EATL)
  • cutaneous T cell lymphoma
176
Q

Presentation of lymphomas

A

Painless lymphadenopathy
Multiple sites affected
Constitutional sx

Hodgkin’s can have pain in affected nodes after alcohol

177
Q

Staging of lymphomas

A

Ann-Arbor

  1. one LN region (can include spleen)
  2. 2+ LN regions on same side of diaphragm
  3. 2+ LN regions on opposite sides of diaphragm
  4. Extranodal sites (liver, BM)

A. No constitutional sx
B. Constitutional sx

178
Q

Reed-Sternberg cell on lymph node biopsy

Dx?

A

Hodgkin’s lymphoma

179
Q

What cell stains do we use for suspected lymphoma biopsy?

A

CD15

CD30

180
Q

Bi-nucleate cell on background of lymphocytes and reactive cells

What is this?

A

Reed-Sternberg cell

- can be multinucleate

181
Q

Tx for Hodgkin’s lymphoma

A
  1. Combination chemo
    - most cases
    - excellent prognosis younger you are
  2. Radiotherapy
    - alongside chemo in bulky/limited disease
  3. Intensive chemo and autologous SCT
    - relapsed pts
182
Q

Autologous vs allogenic SCT

A

Autologous

  • patient OWN SCs
  • used more in multiple myeloma and lymphoma (particularly relapse)
  • no GHD risk, lower risk of infection

Allogenic

  • HLA-matched donor SC
  • used more in leukaemia
  • GVHD, opportunistic infections infertility, secondary malignancy risk
183
Q

High grade NH lymphomas

A

Burkitt’s
Diffuse large B-cell
Mantle cell

184
Q

Low grade NH lymphomas

A

Follicular
Marginal zone
Small lymphocytic

185
Q

Which type of lymphoma is it from the following histology findings on lymph node biopsy?

a) starry sky appearance
b) angular/clefted nuclei
c) nodular appearance
d) bi-nucleate cell on background of lymphocytes and reactive cells
e) sheets of large lymphoid cells

A

a) Burkitt’s
b) Mantle cell lymphoma
c) Follicular
d) Hodgkin’s*
e) Diffuse large B cell (DLBC)
* the rest of the lymphomas are non-Hodgkin’s

186
Q

Types of Burkitt’s lymphoma

A

Endemic: EBV-associated in Africa

Sporadic: EBV-associated outside Africa

Immunodeficiency: Non-EBV associated, HIV/post-tranplant pts

187
Q

Which lymphomas are associated with the following translocations?

a) t(14;18)
b) t(8;14)
c) t(11;14)

A

a) Follicular
b) Burkitt’s
c) Mantle cell lymphoma

188
Q

Which conditions are associated with MALT?

A

H. pylori = gastric MALT

Sjorgen’s syndrome = parotid lymphoma

MALT is a result of chronic antigen stimulation that’s why

189
Q

Tx for B-cell lymphomas

A

Rituximab (anti CD20 found on B cells)

Auto-SCT for relapses

190
Q

Tx for T-cell lymphomas

A

Alemtuzumab (anti CD52 found on T cells)

191
Q

Aggressive lymphoma with large ‘epithelioid’ lymphocytes that occurs in children and young adults

t(2;5) and alk-1 protein expression found

Which lymphoma?

A

Anaplastic large cell lymphoma

192
Q

Aggressive lymphoma with large T-cells that occurs in middle-aged and elderly

Which lymphoma?

A

Peripheral T-cell lymphoma

193
Q

Aggressive lymphoma that occurs after HTVL-1 infection, commonly in Caribbean and Japanese pts

Which lymphoma?

A

Adult T cell leukaemia/lymphoma

194
Q

Lymphoma associated with longstanding coeliac disease

A

Enteropathy-associated T cell lymphoma

195
Q

Lymphoma associated with mycosis fungoides

A

Cutaneous T cell lymphoma

196
Q

Name chronic myeloproliferative diseases and how they can be classified

A

Philadelphia chromosome -ve:

  • polycythaemia vera
  • essential thrombocytopenia - idiopathic myelofibrosis

Philadelphia chromosome +ve:
- chronic myeloid leukaemia

197
Q

Myeloproliferation vs myelodysplasia vs leukaemia

A

Myeloproliferation
- proliferation with FULL differentiation

Myelodysplasia
- proliferation with NO/LITTLE differentiation

Leukaemia
- ineffective proliferation with ineffective differentiation

*degree of overlap

198
Q

Mutation associated with myeloproliferative disorders that are Ph -ve

A

JAK2

199
Q

Causes of polycythaemia

A

Primary

  • polycythaemia vera
  • familial polycythaemia

Secondary

  • disease states (renal Ca)
  • high altitude
  • chronic hypoxia, e.g. COPD
200
Q

Causes of pseudo polycythaemia

A

Plasma volume reduced

  • dehydration
  • burns
  • vomiting
  • diarrhoea
  • cigarette smoking
201
Q

Cause of polycythaemia rubra vera

A

JKA2 V617F point mutation resulting in erythroid precursors dominating bone marrow

202
Q

Positive ix findings for polycythaemia rubra vera

A

Raised Hb, HCT, platelets, WCC (neutrophils, basophils)

Low serum EPO

203
Q

Tx for polycythaemia rubra vera

A

Venesection
Hydroxycarbamide (maintenance)
Aspirin (CVD risk)

204
Q

Features of myelofibrosis

A

Elderly
Pancytopenia-related sx
Hepatosplenomegaly due to extramedullary haematopoiesis

Can present with Budd-Chiari syndrome

205
Q

Positive ix findings for myelofibrosis

A

Blood film

  • tear-drop poikilocytes/dacrocytes
  • leukoerythroblasts

Bone marrow
- fibrosis, ‘dry tap’

Molecular

  • JAK2 +ve 60%
  • MPL mutation
206
Q

Tx of myelofibrosis

A

Supportive

  • blood products
  • splenectomy

Stem cell transplant only curative option

Ruloxitinib, hydroxycarbamide, thalidomide, steroids

207
Q

Features of essential thrombocytosis

A

Incidental finding in 50%
Venous and arterial thrombosis (gangrene, haemorrhage)
Erythromelalgia
Splenomegaly, dizziness, headaches, visual disturbances

208
Q

Positive ix findings for essential thrombocytosis

A

Platelet count
- > 600 x 10^9

Blood film

  • large platelets
  • megakaryocyte fragments

Increased BM megakaryocytes (not reactive)

209
Q

Tx for essential thrombocytosis

A

Aspirin (CVD risk)
Anagrelide (reduce formation of plts)
Hydroxycarbamide

210
Q

Indications for RBC transfusion

A
  1. Hb 70g/l if asx, 80g/l if sx
    - higher threshold if CHD
  2. Major blood loss
  3. Treat iron/folate/B12 deficiency first unless active bleeding
211
Q

Indications for platelet transfusion

A
  1. Consumptive disorders
    - TTP, DIC, HIT
  2. Transfuse when plts < 10 bn/L
  3. Pre procedure, i.e. chemo/surgery
    * DO NOT give if actively bleeding
212
Q

Indications for FFP transufsion

A

Try use Vit K first if appropriate

Use to replace clotting factors in severe liver disease or undergoing massive transfusion (avoid dilution)

  • do not use if active bleeding or undergoing procedure, i.e. surgery
213
Q

Acute adverse reactions to transfusions

A

Immune

  • ABO
  • Febrile non-haemolytic
  • Allergic/anaphylaxis
  • Transfusion related acute lung injury

Non-immune

  • Bacterial infection
  • Transfusion associated cardiac overload
214
Q

Delayed adverse reactions to transfusions

A

Immune

  • Delayed haemolytic transfusion reaction
  • Port-transfusion purpura
  • Transplant-associated GVHD

Non-immune

  • Viral infections
  • Iron overload
215
Q

Based on the clinical sx, which acute transfusion reaction is most likely in the following patients?

a) Mild fever with urticaria
b) Shock with bleeding and dark urine
c) Shock with significantly high fever
d) Shock with SOB and raised JVP
e) Shock with SOB and normal JVP

A

a) Mild allergic reaction
b) ABO incompatibility
c) Bacterial infection of unit
d) Transfusion associated cardiac overload
e) Transfusion related acute lung injury

216
Q

Which immunoglobulins are associated with the following adverse reaction to transfusions?

a) Anaphylaxis
b) ABO incompatibility
c) Delayed haemolytic transfusion reaction

A

a) IgA deficiency increases risk
b) IgM-mediated resulting in intravascular haemolysis
c) IgG-mediated resulting in extravascular haemolysis

217
Q

Compare TACO and TRALI

A

Both
- pulmonary oedema, SOB, occur within hours

TACO
- increased JVP, pulmonary capillary wedge pressure

TRALI
- absence of heart failure signs

218
Q

Breast Ca pt who has undergone chemo required major blood transfusion post-mastectomy

2 days later they have new onset diarrhoea, jaundice, and skin changes to their hands and feet

Top ddx?

A

Transfusion-associated graft-versus-host disease

  • Lymphocytes attack HLA antigens in gut, liver, skin, bone marrow
  • Severe diarrhoea, liver failure, skin desquamation, bone marrow failure
  • FATAL
219
Q

Which adverse reaction is more likely with platelet transfusions?

A

Bacterial contamination

220
Q

Clinical features of platelet disorders

A 
Superficial bleeding into skin, mucosal membranes 
- nosebleed, gum, vaginal, GI tract
- small, superficial bruises 
Bleeding immediately after after injury 
Petechiae
221
Q

Clinical features of coagulation disorders

A

Bleeding into deep tissues, muscles, joints
- haemarthrosis
- large, deep bruises
Delayed but severe bleeding after injury
Bleeding often prolonged

222
Q

Congenital vascular defects

A

Osler-Weber-Rendu syndrome

Connective tissues disease (Ehlers-Danlos syndrome)

223
Q

Acquired vascular defects

A

Senile purpura
Infection (meningococcal, measles, dengue fever)
Steroids
Scurvy (perifollicular haemorrhages)

224
Q

Decreased platelet function disorders

A

Acquired

  • aspirin
  • cardiopulmonary bypas
  • uraemia

Congenital

  • storage pool disease
  • thrombasthenia (glycoprotein deficiency)
225
Q

Low platelet function disorders

A

Decreased production
- bone marrow failure

Increased destruction

  • autoimmune ITP
  • drugs (heparin, DIC, HUS, TTP)
226
Q

3 year old presents with multiple bruising across arms and legs. Mum notes a viral infection 2 weeks ago. He is otherwise fit and well.

Platelet count < 20, 000

What is the mx plan?

A

Acute ITP

  • self-limiting
  • reassure parents
  • safety net regarding any massive/concerning bleeds, especially if any trauma occurs
227
Q

53 year old women comes in complaining of recurrent nosebleeds and increased bruising across her thighs and elbows over last few months. She has a background of RA.

Platelet count < 50, 000

What is the mx plan?

A

Chronic ITP

  • associated with AI disease, CLL, HIV
  • spontaneous remission uncommon, considered indolent disease
  • can consider IVIg, steroids, splenectomy
228
Q

Diagnosis of haemophilias

A 
Increased APTT
Normal PT
Decreased factor assay:
- 8 -> haemophilia A
- 9 -> haemophilia B
229
Q

Mx of haemophilias

A

Avoids NSAIDs and IM injections

A:
Desmopressin (vWF release which is f8 carrier)
Factor 8 concentrates

B:
Factor 9 concentrates

230
Q

Von Willebrand Disease classes

A

Type 1
- low levels of vWF

Type 2
- deficiency in function of vWF

Type 3
- ABSENT vWF; presents like haemophilia

231
Q

Diagnosis of vWF disease

A

Increased APTT, normal PT/INR (could both be normal)
Decreased factor 8
Decreased vWF Ag (normal in type 2 but reduced function)
Normal platelet count

232
Q

Mx of vWF disease

A

Prophylaxis indicated in some pts

Bleeds: desmopressin, vWF, factor 8 concentrates

233
Q

What is vit K needed for?

A

Factors 2, 7, 9, and 10

Protein C, S, and Z

234
Q

Causes of vit K deficiency

A

Warfarin
Malabsorption/malnutrition
Abx therapy (kills gut flora)
Biliary obstruction (reduces absorption of vit K)

235
Q

Clotting study results in DIC

A

Prolonged APTT, PT, TT
Decreased fibrinogen platelets
Increased FDP, D-dimer
Schistocytes

236
Q

Mx for vit K

A

IV vit K or FFP for acute haemorrhage

237
Q

Mx for DIC

A

Treat underlying cause (sepsis, malignancy, trauma, obstetric complications, toxins)
Transfusions of FFP, platelets, cryo
Anticoagulation with heparin

238
Q

Liver disease results in the reduction of which haem factors?

A

2, 5, 7, 9, 10, 11
Fibrinogen
Reduced absorption of vit K
Abnormal platelet function

239
Q

Virchow’s triad

A

Vessel wall
Blood composition
Blood flow (stasis)

240
Q

The risk of thrombosis is increased by:

A. Reduced prothrombin
B. Thrombocytopaenia
C. Reduced protein C
D. Elevated anti-thrombin
E. Increased fibrinolysis
A

C. Reduced protein C

241
Q

Which factor confers the highest risk of thrombosis?

  1. Factor V Leiden
  2. Antithrombin deficiency
  3. Family history of thrombosis
  4. Reduced Factor VII Levels
  5. 3-hour plane flight
A
  1. Antithrombin deficiency

NOTE: thrombotic risk factors can combine to cause a massively increased risk.

242
Q

Which agent has a delayed anticoagulant effect?

  1. Vitamin K
  2. Unfractionated heparin
  3. Warfarin
  4. Low molecular weight heparin
  5. Aspirin
A
  1. Warfarin

Warfarin takes a few days to start working because the factors have a half-life of around 2-3 days.

243
Q

How does warfarin achieve its anticoagulant effect?

  1. Reduction of plasma protein C and protein S
  2. Blocks phospholipid synthesis
  3. Reduction of plasma procoagulant factors
  4. Acts as a cofactor for antithrombin
  5. Inhibits factors II, VII, IX and X
A
  1. Reduction of plasma procoagulant factors
244
Q

Which patient is most likely to benefit from long-term anticoagulation after their DVT?

  1. 57-year-old man after flying from Moscow
  2. 27-year-old woman during pregnancy
  3. 33-year-old woman on OCP
  4. 77-year-old man after hip replacement
  5. 30-year-old man after a long walk
A
  1. 30-year-old man after a long walk

This is because there isn’t an obvious external factor that you can attribute the DVT to

245
Q

A 32-year-old woman develops a DVT after the removal of an ovarian cyst. Her brother and father have had a DVT.

  1. Testing for antithrombin deficiency
  2. Recommend HRT
  3. Continue long-term anticoagulation
A
  1. Testing for antithrombin deficiency
246
Q

A 29-year-old man collapses at work following a pulmonary embolism. He has no family history.

  1. Test for Factor V Leiden
  2. Daily aspirin
  3. Continue long-term anticoagulation
  4. Heparin injections for long-haul flights
A
  1. Continue long-term anticoagulation
247
Q

A 38-year-old woman has had a previous DVT while taking the COCP. She has a second DVT during her second pregnancy.

  1. Test for Factor V-Leiden
  2. Hormone Replacement Therapy
  3. Continue long-term anticoagulation
  4. Fixed low-dose warfarin
A
  1. Test for Factor V-Leiden

Fixed low-dose warfarin is not very good because warfarin has very variable bioavailability.

248
Q

67-year-old man presents with DVT and weight loss, started on LMWH. Which should he receive?

  1. Abdo-pelvic CT scan
  2. Switch to DOAC
  3. Switch to warfarin
A
  1. Abdo-pelvic CT scan

If you come with idiopathic thromboembolic disease and you are > 60 years, you should be offered a CT scan to see if there is any underlying cause.

249
Q

Well’s score results and mx

A

0
- consider other diagnosis

1-2
- D-dimer; if high: USS/CTPA; if low, rule out

3+
- USS affected limb for DVT/CTPA for PE

250
Q

DVT prophylaxis

A

Daily subcut LMWH low dose

Ted stockings

251
Q

Tx of DVT/PE

A

High dose LMWH
+ warfarin/DOACs
LMWH stopped when INR 2-3

Tx is for 3 months minimum
- recurrent VTEs need lifelong tx

252
Q

Why should you continue LMWH when warfarin is commenced post-DVT/PE?

A

Warfarin also affects protein C/S thus leads to a procoagulant state in the first few days before its anticoagulant effect (2, 7, 9, 10 inhibitor)

253
Q

How does heparin work?

A

Potentiates antithrombin III

- inactivates thrombin and f 9, 10 and 11

254
Q

Heparin side effects and antidote

A

Bleeding
Heparin induced thrombocytopenia
Osteoporosis with long-term use

Antidote: protamine sulphate

255
Q

How does warfarin work?

A

Inhibits reductase enzyme needed for active form of vit K to produce f 2, 7, 9, 10 and proteins C, S and Z

256
Q

Target INRs:

a) 1st episode DVT/PE, AF
b) Recurrent DVT/PR, mechanical prosthetic valve

A

a) 2.5

b) 3.5

257
Q

How do you reverse warfarin action?

A

STOP WARFARIN
Slow IV vit K
Prothrombin complex concentrate (octaplex/beriplex over 30 mins)
- if not available, give FFP

258
Q

Which drug reverses dabigatran action?

A

Idracizumab

259
Q

Which drug reverses rivaroxaban and apixaban?

A

Andexanet alfa

- really spenny not common at all

Year 5 Pathology (6 decks)

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