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Haem / Onc 7.5 Flashcards

1
Q

Alpha chains of Hb - how many genes? which chromosome?

A
  • 2 separate alpha-globulin genes

- chr 16

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2
Q

Alpha-thalassaemia: 1/2 absent chains, what blood picture?

A
  • hypochromic, microcytic but often normal Hb
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3
Q

Alpha-thalassaemia: loss of 3 chains, blood picture?

A
  • Hb H disease: hypochromic microcytic anaemia

- splenomegaly

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4
Q

Clinical picture if 4 absent alpha chains in thalassaemia (homozygote)

A

Death in utero: hydrops fetalis

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5
Q

Commonest cell type of cervical cancer?

A

Squamous 80%

adenoca 20%

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6
Q

Most important etiological factors causing cervical cancer?

A

HPV 16, 18, 33

Other RFs:
- smoking, HIV, many partners, high parity, lower socioeconomic status, cop

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7
Q

Mechanism of HPV causing cervical cancer?

A

HPV 16 produces oncogene E6 - inhibits p53

HPV 18 produces oncogene E7 - inhibits RB suppressor gene

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8
Q

What are the preferred opioids in pts with CKD e.g. in palliative care?

A

alfentanil
buprenorphine
fentanyl

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9
Q

Conversion from oral codeine -> oral morphine?

A

Divide by 10

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10
Q

Conversion from oral tramadol -> oral morphine?

A

Divide by 10

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11
Q

Conversion from oral morphine -> oral oxycodone?

A

Divide by 1.5-2

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12
Q

Conversion from 30mg oral morphine -> transdermal fentanyl?

A

12 microgram fentanyl patch

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13
Q

Conversion from 24mg oral morphine -> transdermal buprenorphine?

A

10 microgram buprenorphine patch

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14
Q

Conversion from oral morphine -> subcut morphine?

A

Divide by 2

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15
Q

Conversion from oral morphine -> subcut diamorphine?

A

Divide by 3

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16
Q

Conversion from oral oxycodone -> subcut diamorphine?

A

Divide by 1.5

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17
Q

What is Burkitt’s lymphoma?

What are the 2 main forms?

A

High-grade B cell neoplasm

  1. endemic African form: typically involves maxilla/mandible
  2. sporadic: abdominal e.g. ileo-caecal tumours are commonest, more common in pts with HIV
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18
Q

What gene translocation is associated with Burkitt’s lymphoma?

A

c-myc gene translocation, usually t(8;14)

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19
Q

What are the microscopy findings in Burkitt’s lymphoma?

A

Starry sky appearance: lymphocyte sheets intersperses with macrophages containing dead apoptotic tumour cells

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20
Q

Rx of Burkitt’s lymphoma?

A

Chemotherapy

- tends to produce a rapid response which may cause tumour lysis syndrome

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21
Q

What can be given before chemo for Rx of Burkitt’s lymphoma to reduce risk of tumour lysis syndrome?
How does it work?

A

RASBURICASE
- recombinant version of urate oxidase, an enzyme which catalyses conversion of uric acid to allantoin, which is 5-10x more soluble than uric acid so renal excretion is more effective

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22
Q

Complications of tumour lysis syndrome?

A
  • hypocalcaemia
  • hyperkalaemia
  • hyperuricaemia
  • hyperphosphataemia
  • acute renal failure
    (low calcium, high K, uric acid & phosphate)
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23
Q

What Rx may metastatic bone pain respond to?

A
  • strong opioid analgesia
  • bisphosphonates
  • radiotherapy
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24
Q

What is beta-thalassaemia trait?

What are the features?

A
  • autosomal recessive characterised by mild hypo chromic, microcytic anaemia, usually aSx
  • microcytosis is characteristically disproportionate to the anaemia
  • HbA2 raised >3.5%
    HbA2 = variant of Hb A with 2 delta chains replacing 2 normal beta chains, is found in 1.5-3% of total Hb of healthy adults
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25
Q

What is hereditary angioedema?

A

autosomal dominant condition ass with low plasma levels of the C1-inhibitor protein (C1-INH)

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26
Q

What is the role of C1-INHibitor (low in hereditary angioedema)

A
  • multifunctional serine protease inhibitor - probable mechanism is uncontrolled bradykinin release
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27
Q

Ix in hereditary angioedema?

what is most reliable and used for screening?

A
  • low C1-INH during an attack
  • low C2 & C4, even between attacks
  • LOW C4
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28
Q

Sx of hereditary angioedema?

A
  • attacks may be preceded by painful macular rash
  • painless, non-pruritic swelling of subcut/submucosal tissues
  • may affect upper airways, skin or abdo organs (can present as abdo pain due to visceral oedema)
  • urticaria not usually a feature
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29
Q

Acute Rx of hereditary angioedema?

A
  • IV C1-inhibitor concentrate (FFP if not available)
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30
Q

Prophylaxis of hereditary angioedema?

A

anabolic steroid DANAZOL may help

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31
Q

MoA of cyclophosphamide?

Adverse effects?

A

Akylating agent - causes cross-linking in DNA

  • haemorrhagic cystitis
  • myelosuppression
  • transitional cell carcinoma
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32
Q

MoA of Bleomycin?

Adverse effects?

A

Degrades preformed DNA

- lung fibrosis

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33
Q

MoA of Doxorubicin?

Adverse effects?

A

Stabilises DNA-topoisomerase II complex, inhibits DNA & RNA synthesis
- cardiomyopathy

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34
Q

MoA of Methotrexate?

Adverse effects?

A

Inhibits dihydrofolate reductase & thymidylate synthesis

  • mucositis
  • myelosuppression
  • liver fibrosis
  • lung fibrosis
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35
Q

MoA of 5-FU fluorouracil?

Adverse effects?

A

Pyrimidine analogue inducing cell cycle arrest & apoptosis by blocking thymidylate synthase (works during S phase)

  • myelosuppression
  • mucositis
  • dermatitis
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36
Q

MoA of 6-mercaptopurine?

Adverse effects?

A

Purine analogue that is activated by HGPRTase, decreasing purine synthesis
- myelosuppression

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37
Q

MoA of Cytarabine?

Adverse effects?

A

Pyrimidine antagonist, interferes with DNA synthesis specifically at the S-phase of cell cycle & inhibits DNA polymerase

  • myelosuppression
  • ataxia
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38
Q

MoA of Vincristine & Vinblastine?

Adverse effects?

A

Inhibits formation of microtubules
Vincristine: reverisble peripheral neuropathy, paralytic ileus
Vinblastine: myelosuppression

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39
Q

MoA of Docetaxel?

Adverse effects?

A

Prevents microtubule depolymerisation & disassembly, decreasing free tubulin
- neutropenia

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40
Q

MoA of Cisplatin?

Adverse effects?

A

Causes Cross-linking in DNA

  • ototoxicity
  • peripheral neuropathy
  • hypomagnesaemia
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41
Q

MoA of Hydroxyurea/Hydroxycarbamide?

Adverse effects?

A

Inhibits ribonucleotide reductase, decreasing DNA synthesis

- myelosuppression

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42
Q

General RFs for VTE?

A
  • increased risk with advancing age
  • obesity
  • pregnancy esp puerperium
  • FHx VTE
  • immobility
  • hospitalisation
  • anaesthesia
  • central venous catheter: femoral&raquo_space; subclavian
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43
Q

Underlying conditions which predispose to VTE?

A
  • malignancy
  • thrombophilia e.g. activated protein C resistance, protein C&S deficiency
  • heart failure
  • antiphospholipid syndrome
  • Behcet’s syndrome
  • polycythaemia
  • nephrotic syndrome
  • sickle cell disease
  • paroxysmal nocturnal haemoglobinuria
  • hyperviscosity syndrome
  • homocystinuria
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44
Q

Medication RFs for VTE?

A
  • combined OCP 3rd gen > 2nd
  • HRT: VTE risk higher in women taking oestrogen + progestogen preparations vs those taking oestrogen only preparations
  • Raloxifene & Tamoxifen
  • antipsychotics esp Olanzapine
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45
Q

Pathophysiology of VTE in pregnancy?

A

Hyper coagulable state, majority occur in last trimester

  • increase in factors VII, VIII, X & fibrinogen, decrease in protein S
  • uterus presses on IVC causing venous stasis in legs
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46
Q

Rx of VTE in pregnancy?

A
  • warfarin contra-indicated

- SC LMWH preferred to IV heparin (less bleeding & thrombocytopenia)

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47
Q

Pulmonary causes of eosinophilia?

A
  • asthma
  • ABPA
  • Churg-Strauss
  • Loffler’s syndrome
  • topical pulmonary eosinophilia
  • eosinophilis pneumonia
  • hypereosinophilic syndrome
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48
Q

Infective causes of VTE?

A
  • schistosomiasis
  • nematodes: Toxocara, Ascaris, Strongyloides
  • cestodes: Echinococcus
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49
Q

Causes of eosinophilia (except for pulmonary & infective)?

A
  • drugs: sulfasalazine, nitrofurantoin
  • psoriasis/eczema
  • eosinophilic leukaemia (v rare)
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50
Q

What is the Philadelphia chromosome translocation?

A

t(9;22)

>95% of pts with CML

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51
Q

t(9;22) translocation

  • which malignancy?
  • what is the result?
A
  • CML >95%

- if present in ALL, it is a poor prognostic indicator

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52
Q

What does the t(9;22) translocation lead to?

A
  • part of the Abelson porto-oncogene is moved to the BCR gene on chromosome 22
  • > BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
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53
Q

PML & RAR-alpha gene fusion leads to which translocation?

A

t(15;17)

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54
Q

t(15;17) is seen in which malignancy?

A

APML (M3)

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55
Q

Acute promyelocytic leukaemia (M3) is ass with which translocation?

A

t(15;17)

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56
Q

t(8;14) translocation is ass with which malignancy?

A

Burkitt’s lymphoma

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57
Q

Which translocation leads to MYC oncogene translocating to an immunoglobulin gene?

A

t(8;14)

Burkitt’s

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58
Q

t(11;14) is ass with which malignancy?

A

Mantle cell lymphoma

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59
Q

Which translocation leads to deregulation of the cyclin D1 (BCL-1) gene?

A

t(11;14)

Mantle cell lymphoma

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60
Q

What translocation is ass with Mantle cell lymphoma?

A

t(11;14)

- deregulation of t he cynic D1 (BCL-1) gene

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61
Q

The gene encoding beta-thalassaemia major is on which chromosome?

A

chr 11

- absence of beta-chains

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62
Q

Features of beta-thalassaemia major:

  • how does it present?
  • what sort of anaemia?
  • what happens to HbA, HbA2, HbF?
A
  • presents in 1st yr of life with failure to thrive & hepatosplenomegaly
  • microcytic anaemia
  • HbA Absent
  • HbA2 & HbF raised
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63
Q

Rx of beta-thalassaemia major?

A
  • repeated transfusion -> Iron overload

- SC infusion of Desferrioxamine

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64
Q

On which chromosome are the 2 separate alpha-globulin genes located on?

A

each chr 16

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65
Q

What is Hb H?

When is it found?

A

= 4 beta chains

- found in severe alpha thalassaemia (loss of 3/4 chains)

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66
Q

What malignancy is ass with HTLV-1 infection?

A

adult T cell leukaemia/lymphoma

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67
Q

What malignancy is ass with HIV-1 infection?

A

high grade B cell lymphoma

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68
Q

What malignancy is ass with H pylori infection?

A

gastric lymphoma (MALT)

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69
Q

What malignancy is ass with malaria infection?

A

Burkitt’s lymphoma

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70
Q

What is antithrombin III deficiency?

A
  • autosomal dominant inherited cause of thrombophilia
  • antithrombin III inhibits several clotting factors inc: thrombin, factor IX & X; mediating the effects of heparin
  • therefore deficiency is a heterogeneous group of disorders, leading to inc in these clotting factors
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71
Q

Features of antithrombin III deficiency?

A
  • recurrent venous thromboses

- arterial thromboses do occur but are uncommon

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72
Q

Rx of antithrombin III deficiency:

  • if VTE?
  • during pregnancy?
  • during surgery/childbirth etc?
A
  • VTE -> lifelong warfarin
  • pregnancy -> heparinisation
  • antithrombin III concentrates durign surgery, childbirth etc
  • N.b. pts with antithrombin III deficiency have a degree of resistance to heparin, so anti-Xa levels should be monitored carefully to ensure adequate anticoagulation
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73
Q

Commonest inherited thrombophilia?

A

Factor V Leiden (heterozygous) 5%. VTE RR 4

(prothrombin gene mutation 1.5% RR3
protein C deficiency 0.3% RR 10
protein S deficiency 0.1% RR 5-10
antithrombin III deficiency 0.03 RR 10-20)

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74
Q

c-myc gene translocation is ass with which malignancy?

A

Burkitt’s lymphoma

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75
Q

What is the commonest cause of antithrombin III deficiency?

A

CKD (antithrombin III = particularly small protein easily lost through the nephron in CKD)

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76
Q

What electrolyte disturbance does cisplatin cause?

A

hypomagnesaemia

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77
Q

What is polycythaemia vera?

when does it peak?

A
  • myeloproliferative disorder caused by clonal proliferation of a marrow stem cell -> increase in red cell volume, often accompanied by overproduction of neutrophils & platelets as well
  • incidence peaks in 6th decade
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78
Q

Features of polycythaemia vera?

A
  • hyperviscosity
  • pruritus, typically after a hot bath
  • splenomegaly
  • haemorrhage (2ry to abnormal platelet function)
  • plethoric appearance
  • hypertension in a 1/3 of pts
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79
Q

What blood tests should be done when polycythaemia vera suspected?

A
  • FBC, blood film: raised haematocrit, and neuts, basophils & platelets raised in half of pts
  • serum ferritin
  • U&Es, LFTs
  • JAK2 mutation

(also PRV can show a low ESR and raised leukocyte ALP)

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80
Q

When suspecting polycythaemia vera but JAK2 mutation negative and no obvious 2ry cause, what tests should be done?

A
  • red cell mass
  • arterial oxygen saturation
  • abdo ultrasound
  • serum erythropoietin level
  • BM aspirate & trephine
  • cytogenetic analysis
  • erythroid burst-forming unit (BFU-E) culture
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81
Q

What are the Dx criteria for polycthaemia vera (if JAK2 +ve)?

A

Both need to be positive:
A1: high haematocrit (>0.52 men, >0.48 women) OR raised red cell mass (>25% above predicted)
A2: JAK2 mutation

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82
Q

What are the Dx criteria for polycthaemia vera (if JAK2 -ve)

A

Dx requires A1+2+3+ 1 A or 2B criteria

A1 raised red cell mass>25% or raised haematocrit >0.6M >0.56F
A2 absence of JAK2 mutation
A3 no cause of 2ry erythrocytosis
A4 palpable splenomegaly
A5 presence of an acquired genetic abnormality (exc BCR-ABL) in the haemtopoietic cells

B1 thrombocytosis plts>450
B2 neutrophil leukocytosis of neuts>10 in non-smokers, >12.5 in smokers
B3 radiological evidence of splenomegaly
B4 endogenous erythroid colonies or low serum erythropoietin

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83
Q

What are the different blood transfusion complications?

A
  • immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis
  • infective
  • TRALI: transfusion-related acute lung injury
  • fluid overload
  • other: hyperkalaemia, iron overload, clotting
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84
Q

Why do non-haemolytic febrile reactions to blood transfusion occur?

A
  • due to white blood cell HLA antibodies

- often the result of sensitisation by previous pregnancies or transfusions

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85
Q

Why do acute haemolytic transfusion reactions occur?
Rx?
complications?

A
  • ABO mismatch -> massive intravascular haemolysis
  • Sx start within minutes, inc fever, abdo pain, chest pain, agitation, hypotension

Rx inc stop transfusion, generous IV fluid resuscitation, inform the lab

Complications inc DIC & renal failure

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86
Q

Allergic/anaphylaxis reaction to blood transfusion

  • what happens & why?
  • Rx?
A
  • hypersensitivity reactions to components within the transfusion
  • Sx start within minutes and range insecurity e.g. urticaria - anaphylaxis
  • urticaria - stop transfusion, give antihistamine, can restart transfusion when Sx resolve
  • if severe then Rx urgently by stopping transfusion, give IM adrenaline & supportive Rx, e.g. consider antihistamine, corticosteroids & bronchodilators
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87
Q

What is the transmission risk of vCJD during blood transfusion?

A
  • v small but present absolute risk
  • all donations undergo leucodepletion to reduce any vCJD infectivity present
  • plasma derivatives have been fractionated from imported plasma
  • blood transfusion recipients cannot donate blood
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88
Q

What is acute intermittent porphyria?

A

rare autosomal dominant condition caused by a defect in PORPHOBILINOGEN DEAMINASE (enzyme involved in haem biosynthesis) -> toxic accumulation of delta aminolaevulinic acid & porphobilinogen
- classically presents with abdo & neuropsych Sx in 20-40yrs, more common in females 5:1

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89
Q

Features of acute intermittent porphyria?

A

abdo: pain & vomiting
neuro: motor neuropathy
psych: e.g. depression
cardiac: HTN & tachycardia common

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90
Q

Dx of acute intermittent porphyria?

A
  • classically urine turns deep red on standing
  • raised urinary porphobilinogen (between attacks, more during)
  • assay of red cells for porphobilinogen deaminase
  • raised serum levels of delta aminolaevulinic acid & porphobilinogen
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91
Q

Absorption of vitamin B12?

A
  • binds with intrinsic factor (secreted from parietal cells)
  • active absorbed in terminal ileum
  • small amount passively absorbed without being bound to intrinsic factor
  • mainly used in body for red blood cell development & maintenance of nervous system (myelin)
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92
Q

Causes of vitamin B12 deficiency?

A
  • poor diet
  • pernicious anaemia
  • post-gastrectomy
  • terminal ileum disorders e.g. Crohn’s, blind-loop
  • metformin (rare)
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93
Q

Features of vitamin B12 deficiency?

A
  • macrocytic anaemia
  • sore tongue & mouth
  • neuro Sx e.g. ataxia
  • neuropsych Sx e.g. mood disturbances
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94
Q

Rx of vitamin B12 deficiency?

A
  • 1mg IM hydroxocobalamin 3x/wk for 2 wks then 1x/3months if no neuro involvement
  • is also deficient in folic acid it’s important to treat B12 first (to avoid precipitating subacute combined degeneration of the spinal cord)
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95
Q

What is Wiskott-Aldrich syndrome?

A

1ry immunodeficiency due to combined B & T cell dysfunction

  • X-linked recessive
  • mutation in WASP gene
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96
Q

Features of Wiskott-Aldrich syndrome?

A
  • recurrent bacterial infections e.g. chest
  • eczema
  • thrombocytopenia
  • low IgM levels
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97
Q

What leads to a raised leucocyte ALP?

A
  • leukaemoid reactions (left-shift of immature WBCs)
  • infections
  • myelofibrosis
  • polycythaemia vera
  • steroids, Cushing’s
  • pregnancy, OCP
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98
Q

What leads to a low leucocyte ALP?

A
  • CML
  • pernicious anaemia
  • infectious mononucleosis
  • paroxysmal nocturnal haemoglobinuria
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99
Q

RFs for development of nausea & vomiting after chemo (although common)?

A
  • age<50
  • anxiety
  • concurrent use of opioids
  • type of chemo used
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100
Q

Rx for chemo-related nausea & vomiting?

A

Low-risk: metoclopramide

If high-risk: 5HT3 receptor antagonists e.g. ondansetron are effective, esp if combined with dexamethasone

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101
Q

MoA of Aprepitant

A

Antiemetic which blocks the neurokinin 1 receptor - a substance P antagonist
- licensed for chemo-induced nausea & vomiting & for prevention of post-op nausea & vomiting

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102
Q

Infective causes of generalised lymphadenopathy?

A
  • infectious mono
  • HIV inc seroconversion
  • eczema with 2ry infection
  • rubella
  • toxoplasmosis
  • CMV
  • TB
  • roseola infantum
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103
Q

Neoplastic causes of generalised lymphadenopathy?

A
  • leukaemia, lymphoma
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104
Q

Non-infective/neoplastic causes of generalised lymphadenopathy?

A

autoimmune - SLE, RA
graft vs host disease
sarcoid
- drugs: phenytoin, also allopurinol, isoniazid

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105
Q

What is antiphospholipid syndrome?

A

Acquired disorder of predisposition to venous & arterial thromboses, recurrent fetal loss & thrombocytopenia
- can be 1ry or 2ry e.g. SLE

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106
Q

Complications of antiphospholipid syndrome in pregnancy?

A
  • recurrent miscarriage (aPL is present in 15% of women with recurrent miscarriage)
  • IUGR
  • pre-eclampsia
  • placental abruption
  • pre-term delivery
  • VTE
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107
Q

Rx of antiphospholipid syndrome in pregnancy?

A
  • Start Aspirin 75mg when pregnancy confirmed (urine)
  • Start LMWH after fetal heart on US -discontinue at 34wks
  • increases live birth rate 7X
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108
Q

5 types of sickle cell crises?

A
  • thrombotic, painful
  • sequestration
  • acute chest
  • aplastic
  • haemolytic
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109
Q

Cause of thrombotic sickle cell crisis?

A
  • precipitated by infection, dehydration, deoxygenation
  • painful/vaso-occlusive crises
  • infarcts occur in various organs inc bones (e.g. AVN hip, hand-foot syndrome in children, lungs, spleen, brain)
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110
Q

What happens in a sequestration sickle cell crisis?

A
  • sickling within organs e.g. spleen/lungs causes pooling of blood with worsening of anaemia
  • sickling causes spleen to enlarge causing also pain
  • more common in early childhood as repeated sequestration & infarction of spleen gradually leads to an auto-splenectomy
  • may lead to severe anaemia, marked pallor & cardiovascular collapse due to loss of effective circulating volume
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111
Q

What happens in a acute chest sickle cell crisis?

A
  • dyspnoea, chest pain, pulmonary infiltrates, low PO2
  • commonest cause of death after childhood
  • ‘fever +/- resp Sx, + new pulmonary infiltrates on CXR’
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112
Q

What happens in a aplastic sickle cell crisis?

A
  • parvovirus infection

- sudden fall in Hb

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113
Q

What happens in a haemolytic sickle cell crisis?

A
  • fall in Hb due to an increased rate of homeless (rare)
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114
Q

Features of SVC obstruction?

A
  • dyspnoea (commonest Sx)
  • swelling of face, neck, arms, sometimes conjunctival & periorbital oedema
  • headache: often worse in mornings
  • visual disturbance
  • pulseless jugular venous distension
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115
Q

Causes of SVC obstruction?

A

common malignancies inc: NSCLC, lymphoma
other: metastatic seminoma, Kaposi’s sarcoma, breast ca
Also: aortic aneurysm, mediastinal fibrosis, goitre, SVC thrombosis

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116
Q

Rx of SVC obstruction?

A

General: Dexamethason, balloon venoplasty, stenting
Small cell: chemo + RT
Non-small: RT

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117
Q

What is Hodgkin’s lymphoma?

Age distribution?

A

Malignant proliferation of lymphocytes characterised by the presence of Reed-Sternberg cell
- Bimodal in 3rd & 7th decades

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118
Q

What Sx imply poor prognosis in Hodgkin’s lymphoma?

A

B Sx

  • weight loss >10% in 6months
  • fever >38C
  • night sweats
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119
Q

Histological type of Hodgkin’s lymphoma - commonest? What cells are ass?

A

Nodular sclerosing 70%

  • ass with lacunar cells
  • good prognosis, more common in women
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120
Q

Histological type of Hodgkin’s lymphoma - 2nd commonest? What cells are ass?

A

Mixed cellularity 20%

  • ass with large number of Reed-Sternberg cells
  • good prognosis
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121
Q

Histological type of Hodgkin’s lymphoma - best prognosis?

A

Lymphocyte predominant 5%

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122
Q

Histological type of Hodgkin’s lymphoma - worst prognosis?

A

Lymphocyte depleted (rare)

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123
Q

Factors other than B Sx ass with poor prognosis in Hodgkin’s lymphoma?

A 
age>45
stage IV disease
Hb <10.5
lymphocyte <600 or <8%
male
albumin <40
WCC >15,000
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124
Q

What is idiopathic thrombocytopenia purpura?

A

Immune-mediated reduction in platelet count with Ab against the glycoprotein IIb-IIIa or Ib complex

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125
Q

Ix in ITP?
what is on BM aspirate?
why should it be done before starting Rx?

A

Antiplatelet autoAb (usually IgG)

  • megakaryocytes in the marrow
  • do BM aspirate before steroids to rule out leukaemia
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126
Q

Rx of ITP?

A
  • Oral Prednisolone (80% respond)
  • Splenectomy if plts<30 after 3months steroids
  • IV immunoglobulins
  • immunosuppressive drugs e.g. cyclophosphamide
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127
Q

Features of a 2-level DVT Wells score?

A

Active cancer with Rx within 6m/palliative 1
Paralysis, paresis/recent plaster immobilisation of lower extremities 1
Recently bedridden for 3days+ or major surgery within 12wks 1
Localised tenderness along distribution of deep venous system 1
Entire leg swollen 1
Calf swelling at least 3cm >aSx side 1
Pitting oedema confined to Sx leg 1
Collateral superficial veins (non-varicose) 1
Prev doc DVT 1

Alternatuve Dx at least as likely as DVT -2

DVT likely if 2+

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128
Q

What to do if DVT likely i.e. 2level Wells score 2+?

A
  • US proximal leg veeins within 4h (if negative do a D-dimer)
  • do D-dimer if can’t have US legs within 4h, and give LMWH whilst waiting (which should be done within 24h)
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129
Q

What to do if DVT unlikely i.e. 2level Wells score <2?

A
  • D-dimer
  • if +ve then proximal leg vein US within 4h
  • if can’t be done then give LMWH whilst waiting
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130
Q

Rx of DVT?

A

LMWH/Fondaparinux at Dx - continue at least 5 days or more until INR is >2 for at least 24h
- warfarin within 24h, cont at least 3months - extend if unprovoked

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131
Q

Rx of DVT in active cancer?

A

LMWH 6 months

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132
Q

What Ix do people who have an unprovoked DVT/PE need?

What if they are aged >40?

A
  • Hx & full Ex
  • CXR
  • urinalysis
  • bloods to inc FBC, LFTs, calcium
  • CT abdo-pelvis
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133
Q

When to consider thrombophilia testing?

A
  • consider testing for antiphospholipid Abs if unprovoked DVT/PE?
  • consider testing hereditary thrombophilia if someone has an unprovoked DVT/PE, and they have a 1st degree relative who has had a DVT/PE
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134
Q

What are the different types of tumour markers?

A
  • mAbs against carbohydrate/glycoprotein tumour Ags
  • tumour Ags
  • enzymes e.g. ALP, neurone specific enolase
  • hormones e.g. calcitonin, ADH
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135
Q

What malignancies are AFP ass with?

A

hepaticellular carcinoma

teratoma

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136
Q

What malignancies are S-100 ass with?

A

melanoma

schwannomas

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137
Q

What malignancies are bombesin ass with?

A

SCLC
gastric ca
neuroblastoma

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138
Q

What is multiple myeloma?

A

Neoplasm of bone marrow plasma cells

peak incidence age 60-70

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139
Q

Clinical features of myeloma?

A
  • bone disease: bone pain, osteoporosis + path fractures (typically vertebral), osteolytic lesions
  • lethargy
  • infection
  • hypercalcaemia
  • renal failure
  • others: amyloid e.g. macroglossia, carpal tunnel, neuropathy, hyperviscosity, high total protein
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140
Q

Ix for myeloma:

  • what is in serum & urine?
  • what is in bone marrow?
  • what is done to look at bone?
  • what may be seen on X-ray?
A
  • monoclonal proteins IgG/IgA, Bence-Jones in urine
  • increased plasma cells in bone marrow
  • historically a skeletal survey, but now whole-body MRI
  • Xray: ‘rain-drop skull’ (pepper pot is different)
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141
Q

What are the Dx criteria for multiple myeloma?
- requires 1 major + 1m
- or 3minor
in someone with signs/Sx

A

Major:

  1. plasmacytoma (Bx)
  2. 30% plasma cells in BM
  3. elevated M protein levels in blood/urine

Minor:

  1. 10-30% plasma cells in a BM sample
  2. minor elevations in M protein in blood/urine
  3. osteolytic lesions (on imaging)
  4. low levels of Abs (not produced by cancer cells) in blood
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142
Q

What is the 1ry factor that leads to hypercalcaemia in myeloma?
what are other much less contributing factors?

A

Increased osteoclastic bone resorption caused by local cytokines released by myeloma cells e.g. IL-1, TNF

Others inc: impaired renal function, increased renal tubular Ca reabsorption, elevated PTH-rP levels

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143
Q

Palliative care prescribing: agitation & confusion

  • 1st line drug?
  • other options?
  • palliative end-stage?
A

Haloperidol
others: chlorpromazine, levomepromazine
Palliative: midazolam

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144
Q

Genetics of haemophilia?

A

X-linked recessive disorder of coagulation

  • upto 30% have no FHx
  • A is deficiency of factor VIII
  • B is lack of factor IX
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145
Q

Features of haemophilia?

A
  • haemoarthroses, haematomas

- prolonged bleeding after surgery/trauma

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146
Q

Blood tests in haemophilia?

A 
Prolonged APTT
(normal bleeding, thrombin &amp; PT time)
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147
Q

What is the commonest tumour of the anterior mediastinum?

A

Thymomas

- usually detected between 6th & 7th decades

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148
Q

Associations of thymomas?

What are the causes of death?

A
  • myasthenia gravis 30-40%
  • red cell aplasia
  • dermatomyositis
  • also: SLE, SIADH
  • airway compression, cardiac tamponade
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149
Q

What is ITP: immune thrombocytopenia?

A

Immune-mediated reduction in platelet count

- Abs directed against the glycoprotein IIb/IIIa or Ib-V-IX complex

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150
Q

Acute ITP:
who is it more commonly seen in?
when may it occur?
course?

A

Children, M=F
May follow infection/vaccination
- usually self limiting course over 1-2wks

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151
Q

Chronic ITP:
who is it more commonly seen in?
course?

A
  • young/middle-aged women

- relapsing-remitting course

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152
Q

What is Evan’s syndrome? (think ITP)

A

ITP in ass with autoimmune haemolytic anaemia

153
Q

Features of spinal cord compression?

A
  • Back pain, may be worse lying down & coughing (earliest & commonest Sx)
  • LL weakness
  • Sensory changes: loss & numbness
  • Neuro signs depending on level of the lesion (Above L1 = UMN legs with sensory level, below L1 = LMN signs in legs with perianal numbness with tendon reflexes increased below the level and absent at the level)
154
Q

Rx of spinal cord compression?

A

High-dose oral dexamethasone
Urgent MRI
Urgent onc assessment for consideration of RT/surgery

155
Q

Spinal cord compression - who does it affect?

A

Onc emergency, 5% of cancer pts
Extradural compression e.g. due to vertebral body mets is commonest
Also lung, breast, prostate common

156
Q

PET scan:

  • what is the radio tracer?
  • what does it demonstrate?
  • what are its uses?
A
  • FDG = fluorodeoxyglucose
  • glucose uptake shows 3d image of metabolic activity, which is combined with e.g. CT
  • helps evaluate 1ry & possible metastatic disease
  • cardiac PET not used mainstream currently
157
Q

AIHA: autoimmune haemolytic anaemia

  • what is it characterised by?
  • causes?
A

Positive DAT: direct antiglobulin Coombs test

  • most commonly idiopathic
  • but also infection, drugs, lymphoproliferative etc
158
Q

What is Warm AIHA?
where does intent to occur?
Rx?

A

IgG causes haemolysis best at body temp

  • Extravascular sites e.g. spleen
  • Steroids, immunosuppression, splenectomy
159
Q

Causes of warm AIHA?

A

Autoimmune: SLE
Neoplasia e.g. lymphoma, CLL
Drugs e.g. Methyldopa

160
Q

What is Cold AIHA?
where does intent to occur?
Rx?

A

IgM causes haemolysis best at 4 deg C - features may inc Sx of Raynaud’s 7 acrocyanosis

  • mediated by complement and more commonly intravascular
  • pts respond less well to steroids
161
Q

Causes of Cold AIHA?

A

Neoplasia e.g. lymphoma

Infection e.g. mycoplasma, EBV

162
Q

What is Meig’s syndrome?

A

Ovarian fibroma ass with pleural effusion & ascites

163
Q

Causes of a megaloblastic macrocytic anaemia?

A

B12 deficiency

folate deficiency

164
Q

Causes of a normoblastic macrocytic anaemia?

A
  • etoh, liver disease
  • reticulocytosis
  • myelodysplasia
  • pregnancy
  • hypothyroidism
  • drugs e.g. cytotoxic
165
Q

When does acute myeloid leukaemia occur?

A

1ry disease or
2ry transformation of a myeloproliferative disorder
- more common over age 45

166
Q

Features of AML?

A 
(BM failure)
Anaemia: pallor, lethargy, weakness
Neutropenia: WCC can be v high but functioning neutrophils low, leading to frequent infections etc
Thrombocytopenia: bleeding
Also: bone pain, splenomegaly
167
Q

3 poor prognostic features of AML?

A

> 60yrs
20% blasts after 1st course of chemo
cytogenetics: deletions of chromosome 5 or 7

168
Q

Acute promyelocytic leukaemia M3

  • what translocation is it associated with & what does it lead to?
  • when does it present?
  • what is seen with myeloperoxidase stain?
  • what is often seen on bloods at presentation?
A
  • t(15;17) -> fusion of PML & RAR-alpha genes
  • younger, average age 25yrs
  • AUER RODS
    • DIC or thrombocytopenia
  • good prognosis
169
Q

What is the FAB classification of AML?

M0 - M7

A 
M0 undifferentiated
M1 without maturation
M2 with granulocytic maturation
M3 ACUTE PROMYELOCYTIC
M4 granulocytic &amp; monocytic maturation
M5 monocytic
M6 erytholeukaemia
M7 megakaryoblastic
170
Q

What happens to Hb after intravascular haemolysis?

A

Intravascular haemolysis -> free Hb released -> binds to haptoglobin -> haptoglobin becomes saturated

  • > so other free Hb binds to albumin -> methaemalbumin (detected by Schumm’s test)
  • > free Hb excreted in urine as Hburia & haemosiderinuria
171
Q

Causes of intravascular haemolysis?

A
  • red cell fragmentation: heart valves, TTP, DIC, HUS
  • paroxysmal nocturnal haemoglobinuria
  • G6PD deficiency
  • Cold AIHA
172
Q

Causes of extravascular haemolysis?

A
  • Hbopathies: sickle cell, thalassaemia
  • Hereditary spherocytosis
  • Haemolytic disease of newborn
  • Hot (warm) AIHA
173
Q

What is the commonest inherited thrombophilia in Europeans?

A

Factor V Leiden

174
Q

What does factor V leiden disease effective mean?

A

= Activated protein C resistance

175
Q

What is the genetics of factor V leiden?

A

Gain of function mutation in the factor V leiden protein -> mis-sense mutation
-> activated factor V (a clotting factor) is inactivated 10X more slowly by activated protein C than normal
= activated protein c resistance

  • heterozygotes 5% 4-5x inc risk of venous thrombosis
  • homozygotes 10x inc risk but prevalence 0.05%
176
Q

What is the most useful marker of prognosis in myeloma?

A

B2 microglobulin

177
Q

What is the international prognostic index stages for myeloma?

A

stage I 62median months survival:
B2 micro globulin <3.5
Albumin >35

stage II 45 months: not I/III

Stage III 28months: B2 micro globulin >5.5

178
Q

What is the tumour marker most associated with primary peritoneal cancer

A

CA-125

179
Q

What is thrombocytosis?

What are the causes?

A

Abnormally high platelets, usually >400

  1. Reactive: acute phase reactant
  2. Essential, or as part of another myeloproliferative disorder e.g. CML, PRV
  3. Malignancy
  4. Hyposplenism
180
Q

What is essential thrombocytosis?

A

Where megakaryocytic proliferation results in an overproduction of platelets
- myeloproliferative disorder, overlapping with CML, PRV, myelofibrosis

181
Q

Features of essential thrombocytosis?

A

Platelets >600
JAK2 mutation +ve in 50%
Both venous/arterial thrombosis & haemorrhage can be seen
Characteristic Sx = burning sensation in hands

182
Q

Rx of essential thrombocytosis:
what is widely used?
what can be used in younger pts?
what may be used to reduce thrombotic risk?

A

HYDROXYUREA/HYDROXYCARBAMIDE widely used to reduce platelet count
INTERFERON-alpha in younger
Low-dose aspirin

183
Q 
66y.o. woman referred by GP with anaemia, feeling gen unwell for past 3 wks.
Bloods show:
Hb 8.7
MCV 87
Plt 198
WBC 5.3
Further tests:
Reticulocytes 5.2%
DAT positive, IgG only
Film - spherocytes, reticulocytes
A

Non-Hodgkin’s lymphoma

  • warm haemolytic anaemia
  • ( no suggestion of autoimmune disease, CLL or methyldopa)
184
Q

What is neutropenic sepsis defined as?
When does it occur?
What are the commonest pathogens?

A

Neuts < 0.5 in someone with anticancer Rx +

  • temp >38C
  • or other signs/Sx consistent with clin significant sepsis

Most commonly occurs 7-14days after chemo

Gram-positive organisms, most frequently staph epidermidis

185
Q

Prophylaxis of neutropenic sepsis?

A

a FLUOROQUINOLONE, if anticipated

186
Q

Rx of neutropenic sepsis?

A

Abx immediately if suspected (don’t wait for FBC)

  • Tazocin +/- vancomycin
  • if still febrile/unwell after 48h then alternative Abx e.g. Meropenem +/- vancomycin
  • if not responding after 4-6days, consider Ix for fungal infections e.g. HRCT -> start AMPHOTERICIN B empirically
  • may be a role for G-CSF in selected pts
187
Q

What is MGUS: Monoclonal gammopathy of undetermined significance?
What are the features?

A

= benign paraproteinaemia & monoclonal gammopathy

  • usually aSx
  • no bone pain/increased risk of infections
  • 10-30% have a demyelinating neuropathy
188
Q

Differentiating features of MGUS from myeloma?

A
  • normal immune function
  • normal beta-2 micro globulin levels
  • lower level of paraproteinaemia than myeloma (<30 IgG, <20 IgA)
  • stable level of paraproteinaemia
  • no clinical features of myeloma e.g. lytic lesions on X-ray, renal disease etc
189
Q

What are the features of Hodgkin’s lymphoma?

A
  • lymphadenopathy 75% - painless, non-tender, asymmetrical
  • systemic 25% - weight loss, pruritus, night sweats, fever (Pel-Ebstein)
  • etoh pain in HL
  • normocytic anaemia, eosinophilia
  • raised LDH
  • patchy BM infiltration
190
Q

What is the Ann-Arbor staging of Hodgkin’s lymphoma?

How to subdivide each stage to A/B?

A

I single LN
II 2+ LNs/regions on same side of diaphragm
III nodes on both sides of diaphragm
IV spread beyond LNs

A = no systemic Sx except pruritus
B = weight loss>10% in last 6m, fever>38C, night sweats (poor prognosis)
191
Q

What is ALL?

A

Malignancy of lymphoid progenitor cells affecting B/T cell lineage -> arresting of lymphoid cell maturation & proliferation of immature lymphoblast cells -> BM & tissue infiltration

  • commonest childhood cancer, peaks age 2-5yrs
  • 80% of childhood leukaemia
192
Q

What are the good prognostic indicators in ALL?

A
  • FAB L1 type
  • common ALL
  • pre-B phenotype, precursol B-ALL
  • low initial WBC
  • del(9p)
  • trisomy 4, 10, 17
  • t(12;21) & t(1;19) translocation
193
Q

What are the poor prognostic indicators in ALL?

A
  • FAB L3 type
  • T/B cell surface markers
  • Philadelphia translocation t(9;22)
  • age<2 or >10yrs
  • male sex
  • CNS involvement
  • high initial WBC >100
  • non-Caucasian
  • hyPOdiploid
194
Q

What is the management of aplastic anaemia?

A

Supportive:

  • blood products
  • prevention & Rx of infection

ATG & ALG (anti-thymocyte globulin & anti-lymphocyte globulin)

Stem cell Tx
- allogeneic Tx have 80% success rate

195
Q

ATG & ALG (anti-thymocyte globulin & anti-lymphocyte globulin) for aplastic anaemia Rx:

  • how is it prepared?
  • what else if given with it?
A
  • inject human lymphocytes in animals
  • highly allergenic, may cause serum sickness with fever, rash, arthralgia etc -> STEROID cover given
  • other immunosuppressants may also be given e.g. ciclosporin
196
Q

Conditions ass with Target cells?

A
  • sickle cell, thalassaemia
  • IDA
  • hyposplenism
  • liver disease
197
Q

Conditions ass with Tear-drop poikilocytes?

A

myelofibrosis

198
Q

Conditions ass with spherocytes (round, lack of central pallor)?

A
  • hereditary spherocytosis

- AIHA

199
Q

Conditions ass with basophilic stippling?

A
  • thalassaemia
  • sideroblastic anaemia (BM produces ringed sideroblasts instead of healthy erythrocytes)
  • myelodysplasia
  • lead poisoning
200
Q

Conditions ass with Howell-Jolly bodies?

A

hyposplenism

201
Q

Conditions ass with Heinz bodies?

A
  • G6PD deficiency

- Alpha-thalassaemia

202
Q

Conditions ass with schistocytes (helmet cells)?

A
  • intravascular haemolysis
  • mechanical heart valve
  • DIC
203
Q

Conditions ass with pencil poikilocytes?

A

iron-deficiency anaemia

204
Q

Conditions ass with Burr cells (echinocytes)?

A
  • uraemia

- pyruvate kinase deficiency

205
Q

Conditions ass with acanthocytes?

A

abetalipoproteinaemia

206
Q

Conditions ass with hypersegmented neutrophils?

A

megaloblastic anaemia

207
Q

Blood film in hyposplenism?

A
  • target cells
  • Howell-Jolly bodies
  • Pappenheimer bodies
  • siderotic granules
  • acanthocytes
208
Q

Blood film in IDA?

A
  • target cells
  • pencil poikilocytes
  • dimorphic film of mixed microcytic & microcytic cells if combined with B12/folate deficiency
209
Q

What are the 3 indication of blood product that is CMV-negative & irradiated?

A
  • granulocyte transfusions
  • intra-uterine transfusions
  • neonates upto 28days post-expected delivery date
210
Q

What is the 1 indication for CMV negative (but not irradiated) blood product?

A

pregnancy: elective transfusions during pregnancy (not during labour/delivery)

211
Q

What are the 3 indications for irradiated (but not CMV-negative) blood product?

A
  • BM/stem cell Tx
  • immunocompromised e.g. chemo.congenital
  • pts with prev Hodgkin’s disease
212
Q

How is CMV transmitted in blood products?

A
  • via leukocytes
  • as most blood products (except granulocyte transfusions) are now leucocyte-depleted, CMV-negative products are rarely required
213
Q

Why are irradiated blood products sometimes needed?

A
  • To avoid transfusion graft vs host disease, caused by engraftment of viable donor T lymphocytes
214
Q

FFP: fresh frozen plasma (150-220ml):

  • when is it needed?
  • when may it be used prophylactically?
  • what is the universal donor?
A
  • when PT or APTT > 1.5 and clinically significant without major haemorrhage
  • prophylaxis if invasive surgery with risk of significant bleeding
  • universal donor = AB blood (lacks any anti-A or anti-B Abs)
215
Q

What does cryoprecipitate contain?
when is it suited?
when may it be used prophylactically?

A

15-20ml of: conc factor VIIIc, von willebrand factor, fibrinogen, factor XIII & fibronectin, produced by further processing of FFP

  • clinically most commonly used to replace fibrinogen
  • most suited if fibrinogen concentration <1.5 in clinically significant without major haemorrhage
  • e.g. DIC, life failure, low fibrinogen 2ry to massive transfusion, emergency situation for haemophiliacs or von willebrand disease
  • prophylaxis if invasive surgery with risk of significant bleed with fibrinogen <1.0
216
Q

When is PCC: prothrombin complex concentrate used?

A
  • emergency reversal of anticoagulation in severe bleed or head injury with suspected intracerebral haemorrhage
  • prophylaxis in emergency surgery depending on circumstance
217
Q

What is IgG4-related disease?

A
  • raised IgG4 conc in tissue & serum, can be in any organ system of diverse organ manifestations linked by similar histopathological characteristics
  • e.g. Riedel’s thyroiditis, AI pancreatitis, mediastainl/retroperitoneal fibrosis, periaortitis/periarterities/inflammatory aortic aneurysm, Kuttner’s tumour of submandibular glands, Mikulicz syndrome of salivary&lacrimal glands, maybe sjogrens & PBC
218
Q

What is the commonest inherited bleeding disorder?

inheritance?

A

Von Willebrand’s disease

  • majority autosomal dominant
  • characteristically behaves like a platelet disorder i.e. epistaxis & menorrhagia more common (haemarthroses & muscle haematomas rare)
219
Q

What are the 3 types of von Willebrand disease?

A

1: partial reduction in vWF (80%)
2: abnormal form of vWF
3: total lack of vWF (autosomal recessive)

220
Q

What is the role of von WIllebrand factor?

A
  • large glycoprotein forming massive multimers unto 1,000,000 Da in size
  • promotes platelet adhesion to damaged endothelium
  • carrier molecule for factor VIII
221
Q

Ix of von Willebrand disease?

  • what is prolonged
  • what may be reduced
  • when is platelet aggregation defective
A

PROLONGED BLEEDING TIME

  • APTT may be prolonged
  • factor VIII may be mod reduced
  • defective platelet aggregation with ristocetin
222
Q

Rx of von Willebrand disease?

A
  • Transexamic acid for mild bleeding
  • DDAVP: desmopressin raises levels of vWF by inducing vWF release from Weibel-palade bodies in endothelial cells
  • Factor VIII concentrate
223
Q

Man with type 1 von WIllebrand’s disease due to have tooth extracted at dentist next wk - what is most appropriate Rx to reduce risk of bleeding?

A

Desmopressin

224
Q

What is the most common hereditary haemolytic anaemia in people of northern European descent?

A

hereditary spherocytosis

225
Q

What is hereditary spherocytosis?

A

autosomal dominant defect of red blood cell cytoskeleton

  • normal biconcave disc replaced by sphere-shaped RBC
  • leads to reduced RBC survival as it is destroyed by the spleen
226
Q

What is the presentation & features of hereditary spherocytosis?

A
  • failure to thrive, neonatal jaundice
  • gallstones. splenomegaly common
  • aplastic crisis precipitated by parvovirus
  • degree of haemolysis is variable - can be precipitated by infection
  • elevated MCHC
227
Q

How to Dx hereditary spherocytosis?
If Dx equivocal?
If atypical presentation
What was prev recommended Ix?

A
  • FHx, typical clinical features, lab Ix of spherocytes, raised MCHC, raised reticulocytes then additional tests not required
  • If equivocal then do cryohaemolysis test & EMA binding
  • if atypical then electrophoresis analysis of erythrocyte membranes is method of choice
  • used to be osmotic fragility test but it is unreliable
228
Q

Rx of hereditary spherocytosis?

A
  • folate replacement

- splenectomy

229
Q

What are the most common types of transformations seen in patients with polycythaemia vera?

A

Myelofibrosis + AML (5-15% progress to either, risk of acute leukaemia increased with chemo Rx)

230
Q

What is the most significant cause of morbidity & mortality in polycythaemia?

A

thrombosis

231
Q

Rx of polycythaemia vera?

A

Aspirin
Venesection 1st line Rx
Hydroxyurea = slight inc risk of 2ry leukaemia
Phosphorus-32 therapy

232
Q

What is sideroblastic anaemia?

A

Where red cells fail to completely form haem (where biosynthesis takes place partly in mitochondria)

  • > iron deposits in mitochondria that form a ring around the nucleus (ring sideroblast)
  • congenital/acquired
233
Q

What is the congenital cause of sideroblastic anaemia?

What are the acquired causes?

A

Delta-aminolevulinate synthase-2 deficiency

  • myelodysplasia
  • etoh
  • lead
  • anti-TB meds
234
Q

Ix of sideroblastic anaemia ?

A
  • hypochromic microcytic anaemia

- BM: sideroblasts & increased iron stores

235
Q

Rx of sideroblastic anaemia ?

A

supportive, Rx underlying causes

PYRIDOXINE may help

236
Q

Which stain should be applied to a blood film when you suspect sideroblastic anaemia?

A

Perl’s stain - shows ring sideroblasts

237
Q

What is the pathogenesis of TTP: thrombotic thrombocytopenia purpura?

A
  • abnormally large & sticky multimers of vWF cause platelets to clump within vessels
  • deficiency of ADAMTS13 (metalloprotease enzyme) which breaks down large multimers of vWF
  • overlaps with haemolytic uraemia syndrome
238
Q

Features of TTP?

A
  • rare, typically adult females
  • fever
  • fluctuating neuro signs (micro emboli)
  • thrombocytopenia
  • MAHA: microangiopathic haemolytic anaemia
  • renal failure
239
Q

Causes of TTP?

A
  • post-infective e.g. urine, GI
  • pregnancy
  • tumours
  • SLE
  • HIV
  • drugs: ciclosporin, OCP, penicillin, clopidogrel, aciclovir
240
Q

What is the commonest red blood cell enzyme defect? What is the inheritance?

A

G6PD deficiency

  • commoner in Mediterranean & African
  • X-linked recessive (only affects males)
241
Q

What is the pathophysiology of G6PD deficiency?

A

Reduced G6PD -> reduced glutathione -> increased red cell susceptibility to oxidative stress

242
Q

Features of G6PD deficiency?

A
  • neonatal jaundice
  • intravascular haemolysis
  • gallstones comon
  • splenomegaly may be present
  • Heinz bodies on film
243
Q

Dx of G6PD deficiency?

A

G6PD enzyme assay

244
Q

Precipitants of G6PD deficiency?

A 
Broad (fava) bands
Drugs:
- anti-malarial PRIMAQUINE
- Ciprofloxacin
- Sulph drugs - sulphonamides, sulphasalazine, sulfonylureas
245
Q

Features of lead poisoning?

A
  • abdo pain, fatigue, constipation
  • peripheral neuropathy (motor)
  • blue lines gum margin (20% adults, v rare children)
246
Q 
Ix of lead poisoning:
serum lead level?
FBC?
blood film?
others?
urine?
A
  • blood lead level >10 significant
  • microcytic anaemia
  • basophilic stippling & clover-leaf morphology on film
  • raised serum & urine delta aminolaevulininc acid (makes it difficult to differentiate with acute intermittent porphyria)
  • raised urinary coproporphyrin
247
Q

Rx of lead poisoning?

A 
Chelating agents e.g.
DMSA dimercaptosuccininc acid
D-penicillamine
EDTA
dimercaprol
248
Q

What is Waldenstrom’s Macroglobulinaemia?

A

Lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein
- uncommon, seen in older men

249
Q

Features of Waldenstrom’s macroglobulinaemia?

A
  • monoclonal IgM paraproteinaemia
  • systemic upset weight loss, lethargy
  • hyperviscosity syndrome e.g. visual disturbance
  • hepatosplenomegaly
  • lymphadenopathy
  • cryoglobulinaemia e.g. Raynaud’s

(think organomegaly e.g. spleen, with NO bone lesions)

250
Q

Features of iron deficiency anaemia?

A

koilonychia
atrophic glossitis
angular stomatitis
post-cricoid webs

251
Q

Rx of hiccups in palliative care?

A

Chlorpromazine

- haloperidol, gabapentin also used, dexamethasone if hepatic lesions

252
Q

What is hairy cell leukaemia?

A

Rare malignant proliferation disorder of B cells, more common in males 4:1

253
Q

Features of hairy cell leukaemia?

A
  • pancytopenia, splenomegaly
  • skin vasculitis in 1/3
  • ‘dry tap’ despite BM hypercellularity
  • TRAP stain +ve (tartrate resistant acid phosphotase)
254
Q

Rx of hairy cell leukaemia?

A

1st line Chemo: cladribine, pentostatin
2nd line Immunotherapy: rituximab, IFN-alpha
- splenectomy sometimes required

255
Q

What is IFN-alpha useful for?

A
  • produced by leukocytes, with antiviral action

- hep B, hep C, Kaposi’s sarcoma, metastatic RCC, hairy cell leukaemia

256
Q

What is the philadelphia chromosome?

A

translocation between long arm of chr 9 & 22 t(9;22)(q34;q11)

  • > part of ABL proto-oncogene from chr 9 fused with BCR gene from chr 22
  • > resulting BCR-ABL gene codes for a fusion protein which has XS tyrosine kinase activity
257
Q

Presentation of CML?

A

60-70yrs

  • anaemia - lethargy
  • weight loss & sweating common
  • splenomegaly may be massive - abdo discomfort
  • spectrum of myeloid cells in peripheral blood
  • decreased leukocyte ALP
  • may undergo blast transformation (AML 80% ALL 20%)
258
Q

Rx of CML?

A

IMATINIB 1st line

  • hydroxyurea
  • IFN-alpha
  • allogenic BM Tx
259
Q

MoA of Imatinib?

A
  • inhibitor of tyrosine kinase ass with the BCR-ABL defect

- v high response rate in chronic phase CML

260
Q

What cancers may show raised bombesin?

A

SCLC
gastric ca
retinoblastoma/neuroblastoma

261
Q

A petechial skin rash combined with a slightly elevated APTT and reduced factor VIII activity - most likely Dx?

A

von Willebrand’s disease

262
Q

What is CLL?

A

monoclonal proliferation of well-differentiated lymphocytes, which are almost always B cells 99%
- commonest leukaemia in adults

263
Q

Features of CLL?

A
  • often none
  • bleeding, infections
  • anorexia, weight loss
  • lymphadenopathy more marked than CML
264
Q

Complications of CLL?

A
  • anaemia
  • hypogammaglobulinaemia -> recurrent ifnections
  • WARM AIHA in 10-15%
  • transformation to high-grade lymphoma (Richter’s transformation)
265
Q

Ix for CLL?

A

Smudge cells on film

Immunophenotyping = Dx Ix of choice!!

266
Q

What leads to recurrent infections in CLL?

A

hypogammaglobulinaemia

267
Q

Relative causes of polycythaemia?

A
  • dehydration

- stress: Gaisbock syndrome

268
Q

2ry causes of polycythaemia?

A

COPD
altitude
OSA
XS erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids

269
Q

How to differentiate between true (1ry/2ry) polycythaemia with relative polycythaemia?

A

Red cell mass studies,

In true polycythaemia total red cell mass >35 in males, >32 in females

270
Q

How can 1ry immunodeficiency disorders be classified?

A

According to component of immune system they affect

  • neutrophils
  • B cells
  • T cells
  • Combined B & T cell disorders
271
Q

What are the main neutrophil 1ry immunodeficiency disorders?

A
  • chronic granulomatous disease
  • Chediak-Higashi syndrome
  • Leukocyte adhesion deficiency
272
Q

What are the main B cell 1ry immunodeficiency disorders?

A
  • common variable immunodeficiency
  • Bruton’s (x-linked) congenital agammaglobulinaemia
  • Selective IgA deficiency
273
Q

What are the main T cell 1ry immunodeficiency disorders?

A

DiGeorge syndrome

274
Q

What are the main combined B & T cell 1ry immunodeficiency disorders?

A
  • severe combined immunodeficiency
  • ataxic telangiectasia
  • Wiskott-Aldrich syndrome
275
Q

What is the underlying defect in chronic granulomatous disease?

A

Lack of NADPH oxidase reduces ability of phagocytes to produce reactive oxygen species

  • rec pneumonias & abscesses esp catalase-positive bacteria & fungi
  • negative nitroblue-tetrazolium test
  • abnormal dihydrorhodamine flow cytometry test
276
Q

What is the underlying defect in Chediak-Higashi syndrome?

A

Microtubule polymerisation defect which leads to a decrease in phagocytosis

  • affected children have partial albinism & peripheral neuropathy
  • rec bacterial infections
  • giant granules in neutrophils & platelets
277
Q

What is the underlying defect in Leukocyte adhesion deficiency?

A

Defect in LFA-1 integrin (CD18) protein on neutrophils

  • rec bacterial infections
  • delay in umbilical cord sloughing may be seen
  • absence of neutrophils/pus at sites of infection
278
Q

What is the underlying defect in common variable immunodeficiency?

A

Many varying causes, Nb is a B cell disorder

  • hypogammaglobulinaemia is seen
  • may predispose to autoimmune disorders & lymphoma
279
Q

What is the underlying defect in Bruton’s x-linked congenital agammaglobulinaemia?

A

Defect in Bruton’s tyrosine kinase (BTK) gene that leads to a severe block in B cell development

  • X-linked recessive
  • rec bacterial infections
  • absence of B cells with reduced Igs of all cases
280
Q

What is the underlying defect in selective IgA deficiency?

A

Maturation defect in B cells

  • commonest 1ry Ab deficiency
  • rec sinus & resp infections
  • ass with coeliac disease, may cause false negative coeliac Ab screen
  • severe reactions to blood transfusions may occur (anti-IgA Abs -> anaphylaxis)
281
Q

What is the underlying defect in DiGeorge syndrome?

A

22q11. 2 deletion -> failure to develop 3rd & 4th pharyngeal pouches (T cell disorder)
- congenital heart disease, LDs, hypocalcaemia, rec viral/fungal diseases, cleft palate

282
Q

What is the underlying defect in severe combined immunodeficiency?

A

Many varying causes, commonest = X-linked, due to defect in common gamma chain (protein used in IL-2 receptors etc). Other causes inc adenosine deaminase deficiency

  • rec infections due to viruses, bacteria, fungi
  • reduced Tcell receptor excision circles
  • stem cell Tx may be successful
283
Q

What is the underlying defect in ataxic telangiectasia?

A

Defect in DNA repair enzymes

  • autosomal recessive
  • cerebellar ataxia, telangiectasia, rec chest infections & 10% risk of developing malignancy, lymphoma/leukaemia
  • combined B & T cell disorder
284
Q

What is the underlying defect in Wiskott-Aldrich syndrome?

A

Defect in WASP gene

  • -linked recessive
  • rec bacterial infections, eczema, thrombocytopenia
  • low IgM levels
  • inc risk of autoimmune disorders & malignancy
285
Q

Commonest tumours causing bone metastases?

A

prostate
breast
lung

286
Q

Commonest sites of bone metastases?

A 
Vertebrae
pelvis
ribs
skull
long bones
287
Q

Features of bone metastases?

A

bone pain
pathological fractures
hypercalcaemia
raised ALP

288
Q

Breast cancer RFs?

A
  • BRCA1, BRCA2 - 40% lifetime risk of breast/ovarian
  • 1st degree relative breast ca Dx when premenopausal
  • nulliparity, 1st pregnancy>30yrs
  • early menarche, late menopause
  • combined HRT, cocp
  • past breast ca
  • not breastfeeding
  • ionising radiation
  • p53 gene mutations
  • obesity
  • prev surgery for benign disease
289
Q

Carcinogen Aflatoxin (produced by aspergillum) for what cancer?

A

liver - HCC

290
Q

Carcinogen aniline dyes for what cancer?

A

bladder TCC

291
Q

Carcinogen asbestos for what cancer?

A

mesothelioma

bronchial ca

292
Q

Carcinogen nitrosamines for what cancer?

A

oesophageal

gastric

293
Q

Carcinogen vinyl chloride for what cancer?

A

hepatic angiosarcoma

294
Q

Whats the biggest RF for cervical cancer? which subtypes?

A

HPV

16, 18, 33

295
Q

What are koilocytes in cervical cancer?

A

Infected endocervical cells that undergo changes, leading to:

  • enlarged nucleus
  • irregular nuclear membrane contour
  • nucleus stains darker than normal (hyperchromasia)
  • perinuclear halo may be seen
296
Q

Poor prognostic factors in CLL?

A 
male
age >70
lymphocyte >50
prolymphocytes >10% blood lymphocytes
lymphocyte doubling time <12months
raised LDH
CD38+
297
Q

What chromosomal change in CLL is the most common abnormality seen in 50%, ass with good prognosis?

A

del 13q = deletion of long arm chr 13

298
Q

What chromosomal change in CLL is associated with a poor prognosis?

A

del 17p = deletion of part of short arm of chr 17, seen in 5-10%

299
Q

35y.o. woman who is 16wks pregnant attends AMU with 1st seizure - uncomplicated pregnancy so far.
Febrile, HR 86, BP 125/86
Bloods:
Hb 69 Plts 43 WCC 7.4
Na 137 K 4.9 Ur 18 Cr 278
Urine dip negative for protein & ketones
Schistocytes on blood film

What is the Dx?

A

TTP: thrombotic thrombocytopenic purpura

  • acquired inability to cleave vWF multimers
  • can be prompted by pregnancy
  • leading to platelet deposition & widespread coagulation
  • ADAMTS13 is the protein responsible
  • schistocytes on blood film can indicate intravascular haemolysis (MAHA in TTP)
300
Q

What is cryoglobulinaemia?

A

When Igs undergo reversible precipitation at 4deg C, dissolve when warmed to 37deg C
- 1/3 are idiopathic

301
Q

What are the 3 types of cryoglobulinaemia?

A

I monoclonal 25%
II mixed mono & polyclonal 25%, usually with rheumatoid factor
III polyclonal 50%, usually with RF

302
Q

What is type I cryoglobulinaemia?

What are the associations?

A

monoconal IgG/IgM

- myeloma, Waldenstrom macroglobulinaemia

303
Q

What is type II cryoglobulinaemia?

What are the associations?

A

mixed mono & polyclonal, usually with RF

- hep C, RA, Sjogren’s, lymphoma

304
Q

What is type III cryoglobulinaemia?

What are the associations?

A

polyclonal, usually with RF

- RA, Sjogren’s

305
Q

What are the Sx of cryoglobulinaemia?

A
  • Raynauds only in type I
  • cutaneous: vascular purpura, distal ulceration
  • arthralgia
  • renal involvement (diffuse glomerulonephritis)
306
Q

Rx of cryoglobulinaemia?

A
  • immunosuppression

- plasmapheresis

307
Q

IVDU with hep C, purpuric rash, +ve RF, reduced complement levels - what is the Dx?

A

cryoglobulinaemia type II (ass with hep C)

308
Q

What are the indications for Rx in CLL?

A
  • progressive marrow failure: worsening anaemia, thrombocytopenia etc
  • massive >10cm or progressive lymphadenopathy
  • massive >6cm or progressive splenomegaly
  • progressive lymphocytosis: >50% increase over 2months or lymphocyte doubling time <6months
  • B Sx
  • autoimmune cytopaenias e.g. ITP
309
Q

What is Rx of CLL when in indicated?

A

Rx of choice = FCR
Fludarabine
Cyclophosphamide
Rituximab

310
Q

What are the fundamentals of initial Rx in an acute chest sickle cell crisis?

A
  • O2 for Spo2>95%
  • IVF to maintain euvolaemia
  • adequate analgesia
  • INCENTIVE SPIROmetry in all presenting rib/chest pain
  • Abx to cover atypical
  • early consult with critical care team & haem (senior haematologist will decide whether a simple/exchange transfusion is necessary, with guidelines suggesting target Hb 100-110
311
Q

TTP: what is the Rx of choice?

What else can be used?

A

PLASMA EXCHANGE can be life-saving

- steroids, immunosuppressants, Vincristine can be used after Rx with PEX complete

312
Q

What is the classic pentad of TTP?

A
  • thrombocytopenia
  • microvascular haemolysis
  • fluctuating neuro signs
  • renal impairment
  • fever
313
Q

What is myelofibrosis?

A

Myeloproliferative disorder thought to be caused by hyperplasia of abnormal megakaryocytic

  • > release of PDGF is thought to stimulate fibroblasts
  • haematopoiesis develops in liver & spleen
314
Q

Features of myelofibrosis?

A
  • elderly person with Sx of anaemia is commonest presenting Sx
  • massive splenomegaly
  • hypermetabolic Sx: weight loss, night sweats
315
Q

Lab findings in myelofibrosis?

A
  • anaemia
  • high WCC & plt in early disease
  • tear-drop poikilocytes in early disease
  • unobtainable BM Bx - ‘dry tap’ therefore trephine Bx needed
  • high rate & LDH (reflection of increased cell turnover)
316
Q

Most useful follow-up Ix to detect testicular teratoma disease recurrence?

A

AFP & beta-hCG

317
Q

MoA of cisplatin?

A

Causes cross-linking of DNA

318
Q

What sort of homeless does hereditary spherocytosis cause?

A

EXTRAvascular

319
Q

Drug causes of pancytopenia?

A 
Abx: Trimethoprim, chloramphenicol
Anti-rheum: gold, penicillamine
Carbimazole
Anti-epileptics: crabamazepine
Sulfonylureas: tolbutamide
Cytotoxics
320
Q

What is protein C deficiency?

What are the features?

A
  • autosomal dominant condition leading to increased risk of thromboses
  • VTE
  • skin necrosis after warfarinisation (when 1st started, protein C biosynthesis is reduced -> temp procoagulant state ->thrombosis in venues -> skin necrosis
321
Q

What is the most common clinically significant primary immunodeficiency?

A

CVID: common variable immunodeficiency

IgA deficiency is more common, but most are aSx

322
Q

Features of CVID: common variable immunodeficiency?

A
  • raised serum Igs
  • heterogeneous clinical features
    Usually 3 of:
  • hypogammaglobulinaemia of 2+ isotypes (low IgG/A/M). IgG more likely to be deficient than IgM
  • rec sinopulmonary infections
  • impaired functional Ab responses e.g. absent isohaemagglutinins, poor responses to protein/polysaccharide vaccines etc
323
Q

What is the best screening test in-between attacks of hereditary angioedema?

A

serum C4

324
Q

MoA of cyclophosphamide?

A

alkylating agent that causes cross-linking of DNA

325
Q

what is Mesna ? (cyclophosphamide)

A

2-mercaptoethane sulfonate Na

  • acrolein is a metabolite of cyclophosphamide that’s toxic to urothelium
  • mesna binds to it & inactivates to to help prevent haemorrhagic cystitis
326
Q

Adverse effects of cyclophosphamide?

A

haemorrhagic cystitis (incidence reduced by use of hydration & mesna)
myelosuppression
TCC

327
Q

Features of Falcon anaemia?

A 
autosomal recessive
aplastic anaemia
inc risk of AML
neurological
skeletal abnormalities: short stature
cafe au lait spots
328
Q

Causes of hyposplenism?

A 
splenectomy
sickle cell
coeliac, dermatitis herpetiformis
Graves disease
SLE
amyloid
329
Q

Ix of choice for CLL?

A

immunophenotyping

330
Q

What is paroxysmal nocturnal haemoglobinuria?

A

Acquired disorder leading to haemolysis (mainly intravascular) of haem cells

  • thought to be caused by increased sensitivity of cell membranes to complement due to a lack of GPI: glycoprotein glycosyl-phosphatidylinositol
  • more prone to venous thrombosis
331
Q

Pathophysiology of paroxysmal nocturnal haemoglobinuria?

A

GPI is like an anchor which attaches surface proteins to the cell membrane

  • complement-regulating surface proteins e.g. DAF: decay-accelerating factor, are not properly bound to the cell membrane due to a lack of GPI
  • thrombosis thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation
332
Q

Features of paroxysmal nocturnal haemoglobinuria?

A
  • acquired, chronic intrinsic haemolytic anaemia
  • RBCs, WBCs, platelets or stem cells may be affected -> pancytopenia
  • Hburia: dark urine in the morning classically
  • thrombosis e.g. Budd-Chiari syndrome
  • aplastic anaemia may develop in some
  • +ve Ham test
333
Q

How to Dx paroxysmal nocturnal haemoglobinuria: what is the gold standard?
what used to be used?

A
  • Flow cytometry of blood to detect low levels of CD59 & CD55*
  • Ham’s test: acid-induced haemolysis (normal RBCs don’t)
334
Q

Rx of paroxysmal nocturnal haemoglobinuria?

A
  • blood product replacement
  • anticoagulation
  • Eculizumab, a mAb directed against terminal protein C5, being trialled & may help reduce intravascular haemolysis
  • stem cell Tx
335
Q

What is the Ix if you otherwise can’t Dx hereditary spherocytosis on Hx, FHx etc alone?

A

EMA binding test - uses flow cytometry to determine the amount of fluorescence (reflecting EMA bound to specific transmembrane proteins) derived from individual red cells

336
Q

Sx & findings of spinal metastases?

A
  • unrelenting lumbar back pain
  • any thoracic/cervical back pain
  • worse with sneezing, coughing, straining
  • nocturnal
  • ass with tenderness
337
Q

If Sx & findings of spinal metastases (without neuro features) what is next best step?

A

Whole MRI spine within 1 week (24h if neuro Sx & suspect for SCC)

338
Q

What is the main purpose of requesting irradiated food product?

A

Reduces the risk of transfusion graft vs host disease as it is T-cell depleted

339
Q

What are the porphyrias?

A

Abnormality in enzymes responsible for biosynthesis of haem

  • results in overproduction of intermediate compounds (porphyrins)
  • can be acute/non-acute
340
Q

AIP: acute intermittent porphyria

  • what is the enzyme defect?
  • how does it typically present?
  • what happens to urine?
A
  • defect in porphobilinogen deaminase - autosomal dominant
  • female in 20-40s with abdo Sx & neuropsych Sx
  • HTN & tachycardia common
  • urine turns deep red on standing
341
Q

PCT: porphyria cutanea tarda

  • what is the enzyme defect?
  • how does it classically present?
  • what is elevated in the urine and what happens under Wood’s lamp?
  • Rx?
A
  • uroporphyrinogen decarboxylase, commonest hepatic porphyria
  • may be caused by hepatocyte damage e.g. etoh, oestrogens
  • classically photosensitive rash with bull, skin fragility on face & dorsal aspect of hands
  • urine: elevated uroporphyrinogen, pink fluorescence
  • Rx with Chloroquine
342
Q

Variegate porphyria: what is the enzyme defect?
how does it present?
where is it more common?

A
  • defect in protoporphyrinogen oxidase
  • photosensitive blistering rash, abdo & neuro Sx
  • autosomal dominant, more common in South Africans
343
Q

What is Mantle cell lymphoma?
What are the genetics?
What are the features?

A
  • B-cell lymphoma
  • CD5+, CD19+, CD22+, CD23-, CD10-
  • ass translocation t(11;14) causing over-expression of the cyclin D1 (BCL-1 gene)
  • poor prognosis, widespread lymphadenopathy
344
Q

What is methaemoglobinaemia?

A
  • Hb which has been oxidised from Fe2+ -> Fe3+
  • normally regulated by NADH metHb reductase, which transfers electrons from NADH -> metHb resulting in reduction of metHb to Hb
  • tissue hypoxia as Fe3+ can’t bind O2, so oxygen dissociation curve shifts to the Left
345
Q

Congenital causes of methaemoglobinaemia?

A
  • Hb chain variants: HbM, HbH

- NADH metHb reductase deficiency

346
Q

Acquired causes of methaemoglobinaemia?

A
  • drugs: sulphonamides, nitrates, dapsone, sodium nitroprusside, primaquine
  • chemicals: aniline dyes
347
Q

Features of methaemoglobinaemia?

A
  • ‘chocolate’ cyanosis
  • dyspnoea, anxiety, headache
  • severe: acidosis, arrhythmias, seizures, coma
  • normal pO2 but decreased oxygen saturation
348
Q

Rx of Methaemoglobinaemia?

A
  • congenital NADH - methaemoglobin reductase deficiency -> Ascorbic acid
  • acquired -> IV methylene blue
349
Q

What is a leukaemoid reaction?

A

Presence of immature cells e.g. myeloblasts, promyelocytes & nucleated red cells in the peripheral blood
- may be due to infiltration of BM causing immature cells to be ‘pushed out’ or sudden demand for new cells

350
Q

Causes of leukaemoid reaction?

A
  • severe infection
  • severe haemolysis
  • massive haemorrhage
  • metastatic cancer with BM infiltration
351
Q

How to differentiate a leukaemoid reaction from CML?

A

LR:

  • high leucocyte ALP score
  • toxic granulation (Dohle bodies) in the white cells
  • ‘left shift’ of neutrophils i.e. 3 or less segments of the nucleus

CML:
- low leucocyte ALP score

352
Q

Classic train of paroxysmal nocturnal haemoglobinuria?

A
  1. haemolytic anaemia
  2. pancytopenia
  3. venous thrombosis
353
Q

In essential thrombocytosis, apart from a JAK2 mutation, Which is the most likely other gene mutation responsible?

A

CALR = Calreticulin (20%)

354
Q

What is the Ag found in heparin-induced thrombocytopenia?

A

PF4 (platelet factor 4) complex

355
Q

leucocyte ALP score in myelofibrosis?

A

high

356
Q

MoA of Docetaxel?

A

Prevents microtubule depolymerisation & disassembly, decreasing free tubular

357
Q

What is the triad in HUS: haemolytic uraemia syndrome?

A
  1. acute renal failure
  2. MAHA
  3. thrombocytopenia
358
Q

Causes of HUS?

A
  • post-dysentery (classically E. coli ‘verotoxigenic’, ‘enterohaemorrhagic’)
  • tumours
  • pregnancy
  • ciclosporin, OCP
  • SLE
  • HIV
359
Q

Ix in HUS?

A

FBC: anaemia, thrombocytopenia, fragmented blood film
U&E: acute renal failure
stool culture

360
Q

Rx of HUS?

A

Supportive e.g. fluids, blood transfusion & dialysis if required
- complicated indications for plasma exchange - generally when v severe & not ass with diarrhoea

361
Q

Haptoglobin in intravascular haemolytic anaemia?

A

LOW

  • binds to free Hb released from lysed RBCs
  • complexes removed from plasma by hepatic reticule-endothelial cells
  • haptoglobin levels fall if the rate of homeless is greater than the rate of haptoglobin production
362
Q

MoA of Capecitabine?

A

Antimetabolite pro-drug of 5-FU but is ORAL

363
Q

skin necrosis after starting warfarin - what is the Dx?

A

protein C deficiency

autosomal dominant

364
Q

Dysregulation of coagulation & fibrinolysis resulting in widespread clotting - Dx?

A

DIC

365
Q

Bacterial toxin initiation of apoptosis & thrombogenesis - Dx?

A

HUS

366
Q

Abnormal placental perfusion & vascularisation?

A

Pre-eclampsia

367
Q

Acquired inhibition of ADAMTS13, preventing cleavage of vWF multimers - Dx?

A

TTP

368
Q

Cytotoxic that prevents microtubule depolymerisation & disassembly, decreasing free tubulin?

A

Docetaxel

nb can cause neutropenia

369
Q

high BANDS on FBC = high rate of granulopoiesis so increase in granulocytes at different stages of maturation
Dx?

A

CML

370
Q

What malignancies are ass with EBV?

A

Hodgkins & Burkitt’s lymphoma

nasopharyngeal carcinoma

371
Q

APML: what translocation is it ass with?

what chromosomal deletions are ass with poor prognosis?

A

t(15;17)

deletions of chr 5/7

372
Q

Rx when indicated in CLL?

A

chlorambucil reduces lymphocyte count

Fludarabine

373
Q

What must you give before Fludarabine in Rx for CLL and why?

A

Septrin or monthly nebulised Pentamidine to reduce risk of PCP because it causes profound lymphopenia which increases risk of opportunistic infections

374
Q

Vena-Occlusive disease?

= complication of chemo pre-BM Tx

A
  • fluid retention, hepatomegaly, jaundice, multi-organ failure
  • Dx = US abdomen to help, Liver Bx shows centrilobular necrosis
    Rx = supportive
375
Q

ALL - Dx?

A 
Blast on blood smear
BM Bx = Dx
LP to detect CNS involvement
CXR to look for mediastinal mass
U&amp;E to check tumour lysis
Immunophenotype to establish if blast cells origin is B/T
DNA mutation testing
376
Q

Before starting chemo Rx in ALL, what should be doe if blast cell count is Very high?

A

needs Leukapharesis to prevent slugging of capillary beds - can be life-saving

377
Q

Test that has >95% sensitivity to Dx von willebrands?

A

PFA-100

378
Q

ITP: what do you do before starting steroids?

A

BM aspirate to show megakaryocytes - and rule out leukaemia before starting steroids!

exam (21 decks)

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