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Haematology Flashcards

1
Q

Adverse effects of imatinib?

A

Weight gain
Oedema
Nausea
Vomiting

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2
Q

Which 1 of the 3 antiphospholipid test confers the most risk of clotting events?

A
  1. Lupus anticoagulant
  2. anti-B2 glycoprotein 1
  3. IgM anticardiolipin antibody
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3
Q

Which agent reduces mortality in trauma patients at risk of bleeding?

A

Prothrombinex

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4
Q

What are the indications for Vitamin K warfarin reversal in a patient with an INR:
4.5
>4,5 -10 + high risk of bleeding
>10

A

4.5:
stop warfarin until INR approaches therapeutic range and then resume dose
Check INR in 24 h

> 4.5 - 10 - high risk of bleeding:
Cease warfarin
Give 1-2 mg PO or 
0.5-1 mg IV
Check INR in 24 h
> 10:
cease
Vit K3-5 mg PO or IV
Prothrombinex (FII, IX, X)if bleeding risk high.
Check INR after 12-24h.
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5
Q

17p deletion good or poor prognosis?

A

Always poor.

17 p in CLL

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6
Q

Rivaroxaban is CI in pts with eGFR

A

False.

Use with caution.

CI if eGFR

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7
Q

Co-administration of posaconazole with Rivaroxaban will increase risk of bleeding. T/F

A

True, Posa inhibits CYP3A4

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8
Q

MOA Rivaroxaban? How to monitor?

A

Anti-Xa inhibitor. No reversal agent.

Assay by anti-Xa testing

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9
Q

When do you stop Rivaroxiban/apixiban prior to elective Sx?

A

Elderly - 2-3 days prior, clearance 44-52 h

Young - 1-2 d prior, clearance 20-36 h

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10
Q

Predictors of recurrence after DVT?

A

+ve D-dimer 2 weeks after cessation of warfarin

Heritable thrombophilias and low protein C levels are low risk

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11
Q

What are the strong RF for recurrence after DVT?

A

PE/DVT

> 2 thrombotic events

Male sex

Residual vein thrombus

Vena cava filter

Continued oestrogen use

Cancer

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12
Q

What is the role of hepciden?

A

Negative regulator of Fe, blocks feroportin and the free movement of Fe across cells

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13
Q

What happens to hepciden in anaemia?

A

decreases hepciden

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14
Q

What happens to hepciden in inflammation?

A

Increases transcription of hepciden through IL6 via Stat3, LPS

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15
Q

What are the disease associations for the following haemoglobinopathies?

Thalassemia

B-thalassaemia

a-thal

Haemoglobinopathies

Sickle cell anaemia

Abnormal Hb

High affinity Hb

A

Thalassemia - micorcytic anamia +normal ferritin

B-thalassaemia - Hb electrophoresis demonstrates increased HbA2

a-thal - molecular test for a-chain deletion

Haemoglobinopathies - abnormal Hb molecules

Sickle cell anaemia - Vascular complications

Abnormal Hb - Anaemia Hb D, O, C, S

High affinity Hb - Polycythemia. Dx ABG paO2

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16
Q

Hydroxyurea has been shown to reduce acute on chronic complication of SCD. T/F

A

True

CI in pregnancy

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17
Q

What is the commonest inherited bleeding disorder?

A

vWD, 1 in 100.

Deficient or defective vWF

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18
Q

How does vWF bind to sub endothelium? Role of vWF?

A

primary binding site on platelets is GP1b-IX-V

required for platelet adhesion, aggregation and stabilises FVIII

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19
Q

What are the types of vW disease?

A

Type 1-reduced levels, partial reduction in vWF (80% of pts). AD

Type 2- mutations in vWF functional (binding sites) defect, abnormal form of vWF

Type 3 – severe deficiency, total lack of von willebrand factor (AR)

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20
Q

How do you dx Waldenstrom’s macroglobulinaemia?

A

Presence of any size serum IgM paraprotein

Bone marrow aspirate: inflitration with snake lymphocytes demonstrating plasmacytoid/plasma cell differentiation

Immunophenotype (flow cytometry) - B cell lymphoma, IgM CD19/20+, CD10 and CD5

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21
Q

What feature do you see on film with lead poisoning?

A

Basophilic stripping

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22
Q

What feature do you see on blood film with Fe def anaemia?

A

Target cells

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23
Q

Tx for ITP?

Plts 30, no bleeding

A

Plts 30 and no bleeding
- observation

IVIG can be used instead of steroids when a more rapid increase in plt count is requiored

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24
Q

APTT is a measure of intrinsic pathway (FXI, IX, VIII). T/F

A

True

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25
Q

APTT does not correct on mixing and no bleeding diathesis. Aetiology?

A

Lupus anticoagulant most common

FXII and HMWK/Prekalikrein antibody rare

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26
Q

APTT does not correct and bleeding diathesis. Aetiology?

A

FVIII inhibitor (time dependent)

FIX inhibitor

FXI inhibitor (rare)

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27
Q

Which NOAC can be removed with dialysis?

A

Haemodiaylsysis works for dabigatran as low protein binding, not for other NOACs as has high protein binding

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28
Q

Does 5q deletion indicate good or poor prognosis in myelodysplastic syndrome?

A

Good prognosis

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29
Q

Tx for myelodyplastic syndrome?

A

Supportive care and iron chelating therapy

Azacitadine

Lenolidamide

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30
Q

What are the RF for myelodysplastic syndrome?

A

DNA damage from previous CTx or radiation, inherited defects in DNA repair

Down syndrome

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31
Q

What drug has been shown to improve survival in Myelodysplasia?

A

Azacitidine

- a DNA hypomethylating agent

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32
Q

What does the film morphology show in Myelodysplasia?

A

Anisopoikilocytosis

tear drop cells

oval macrocytes

occasional nucleated red blood cells

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33
Q

What complement change is PNH associated with?

A

decrease in CD59

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34
Q

What complement change is mesangiocapillary glomerulonephritis associated with?

A

Production of C3 nephritic factor

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35
Q

How do you diagnose haemochromatosis?
What levels do you aim for phlebotomy?
Risk of progressing to fibrosis?

A

Tranferrin saturations >60% in M, >50% in F, most sensitive test
Liver Bx provides definitive Dx

  • Serum ferritin
    • acute phase reactant
    • can be elevated by EtOH, steatosis, viral overlaid
    • a level of >1000 in absence of above used to indicate the need for biopsy
    • the negative predictive value of a normal transferrin saturation and serum ferritin is 97%.NO FURTHER TESTING.
  • Liver biopsy
    • grade 3 hepatocyte Fe accumulation with an acinar distribution pattern consistent with homozygous genetic haemochromotosis
      • stained with Perl’s prussian blue

Phlebotomy
- Aim serum ferritin maintain levels

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36
Q

What is the mutation in haemochromatosis?

A

HFE gene located on chromosome 6.

2 missense mutations: C282Y (85%) and H63D (20%)

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37
Q

When if FFP indicated?

A

To replace coagulation factors

Used when PT/PTT supratherapeutic

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38
Q

When is cryoprecipitate indicated?

A

Contains fibrinogen, vWF, FVIII, FXIII, Fibronectin (5Fs)
Its a plasma component enriched with fibrinogen.
Used in DIC to replace fibrinogen

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39
Q

What is cerebral venous thrombosis? Presentation? Dx?

A

Rare, presents in immediate post part period.

Clinical:

Headache

Vomiting

Focal or generalised seizures

Confusion

Blurred vision

Focal neurological deficits

Altered consciousness

Dx:

MRI

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40
Q

What is the hallmark of Factor VII inhibitor?

A

Bleeding that is first noted after a surgical procedure.

APTT is prolonged

PT is normal

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41
Q

Is there a prolonged APTT in antiphospholipid syndrome?

A

Yes however thrombosis is the common presentation

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42
Q

What is the most common inherited hypercoagulable state? Which hypercoagulable state is most likely to clot?

A

Factor V Leiden mutation and prothrombin gene mutation account for 50-60% of cases

patients with defects in Protein C,S and antithrombin are more likely to clot

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43
Q

Mechanism of Factor V mutation leading to thrombosis?

A

Causes a resistance to the normally inhibitory effects of protein C

Heterozygosity for the factor V Leiden mutation increases the lifetime risk for thrombosis 7-fold

Homozygosity raised the risk 20 fold

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44
Q

Mechanism of Prothrombin gene mutation leading to thrombosis?

A

A gain of function mutation resulting in elevated levels of prothrombin.

Heterozygous carrier have increased risk of 3-4 fold of venous and possibly arterial thrombosis

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45
Q

Which antiphospholipid abs has the strongest RF for thrombosis? Lupus, anticardiolipin or B2-glycoprotein?

A

Lupus anticoagulant - highest risk of thrombosis and adverse pregnancy outcomes after 12 weeks gestation

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46
Q

Is Hepcidin increased or decreased in anaemia of chronic disease?

A

Increased in order to prevent further iron release into the blood

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47
Q

Myelodyplasia: what therapy has prolonged survival compared with supportive care? Therapy fro 5q sydnrome?

A

Azacitdine

5q syndrome indicates good prognosis. Responds to Lenalidomide, reduces risk of transformation to AML.

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48
Q

GVHD. What is the key cell type involved?

A

T cell mediated disease. The principle antigenic targets of the T cells of the graft are the host MHC molecules if the patient and donor MHC molecules differ.

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49
Q

What diseases are associated with each of the cryoglobulinaemia?

A

Type 1 - Waldenstrom’s or MM, produces few complement abnormalities

Type 2 - persistent viral infections, HCV, HIV

Type 3 - systemic rheum conditions

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50
Q

PT high, aPPT normal. Cause?

A

Problem with FVIII, IX, XI, XII

Heparin the most common

Factor VIII inhibitor if bleeding present

Antiphospholipid syndome in clotting patient

vWD

Haemophilia

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51
Q

PT high, aPPT high. Cause?

A

Defect in the common pathway e.g. def prothrombin, fibrinogen, factor V or X.
Combined factor deficiencies.

most common cause is RHF with liver congestion, very high PT!

Medications

  • abx, not as elevated as RHF
  • Warfarin
  • Liver disease, Vit K def, excess heaprin, DIC
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52
Q

Which thalassaemia combination gives the highest risk of having a child with a severe form of thalassaemia?

A

Trait + Trait

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53
Q

What does a normal Hb electrophoresis pattern contain?

A

HbA 97%

HbA2

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54
Q

Genetic defect in B thal? Types?

A

defect in B-genes
Normal Hb contains 2 alpha and 2 beta

B-thalassaemia minor (deletion of 1 B-globin gene)

  • mild microcytic anaemia or no anaemia.
  • Asymptomatic.
  • 2-3 fold elevation of HbA2, slight increase in HbF on Hb electrophoresis.

B-thal major (deletion of both B-globin genes):
Resulting severe anaemia -> elevated EPO levels
Hb electrophoresis shows high HbF and HbA2
Fetus and newborn not affected as a2y2 until y switches to beta -> severe anaemia, pallor, growth retardation and heptosplenomegaly due to extramedullary haemopoiesis.

B- thal intermedia (homozygous)

  • not all pts with homozygous have full clinical severity
  • modulating defects include minor qualitative defects of the B-globin, coinheritance of a-thal trait and increased prod of HbF
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55
Q

What is the best way to prevent post thrombotic syndrome after DVT? What is post thrombotic syndrome?

A

Exercise training.

Is the development of S&S of chronic venous insufficiency following a DVT

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56
Q

HITS, what are the 4Ts? Score numbers?
Presentation
Ix
Tx

A

Thrombocytopenia, PLT count fall > 50%

Timing of PLT count fall, 5-10 days (HITs type 2, type 1 is in 1-2 d and recovers spontaneously)

Thrombosis or other sequel

Other cases for thrombocytopenia present

0-3 = low probability

4-5 = intermediate

6-8 = high probability

Presentation:
Fever, chills, dyspnoea, chest pain
THROMBOEMBOLISM (large vessel venous or arterial) is the most common manifestation

Ix:
Immunoassays identify antibodies against heparin/platelet factor 4 (PF4) complexes.
Functional assays measure the platelet-activating capacity of PF4/heparin-antibody complexes.
Functional assays have greater specificity than immunoassays but are time-consuming and not widely available; many institutions offer only immunoassays

Tx:

Heparin cessation

Tx with non heparin anticoagulant:

Danaparoid (LMWH), Fondaparinux (synthetic Factor Xa inhibitor) lepirudin (direct irreversible thrombin inhibitor), argatroban (direct thrombin inhibitor)

Bivalirudin is indicated only in pats with HIT or at risk for HIT undergoing acute cardiac interventions.

Lepirudin is renally cleared.

Argatroban is cleared through liver.

Dx of Pure red cell aplasia?

A very low reticulocyte count,

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57
Q

DDx of microcytic anaemia?

A

Fe def

Thalassaemia

Less common

  • anaemia of chronic disease
  • myelodyplasia
  • sideroblastic anaemia
  • hyperthyroidism
  • heavy metal poisoning
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58
Q

What are the 2 major causes of non-restricted Fe def anaemia?

A
  1. Absolute Fe def - absent stores
  2. Functional Fe def - insufficient availability of Fe in the setting of normal to increased Fe stores e.g. anaemia of chronic disease, erythropoietin therapy
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59
Q

What factors are involved in the Fe cycle?

A

Duodenal enterocytes - absorb

Erythroid precursors - utilise

Reticuloendothelial macrophages - Fe storage and recycling

Hepatocytes - Fe storage and endocrine regulation

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60
Q

What form of Fe do duodenal enterocytes absorb? How does Fe exit enterocyte?

A

Ferrous Fe2+

Ferroportin exports Fe into the plasma

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61
Q

What is the role of transferrin and transferrin receptor?

A

Transferrin carries Fe in the plasma

Transferrin receptor mediates uptake into cells

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62
Q

What is the role of Hepcidin in Fe absorption? When does it increase/decrease?

A

Binds to ferroportin and induces its degradation

Hepcidin increases in Fe overload

Hepcidin decreases in Fe def

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63
Q

What is the major cause of Fe def anaemia in affluent countries?

A

Blood loss

  • GI bleeding e.g. ulcers, malignancy, diverticulitis
  • Menstruation
  • Diet
  • Coeliac disease, partial gastrectomy, PRV etc
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64
Q

What do the Fe studies show in Fe def? Soluble transferrin receptor?

A

Ferritn reduced

Transferrin increased

TIBC increased

Transferrin saturation reduced

Soluble transferrin receptor increased (derived from bone marrow erythroid precursors and directly proportional to erythropoietic rate

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65
Q

Causes of elevated Ferritin?

A

Inflammation

Liver disease

Infection

Malignancy

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66
Q

What is the 1st/2nd/3rd line Mx of Fe def? How do you monitor response?

A

1st Orals

2nd IV

3rd IM

Monitoring Hb and reticulocyte count

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67
Q

What are the causes of anaemia of chronic disease?

A

Infectious

Neoplastic

Inflammatory

Have an inappropriately low reticulocyte count

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68
Q

What are the mechanisms of anaemia of chronic disease?

A
  • Altered/abnormal Fe homeostasis e.g. reduced absorption, trapping of Fe in macrophages
  • Reduced RBC production by the bone marrow e.g. toxicity of erythroid precursors, cytokine mediated effects
  • Blunted response to erythropoietin e.g. blunted production, reduced receptors, reduced responsiveness
  • Shortened red cell survival e.g. erythrophagocytosis, cytokine and free radical damage
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69
Q

How do you Dx anaemia of chronic disease?

A

Ferritin normal

Transferrin saturation reduced

Transferrin reduced to normal

Soluble transferrin receptor normal

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70
Q

How can you differentiate between anaemia of chronic disease and Fe def anaemia?

A

Soluble transferrin receptor is increased in Fe def anaemia, normal in ACD

Cytokine levels increased of ACD

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71
Q

How do you Mx ACD?

A

Tx underlying cause

If mild, no intervention

Measure erythropoietin level to guide

Fe replacement therapy if Fe def and with erythropoietin therapy

Supportive care - transfusion warranted for severe symptomatic anaemia

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72
Q

What are the strongest RF for VTE?

A

What is the strongest RF for VTE?

Previous VTE

Fracture of LL

Hip/knee replacement

Hospitilisation for HF or AF/flutter within previous 3 months

Major trauma

MI within 3 months

Spinal cord injury

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73
Q

Which malignancies have the highest risk fro VTE?

A

Brain

GI

Haem

Lung

Pancreas

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74
Q

Which cytokines are involved in haem disease?

A

IL -3,7,9,11 - odd number

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75
Q

What is the Tx for ATRA syndrome?

A

Stop ATRA and give dexamethasone 10 mg IV BD

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76
Q

What is ATRA syndrome due to? S&S?

A

Cytokine release following differentiation of APL cells.
Causes fluid retention and capillary leak.
Occurs in 1/3 of patients.
Lower rates of ATRA syndrome if chemo is commenced with ATRA.

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77
Q

What are the RF for ALL?

A 
Male- incidence 30% higher in males
Children 2-5 y
Caucasion
Down’s syndrome – 20 x risk for leukemia
Radiation exposure
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78
Q

What is the best CTx for Philadelphia +ve ALL?

A

Imatinib

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79
Q

What is the MOA of Imatinib? What is the main transporter of Imatinib?

A

Blocks abl function by interfering with ATP binding.
OCT-1 (organic Cation Transporter 1).
Pts with suboptimal response have lower OCT-1 activity.

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80
Q

What is the most effective Tx of MDS with chromosome 5q syndrome (5q31 deletion)?

A

Lenalidomide.

Can reduce transfusion requirements and reverse cytologic and cytogenic abnormalities.

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81
Q

What is the HASFORD prognostic score?

A 
Measures the response post interferon a Tx in CML. Prognostic score for survivial.
APS BEB
Age
Platelets
Slpeen size
Basophils
Eosinophils
Blasts
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82
Q

What is the Tx for chronic phase CML?

A

Imatinib
Hydroxyurea bulk reduction
IFNa +/- ARA-C
Bone marrow transplant remains the only known curative therapy=sibling allograft (ALLOGENIC)

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83
Q

What are the features of complete haematological response in the Tx of CML?

A

Complete normalization of peripheral blood
No immature cells in peripheral blood
No S&S of disease including disappearance of splenomegaly
No Philadelphia chromosome

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84
Q

What are the AE of imatinib?

A 
Weight gain
Odema
Muscle cramps
Nausea
Deranged LFTs
Porphyria-rash
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85
Q

What is the main mechanism of imatinib resistance in CML?

A

Mutations of BCR-ABL kinase domain.

Outgrowth of leukemic subclones secondary to BCR-ABL mutation.

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86
Q

What is the next line of Tx if a pt with CML is intolerant to Imatinib?

A

Dasatinib.
Induces cytogenic and haematoligcal response in pts with CML or Philadelphia +ve ALL who cannot tolerate or are resistant to Imatinib.

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87
Q

What is Hodgkin’s lymphoma? Histological classification and prognosis of each?

A

A malignant proliferation of lymphocytes characterised by the presence of Reed Sternberg cell.
Lymphocyte predominant – best prognosis
Lymphocyte deplete – worst prognosis
Mixed cellular –good prognosis
Nodular sclerosing – most common, good prognosis

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88
Q

What are the poor prognostic factors for Hodgkin’s lymphoma?

A 
Lymphocyte deplete
B symptoms
Weight loss > 10% in last 6 months
Age> 45y
Stage IV
Hb  15, 000/uL
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89
Q

What is the most common inherited bleeding disorder?

A

Von Willebrand’s disease

AD

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90
Q

What are the types of VWD?

A

Type 1-partial reduction in vWF (80% of pts)
Type 2- abnormal form of vWF
Type 3 – total lack of von willebrand factor (AR)

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91
Q

What is the role of vWF?

A

Large glycoprotein which forms massive multimers up to 1, 000, 000 Da in size and promotes platelet adhesion to damaged endothelium.
Carrier molecule for factor VIII.

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92
Q

What is the treatment for vWD?

A

Tranexamic acid for mild bleeding
Desmopressin (DDAVP) to raise levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
Factor VIII concentrate

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93
Q

What is the main AE of DDVAP (vasopressin)?

A

Hyponatraemia

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94
Q

What is a leukamoid reaction?

A

Describes the presence of immature cells such as myeloblasts, promyelocytes and nucleated red cells in the peripheral blood. May be due to infiltration of the bone marrow causing the immature cells to be pushed out or sudden demand for new cells.
Causes are severe infection, severe haemolysis, massive haemmorhage, metsatic can with bone marrow infiltration.

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95
Q

How can you differentiate leukamoid reaction from CML?

A

Leukamoid reaction
-high leucocyte alkaline phosphatase score
toxic granulation (Dohle bodies) in the white cells
Left shift of neutrophils i.e. three or less segments of the nucleus.
CML
-low leucocyte alkaline phosphatase score.

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96
Q

What are the features of amyloid light chain amyloidosis?

A 
Nephrotic range proteinuria
Acquired factor X def leading to high INR
Postural hypotension
Macroglossia
Low grade plasma dyscrasia
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97
Q

What is the purpose of a mixing study?

A

To asses if the pt has a factor def or an clotting factor inhibitor present.
If the mixing study corrects, pt has factor def.
If it does not correct, pt has a clotting factor inhibitor present.

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98
Q

What factors are involved in the extrinsic pathway?

A

Tissue factor III
VII
PT checks extrinsic pathway.

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99
Q

What factors are involved in the intrinsic pathway?

A 
XII (Prekallikrein)
HMWK
VIII
IX
XI
XII
APTT checks intrinsic pathway
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100
Q

Which pathway does the thrombin clotting time check?

A

The common pathway (Factor X)

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101
Q

What is romiplostim?

A

A fusion protein analogue of thrombopoietin, a hormone that regulates platelet production.
Romiplostim stimulates the patient’s megakaryocytes to produce platelets at a more rapid than normal rate thus overwhelming the immune system’s ability to destroy them.

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102
Q

what are the AE of romiplostim?

A

Myalgia
Joint and extremity discomfort
Insomnia
Thrombocytosis ->clots and bone marrow fibrosis

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103
Q

Which medications will enhance the effects of warfarin? Which will reduce the effects of warfarin?

A

Warfarin is a CYP3A4 substrate
CYP3A4 inhibitor-erythromycin, other macrolides, protease inhibitors (ritonavir, indinavir, nelfinavir), azole antifungals, aprepitant and verapamil. Will inhibit metabolism of warfarin.
CYP3A4 inducer- Carbamazepine and phenytoin, increase metabolism of warfarin and reduce effects.

104
Q

How do you diagnose antiphospholipid syndrome?

A

Persistently positive test (at least 2 positives, 6 weeks apart)

  • Anticardiolipin test
  • Lupus anticoagulant test
  • Anti-beta2 glycoprotein I test
105
Q

How do you treat antiphospholipid syndrome? Non pregnant vs pregnant

A

No hx of thrombosis – no Tx
If SLE, CTD, Hx of miscarriage – low dose aspirin
Previous VTE – life long warfarin
If pregnant- aspirin and unfractionated heparin may reduce chance of miscarriage.

106
Q

What is the most common cause of familial thrombophilia?

A

Factor V leiden (activated protein C resistance)

107
Q

Which coagulation abnormality is resistant to the effect of heparin?

A

Anti-thrombin deficiency as anti-thrombin required

108
Q

Which 2 conditions will have a raised APTT and TCT?

A

Heparin
DIC (raised D-dimer, low fibrinogen)
Liver disease

109
Q

Which clotting factor is found in cryoprecipitate?

A

Factor VIII

110
Q

List the myeloproliferative disorders

A

Polycythemia Essential thrombocythaemia
Myelofibrosis
Myelodyplasia

111
Q

What are the secondary causes of polycythaemia?

A 
Due to appropriate increase in erythropoietin
-High altitiude
-Lung disease
-CVD: R-L shunt
-Heavy smoking
-Increased affinity of Hb e.g. familial polycycthaemia
Due to inappropriate increase in erythropoietin
-renal disease e.g. RCC, Wilm’s tumour
HCC
Adrenal tumours
Cerebella haemangioblastoma
Massive uterine fibroma
112
Q

How do you Dx PCV?

A

Presence of both major and one minor criteria or the presence of 1st major criteria and 2 minor criteria.
Major:
-Hb > 185 in M, >165 in F
-presence of JAK2 tyrosine kinase V617F or other functionally similar mutation such as JAK2exon 12 mutation
Minor
-bone marrow Bx showing hypercellularity for age witgh trilineage growth with prominent erythroid, granulcytic and megakaryocytic proliferation
-serum erythropoietin level below the reference range for normal
Endogenoous erythoid colony formation in vitro

Ix:
Elevated platelets

113
Q

What are the clinical features of PCV.

Tx

A 
HT
Angina
Intermittent claudication
Tendency to bleed
Severe itching after a hot bath
Gout
Peptic ulceration

Tx:
Low dose aspirin to reduce thrombotic events.

VENESECTION best overall survival
- perform once or twice weekly until HCT is 40-45%.
Fe def will develop.
>60y + previous thrombotic event
- hydroxyurea + phlebotomy to decrease subsequent risk of thrombosis

114
Q

What lab features distinguish between primary and secondary PCV?

A

Primary-low EPO

Secondary- normal or raised EPO

115
Q

What is Gaisbock’s syndrome (AKA stress erythrocytosis)? What are the features?

A

An apparent rise of the erythrocyte level in the blood.
Features
-normal RCV
-reduced plasma volume
- often caused by loss of body fluids through burns, dehydration and stress.

116
Q

What are the lab features of ET?

A

Normal Hb and WCC
Platelet count ~600, may be as high as 2000
JAK2 mutation in 50% of pts

117
Q

What are the lab features of myelofibrosis?

A

WCC>100
Platelet count may be very high but in later stages thrombocytopenia occurs
Bone marrow aspiration often unsuccessful
Bone marrow trephine demonstrates markedly increased fibrosis
Increased numbers of megakaryocytes
Leucocyte alkaline phosphatase score is normal or high
High serum urate
Low serum folate levels
Philadelphia chromosome ABSENT

118
Q

Which lab investigation will help you distinguish between myelofibrosis and CML?

A

Bone marrow appearance

Absence of Philadelphia chromosome in myelofibrosis

119
Q

What are the lab features of myelodysplasia?

A

Pancytopenia
-anaemia
neutropenia
monocytosis
thrombocytopenia
Bone marrow usually shows increased cellularity despite pancytopenia
Ring sideroblasts are present in all types

120
Q

What is the value for an elevated HCT in M and F?

A

M=>60%

F = >57%

121
Q

What sign is classically seen in pts with protein c def commenced on warfarin?

A

Skin necrosis

122
Q

How is MM Dx?

A

Presence of at least 10% clonal bone marrow plasma cells and serum or urinary monoclonal protein

123
Q

What is the most common presentation of MM?

A

Bony lesions 80%
Anaemia 73%- related to bone marrow infiltration or renal dysfunction
Bone pain -58%
Renal impairment – 20-40% due to tubular damage from excess protein load, dehydration, hypercalcaemia and use of nephrotoxic medications

124
Q

Warfarin exerts anti-thrombotic effects via depletion of which factor?

A

FII (prothrombin) is converted to thrombin.

Warfarin inhibits Vit K dependent synthesis os II,VII,IX,X

125
Q

What is the commonest cause of activated protein C resistance?

A

Factor V leiden mutation. Accounts for 40-50% of inherited thrombophilia in Caucasians.

126
Q

What is myeloid metaplasia?

A

A complication of PCV.
Caused by progressive fibrosis of the bone marrow and shift hematopoisesis from marrow to the liver and spleen. Some of the largest spleens seen are in MM and agnogenic myeloid metaplasia (AMM).

127
Q

What do you see on the blood film in myeloid metaplasia?

A

Tear drop cells and leukoerythrocytoblastic picture are characteristic.

128
Q

What Ix result is most suggestive of intravascular haemolysis? What is the mechanism?

A

Urinary haemosiderin.

Free Hb released in intravascular haemolysis. Free Hb is excreted in urine as haemoglobinuria, haemosiderinuria

129
Q

Which karyotypes are favourable in AML?

A

t(8:21)
t(15:17)
Inv (16)

130
Q

Why is cytogenentics important?

A

Predicts prognosis.
•Good - t(15:17), t(8:21), inv(16)

  • Intermediate (Normal karyotype, Y-
  • Poor - del7, del5q, inv(3), t(3:3), t(6:9), t(9:22), 11q23, complex cytogenetics >=3 abn
131
Q

What is the strongest adverse prognostic factor in AML?

A

Age > 60 y. CTx has not been shown to improve survival

132
Q

What is the strongest good prognostic factor in ALL?

A

Paediactric age group is the strongest good prognostic factor

133
Q

What is the 1st line Tx for CLL?

A

Chlorambucil

2nd line Tx- Fludarabine

134
Q

List the myeloproliferative disorders under heading BCR-ABL +ve and BCR-ABL –ve.

A

BCR-ABL +ve -> CML

BCR-ABL –ve -> PCV, Essential thrombocythemia, Myelofibrosis

135
Q

List the plasma cell dyscrasias

A

MGUS monoclonal gammopathy uncertain significance
MM
Amyloidosis (like MGUS with attitude)

136
Q

Causes of microcytic anaemia

A

Fe def
Thalassaemia
Anaemia of chronic disease
Sideroblastic anaemia

137
Q

Causes of macrocytic anaemia (megaloblastic)?

A

Megaloblastic

  • Vit B12 def
  • folate def
  • pervicious anemia
  • drugs e.g. hyroxyurea, azathioprine, zidovudine
  • congenital enzyme def in DNA synthesis e.g. orotic aciduria
  • myelodysplasia due to dyserythropoiesis
138
Q

Causes of macrocytic anaemia (Normoblastic)?

A

Pregnancy
Alcohol
increased Reticulocytes e.g. haemolysis, haemmorhage
Liver disease
Hypothyroidism
Drug therapy e.g. azathioprine
Cold agglutins due to autoagglutination of red cells

139
Q

Causes of normocytic anaemia

A 
Blood loss
Anaemia of chronic disease
Renal failure
AI rheumatic disease
Marrow infiltration/fibrosis
Endocrine disease
Haemolytic anaemias
140
Q

What is PNH characterized by?

A

Intravascular haemolysis
Venous thrombosis
Haemoglobinuria

141
Q

What is the defect in alpha thalassaemia due to?

A

Gene deletion

142
Q

What is the defect in beta thalassaemia due to?

A

Point mutation resulting in decreased beta globin synthesis

143
Q

Is the INR useful to determine liver function?

A

No. PT is a better indicator.

144
Q

What are the causes of an elevated PT and normal APTT?

A 
VII def
VII inhibitor
Vit K def
Liver disease
Warfarin
145
Q

What are the causes of a normal PT and elevated APTT?

A

Inhibitors
Lupus anticoagulant
Heparin -elevated TT and reptilase normal

146
Q

What are the causes of and elevated PT and APTT?

A 
Inhibitors
Liver disease
DIC
Heaprin and warfarin
V, X, II and fibrin def
Combined factor def
147
Q

What results would you expect in regards to haemostatic function for the Haem A/B?

A

PT normal, aPPT elevated, TT N, Fib N, Plt N, Platelet function analysis (PFA) N

148
Q

What results would you expect in regards to haemostatic function for the vWD?

A

PT N, aPPT elevated, TT N, Fib N, plt N, PFA A

149
Q

What results would you expect in regards to haemostatic function for the DIC?

A

PT elevated, aPPT elevated, TT elevated, Fib low, Plt low, PFA A

150
Q

What results would you expect in regards to haemostatic function for the TTP?

A

PT N, aPPT N, TT N, Fib N, plt low, PFA A

151
Q

What results would you expect in regards to haemostatic function for the decreased Plts ?

A

PT N, aPPT N, TT N, Fib N, plts low, PFA A

152
Q

What results would you expect in regards to haemostatic function for the Abn platelet?

A

Pt N, aPPT N, TT N, Fib N, Plt N, PFA A

153
Q

What results would you expect in regards to haemostatic function for the CTD/VD?

A

PT N, aPPT N, TT N, Fib N or elevated, Plt N, PFA N

154
Q

What are the thresholds for transfusion of blood components?

A

Platelets Spontaneous bleeding
Fibrinogen 1.5
APTT no data

155
Q

What are the indications for prothrombinex?

A

warfarin reversal

156
Q

What does prothrombinex contain?

A

Conc FII, IX, X and low levels of VII

157
Q

Complication of prothrmobinex?

158
Q

What is the indication for recombinant FVIIa?

A

Control of bleeding or procedural prophylais in pts with inhibitrs to coagulation factors VIII or IX

159
Q

What is the haem indication for desmopressin (DDAVP)?

A

Mild vWD
MDS
Enhance haemostasis in platelet dysfunction defects e.g vWD
Increases vWF and FVIII levels
Effect within 30-60 minutes and sustained for 6-12 hours

160
Q

What are the complications of desmopressin?

A

Hyponataemia and tachyphylaxis

161
Q

What are the causes of HTR?

A

Febrile = RED

•Donor RBC Ag reacting with recipients pre-existing alloantiboes.
•Can occur with other products FFP, IVIG
•Usually due to clerical/procedural error
•High risk patients are:
repeated transfusions
multiparous

162
Q

What are the symptoms of HTR?

A
  • Fevers, back pain due to renal blockage, pain at infusion site
  • Anaemia
  • Jaundice
  • ATN
  • DIC
163
Q

Dx of HTR?

A
  • DAT
  • Repeat X-match done and recipient
  • Urine
  • FBC-Hb
  • Used packs
  • BC
164
Q

What is the cause of NFHTR?

A

• Recipients Ab reacts with donor white cells

165
Q

What are the immunological causes of delayed/chronic TF reactions?

A 
Delayed HTR (5-10 days later)
GVHD
TRIM
Alloimmunisation from repeated transfusions
Post transfusion purpura
166
Q

What is the mechanism of GVHD?

A

Occurs after stem cell or BM transplant
Recipient cannot amount an immune response to the donor lymphocytes (DL) due to HLA one-way compatibility or immunosupresion

167
Q

What is the clinical presentation of GVHD?

A
  • Occur 2-30 days post TF
  • Rash- erythmeatous with macules and papules —> erythroderma
  • Fever
168
Q

Tx of GVHD?

A
  • Acute: High dose methylpred

* Chronic: Prednisone

169
Q

What are the viral causes of transfusion reactions?

A 
aHIV
HBV
HCV
HTLV
Creuztfeldt-Jakob Disease
170
Q

What factors make up the Well’s score?

A 
Prior Hx TE 1.5
HR > 95 bpm 1.5
Recent Sx/immob in previous 4 weeks 1.5
Haemoptysis 1
Active malignancy 1
Clinical signs of a DVT (pain palpation/oedema) 3
Unlikely alternative Dx 3
>4 = PE likely
171
Q

What factors make up the Geneva Score?

A 
Age>65y 1
Prior TE 3
HR >95 5
HR 75-94 3
Recent Sx/limb immbolisation 2
Haemoptysis 2
Active malignancy 2
Clinical signs DVT 3
Pain on palpation/oedema 4
>5 = PE likely
172
Q

How do you monitor LMWH?

A

Anti-XA levels
renal function ml/min 48h
Normal >60 - nor required

173
Q

Which NOACs target Xa and their half-life?

A

Apixiban 8-15 h, CYP 450 15%
Rivaroxiban 9-13 h, CYP 450 32%
Edoxaban 10-14 h, CYP 450 30% (not available in Australia)
Renal excretion 25-35% for above
Above drugs inhibit, not deplete factors therefore replacement of factors only effective if able to bypass or overwhelm inhibition of Xa or thrombin

174
Q

Which NOACs target IIa?

A

Dabigatran 12-14h

No Cyp450 activity

175
Q

Indications for dabigatran (PBS)?

A

Prevention of TE in pts who have undergone major orthopaedic lower limb Sx
Stroke prevention in non-valvular AF

176
Q

Indications for rivaroxiban (PBS)?

A

Prevention of TE in pts who have undergone major orthopaedic lower limb Sx
Stroke prevention in non-valvular AF
Tx of acute symptomatic DVT without symptomatic PE and to prevent recurrent VTE
Tx of acute PE to prevent recurrent VTE

177
Q

Are NOACs inferior or non-inferior to warfarin fro the prevention of stroke/embolism in AF, Tx of DVT/PE?

A

Non inferior

178
Q

What are the differentiators between the NOACs Dabigatran, Apixiban and Rivaroxiban?

A

Dabigatran 150 mg was associated with a reduction in ischameic stroke
Rivaroxiban OD was associated with a lower rate of fatal bleeding
Apixiban was associated with a reduction in all cause but not CV mortality

179
Q

How long do you continue Tx for a 1st episode VTE after 3 months of Tx with NOAC?

A

•VTE associated with temporary RF e.g. Sx
stop anticoagulation

•Cancer associated VTE
complete 6 months of Tx
If ongoing cancer therapy Tx then cont for another 6 months
If no more Cancer Tx than stop

•Unprovoked VTE
stop anticoagulation
risk assessment for recurrent VTE, if high risk and low risk bleeding than complete 12 months of Tx. If low recurrence risk and high bleeding risk than stop.

180
Q

What is the impact of oral and non-oral hormones on VTE?

A
  • 2-6 fold increased risk of VTE
  • limited data on non oral hormones
  • Family Hx TE -> 2-4 fold increase risk TE
  • Prior Hx of TE -> recurrence rate 3% per year if OCP continued
  • Hormone releasing IUD better than oral preparations
  • increased risk with thrombophilia
181
Q

What is eculizumab?

A

A C5 monoclonal antibody used in the treatment of PNH?

182
Q

What is the leading cause of death in beta thalassaemia major?

A

Heart failure secondary to a severe iron induced cardiomyopathy in poorly chelated patients.

183
Q

What globins do the following contain: HbA (normal), HbA2 (minor) and HbF (fetal)?

A 
Normal HbA (a2b2)
Minor HbA2 (a2,delta2)
Fetal HbF (a2, y2)
184
Q

List the classifications of alpha thalassaemia’s?

A

Silent carrier state = a-/aa, 1 gene deletion, normal Hb
Alpha thalassemia trait = a-/a- or aa/–. 2 gene deletions, HbA -> mild anaemia
Hb H = –/-a, 3 gene deletions, HbH -> moderate anaemia
Hb Barts = –/–, 4 gene deletions, fetal hydrops

185
Q

Which haem disorder provide protections from plasmodium falciparum?

A

G6PD def
Sickle cell trait
Alphal thal

186
Q

Transfusions transmitted infections are most likely to occur with which blood product?

187
Q

What is the cause of a haemolytic transfusion reactions?

A

ABO incompatibility
Donor RBC antigens reacting with recipients pre-existing allo-antibody
Mx: DAT, repeat Xmatch

188
Q

What is the cause of a febrile non-haemolytic transfusion reaction (FNHTR)?

A

Recipient Antibodies against the donor’s leucocytes

Mx: Self limiting without complications

189
Q

What is the cause of TRALI?

A

Donor’s antibody reacting to recipients leucocytes (opposite of Febrile non haem transfusion reaction)
Mx by informing public health and donor to stop donating.

190
Q

What is the cause of Delayed transfusion reactions (GVHD)?

A 
Recipient unable to mount an immune response to donor’s lymphocyte.
High mortality (>85%)
Mx by using irradiated products.
191
Q

What is the Tx for ITP?

A

Prednisone

192
Q

What is the Tx for Thrombotic Thrombocytopenic Purpura?

A

Plasma exchange

193
Q

Leucodepletion reduces the risk of which transfusion associated infection?

194
Q

What is the most appropriate Tx for prevention of Fe overload in transfusion dependen pts?

A

Desferroxamine

195
Q

How do you prevent FNHTR in a pt requiring regular transfusions?

A

Leucodepletion

196
Q

What is the Tx for HITS?

A

Stop heparin

Commence Danaparoid

197
Q

What is the risk of acquiring HIV, HCV, HBV, HTLV and malaria from a screened blood transfusion due to the infectious window period of HIV?

A 
HIV- 1 in 5, 000, 000
HCV 1 in 2.7 million
HBV 1 in 739 000
HTLVI and II is 1 in 17.5 milliom
Malaria 1 is 1 in 4.9-10 million
198
Q

What type of anaemia does RBC aplasia produce?

A

Normochromic normocytic anaemia with elevated EPO levels

Erythroblasts will be absent in the bone marrow therefore diminished reticulocytes

199
Q

which factors are Vitamin K dependent?

A

2,7,9,10, Protein C and S
F7 and Protein C have the shortest half life and therefore decrease first
Vit K def manifest with prolonged PT time first then aPTT prolonged in severe def

200
Q

What are the major causes of Vit K def?

A

Dietary intake
Intestinal malabsortpion
Liver disease

201
Q

What do you expect to see on a peripheral blood smear of a pt with AIHA?

A

Microspherocytes

202
Q

What do you expect to see on a peripheral blood smear of a pt with B12 def?

A

Macrocytosis and PMN with hypersegmented nuclei

203
Q

What do you expect to see on a peripheral blood smear of a pt with MAHA (TTP/HUS)?

A

Schistocytes

204
Q

What do you expect to see on a peripheral blood smear of a pt with Sickle cell disease?

A

Sickle cells

205
Q

What do you expect to see on a peripheral blood smear of a pt with thalassaemia or liver disease?

A

Target cells

206
Q

Which malignancies are associated with pure red cell aplasia?

A

Thymomas and lymphomas

207
Q

How do you manage asymptomatic essential thrombocytosis?

A

FBC q 3 months
Group patients into low, intermediate or high risk
-intermediate: regular RBC q 3 months and low dose aspirin for mild vasomotor symptoms
-high – hydroxyurea and aspirin

If neutropenia from hydroxyurea than Anegralide which reduced shedding of platelets from megakaryocytes.
Hydroxyurea has superior benefit.

-pregnant and high risk – interferon alpha 2b and anti-plt Tx

208
Q

What is the MOA of anagrelide?

A

Inhibitor of cAMP phosphodiesterase III that reduces plt production and at higher doses inhibits plt aggregation

209
Q

Indications for platelet transfusion

A
  • I bag of platelets = 60 ml = 4 Unit = 20-30 platelet rise.
  • Thrombocytopenia
  • Defective pleatelt function
  • Surgical pt platelets
210
Q

Indications for FFP?

A
  • contains all coagulation factors
  • used for correction of bleeding where multiple co-agulation factor
  • deficiencies are present
  • DIC
  • liver dysfunction
  • dilutitional coag
  • TTP to replace DAMTS-13 enyme
  • effects immediate and not sustained
  • number to correct ?15 ml/kg
211
Q

What does cryoprecipitate contain?

Indications for cryoprecipitate? (5Fs)

A
  • contains 5Fs: fibrinogen, vWF, FVIII, FXIII, Fibronectin (5Fs)
  • 10-15 ml = 200 mg Fib
  • Average bag 30 ml (20-40 ml)
  • 150 ml = 2 g ->raise level of fibrinogen 0.7 g/L
  • Fibrinogen defi
  • dysfinrinogenaemia
  • DIC
  • can be used in vWD
  • used in any condition that gives you low fibrinogen
212
Q

Indications for Prothrombinex?

A

Contains Vitamin K dependent factors and used in warfarin reversal

213
Q

Indications for Recombinant Factor VIIa?

A

consist of activated FVII
Used to control bleeding or procedural prophylaxis with patients with inhibitors to coagulation FVIII or IV (Haemophilias)

214
Q

Indication for Desmopressin?

A

increase vWF and FVIII levels in vWD

215
Q

Indication for tranexamic acid?

A

Displaces plasminogen from fibrin and inhibits fibrinokysis

Used for mucosal bleeding

216
Q

Treatment for Hodgkin lymphoma?

A

ABVD for 2 -3 cycles and RTx

217
Q

Spherocytes strongly suggestive of?

218
Q

Schistocytes and helmet cells suugetive of?

A

Microangiopathic contribution of haemolytic anaemia

219
Q

tear drop shaped erythrocytes, nucleated erythrocytes and immature granulocytes strongly suggestive of?

A

Primary myelofibrosis

220
Q

JC virus. What, cause, clinical, Dx, Tx?

A

Lytic lesions of oligodendrocytes and astrocytes resulting in multiple areas of demyelination in the CNS
PML lesions are assymetrical demyelinated plaque areas with irregular borders surrounded by macrophages and irregular astrocytes with large, multiple nuclei.

Cause:
Human polymavirus - JC virus
5% of the world is infected with the JC virus however they remain asymptomatic and virus remains quiescent in the kidneys, bone marrow and lymphoid tissue)

Clinical:
Muscle weakness
Sensory deficit
Cognitive dysfunction
Language impiaremnet
Co-ordination and gait difficulties

Dx:
JC virus DNA in CSF by PCR
or JC virus DNA or proteins by insitu hybridization of immunohisto on brain Bx sample

Tx:
Supportive
Cease or decrease immunosuppression
No specific anti-viral drugs for JC virus
Recovery of immune system can trigger IRIS. In HIV neg pats with PML-IRS Tx with corticosteroids

221
Q

CLL: What, Epid, Aet, Ix, Dx, Tx, Complications?

A

a monoclonal disorder characterised by a progressive accumulation of functionally incompetent lymphocytes.
Incurable.

Epid:
Commonest haem malignancy
65-70 y
M:F 1:1

Aet:
Unknown
Genetics

Causes?
Clinical:
SOB
Fatigue
Lymphadenopathy
Splenomegaly
B-symptoms
Ix:
FBC - Hb  5000/microlitre
Blood film - smudge/smear cells
Flow cytometry - CD5, CD19, CD23
BM Bx - MB infiltration by leukaemic cells

Dx:
Following criteria:
Absolute lymphocyte count in the peripheral blood ≥ 5000/microL [5 x10(9)/L], with a preponderant population of morphologically mature-appearing small lymphocytes.
Demonstration of clonality of the circulating B lymphocytes by flow cytometry of the peripheral blood.
A majority of the population should express the following pattern of monoclonal B-cell markers: extremely low levels of Sm Ig and either kappa or lambda (but not both) light chains, expression of B-cell associated antigens (CD19, CD20, CD21, CD23, and CD24), and expression of the T-cell associated antigen CD5.

Prognosis:
Depends on clinical stage and rate of disease progression:
lymphocyte doubling time and serum β2-microglobulin level, immunophenotyping, cytogenetic studies, fluorescence in situ hybridization testing, and mutational gene assessment (del(17p13) (p53)

Tx:
Observation if asymptomatic

Symptomatic/advanced
1st - Fludarabine CR combination with Ritux or single agent Cx.

Adjunct allogenic SCT
- Allogeneic HSTC is the only curative treatment but is associated with a high risk of morbidity and mortality

Poor ECOG - Obinutuzumab + chlorambucil or mono therapy with chlorambucil or Ritux

Cx:
Febrile neutropenia
TLS
Hypogammaglobulinaemia
AIHA
ITP
Richter transformation - NHL
Fludarabine induced interstitial lung disease
222
Q

What is the most common peripheral aneurysm? Presentation? Complication?

A

Popliteal artery aneurysms
At presentation 50-80% are symptomatic (thrombosed or embolising distally)
Rupture rates are

223
Q

What is erythromyelgia?

A

Condition characterized by intense burning pain, erythema and increased skin temperature primarily of feet and hands.

Symptoms vary between pts, can flare up or be continuous.
Bilateral involvement.
UL can be involved- fingers.
Classic description of erythromyelgia is red, painful, warm hands and feet bought on by warming or hanging the limb downward and relieved with cooling and elevation.

224
Q

What is Buerger’s disease (thromboangiitis obliternas)?

A

A rare disease of the arteries and veins in the arms and legs.
Blood vessels become inflamed, swell and can become blocked with blood clots.
This can lead to infection and gangrene.
All patients are smokers!!
First affects hands and feet and may affect larger areas of arms and legs.

225
Q

Pt with ITP post splenectomy has moderate thrombocytopenia and Howells jolly bodies. A symptomatic. Next step?

A

Watch and wait as no symptoms.

Howell jolly bodies suggest functional a splenic.

226
Q

What is CML due to?

A

chromosomal translocation between chromosomes 9 and 22. Results in abnormal BCR-ABL fusion gene -> unregulated proliferation.

227
Q

What is the MOA of hydroxyurea?

A

Causes inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor. An S-phase specific.

228
Q

What do you expect in the BM and peripheral cell counts with Myeloproliferative neoplasm vs. myeloproliferative syndrome?

A

MPN

  • hypercellular BM (except MF)
  • increased peripheral cell countse.g. ER, CML, PRV

MDS
- hypercellular BM (except hypoplastic MDS) and peripheral cytopenias

Both have risk of transforming to AML

229
Q

Aplastic anaemia. What, pathophys, Dx, Tx

A

BM fails to produce blood cells resulting in a hypocellular BM and pancytopenia.

Acquired or Congenital (20%).
Most common congenital form is Fanconi anaemia, AR or X-linked.

Pathophys:
In acquired, immune dysfunction and abnormal expression of suppressor T cells if often present.
Small PNH clones identified in 50% of pts with aplastic anaemia (Dx by absence of CD 55 and CD59).

Dx:
Bone marrow aspitate and Bx
- hypocellualr BM with increased fat space and decrease in hamatopoietic elements.
- reticulocytes LOW
- DAT is -ve

Tx:
HLA compatible sibling allogenic HSCT as initial therapy. Cure rate of 75-90%.

Non HSCT candidates:
- antithymocyte globulin and cyclosporine therapy which has resulted in long term suvival in 60-85%

230
Q

What is the immediate Mx to reduce the risk of perioperative bleeding in a pt with ITP, plt count 30 who underwent an urgent procedure ?

A

Platelet transfusion
Adjunct Tx with high dose glucocorticoids or 100 mg and IVIG also appropriate.

Prednisone is used in Tx but takes time to work.

231
Q

MM. Dx?

A

> 10% clonal malignant plasma cells on BM and serum or urinary monoclonal paraprotein e.g. IgG kappa.

232
Q

MM. When to Tx?

A

CRAB symptoms or any 1 of the following biomarkers of malignancy consider Tx:
clonal bone marrow plasma cell > 60% or >1 lytic lesion on MRI

233
Q

Dx of MGUS?

Tx?

A

No symptoms

low paraprotein,

234
Q

Dx of smouldering/asymptomatic myeloma?

A

high paraprotein > 30 g/L
>10% plasma cells in bone marrow
No CRAB features
10% pa will progress in the 1st 5 years

Tx:
Close FU blood test +/- xr

235
Q

Indication for Bortezumab in MM?

AE?

A

Relapsed or 1st line with steroids for pts with renal failure

AE:
Peripheral neuropathy severe, takes years to resolve

236
Q

MM. 1st line therapy?

A

Autologous SCT - best overall survival
Initial induction CTx. Standard therapies consist of:
Proteasome inhibitor e.g. bortezomib OR
immunomodulatory agent e.g. thalidomide or lenalidomide PLUS
alkylating agent cyclophosphamide or melphalam
PLUS
Steroid (Dex/Pred)

237
Q

When is Lenolidamide indicated? AE?

A

Second line therapy for failed Tx with Thalidomide.

More myelotoxicty.
Less neuropathy.
Risk of secondary primary malignancies.

238
Q

What is a common complication of HL after mantle therapy (RTx to lymph nodes of neck, chest and axillar, sometimes upper abdomen)?

A

Hypothyroidism most common after neck irradiation

Takes place in 1st 5 years but some take place beyond 10 years

239
Q

What is the most common cause of ACQUIRED Protein C resistance?

A

Pregnancy

Factor V Leiden is the most common cause of INHERITED

240
Q

CML:
What
Clinical
Ix

A 
Disorder characterised by myeloid proliferation
Consist of:
chronic
accelerated
blast phase -> AML 80% or ALL 20%
Clinical:
Asymptomatoc
Fatigue
Night sweats
weight loss
abdo pain
early satiety
bleeding
Splenomegaly most common finding
Ix:
9:22 translocation or
BCR-ABL fusion transcript
Bone marrow: hypercellular with myeloid hyperplasia
Chronic phase:
- WCC high
Hb low or normal
Plts normal or high
Blood film = neutrophilia and left shifted granulopoiesis and basophilia

Tx:
All patients treated, even if asymptomatic.
Chronic phase: Imatinib 1st line
More potent BRC-ABL inhibitors, Nilotinib and Dasatinib are used in pts intolerant or have disease resistant to imatinib.

HSCT is reserved for eligible patients in accelerated or blast phase of disease or disease resistance to BCR-ABL inhibitor regardless of phase.

The best chance of long term survival is ALLOGENIC BMT

241
Q 
Myelodyplastic syndrome:
What
Presentation
Ix 
Tx
A

Clonal haemotopoietic stem cell disease characterised by cytopenia, dysplasia, ineffective haematopoiesis and increased risk of development to AML

Presentation:
Fatigue
Easy bleeding
Infections due to neutropenia- common cause of death

Ix:
Normocytic or macrocytic anaemia
Blood film: dysplastic changes such as nucleated erythrocytes and hypolobated, hypogranular neutrophils

BM: Hypercellular and dypslasia identified in affected line

Tx:
Supportive with transfusions and GCSF when septic
Azacitidine (DNA hypomethylating agent) improves survival

242
Q

Key distinguishing points in myeloproliferative disorders.

A

CML = BRA ABL +ve

ET = platelet count > 600 x109/L (600, 000/uL) on 2 separate occasions 1 month apart

PCV = increase Hb, JAK 2 +ve

Myelofibrosis = WCC>100, high leucocyte ALP

Myelodysplasia = pancytopenia

243
Q

AML:

A

proliferative leukaemic cells leading to accumulation of blast cells.

Presentation:
fatigue
bruising
infection

Ix:
pancytopenia

Cytogenetics:
FLT3 poor prognosis
KIT = poor
NPM1 = reduce risk of relapse, improved CR
Age> 60 biggest predictor of poor prognosis

Tx:
7:3 Ida in elderly

APML presents with DIC.

244
Q

APML:

A

characterised by translocation of retinoic acid receptor on Ch17.
t (15:17) most common translocation, >98%

Presentation:
DIC

Tx:
ATRA and anthracyclines = complete remission in >90% of cases and cure in >80%

Complication:
Differentiatio syndrome - pul infiltration by diff APML blasts. Tx with steroids.

245
Q

ALL:

A

accumulation of malignant immature lymphoid cells
Most common in children

Epid:
Bimodal, 4-10 y and then >50y

Presentation:
Non specific
pancytopenia
Bone pain, splenomegaly and lymphadenopathy common

Dx:
FISH - t(9:22), philadelphia chromosome = poor prognosis

Tx:
Imatinib if positive t(9:22) PLUS
anthracyclines, corticosteroids and vincristine
intrathecal MTx to prevent CNS relapse

Pts in first remission should be considered for allogenic BMT due to high relapse rate.

246
Q

Waldenstrom hyperviscosity syndrome.

Initial Ix and Mx.

A

Ix:
Plasma viscosity measurement to Dx and Tx

Tx:
plasmaphoresis
then cytoreductive therapy

247
Q 
drug-induced neutropenia or agranulocytosis:
Presentation
Dx criteria
Ix
Tx
A

Presenation:
fever, mouth sores, or gingival disease inflammation -> suggest BM failure.

Dx:
The diagnosis is confirmed when all of the following are present:

●Low to absent absolute neutrophil count
●Absence of anemia and thrombocytopenia
●A hypocellular bone marrow that shows normal erythropoiesis and megakaryocytopoiesis, but few if any granulocytic precursors.
●Return of the neutrophil count to normal when the offending agent is stopped, with or without the concomitant use of a granulocyte colony-stimulating factor

Ix:
BM unless clear source of offending drug

Tx:
Stop drug
GCSF if pt ill from infection or evidence of BM suppression

248
Q

AIHA: Abs associated.

A

Antibodies are IgG = 80% or IgM = 20%

249
Q

Warm AIHA

A

Caused by IgG abs that bind erthrocyte Rh antigens at 37 degrees.

Can be Idiopathic or associated with other AI, lymphoproliferative, malignant or drug related.

Haemolysis is caused by clearance of antibody -coated erythorcytes to the Fc receptor on splenic macrophages. Partial phagocytsois leads to sphercytes which become entrapped and removed by the spleen.

Presentation:
Rapid or more insidious symptoms of anaemia or jaundice.
Mild splenomegaly.

Blood film: SPHEROCYTES
DAT +ve for IgG and NEGATIVE or weakly positive for COMPLEMENT.

TX:
CORTICOSTEROIDS
Splenectomy for non responders.

250
Q

Cold AIHA

A

Caused by binding of IgM abs to erythrocytes antigens, typically I or i at temperatures below 37 degrees with max activity at 4 degrees.

Aetiology:
Few weeks after EBV infection or mycoplasma.

IgM abs fix COMPLEMENT to erthythrocyte membrane -> erythrocyte clearance by DIC or binding to macrophages in the liver.

Ix:
Anaemia is mild, moderate and chronic.

Cold agglutination leads to falsely elevated MCV.

Blood film- clumping or AGGLUTINATION of erythrocytes
IgG negative, strongly positive for C3

Tx:
Avoidance of cold temperatures
Chlorambucil, cyclophosphamide, and, more recently, rituximab, have shown benefit.

corticosteroids and splenectomy are INEFFECTIVE!

251
Q

G6PD:

A

Congenital haemolytic anaemia
MOST COMMON ERYTHROCYTE ENZYME DEFECT.
Mutations on X chromosome.
Inability of erthrocyte to generate (NADPH) and maintain glutathione in a reduced state.

Epid:
M>F
African
Heterozygous def protects against P. falciparum

Causes:
African variant leads to episodic haemolysis in response to Infection, Drugs e.g. dapsone, bactrim ad nitrofuratoin,

Mediteraanean variant leasd to chronic haemolysis associated with favism.

Ix:
Blood fils:
bite cells
A brilliant cresyl blue stain may reveal Heinz bodies (denatured oxidosed Hb)

In African american variant, check G6PD levels a few months after the episode as may be elvated

Tx:
Supportive during acute crisis.
Stop drug, treat infection.

252
Q

Sickle cell disease (HbS):

A

Results from point mutation leading to a single amino acid substitution at the 6th position of the B-globin chain.

Sickle cell trait = HbAS, 8-9% of blacks. Benign condition mostly.

Genotypes:
Homozygous SS (HbSS)
- moderate to severe anaemia
-frequent painful crisis
- reduced life expectancy

Sickle - Bo thalassaemia (HbSB0)
- may closely mimic HbSS

Sickle B+thal (HbSB+) and
- less severe anaemia and lower crisis

HbSC disease (HbSC)
- less severe anaemia and lower crisis
- higher frequency of ocular complications and bony infarcts has been noted in Hb SC disease because of increased blood viscosity
Phenotypic differences exist amongst these genotypes.

REFER to evernote table

Mx:
Hydroxyurea - decreased mortlaity (teratogenic)

Erythrocyte transfusion:
Acute indications:
stroke
symptomatic anemia
acute chest syndrome, and surgical interventions

Erythrocyte exchange transfusion: indicated for:
acute ischemic stroke
acute chest syndrome with significant hypoxia and
multiorgan failure/hepatopathy,
as well as in individuals in whom simple transfusion would raise the hemoglobin level to greater than 10 g/dL (100 g/L).

Chronic transfusions may decrease stroke recurrence but may be associated with Fe overload and vascular difficulties and alloumminisation,i ncreased risk for a delayed hemolytic transfusion reaction.

Can lead to moyamoya syndrome.

253
Q

Complications of SCD

A 
Pain crisis:
due to vasococclusion
Tx:
- hydration
- non oipoid and oipoid
- incentive spiro to reduce chest syndrome

Stroke
- Tx erythrocyte exchange transfusion to reduce HbS concetration to

254
Q 
Blood films:
Acanthocyte (spur cell)
Basophilic stipping
Bite cell
Elliptocyte
Macro-ovalocyte
Ringer sideroblast
Schistocyte (helmet cell)
Spherocytes
Teardrop
Target cell
Heinz body
Howell jolly bodies
A

Acanthocyte (spur cell)
- liver disease

Basophilic stipping
- lead poisoning

Bite cell
- G6PD def

Elliptocyte (long oval shaped)
- herid elliptocytsois

Macro-ovalocyte

  • megaloblastic anaemia
  • marrow failure

Ringer sideroblast
- sideroblastic anaemia
Excess Fe in mitochondria

Schistocyte (helmet cell)

  • TTP/ITP/HUS/HELLP
  • heart valve prsothesis

Spherocytes

  • herid spherocytosis
  • drug and infection-induced hemolytic anemia.

Teardrop

  • Bone marrow infiltration (e.g.,
    myelofibrosis) .

Target cell
- HbC disease, Asplenia, Liver
disease, Thalassemia (HALT).

Heinz body
-G6PD deficiency; Heinz
body–like inclusions seen in
α-thalassemia

Howell jolly bodies
- Basophilic nuclear remnants
found in RBCs
- functional hyposplenia or asplenia

255
Q

Amyloid deposits: which protein is universally present?

A

Serum amyloid P (SAP)

256
Q

Heparin with prolonged aPPT. Coagulation test corresponding to heparin?

A

Increased aPPT
Increased TT - measures final step of coag cascade, conversion of fibrinogen to fibrin.
Normal reptilase test

MK (28 decks)

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