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Haematology Flashcards

1
Q

Causes for anaemia with low retics

A

Marrow Problem:

Iron, B12, folate, PRCA, AA, anaemia of chronic disease

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2
Q

Causes for anaemia with high retics

A

Hemolysis
Thal
Blood loss

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3
Q

Microcytic anaemia causes

A 
Thal
Anaemia of chronic dis
Iron def
Lead poisoning
Siderblastic anaemia
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4
Q

Normocytic anaemia causes

A 
Renal failure
Blood loss
Haemolytic anaemia
Anaemia of chronic dis
Bone marrow failure - AA, infiltration, chemo, PRCA
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5
Q

Macrocytic anaemia causes

A 
Megaloblastic - B12, folate, cytotoxic drugs
ETOH
Myelodysplasia
Hypothyroidism
CLD
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6
Q

Target cells

A

Iron def
Liver disease
Haemoglobinopathies
Post splenectomy

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7
Q

Stomatocyte

A

Liver disease, ETOH

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8
Q

Pencil cell

A

Iron deficiency

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9
Q

Spherocyte

A

Warm Hemolysis, septicemia, hereditary spherocytosis

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10
Q

RBC Fragments

A

DIC, HUS, microangiopathy, TTP

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11
Q

Elliptocyte

A

Hereditary elliptocytosis

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12
Q

Tear drop/ poikilocytes

A

myelofibrosis, extramedullary haemopoesis

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13
Q

Ferritin role in iron regulation

A

Iron which is not required is stored by ferritin

Water soluable

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14
Q

Hepcidin Role in iron regulation

A

Expression mostly in the liver
Regulates iron absorption and the distrubution of iron to tissues

-Binds to ferroportin in the enterocyte or reitculocyte and breaks down ferroportin so irons remains within the cell and does not go into blood stream

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15
Q

Regulators of Hepcidin expression

A

Increase Hepcidin:

  • Inflammation
  • Excess iron

Low levels Hepcidin

  • Iron def
  • Hypoxia (EPO)
  • Erythropoesis
  • Haemalytic anaemia, Thal, Haemachromatosis (inappropriately low)
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16
Q

Role for Soluble transferrin receptor in iron deficiency

A

In absence of erythroid hyperplasia, Iron def is prinicipal cause of raised soluble transferrin receptor

NOT elevated in anaemia of chronic disease

Helpful in differentiating iron def and inflammation from anaemia of chronic disease

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17
Q

What is the role for globin chains in Hb structure

A

Protect haeme from oxidation, so that they are efficient in transporting O2

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18
Q

Adult Hb

A

HbA - alpha2Beta2

HbA2- alpha2delta2

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19
Q

HbF

A

Alpha2gamma2

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20
Q

HbS pathology

A

Sickle Cell anaemia

-Valine for glutamic acid in 6th position of beta chain

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21
Q

Sickle cell anaemia vs disease

A

SCA - homozygous for HbS

SCD - Coinheritance of Beta thal gene

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22
Q

HbE cause

A

G to A in codon 26 of beta globin gene

  • Structurally abnormal
  • Behaves like Beta thal mutation
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23
Q

Complications and Mx of Transfusion dependent Beta thal major

A

Cx:
-Iron overload, OP, endocrinopathies, renal impairment

Mx
-Transfusion to avoid bony deformity, Iron chelation, consider splenectomy, Mx complications from iron overload

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24
Q

Precipitants of Sickle cell crisis

A 
Hypoxia
Hypo/hyperthermia
Altitude
Acidemia
Pregnancy
Sepsis
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25
Q

Ix that suggest intravascular haemolysis

A

Raised plasma haemoglobin
Haemoglobinuria
Urinary haemosiderin
Methaemalbuminaemia

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26
Q

Hereditary Spheroctosis

A

Autosomal Dominant
MCHC increase >360g/L
Defect in cytoskeleton of RBC membrane

Features:
-Jaundice, splenomegaly, gall stones, leg ulcers, haemolytic crisis, aplastic crisis

Dx:
-Blood film, negative DAT, flow cytometry, reduced binding of eosin-5 maleimide

Mx: Splenectomy +/- folate

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27
Q

Dx and Mx of warm AIHA

A

Extravascular hemolysis
Antibody reacts with RBC at 37 degrees (IgG mediated)

Causes classically:
-SLE, CLL/lymphoma, Drugs

Dx: Hemolysis screen positive, Spherocytes, Positive DAT

Mx:

  • Supportive and transfusion
  • Steroids
  • IVIG
  • Folate (increased RBC turnover)
  • Aza/Mercaptopurine
  • Consider DVT prophylaxis

Second line:
-Rituximab, +/- Splenectomy, IVIG

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28
Q

Associations of cold agglutinins

A

Mycoplasma pneumoniae
EBV
Lymphoma

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29
Q

Cold agglutinins haemolysis Dx and Mx

A

DAT +ve to C3d only not IgG
Features of intravasular haemolysis

-Mx:
Keep warm
Rituximab
Steroids only helpful if it is mixed cold and warm haemolysis

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30
Q

MAHA definition and causes

A

Hamolytic anaemia and thrombocytopenia

Causes:

  • TTP
  • HUS/aHUS
  • Pregnancy
  • DIC - Prosthetic valves
  • Drugs: Gemcitabine
  • Cancer
  • SLE
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31
Q

Diagnosis and Mx of TTP

A

Low ADAMTS 13 <10%

Tx

  • Apheresis, FFP, steroids, Rituximab
  • Caplacizumab (anti vWF - not available yet)
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32
Q

PNH Features

A

Pancytopenia
VTE
Chronic paraoxysmal intravascular haemolysis, dark urine

Defective protein PIG-A whish is essential for formation of the GPI anchor; a structure that attaches several srface proteins to the cell membrane: CD55/CD59 (protects RBC from complement mediated lysis)

Cells sensitive to complement mediated lysis

Gold Standard Ix:
-Flow cytomettry lack of CD55/CD59

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33
Q

PNH Mx

A

Eculizumab
Anticoagulation lifelong after 1st thrombosis
Transfusions +/- iron infusions

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34
Q

Universal plasma donor

A

AB blood type

Have no antibodies in serum

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35
Q

Massive transfusion protocol

A

Start with/ RBC:FFP:Plt close to 1:1:1 ratio
(4 units blood and FFP, and one pool platelets)
-Next pack add in Cryo 8-10 units

After increased ratio of plasma to RBCs improves mortality

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36
Q

TACO Definition and Mx

A

Transfusion Associated Circulatory Overload

  • Within 2 hours and rapid
  • Usually after large volume
  • HTN common

CXR: pulmonary oedema

Mx: O2, Frusemide, ventilatory support

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37
Q

TRALI definition and Mx

A

Transfusion Related Acute Lung Injury

  • Within 6 hours, progresses to ARDS
  • Initiated by small volume
  • Moderate hypotension

Mx: O2 and ventilatory support

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38
Q

Acquired Thrombophilias

A

APLS

Cancer - LMWH better than warfarin

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39
Q

Hereditary Thrombophilias

A

F5 Leiden/APC resistance
Prothrombin gene mutation
Antithrombin deficiency
Protein C and Protein S deficiency

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40
Q

VTE Duration of anticoagulation

A

Provoked (except cancer)
-3-6 months

Unprovoked

  • Minimum 6 months
  • Decision to stop based on:
  • -# of previous events; >1 cont.
  • -Male&raquo_space;>female recurrence
  • -High risk thrombophilia
  • -Mobility
  • -Elevated D-dimer at completion of initial Rx phase
  • -Obesity
  • -Sequelae of clot: PulmHTN, PPS
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41
Q

CAPS Defintion and Mx

A

Characterised by widespread thrombotic disease with multiorgan failure
-Mortality ~50% despite anticoagulation and immunosuppression

Mx:
-Steroids, immunosuppression, PLEX, aggressive anticoagulation

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42
Q

APLS Diagnostic Criteria

A

1 clinical and 1 lab criteria needed

Clinical:

  • Vascular thrombosis
  • 3x miscarriages
  • 1x stillbirth
  • 1x premature birth due to placental insufficiency or eclampsia

Lab:
-B2GP, LAC, or Anticardiolipin positive in high titres on 2 or more tests 12 weeks a part

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43
Q

Lupus anticoagulant testing

A
  • Suspect when prolonged APTT
  • Fails to correct with mixing
  • Normal TCT
  • Prolonged reptilase time
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44
Q

Corrected APTT testing

A

First mix plasma with normal plasma. If it corrects, then factor deficiency will correct, but an inhibitor will not correct.

Correction is defined as coming back within 4-5 seconds of controlled plasma’s APTT

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45
Q

Which APLS Ab is the most thrombotic

A

Lupus anticoagulant

Also the more Abs positive the higher the risk of thrombosis

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46
Q

APLS and Pregnancy:

APLS Abs and previous thrombosis, but no pregnancy complication

A

Cont with therapeutic anticoagulation

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47
Q

APLS and Pregnancy:

APLS Abs and no prior thrombosis or pregnancy complication

A

Monitor in antepartum period

Post partum prophylaxis for 6 weeks

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48
Q

APLS and Pregnancy:

APLS Abs and >1 fetal loss after 10 weeks

A

low dose aspirin and prophylactic LMWH during pregnancy

+Post partum prophylaxis for 6 weeks

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49
Q

APLS and Pregnancy:

APLS Abs and Hx of preeclampsia

A

Low dose aspirin in 2nd and 3rd trimester

Post partum prophylaxis

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50
Q

VTE prophylaxis in pregnancy if not APLS

A

prophylactic LMWH if prev unprovoked VTE or whilst on COCP

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51
Q

MOA of heparins/LMWH/Fondaparinux

A

Inhibit coagulation through antithrombin
-Directly inhibit factors II, X (and IX , XI)

Fondaparinux: pentasaccharide used in HITS with normal renal function

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52
Q

MOA DOACs

A

Rivaroxaban and apixaban block factor Xa

Dabigatran blocks thrombin activity

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53
Q

Dabigatran level test

A

Dilute Thrombin Clotting Time (TCT)

Trade name: Haemoclot

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54
Q

How long to W/H DOACs prior to OTs

A

Low risk: 24 hours pre op

High risk: 2-3 days prior

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55
Q

Dabigatran reversal methods

A

Idarucizumab
HDx
Activated charcoal if just recently ingested

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56
Q

Apixaban and Rivaroxiban reversal

A

Limited evidence
Some case reports suggest prothrombinex

Andexanet Alfa (Decoy Xa level for these agents to bind to) - not PBS approved

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57
Q

DAT testing

A

Detects antibodies attached to RBCs

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58
Q

Red blood cell modifications:

A

ALL PRBCs are leucodepleted

Irradiated
-For prevention of Transfusion related GVHD as there are still very few leucs in PRBC

Washed
-IF previous allergic rxn to plasma

CMV seronegative
-For Tx and Pregnant patients

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59
Q

Platelets

A

Single donor or pooled from multiple

Lasts 5 days at room temp (most likely to cause sepsis due to this)

Indication:

  • Bleeding in setting of severe thrombocytopenia
  • No effective in patients with rapid platelet destruction (e.g. ITP, TTP)
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60
Q

FFP

A

Plasma with coagulation factors (V, VII, VIII)

Potential to cause infusion rxn or allergic rxn as contains all plasla proteins, antigens, viruses that were in blood at time of collection

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61
Q

Cryoprecipitate

A

From FFP precipitate when thawed

Rich in fibrinogen, FVIII, XIII, vWF, and fibonectin

Indication:
-Only fibrinogen replacement like in DIC

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62
Q

Prothrombinex

A

Coagulation factor concentrate (II, IX, X and low level of VII)
Also contains antithrombin and heparin

Indication:
warfarin reversal

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63
Q

Immediate Haemolytic transfusion rxn

A

Usually due to ABO incompatibility

Results in massive intravasular hemolysis and possibly DIC

Mx

  • Stop transfusion
  • IV saline/resus
  • Correct DIC
  • Aim UO >100 ml/hr
  • Recheck blood group and Xmatch
  • hemolysis screen
  • Culture unit for bacteria (clostridium welchii)
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64
Q

Delayed haemolytic Transfusion Reaction

A

Extravascular hemolysis
Antibody coated RBCs are cleared by reticular system

Usually prevented by Xmatch

Occurs 1-2 weeks post transfusion

Supportive Mx, Ix with hemolysis screen

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65
Q

Febrile non hemolytic transfusion reaction

A

Definition:
-Increase temp >1 degree C

Cause:
- Patient’s Antibodies against donor leukocytes and cytokine storm (most likely cause)

Prevention:
-Leucodepletion (which is done to all RBCs now)

Mx
-Stop transfusion and supportive Mx and exclude other causes

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66
Q

Transfusion associated GVHD

A

Transfusion of viable T cells that then proliferate and attack the recipient

Onset: 8-10 days
>90% fatal

Presentation:
Fever, rash, N+V+D, hepatitis, pancytopenia

Ix: Tissue typing and Bx

Prevention: Irradiation of RBCs

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67
Q

Allergic Rxn with transfusion

A

Most commonly due to IgA

-Screen for IgA deficiency/antibodies

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68
Q

Post transfusion Purpura

A

Profound thrombocytopenia <10, wet purpura (mucosa), platelet refractoriness

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69
Q

Which virus has the highest risk of transmission with transfusion

A

Hep B

1/800,000

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70
Q

Factors produced by normal endothelium to prevent platelet adhesion

A

NO

Prostacyclin

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71
Q

Aspirin MOA

A

prevents platlet aggregation by COX inhibition which prevents formation of thromboxane A2 which promotes platelet aggregation

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72
Q

Clopidigrel and Ticagrelor and prasugrel MOA and which is reversible

A

Blocks ADP from binding to P2Y12 receptor on platelets

Role of P2Y12 receptor activation is to promote binding of GPIIb/IIIa receptor to fibrinogen to form clot

Ticagrelor is the only reversible one.

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73
Q

Tirofiban MOA

A

GPIIb/IIIa receptor blocker

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74
Q

Dipyridamole MOA

A

Phosphodiaesterase inhibitor which prevents cAMP to be changed to AMP.
Increased cAMP decreases Calcium release from platelet which prevents aggregation of platelets

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75
Q

APTT is a measure of which pathway?

A

Intrinsic pathway
Above factor 10

Measures the clotting time of the plasma (without tissue factor I.E extrinsic pathway)

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76
Q

PT is a measure of what pathway?

A

Extrinsic pathway

Factor 7 essentially

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77
Q

APTT and PT together assess a problem in what part of the coagulation cascase

A

The final common pathway (Factor 10 and down)

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78
Q

What does INR measure

A

Measures the clotting time of plasma in the presence of optimal concentration of tissue factor AKA thromboplastin.

Indicates overall efficiency of the extrinsic clotting system

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79
Q

Causes for prolonged APTT that correct with mixing

A

Factor deficiency
Derranged LFTs
Vit K deficiency

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80
Q

Causes for prolonged APTT that DO NOT correct with mixing

A

Lupus anticoagulant
Factor specific inhibitors
Heparin
Abnormal Fibrinogen

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81
Q

Causes of prolonged Thrombin Clotting Time when performed after prolonged APTT doesnt correct with mixing

A

TCT reflects the action of thrombin on fibrinogen

Abnormal fibrinogen
Heparin
Paraprotein esp IgM

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82
Q

Reptilase Time

A

Uses reptiliase instead of thrombin

Unaffected by heparin
Remains prolonged with abnormal fibrinogen

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83
Q

Haemophilia A

A

Factor 8 Deficiency

X linked recessive

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84
Q

Haemophillia B

A

Christmas disease
Factor 9 deficiency
X linked recessive

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85
Q

Differentiating platelet defects from clotting factor deficiency

A

Platelets defect:

  • Skin, mucus membranes, GI
  • Bleeding after minor cuts
  • Petechiae
  • Immediate bleeding after surgery

Clotting Factor Def:

  • Deep in soft tissues, muscles, and joints
  • Large ecchymoses
  • Delayed and severe bleeding after surgery
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86
Q

Haemophilia A Mx

A
  1. Biostate
    - Factor 8 and vWF - plasma derived
  2. Recombinant Factor 8
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87
Q

Haemophilia B Mx

A

Factor 9 replacement either plasma derived (MonoFIX) or recombinant (BeneFIX)

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88
Q

DDAVP for haemophilia patients and SE

A

Can be used in mild cases
Stimulates transient 3-4x increase in Factor 8 and vWF levels as released from storage sites

SE:
Hyponatremia
Fluid retention
Tachyphylaxis

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89
Q

Antifibrinolytic therapy for haemophilia

A

Epsilon aminocaproic acid and tranexamic acid

MOA:
Tranexamic acid binds to lysine residue on fibrin so plasmin cannot cleave it, thus stabilising clot

Useful in mucocutaneous membrane bleeding

90
Q

3 late complications of haemophilia

A
  • Joint destruction due to haemarthroses
  • Transmission of blood bourne infection
  • Development of inhibitor antibodies
91
Q

When to suspect inhibitors in haemophilia

A

-Polyclonal antibodies inhibiting the function of exogenous FVIII and FIX

Suspect when:

  • Mild and mod haemophilia when bleeding phenotype changes
  • Severe haemophilia when they dont respond to treatment
92
Q

Diagnosing an inhibitor in haemophilia

A
  • Fail to increment in factor levels when given bolus
  • APTT mix: fail to correct, when previously would have
  • Bethesda assay: establishes Dx and quantifies the antibody titre
93
Q

Mx of haemophilia with inhibitor

A

Activated PCC

  • FEIBA (longer half life)
  • -Contains activated Vit K dependent factors, 2, 10a, and trace amounts of 7a and 9a

-Recombinant Factor 7a (novo7)

PLEX (rapid)

Immune tolerance induction (steroids, IVIG, Rituximab, cyclo)

94
Q

Novo Seven indications

A

Anything with an inhibitor

Factor 7 deficiency

95
Q

What is the most common bleeding disorder in the community

96
Q

Types of vWD

A

Type 1 - PArtial deficiency

Type 2 - Qualitative defect in vWF

Type 3 Severe deficiency in vWF

97
Q

Features, Diagnosis, and Mx of Type 1 vWD

A

AD

mucocutaneous bleeding
bruising
Excessive bleeding from trivial wounds
Excessive menstrual bleeding

Dx
-History and vWF <20%

Mx

  • DDAVP (except if pregnant or Hx of IHD)
  • Tranexamic acid
98
Q

Mx of Type 2 and 3 vWD

A

Biostate ( contiains factor 8 and vWF)

99
Q

Bernard Soulier Syndrome

A

Inherited platelet disorder

  • Giant platelets and clinically looks like vWD
  • GP1b-9-5 abnormality
100
Q

Glanzmann thrombasthenia

A

Defect in GPIIb/IIIa

101
Q

Pathophysiology of ITP

A

Platelets coated with IgG aotoantibodies undergo accelerated clearance through Fc receptors expressed by macrophages predominantly in the spleen and liver

Megakaryocyte dysfunction as well in the marrow

Also relative TPO defiency (normal when it should be high)

102
Q

Mx of ITP

A

Platelets >30 - observe

Platelets < 30

  • Steroids
  • IVIG
  • Anti D
  • Rituximab
  • TPO mimetics: Eltrombopeg, Romiplostin (SE: rebound thrombocytopenia when stopped suddenly, increased bone marrow fibrosis )

Role for splenectomy if refractory or multiple relapses (2/3) will respond

103
Q

Gestational Thrombocytopenia

A

Benign, no increased risk of bleeding

Occurs in 2nd or 3rd trimester

Range 70-150

Normal after delivery

104
Q

TTP Diagnosis

A

Classic Pentad:

-Thrombocytopenia, MAHA, Fever, neurologic, renal impairment

105
Q

Pathophysiology of TTP

A

Large multimers of vWF due to ADAMTS13 deficency

-If acquired: Antibody against ADAMTS13

Secondary TTP due to cancer, drugs, BM transplant, infection, chemo - Does NOT have ADAMTS13 deficiency

106
Q

Differentiating HUS from TTP

A

HUS/aHUS has normal ADAMTS13 level

107
Q

Mx of TTP

A

PLEX (80% respond)
FFP
Immunosuppression

20% die in first month

108
Q

HITTS

A

Thrombocytopenia caused by antibody mediated platelet activation secondary to heparin
-More so with heparin than clexane

Occurs 4-10 days post heparin
Transient prothrombotic disorder initiated by heparin

109
Q

Pathophysiology of HITTS

A

HIT antibodies are directed against neoepitopes on a self protein - PF4 that are expressed when PF4 (on platelets) is bound to heparin

110
Q

Diagnosis of HITTS

A

Thrombocytopenia AND

  • One or more HIT associated event
  • -Arterial or venous thrombosis
  • -Skin lesion/necrosis at injection site
  • -Acute systemic reaction to heparin

-Detection of HIT antibodies in patient serum or plasma (ELISA)

111
Q

Mx of HITTS

A

Cease heparin and use alternative anticoagulant

  • Danaparoid
  • Direct thrombin inhibitor (Bivalirudin/Argatroban)
  • Fondaparinux (synthetic herparin pentasaccharide)
112
Q

Most common cause of activated protein C resistance

A

Factor V leiden mutation

113
Q

MCV of Thal compared to iron deficiency

A

MCV waaaay down in thal and proportionally down in iron deficiency

114
Q

Transferrin in CLD

A

Transferrin produced by the liver, so transferrin sats may artificially go up because there is not as much transferrin produced, but not in iron overload

115
Q

Where is the most iron stored in the body

116
Q

Pathophysiology of anaemia of chronic disease

A

Diversion of Fe from circulation with less available Fe to erythroid precursors

  • Increased synthesis of ferritin bu (IL-1 and TNF alpha) leads to increased storage
  • Decreased duodenal absorption
  • Blunted EPO response
  • Reduced RBC half life due to cytokines
117
Q

Anaemia of chronic disease Ix results

A

Normocytic anaemia
Low Retics

Ferritin >100 more likely ACD
IF Ferritin 30-100; do soluble transferrin receptor to differentiate between IDA and ACD (Normal in ACD)

118
Q

B12 absorption

A

B12 released from protein in acidic stomach and binds to R-protein
Intrinsic factor released in stomach but binds to B12 in small intestine
B12/IF find to receptor cubilin and absorbed to portal system via terminal ileum

Transcobalamin 2 - Active - transfer B12 to tissues/BM

B12 stored in liver

119
Q

Pernicious anaemia pathophysiology and testing

A

AI destruction of gastric mucosa leads to gastric atrophy and achlorhydria + decreased IF

Ix

  • IF Ab ( specific)
  • Parietal cell Ab (sensitive)
120
Q

B12/Folate tests

A

Macrocytic anaemia
Hypersegmented neutrophils
Low retics, pancytopenia

BMAT: megaloblastic changes
-intrameduallary hemolysis posssible

Holo-transcobalamin 2

121
Q

Best assessment of long term folate stores

A

Red cell folate level

122
Q

Folate rescue therapy in MTX toxicity

A

Folinic acid (leucovorin)

123
Q

Schistocytes

124
Q

Causes of MAHA

A
  • TTP
  • HUS
  • Pre-eclampsia
  • Malignant HTN
  • Prosthetic valve
  • Cancer
  • Drugs
125
Q

Evan’s Syndrome

A

AIHA + ITP

126
Q

Paraoxysmal Cold Haemoglobinuria

A

IgG mediated

Intravascular haemolysis

127
Q

Cold agglutinins

A

IgM
Intravascular and extravascular hemolysis

Associations:
Lymphoma
Mycoplasma
EBV

DAT: C3d only not IgG

128
Q

G6PD Deficiency

A

Get acute hemolytic crisis
Susceptibility to oxidative stress (can’t form NADPH which is protective against this stress)
X linked genetics

Film: Bite and blister cells

G6PD assay can only be done when not hemolysing or will be falsely elevated

Mx: Avoid precipitants
-Antimalarials, sulphur drugs, aspirin, Vit K analogues, fava beans

129
Q

Pyruvate kinase deficiency

A

Chronic hemolysis
Reduced ATP formation, so RBC rigidity
Autosomal recessive genetics

Film: Thorny apple cells

130
Q

Triggers for sickle cell crisis in sickle cell trait

A

Rare

fever
Hypoxia
Acidosis
General anesthesia

131
Q

Acute chest syndrome in Sickle cell disease

A

Most common cause of death post puberty in sickle cell

-SOB, hypoxia, pulmonary infiltrates

132
Q

Mx of sickle cell disease

A 
Avoid triggers
Folic acid
Vaccines for functional asplenia
Exchange transfusions
Hydroxyurea (increase HbF levels and prevent crisis)

Consider stem cell transplant as may be curative, but high mortality

133
Q

Crizanlizumab

A

Anti P selectin Antibody for prevention of pain crises in sickle cell disease

P selectin - adhesion molecule which is upregulated in inflammation, plays a role in sickle crises and vasoocclusion

134
Q

DIC is most assocaited with which acute leukemia

A

APML (acute promyelocytic leukemia)

135
Q

Wells Criteria

A 
Clinical Sx of DVT
Other Dx less likely
HR >100
Immbolisation > 3 days or surgery in last 4 weeks
PRevious DVT/PE
Hemoptysis
Malignancy
136
Q

Most specific test for confirming the diagnosis of complement mediated hemoysis

137
Q

MOA Fibrinolytics

A

Concert plasminogen to plasmin which breasks down fibrin

138
Q

How to assess apixaban level

A

modifed Xa level

139
Q

How to assess Rivaroxaban level

A

Modified anti Xa level

PT will be slightly high

140
Q

How to assess Dabigatran level

A

TCT high

Hemoclot

141
Q

Poor Prognostic features in AML

A
  • FLT3 positive
  • cKIT gene
  • High WCC count at presentation
  • Secondary AML or therapy related AML
  • Monosomy 7
  • Complex cytogenetics
142
Q

Good prognostic factors in AML

A
  • t(15;17)
  • t(8;21)
  • Inv16
  • NPM positie
  • CEBPA positive
143
Q

Most important molecular prognostic marker in AML with normal cytogenetics

A

FLT3

-Drives TKI activity and proliferation

144
Q

Midostaurin

A

kinase inhibitor that inhibits FLT3 - improves OS in FLT mutated AML

145
Q

APML

A

Acutely life threatening, but curable.

  • Malignant promyelocytes
  • t(15;17) = Differentiation block (PML-RARalpha)

Morphology:

  • Hypergranular promyelocytes
  • +++ Auer rods, “faggot cells”
  • Bilobed or reniform nucleus

Cx:
-DIC

Mx:
-All Trans retinoic acid (ATRA)

146
Q

ATRA Syndrome

A

Hyperleukocytosis ad pulmonary infiltrates as APML cells differentiate into granulocytes following ATRA

Rx: Steroids and ventilatory support

147
Q

APML translocation

A

t15;17 (PML-RARalpha)

148
Q

CML translocation

A

t(9;22) BCR-ABL - Philidelphia
chromosome

-Produces dysregulated protein kinase -drives unchecked proliferation

149
Q

MPD genetics

A

JAK-2 V617F mutation

150
Q

CMML genetics

A

5q minus syndrome

151
Q

B-LPDs genetics

A

IgH promoter (14)
Ig LC promoters (2 and 22)
Oncogenes: cMYC (8), CYCD1 (11), BCL2 (18)

152
Q

Clinical hallmarks of CML

A

High WCC with full spectrum of myeloid maturation series in peripheral blood

Basophilia and eosinophilia

Splenomegaly

Morphology:

  • Bimodal distribution favoring myelocytes and neutrophils
  • If blasts >10% then progression to accelerated phase
153
Q

CML Treatment

A

First line: TKIs
-Imatinib, dasatinib, nilotinib, Ponatinib

Allogenic stem cell transplant in selected cases - failed TKI

Second Line:
-Interferon, cytarabine

T315i mutation - resistance to most TKIs except ponatinib

154
Q

PRV mutation

A

JAK2 V617F

  • Tyrosine kinase in EPO and TPO receptor
  • Turned on in the absence of EPO
  • Thrombogenic
155
Q

ET mutations

A

JAK2V617F
CALR
-Phenotype: younger age, high plts, lower risk of thrombosis, better survival
MPL

156
Q

ET Tx

A

Risk stratify

Aspitin if high risk and/or vasomotor Sx
-High risk features: Age >60, Hx of thrombosis, Plt count >1000

Myelosuppression if high risk

  • Hydroxyurea
  • Anagrelide
  • Interferon
157
Q

PRV Tx

A

Venesect to Hct <0.45
Aspirin for all
Anticoagulation if Hx of thrombosis
consider hydroxyurea if high risk/thrombocytosis

158
Q

Myelofibrosis Tx

A

JAK2 inhibitors

  • improve Sx and QoL, not survival
  • Regardless of JAK2 mutation status
159
Q

MDS treatment shown to improve survival and decrease progression to AML in high risk MDS

A

Azacitadine

160
Q

5q Minus Syndrome

A

Form of MDS

Phenotype:
-Middle aged or older female, refractory anaemia (marked macrocytosis), preserved or elevated platelets

Bone Marrow:

  • Hypercellular, but <5% blasts
  • Increased hypolobular megakaryocytes

PAthophysiology
-?insufficient SPARC and RPS14

Mx
-Lenalidomide

Good prognosis

161
Q

Burkitt Lymphoma Mutations

A

cMYC (chromosome 8) Driven by IgH enhancer
t (8;14) or t(2;8) or t(8;22)

Mature B cell neoplasm

162
Q

Mantle cell lymphoma mutations

A 
Cyclin D1 (chromosome 11)
t(11;14)
163
Q

Follicular lymphoma mutations

A

BCL-2 (chromosome 18) - Anti apoptosis protein

t(14;18)

164
Q

What virus is implicated in the pathogenesis of splenic marginal zone lymphoma

A

Hepatitis C

165
Q

Approach to Lymphoma diagnosis

A

BIOPSY!
-Excisonal is best, but core Bx ok

Then stage disease

  • PET/CT
  • BMAT

LDH and viral serologies

166
Q

High Grade NHLs

A

Burkitt’s lumphoma
DLBCL (most common NHL)
Mantle Cell lymphoma

167
Q

Low Grade NHLs

A

Follicular lymphoma
Small lymphocytic lymphoma/CLL
Marginal zone lymphoma

168
Q

EBV associated with which lymphomas

A

Burkitts
Hodgkins
HIV associated lymphoma
PTLD (post transplant lymphoproliferative disorder)

169
Q

HTLV1 associated with what lymphoma

A

Adult T cell lymphoma/leukemia

170
Q

HHV8 associated with which lymphoma

A

Primary effusion lymphoma

171
Q

Hodgkins lymphoma

A

Bimodal age distribution

  • > 75% present with mediastinal/upper torso adenopathy
  • Most common cause of SVC obstruction in young adults

Morphology:
-Reedsternberg cells

Poor prognosis

  • Male
  • Hb <10.5
  • WCC >15
  • Increased macrophages (CD68 positive cells)
  • Alb <40
  • Age >45
172
Q

Tx Hodgkins

A

Limited:
ABVD Chemo +/- involved field RTx

Advanced:
ABVD
OR eBEACOPP

Anti PD1 - can be trialled

Auto SCT for relapse
Allo SCT for relapse post autograft

173
Q

Double Hit Lymphoma Mutations

A

MYC and BCL2/BCL6

Poor outcomes

174
Q

Ann Arbor Staging:

Stage 1

A

Lymphoma located in single region

175
Q

Ann Arbor Staging:

Stage 2

A

Lymphoma located in 2 seperate regions, confined to one side of the diaphargm

176
Q

Ann Arbor Staging:

Stage 3

A

Lymphoma involves nodes or organs on both sides of the diaphragm

177
Q

Ann Arbor Staging:

Stage 4

A

Diffuse or disseminated involvement of one or more extra lymphatic organs, including liver, bone marrow, nodular involvement of lungs

178
Q

Ann Arbor Staging:

A or B

A 
A= Absence of B Sx
B= Presence of B Sx
179
Q

Hodgkins lymphoma CD stains

A

CD30, CD15

180
Q

Second cancers in Hodgkins lymphoma

A

AML
NHL
Breast cancer
Solid organ cancers (thyroid, lung, bone, brain)

181
Q

Brentuximab vedotin

A

Drug Ab Conjugate
Anti CD30
Releases MMAE toxin and causes apoptosis

For relapsed Hodgkins

182
Q

Commonest indolent NHL

A

Follicular lymphoma

183
Q

Mx of Follicular lymphoma

A

Advanced stage at presentation usually, often asymptomatic

Limited:
-Curative intent RTx

Advanced:
-Asymptomatic and low tumor burden: watch and wait
-Symptomatic or high tumor burden: Chemoimmunotherapy
(Obinotuzumab +CHOP/Bendamustine)

Cyclophosphamide, Vincristine, Doxirubicin, Pred = CHOP

Bendamustine shown to have better outcomes and less toxic

If old and frail can trial ritux and lenalinamide instead of chemo

184
Q

Lenolidamide MOA

A

Thalidomide analogue

Increases proliferation and activity of Tcells and NK cells, inhibits proinflammatory cytokines, causs delay in tumor growth, inhibits angiogenesis

185
Q

DLBCL

A

H+E: large centroblast like cells diffusely CD20 positive

Mx:
RCHOP
Polatuzumab vedotin (not on PBS)-Binds to CD79b and releases MMAE to trigger apoptosis

Genes for prognosis:
Good = GCB (Germinal cental B cell)
Bad =ABC (activated B cell)

186
Q

Mosunetuzumab

A

Bispecific T cell engager (BITE)
Targets CD3 and CD20

Redirects T cells to engage and eliminate malignant B cells

Future area for lymptoma treatment

187
Q

Mx Mantle Cell Lymphoma

A

Aggressive clinical behavior

Mx:
Venetoclax (BCL2 inhibitor) and Ibrutinib

188
Q

CLL Features

A

Most common adult leukemia

Features:

  • Lymph >5x10^9
  • Smear cells on film
  • CD5/19/23/20 (T cell and B cell positive)
  • HLA DR200

Poor Prognostic factors:

  • Del17p13.1
  • p53 mutation
189
Q

Smear cells

190
Q

CLL Mx

A

Younger patients:
-Ritux +FCR

Unfit patients:

  • Ritux +Chlorambucil
  • Ibrutinib

Del17p:
-Venetoclax + Rituximab

191
Q

Car T cells

A

Chimeric Antigen Receptor T cell

CD19 targeted T cells

Genetic therapy where T cells from patients are modifed and re-infused

192
Q

Peripheral T cell Lymphoma (PTCL)

A

Worse prognosis than B cell NHL

Mx

  • Romidepsn (HDACi)
  • Pralatrexate
193
Q

Diagnostic criteria for MGUS

A
  • Serum paraprotein <30g/L
  • Bone marrow clonal plasma cells <10%
  • No end organ damage
194
Q

Diagnostic Criteria for smouldering myeloma

Asymptomatic

A
  • Serum paraprotein >30g/L and/or bone marrow clonal plasma cells >10%
  • No end organ disease
195
Q

Diagnostic criteria for multiple myeloma

Symptomatic

A
  • Paraprotein in serum and or urine
  • Bone marrow clonal plasma cells or Bx proven plasmacytoma
  • Any myeloma related organ or tissue impairment
196
Q

Presentation of MM

A

ROTI (Myeloma-Related Organ or Tissue Damage)

CRAB

  • Ca level >0.25 mmol/L above ULN or >2.75 mmol/L
  • Renal insufficiency: Cr >173 mmol/L
  • Anaemia: Hb 2g/dl below the lower limit of normal or Hb <10 g/dl
  • Bone lesions: Lytic lesions or osteoporosis with compression fractures

Plus possibly
Hyperviscosity
Amyloidosis
Bacterial infections (>2 in 12 months)

197
Q

Why is a bone scan sometimes negative in MM

A

IT is n osteoclastic process not osteoblastic as seen in malignancies

198
Q

Staging for MM based on what factors

A

B2MG and albumin

199
Q

Renal disease in MM

A

Cast nephropathy most common
-Tubular disease direct damage to PCT with reduced re-absoprtion of LC

Others:
-Monoclonal Ig deosition disease
-Hypercalcemia
Amyloid
0Cryoglobulins
-Fanconi's syndrome
200
Q

MM Flow cytometry

A

CD138, CD19, CD56, kappa and lambda chain expression

201
Q

FBE in MM

A

Rouleaux, cytopenias, Macrocytosis

202
Q

IgM paraprotein most associated with what

A

MGUS
Lymphoma
Waldenstrom’s Macroglobulinaemia

Rarely ever MM

203
Q

Best test to look for isolated plasmocytoma

A

PET or sestimibi

204
Q

Bad cytogenetics in MM

A

Chromosome 13 deletion
Hypodiploidy
T(4:14)
T(14:16)

205
Q

Good cytogenetics in MM

A

T (11:14) - mutation in cyclin D

206
Q

OVerall risk of progression of MGUS to MM

207
Q

Thalidomide MOA

A

Blocks angiogenesis
T cell stimulator
Works on protein cereblon

208
Q

Thalidomide SE

A 
Constipation
Somnolence
Tremor
Painful neuropathy
Thrombosis
Skin Rash 
oedema
209
Q

Bortezomib MOA

A

Proteasome inhibitor

-Anti-apoptosis genes blocked

210
Q

Mx of Transplant candidate with MM

A

Induction:
-Cyclophosphamide +Bortezomib+Dxm for 4 months

Melphalan stem cell transplant

Maintainence:
-Steroids + Thalidomide/Lenolidomide

211
Q

Mx of Non-Transplant candidate with MM

A

Lenolidomide+Dex

OR (VCD)
Bortezomib +Melphalan/Cyclophosphamide +PRed

212
Q

Downsides of melphalan in MM

A

Not used in Tx eligible patients because:

  • Stem cell toxicity
  • Slower response rates
  • Beware in renal function
  • cyclo better toelrated
213
Q

Benefits of Autologous SCT in MM

A 
Suitable for patients <70
Most benefit in age <60
Mortality rate 1%
Superior to conventional therapy
Improved survival rates, but not a cure
214
Q

Definite indications for autologous SCT in lymphoma

A

Relapsed NHL
Relapsed HD
Incomplete response to primary therapy in NHL

No indication in refractory disease

215
Q

Allogenic vs autologous SCT in Hodgkins

A

Allogenic has higher mortality

216
Q

Carfilzomib

A

Proteasse inhibitor for treatment of MM

-More effective than Bortezomib in relapsed MM (For second line treatment only right now)

217
Q

Daratumumab

A

Anti CD38 for MM yet to be approved

218
Q

Elotuzumab

A

Anti-SLAMF7 (CS1) for MM treatment not yet approved

219
Q

Platelet Function disorder vs Coagulopathy

A

Platelet Function disorder:

  • Mucosal bleeding and petechiae common
  • Prolonged bleeding from skin cuts
  • Sex equal

Coagulopathy

  • Deep haematomas common
  • > 80% male
220
Q

What is VWF

A

Plasma protein that mediates initial adhesion of platelets at sites of vascular injury and binds FVIII in the circulation

221
Q

Immunophenotype of reed sternburg cells

A

Cd15 and cd30

222
Q

Antigen implicated in HITs

A

Pf4

Platelet factor 4

Bpt (15 decks)

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