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FRACP written exam preparation > Haematology > Flashcards

Haematology Flashcards

1
Q

4 malignancies associated with EBV

A
  1. Hodgkins
  2. Burkitts lymphoma
  3. PTLD
  4. Nasal NK cell lymphoma
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2
Q

3 haematological malignancies associated with HIV

A
  1. Cerebral DLBCL
  2. Hodgkins lymphoma
  3. DLBCL
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3
Q

Haematological malignancy associated with:

  1. HTLV-1
  2. HHV-6
A
  1. HTLV1 is associated with acute T lymphoblastic leukaemia/lymphoma
  2. HHV6 is associated with primary effusion lymphoma
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4
Q

How do you make the diagnosis of AML on the following parameters?

  1. Peripheral blast cell count
  2. Cytochemistry
  3. Immunophenotyping
A
  1. > 20% blasts in bone marrow or blood
  2. Myeloperoxidase positive
  3. Myeloid antigen positive on immunophenotyping (CD13, CD 33 positive)
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5
Q

Name 2 positive prognostic markers for AML.

A
  1. t(15;17)

2. NPM1 mutation

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6
Q

Name 3 negative prognostic markers for AML.

A
  1. Age >60 (strongest adverse prognostic factor)
  2. FLT-ITD3 receptor mutation in a normal karyotype
  3. Philadelphia chromosome, complex cytogenetics, 11q23 abnormalities
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7
Q

How do you diagnose acute lymphoblastic leukaemia (ALL) on these following parameters?

  1. Blast count
  2. Flow cytometry
A
  1. Blast count of >20% on blood or bone marrow WITHOUT auer rods
  2. Flow cytometry:
    B cells - CD 19, CD 20
    T cells - CD2, 3, 4, 8
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8
Q

How does Blinotumomab work?

A

A Bispecific T-cell engaging antibody (BiTE) targeting CD3 on host T cells and CD19 on malignant B cells. This allows host T cells to get close to the malignant B cells and cause death via cytotoxicity.
Used in refractory/relapsed B-ALL.

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9
Q

How do you diagnose CLL?

A

Flow cytometry. Need to demonstrate clonality of CD5 and CD19 positive B cell by showing kappa or lambda light chain restriction.

Smear cells on blood film with numerous mature lymphocytes present.

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10
Q

Describe 3 stages of CLL.

A

Stage 1: lymphocytosis only
Stage 2: Lymphadenopathy
Stage 3: Cytopenias cause by BM infiltration, ie non immune.

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11
Q

Prognostic markers for CLL on FISH

A

13q deletion - good prognosis

11q and 17p deletion - poor prognosis (often rapidly evolving, therapy resistant)

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12
Q

Describe the treatment modalities for CLL.

A

Treat only when symptomatic.

First line - oral chlorambucil or FCR
Second line: Alemtuzumab (Anti-CD52) in patients with p53 mutation
ASCT in poor prognostic patients who are suitable

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13
Q

Describe 4 features of 5q- syndrome

A

A specific category of MDS.

  1. Elderly Females
  2. Macrocytic anaemia
  3. Thrombocytosis
  4. Responds to lenalidomide
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14
Q

When should you consider iron chelating therapy?

A

After transfusion of more than >20 units

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15
Q

How do you risk stratify MDS?

A

Using IPSS/WPSS classification

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16
Q

Describe the Ann-Arbor staging.

A

Stage 1 - single nodal group
Stage 2 - more than one nodal group on the same side of the diaphragm
Stage 3 - nodal groups on both sides of the diaphragm
Stage 4 - bone marrow/extranodal involvement

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17
Q

Describe how brentuximab vendotin works.

A

Anti-CD30 monoclonal antibody which binds to CD30 and delivers the MMAE which is a microtubule disrupting cytotoxic agent.

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18
Q

What are the poor prognostic markers of follicular lymphoma?

A

Refer to FLIPI index.

Nodal groups >4
Age >60
Stage III/IV disease
Hb <120

Any single point of above pertains poorer prognosis.
Note: Stage III follicular lymphoma is treated like DLBCL with RCHOP.

Consider maintenance rituximab upto 2 years in high risk FLIPI.

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19
Q

Describe the 3 phases of CML.

A

Chronic phase - blast count <15%, basophils <20%, platelets >100

Blast phase - >30% blast cells of either myeloid OR lymphoid origins

Accelerated phase - in between the two, blast count of 15-29%, basophils >20%, platelets <100

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20
Q

What mutation leads to TKI resistance?

A

T315I. Poor prognosis.

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21
Q

Describe 3 diseases in which JAK2 mutations are present and their incidence.

A

PV - virtually present in all
ET 60%
PMF 65%

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22
Q

What is the role of calreticulin in ET and PMF?

A

Present in JAK 2 negative ET and PMF.
Mutated chaperone molecule which constitutively activates MPL cytokine receptor signalling.
Better prognosis than JAK 2-V617K mutation in PMF and ET.

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23
Q

What are the venesection targets in PRV?

A

Male: HCT <0.45
Females: HCT <0.40 to render iron deficiency

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24
Q

How do you manage PRV?

A
  1. Venesection in the first instance
  2. Use hydroxyurea if intolerant of phlebotomy, splenomegaly, resistant thrombocytosis.
  3. Aspirin
  4. Can consider further cytotoxics such as chlorambucil in elderly and IFN alpha
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25
Q

How do you manage ET?

A
  1. Treat with aspirin and hydroxyurea until PLT <600

2. Consider interferon alpha if pregnant

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26
Q

Describe the prognostic index for multiple myeloma.

A

Stage 1 - B2MG <3.5, albumin >35
Stage 2 - B2MG between 3.5 and 5.5, albumin <35
Stage 3 - B2MG >5.5

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27
Q

What are the poor prognostic features of myeloma on cytogenetics?

A 
del13
del17p
t(4;14)
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28
Q

What is the effect of dabigatran on APTT and TCT?

A

APTT and dabigatran shows some linear relationship.
Thrombin clotting time is exquisitely sensitive to presence of any dabigatran therefore high level indicates that dabigatran is present.

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29
Q

Determine the level of dabigatran on the following situations:

  1. Normal TCT and normal APTT
  2. Prolonged TCT but normal APTT
  3. Prolonged TCT and APTT
A
  1. Dabigatran would be minimally present/not present
  2. Likely presence of low dabigatran activity
  3. Significant drug activity present. Do a modified thrombin time.
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30
Q

How do you measure apixaban/rivaroxaban activity?

A

Via modified anti-Xa level which needs to be drug specific.

APTT/PT are completely unreliable.

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31
Q

How does andexenate work?

A

decoy factor Xa receptor which has no protease function which binds to rivaroxaban/apixaban with higher affinity than natural factor Xa thereby reversing its effect.

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32
Q

Describe 3 severity of Haemophilia.

A

Depends on level of factors.

Severe <1%
Moderate 1-5%
Mild 5-40%

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33
Q

What is the effect of factor prophylaxis vs on demand replacement in haemophilia A?

A

Factor prophylaxis was effective in reducing joint damage, however was associated with greater factor 8 units transfused and significant cost.

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34
Q

What mutations are associated with hereditary spherocytosis?

A

Mutations of genes encoding ankyrin, spectrin, or band 3 red cell proteins.

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35
Q

How do you distinguish between MDS and aplastic anaemia on a bone marrow aspirate?

A

Look at the megakaryocytes which are the most reliable lineage to use. Small mononuclear or aberrant megakaryocytes are typical of MDS, whereas megakaryocytes are markedly reduced or absent in severe AA.

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36
Q

What is the overlap between aplastic anaemia and paroxysmal nocturnal haemoglobulinaemia?

A

around 50%. Mutation of PIGA responsible for PNH occurs in setting of acquired aplastic anaemia.

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37
Q

When do symptoms of hyperviscosity occur in Waldenstroms macroglobulinaemia?

A

Serum viscosity of around 4.08 cP which corresponds to serum IgM level of 30g/L

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38
Q

What haematological malignancy is associated with hepatitis C?

A

splenic marginal zone lymphoma

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39
Q

Describe the pathogenesis of aHUS

A

Genetic, chronic systemic disorder due to uncontrolled complement activation.
Associated with mutation in genes encoding both complement regulators (factor H, I, membrane cofactor protein and thrombomodulin) and activators (factors B and C3)

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40
Q

3 conditions associated with AIRE mutation leading to autoimmune polyendocrine syndrome type 1

A
  1. Mucocutaneous candidiasis
  2. Hypoparathyroidism
  3. Addisons disease

Also at risk of developing other autoimmune diseases including type 1 DM, hypothyroidism, pernicious anaemia, alopecia, vitiligo, hepatitis, ovarian atrophy and keratitis.

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41
Q

Three types of vWD?

A

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

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42
Q

Why do you get falsely positive VDRL test occur in antiphospholipid syndrome?

A

VDRL and RPR reagent contains cardiolipin.

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43
Q

What proportion of APLS have SLE?

A

About 30-40%

5% have lupus like syndromes

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44
Q

Name 4 drugs associated with rise in antiphospholipid antibodies.

A

Usually of IgM type.

  1. Antiepileptics - phenytoin, ethosuximide
  2. Amoxicillin
  3. Hydralazine
  4. Chlorothiazide
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45
Q

What was APLASA study and what were its conclusions?

A

Study looking at aspirin prophylaxis in individuals with aPL positivity:

●Asymptomatic individuals who are persistently positive for aPL have a low annual incidence of acute thrombosis.
●These individuals do not benefit from low-dose aspirin.
●Thrombotic events in this population are unlikely in the absence of additional risk factors for thrombosis

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46
Q

How would you manage patients with aPL antibodies and concurrent SLE?

A
  1. Aspirin and hydroxychloroquine will reduce the thrombotic risk
  2. Address modifiable risk factors such as smoking, hyperlipidaemia, hypertension
  3. If clot occurs, manage with clexane then warfarin. Currently no evidence exists for NOACs.
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47
Q

What enzyme is deficient in porphyria cutanea tarda?

A 
Uroporphyrinogen decarboxylase (UROD)
Results in acccumulation of uroporphyrinogen and hepta, hexa and penta-carboxyl prophyrinogen in the liver, which then accumulates in the skin and are photosensitizing, and cause LFT derangements.
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48
Q

Enzyme deficient in sideroblastic anaemia?

A

ALA synthase

Responsible for pathway between formation from glycine+succinyl-COA to delta-aminolevulinic acid

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49
Q

How do you differentiate leukaemoid reaction from CML?

A
  1. High leucocyte alkaline phosphatase score
  2. Toxic granulation in the WBCs (Dohle bodies)
  3. Left shift of neutrophils - ie, 3 or less segments of the nucleus
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50
Q

4 functions of the spleen?

A
  1. Clearance of microorganisms and particulate antigens from the blood stream
  2. Synthesis of immunoglobulin G (IgG), properdin (an essential component of the alternate pathway of complement activation), and tuftsin (an immunostimulatory tetrapeptide)
  3. Removal of abnormal red blood cells (RBCs)
  4. Extramedullary hematopoiesis in certain diseases
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51
Q

6 causes of splenomegaly

A
  1. Immune work hypertrophy (eg sepsis)
  2. RBC destruction work hypertrophy
  3. Congestive (Splenic vein thrombosis, CLD)
  4. Myeloproliferative - CML
  5. Neoplastic - CLL, lymphoma
  6. Infiltrative - sarcoidosis
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52
Q

Gold standard for diagnosis of iron deficiency?

A

Reduced bone marrow iron stores on BM aspirate - Perl stain for haemosiderin.

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53
Q

Consequence of defects in Glycosylphosphatidylinositol synthesis?

A

GPI is a glycolipid which acts as an anchor for adherence of CD55/59 on the RBC surface, making them more susceptible to complement-mediated destruction.

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54
Q

Bernard Soulier syndrome

Glanzmann’s thrombasthenia

A

BSS: Autosomal recessive defect in glycoprotein Ib-Ix, the vWF receptor.

GT: Low level/defective GP IIb/IIIa, a fibrinogen receptor

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55
Q

Indications for treatment of CLL

A
  1. Progressive marrow failure
  2. B symptoms
  3. Doubling time <6 months
  4. Bulky disease as defined by LN >10cm, massive splenomegaly (>6cm below costal margin), progressive symptomatic lymphadenopathy
  5. Uncontrollable autoimmune phenomena (ITP or AIHA)
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56
Q

Mutations in hereditary haemochromatosis

A

Mutation of HFE gene in HLA class I region on chromosome 6. Missense mutation:

  1. C282Y mutation - substitution of tyrosine for cysteine at amino acid position 282
  2. H63D - aspartic acid substituted for histidine in position 63

C282Y homozygosity or compound heterozygosity is found in most patients with HH.

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57
Q

Indications for liver biopsy in hereditary haemochromatosis

A

1 All homozygotes with clinical evidence of liver disease

  1. All homozygotes with serum ferritin >1000
  2. All homozygotes older than age 40 with other risk factors for liver disease
  3. Compound C282Y heterozygotes with elevated transferrin saturation, particularly those who have had abnormal liver enzymes or clinical evidence of liver disease.
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58
Q

Diagnosis of hereditary haemochromatosis?

A

Transferrin saturation >45% in the absence of other causes of iron overload.

A value greater than 60% in men and 50% in women is highly specific.

However, approximately 30% of women younger than 30 years who have hemochromatosis do not have elevated transferrin saturation.

At present, only homozygosity for C282Y and compound heterozygosity for C282Y/H63D should be considered indicative of hereditary hemochromatosis. C282Y heterozygosity may contribute to iron overload due to other conditions, but it should not be considered the sole cause of iron overload and it should not be considered diagnostic of hereditary hemochromatosis.

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59
Q

Management of hereditary haemochromatosis

A
  1. In the induction phase, weekly phlebotomy with blood removal of 7 mL/kg per phlebotomy (not to exceed 550 mL per phlebotomy).
  2. Monthly ferritin evaluation until down to normal range, then bimonthly until ferritin <50
  3. In the maintenance phase, the phlebotomy should be performed every 2-4 months. The interval between procedures is determined by the level of ferritin, which should be lower than 50 mcg/mL
  4. If concurrent anaemia precludes phlebotomy - use iron chelation agent
  5. Avoid oral iron loading with food, medications etc, avoid alcohol
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60
Q

Causes of acquired thrombophilia A (factor 8 inhibitor)

A
  1. Idiopathic - 50%
  2. Autoimmune 15%
  3. Malignancy 12%
  4. Peripartum factor 8 inhibitor 8%
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61
Q

Management of acquired factor 8 inhibitor

A

Replace the factor, then remove the antibody.

Replacement depends on titre of the antibody:

  1. High titre antibody >5 bethesda units
    - Recombinant factor 7a
    - Activated prothrombin complex concentrate
    - Porcine factor 8 concentrate
  2. Low titre antibody
    - Human or porcine factor 8 concentrate
    - Desmopressin

Remove the antibody with Rituximab, cyclophosphamide, cyclosporin, IVIG, or plasmapheresis.

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62
Q

5 clinical features of primary myelofibrosis

A
  1. Anaemia
  2. Bone marrow fibrosis
  3. Extramedullary haematopoiesis
  4. Hepatosplenomegay
  5. Leucoerythroblastosis with tear drop cells in blood film

JAK 2 positive in 50-60%
Majority of JAK 2 negative patients have CAL-R mutation

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63
Q

Complications of primary myelofibrosis and their treatment

A
  1. Portal hypertension - increased portal flow resulting from marked splenomegaly and to intrahepatic obstruction resulting from thrombotic obliteration of small portal veins. May need splenectomy
  2. Splenic infarction - analgesia, splenectomy, splenic radiation
  3. Increased susceptibility to infection
  4. Extramedullary haematopoiesis - can involve any sites, may result in bleeding, spinal cord compression, seizures, hemoptysis, and/or effusions. Treated with low dose radiation
  5. Osteosclerosis causing pain
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64
Q

Prognosis of myelofibrosis

A

The median length of survival for patients with primary myelofibrosis is 3.5-5.5 years. The 5-year survival rate is about half of that expected for age- and sex-matched controls. Fewer than 20% of patients are expected to be alive at 10 years. [13] The common causes of death in patients with primary myelofibrosis are infections, hemorrhage, cardiac failure, postsplenectomy mortality, and leukemic transformation. Leukemic transformation occurs in approximately 20% of patients with primary myelofibrosis within the first 10 years.

CAL-R positivity is a favourable prognostic factor.
Use DIPSS scoring for prognostication.

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65
Q

Mechanism of action of ruloxitinib

A

JAK1/2 inhibitor
Used in primary myelofibrosis.
Effective in reduction of spleen volume, symptoms, quality of life

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66
Q

Treatment of PMF (other than JAK1/2 inhibitors)

A
  1. Hydroxyurea
  2. IFN alpha in young patients - 50% responds with improvement in splenomegaly and anaemia
  3. Androgens (such as danazol) - 30% respond
  4. Thalidomide and prednisone - may improve cytopenias, however also increases WBCs or platelets significantly in the first 4-8 weeks, and may require further cytoreductive therapy
  5. Splenectomy may be considered for patients with overt portal hypertension, progressive anemia requiring transfusions, or symptomatic splenomegaly refractory to hydroxyurea. However splenectomy is associated with high perioperative risk, and higher risk of transformation to AML.
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67
Q

Mechanism of action of hydroxyurea

A

Hydroxyurea is an inhibitor of deoxynucleotide synthesis. It is less leukemogenic than alkylating agents (busulfan) are. Hydroxyurea’s myelosuppressive effects last a few days to a week and are easier to control than those associated with alkylating agents. It is lethal to cells in the S phase and is cell-cycle specific

68
Q

Haemoglobin C disease

A

HbC is astructural variant of normal hemoglobin A (Hb A) caused by an amino acid substitution of lysine for glutamic acid at position six of the beta hemoglobin chain.

This mutated form reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy. In those who are heterozygous for the mutation, about 28–44% of total hemoglobin (Hb) is HbC, and no anemia develops.

In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia

Hemoglobin C is mainly of clinical significance when inherited in combination with Hb S (Hb SC disease), or when co-inherited with β-thalassemia (hemoglobin C–β thalassemia). In HbSC - less vasoocclusive crisis, but more significant retinopathy, ischemic necrosis of bone, and priapism compared to pure HbSS

69
Q

3 types of haemoglobin in normal population

A

The oxygen carrying capability of the red blood cells (RBCs) relies on hemoglobin, a tetramer protein that comprises 4 globin chains bound to the heme molecule. There are 4 major types of globins: alpha (α), beta (β), gamma (γ), and delta (δ). The dominant hemoglobin in adults (hemoglobin A) is composed of 2 alpha and 2 beta chains. Two minor forms of hemoglobin constitute a small percentage of normal blood: hemoglobin F (fetal), composed of 2 alpha chains and 2 gamma chains, and hemoglobin A2, composed of 2 alpha chains and 2 delta chains.

70
Q

3 clinically relevant manifestations of alpha thalassaemia (other than Hb Barts/hydrops fetalis)

A
  1. Silent carrier - (-α/αα) or alpha thalassemia-2 trait.
    No clinical abnormalities and may be hematologically normal or have slight reductions in RBC mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).
  2. Alpha thalassemia trait
    Inheritance of 2 normal alpha-globin genes through either heterozygosity for alpha(0) thalassemia (αα/–) or homozygosis for alpha(+) thalassemia (-α/-α).
    Clinically normal but frequently have minimal anaemia and reduced MCV and MCH.
  3. Haemoglobin H disease
    (-α/–) or aka alpha thalassemia intermedia.
    Abundant formation of HbH which is characterized by a high ratio of beta globin to alpha globin and a 2-fold to 5-fold excess in beta-globin production. The excess beta chains aggregate into tetramers, which account for 5-30% of the hemoglobin level in patients with HbH disease.

HbH has a high affinity for oxygen and has no Bohr effect or heme-heme interaction; therefore, it is an ineffective supplier of oxygen to the tissues under physiologic conditions. RBCs that contain HbH are sensitive to oxidative stress; thus, they may be more susceptible to haemolysis when oxidants such as sulphonamides are administered.

71
Q

Beta thalassemia - laboratory diagnosis

What about diagnosis of alpha thalassemia?

A

Heinz bodies, which represent inclusions within RBCs consisting of denatured hemoglobin (Hb), may also be seen in the peripheral blood. [7]

Elevation of the Hb A2 level, demonstrated by electrophoresis or column chromatography, confirms the diagnosis of beta thalassemia trait. The Hb A2 level in these patients usually is approximately 4-6%. In rare cases of concurrent severe iron deficiency, an increased Hb A2 level may not be observed, although it becomes evident with iron repletion. The increased Hb A2 level also is not observed in patients with the rare delta-beta thalassemia trait. An elevated Hb F level is not specific to patients with the beta thalassemia trait.

In contrast, alpha thalassemia has normal HbA2 level.
Establishing the diagnosis of the alpha thalassemia trait requires measuring either the alpha-beta chain synthesis ratio or performing genetic tests of the alpha-globin cluster (using Southern blot or polymerase chain reaction [PCR] assay tests

72
Q

HbH disease

A

Due to 3 alpha gene deletion

Leads to formation of 2 types of unstable tetramers consisting of 4x gamma chains (Hb Barts) and 4x beta chains (HbH)

73
Q

Risk stratification for essential thrombocytosis

A

●High-risk disease – History of thrombosis at any age and/or age >60 with a JAK2 V617F mutation
●Intermediate-risk disease – Age >60, no JAK2 mutation detected, and no history of thrombosis
●Low-risk disease – Age ≤60 with JAK2 mutation and no history of thrombosis
●Very low-risk disease – Age ≤60, no JAK2 mutation detected, and no history of thrombosis

High risk - anticoagulation +/- aspirin and hydroxyurea

Intermediate risk - could consider hydroxyurea

Low/very low risk - aspirin if symptoms or cardiovascular risk factors are present, otherwise observe only

74
Q

4 necessary criteria for diagnosis of pure red cell aplasia

A
  1. Normocytic, normochromic anemia; rarely, macrocytic
  2. A very low (or zero) reticulocyte percentage, and an absolute reticulocyte count <10,000/microL
  3. Normal white blood cell and platelet counts
  4. A normocellular bone marrow that shows normal myelopoiesis, lymphopoiesis, and megakaryocytopoiesis, but few if any erythroid precursors.
75
Q

6 causes of pure red cell aplasia

A
  1. Idiopathic (presumed immune mediated)
  2. Thymoma
  3. Haem malignancies - LGL, myeloma, MDS etc
  4. Parvovirus infection
  5. ABO incompatible haematopoietic transplantation
  6. Drugs - phenytoin, cotrimoxazole, EPO (Anti-EPO antibodies)
76
Q

Treatment of idiopathic PRCA without obvious secondary cause

A
  1. Supportive treatment initially
  2. If no remission despite supportive treatment, prednisone
  3. If prednisone does not work, then either cyclosporine or cyclophosphamide. Cyclosporine has better response rates than cyclophosphamide.
77
Q

Major body iron stores

A

Normal body iron content - 3-4g
2g in RBC haemoglobin
Proteins (myoglobin, cytochrome, catalase) - 400mg
Plasma iron bound to transferrin - 3-7mg
Rest are in storage iron - haemosiderin and ferritin in liver, spleen and bone marrow

78
Q

How is iron absorbed?

A

Absorbed iron can be Non-Haem iron (90%) or haem iron (10%). Absorbed in the duodenum.

Non haem iron are absorbed in Ferrous state Fe2+ into duodenal cells via DMT1. Exported out from duodenal enterocytes into plasma via ferroportin.

Haem iron are complexed with protoporphyrin and are more bioavailable. Absorption is not well understood.

Iron in plasma is carried by transferrin. Transferrin receptors mediates uptake into cells.

79
Q

Typical iron study findings in iron deficiency

A

Transferrin saturation reduced
Transferrin increased
Increased TIBC
Reduced ferritin

Soluble transferrin receptors increased - directly proportional to erythropoietic state, inversely proportional to iron stores.

80
Q

Main source of dietary B12 and folate

A

B12: Fish, meat, poultry, eggs, milk products
Folate: diet is the only source. In fruit and vegetables, beef. Absorbed in small bowel.

81
Q

Serologic testing of pernicious anaemia

A

Intrinsic factor antibodies - very specific, but only 50% sensitive

Parietal cell antibodies - sensitive but non specific (positive in 15% of normal females)

Therefore ideally should test for both!

82
Q

What is the best test for folate deficiency?

A

Red cell folate - 95% of folate is in RBCs. Best assessment of long term stores and is less variable.

Serum folate is indicative of recent intake and is susceptible to variation.

83
Q

3 causes of intravascular haemolysis

A
  1. Fragmentation (eg: causes of MAHA, DIC, mechanical haemolytic anaemia, preeclampsia, malignant hypertension)
  2. PNH
  3. Paroxysmal cold haemoglobinuria
84
Q

5 causes of extravascular haemolysis

A
  1. Red cell membrane defect
  2. RBC enzyme defect (eg: G6PD deficiency)
  3. Immune mediated
  4. Metabolic defect
  5. Bacteria/parasitic infections such as malaria
85
Q

Name 5 causes of MAHA

A
  1. HUS/TTP
  2. aHUS - inherited dysregulation of complement system due to mutation in complement factor H gene
  3. Renal allograft reejction
  4. Pre-eclampsia/HELLP
  5. Malignant hypertension
86
Q

Classical pentad of TTP

A
  1. haemolysis with RBC fragmentation
  2. Renal failure
  3. Neurological impairment
  4. Thrombocytopenia
  5. Fever
87
Q

Management of TTP

A
  1. Plasma exchange - urgent, to get rid of large vWF and replace normal ADAMTS13
  2. Avoid platelet transfusion

Further management depends on specific aetiology

  1. If aHUS - eculizumab
  2. If hereditary TTP - ADAMTS13 replacement with FFP infusions
  3. Immunosuppression with rituximab and prednisone if it is an autoimmune cause of ADAMTS13 deficiency
88
Q

PNH

A

Somatic mutation of pig-A gene (phosphatidylinositol glycan A) which is essential for the formation of GPI anchor. Results in loss of several surface proteins which usually protects cells from complement mediated damage - CD55/59.

Manifests paroxysmal intravascular haemolysis
Increased risk of thrombosis eg: in large veins such as portal veins

Diagnose with flow cytometry testing for CD55/59 on red cells and neutrophils.

Treatment - transfusion, stem cell transplant, thrombosis management, eculizumab (recues transfusion requirement and cessation of haemoglobinuria)

89
Q

Paroxysmal cold haemoglobinuria

A

Rare form of AIHA with acute intravascular haemolysis after exposure to cold.

Due to presence of biphasic IgG anti-P antibody (Donath-Landsteiner antibody) which binds to RBC at low temperatures and upon warming complement mediated lysis occurs.

Management - cold avoidance, folate supplement, prednisone, IVIG. Unlike other AIHAs, splenectomy is NOT USEFUL.

90
Q

Management of warm AIHA

A
  1. Prednisone 1mg/kg then taper
  2. Splenectomy and vaccination (after steroids, best second line therapy)
  3. Rituximab

Supportive treatment such as IVIG and folate supplement are also important.

91
Q

Cold AIHA

A

Almost always secondary cause - associated with lymphoproliferative disease, mycoplasma, EBV, autoimmune disease.

IgM mediated causing both intravascular and extravascular haemolysis.

Management: cold avoidance, chlorambucil especially if underlying LPD, rituximab.

Unlike warm AIHA, does not respond to splenectomy or steroids.

92
Q

Hereditary spherocytosis

A

Often due to mutation of ankyrin, spectrin
Autosomal dominant. Family history in 75%
Typical blood film picture of polychromasia, prominent spherocytes and family history is enough to make the diagnosis.

Flow cytometry will show reduced eosin-5-maleimide binding (EMA)

Management is with folate supplementation, splenectomy.

93
Q

Pyruvate kinase deficiency

A

Autosomal recessive, rare.
RBC glycolytic pathway is affected with reduced ATP formation leading to RBC rigidity.
Results in chronic haemolysis.

94
Q

G6PD deficiency

A

X linked, common.
G6PD is involved in hexose-monophosphate shunt which allows regeneration of NADPH which is important for generating reduced glutathione.

Reduced glutathione absorbs oxidative stress.

Increased susceptibility to oxidative stress and episodes of acute haemolysis.

Hemizygous males are affected.
Homozygous females are affected.
Heterozygous females have variable manifestations depending on extent of X inactivation.

95
Q

How do you make the diagnosis of G6PD deficiency?

A

Test for enzymes when patient is STABLE.

If tested during acute haemolysis, can be falsely negative as reticulocytes have higher G6PD levels.

96
Q

4 disease associations with ITP

A

ITP is a diagnosis of exclusion - need to look for disease associations:

  1. Lymphoproliferative diseases eg CLL
  2. Autoimmune disease RA/SLE
  3. H pylori
  4. Hep C
97
Q

Management of ITP

A

Aim of the management is to maintain platelet count high enough to prevent significant bleeding.

  1. Can observe if >30
  2. Prednisone 1-2mg/kg (high response rate but also high relapse rate)
  3. IVIG - more rapid response
  4. Splenectomy with vaccination is the most effective therapy.

Other therapies include immunosuppressive meds such as azathioprine, rituximab, danazol

98
Q

Heparin induced thrombocytopenia

A

IgG antibody that recognizes heparin-PF4 complex and causes platelet activation and consumption via Fc receptor.

Typically develops 5-14 days after heparin commencement
Heparin falls by >50% but rare to have severe thrombocytopenia <15
High risk of thrombosis.

PF4 immunoassay has high sensitivity but low specificity (therefore useful if negative)

99
Q

3 types of normal haemoglobin

A

HbA - a2b2, main haemoglobin
HbA2 - a2d2, minor haemoglobin 2-3%
Hb F - a2y2, primarily from neonates, minor haemoglobin in adults.

100
Q

What is the difference between a0 thal and a+ thal?

A

a0 thalassaemia - deletion or inactivation of both alleles on a single chromosome.
If both chromomes are a0, then it leads to hydrops fetalis and intrauterine death

a+ thalassaemia - one allele inactivation on the single chromosome. 3 subtypes exist:

  1. Silent carrier a-aa
  2. Alpha thalassaemic trait aa– or a-a-
  3. HbH disease -a–
101
Q

Can you diagnose alpha thalassaemic trait or silent carrier on haemoglobin electrophoresis?

A

No. Requires molecular studies to diagnose.

If you have alpha thalassaemic trait with –aa, they may occasionally have HbH cells. However with a-a- phenotype, HbH cells are rare.

102
Q

Beta thalassaemia trait/minor

A

1 gene deletion resulting in reduced beta globin synthesis.
As a result, reduced HbA (a2b2) formation, with compensated increase in HbA2 (a2d2) as there are excess alpha chains.

Mild anaemia only on FBC. Clinically asymptomatic.

High performance liquid chromatography will show increased HbA2 and HbF

103
Q

What can cause false negative result on high performance liquid chromatography in diagnosis of beta thalassaemia trait/minor?

A

Iron deficiency. Reduces Hb A2 level therefore must always assess iron status.

104
Q

Beta thalassaemia major management

A
  1. Transfusion support - aim Hb 90-100 to suppress extramedullary haematopoiesis
  2. Manage endocrine failures - sex hormones, thyroid disease, GH
  3. Stem cell transplant
  4. Iron chelation therapy - generally to aim ferritin <1000. Ferritin >2500 associated with high cardiac risk.
105
Q

HbC disease

A

Abnormal hemoglobin in which substitution of a glutamic acid residue with a lysine residue at the 6th position of the β-globin chain

Heterozygosity for HbC is clinically silent - homozygosity results in mild haemolytic anaemia as this mutated form has reduced RBC plasticity.

106
Q

Sickle cell disease

A

Glutamine to valine substitution at codon 6
Autosomal recessive

Management is with hydroxyurea which causes foetal haemoglobin induction with decrease in HbS level in blood
Transfuse as required
Monitor HbS level

107
Q

When should you initiate phlebotomy in hereditary haemochromatosis?

A

Once HH due to C282Y homozygosity or compound heterozygosity C282Y/H63D is diagnosed, initiation of treatment depends on ferritin level:

  1. Ferritn 300-1000 with normal LFTs - start phlebotomy
  2. Ferritin >1000 and/or LFTs abnormal – liver biopsy to confirm iron overload, then start phlebotomy
  3. Ferritin <300 and normal LFTs – observe, retest in 1 year
108
Q

Lupus anticoagulants and their venous/arterial associations

A

LAC - strong risk factor for both venous and arterial thrombosis (RR 3-10 for venous, RR 10 for arterial)

ACLA - associated with arterial thrombosis (RR 1.5-10) but NOT WITH VENOUS THROMBOSIS.

Anti-B2 glycoprotein - associated with venous thrombosis with RR 2.4.

109
Q

What is the significance of splanchnic vein thrombosis?

A

Prevalence of JAK 2 was 49% in patients with idiopathic SVT

110
Q

What is the role of Dilute russel viper venom test?

A

Factor 10 and 5 requires phospholipids to act on in order to cause thrombin formation.

Russel viper venom stimulates ++ factor X to become Xa directly. For this to occur, phospholipids need to be present.

APLA binds to phospholipids and delay these reactions from happening - therefore DRRV test is SENSITIVE to presence of APLA.

False positives can occur with anti-Xa drugs.

111
Q

What is APTT-actin?

A

Low phospholipid reagents which are sensitive to presence of LA.

112
Q

Management of acute haemolytic transfusion reaction

A
  1. Stop transfusion
  2. Vigorous IVF to induce diuresis and to avoid renal failure
  3. DAT, Hb level and repeat group and hold and cross match, urine for haemosiderin testing
  4. Alert blood bank immediately
113
Q

Delayed haemolytic transfusion reaction

A

Due to an anamnestic antibody response occurring after re-exposure to a foreign red cell antigen previously encountered by transfusion, transplantation, or pregnancy.

The antibody, often of the Kidd or Rh system, is undetectable on pretransfusion testing but increases rapidly in titrefollowing the transfusion.

Seen generally within 3 to 30 days after transfusion. Hemolysis is usually extravascular, gradual, and less severe than with acute reactions, but rapid hemolysis can occur. A falling hematocrit, slight fever, mild increase in serum unconjugated bilirubin, and spherocytosis on the blood smear may be noted. The diagnosis is often made by the blood bank when a new positive direct antiglobulin test and a new positive antibody screen are found when more blood is ordered.

114
Q

Prognostic value of following molecular genetic markers in AML with normal karyotype

FLT3-ITD
NPM1
CEBPA

A

CEBPA mutation - good prognosis

NPM1 mutation/FLT3-ITD negative - good prognosis

FLT3-ITD positive - bad prognosis

115
Q

What is the efficacy of azacitidine in intermediate/high risk MDS?

A

When compared with low dose ara-C, improves overall survival, transfusion independence, quality of life.

116
Q

Difference between RAEB1 and RAEB2 MDS

A

Number of blasts - RAEB1 has 5-9% blasts, while RAEB2 has 10-19% blasts.

Accordingly RAEB2 has higher 5 year risk of AML (21% vs 34.5%)

117
Q

Which MDS type has the lowest risk of 5 year AML transformation?

A

RARS - refractory anaemia with ringed sideroblast. Has >15% ringed sideroblasts.

118
Q

Direct coombs test vs indirect coombs test

A

Direct coombs test - used to test for AIHA. Patient’s blood is taken then RBCs are incubated with antihuman antibodies (coomb’s reagent). If RBCs are coated with autoimmune antibodies, then RBCs will agglutinate.

Indirect coombs test - Used to test antigens on RBC surface eg for ABO incompatibility testing. Donor RBCs are combined with recipient’s serum (which will have antibodies) then coomb’s reagent is added to see if agglutination occurs (which means that the recipient’s antibodies have coated the donor RBCs)

119
Q

Describe the mechanism of efficacy of corticosteroids and splenectomy in AIHA

A

Splenic macrophages have Fc receptors which recognize IgG1 and IgG3 only.

Corticosteroids downregulate Fc receptors on macrophages and also decrease autoantibody formation.

Splenectomy removes major site of RBC destruction. However given that the splenic macrophages only remove IgG coated cells, it doesn’t remove antibodies targeting C3b on RBCs which are destroyed in liver.

120
Q

Factors which decrease/increase transferrin synthesis

A

Transferrin synthesized in the liver.

Production increased in Fe deficiency, also induced by OCT, HRT.

Production decreased in iron overload and also acute inflammation/infection (acute phase negative reactant)

121
Q

How does C282Y mutation cause hereditary haemochromatosis?

A

Disrupts HFE-B2MG-TFR1 complex.
HFE-B2MG complex usually interacts with transferrin receptor and decreases the affinity of the transferrin receptor for interaction with transferrin.

C282Y mutation leads to increased iron transfer into stores and also increases the expression of DMT1 on intestinal cells leading to increased absorption.

122
Q

3 A’s of haemochromatosis

A

Asthenia - fatigue, impotence
Arthralgia - especially 2nd and 3rd MCPJ
Aminotransferase elevation

123
Q

What is the venesection target in haemochromatosis?

Efficacy of venesection on HH?

A

Weekly venesection until ferritin <50 and transferrin saturation <20%

Then maintain ferritin <100

Venesection improves asthenia, LFT derangements and pigmentation.
Some improvement in arthralgia and diabetes
No effect on impotence, cirrhosis and HCC.

Therefore need to venesect in the EARLY stages of the disease before end organ complications occur.

124
Q

What is the mechanism of disease in iron overload?

A

When serum iron exceeds transferrin, iron is bound to low molecular weight compounds to form non transferrin bound iron (NTBI). NTBI is readily taken up by hepatocytes and cardiac myocytes and anterior pituitary cells and pancreatic beta cells and cause oxiant damage.

125
Q

Differences between light chain deposition disease and cast nephropathy

A

LCDD - light chains (mainly kappa) deposited in glomerulus causing glomerulosclerosis.

Cast nephropathy - causes direct tubular cellular damage, formation of cast leading to decreased tubular urine flow.

Kappa light chains are more likely to cause LCDD and PCT dysfunction, while as lambda light chains are more likely to cause AL amyloidosis.

126
Q

3 major risk factors for progression from MGUS to MM

A
  1. Size of the M band
  2. IgM or IgA monoclonal protein had an increased risk of progression to disease compared to IgG
  3. Elevated serum free light chains
127
Q

5 side effects of thalidomide

A
  1. Constipation
  2. Tremor
  3. Painful neuropathy
  4. Thrombosis
  5. Oedema

Thalidomide and lenalidomide as a single agent does not increase the thrombotic risk significantly, but risk increases if concurrent dexamethasone use or chemotherapy. Therefore consider aspirin, LMWH prophylaxis or warfarin if concurrent thal/dex or len/dex use depending on patient’s thrombotic risk.

128
Q

What is the treatment of choice in patients with myeloma not eligible for AuSCT?

A

Melphalan and prednisone in combination with either thalidomide or bortezomib.

Melphalan cannot be used in AuSCT eligible patients as they are stem cell toxic.

129
Q

5 causes of aplastic anaemia

A
  1. Viral: Parvovirus B19 (although more commonly causes PRCA), HBV/HCV, HIV, EBV
  2. Chemical - benzene, glue vapours
  3. PNH - 1/3 develop AA
  4. Thymoma
  5. Immune mediated - SLE, GvHD, eosinophilic fasciitis

Most cases in adults are however idiopathic (80%)
Pregnancy can also cause transient AA.

130
Q

Management of aplastic anaemia

A

Depending on severity - if moderate (ie, BM cellularity <30% with 2/3 cell lines reduced), supportive treatment with antibiotics and treatment.

If severe, needs definitive treatment with:

  1. Immunosuppression - IV ATGAM (horse), prednisolone, cyclosporine maintenance therapy to maintain response
  2. Allogeneic stem cell transplant

Younger age ie <49 years, aim early allogeneic transplant with little transfusion as possible (due to risk of alloimmunization)

Older age >50 - immunosuppression as risk of GvHD and transplant related mortality is too high.

131
Q

Compare and contrast horse derived ATG vs rabbit derived ATG

A

Both are made by injecting human thymocytes and harvesting antibodies.

Horse ATG is superior to rabbit ATG in terms of overall response rate and 5 year overall survival. Therefore use horse ATG first line over rabbit ATG.

132
Q

Septic risk in neutropenia

A

Risk is relatively low down to around 0.5 x 10e9, then rises sharply.

Risk is greater in context of:

  1. Falling count (progressively decreasing availability)
  2. Lack of precursors
  3. Prolonged length of neutropenia
133
Q

5 causes of drug induced neutropenia

A
  1. Carbimazole
  2. PTU
  3. Sulphonamides
  4. Antiepileptics
  5. Rituximab
134
Q

Causes of acute acquired neutropenia

A
  1. Drugs
  2. Viral (hep B, HIV)
  3. Severe bacterial sepsis - poor prognosis
  4. Nutritional - B12/folate/copper deficiency
  5. Hypersplenism

Blood taken from during haemodialysis can cause falsely negative neutrophil count as dialysis membrane causes complement activation and causes attachment of neutrophils onto lung endothelium. Not a true neutropenia.

135
Q

3 main causes of chronic neutropenia

A
  1. Chronic idiopathic neutropenia - neutrophil equivalent of adult ITP. most are mild and never requires treatment. Diagnosis of exclusion. Seen in autoimmune diseases
  2. LGL syndrome - neutropenia associated with increased large granular lymphocyte syndromes (such as NK cells). Not malignant, may regress spontaneously.
  3. Felty’s syndrome - triad of RA, splenomegaly and neutropenia. 1% of RA patients. Probably AI basis and seen in higher RF/ANA levels. often also have LGL syndrome concurrently.
136
Q

Cyclic neutropenia

A

Autosomal dominant mutation of neutrophil elastase (ELANE). Usually mild but can be severe. Cyclic neutropenia over 3 weeks. Regular GCSF reduces nadir and risk of infection.

137
Q

ABO blood group and vWF level

A

Levels of vWF correlate with ABO blood type. Individuals with type O blood normally have the lowest levels of vWF, approximately 50-75% of the vWF levels found in persons with other blood types. vWF levels should be compared with an ABO blood group type–specific range from the laboratory where the test is performed.

138
Q

Mechanism of action of tranexamic acid

A

Tranexamic acid is a synthetic analog of the amino acid lysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen or plasmin. This prevents plasmin from binding to and degrading fibrin and preserves the framework of fibrin’s matrix structure

139
Q

Indications for FFP

A

FFP transfusion is indicated in hemorrhaging patients to replace labile and lost coagulation factors. Clinical circumstances fulfilling this criterion include:

  1. Massive transfusion
  2. Cardiopulmonary bypass
  3. Extracorporeal pulmonary support techniques
  4. Decompensated liver disease
  5. DIC regardless of the cause

Plasma contains all of the coagulation factors. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Thawed plasma has lower levels of factors V and VIII and is not indicated in patients with consumption coagulopathy

140
Q

Indications for cryoprecipitate

A

Cryoprecipitate is prepared by thawing fresh frozen plasma at 4 degrees and collecting the precipitate. Cryoprecipitate contains high concentrations of factor VIII and fibrinogen and vWF. Cryoprecipitate is used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy.

141
Q

What is the relationship between INR and factor level?

A

Non-linear relationship.
Zone of normal haemostasis is anywhere between INR of 1.0 to 2.0. Around INR of 2.0, coagulation factor level is around 30%.

142
Q

5 causes of prolonged TCT (thrombin clotting time)

A
  1. Heparin
  2. Dysfibrinogenaemia
  3. Hypofibrinogenaemia
  4. Increased fibrin degradation product - interferes with fibrin polymerisation
  5. Thrombin inhibitor eg dabigatran
143
Q

Clinical bleeding patterns in:

  1. Platelet dysfunction
  2. Coagulopathy
A
  1. Platelet dysfunction - mucosal bleeding, petechiae, prolonged bleeding from skin cuts
  2. Coagulopathy - deep haematomas and haemarthroses. Tends to be males. Mucosal bleeding/petechiaes are rare.
144
Q

What proportions of haemophilias are spontaneous mutations?

A

30%

Others are X linked recessive.

145
Q

Current evidence based indications for Dabigatran

What about for rivaroxaban?

A
  1. Stroke prevention for non-valvular AF
  2. Thromboprophylaxis post hip and knee replacement surgery

Rivaroxaban - as above plus treatment of acute DVT and prevention of DVT/PE.

146
Q

Treatment for Hodgkins lymphoma

A

Depends on stage.

  1. Limited stage - abbreviated ABVD 4 cycles + radiotherapy
  2. Stage IIB/Advanced stage - either full 6 cycles of ABVD or eBEACOPP.
147
Q

What is contained in ABVD regime for Hodgkins lymphoma and what are its 4 main side effects?

A

Adriamycin
Bleomycin
Vinblastine
Darcabazine.

Side effects - hair loss, neutropenia, heart/lung toxicities from Adriamycin and bleomycin.

Low risk of infertility compared to eBEACOPP.

148
Q

What treatment options are available in relapsed hodgkins disease after ABVD or eBEACOPP?

A
  1. Repeat chemotherapy followed by AuSCT
  2. Brentuximab vedotin - CD30 monoclonal antibody which delivers cytotoxic MMAE, a potent antitubulin agent. CD30 is expressed in HRS cells.
149
Q

Role of rituximab maintenance therapy for follicular lymphoma post R-CHOP

A

Standard of care. PRIMA study shoed that rituximab 2 monthly maintenance therapy prolonged remission compared to observation only.

150
Q

What is the clinical significance of ‘double hit’ DLBCL?

A

Dual positivity to BCL-2 and C-MYC.
Portends a poor prognosis with chance of survival at 33%. Needs high intensity chemotherapy involving R-CHOEP or other high intensity protocol such as hyperCVAD, AuSCT.

151
Q

What constitutes cryoprecipitate?

A

Formed from thawing fresh frozen plasma at 4 degrees and removing the precipitate.
Rich in fibrinogen, vWF, factor 8 and 13

152
Q

Describe B12 absorption and metabolism

A

Main source of B12 is from fish, poultry, egg, milk, meat.

  1. Ingested B12 released from food via pepsin and acid
  2. Initially bound to R protein (transcobalamin I or haptocorrin)
  3. Pancreatic enzymes release cobalamin from R protein and allow binding to IF (secreted from paretal cells)
  4. At terminal ileum, B12-IF complex binds to receptor (cubilin), uptake by receptor mediated endocytosis and absorbed into the portal blood system. Circulates in the blood as transcobalamin 2-B12 complex.
153
Q

Most common cause of B12 deficiency

A

Pernicious anaemia - autoimmune destruction of gastric mucosa/parietal cells leading to atrophic gastritis and reduced IF.

Associated with blood group A, vitiligo, thyroid disease, addisons disease.

154
Q

indications for treatment in follicular lymphoma

Treatment regimen?

A

Based on attempts of improving quality of life:

  1. Local symptoms due to progressive or bulky nodal disease
  2. Compromise of normal organ function due to progressive or bulky disease
  3. Presence of systemic B symptoms (ie, fevers, weight loss, night sweats)
  4. Presence of symptomatic extranodal disease, such as effusions
  5. Cytopenias due to extensive bone marrow infiltration, autoimmune hemolytic anemia or thrombocytopenia, or hypersplenism
  6. An increase in disease tempo

Treatment regimen can be either bendamustine and rituximab with rituximab maintenance, R-CHOP, RCVP

155
Q

4 tumours which secrete EPO

A
  1. RCC
  2. HCC
  3. Pheochromocytoma
  4. Uterine fibroids
156
Q

Role of thrombin-thrombomodulin

A

Thrombin (bound to thrombomodulin on the surface of endothelial cells) also slows its own production by creating a separate negative feedback loop. It does this by converting protein C to activated protein C (aPC), a protease that acts as a potent natural anticoagulant. aPC degrades activated factor Va (and activated factor VIIIa, upstream in the coagulation cascade), ultimately reducing thrombin production

157
Q

Anticoagulation in setting of Factor V leiden heterozygosity/homozygosity

A

There is an increased risk of VTEs with FVL, however it is a very COMMON mutation and most of the mutation carriers do not develop VTE during their life time (only about 5%). Therefore usually prophylactic or lifelong anticoagulation after VTE is not required.

158
Q

When would you treat superficial thrombophlebitis?

A

Treat for 4 weeks with anticoagulation when:

  1. Thrombus greater than 5cm
  2. Thrombus within 5cm of saphenofemoral junction or saphenopopliteal junction
  3. Medical risk factors for DVT (eg, prior DVT, thrombophilia, malignancy, estrogen therapy

Otherwise treatment is compression, anti-inflammatories, topical agents

159
Q

When should you stop following anticoagulation prior to surgery?

  1. Warfarin
  2. Dabigatran/Rivaroxaban
A
  1. Warfarin - 5 days prior to surgery (ie, -6 days before surgery date), check INR day before, given vit K 1-2mg if still high. This is based on half life of 36 to 42 hours.

Bridge with Clexane only if deemed at very high risk of thromboembolism (recent stroke, mechanical heart valve, CHADS2 score of 5/6). Bridge with Clexane 3 days prior to surgery.

Warfarin is restarted within 12-24 hours with bridging Clexane only if high risk of thrombosis.

  1. Dabigatran/Rivaroxaban
    Stopped 2-3 days prior to surgery if normal renal function, or 2-4 days if impaired renal function.

Given that peak effect takes place 2-3 hours after dosing, bridging is usually not required.
If low bleeding risk post op, start 1 day post surgery
If high bleeding risk post up, restart 2-3 days post surgery.

If using Clexane bridging, needs to be stopped 24 hours before surgery, based on half life of 3-5 hours.
If once a day dosing is used, one-half of the total daily dose is given on the morning of the day before surgery. If twice daily dose is used, the evening dose night before the surgery is omitted.

160
Q

Reptilase time

A

Reptilase time (RT) is a blood test used to detect heparin contamination.

Reptilase, an enzyme found in the venom of Bothrops snakes, has activity similar to thrombin. Unlike thrombin, reptilase is resistant to inhibition by antithrombin III.

Thus, the reptilase time is not prolonged in blood samples containing heparin, hirudin, or direct thrombin inhibitors, whereas the thrombin time will be prolonged in these samples.

Other causes of prolonged TCTs will not be affected by reptilase time (eg: hypofibrinogenaemia, dysfibrinogenaemia, increased FDP)

161
Q

Action of bivalirudin/lepirudin

A

Direct thrombin inhibitors - parenteral form

162
Q

How do you measure rivaroxaban level?

A

Modified anti-Xa level

PT can also be done but less reliable.

163
Q

Difference between kappa and lambda chains

A

Kappa chains - more are produced, circulates as monomers therefore easily filtered, therefore causes more LCDD and PCT dysfunction

Lambda chains - circulates as dimers therefore not as easily filtered, causes more amyloidosis.

164
Q

MoA of thalidomide

A

Anti-proliferative effect by binding to cereblon and inactivating it

165
Q

Fanconi Anaemia

A

AR or X linked disorder.
Congenital malformations exist in 60-70% with café au lait spots, hypopigmentation, abnormal thumbs, microcephaly and short stature, hypogonadism and delayed development.

All recognized 15 defects are involved in DNA repair and stabilisation.

BM biopsy will show hypocelluar marrow with dysplastic cells.
Specific test includes chromosomal fragility in lymphocytes when exposed to DiEpoxybutane (DEB) or Mitomicin C (MMC)

Siblings should be tested as there are phenotypic variations.

Increased long term risk of complete bone marrow failure, acute leukaemia/MDS, solid cancers.

Allogeneic stem cell transplant is curative.
Supportive treatments include androgens (oxymethalone) in which anaemia responds the best, transfusion, GCSF.

FRACP written exam preparation (18 decks)

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