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Haematoogy Flashcards

1
Q

RBC with a purple spot in it

Name
Conditions that cause it

A

Howell-Jolly bodies
- nuclear remnants

1) Post splenectomy
2) Hyposplenism
(E.g. sickle cell disease, coeliac, IBD, myeloproliferative, amyloid)
3) Megaloblastic anaemia

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2
Q

Anaemia cut off men and women

A

<135g/L men

<115g/L women

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3
Q

Anaemia causes

A

Reduced production
Increased loss of RBC (haemolytic anaemia)
Increased plasma volume (pregnancy)

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4
Q

Signs of anaemia

A

Pallor

If <80 - tachycardia, flow murmurs —> HF

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5
Q

Anaemia associated with cancer/systemic disease

A

Fe deficiency
Anaemia of inflammation
Leucoerythroblastic anaemia
Haemolytic anaemia

NB: renal cell cancer and liver cancer can cause secondary polycythaemia

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6
Q

Causes of iron deficiency anaemia

A

Blood loss until proven otherwise

  • GI - ulcers, gastritis, polyps, colorectal cancer
  • Menorrhagia
  • Hookworm
  • increased utilisation - pregnancy/lactation/children
  • Decreased intake (premature, child)
  • Decreased absorption (coeliac, post gastric surg
  • Intravascular haemolysis (Microangiopathic, haemolytic anaemia, PNH)
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7
Q

Teardrop RBCs, nucleated RBCs, immature myeloid cells

Condition

Causes

A

Leuco-erythroblastic anaemia
- red and white cell precursor anaemia

Malignancies
Infection
Myelofibrosis

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8
Q

Causes of hereditary anaemia

A

1) Membrane defects
- Hereditary spherocytosis
2) Red cell metabolism
- G6PD deficiency
3) Hb
- Thalassaemias
- Sickle cell disease

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9
Q

Consequences of haemolytic anaemias

A 
Normocytic Anaemia (+/-)
Increased reticulocytes/erythroid hyperplasia

Increased folate demand
Susceptibility to parvovirus B19
Gallstones
Risk of iron overload and osteoporosis in chronic haemolytic anaemias

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10
Q

Bone marrow film showing erythroid progenitors, all look the same.
Low reticulocytes in blood

A

Parvovirus B19

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11
Q

What is Gilbert syndrome

Genotype

A

Bilirubin conjugation impaired = High uncojugated billirubin

Autosomal recessive
UGT 1A1 TA7/TA7 genotype

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12
Q

Clinical features of haemolytic anaemia

A 
Pallor 
Jaundice
Splenomegaly (if spleen destroying RBCs)
Pigmenturia
FH
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13
Q

Anaemia
Increased reticulocytes
Polychromasia

A

Haemolytic anaemia

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14
Q

Specific lab changes in intravascular haemolytic anaemia

A

All:
Reticulocytes, polychromasia

Intravascular:
Hyperbillibrubinaemia
LDH high
Absent haptoglobins
Haemoglobinuria
Haemosiderinuria (brown urine)
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15
Q

Inheritance of hereditary spherocytosis

type of haemolysis

Blood film

A

AD in 75%
De novo/AR mutations in 25%

Extravascular - splenomegaly

Blood film showing RBC lacking central pallor, small and round, Mean cell Hb increased, polychromatic cells

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16
Q

Osmotic fragility test used for

More up to date test for this condition

A

Hereditary spherocytosis

Eosin 5 malamide (EMA) Die binding test - reduced binding

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17
Q

Blood film showing RBC lacking central pallor, small and round, Mean cell Hb increased, polychromatic cells

What test can be done to confirm condition

A

Hereditary spherocytosis

Osmotic fragility test
Die binding test - reduced binding

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18
Q

G6PD deficiency inheritance

G6PD function

A

X-linked - severe disease in hemizygous boys and homozygous girls

G6PD catalyses 1st step in pentose phosphate pathway - generates NADPH to maintain glutathione - needed to protect RBC against oxidative stress

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19
Q

Acute episodic haemolysis

Methyviolet stain of blood shows - heinz bodies - what are these

A

G6PD deficiency

Peripheral inclusions formed of denatured Hb - characteristic of oxidative haemolysis

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20
Q

Blood film in G6PD deficiency
Other test

What stain and what does it show

A

Contracted cells
Nucleated RBcs
Bite cells
Hemighosts

Enzyme assay 2-3 months after crisis

Methyviolet - Heinz bodies

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21
Q

Agents that provoke haemolysis in G6PD deficiency

A 
Antimalarials - primaquine
Antibiotics - Sulphonamides, Ciprofloxacin, Nitrofurantoin
Dapsone, Vit K,
Fava beans
Moth balls
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22
Q

Blood film showing RBC with spiky projections

  • what are these called
  • In what condition do they occur
  • symptoms of this condition
A

Echinocytes

Pyruvate kinase deficiency - autosomal recessive

Haemolytic anaemia. Hereditary enzyme defect
Severe neonatal jaundice, splenomegaly, haemolytic anaemia

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23
Q

Blood film shows basophilic stippling -

What is it

Causes

A

Accelerated erythropoeisis or defective Hb synthesis, small dots in the periphery are seen

Lead poisoning
Megaloblastic anaemia
Myelodysplasia
Liver disease
Haemoglobinopathy e.g. thalassaemia
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24
Q

Principles of management for haemolytic anaemias

A

Folic acid supplementation
Avoid precipitating factors
RBC transfusion/exchange
Immune against hepA/B
Monitor for gall stones, iron overload, osteoporiss
Cholestectomy for symptomatic gall stones
Splenectomy if indicated

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25
Q

What is Virchow’s triad

A

Blood
Flow
Vessel wall

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26
Q

Factors in blood that predispose to thrombosis

A

1) High platelets
2) Coagulation system (triggered by TF, generates thrombin, thrombin converts fibrinogen to fibrin aka the clot)
3) Viscosity (haematocrit, protein/paraprotein)

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27
Q

Physiological anti-coagulant

A

TFPI
- neutralises TF and VIIa complex

Protein C and S

  • Thrombin activates TM
  • TM opens receptor to bind + activate protein C
  • In presence of protein S, APC inactivates FV and FVIII

Antithrombin
- Binds thrombin 1:1 and stops it’s generation
(NB: heparin acts by augmenting antithrombin effect)

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28
Q

Vessel wall - normal state with regards to thrombosis

A

Anti-thrombotic

  • Expresses anticoagulant molecules (Thrombomodulin, Protein C receptor, TF pathway inhibitor, Heparens)
  • Doens’t express TF
  • Secretes antiplatelet factors (Prostacyclin, NO)
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29
Q

Vessel wall pro-thrombotic state

A

Due to injury/inflammation

  • Anticoagulant molecules downregulated
  • Adhesion molecules upregulated
  • TF expression
  • Prostacyclin production decreased
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30
Q

Blood flow promoting thrombosis

A

Stasis

  • Accumulation of activated factors
  • Promotes platelet adhesion
  • Promotes leukocyte adhesion and transmigratuon
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31
Q

Causes of blood stasis that may promote thrombosis

A
  • Surgery, travel, paraparesis
  • Tumour, pregnancy
  • Polycthaemia, paraprotein
  • Vascular abnormalities
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32
Q

Dose of anticoagulant therapy principles

A

High dose - therapeutic

Low dose - prophylaxis

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33
Q

Immediate acting anticoagluants

A
  • Heparin(IV,SC) - unfractionated or LMWH
    Promotes antithrombin III which inactivates thrombin and factors 9, 10, 11
  • Direct acting (oral) - anti-Xa (rivaroxiban) and anti-IIa
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34
Q

Delayed acting anticoagulants

A

Vit K antagonists - Warfarin

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35
Q

Heparin use
Positives
Negatives

Antidote

A

Immediate anticoagulant - potentiates anti-thrombin
+ve: Immediate use and easy administration
-ve: Not long term because injections and risk of osteoporosis, bleeding and heparin induced thrombocytopenia (HIT) –> osteoporosis

Use LMWH over unfractionated because needs monitoring

Antidote: Protamine sulphate

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36
Q

Rivaroxiban use

A

Anti-Xa direct acting anticoagulant

+ve: Fast on and off effect, oral, useful in long term, short half life, no monitoring

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37
Q

Warfarin use

Factors affects

A

Vit K antagonist - delayed anticoagulant - Factor II, VII, IX and X fall but so do protein C and S, Z

-ve: delayed - a week before stable, NEEDs monitoring with INR, interaction with other drugs, teratogenic
+ve: reversed with vitamin K

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38
Q

Warfarin monitoring

A

INR - derived from prothrombin time

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39
Q

Reversal of heparin

A

Protamine

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40
Q

ThromboProphylaxis for patients art risk

A 
Options
LMWH e.g. tinzaparin low dose
Rivaroxiban
TED stockings (ONLY IF surgery of if heparin CI)
Intermittent compression (to increase flow)
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41
Q

Treatment of DVT/PE

A

Options

1) LMWH (tinzaparin 175) + warfarin
- stop LMWH once INR >2 for 2 days
- Continue for 3-6 months

2) Start DOAC and continue for 3-6 months

If cancer pt, continue LMWH not warfarin

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42
Q

Risk of recurrence of thrombosis

A 
High risk - idiopathic VTE
- consider long term anticoagulation
Low risk - surgery
- No need for long term
Minor precipitants - COCP, flights, trauma
- 3 months usually adequate
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43
Q

Classification of Fe deficiency anaemia causes

A

Blood loss - main
Increased use - pregnancy/lactation, children
Decreased intake - premature, children, elderly
Decreased absorption - coeliac, post gastric surgery
Intravascular haemolysis - MAHA, haemolytic anaemia, PNH

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44
Q

Sickle cell disease define

Inheritance

A

Pathological effects of sickling

Autosomal recessive
Single base mutation GAG -GTG Glut-Val at codon 6 on beta chain

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45
Q

Sickle cell disease key features

A 
Anaemia 60-80g/
Splenomegaly
Folate deficiency
Gall stones
Aplastic crisis (parvovirus B19)
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46
Q

Vado-occlusive and infarction symptoms of sickle cell disease

A 
Stroke
Infections (hyposplenism, CKD)
Crises (splenic, sequestration, chest and pain)
Kidney
Liver (gall stones)
Eyes (retinopathy)
Dactylitis 
Mesenteric ischaemia
Priapism
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47
Q

Acute sickle cell treatment

A

Opioid analgesia for painful crises

Exchange transfusion in severe crises

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48
Q

Chronic tx for sickle cell anaemia

A

All should be on penicillin, pneumococcal vax, HIB vac

Some benefit from
Folic acid and hydroxycarbamide
Regular exchange transfusions
Doppler monitoring in early childhood for prophylactic exchange if turbulent flow

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49
Q

4-6months old severe anaemia, failure to thrive, hepatosplenomegaly, bony deformity, severe anaemia, heart failure

Diagnosis and treatment

A

Dx by Hb electrophoresis (Guthrie test at birth)

Beta thalassaemia major (B0/B0)

Blood transfusions with desferrioxamine to stop iron loading plus folic acid

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50
Q

Morning haemoglobunuria, thrombosis

Test to do

A

Ham’s test or immuno phenotype shows altered GPI on RBC - complement mediated lysis - Intravascular haemolysis

= Paroxysmal nocturnal haemoglobinuria
NON IMMUNE

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51
Q

1st line investigations in a haemolytic anaemia picture

A 
DAT (for autoimmune haemolysis)
Urinary haemosiderin/Hb
Osmotic fragility/dye binding test
G6PD +/- PK activity
Hb separation A and F %
Heinz body stain
Hams test/FACs of GPI linked proteins
Thick and think blood film
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52
Q

Malaria associated with haemolytic anaemia

A

Plasmodium falciparum

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53
Q

Neutrophilia causes

A 
Corticosteroids
Underlying neoplasia
Tissue inflamation e.g. colitis, pancreatitis
Myeloproliferative/leukaemic disorders
Infection (most common)
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54
Q

True polycythaemia causes

A

= Raised red cell mass

1) Secondary
- Appropriate - high altitude, hypoxic lung disease, cyanotic heart disease
- Inappropriate - HCC, Renal cancer, bronchial cancer

2) PV
- Clonal myeloproliferative disorder (acquired mutation in JAK2 V617F)

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55
Q

Types of WBC

A

Mature:
Phagocytes: Granulocytes (neut, eos, baso), monocytes
Immunocytes: T lymphocytes, B lymphocytes, NK cells

Immature:
Blasts, promyelocytes, myelocytes

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56
Q

Investigating a high WBC count

A

Hb and MCV: Are RBC and platelets abnormal too
WBC and automated differential: 1 lineage only raised = BM healthy
Blood film: Morphology, how mature cells in PB are

(If grossly immature cells in blood - AML

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57
Q

Causes of eosinophilia

A

Reactive

  • Parasitic
  • Allergic (asthma, rheumatoid etc.)
  • Underlying neoplasm esp Hodgkin, T-cell NHL
  • Drugs (reaction erythema multiforme)

Chronic eosinophilic leukaemia

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58
Q

Monocytosis causes

A

TB, brucella, typhoid
Viral: CMV, VZV
Sarcoidosis
Chronic myelomonocytic leukaemia (MDS)

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59
Q

What are myelodysplastic syndromes (MDS)

A

Heterogeneous group of acquired haemopoietic stem cell disorders

  • -> clone of marrow stem cells with abnormal maturation = numeric and functional reduction in blood cells =
    1) Cytopenia(s)
    2) Qualitative (functional) abnormalities of erythyroid, myeloid and megakaryocyte maturation
    3) Increased transformation to leukaemia (chance depend on type of MDS)
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60
Q

MDS epidemiology

Blood and BM morphological features

A

Elderly usually
Develops over weeks + months
Signs and symptoms of general marrow failure

Pegler Huet anomaly - bilobed neutrophils
Dygranulopoeisis
Dyseryrthropoiesis of RBC
Micro-megakaryocytes
Increased proportion of blast cells in BM

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61
Q

MDS classification

A

Dependent on proportion of blast cells in BM

  • 5-9% = refractory anaemia with excess blasts 1
  • 10-19% = refractory anaemia with blasts 2

Generally, the greater the BM blasts, more likely to get a cytogenic abnormality
- exception is 5q syndrome - by definition is a cytogenic abnormality

nb: AML = BM >/= 20% blast cells

62
Q

Evolution of MDS

Treatment

A

1) Deterioration of blood counts
2) AML development
3) As a rule of thumb: 1/3 die from infection, 1/3 die from bleeding, 1/3 die from acute leukaemia

Only 2 tx to prolong survival
1) Allogenic stem cell transplant
2) Intensive chemotherapy
But only a minority of MDS benefit from them. Give:
- Supportive care
- Biological modifiers
- Oral chemo
- Low dose chemo
- Intensive chemo/SCT (for high risk MDS) - AML type regimens
63
Q

Bone marrow failure

Causes

A

Damage or suppression of stem or progenitor cell

1) Primary BM failure
- Congenital: Fanconi anaemia (multipotent stem cell)
- Diamond-Blackfan anaemia (red cell progenitor)
- Kostmann’s syndrome (neutrophil progenitors)
- Acquired: Idiopathic aplastic anaeia (multipotent stem cell)

2) Secondary BM failure - far more common, due to infiltration/damage of BM
- Haematological (leukaemia, lymphoma, myelofibrosis)
- Non haematological (solid tumours)
- Radiation
- Drugs
- Chemicals
- Autoimmune
- Infection (parvovirus, viral hepatitis)

64
Q

Drugs related to BM failure

A

Predictable (dose dependent) - cytotoxic drugs
Idiosyncratic (not dose dependent) - Phenylbutazone, Gold salts
Antibiotics - Chloramphenicol, sulphonamide
Diuretics - Thiazides
Antithyroid drugs - carbimazole

65
Q

Aplastic anaemia diagnosis

Classification

A

1) Blood - pancytopenia
2) Marrow - hypocelullar

  • Idiopathic - majority (70-80%)
  • Inherited: DC, Fanconia anaemia, Schwachman-Diamond syndrome
  • Secondary: Radiation, drugs, Viruses, Immune (sle)
Also classified as severe aplastic anaemia or non-severe aplastic anaemia
- severe = 2 PB features
1) Reticulocytes <1%
2) Neutrophils <0.5 
3) Platelets <20
\+ BM <25% cellularity
66
Q

Differential diagnosis for pancytopenia and hypocellular BM

A

1) Hyoplastic MDS/AML
2) Hypocellular ALL
3) Hairy cell leukaemia
4) Mycobacterial
5) Anorexia nervosa

1st thought should be aplastic anaemia but these are differentials

67
Q

Management of BM failure

A
  1. Seek and remove cause
  2. Supportive: Blood/platelet transfuson, antibiotics, iron chelation
  3. Immunosuppressive therapy (anti-thyomcyte globulin, steroid, cyclosporine)
  4. Drugs to promote BM recivery: Oxymethone
  5. SCT
  6. Other treatments if refractory
68
Q

Treatment of aplastic anaemia

A

1) Supportive
- Blood products
- Antimicrobials
- Iron chelation when ferritin >1000mcg/l
2) Specific treatment based on age/severity
- Immunosuppressive therapy - ALG, ciclosporin - older pt
- Androgens - oxymethalone
- SCT - younger pt with doner (80% cure), VUD/MUD for >40yrs (50% survival)

69
Q

Complications following immunosuppresive therapy for aplastic anaemia

A
  1. Relapse (35% over 15yrs)
  2. Clonal haemotological disorders - MDS, leukaemia
    - 20% risk over 10 yrs
  3. Solid tumours - 3% risk
70
Q

Fanconi anaemia

A

Most common inherited aplastic anaemia
X-linked or AR
Abnormalities in DNA repair –> chromosomal fragility

  • Short stature
  • Hypo pigmented spots and cafe-ai-lait
  • Abnormality of thumbs
  • Microcephaly/hydrocephaly
  • Hypogonadism
  • Developmental delay
    30% have no abnormalities

Complications: AA (90%) , Leukaemia (10%) , Liver disease, MDS (32%), Cancer (5%)

71
Q

Dyskeratosis congenita

A 
Genetic basis - telomere shortening  - can be x-linked, AR or AD
Inherited disorder characterised by:
- Marrow failure
- Cancer predisposition
- Somatic abnormalities

Classic triad of: Skin pigmentation, leukoplakia, nail dystrophy

Somatic abnormaliyies/complications: Skin pigmentation (89%), Nail dystrophy (88%), BM failure (85.5%), Leucoplacia (78%)

72
Q

AML chromosomal abnormalities

A 
t(15;17) - acute promyelocytic leukaemia
t(5;8)
t(8;21)
Trisomy 8, trisomy 21
Inv(17)
Deletion (5/5q or 7/7q)

Remember there are also molecular abnormalities - look for using PCR

73
Q

Myeloblast appearance on blood film

AML causes

A

V fine granules
Cytoplasm

Unknown = 90%
Familial, Down's
Irradiation
Anti-cancer drugs
Cigarrete smoking
74
Q

Leukamogenesis in AML

A

2 genetic hits requires
Type 1: proliferative and survival
Type 2: blocks differentiation

75
Q

Acute promyelocytic leukaemia

A

T (15;17) - fusion PML, RARA gene. Type 2 abnormality
Block in maturation later than other AML - promyelocytes with lots of Auer rods

DIC - low platelets, low fibrinogen, d dimer +ve = bleeding/haemorrhage
Responds to all-trans retinoic acid

76
Q

T (8;21)

A

AML - most common karyotypic abnormality in AML
Fusion of RUNX1 (encoding CBFalpha) with RUNX1T1

Relatively good prognosis
- not all blast cells, some maturation

77
Q

AML vs ALL diagnosis

A

20% BLAST BM cells
Cytology: AML have auer rods
Cytochemistry: AML +ve staining for myeloperoxidase, sudan black, non-specific esterase

Immunophenotyping:
AML
- MPO, CD13, CD33, CD14, CD15, glycophorin
ALL
- Precursor B cell - CD19, CD20, TdT, CD10 +/-ve
- B cell - CD19, CD20, sIg
- T-cell: CD2, CD3, CD4, CD8, TdT

Both AML and ALL have CD-34, CD45, HLA-DR

78
Q

AML clinical features

AML diagnosis

A

BM failure: Anaemia, thrombocytopenia, neutropenia
Local infiltration: Hepatosplenomagaly, gum infiltration, lymphadenopathy (much less than ALL), Skin or other sites

Blood count and film
BM morphology
Immunophenotyping - more so to follow up disease
Cytogenic analysis on BM
Molecular studies (when needed)
79
Q

AML treatment

A

Supportive
- Red cells (in anaemia), platelets (if <10 or bleeding), FFP (if DIC), Antibiotics, Long line, Allopurinol (prevent breakdown of blood products leading to renal failure), fluid and electrolyte balance

Chemo - damages DNA of leukaemic cells as they are continuously dividing and lack cell cycle checkpoint control
- usually combination chemo 4-5 courses ~ 6 months

Consider transplant if poor prognosis

Nb: ATRA for promyelocytic leukaemia
TK inhibitors for rare PH +ve

80
Q

ALL features

A

PB: anaemia, thrombocytopenia, neutropenia

BM and other organs - lymphadenopathy (v often), Hepatosplenomegaly, Tests, CNS, kidneys, Bone (pain in long bones)

81
Q

t (9;22) in which conditions and prognosis

A

ALL and CML

Poor prognosis but better now because TK inhibitors e.g. imatinib

82
Q

ALL diagnosis

treatment

A 
Blood count and film
- Anaemia, Neutropenia, Thrombocytopenia
BM aspirate
- 20% blasts
Immunophenotyping
Cytogenetic/molecular analysis
Blood group, LFTs, urea, Cr, electrolytes, uric acid, coagulation screen

Supportive: blood products, antibiotics
Specific: Systemic chemo, CNS directed for all, Molecular targeted tx, transplantation
~2yrs for girls
3 yrs for boys

5 yr disease free survival 80% children
5yr disease free survival 30-40% adults

83
Q

What is lymphoma

Where found

Types

A

Neoplastic tumour of lymphoid cells

Lymph nodes, BM, blood
Lymphoid organs: spleen or gut associated lymphoid tissue
Skin (often T cell disease)
Rarely anywhere

NHL - 80% - B cell or T cell - precursor or peripheral of each - more widespread at presentation than HL
HL - 20% - classical or lymphocyte predominant. Spreads continuously to adjacent lymph nodes. Often localised to one lymph node

84
Q

3 reasons why lymphoma risk is present

Risk factors

A

1) Rapid cell proliferation - risk DNA replication error
2) Depend on apoptosis (90% normally die in germinal centre) - apoptosis switched off, acquired DNA mutation in pro-apoptotic genes
3) DNA molecules 1. cut and rejoined plus 2. undergo deliberate mutations for Ig and T cell receptor diversity - Recombination errors and new point mutations

Constant antigenic stimulation
Infection
Loss of T cell function

85
Q

Lymphomas due to chronic antigenic stimulation

A

Gastric MALT: H.pylori. Mariginal zone NHL of stomach - B cell - tx with omep 20mg, Clarith 500mg, amox 1gm bd

Sjogren syndrome Marginal zone NHL of parotid lymphoma = B cell

Coeliac - small bowel enteropathy associated T-cell NHL
- responds poorly to chemo generally fatal - aim to prevent

Hashimoto’s thyroid

86
Q

Lymphomas due to infectious agents

A

HTLV1 infects T cells by vertical transmission - Japanese and Caribbean - may develop Adult T cell leukaemia lymphoma

EBV infects B lymphocytes . Usually maintained by T cells. But if immumosuppression/loss of normal T cells, increased risk of B cell lymphomas

  • HIV
  • Iatrogenic (renal, heart, pancreas transplant immunosuppression)
  • Post transplant lymphoproliferative disorder
87
Q

Mantle cell lymphoma buzzwords

A

Pre-greminal centre cell. Mantle zone expands and then spreads thoughout node.

11;14
Aberrant CD5 and Cyclin D1 expression = dx
Low grade (slowly progressing)

Median survival 3-5yrs

88
Q

Follicular lymphoma buzzwords

Treatment

Prognosis

A

Lymphadenopathy of middle ages/elderly. Indolent
CD10, bcl6+,
14;18 involving bcl-2 gene

Microscopy: Node effaced by round structures (neoplastic follicles)
Indolent but can transform to high grade lymphoma (composed of large rapidly proliferating cells)

Incurable, median survival 12-15yrs
Wait and watch and treat only if nodes compressing bowel, ureter, vena cava, massive painful nodes
- R-CVP
- Maintenance rituximab delays next progression

89
Q

CLL/Small lymphocytic lymphoma buzzwords

Prognosis

A

From naive or post-germinal centre memory B cells
CD5 (not on mature B cells normally), CD23 +

Lymphocytosis, smear cells, thrombocytopenia
Microscopy: lymph node has no germinal centre, just sheets of small lymphocytes

Indolent. Median survival ~10-15yrs. Can transform to high grade lymphoma where sheets of large cells would be seen (Richter transformation)

IgH mutated survival ~25yrs
IgH unmutated survival ~8yrs
Do FISH as 17p deletion (p53 deleted) = poor prognosis

90
Q

Burkitt’s Lymphoma buzzwords

A

Jaw of abdo mass childre/young adults
EBV associated

Germinal centre origin
Starry sky appearance

C-myc translocation - removes break on cycle

91
Q

Diffuse large B cell lymphoma buzzwords

Treatment

A

Lymphadenopathy in middle aged/elderly -
30-40% of NHL

Germinal centre or post-germinal centre B cell
Sheets of large lymphoid cells
Germinal centre phenotype DC10 +ve = good prognosis
p53 +be, high proliferative fraction = poor prognosis

R-CHOP: Rituximab, Cyclophoshamid, Adriamycin, Vincristine, Prednisolone
x 6-8 cycles
Aim is curative ~ 50%
Relapse - Autologous SCT saves 25%

92
Q

T cell lymphomas buzzwords

A

Eosinophils aggressive

Adult T cell leukaemia/lymphoma - Carribean/Japan, HTLV1 associated

Enteropathy associated T cell lymphoma - Coeliac

Cutaneous T cell lymphomas - e.g. mycosis fungoides

Anaplastic large cell lymphoma - children/young

  • ALk-1 protein staining
  • 2;5
  • Sheets of anaplastic (nuclei wide), large lymphocytes
93
Q

Classical Hodgkin lymphoma buzzwords

A

Owls eye appearance cells with prominent nuceloli - Reed steinberg cells
CD15 + CD30
CD20 - originate from B cells - germinal/post-germinal centre
EBV associated
Young and middle aged

Types: Nodular sclerosis, Mixed cellularity, lymphocyte rich/delepted

94
Q

Non classical hodgkin lymphoma buzzword

A

No EBV association
Negative for CD15, CD30, +ve for CD20

Called nodular lymphocyte predominant hodgkin lymphoma

95
Q

Hodgkin lymphoma staging

Treatment

Prognosis

A 
Ann Arbour staging
I; one group of nodes
II: >1 group nodes same side diaphragm
III; nodes above and below diaphragm
IV: extra-nodal spread
B if fever, night sweats, unexplained weight loss
Chemo - preserves fertility. 2-6 cycles
Adriamycin (se cardiomyopathy)
Bleomycin (se pulmonary fibrosis)
Vinblastine
DTIC

+/-

Radiotherapy: field only
(risk of breast Ca after 25y, Leukaemia 3% after 10yrs, lung/skin cancer)

PET-CT after 2 cycle ABVD to assess response and guide radiotherapy need at end of chemo

Prognosis ~ 50-90% cure
Stage I or II: 80% cured
IV: Only 50% cured

96
Q

Staging of non-hodgkin lymphoma

A

As for hodgkin lymphoma - ann arbour staging:
I; one group of nodes
II: >1 group nodes same side diaphragm
III; nodes above and below diaphragm
IV: extra-nodal spread
B if fever, night sweats, unexplained weight loss

Use CT or PET
+ BM biopsy
+ /- LP

Prognostic markers
LDH
Performance status
HIV serology
Hep B serology
97
Q

CLL treatment principles

A

Supportive and prophylaxis and tx of infections
Prophylactic aciclovir, immunisation against pneumococcus and seasonal flu, IVIG if hypogammaglobulinemia and recurrent bacterial infection

Autoimmune phenomena
1st line steroids. 2nd line rituximab
Irridaed blood products if risk of TA GVHD

If Richter transformation
R-CHOP

Leukaemia directed treatment
Wait and watch. Don’t tx stage A
Tx only if:
- progressive lymphcytois >50% increase in 2 months or doubles in <6months
- progressive BM failure: Plt <100, Hb <100, neutrophils <1
- progressve lymphadenopathy/splenoegaly
- systemic symptoms

1st line (Tpp53 intact)
Chemo immunotherapy

Tp53/17p deleted CLL/ refractory disease

  • Imbrutinib (Bruton tyrosine kinase inhibitor)
  • Venetoclax (anti Bcl-2 oral agent)
98
Q

Multiple myeloma key features

A 
Monoclonal plasma cells - have expanded ER and golgi
- nucleus pushed to 1 side
Paraprotein
Anaemia
End stage renal failure
Infection
Osteolytic lesions

Normal PC suffers chromosome incident –> incorrect translocation of genetic material –> limited acccumulation of some monoclonal PCs = MGUS (harmless)
1% with MGUS pick up more mutations (e.g KRAS) –> MM

99
Q

Multiple myeloma diagnosis

MGUS characteristics

A

Calcium elevated
Renal impairment
Anaemia
Bone lesions

+ monoclonal protein (on serum electrophoresis)

X-ray of spine if back pain
Lab tests (Ca, renal impairment, anaemia)
Immunophenotype: CD138, CD38, monotypic cytoplasmic Ig.
- ve CD19, CD20 and sIg
BM: 40-90% plasma cells (all either kappa or lambda +)

MGUS

  1. monoclonal serum protein <30g/l
  2. BM plasma cells <10%
  3. Annual risk of progression to MM ~1-2%
  4. Rare in young
100
Q

Multiple myeloma treatment approaches

A

Steroids
Immunomodulatory drugs
Classic chemo agents - mephalan, cyclophosphamide
Proteasome inhibitors - bortezomib; carfilxomib

101
Q

RBC transfusion indications

Aim of transfusion

Special requirements for RBC transfusion

A

1) Major blood loss >30% volume
2) Perio-op/critical care if Hb <70/80g/L
3) Post chemo or ACS threshold is Hb <80g/L
4) Symptomatic anaemia

Aim for Hb 70-90g/L
Unless CVS and then aim for 100g/L

Transfuse only 1 unit at a time
Ensure fe/folate/b12 deficiency treated first

  • CMV negative blood for intra-uterine and neonatal transfusions
  • Irradiated blood for immunosuppressed
  • Washed if concern of severe allergic reaction
102
Q

FFP transfusion indication

A

1) Massve transfusion if blood los >150ml/min
2) DIC ONLY IF BLEEDING
3) Liver disease and risk if PT 1.5x normal

Really only for bleeds
Use vit K first
1 unit = 250ml - adult dose is 4-6 units

103
Q

Platelet transfusion indications

A

1) Platelets <10 with no bleeding
2) Bleeding and platelets <30
3) Massive transfusion aiming for plt >75
4) Prevent bleeding in surgery if <50 (<100 in eye/CNS)
5) Prevent bleeding post chemo if <10 (<20 if sepsis)

One unit raises platelets by 30-40

Contraindications to prophylaxis (even if above)

  • HIT
  • TTP
  • ITP
  • Chronic BM failure
104
Q

Monitoring blood transfusion reactions

Signs to look out for

A

Baseline temp, BP, HR, RR
Repeat after 15 mins
Repeat hourly and at end of transfusion

Symptoms: Fevers, rigors, flushing, vomiting, dyspnoea, tachycardia, pain at transfusion site, loin/chest pain, urticaria, itching, headache, collapse

105
Q

Acute transfusion reactions

A

Stop transfusion and call a doctor

MIld fever or urticarial only = Febrile non-haemolytic transfusion or mld allergic reaction]

Significant changes in observations with shock/collapse

  • Bleeding, dark urine = ABO incompatability
  • Swelling, wheezing = severe allergic reaction/anaphylaxis
  • High fever - bacterial contamination

Significant breathlessness

  • Raised CVP - TACO
  • Normal CVP - TRALI - due to anti-WBC antibodies (HLA or neutrophil Abs) in dono - reacts with patient’s WBC and aggregates stuck in pulmonary capillaries –> lung damage
106
Q

GVHD symptoms

Treatment

A

Donor lymphocytes attack patients gut, liver, skin and BM –> severe diarrhoea, liver failure, skin desquamation, BM failure + death weeks to months post transfusion

Prevent - irradiate blood components for immunosuppressed or HLA matched

107
Q

Delayed transfusion reactions

A 
Delayed haemolytic transfusion reaction
GVHD
Post transplantation purpura
Viral infections
Iron overload
108
Q

Thalassaemia
vs
Haemoglobinopathy

What is Hb molecule made up off

A

Thalassaemia = Genetic disorder of globin chain synthesis

Haemoglobinopahy = Any disorder of globin chain synthesis

Haemoglobin molecule made up of 4 globin chains, each with a haem group in the middle

Alpha gne on chr 16
Beta, gamma, delta globin genes on chr 11
HbF = 2 alpha, 2 gamma
HbA2 = 2 alpha, 2 delta
HbA = 2 alpha, 2 beta
109
Q

SCD symptoms in child

A

Dactylitis
Splenic sequestration - severe anaemia, shock, death
Immature immune systems - pneumococcus, parvovirus B19, HI and meningococcus
Folic acid need greater

110
Q

betha thalassaemia major clinical picture

A

Anaemia - HF, growth retardation
Erythropoietic drive –> bone expansion and extramedullary haematopeisis - hepatosplenomegaly
Iron overload - HF, gonadal failure

111
Q

Fragmented red cells, microspherocytes, had a GI infection recently

A

HUS

112
Q

TTP classical signs

A 
MAHA
Thrombocytopenia
Fever
Neurological abnormalities
Renal impairment

Is autoimmune
Underlying defect is deficiency of vWF cleaving protease (ADAMTS13) –> large vWF multimers form –> widespread platelet thrombi

Tx is plasma exchange (gets rid of Ab and replaces deficient protein.

113
Q

Microcytic anaemia causes

A

Fe-deficiency anaemia
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia (in absence of anaemia)

114
Q

Causes of normocytic anaemia

A 
BM failure
Blood loss (acutely)
Hypothyroid
Haemolytic anaemia
Pregnancy
Anaemia of chronic disease
Renal failure
115
Q

Causes of macrocytic anaemia

A

Megaloblastic: folate deficiency + B12 deficiency

Non megaloblastic:

  • Reticulocytosis
  • Alcohol (macrocytosis without anaemia)
  • Liver disease
  • Pregnancy
  • Hypothyroid

Haem:

  • Myelodysplasia
  • Myeloproliferative
  • Myeloma
  • Aplastic anaemia
116
Q

Megaloblastic anaemia blood film

A

Hypersegmented polymorphs
Leucopenia
Thrombocytopenia
Macrocytosis (oval)

117
Q

Anaemia of chronic disease

Causes

A

Normocytic or Microcytic

Chronic infection
Vasculitis
Rheumatoid arthritis
Malignancy

118
Q

Low Fe, High TIBC(Transferrin), low ferritin

A

Fe deficiency anaemia

119
Q

Low Fe, Low TIBC (transferrin), high ferritin

A

Anaemia of chronic disease

120
Q

Causes of sideroblastic anaemia

A 
MPD
MDS
Lead
Alcohol
B6 deficiency (Tb drugs)
Chemo/radio
121
Q

High Fe, normal TIBC, high ferritin

A

Sideroblastic anaemia

Chronic haemolysis or Haemochromatosis
Same or low TIBC

122
Q

What are ringed sideroblasts

A

Erythroid precursors with iron deposited in mitochondira in a ring around nucleus

123
Q

Plummer vinson syndrome

A

Fe deficiency - also koilonychia (spoon nails), brittle hair/nails
Difficulty swallowing
Cheilosis (cracking of mouth corners)
Glossitis

124
Q

What is pernicious anaemia

Management

A

Macrocytic megaloblastic anaemia
B12 deficiency

Autoimmune atrophic gastritis

Parietal cell antibodies (90%), Intrinsic factor antibodies (50%), Schilling test (outdated)

Replenish B12 with IM hydroxocobalamin

125
Q

B12 deficiency features

Intake of B12

A

Pernicious anaemia

Mouth: glossitis, angular cheilosis
Neuropsych: Irritable, depression, psychosis, dementia
Neuro: Paraesthesia, peripheral neuropathy

Meat and dairy (b12 deficiency = vegan)

126
Q

Folate deficiency features

Management

A

Macrocytic, megaloblastic anaemia

Malabsorption: Coeliac
Drugs: Alcohol, methotrexate, trimethoprim, phenytoin

Give folic acid if you know it is the cause
DO NOT GIVE IF YOU DON’T as exacerbates B12 deficiency neuropathy

127
Q

Cold agglutin disease

Mediated by what

Causes

Management

A

IgM. Intravascular haemolysis
DAT (direct antiglobulin test) +ve

Primary idiopathic
Lymphoma
Infections: EBV, mycoplasma

Avoid underlying condition
Avoid cold
Chlorambucil (chemo)

128
Q

Warm agglutin disease
DAT result

Mediated by what

Causes

Management

A

IgG. Extravascular haemolysis.
DAT (direct antiglobulin test) +ve

Primary idiopathic (mostly)
CLL
Methyldopa

Steroids
Splenectomy
Immunosuppression

129
Q

Paroxysmal cold haemoglobinuria
DAT result

Causes

Specific blood test marker

Management

A

DAT (direct antiglobulin test) +ve

Viral infection: Measles, syphilis, VZV

Donath-Landsteiner antibodies
- stick to RBCs in cold –> complement mediated haemolysis on warming

No management needed as self-limiting

130
Q

Paroxysmal nocturnal haemoglobinuria

DAT result

Mediated by what

Causes

Management

A

DAT -VE

Acquired loss of GPI surface marker on RBC (Ham’s test) –> complement mediated lysis = intravascular haemolysis

  • Morning haemoglobinuria
  • Thrombosis
  • Budd chiari syndrome

Folate, iron. Prophylactic vaccination
Eculizumab prevents complement binding to RBCs

131
Q

Budd chiari syndrome

A

Hepatomegaly
Ascites
Abdo pain

132
Q

MAHA

DAT result

Mediated by what

Causes

Management

A

DAT -ve

RBC damage –> schistocytes due to mechanical forces

HUS
TTP (Antibodies against ADAMTS13)
DIC
Pre-eclampsia

Plasma exchange
Supportive

133
Q

Primary haemostasis

A

Platelet aggregation

Vessel injury
Platelt bind via Gp1b (vWF)
Thromboxane + ADP release –>
Platelet aggregation vi Gp2b/3a (fibrinogen receptor)

134
Q

Secondary haemostasis

A

Exrinsic pathway (PT)

  • TF-VII
  • X–> Xa
  • Xa-5a –> generates thrombin but mainly activates intrinsic pathway
Intrinsic pathway (aPTT)
- Starts with 12
- 11
- 9
- 8
--> Xa
Xa-5a --> Thrombin burst

Common:
Thrombin converts fibrinogen to fibrin - Stable clot

Fibrinolysis = breaks down fibrin into fibrin degradation products

  • TPA (tissue plasminogen activator) and urikinase convert plasminogen to plasmin
  • plasmin degrades fibrin
135
Q

What is factor V Leiden

A

APC resistance so Factor V not broken down

136
Q

Most thrombogenic condition

A

Lack of antithrombin

137
Q

ITP treatment

A

> 50,000
- No symptoms, no treatment

20,000-50,000
- Only treat if bleeding -> steroids, IVIG

<20,000

  • No symptoms - Steroids
  • Bleeding - Steroids, IVIG, Hospital
138
Q

Thrombocytopenia causes

A

Reduced production

  • EXCLUDE AML + Myeloblastic anaemia!!!
  • BM failure

Destruction

  • AITP
  • Drugs e.g. heparin, DIC, TTP, HUS
139
Q

Haemophilia diagnosis

Severity

Treatment

A

X-linked recessive. Deep bleeding

A more common.
High aPTT, normal PT, low VIIIa or IXa
Bleeding time normal

Severity depends on factor level

  • Sev: <1%
  • Mod: 1-5%
  • Mild: 5-25%

A Rx: Desmopressin, FVIII concentrates
B Rx: FIX concentrates

140
Q

vWF diagnosis

A

High aPTT, normal PT, low FVIII, low vWF
Increased bleeding time (normal TT)

Autosomal dominant

141
Q

DIC diagnosis

Causes

A

High PT, high aPTT, high TT, low platelets, low fibrinogen, high D-dimer

Malignancy, Sepsis, Toxins, Trauma

142
Q

Liver clotting factors synthesis

Liver disease picture

A

Fibinogen
2, 7, 9, 10 + 5, 11

Low synthesis of above factors, less vit K absorption, abnormalities of platelet function

High PT, high aPTT, norm or high TT
AST high

143
Q

Vit K deficiency

A

high aPTT, high PT, rest norm

Warfarin, Antibiotics, malabsorption, biliary obstruction

IV vit K or FFP in acute haemorrhage

144
Q

Managing high INR in warfarin patients

A

therapeutic - 5:
- low/omit next dose and resume when normal

5-9, no bleeding

  • low/omit next dose and resume when normal
  • Omit dose and give vit K

> 9

  • omit dose and vit K 3-5mg, repeat if need
  • resume therapy at lower dose when INR normal

> 20; serious bleed

  • OMIT
  • Vit K 10mg slow IV infusion
  • FFP or PCC
  • Repeat vit K every 12 hrs as needed

NB: Prothrombin complex concentrate is for emergency reversal of warfarin in either

  • severe bleeding or
  • head injury with suspected intracerebral haemorrhage
145
Q

Target INR for warfarin patients

A
  1. 5
    - Everything else aka 1st episode DTV/PE, AF, cardioversion
  2. 5
    - Recurrent DVT/PE
    - Mechanical prosthetic valve
    - Antiphospholipid syndrome
146
Q

Cyclin D1 over expression

A

Mantle cell lymphoma

Pre-greminal centre cell. Mantle zone expands and then spreads thoughout node.

11;14
Aberrant CD5 and Cyclin D1 expression = dx
Low grade (slowly progressing)

Median survival 3-5yrs

147
Q
  • ALk-1 protein staining
  • 2;5
  • Sheets of anaplastic (nuclei wide), large lymphocytes
A

Anaplastic T cell lymphoma

Children/adults. Lymphadenopathy.
Aggressive
Alk-1 = better prognosis

148
Q

ABVD therapy for what?

Side effects

A

Hodgkin lymphoma

Chemo - preserves fertility. 2-6 cycles
Adriamycin (se cardiomyopathy)
Bleomycin (se pulmonary fibrosis)
Vinblastine
DTIC

+/-

Radiotherapy: field only
(risk of breast Ca after 25y, Leukaemia 3% after 10yrs, lung/skin cancer)

149
Q

Obstetric haematology

A

Macrocytic anaemia, thrombocytopenia, neutrophilia

Pro coagulant state, hypofibrinolytic

150
Q

Platelets >600 x 10^9

Thrombosis/bleeding, headaches

A

ET

Mutations in JAK2, calreticulin and MPL

Rx: Aspirin
Hydroxycarbamide
Anagrelide (not commonly)

151
Q

Leukoerythroblastic picture
JAK2/Calreticulin +ve

Management

A

PMF

Supportive
Hydroxycarbamide (try but can worsen anaemia)
Ruxolotinib (JAK2 inhibitor)
Allogenic SCT

152
Q

Massive leucocytosis 50-200
Neutrophils and myelocytes
Basophils

Hepatosplenomegaly

A

CML
9;22

Chronic phase –> Advanced phase –>Blast crisis

Path (6 decks)

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