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haem Flashcards

1
Q

What might you see on a blood film in these conditions: Abetalipoproteinaemia, liver disease, hypospenism. Histologist reports RBCs showing spicules of different sizes, shapes and distribution.

A

acanthocytes

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2
Q

in what conditions might you see basophilic stippling?

A

small dots at the periphery are seen due to accelerated erythropoiesis or defective Hb synthesis

seen in

lead poisoning

megaloblastic anaemia

myelodysplasia

liver disease

haemoglobinapthy e.g. thalassaemia

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3
Q

When might you see Burr Cells/ Echinocytes?

A

PUGS

Pyruvate Kinase Deficiency

Uraemia

GI bleed

Stomach carcinoma

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4
Q

Heinz bodies are assoc with?

A

***G6PD deficiency

glucose 6 phosphate dehydrogenase

+

chronic liver disease

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5
Q

Howell-Jolly bodies assoc with?

A

Post splenectomy/ Hyposplenism

e.g in sickle cell disease, coeliac disease, congenital, UC/ Crohns, myeloproliferative disease, amyloid

megaloblastic anaemia,

hereditary spheroctosis

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6
Q

Which of these anomalies would you not see on a blood film of a patient with megaloblastic anaemia?

a) basophilic stippling
b) target cells- codocytes
c) howell-jolly bodies
d) hypersegmented polymorphs (right shift)

A

codocytes

these are cells with bulls eye appearance in central pallor. and are seen in iron deficiency anaemia rather than megaloblastic anaemia

all other features may be seen on blood film

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7
Q

pelger huet cells associated with?

A

congenital (lamin B receptor mutation)

Acquired (called Pseudo pelger huet cells):

myelodysplastic syndromes

AML

CML

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8
Q

What is the definition of anaemia in males and females?

A

males: <13.5g/dL (<135g/L)
females: <11.5 g/dL (<115g/L)

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9
Q

Signs and symptoms of anaemia?

A

symptoms:

lethargy, SOB, faintness, palpitations, headaches, tinnitus, anorexia

Signs:

pallor (in severe anaemia), tachycardia, flow murmurs

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10
Q

causes of microcytic anaemia

A

Iron deficiency Anaemia

Anaemia of chronic disease

Thalassaemia

sideroblastic anaemia

Lead poisoning

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11
Q

Causes of normocytic anaemia

A

Acute blood loss

Anaemia of chronic disease

Pregnancy

Haemolysis

Renal failure

Bone marrow failure

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12
Q

what is sideroblastic anaemia?

A

a form of anaemia in which BM produces ringed sideroblasts rather than normal erythrocytes.

in sideroblastic anaemia, the body has iron available but cannot incorporate it into Hb

-> iron buildup in organs such as liver, heart, spleen, kidney can lead to organ failure/ damage

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13
Q

what ferritin/ Fe/ TIBC/ Transferrin results would you see in a patient with sideroblastic anaemia?

A

High ferritin

High Fe

High transferrin saturation

Normal/ Low TIBC

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14
Q

causes of macrocytic anaemia

A

FATRBC

Folate deficiency

Antifolates e.g. phenytoin, methotrexate

Thyroid- hypothyroidism

Reticulocytosis - release of immature cells e.g. w haemolysis

B12 deficiency

Cirrhosis (alcohol excess/ liver disease)

myelodysplastic syndromes

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15
Q

a microcytic, hypochromic anaemia with anisocytosis and polikilocytosis + pencil cells

on examination, you find koilonychia, atrophic glossitis, angular cheilosis, post-cricoid webs, brittle hair and nails

what is it?

A

iron deficiency anaemia

causes: always bleeding until proven otherwise

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16
Q

what Iron/ Ferritin/ TIBC/ Transferrin levels will you see in iron deficiency anaemia?

A

low Fe

Low ferritin

High TIBC

High Transferrin

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17
Q

causes of iron deficiency anaemia

A

Blood loss:

GI loss

menorrhagia

peptic ulcer/ gastritis

meckels diverticulum

polyps/ colorectal Ca

Increased utilisation:

Pregnancy/ lactation

children/ infants

decreased intake:

suboptimal diet

decreased absorption:

coeliac disease

post gastric surgery

intravascular haemolysis:

paroxysmal nocturnal haemoglobuniria

MAHA

-> chronic loss of Hb in urine

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18
Q

NICE guidelines for IDA with no obvious cause?

A

OGD + colonoscopy

urine dip

coeliac investigations

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19
Q

IDA mx?

A

treat the cause

oral Iron

if severe, IV iron

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20
Q

what are some side effects of oral iron?

A

black stools

nausea

abdo discomfort

diarrhoea/ constipation

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21
Q

IL6, cytokine- driven inhibition of red cell production

ferritin is high.

Fe sequestered in macropahges to deprive invading bacteria of Fe

A

anaemia of chronic disease

e.g.

with chronic infection (TB)

vasculitis (chronic inflammation)

rheumatoid arthritis

malignancy

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22
Q

Ringed sideroblasts seen in bone marrow:

erythroid precursors with iron deposited in mitochondria in a ring around the nucleus

On peripheral blood smear: basophilic stippling (cytoplasmic granules of RNA precipitates) and Pappenheimer bodies (cytoplasmic granules of iron)

what condition?

A

sideroblastic anaemia

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23
Q

Causes of Sideroblastic anaemia

A

myelodysplastic syndrome

e.g. refractory anaemia with ringed sideroblasts

excessive alcohol use (most common cause- and reversible!)

B6 pyridoxine deficiency (e.g. isoniazid tx)

lead posioning

copper deficiency

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24
Q

Tx of sideroblastic anaemia

A

if severe, may need transfusion

treat the cause

and Pyridoxine (Vit B6)

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25
Q

what are the fe/ ferritin/ TIBC levels in haemochromatosis?

A

high Fe

high Ferritin

Low/ N TIBC

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26
Q

how does ferritin change with inflammation/ infection/ malignancy

A

ferritin is an acute phase protein and increases with inflammation/ infection/ malignancy

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27
Q

what are the causes of megaloblastic anaemia?

A

Vit B12/ folate deficiency

or cytotoxic drugs e.g. antifolates

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28
Q

most common cause of macrocytosis without anaemia?

A

alcohol

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29
Q

what are some blood film findings with megaloblastic anaemia?

A

hypersegmented neutrophils

increased MCV (macrocytosis)

anaemia

thrombocytopenia

Howell-Jolly bodies

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30
Q

Causes of Vit B12 deficiency

A

normal sources of B12: meat and dairy products

Dietary: vegans

Malabsorption:

stomach (pernicious anaemia/ post gastrectomy)

terminal ileum (crohns/ tropical sprue/ ileal resection)

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31
Q

anaemia

with glossitis, angular cheilosis

+ dementia, depression, psychosis

+ peripheral neuropathy, parasthesiae

what is the condition?

A

b12 deficiency anaemia

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32
Q

loss of vibration and proprioception in hands, absent ankle reflex

in vit B12 deficiency

what is this?

A

peripheral neuropathy

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33
Q

what may develop in a patient with vit b12 deficiency, where weakness, numbness and tingling in peripheries progressively worsens

A

subacute combined degeneration of the spinal cord

prolonged deficiency leads to irreversible nervous system damage.

patchy losses of myelin in the dorsal and lateral columns.

patients present with weakness of legs, arms, trunk, tingling and numbess that progressively worsens.

vision changes and change of mental state may be present.

bilateral spastic paresis may develop

Babinskis may be +ve

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34
Q

treatment of vit b12 deficiency?

A

replace the Vit B12

IM Hydroxocobalamin

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35
Q

investigation for pernicious anaemia?

A

anti-parietal cell antibodies (90%)

anti-IF antibodies (50%)

Schilling test (outdated)

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36
Q

causes of folate deficiency

A

source of folate: leafy green vegetables, nuts, liver

causes:

poor diet

increased demand: pregnancy, increased cell turnover (malignancy, haemolysis etc)

malabsorption: coeliac, tropical sprue
drugs: alcohol, antiepileptics (phenytoin), methotrexate, trimethoprim

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37
Q

folate deficiency treatment?

A

oral folic acid

only give if cause of anaemia is known, as folic acid may exacerbate neuropathy of B12 deficiency

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38
Q

normal life span of RBCs

A

120 days

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39
Q

features of all haemolytic anaemias

A

increased unconjugated Bilirubin

increased reticulocytes (increased MCV, polychromatosis)

increased urobilinogen

increased LDH

may have pigmented gallstones

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40
Q

features of extravascular haemolytic anaemia

A

removal by reticuloendothelial system

  • splenomegaly
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41
Q

features of intravascular haemolysis

A

increased free plasma Hb

decreased Haptoglobin (binds free Hb)

haemoglobuniura (dark red urine)

methaemalbuminaemia (haem + albumin in blood)

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42
Q

causes of inherited haemolytic anaemia

A

membrane defect:

hereditary spherocytosis

hereditary elliptocytosis

enzyme defect:

G6PD deficiency

Pyruvate Kinase deficiency

Haemoglobinopathies:

Sickle Cell disease

thalassaemias

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43
Q

coinheritance of what condition further increases risk of cholelithiasis in chronic haemolytic anaemia?

A

Gilberts Syndrome

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44
Q

Causes of acquired haemolytic anaemia

A

Immune:

autoimmune haemolytic anaemia (warm/ cold)

alloimmune- haemolytic transfusion reactions

non-immune:

Microangiopathic haemolytic anaemia

Mechanical e.g. metal valves, trauma

Paroxysmal nocturnal haemoglobinuria

infections (e.g Malaria), drugs

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45
Q

deficiency of what enzyme in Gilbert’s syndrome?

A

UDP-glucuronosyl transferase 1

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46
Q

hereditary spherocytosis

  • what inheritance pattern
  • what membrane protein is defective/ deficient
  • diagnostic tests
A

Autosomal dominant (25% are auto recessive or de novo)

Spectrin (most common) or ankyrin or protein 4.2/ band 3 deficiency/defect

diagnosis via osmotic fragility test (increased lysis in hypotonic solutions), -ve coombs test, spherocytes on blood film, eosin-5-maleimide (decreased binding)

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47
Q

pallor, jaundice, splenomegaly, pigmenturia

bloods show increased Br, increased LDH and decreased/absent haptoglobins

Blood film shows spherocytes

Osmotic fragility positive and decreased binding of dye eosin-5-maleimide

A

Hereditary spherocytosis

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48
Q

what complications may occur with hereditary spherocytosis?

increased susceptibility to?

A

aplastic anaemia with parvovirus B19 infection

develop gallstones due to increased uric acid production

-> calcium bilirubinate gallstones

increased iron overload/ osteoporosis

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49
Q

treatment of hereditary spherocytosis

A

splenectomy - definitive treatment

folic acid due to increased folate demand

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50
Q

hereditary elliptocytosis

  • inheritance pattern
  • mutation in which protein
A

almost all are autosomal dominant

spectrin mutations most common

severity ranges from asymptomatic to hydrops fetalis

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51
Q

a severe form of elliptocytosis that is autosomal recessive

abnormal sensitivity of red blood cells to heat

spectrin deficiency

A

hereditary pyropoikilocytosis

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52
Q

a hereditary haemolytic anaemia where RBC is oval-shaped.

defect lies in band 3 protein.

greater robustness of cells to osmotic pressures/ temp changes

resistance to infected by plasmodium falcuparum

common in malaysia and papau new guinea

A

southeast asian ovalocytosis

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53
Q

pyruvate kinase deficiency

  • most common inheritance pattern
  • what pathway does it affect
A

autosomal recessive

pyruvate kinase converts phosphoenol pyruvate + ADP -> ATP + pyruvate

so in pyruvate kinase deficiency, low ATP and pyruvate

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54
Q

may only present at times of stress e.g. pregnancy and infections

symptoms from birth, limited to or most severe during childhood.

autosomal recessive condition

mild-severe haemolytic anaemia

severe neonatal jaundice

splenomegaly

Blood film showing echinocytes

A

Pyruvate Kinase deficiency

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55
Q

what shifts the oxygen dissociation curve to the right?

reduced affinity of Hb to O2

A

pyruvate kinase deficiency (causes increased 2-3 DPG aka 2-3 BPG)

increased temp

low pH

high CO2

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56
Q

G6PD deficiency

  • inheritance pattern
  • what pathway is affected
A

X linked

commonest RBC enzyme defect

G6PD catalyzes 1st step in pentose phosphate pathway

  • generates NADPH required to maintain intracellular glutathione.

glutathione protects RBCs from oxidant damage. low glutathione in G6PD deficiency -> susceptibility to oxidant damage

e.g drugs, fava beans, acute infections, acute stressors

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57
Q

rapid anaemia and jaundice, with blood film showing Heinz bodies and bite cells

precipitated by drugs like primaquine, sulfonamides, nitrofurantoin, aspirin, broad beans/ favism, acute infections, moth balls

A

G6PD deficiency

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58
Q

treatment of G6PD deficiency

A

avoid precipitants

if severe- transfuse

genetic screening

folic acid supplementation

immunisations against blood borne viruses (Hep A/B)

cholecystectomy for symptomatic gallstones

splenectomy if indicated

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59
Q

does G6PD deficiency cause intravascular or extravascular deficiency?

A

intravascular haemolysis

  • causes dark urine
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60
Q

what are some oxidants causing acute episodes of G6PD deficiency?

A

fava beans

antimalarials e.g. primaquine

antibiotics e.g. sulfonamide, nitrofurantoin

infections

moth balls

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61
Q

what would be see on blood film in G6PD deficiency

A

Heinz bodies (inclusions within RBC composed of denatured Hb)

and

Bite cells (caused by splenic removal of denatured Hb)

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62
Q

diagnosis of G6PD deficiency

A

G6PD enzyme assay 2-3 months after a crisis

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63
Q

Sickle Cell Disease

  • pattern of inheritance
  • what is the mutation
A

autosomal recessive

single base mutation GAG-> GTG

Glu -> Valine at codon 6 of beta chain

HbA -> HbS

HbSS: sickle cell anaemia

HbAS - sickle cell trait

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64
Q
A
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65
Q

when does sickle cell anaemia manifest? (at what age)

A

3-6 months

coinciding with decreasing fetal Hb

HbF

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66
Q

symptoms of a child with sickle cell anaemia

A

Hand-foot syndrome:

dactylitis

painful crises

stroke

acute chest syndrome

***Splenic sequestration- can lead to severe anaemia, shock and death

very susceptible to bacteraemia- due to immature immune system

parvovirus B19 may lead to aplastic crisis

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67
Q

what is splenic sequestration and when is it most likely to happen?

A

splenic sequestration is the acute pooling of a large proportion of circulating RBCs in the spleen

spleen enlarges acutely

Hb falls acutely and death can occur

doesnt happen in older children because recurrent infarction has left the spleen small and fibrotic

occurs most commonly in children 1-3 yrs old

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68
Q

sickle cell anaemia management in a child

A

analgesia for painful crises

**Folic acid - hyperplastic erythropoiesis, growth sports

Penicillin V + Pneumovax + HiB vaccine

Carotid doppler monitoring in early childhood with prophylactic exchange transfusion if turbulent carotid flow

Hydroxycarbamide to prevent sickling crises

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69
Q

what complication of sickle cell anaemis is more common in adults than in children:

  1. hand foot syndrome
  2. hyposplenism
  3. red cell aplasia
  4. splenic sequestration
  5. stroke
A

hyposplenism

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70
Q

siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count- likely diagnosis?

  1. splenic sequestration
  2. Parvovirus B19 infection
  3. Folic acid deficiency
  4. Haemolytic crisis
  5. Vit B12 deficiency
A

Parvovirus B19

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71
Q

A 6 year old Afro Caribbean boy presents with chest and abdo pain

Hb is 63g/L, MCV 85 fl and blood film shows sickle cells

likely diagnosis?

  1. sickle cell trait
  2. sickle cell anaemia
  3. sickle cell/ beta thalassaemia
A

sickle cell anaemia

in sickle cell trait- usually asymptomatic except under stress

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72
Q

complications of sickle cell anaemia that usually presents in adults

A

hyposplenism - small fibrotic spleen

or no spleen if post splenectomy

chronic kidney disease

retinopathy

pulmonary HTN

mesenteric ischaemia

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73
Q

complications of sickle cell anaemia in teenage years

A

impaired growth

gallstones

priapism - persistent painful erection

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74
Q

Beta Thalassaemia

  • inheritance pattern
  • mutation in what gene
A

Autosomal recessive

mutation in the HBB gene on chr 11

-> decreased beta chain synthesis and excess alpha chains

Increased HbA2 and HbF seen

B thal major: Skull bossing, maxillary hypertrophy, hairs on end skull Xray

Hepatosplenomegaly

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75
Q

Skull bossing, maxillary hypertrophy, hairs on end skull Xray

Microcytic anaemia

increased % of HbA2

A

thalassaemia major

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76
Q

how does b thalassaemia minor present

A

asymptomatic carrier

mild anaemia

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77
Q

when and how does b thalassaemia major present?

A

at 3-6 months as HbF falls

severe anaemia

FTT
hepatosplenomegaly due to extramedullary erythropoiesis

bony deformity

heart failure

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78
Q

Diagnosis of B thalassaemia

A

Guthrie card test

Hb electrophoresis

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79
Q

Treatment of beta thalassaemia

A

Blood transfusions + Desferrioxamine

Folic acid

Bone marrow transplant may offer possibility of cure in young ppl w HLA-matched donor

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80
Q

what is this

A

hereditary spherocytosis

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81
Q

what is this

A

hereditary elliptocytosis

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82
Q

what is this

A

sickle cell anaemia

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83
Q

what is shown on this blood film

likely diagnosis?

A

Bite cells

G6PD deficiency

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84
Q

what is shown in this blood film

likely diagnosis?

A

G6PD deficiency

Heinz bodies

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85
Q

what are the two most important acquired haemolytic anaemias in children?

A

autoimmune haemolytic anaemia

Haemolytic uraemic syndrome

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86
Q

prognosis of

alpha thalassaemia trait (2)

HbH disease (3 alpha chains deleted)

Alpha thal major (4 deleted)

A

alpha thal trait -> asymptomatic, mild anaemia

HbH disease -> moderate anaemia, hepatosplenomegaly.

microcytic hypochromic anaemia w target cells and Heinz bodies

Alpha major: incompatible with life. hydrops fetalis

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87
Q

secondary causes of a true polycythaemia

A

Raised EPO

due to

Renal Cell Carcinoma

HCC
Bronchial Ca

High Altitude

Cyanotic Heart disease

Hypoxic Lung disease

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88
Q

+ve direct antiglobulin test (coombs)

increased Br, increased LDH

blood film shows spherocytes

assoc with CLL, SLE, lymphoma, drugs like methyldopa/ penicillin

what condition?

A

warm AIHA

  • autoantibodies IgG binds to RBCs at 37 degrees
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89
Q

what type of autoantibody in cold AIHA?

A

IgM

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90
Q

what type of autoantibody in warm AIHA?

A

IgG

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91
Q

management of warm AIHA

A

steroids

splenectomy if indicated

immunosuppression

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92
Q

positive coombs test

Raynaud’s phenomenon

assoc w lymphoma, EBV, mycoplasma infections

what condition?

A

Cold AIHA

IgM

binds to RBC <37 degrees

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93
Q

Tx of cold AIHA

A

treat underlying condition

avoid the cold

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94
Q

what antibodies are associated with paroxysmal cold haemoglobinuria?

A

Donath-Landsteiner antibodies

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95
Q

Haemoglobinuria (dark red/ brown urine) after exposure to cold temperatures

+ often after infection e.g measles, syphilis, VZV

A

Paroxysmal cold haemoglobinuria

can occur when blood passes through cold extremities in cold weather. when blood returns to the warmer central circulation, the RBCs are lysed with complement, causing intravascular haemolysis

-> haemoglobinuria and anaemia

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96
Q

Paroxysmal cold haemoglobinuria

  • what is the autoantibody involved
  • what infections may typically trigger this?
A

Donath-Landsteiner antibodies

aka polyclonal IgG anti-P autoantibody

assoc w syphilis, post viral infection (measles, mumps, influenza etc), mycoplasma/ h influenzae

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97
Q

the only acquired intrinsic defect in the cell membrane leading to haemolytic anaemia

A

paroxysmal noctural haemoglobinuria

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98
Q

red urine most pronounced in the morning (when urine is more concentrated)

+ tiredness, SOB, palpitations

Bloods show low Hb, raised LDH, raised Br, decreased Haptoglobin, raised reticulocytes

Hams test +ve

A

paroxysmal nocturnal haemoglobinuria

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99
Q

Paroxysmal nocturnal haemoglobinuria

  • where is the defect
  • what happens
A

acquired defect of surface protein CD55 on the RBC

  • > complement cascade attacks the RBCs
  • > intravascular haemolysis
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100
Q

Diagnostic tests for Paroxysmal nocturnal haemoglobinuria

A

GOLD standard is flow cytometry for CD55 and CD59 on white and red blood cells

Hams test: RBCs placed in mild acid, a positive result (increased RBC fragility) is suggestive (low sensitivity and specificity)

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101
Q

complications / common symptoms of Paroxysmal nocturnal haemoglobinuria

A

**increased risk of thrombosis

esp in hepatic vein -> budd-chiari syndrome

portal vein -> portal vein thrombosis

mesenteric ischaemia

cerebral venous thrombosis

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102
Q

tx for Paroxysmal Nocturnal Haemoglobinuria?

A

Acute attacks: Iron/ folate supplements if needed

thromboprophylaxis with warfarin

eculizumab - a monoclonal antibody that prevents complement from binding RBCs

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103
Q

pentad of TTP

A

MAHA

low Pl

Fever

Neuro+

Nephro impairment

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104
Q

what is going on in TTP that causes the features of MAHA, low Pl, fever, and neuro and kidney impairment?

A

TTP is a rare disorder of the blood coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body

  • > autoimmune condition: autoantibody inhibits enzyme that cleaves vWF. this leads to excessive vWF and pl adhesion/activation
  • > consumption of pl leads to low Pl
  • > these thrombi can cause damage to many organs including the kidneys, heart, brain, CNS

(fatality rate used to be 95% before plasma exchange!!!)

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105
Q

Tx of TTP

A

plasmapheresis - exchange transfusion of patients blood plasma

+

corticosteroids

+ rituximab

+ maybe additional immunosuppressants e.g. vincristine, cyclophosphamide, splenectomy

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106
Q

what is the triad of haemolytic uraemic syndrome?

A

Haemolytic anaemia

Acute kidney failure (uraemia)

thrombocytopenia

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107
Q

Haemolytic Uraemic syndrome

  • most common cause
  • most common age group
A

E coli O157:H7 which causes a preceding episode of infectious bloody diarrhoea

(can also be Shigella/ campylobacter)

HUS is a medical emergency!!!

most common cause of acquired acute renal failure in childhood.

30% may suffer residual renal injury

the primary target is the vascular endothelial cell.

Shiga-toxin-activated endothelial cells then become thrombogenic -> MAHA + low Pl

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108
Q

what is the primary target in Haemolytic Uraemic Syndrome that underlies the symptoms?

A

renal vascular endothelial cells

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109
Q

Microangiopathic Haemolytic Anaemia:

how are RBCs destroyed?

what will investigations show?

what are some common causes?

A

endothelial layer of small vessels damaged -> fibrin deposition and pl aggregation -> RBCs forced through fibrin mesh causing mechanical RBC destruction/ fragmentation

Blood film- shistocytes

Causes:

HUS

DIC

TTP

Malignancy

HELLP syndrome

SLE (due to Immune complexes aggregating w platelets, forming intravascular thrombi)

Eclampsia

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110
Q

what factors make up the intrinsic pathway?

A

12

11

9

(8) - fVIIIa that converts X->Xa alongside IXa

10

* rmb the next factor starts with the last letter of the previous factor!

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111
Q

what factors are involved in the extrinsic pathway?

A

Tissue factor

7

TF + fVIIa converts X -> Xa

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112
Q

what factors / components make up the final common pathway of the clotting cascade?

A

Xa (from intrinsic/ extrinsic pathway) + fVa

convert prothrombin -> thrombin (IIa)

IIa converts Fibrinogen -> Fibrin

XIIIa converts FIbrin -> fibrin clot

Plasmin degrades fibrin clot into fibrin degradatin products

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113
Q

Plasmin

What is it and what does it do?

How is it formed?

What inhibits plasmin?

A

Plasmin is a serine protease that acts to dissolve fibrin blood clots

Tissue plasminogen activators convert Plasminogen -> plasmin

Plasmin is inhibited by alpha 2 anti plasmin and alpha 2 macroglobulin

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114
Q

what is the first step of forming the haemostatic plug?

A

platelet adhesion

either by binding directly to exposed collagen via gpIa

or

to vWF via gpIb

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115
Q

how do you monitor warfarin therapy?

which pathway does it look at?

A

Prothrombin Time

  • Extrinsic Pathway
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116
Q

what is the next step in forming a haemostatic plug after platelet adhesion?

A

Platelet aggregation

expression of gpIIb/IIIa on pl surface

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117
Q

what is the step after platelet aggregation in the process of forming a haemostatic plug?

A

Fibrinogen binding

then forming a stable fibrin clot through a thrombin (fIIa) burst

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118
Q

Thromboxane A2 / Prostacyclin PgI2

which one increases and which one inhibits platelet aggregation?

A

Thromboxane A2 - prothrombotic

Prostacyclin PgI2- inhibits platelet aggregation

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119
Q

what are protein C and protein S?

A

Protein C and protein S (cofactor) proteolytically inactivate fVa and fVIIIa

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120
Q

what does Tissue Factor Pathway Inhibitor do?

A

antithrombotic

TFPI can reversibly inhibit fXa

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121
Q

what does Antithrombin III do

what drug influences this?

A

Antithrombin III inactivates thrombin, fXa and fIXa

Heparin increases Antithrombin III activity

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122
Q

how to monitor final common pathway?

A

thrombin time

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123
Q

how to assess intrinsic pathway?

when do you use it?

A

APTT

to monitor unfractionated Heparin therapy

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124
Q

auto dominant genetic condition leading to abnormal blood vessel formation in skin, mucous membranes and in lung, liver, brain.

telangiectasia - may occur on skin, mucosal linings of nose and GI tract

nosebleeds extremely common

arteriovenous malformations in lungs (haemoptysis/ haemothorax), liver, brain (haemorrhage)

A

Osler-Weber-Rendu

Aka

Hereditary Haemorrhagic telangiectasia

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125
Q

presentation of coagulation disorders vs platelet disorders/ vascular defects

A

Platelet disoders/ vascular defects

  • superficial bleeding into skin, mucosal membranes
  • bleeding immediate after injury/ surgery
  • petechiae
  • small, superficial bruises

vs

Coagulation disorders

  • bleeding into deep tissue, muscles, joints
  • delayed, but often severe bleeding after injury
  • bleeding often prolonged
  • large deep bruises (ecchymoses)
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126
Q

low Platelet count, purpuric rash, petechiae, blood blisters in mouth

increased tendency to bleed->

bleeding from nostrils/ gums + menorrhagia

acute, usually following an infection, usually spontaneously remits within 2 months

A

autoimmune thrombocytopenic purpura

anti pl antibodies (IgG) against gpIIb/IIIa

treatment with careful observation in mild cases.

if v low pl counts/ significant bleeding: tx w corticosteroids, IVIG, imunosuppressive drugs or even platelet transfusions.

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127
Q

Tx of low Platelet count in autoimmune thrombocytopenic purpura

  • if 20-50000 platelet count + not bleeding?
  • if 20-50000 platelet count + bleeding?
  • if <20000, and not bleeding?
  • if <20000 + bleeding
A

20-50000 platelet count + not bleeding: No tx

20-50000 platelet count + bleeding: steroids, IVIG

  • if <20000, and not bleeding: steroids
  • if <20000 + bleeding: steroids, IVIG, hospitalization
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128
Q

Acute ITP vs Chronic ITP

  • usual age
  • preceding infection present?
  • onset of symptoms
  • platelet count at presentation
  • duration
  • spontaneous remission?
A

Acute vs Chronic ITP

  • children (2-6 yrs) vs Adults
  • chronic ITP usually affects women
  • preceding infection common in acute ITP
  • abrupt onset in acute ITP but onset can be abrupt- indolent with chronic ITP
  • platelets < 20000 at presentation w acute/ vs <50000 w chronic ITP
  • acute ITP usually 2-6 weeks and spontaneously remits whereas chronic is long term and assoc w other autoimmune diseases, and is unlikely to remit.
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129
Q

features of extramedullary haemopoiesis

A

hepatosplenomegaly

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130
Q

consequences of haemolytic anaemia

A
  • Anaemia(+/-) as bone marrow may compensate
  • Erythroid hyperplasia with increased rate of red cell production and circulating reticulocytes
  • Increased folate demand
  • Susceptibility to effect of parvovirus B19 - can cause aplastic anaemia in patients with haemolytic anaemia who already have RBC with very low lifespan.
  • Propensity to gallstones(cholelithiasis) - due to increased generation of bilirubin
  • Increased risk of: iron overload (irrespective of transfusion due to increased intestinal absorption), osteoporosis
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131
Q

why does LDH increase during haemolytic anaemia?

A

LDH is a glycolytic enzyme inside RBCs- and is thus, a sensitive marker of intravascular heamolysis

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132
Q

whats the difference where the protein defect is between hereditary spherocytosis and hereditary elliptocytosis?

A

hereditary spherocytosis: vertical interaction

hereditary elliptocytosis: horizontal interaction

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133
Q

what is Pyrmidine 5 nucleotidase deficiency?

what is seen on blood film?

A

Pyrimidine 5 nucleotidase removes pyrimidine - which is toxic to RBCs

Blood film will show basophilic stippling

seen in lead poisoning as lead is a significant inhibitor of the enzyme pyrimide 5 nucleotidase.

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134
Q

when should you do a splenectomy in a child?

A

transfusion dependent

signs of growth delay

physical limitation Hb<8g/dL

hypersplenism

do not perform before 3 years of age

ideally perform before 10 years to maximise prepubertal growth

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135
Q

what malignancies may result in iron deficiency?

A

GI cancers- gastric, colon, rectal

Urinary tract ca- Renal cell carcinoma, Bladder Ca

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136
Q

Leucoerythroblastic anaemia

  • what is it
  • what features on blood film?
A

leucoerythroblastic anaemia is any anaemic condition resulting from space occupying lesions in the bone marrow e.g. bone mets

the circulating blood contains immature cells of the granulocytic series and nucleated RBCs

Blood film shows teardrop RBCs, aniso/ poikilocytosis, nucleated RBCs, immature myeloid cells

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137
Q

what are some causes of leucoerythroblastic anaemia?

A

marrow infiltrative disorders include:

myelomas

malignancy (any, breast, prostate, lung, leukaemia, lymphoma)

myelofibrosis (massive splenomegaly, dry tap on BM aspirate)

severe infection: TB, severe fungal infection

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138
Q

what are some causes of neutrophilia?

A

corticosteroids may transiently cause rise in neutrophil blood levels

underlying neoplasia

tissue inflammation e.g. colitis, pancreatitis

myeloproliferative/ leukaemic disorders

localised and systemic infections: actue bacterial, fungal, certain viral infections

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139
Q

how to differentiate between reactive/ malignant neutrophilia on blood film

A

reactive neutrophilia: presence bands, toxic granulation and signs of infection/ inflammation

in malignancy:

neutropenia + myeloblasts (AML)

neutrophilia + basophilia + immature cells suggest CML

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140
Q

Eosinophilia: what are some causes of reactive eosinophilia

A

o Parasitic infestation

o allergic diseases e.g. asthma, rheumatoid, polyarteritis nodosa, pulmonary eosinophilia.

o Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)

o Drugs (reaction erythema mutiforme)

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141
Q

what malignant condition sees a monocytosis?

A

chronic myelomonocytic leukaemia

infectious causes that cause a monocytosis include TB and brucella

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142
Q

what are some causes of basophilia?

A

pox viruses

CML

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143
Q

Smear cells seen in?

A

CLL

(most often assoc w abnormally fragile lymphocytes)

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144
Q

Bone marrow infiltration causes what changes to blood film?

A

leucoerythroblastic picture

immature myeloid cells

nucleated RBCs

teardrop RBCs

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145
Q

Lymphoma

  • what is it?
  • where may it be found?
A

Lymphomas are neoplastic tumours of lymphoid cells.

usually found in lymph nodes, bone marrow and or blood (via the lymphatic system)

and in lymphoid organs such as the spleen, MALT

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146
Q

why are lymphocytes particularly at risk of neoplasm/ malignancy?

A

rapid cell proliferation in immune response risks DNA replication error

dependent on apoptosis (in the germinal centre) -> apoptosis may get switched off in the germinal centre, there may be acquire DNA mutations in the pro apoptotic genes

DNA molecules are cut and rejoined and undergo deliberate point mutation to generate immunoglobulin and T cell receptor diversity -> potential for recombination errors and new point mutations

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147
Q

Gastric MALToma

what causes the chronic antigenic stimulation that may lead to gastric MALToma

A

Helicobacter pylori

-> marginal zone non-hodgkins lymphoma of the stomach

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148
Q

Known risk factors of lymphoma:

A

constant antigenic stimulation (will increase risk of DNA replication error)

infection (direct viral infection of lymphocytes e.g. EBV)

loss of T cell function (e.g. HIV)

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149
Q

what causes constant antigenic stimulation that may result in marginal zone lymphoma of the thyroid gland?

A

Hashimoto’s Disease

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150
Q

What causes chronic antigenic stimulation that may predispose to developing parotid lymphoma?

A

Sjogren’s syndrome

-> marginal zone non-hodgkins lymphoma of the parotids

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151
Q

a lymphoma caused by HTLV-1 infection

HTLV-1 infects T cells

common in the Carribean and Japanese population

what lymphoma is associated?

A

Adult T cell leukaemia/ lymphoma

*nuclei of ATL cells have characteristic cloverleaf appearance

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152
Q

what causes constant antigenic stimulation, predisposing the patient to small bowel T cell lymphoma?

A

Coeliac disease

-> enteropathy associated T-cell Non-Hodgkins Lymphoma (EATL)

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153
Q

what virus is associated with Adult T cell leukaemia/ lymphoma?

A

HTLV-1

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154
Q

HIV and EBV infection

  • how may this lead to lymphoma?
A

EBV infects B lymphocytes and causes proliferation of EBV antigen expressing B cells

Healthy carrier state dependent on T cells recognising EBV antigen expressing B cells

in HIV -> loss of normal T cells increases risk of B cell lymphoma!

*also seen in post transplant patients (post transplant lymphoproliferative disorder)

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155
Q

what is the most common type of lymphoma?

A

B cell Non Hodgkins lymphomas

(80%)

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156
Q

t(11;14)

A

Mantle Cell Lymphoma

rmb Mant11e

157
Q

t(2;5)

A

Anaplastic large cell lymphoma

158
Q

Of the common B cell non-hodgkin lymphomas,

which are high grade?

which are low grade?

A

High Grade:

V aggressive: Burkitt’s
Aggressive: Diffuse Large B cell, Mantle Cell

Low Grade:

Indolent-

Follicular, small lymphocytic/ CLL, marginal zone lymphoma, mantle zone lymphoma

159
Q

an indolent, mostly incurable lymphoma.

t(14;18) translocation

bcl-2 gene overexpression -> increased bcl-2 protein (prevents apoptosis in tumour cells)

Histopathology shows follicular pattern. Morphology shows centroblasts and centrocytes.

Blood smear may show buttock cells.

Stains positive for B cell marker CD10.

translocations at bcl6 could also be involved.

A

Follicular lymphoma

(35% of all non hodgkins lymphoma)

Tx: watch and wait

or if needed, rituximab- cyclophosphamide, vincristine, prednisolone

160
Q

Histopath shows small lymphocytes, naive or post germinal centre memory B cells, CD5+, CD23+ (abnormal markers)

Indolent, but can undergo richter transformation

A

Small lymphocytic leukaemia / CLL

161
Q

CLL vs SLL?

A

CLL and SLL are essentially the same disease process with slightly different presentations - CLL is primarily seen in the BM, SLL in the LNs

they are both lymphoproliferative diseases

that mainly affect the elderly (mean age 65-70)

162
Q

MALT (mucosal associated lymphoid tissue) lymphoma / Marginal zone NHL

  • what sites are normally affected?
  • treatment?
A

mainly at extranodal sites. e.g. gut, lung, spleen, thyroid, parotid

arise in response to chronic antigen stimulation

treatment involves removing the antigenic stimulation e.g. H pylori eradication

163
Q

what is the H pylori triple therapy for eradication?

A

omeprazole, clarithromycin and amoxicillin

164
Q

Male predominance, lymph nodes affected, GI tract or disseminated disease at presentation

t(11;14)

Cyclin D1 overexpression/ dysregulation

median survival rate 3-5 years

Histology may show angular nuclei

A

Mantle Cell lymphoma

an aggressive NHL

Tx involves Rituximab-CHOP

Auto-SCT for relapse

maintenance rituximab delays the time to next progression

165
Q

what is overexpressed in Mantle Cell lymphoma?

A

Cyclin D1

166
Q

Mandibular mass/ abdo mass in children/ young adults

EBV associated

histology shows germinal centre cell origin with starry sky appearance

t(8;14) - c-myc oncogene translocation can be detected using FISH stain

aggressive disease

A

Burkitts lymphoma

167
Q

what virus is most commonly associated with burkitt’s lymphoma?

A

EBV

168
Q

in Burkitt’s lymphoma,

what oncogene is overexpressed?

A

c-myc

169
Q

What immunodeficiency is associated with burkitts lymphoma?

A

HIV / post transplant patients

170
Q

richter’s transformation:

history of B cell CLL/ hairy cell laukaemia

Histology shows “sheets of large lymphoid cells”

A

Diffuse Large B Cell lymphoma (DLBCL)

(30-40% of NHL)

aggressive

tx: rituximab-CHOP (6-8 cycles)

Auto-SCT for relapse

aim of tx is curative

171
Q

affects middle aged/ elderly

*Large T cell lymphocytes

Aggressive

Often with associated reactive cell population esp eosinophils

Lymphadenopathy and extranodal sites

A

Peripheral T Cell lymphoma

172
Q

what lymphoma is associated with longstanding coeliac disease?

A

EATL

Enteropathy Associated T cell lymphoma

173
Q

what lymphoma is associated with mycosis fungoides?

A

Cutaneous T cell lymphoma

174
Q

Affects mainly children/ young adults

Histology shows large ‘epitheliod’ lymphocytes

t(2;5) and Alk-1 protein expression

Aggressive.

A

Anaplastic large cell lymphoma

175
Q

Hodgkins Lymphoma

  • how does it present
  • associated with which virus
  • affects which age groups
A

presents as asymmetrical painless lymphadenopathy.

most often single node and spreads contiguously to adjacent LNs

+/- obstructive/mass effect symptoms

B symptoms may be present: fever>38, night sweats, weight loss

pain in affected nodes after alcohol

assoc w EBV

bimodal age incidence - 20-30 and >60

176
Q

what is the most common subtype of hodgkins lymphoma?

A

nodular sclerosing

80%

good prognosis

peak incidence in young women

177
Q

Reed sternberg cell

binucleate/ owl eyed cell on a background of lymphocytes and reactive cells

LN/ BM biopsy - cells stain with CD15 and CD30

A

Hodgkins Lymphoma

178
Q

what is the form of non classical hodgkins lymphoma?

A

nodular lymphocyte predominant hodgkins lymphoma

*expresses CD20 instead of CD15/30

no association w EBV

** Reed sternberg cell variant with popcorn shaped nucleus

indolent but can transform to high grade B cell lymphoma unlike classical HL

179
Q

Staging of Hodgkins Lymphoma

A

· I; one group of nodes

· II; >1 group of nodes same side of the diaphragm

· III; nodes above and below the diaphragm

· IV; extra nodal spread (other organs)

· Suffix A if none of below, B if any of below

o Fever, night sweats

o Unexplained Weight loss >10% in 6 months

**RMB that spleen is considered a LN

180
Q

which of the subtypes of hodgkins lymphoma carry a good prognosis and which carry a poor prognosis?

A

good:

nodular sclerosing

mixed cellularity

lymphocyte rich

poor:

lymhocyte depleted

181
Q

treatment of Hodgkins Lymphoma

Chemotherapy

Radiotherapy

A

Chemotherapy:

ABVD: adriamycin, bleomycin, vinblastine, dacarbazine

2-4 cycles in stage 1/2, 6-8 in stage 3

given at 4 wkly intervals

prognosis excellant esp in the young. preserves fertility but can cause long term pulmonary fibrosis, cardiomyopathy

Radiotherapy:
HL is highly responsive to radiotx

usually given at the end of chemo to small area of diseased nodes

risk of collateral damage: BrCa, Leukaemia/ MDS, lung/skin Ca

182
Q

what are the chemotherapy drugs used in hodgkins lymphoma tx?

A

ABVD

Adriamycin, Bleomycin, Vinblastine, Dacarbazine/DTIC

cycles given at 4 wkly intervals

SE: Adriamycin- cardiomyopathy

Bleomycin- Pulm fibrosis

183
Q

Tx of Hogdkins Lymphoma in relapse patients

A

Autologous SCT

+ Intensive chemo

184
Q

the vessel wall is normal antithrombic,

what does it express it on its surface?

what factors are produced?

A

· Expresses anticoagulant molecules

o Thrombomodulin

o Endothelial protein C receptor

o Tissue factor pathway inhibitor

o Heparans

· Does not express tissue factor

· Secretes antiplatelet factors

o Prostacyclin, NO

185
Q

what makes the vessel wall prothrombotic?

A

infection, cancer, vasculitis, trauma

anticoagulant molecules downregulated

adhesion molecules upregulated

TF may be expressed

prostacyclin production decreased

*inflammation and malignancy impt stimulants for thrombosis

186
Q

how does stasis promote thrombosis?

A

accumulation of activated factors

promotes platelet adhesion

promotes leukocyte adhesion and transmigration

hypoxia produces inflammatory effect on endothelium

187
Q

causes of blood stasis?

A

immobility- surgery, long haul flights, paraparesis

compression- tumour, pregnancy

viscosity- paraprotein, polycythaemia

congenital- vascular abnormalities

obese, elderly

188
Q

during surgery, what factors combine to increase risk of clots?

A

trauma

inflammation

reduced flow

189
Q

in malignancy, what factors combine to increase risk of clots?

A

tissue factor on tumour

inflammation

reduced flow (compressive effects) or poor vasculature architecture

190
Q

in pregnancy, what factors combine to increase risk of clots?

A

reduced flow (compression effect)

decreased protein S

increased fVIII, fibrinogen

191
Q

acute treatment of DVT/ PE

A

LMWH subcut (175 units/kg) and Warfarin

or DOACs (directly acting anticoagulants)

LMWH subcut works immediately by potentiating Antithrombin III

Warfarin has a delayed effect and needs to be used with LMWH as it transiently increases risk of clots by reducing protein C/S levels.

DOACs- rivaroxaban (antiXa) and dabigatran (anti IIa)

192
Q

anticoagulant that potentiates antithrombin III

  • what factors are thus inhibited?
  • how is this drug given? (oral/im etc)
  • is monitoring required?
A

Heparin

  • thrombin and fIXa/ fXa/ fXIa inactivated
  • LMWH is given subcut and does not require any monitoring except in late pregnancy and renal failure
  • Unfractionated heparin is given IV and needs to be monitored (APTT)
193
Q

if necessary, how to monitor LMWH activity?

A

can use anti-Xa assay to monitor

in renal failure patients, extremes of weight or risk

194
Q

antidote for heparin?

A

protamine sulphate

195
Q

when do you use unfractionated heparin over LMWH?

A

renal impairment

196
Q

what side effects are associated with heparin tx?

A

Bleeding

*Heparin induced thrombocytopenia (HIT): low Pl and HIT predisposes to thrombosis (paradoxically) as pl release microparticles that activate thrombin (HITT- heparin induced thrombocytopenia and thrombosis)

Osteoporosis with long term use

197
Q

DOACs

e. g. of drugs
- what mode of administration
- what monitoring

A

anti Xa e.g. rivaroxaban, apixaban, edoxaban

anti IIa e.g. dabigatran

oral administration

no monitoring required

immediated acting

also useful long-term (taking over warfarin)

198
Q

Warfarin

  • how does it work
  • mode of administration
  • how to monitor?
A

inhibits effect by preventing recycling of Vit K, inhibits Vit K dependent carboxylation of factors 2, 7, 9, 10.

and proteins C, S and Z

onset of action is delayed takes about 2-5 days for factors to fall due to the long half lives of the factors.

* also transiently increases risk of clots initially if given alone

monitor PT time. (INR)

199
Q

warfarin overdose tx?

A

Vit K

or factor concentrates

200
Q

Which anticoagulants can you use in pregnancy?

A

only Heparin is safe

Warfarin is teratogenic.

DOAC- no data. avoid

201
Q

What is the target INR in those with recurrent DVT/ PE while on warfarin therapy?

A

3-4

~3.5

202
Q

what is the target INR of a patient w a mechanical heart valve?

A

~3

(2.5-3.5)

203
Q

what is the target INR in 1st episode DVT/ PE, atrial fibrillation, cardiomyopathy, symptomatic inherited thrombophilia, cardioversion?

A

2-3

~2.5

204
Q

what is the target INR of a pt with antiphospholipid syndrome and coronary artery thrombosis?

A

if antiphospholipid syndrome and arterial thrombosis >3.0

otherwise both conditions aim 2.5 (2.0-3.0)

205
Q

if 1st VTE with known cause, how long would you prescribe oral anticoagulants for?

A

3 month course

206
Q

e.g. of LMWH

A

Tinzaparin 4500u

Clexane 40mg

207
Q

if Cancer VTE/ 1st VTE unknown cause, how long would you prescribe a course of anticoagulants for?

A

3-6 months

in 1st VTE unknown cause- possibly lifelong

208
Q

if 1st VTE in thrombophilic patient, hwo long would you prescribe anticoagulation for?

A

3 months, possibly lifelong

209
Q

Bleeding Risk Assessment

  • Patient risk factors
  • Procedure risk factors
A

Patient

o Bleeding diathesis (eg haemophilia, VWD)

o Platelets < 100, BP > 200 syst or 120 dias

o Acute CVA in previous month (H’gge or thromb)

o Severe liver disease, severe renal disease

o Active bleeding

o Anticoag or anti-platelet therapy

Procedure

o Neuro, spinal or eye surgery

o Other with high bleeding risk

o Lumbar puncture/spinal/epidural in previous 4 hours

210
Q

in Recurrent VTE, how long would you prescribe anticoagulants for?

A

lifelong

keep INR 3.5 if recurrent clots even on warfarin

211
Q

Tx of a DVT/PE

  • in pt with cancer what oral anticoagulant do you use long term?
A

LMWH + Warfarin immediately

and stop LMWH when INR >2 for 2 days

OR

start DOAC

continue warfarin/ DOAC for 3-6 months

In patients with cancer, continue LMWH not warfarin

212
Q

when might you consider thrombolysis?

A

only in life threatening PE or limb threatening DVT

Risk of haemorrhage ~4% which is a risk not worth it for a simple DVT, but worth it for stroke

213
Q

who is more likely to get a recurrent clot?

someone young with no risk factors and no obvious cause

or

someone post surgery/ on the OCP

A

the young person with the idiopathic clot!

definitely follow up with 6 months anticoagulation, possibly lifelong

idiopathic VTE highest risk of recurrence

surgical lowest risk of recurrence

minor precipitants (cocp, flights, trauma) -> intermediate risk

214
Q

what anticoagulant is most effective in preventing clots w mechanical heart valves?

A

warfarin

215
Q

if INR is too high e.g. 5-8 but no bleed, what is the protocol?

A

withhold few doses

reduce maintenance

restart when INR <5

216
Q

if INR too high (5-8) w some minor bleeding, what is the protocol?

A

stop warfarin.

Slow IV vit K

restart when INR <5

217
Q

if INR too high >8, no bleed/ minor bleed

what is the protocol?

A

stop warfarin

oral/ IV vit K

check INR daily

218
Q

if INR is high (>8) and major bleeding

what is the protocol?

A

stop warfarin

Give Prothrombin complex concentrate (if unavailable, give FFP)

+ IV vit K

219
Q

Philadelphia chromosome +ve

A

CML

220
Q

In true polycythaemia, what happens to the red cell mass and plasma volume?

In relative polycythaemia, how is this different?

A

True polycythaemia:

increased red cell mass

normal plasma vol

relative polycythaemia:

normal red cell mass

low plasma vol

  • > appears to be a relative/ pseudopolycythaemia
    e. g. with alcohol, diuretics, obesity
221
Q

what conditions may see a relative / pseudopolycythaemia?

A

alcohol

obesity

diuretics

222
Q

some causes of true secondary polycythaemia

A

high altitude, cyanotic heart disease, hypoxic lung disease

inappropriate- renal cell cancer/ other renal disease, uterine myoma, other tumours

223
Q

in acute leukaemia (ALL and AML)

what % of blasts are seen in BM

A

immature blasts >20% of BM cells

224
Q

in a myeloproliferative disorder e.g. polycythaemia rubra vera, what processes may be disrupted by mutation?

A
  1. prolong cell survival
  2. increase cell proliferation
  3. may impair cellular differentiation
    e. g. creation of novel fusion gene or disruption of proto oncogene
225
Q

headaches, lightheadness, stroke

blurred vision

plethoric, red nose/ face, gout

aquagenic pruritus and peptic ulceration (due to increased histamine release)

JAK2 (V167F) mutation

O/E: splenomegaly, plethora, thrombosis

Raised Hb, HCT, + possibly increased WCC/ Platelets

A

Polycythaemia rubra vera

symptoms of hyperviscosity and increased histamine release

splenomegaly

erythromelalgia (red painful extremities)

retinal vein engorgement

Gout due to increased red cell turnover

226
Q

IX of suspected polycythaemia rubra vera

where Hb high/ Hct High etc

A

JAK2 V617 mutation - look for

Low serum EPO

Bone marrow aspiration and trephine biopsy

227
Q

tx of polycythaemia rubra vera

A

reduce hyperviscosity

venesection

cytoreductive therapy for maintenance: hydroxycarbamide

reduce risk of thrombosis:

aspirin

and keep Pl below 400 x109/L

228
Q

definition of essential thrombocythaemia

A

chronic myeloproliferative disease involving the megakaryocyte lineage

megakaryocytes dominate the BM

sustained thrombocytosis >600 x109/L

229
Q

what condition may ruxolotinib JAK2 inhibitor be used in?

A

myelofibrosis

230
Q

venous and arterial thrombosis

e.g. stroke, MI, PE

Erythromelalgia - red painful burning sensation in the extremities

mucous membrane / cutaneous bleeding

headaches, dizziness, visual disturbances, modest splenomegaly

Pl count high, no other cell lines affected.

what condition?

A

Essential thrombocythaemia

  • incidental finding in 50%

50% associated with JAK2

Blood film shows large platelets and megakaryocyte fragments

Increased BM megakaryocytes

231
Q

Tx of essential thrombocythaemia?

A

Aspirin to prevent thrombosis

Anagrelide: to inhibt maturation of platelets from megakaryocytes

Hydroxycarbamide: antimetabolite

232
Q

a myeloproliferative disease with proliferation of mainly megakaryocytes and granulocytic cells, associated with reactive bone marrow fibrosis and extramedullary haematopoiesis

usually in elderly

may be secondary to other haematological disease:

e.g. progression from PV or ET

A

myelofibrosis

233
Q

Blood film- tear drop poikilocytes (dacrocytes) and leukoerythroblasts

Dry tap on BM biopsy

extramedullary haemopoiesis - massive splenomegaly (budd chiari syndrome may present), hepatomegaly

pancytopenia: anaemia, thrombocytopenia, neutropenia

hypermetabolic state: weight loss, fatigue, night sweats, hyperuricaemia

A

myelofibrosis

234
Q

in myelofibrosis

  • what is found on BM aspirate
  • treatment
  • prognosis
A

fibrosis of BM, deposition of collagen and later osteosclerosis

Tx:

blood transfusions for anaemia

pl transfusion often ineffective

splenectomy for symptomatic relief

hydroxycarbamide: cytoreductive therapy

Ruxolotinib JAK2 inhibitor

SCT in young patients may be curative

prognosis: median 3-5 yrs

bad prognostic signs: sever anaemia, thrombocytopenia, massive splenomegaly

235
Q

features of anaemia/ bleeding/ brusing

FLAWS, gout

O/E: massive splenomegaly +/- hepatomegaly

FBC: Hb/ Pl usually well preserved. Massive leucocytosis. 50-200 x 109/ L Normal (4-11)

Blood film: neutrophilia + basophilia + myelocytes (mature myeloid cells)

Philadelphia chromosome +ve

what condition?

A

CML

236
Q

Ix in CML?

A

PCR for BCR-ABL (philadelphia chr) fusion gene

Ph Chr +ve in 80%

t(9;22)

WCC, FBC

Blood film: neutrophils, myelocytes, basophilia

Can monitor disease and treatment response with FBC, BCR-ABL:ABL ratio

237
Q

chronic phase vs accelerated phase vs blast phase of CML?

no of blasts in BM/blood

A

chronic (80% of pts): <5% blasts

indolent

Accelerated: 10%-19% blasts

increasing manifestations e.g. splenomegaly

Blast crisis: >20% blasts

median survival 3-6 months

resembles acute leukaemia

238
Q

t(9;22)

A

produces philadelphia chrosome (BCR-ABL gene)

seen in CML

expresses a fusion oncogene with tyrosine kinase activity

can be detected using FISH

239
Q

how to monitor disease and response to therapy in CML

A

FBC and WCC count

cytogenetics and detection of Ph chr - reduction in % of Ph Chr expressed

RT-PCR of BCR-ABL fusion transcript. can calculate BCR-ABL: ABL ratio

successful therapy means this will drop

e.g. complete response: 0% Ph +ve

partial response 1-35% Ph +ve

BCR-ABL transcripts reduce from 100% to the best - 0.001%

240
Q

a heterogenous group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells

-> functionally defective cells + numerical reduction

A

Myelodysplastic Syndrome

241
Q

Treatment of CML

A

Imatinib*

a BCR-ABL tyrosine kinase inhibitor

or

if resistant -2nd line: Dasatinib/ Nilotinib

young patients- possible allogeneic SCT

242
Q

typically seen in elderly

Hypercellular BM - 5-19% blasts (<5% is normal. >20% is acute leukaemia)

BM failure and cytopenias- infection, bleeding, fatigue

Blood film: Pseudo-Pelger-Huet anomaly, hypogranulation of neutrophils, micromegakaryocytes, hypolobulated nuclei, ringed sideroblasts (abnormally high iron accumulation - seen w prussian blue stain)

may also see myeloblasts w Auer rods

A

Myelodysplastic syndrome

243
Q

megakaryocytes with hypolobulated nuclei and <5% blasts

blood features: anaemia, normal or increased pl

what subtype of MDS?

A

MDS w 5q deletion

responds v well to treatment

244
Q

BM shows 10-19% blasts or Auer rods

blood features- cytopenias or 10-19% blasts or Auer rods

what subtype of MDS?

A

refractory anaemia with excess blasts II (RAEB II)

245
Q

bone marrow shows 5-9% blasts

Blood: cytopenias, <5% blasts, no auer rods

what subtype of MDS?

A

Refractory Anaemia with Excess Blasts (RAEB I)

246
Q

Bone marrow shows erythroid dysplasia with >15% ringed sideroblasts

blood features: anaemia, no blasts

what subtype of MDS?

A

Refractory anaemia with ringed sideroblasts

247
Q

Bone marrow shows dysplasia in >10% cells in 2 or more cell lines and >15% ringed sideroblasts

blood: cytopenia in 2 or more cell lines

what subtype of MDS?

A

refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD + RS)

248
Q

Bone marrow shows erythroid dysplasia w <5% blasts

blood: anaemia, no blasts

what subtype of MDS?

A

Refractory Anaemia

249
Q

Bone marrow shows dysplasia in >10% cells in 2 or more cell lines

Bloods: cytopenia in 2 or more cell lines

what subtype of MDS?

A

refractory cytopenia with Multilineage dysplasia

RCMD

250
Q

myelodysplatic syndrome

complications

A

development of AML

(AML from MDS has extremely poor prognosis)

1/3 die from infection, 1/3 die from bleeding and 1/3 from acute leukaemia

251
Q

Treatment of Myelodysplastic syndrome

A

Allogeneic SCT

Intensive chemotherapy- AML type regimen

most will just have:

supportive care: transfusions, ABx, Growth factors (EPO, G-CSF) given by subcut injection

biological modifiers- immunosuppressive therapy, azacytidine, lenalidomide

Oral chemo: hydroxyurea

low dose chemo- low dose cytarabine

252
Q

BM failure: Anaemia/ Leucopenia/ Thrombocytopenia

Blood- anaemia or even pancytopenia

trephine biopsy shows a hypocellular BM (<25% cellularity)

A

aplastic anaemia

253
Q

Management of Aplastic Anameia

A

seek a cause e.g. drug/ occupational exposure history

supportive- blood/pl transfusions (leucodepleted, CMV neg, irradiated blood), ABx, iron chelation therapy due to transfusion (when transferrin >1000)

drugs to promote marrow recovery- growth factors and oxymetholone/ Danazol (androgen)

SCT - for younger pts w donor (<35)

immunosuppressants e.g. anti lymphocyte globulin and ciclosporin for >50 yr

254
Q

what are some secondary causes of aplastic anaemia?

A

malignant infiltration of BM

radiation

Drugs e.g. carbimazole, chloramphenicol, carbamazepine

viruses e.g. Parvovirus B19

SLE

255
Q

AA is closely linked to development of which conditions in the future?

A

MDS, leukaemia

paroxysmal nocturnal haemoglobinuria

solid tumours

256
Q

Fanconi anaemia

  • inheritance pattern
  • presentation
A

most common form of inherited AA

most commonly autosomal recessive

causes Pancytopenia

presents at 5-10 yrs

with skeletal abnormalities (thumbs), renal malformations, microophthalmia, short stature, skin pigmentation (cafe au lait spots/ hypopigmentation)

257
Q

fanconi anaemia increases the risk of progression to which conditions?

A

30% progress to MDS

and 10% to AML

treatment= supportive + androgens can transiently improve counts but consider SCT

258
Q

Classical triad of abnormal skin pigmentation, nail dystrophy, oral leukoplakia

+

BM failure, cancer predisposition and somatic abnormalities

A

dyskeratosis congenita

259
Q

Diamond-Blackfan syndrome

A

pure red cell aplasia

normal WCC and platelets

presents at 1yr/ neonatal

dysmorphology

260
Q

what is the most common inheritance pattern of dyskeratosis congenita?

A

x-linked recessive.

Classical triad of abnormal skin pigmentation, nail dystrophy, oral leukoplakia

+

BM failure, cancer predisposition and somatic abnormalities

261
Q

Schwachman-Diamond syndrome

A

primarily neutrophilia

skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature

AML risk

262
Q

80% of cases diagnosed on routine bloods

if symptomatic:

symmetrical painless lymphadenopathy

BM failure- anaemia, infections, bleeding

weight loss, low grade fever, night swetas

splenomegaly & hepatomegaly

assoc with AIHA, ITP

may undergo Richter’s transformation

WCC: high WCC with lymphocytosis

A

CLL

*smear CLLs

BM- lymphocytic replacement, anaemia, thrombocytopenia

Low serum Ig

263
Q

CLL

  • which prognostic markers are good and which are bad

LDH

CD38

11q23 deletion

Low ZAP-70

Hypermutated Ig gene

13q14 deletion

A

Bad:

High LDH (marker of tumour turnover)

CD38 +ve

11q23 deletion

Good:

Low ZAP-70

Hypermutated Ig gene

13q14 deletion

264
Q

Binet Staging A, B, C

via CT/ PET scan

A

Stage A:

High WBC

<3 groups of enlarged LNs

usually no tx required

Stage B:

>3 groups of enlarged LNs

Stage C:

anaemia or thrombocytopenia

265
Q

cell markers on normal B cell vs B-CLL cells

CD5

CD19

A

Normal:

CD5- CD19+

B-CLL:

CD5+ CD19-

266
Q

treatment of CLL

A

many patients undergo watchful waiting if asymptomatic with slowly progressive disease

1st line: alemtuzumab (depletes lymphocytes)

supportive: abx, vaccination, e.g. aciclovir, PCP prophylaxis, IVIG, pneumovax

young patients: allogeneic SCT

Autoimmune phenomena: 1st line steroids. 2nd line Rituximab

267
Q

Classify these conditions into their groups of very aggressive/ aggressive/ indolent

Burkitt’s Lymphoma

Mantle Cell Lymphoma

Follicular

Small lymphocytic/ CLL

MALT

Diffuse Large B cell

ALL

A

Very aggressive:

Burkitts

ALL

Aggressive:

Diffuse Large B cell

Mantle Cell

Indolent

Small lymphocytic/CLL

Follicular

MALT

the indolent ones are more incurable whereas the aggressive ones are most curable

268
Q

Treatment for DLBCL

A

6-8 cycles of Rituximab-CHOP

aim of therapy is curative

if relapse-> 2nd line tx: autologous SCT

269
Q

what drugs does R-CHOP consist of?

A

Rituximab (anti CD20)

Cyclophosphamide

Adriamycin

Oncovin aka Vincristine

Prednisolone

270
Q

tx for follicular lymphoma

A

Watch and wait. only treat if indicated e.g recurrent infections, nodes compressing bowel/ureter

may require 2-3 chemotherapy schedules over the 12-15 yr period

each chemotherapy becomes less and less effective

1st line: R-CVP

271
Q

Tx of Gastric MALToma

A

eradication of H pylori:

omeprazole/ clarithromycin/ amoxicillin

repeat breath test at 2months and endoscopy every 6 months for 2 yrs then annually

if eradication therapy fails then chemo

272
Q

which surface protein do both CD4+ and CD8+ T cells have?

A

CD3

273
Q

what may undergo richter transformation to DLBCL?

A

CLL

hairy cell leukaemia

274
Q

CLL prophylaxis and treatment of infections

A

Aciclovir

PCP prophylaxis for those receiving fludarabine or alemtuzumab

IVIG for those w hypogammaglobulinaemia and recurrent bacterial infections

Immunisation against pneumococcus and seasonal flu

275
Q

CLL autoimmune phenomena e.g. AIHA

mx?

A

1st line steroids

2nd line rituximab

276
Q

why does pregnancy cause a mild anaemia physiologically?

A

red cell mass increases

but plasma volume rises further

overall net dilution

277
Q

normal blood changes in pregnancy

A

mild anaemia

macrocytosis

neutrophilia

thrombocytopenia

278
Q

Pregnancy demands increased requirements of?

-may need supplementation

A

Iron requirement

Recommend to take 60mg Fe daily during pregnancy if fe deficient

Folate requirement (400mcg / 5mg in pregnancy)

  • to reduce risk of neural tube defects

supplementation before conception til 12 wks gestation

279
Q

Normal values of Pl in pregnancy?

  • why is pl count impt
A

175-200 normal

if platelets between 70-80, have to assess safety for epidural anaesthesia.

>70 required for epidural

>50 sufficient for delivery

280
Q

causes of low Pl in pregnancy

A

physiological: gestational (normal for a drop of 10%)

preeclampsia (proportional to pl count)

immune thrombocytopenic purpura (may require IVIG)

TTP, MAHA

281
Q

a hypercoagulable state in pregnancy is seen due to?

A

fVIII and vWF increase 3-5 fold

fibrinogen increases 2 fold

fVII invreases 0.5 fold

Protein S falls

-> 7, 8, vwf and fibrinogen increase and anticoagulant protein s falls

allows rapid control of bleeding from placental site at time of delivery

net effect: a procoagulant state which increases rate of thrombosis. increased thrombin generation, increased fibrin formation, decreased fibrinolysis

282
Q

Prevention of thrombosis in pregnancy:

A

women with risk factors (age, weight) should receive prophylactic heparin + TED stockings

either throughout pregnancy or in the post partum period

mobilise early, maintain hydration

283
Q

Tx of DVT/ PE in pregnancy

A

LMWH - will not cross placenta

monitor antiXa

stop for labour or planner delivery esp for epidural.

Epidural: wait for 24h after tx dose and 12h after prophylactic dose

284
Q

Tx of antiphospholipid syndrome in pregnancy·

A

Recurrent miscarriage + persistent Lupus anticoagulant (LA)/ anticardiolipin Abs (ACL)

>3 consecutive miscarriages before 10 weeks of gestation OR

One or more morphologically normal fetal losses after the 10th week of gestation OR one or more preterm births before the 34th week of gestation owing to placental disease.

Treatment of aspirin and heparin increase chances of live births

285
Q

sudden onset shivers, vomiting, shock, DIC
86% mortality

presumed due to tissue factor in amniotic fluid

A

amniotic fluid embolism

286
Q

high HbA2 in blood (>3.5%) suggests?

A

Beta thal

287
Q

Process of Autologous SCT:

A
  • Growth factor injected into patient
  • Collect stem cells and freeze
  • High dose chemo given to pt
  • Thaw and reinfuse pt with their stem cells

To allow higher dose chemo

suitable for ALL, CLL, myeloma, lymphoma, solid tumours

288
Q

process for allogeneic transplant:

A
  • high dose chemo +/- radio to patient until BM is fried
  • donor donates BM stem cells to complete replace recipients BM w healthy cells

suitable for ALL/AML, CML/CLL, myeloma, BM failure, lymphoma, congenital immune deficiencies

289
Q

Which chromosome is HLA gene found on?

A

chr 6

290
Q

what cell surface marker is expressed on stem cells?

A

CD34

291
Q

what affects outcome of SCT?

e.g. age/ gender/ disease phase

A

age >40

late in disease phase

female into male recipient

>1 yr to BMT

non sibling donor

292
Q

Paediatric Haemotology: what differences are there?

A

low [Hb]

higher lymphocytes

smaller MCV

293
Q

Neonatal Blood count: how is it different from that of an adult?

A

WCC, neutrophil and lymphocyte counts are high

[Hb] and MCV high

Neonates have higher % HbF so disorders of beta globin genes are much less likely to be manifest

Enzyme levels in red cell also differ, e.g. G6PD concentration is about 50% higher than in adults

294
Q

causes of polycythaemia in a neonate:

A

twin to twin transfusion syndrome

fetal hypoxia

Placental insufficiency

295
Q

Potential causes of anaemia in the neonate:

A

twin to twin transfusion

fetal to maternal transfusion

parvovirus b19

haemorrhage from cord/placenta

anticoagulant drugs

296
Q

Congenital leukaemia is particularly common in ?

A

Down’s syndrome

The leukaemia is myeloid with major involvement of the megakaryocyte lineage

The most remarkable feature is that it usually remits spontaneously and relapse 1-2 years later in only about a quarter of infants

297
Q

what globin chains make up HbF

A

a2 gamma2

298
Q

what globin chains make up HbA2?

A

2 alpha and 2 delta chains

299
Q

what globin chains make up HbA?

A

2 alpha + 2 beta chains

300
Q

bleeding following circumcision

haemarthroses

deep bruises, prolonged bleeding after surgery/ trauma

prolonged APTT

normal PT

what conditions?

what ix?

inheritance pattern

A

Haemophilia A or B

Ix: fVIII/ fIX assay

if low fVIII-> Haemophilia A

if low fIX -> Haemophilia B

both are X-linked recessive conditions

may have had umbilical cord bleeding, haematoma during vaccinations

301
Q

Mx of Haemophilia A/B

A

Counselling of family

Treatment of bleeding episodes

fVIII/ fIX concentrates as replacement life-long

in haemophilia A: desmopressin (which increases vwf release of fVIII as vwf is a fVIII carrier)

Avoid NSAIDs and IM injections

302
Q

mucosal bleeding

bruises

post traumatic bleeding

increased APTT, increased bleeding time, decreased fVIII, decreased vWF + decreased ristocetein cofactor activity

normal INR and pl count

what condition?

A

von Willebrand disease

vWF carries fVIII in circulation. so defective/ reduced vWF also causes reduced fVIII.

mostly auto dominant

303
Q

mx of von willebrand disease?

A

desmopressin

VWF and fVIII concentrates

304
Q

AML

  • age of incidence
  • mutations seen
  • pathognomonic features
A

bimodal incidence: peak in under 2s and in 65-70yos

many mutations assoc with AML

t(5;8), inv(16), t(8;21), trisomy 8, trisomy 21

>20% myeloblasts on BM + Auer Rods

305
Q

Risk factors for developing ALL/AML

A

ionising radiation- radiotx

chemotx

benzene

MDS/ myeloproliferative disorders

Downs: signficantly increased risk of AML

306
Q

t(15;17)

excess of abnormal promyelocytes

DIC

PML-RARA fusion protein

A

Acute promyelocytic leukaemia

307
Q

how to differentiate AML and ALL

A

cytological features on histology (AML has fine granules & more cytoplasm than ALL)
cytochemistry (Myeloperoxidase +ve, Sudan Black B +ve, Non specific esterase +ve in AML)

Immunophenotyping:

ALL: CD19 (B cells), CD3 (T cells), CD34 (stem cells)

AML: CD34 (stem cells), MPO (Myeloid cells), CD13/ CD33

308
Q

AML

  • typical features
  • more specific features
  • Blood film features
A

BM failure- effects of pancytopenia

Splenomegaly, hepatomegaly

Gum infiltration if monoblasts/ monocytic

Skin infiltration/ CNS involvement + hypoK

Blood film: circulating blasts with granules. auer rods.

if unclear- immunophenotyping

309
Q

treatment of AML

A

Supportive care:

blood products, abx, FFP/Cryoprecipitate if DIC, allopurinol, fluid and electrolytes to prevent tumour lysis syndrome

Chemotherapy

Consider Allo SCT in young

Specific for acute promyelocytic leukaemia: ATRA

310
Q

ALL

  • peak age incidence
  • clinical features
A

peak incidence in childhood

BM failure - pancytopenia

hepatosplenomegaly

lymphadenopathy

thymic enlargement

testicular enlargement

bone pain

311
Q

ALL Ix

A

· Blood count and film, bone marrow aspirate

· Immunophenotyping – matters as T (15%) and B-lineage (85%) ALL may be treated differently

· Cytogenetic/molecular genetic analysis - Ph positive need imatinib, treatment must be tailored to the prognosis

· Blood group, LFTs, creatinine, electrolytes, calcium, phosphate, uric acid, coagulation screen

312
Q

tumour lysis syndrome

A

complication of treating cancer where large amts of tumour cells are lysed at the same time

occurs most commonly after tx of lymphomas and leukaemias

high K, high PO4, high Uric acid, high blood urea nitrogen

may cause acute kidney failure, seizures, cardiac arrhythmias and death

313
Q

Tx of ALL

A

· Specific therapy – systemic or CNS-directed chemotherapy

· Supportive care – blood products, antibiotics, general medical care, prophylaxis for Pneumocystis jiroveciiinfection

· Hyperuricaemia: hydration, urine alkalinization and allopurinol or rasburicase

· Hyperphosphataemia; Al(OH)3, calcium

· Hyperkalemia: fluids, diuretics

· Extreme leukocytosis (WBC > 200 × 109/l): leukapheresis, sometimes haemodialysis

314
Q

when to transfuse red cells:

A

major blood loss: >30% blood vol lost

peri op, crit care: Hb<70g/L

post chemo: Hb <80g/L

symptomatic anaemia- IHD, breathless, ECG changes

Give ABO/D compatible, O- in emergency

transfuse 1 unit RBC over 2-3h

1 unit should increase Hb by 10g/L in a 70/80kg patient

315
Q

In Blood transfusions some special requirements

A

· CMV -ve blood - only required for intra-uterine and neonatal transfusions (new guidance 2012). Also for elective transfusion in pregnant women (baby in-utero is exposed to maternal transfusion)

Irradiated blood - required for highly immunosupressed patients, who cannot destroy incoming donor lymphocytes: which can cause (fatal) transfusion associated graft versus host disease (TA-GvHD)

· Washed - red cells and platelets are only given to patients who have severe allergic reactions to some donors’ plasma proteins

316
Q

indications for platelet transfusion:

A

prevent bleeding (surgery): Pl< 50 or if critical site like CNS, eye: <100

prevent bleeding post chemo: pl<10 (<20 if sepsis)

consumptive disorders e.g. DIC

transfuse 1 u pl over 20-30 min

One unit of platelets is an adult treatment dose: usually raises platelet count by 30-40 x109/L

Platelet transfusion is contraindicated in heparin-induced thrombocytopenia (HIT) and TTP

317
Q

FFP

  • indications
A

FFP contains all clotting factors

DIC with bleeding

Liver disease + risk: PT ratio >1.5 x normal

Blood loss >150ml/min

318
Q

pt just had a blood transfusion,

rise in temperature (low fever), chills, rigors.

what is this?

how to manage?

A

febrile non-haemolytic transfusion reaction

occurs during/soon after transfusion

WBC can release cytokines during storage- rarer now that blood is leucodepleted

mx: stop or slow transfusion, may need to treat with paracetamol

319
Q

pt just had a transfusion, common especially w plasma

mild, urticarial itchy rash

+/- wheeze

what is the cause?

mx?

A

allergic transfusion reaction

allergy to a plasma protein from donor

more common in patients with history of atopy/ allergies

usually have to stop or slow transfusion

mx: IV antihistamines to treat

320
Q

pt has just had transfusion

1-2h post transfusion

restless, abdo/loin pain, vomiting, fever, collapse, haemoglobinuria (dark urine)

signs: BP drops, HR goes up, temp high

what has happened?

A

ABO incompatibility

  • most severe: A blood group into group O

A/ B IgM antibodies are naturally occuring in plasma

potentially fatal intravascular haemolysis

take samples for FBC, biochemistry, coagulation, repeat cross match and direct antiglobulin test

321
Q

pt has had a blood transfusion

high fevers, rigors, vomiting, flushing, collapse

hypotension, high HR (shock) and High fever

what has happened?

A

Bacterial contamination

presents very similarly to wrong ABO blood

bacterial growth can cause endotoxin production which causes immediate collapse

Platelets > red cells > frozen components in terms of (storage temp)

322
Q

prevention of bacterial contamination

A

· Donor questioning + arm cleaning + diversion of first 20mL into a pouch (used for testing)

· Red cells: Store always in controlled fridge 40C; shelf-life 35 days. If out for >½ hour, need to go back in fridge for 6 hours. Complete transfusion of blood within 4.5h of leaving fridge i.e. transfuse over 4hrs max

· Platelets: stored at 220C; shelf-life 7 days (as now screened for bacteria before release)

· All components: look for abnormalities e.g. clumps of discoloured debris; brown plasma etc

323
Q

pt has had a blood transfusion

shock- drop in BP and increased HR, very breathless with wheeze

+ laryngeal and facial oedema

what is happening?

A

anaphylaxis

severe, life thrreatening reaction soon after start of transfusion

IgE antibodies in pt cause mast cell release of granules & vasoactive substances. Most allergic reactions are not severe, but some can be e.g. in IgA deficiency

324
Q

pt has had a transfusion

acute SOB, dry cough, fever

normal JVP, low O2 sats, high HR, high BP

CXR shows bilateral pulmonary infiltrates during/ within 6h of transfusion

what happened?

A

TRALI

transfusion related acute lung injury

acute non-cardiogenic pulmonary oedema that occurs within 6h following a blood transfusion.

anti-WBC abs in donor interact with corresponding Ag on patient’s WBCs-> aggregates of WBCs get stuck in pulmonary capillaries

-> release neutrophil proteolytic enzymes and toxic O2 metabolites that cause lung damage

325
Q

fluid overload following blood transfusion

pulmonary oedema

SOB, hypoxia, high HR, high BP

CXR shows fluid overload/ cardiac failure

what is happening?

A

transfusion associated circulatory overload

TACO

esp in those w cardiac failure, renal impairment, hypoalbuminaemia

326
Q

blood transfusion over 24 h ago

usually occurs 5-10 days after

jaundice, haemoglobinuria

high Br, low Hb, high reticulocytes

what is happening?

A

Delayed haemolytic transfusion reaction

extravascular haemolysis that takes 5-10 days

Test U&Es as can cause renal failure

repeat G&S for new antibody?

327
Q

History of transplant/ transfusion

severe diarrhoea, liver failure, skin dequamation, bone marrow failure

-> death weeks to months post transfusion

what has happened?

A

Transplant/ transfusion assoc GVHD

rare but always fatal

Donors blood contains some lymphocytes (normally the host’s immune system recognises these as foreign and destroys. them)

In susceptible patients - lymphocytes not destroyed

lymphocytes recognise patient’s tissue HLA antigens as foreign- attack gut, liver, skin, bone marrow

Prevent: irradiate blood components for very immunosuppressed pts who cannot destroy incoming donor lymphocytes

328
Q

transfusion of blood or platelets

purpura appears 7-10 days after

resolves in 1-4 wks

purpura = pin prick red/ purple blood spots due to v low platelets <20 x 109

what is happening?

A

Post transfusion Purpura

· Affects HPA -1a negative patients - previously immunised by pregnancy or transfusion (anti-HPA-1a antibody)

treatment: infusion of IVIG

329
Q

in haemolytic disease of the fetus/ newborn, what antibody crosses the placenta?

A

Anti-D IgG antibodies

cross the placenta and bind and destry fetal red cells

-> fetal anaemia, hydrops fetalis and neonatal jaundice/ kernicterus

330
Q

when are Rh-ve women screened for anti-D antibodies?

A

at booking 12 wks and 28 wks

331
Q

Mx of mother with anti-D antibodies and RhD+ fetus

A

· Monitor fetus for anaemia – MCA Doppler US

· Deliver baby early, as HDN gets a lot worse in last few weeks of pregnancy

If necessary, intra-uterine transfusion can be given to fetus in specialised centres, highly skilled - needle in umbilical vein

· At delivery - monitor baby’s Hb and bilirubin for several days as HDN can get worse for few days

· Can give exchange transfusion to baby if needed to decrease bilirubin and increase Hb; plus phototherapy to drop bilirubin

332
Q

prevention of Haemolytic Disease of Fetus/ Newborn

A

Anti-D Ig

prophylaxis

RhD +ve (fetal) red cells get coated with anti-D Ig which are removed by the mother’s reticuloendothelial system (spleen) before they can sensitise the mother to produce anti-D Abs

· To be effective - must give anti-D injection within 72 hours of the ‘sensitising event’

e.g. spontaneous miscarriages if surgical evacuation needed, amniocntesis and CVS, abdo trauma, external cephalic version, stillbirth or intrauterine death

333
Q

what dose of anti-D to give at what phase?

A

125iu of Anti-D covers 1 ml of fetal blood

at least 250iu for events before wk 20

and at least 500iu for events any time after wk 20

larger does needed for larger bleed - do Kleihauer test to determine dose needed

so 500iu - up to 4ml, 1250iu - 10ml, 1500iu- 12ml

334
Q

when is routine antenatal anti-D prophylaxis given?

A

1500iu anti-D at 28-30 wks

or 2 doses (1 at 28 wk and another at wk 34)

within 72h after delivery

335
Q

what are some other antibodies that can cause haemolytic disease of newborn?

A

anti-c, anti-kell antibodies

anti-A and anti-B

336
Q

where is basophilic stippling seen?

A

beta thal trait

lead poisoning

alcoholism

sideroblastic anaemia

megaloblastic anaemia

myelodysplasia

337
Q

what conditions might show target cells/ codocytes on blood film

A

iron deficiency anaemia

thalassaemia

hyposplenism

liver disease

338
Q

Bone marrow shows <10% clonal plasma cells.

IgG/IgA <30g/l

no symptoms/ no CRAB

A

MGUS

monoclonal gammopathy of undertermined significance

no treatment needed

small transformation rate (1-2% risk progression to MM)

339
Q

features of multiple myeloma

A

CRAB

hypercalcaemia - stones, bones, groans, moans

renal impairment

anaemia

bone pain, osteolytic lesions, fractures, osteoporosis

340
Q

Ix of Multiple myeloma

A

serum Ca, high ESR

Xray/ MRI bone pain areas

blood film shows Rouleaux formation

Urine: bence-jones protein

serum protein electrophoresis: dense narrow band

BM aspirate: >10% plasma cells

341
Q

what % plasma cells is found in a normal BM

A

5%

342
Q

what is the first investigation you want to do when you suspect Multiple myeloma?

A

serum protein electrophoresis

  • paraprotein detected
343
Q

what is seen on BM aspirate of someone with MM?

A

MM can have 40-90% plasma cells in their BM

may look like normal plasma cells

clumped chromatin, rare nucleoli, immature plasmablasts, less abundant cytoplasm

344
Q

what cell surface markers are found on multiple myeloma cells

A

CD38, CD138

negative for CD19, 20 (usually expressed on B cells),

345
Q

myeloma bone disease: possible complications

A

80-90% have lytic lesions

pathological fractures

spinal cord compression leading to paralysis

hypercalcaemia

bone pain -> affecting QOL, independence, mobility

too many osteoclasts (from increased IL6) and not enough active osteoblasts

346
Q

what investigations for myeloma bone disease

A

X ray - for lytic lesions

MRI- High sensitivity for marrow infiltration, response monitoring possible, expensive & limited availability

CT – full body CT is the standard used in Imperial to diagnose as it detects very small lesions (high sensitivity). Good for radiotherapy planning but higher radiation dose

PET - detects active disease

347
Q

why does multiple myeloma cause renal failure?

A

free light chains cause injury to kidneys - active inflammatory mediators in the proximal tubule epithelium

-> leads to amyloidosis (AL chains)

cast nephropathy

348
Q

treatment of multiple myeloma

A

supportive for CRAB symptoms including bisphosphonates

Auto-SCT - curative, best for younger patients

steroids

Classical cytostatic drugs (relatively low dose) eg. melphalan

Proteasome inhibitors – prevent misfolded proteins from being degraded, which accumulates in myeloma cells (esp effective as myeloma produces a lot of proteins)

e.g. bortezomib

IMIDs – thalidomide, lenalidomide, pomalidomide (also used in MDS). Reduces cell turnover by affecting transcription factor relevant for plasma cells

349
Q

what is the normal life span of platelets?

A

10 days

350
Q

what do platelets release to trigger platelet activation?

A

release of ADP and thromboxane

351
Q

what is the common progenitor of thromboxane A2 and prostacyclin PgI2?

A

Cyclic endoperoxidases

This is converted into thromboxane A2 via thromboxane synthetase and to prostacyclin PgI2 via prostacyclin synthase

Arachidonic acid is converted to cyclic endoperoxidases via cyclo oxygenase

352
Q

what does tissue factor pathway inhibitor inhibit?

A

TF-fVIIa complex

353
Q

what is factor V leiden?

A

factor V leiden cannot be cleaved by activated protein C

354
Q

Bone marrow shows >10% clonal plasma cells

IgG/IgA >30g/L

no CRAB symptoms, no organ damage

no treatment needed

A

smouldering MM

355
Q

what is Clopidogrel?

A

an antiplatelet

an ADP inhibitor

irreversible non competitive inhibitor

inhibits ADP binding to its Platelet membrane receptors -> inhibiting activation of gpIIb/IIIa

356
Q

how does aspirin work as an antiplatelet?

A

inhibits cyclo oxygenase enzyme and affects the thromboxane A2 pathway

it is the most widely used antiplatelet treatment

357
Q

how does dipyridamole work?

A

antiplatelet

inhibits platelet aggregation by blocking the reuptake of adenosine formed from precursors released by RBC after microtrauma

358
Q

christmas disease aka?

A

haemophilia B

359
Q

DIC

  • what happens?
A

systemic activation of coagulation and fibrinolysis caused by sepsis, obstetric complications, reaction to toxin, etc

  • > intravascular deposition of fibrin -> thrombosis of small and midsize vessels with organ failure
  • > depletion of platelets and coagulation factors -> bleeding
360
Q

DIC

  • blood test results
A

APTT, PT, TT increased

fibrinogen decreased

increased fibrin degradation products

low platelets and increased shistocytes (MAHA)

tx of underlying disorder

platelet transfusion, FFP

361
Q

how does liver disease affect clotting factors?

A

decreased synthesis of 2, 5, 7, 9, 10, 11 and fibrinogen

decreased absorption of Vit K

abnormalities of pl function

tx: vit K, FFP, cryoprecipitate

362
Q

sideroblastic anaemia

  • diagnosis
  • treatment
A

sideroblastic anaemia

  • ineffective erythropoiesis -> iron loading causing haemosiderosis (endocrine, liver, cardiac damage)
    diagnosis: ring sideroblasts seen in marrow
    tx: remove the cause (e.g. MDS, following chemo, alcohol excess, lead excess), and Pyridoxine (Vit B6 promotes RBC production)
363
Q

what are sideroblasts?

A

sideroblasts are atypical, abnormal nucleated erythoblasts with granules of iron accumulated in the mitochondria surrounding the nucleus.

ring sideroblasts: iron laden mitochondria form a ring around the nucleus

the body has iron available but cannot incorporate it into Hb.

peripheral blood smear: basophilic stippling, pappenheimer bodies (cytoplasmic granules of iron)

364
Q
A

stomatocytes

RBCs that have a fish mouth appearance or ‘smiling face’ appearance.

usually seen in alcoholics, liver disease, and hereditary stomatocytosis.

365
Q

what conditions are associated w stomatocytes?

A

alcoholics, liver disease, and hereditary stomatocytosis.

366
Q

Bernard- soulier syndrome

A

mutation of glycoprotein 1 b

bleeding disorder

367
Q

Glanzmanns thrombasthenia

A

mutation of gpIIb/IIIa

-> blood coagulation

368
Q

what causes the most severe ABO incompatible blood transfusion?

what blood group to what?

A

Group A into goup O recipient

369
Q

Delayed haemolytic transfusion reactions

most frequent antibodies against?

A

Kidd (Jk) and Rh systems

these occur when pts are sensitised from previous transfusions/ pregnancies, and therefore have antibodies against red cell antigens which are not picked up by routine blood bank screening if they are below detectable limits.

370
Q

blood film features suggesting hyposplenism

A

howell-jolly bodies

target cells

acanthocytes

371
Q

TIBC / transferrin saturation levels in IDA

A

TIBC / Transferrin High

Transferrin saturation LOW

low Fe, low ferritin

372
Q

TIBC/ transferrin saturation lvls in haemochromatosis

A

TIBC/ transferrin LOW

transferrin saturation high

Iron high, ferritin high

373
Q

TIBC/ transferrin saturation of anaemia of chronic disease

A

TIBC/ transferrin low

Transferrin saturation low

Fe low

Ferritin high

374
Q

chronic haemolysis

TIBC/ transferrin saturation

A

transferrin/ TIBC low

Transferrin saturation high

Iron High

Ferritin High

375
Q

complications of HELLP syndrome

A

liver and renal failure

pulmonary oedema

DIC

placental abruption

376
Q

acute fatty liver of pregnancy

A

life threatening rare complication of pregnancy

deranged LFTs, often accompanied by abnormal coagulation, leukocytosis and hypoglycaemia

377
Q

how does alcohol excess cause thrombocytopenia?

A

alcohol is a direct bone marrow suppressant thereby inhibiting megakaryocyte development and platelet production.

378
Q

causes of high ESR

A

inflammation

pregnancy

anaemia (mild)

autoimmune conditions eg. SLE/ RA

infections

lymphoma/ multiple myeloma

some drugs

379
Q

Causes of low ESR

A

congestive cardiac failure

low fibrinogen

low plasma protein

polycythaemia

sickle cell anaemia

hyperviscosity

leukaemia e.g CLL

380
Q

why may smokers experience polycythaemia

A
  1. increased EPO secretion from hypoxia
  2. smokers have reduced plasma volume, thus increasing the relative [Hb]

aka Smokers polcythaemia “combined”

381
Q

von willebrands disease is characterized by abnormal platelet aggregation when exposed to what abx?

A

Ristocetin

an abx no longer clinically used

causes vWF to bind the gpIb

if defective vwf then platelet aggregation does not occur

382
Q

Pel ebstein fever

A

cyclical fever lasting 1-2 wks

in Hodgkins lymphoma

rare

383
Q

B symptoms

A

Fever >38/ Pel-ebstein fever

Night sweats

Weight loss: unintential, loss of >10% of normal body weight over period of 6m or less

384
Q

Stage I hodgkins

A

single lymph node region involved

385
Q

stage II hodgkins

A

involvement of two or more LN regions on same side of the diaphragm

386
Q

mild von wellibrands disease scheduled for dental extraction

she had one previously where she required 2 units of blood transfused.

what is the most appropriate tx prior to surgery?

A

Desmopressin.

acts to increased vWF and fVIII concentration by encouraging its release from endothelial cell storage sites.

Not efficacious in type III (profound deficiency in vWF)

if mod- severe. Cryoprecipitate - contains vWF and fVIII etc

387
Q

clinical manifestations of Bare Lymphocyte Syndrome

apart from recurrent infections/ FTT

A

sclerosing cholangitis

with hepatomegaly and jaundice

388
Q

what does muromonab do (OKT3)?

A

efficiently clears T cells from the recipients circulation

used to treat rejection episodes in patients who have undergone allograft transplantation.

389
Q

immunosuppressive effects of corticosteroids

A

inhibits prostaglandin formation

reduces no of circulating B cells

inhibits monocyte trafficking

inhibits T cell prliferation

reduces expression of inflamatory cytokines e.g. IL 1, TNFa

path (6 decks)

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