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Phase 2a Gold Standard > Haematology > Flashcards

Haematology Flashcards

1
Q

How is the extrinsic pathway of the coagulation cascade started

A

External damage to endothelial tissue exposes tissue factor (3), activating it.

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2
Q

How is the intrinsic pathway of the coagulation cascade started

A

Collagen exposure activates 12 to 12a

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3
Q

Describe the extrinsic pathway of the coagulation cascade

A

3,7,10
endothelial damage = 3 (tissue factor) -> 3a.
3a = 7 -> 7a
7a + calcium -> activate 10 to 10a

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4
Q

Describe the intrinsic pathway of the coagulation cascade

A

12,11,9,8,10
Collagen exposure causes activation of 12 -> 12a
12a = 11 -> 11a
11a activates 8 and 9 to 8a and 9a.
8a and 9a activate 10 to 10a.

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5
Q

Describe the common pathway of the coagulation cascade

A

10a and 5a and calcium -> 2 to 2a (thrombin).
2a activates 1 (fibrinogen) to 1a (fibrin)
2a activates Stabilising factor (13) to 13a, which forms stable clot with 1a and calcium.

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6
Q

What is PT, and how is this used to calculate INR. Reasons INR may be raised

A

Prothrombin time - Coagulation speed through extrinsic pathway (3,7,10)
INR = (patient’s PT/reference PT)

Vit K deficiency, Anticoags, liver disease, disseminated intravascular coagulation

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7
Q

What is APTT and what conditions affect this BUT NOT PT

A

Activated Partial Thromboplastin Time
Coagulation speed through intrinsic pathway

Affected by:
haemophilia A, B and Von Willebrand Disease

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8
Q

Give MCV values in microcytic, normocytic and macrocytic anaemias

A

Avg RBC volume

Micro - MCV <80
Normo - MCV 80-95
Macro - MCV 95+

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9
Q

General anaemia signs

A

Pale skin
Conjunctival pallor
Bounding pulse/tachycardia
Dizziness
Fatigue
Postural hypotension

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10
Q

General anaemia symptoms

A

Tiredness, short of breath, headaches, palpitations, dizziness, syncope

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11
Q

Causes of microcytic anaemia

A

TAILS

T - Thalassaemia!
A - Anaemia of chronic disease
I - Iron deficiency anaemia!
L - Lead poisoning
S- Sideroblastic anaemia!

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12
Q

Causes of normocytic anaemia

A

Can be haemolytic or non haemolytic.
AAAH

A - Acute blood loss
A - Anaemia of chronic disease
A - Aplastic anaemia
H - Haemolytic anaemias (other card)

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13
Q

Normocytic haemolytic causes of anaemia (5)

A

Normocytic

Sickle cell
G6PD
AHA
Hereditary spheryocytosis
Malaria

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14
Q

Causes of macrocytic anaemia

A

Can be Megaloblastic (large RBC) or normoblastic.

Megaloblastic - Due vitamin deficiency leading to impaired DNA synthesis preventing cells from dividing normally.
- B12 deficiency
- Folate deficiency

Normoblastic -
- Alcohol
- Hypothyroidism
- Liver disease
- Drugs such as azathioprine

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15
Q

How is iron normally stored and made available?

A
  • Iron exists bound to haem/myoglobin (Fe2+) or unbound (Fe3+)
  • Fe2+ absorbed directly into duodenum so Fe3+ must first be turned into Fe2+ by ferri-reductase enzymes
  • Fe2+ ions bind to ferritin in duodenal cells for storage
  • When iron required, Fe2+ turned into Fe3+ by hephaestin
  • Fe3+ binds to transferrin for transport where it is delivered to tissue
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16
Q

Define Iron Deficient Anaemia with MCV, and give risk factors

A

Anaemia caused by low blood iron (Most common anaemia). Microcytic anaemia

  • Bowel Cancer
  • Pregnancy
  • Blood loss
  • IBS/IDS
  • Coeliac
  • H Pylori infection (also proton pump inhibitor use)
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17
Q

Causes of iron deficiency anaemia

A
  • Increased loss (e.g. chronic GI blood loss) (Most common)
    > Colon cancer
    > Gastric ulceration
    > NSAID/Aspirin use
  • Malabsorption (Coeliac, helicobacter pylori, gastrectomy)
  • Increased need (pregnancy, growing children)
  • Dietary deficiency (rarer)
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18
Q

6 Signs and 5 symptoms of Iron Deficient Anaemia

A
  • Pallor
  • Conjunctival pallor
  • Atrophic Glossitis (smooth tongue due to atrophy of papillae on surface of tongue)
  • Koilonychia (spoon shaped nails)
  • Angular cheilosis (mouth corner ulcers)
  • Dry rough skin

Dyspnoea, fatigue, headache, restless leg syndrome

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19
Q

Investigations of iron deficient anaemia

A

1st - FBC -> low MCV, low Hb (MICROCYTIC)

Serum iron
Serum ferritin
Transferrin saturation (serum iron/total iron binding capacity) ALL LOW

TIBC will be high (negative correllation)

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20
Q

Signs specific to iron deficiency anaemia

A

Pica - Cravings for non food items as food
Hair loss
Restless leg syndrome

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21
Q

Why is acid required for iron absorption?

A

Stomach acids keep iron in soluble Fe2+ form. When acid drops it changes to Fe3+, which is insoluble

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22
Q

Management of iron deficient anaemia with side effects

A

Treat underlying cause

  • Oral iron supplements: ferrous sulphate, ferrous fumarate
    Side effects: constipation, diarrhoea, nausea, black stools
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23
Q

Pernicious anaemia definition with MCV and pathophysiology

A

B12 deficiency due to autoimmune destruction of intrinsic factor (megaloblastic)

Intrinsic factor is secreted by parietal cells and is essential for absorption of B12 in ileum. Antibodies form against intrinsic factor or parietal cells, causing atrophy of gastric mucosa, preventing absorption of vitamin B12.

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24
Q

Pernicious Anaemia Investigations

A

1st - FBC - macrocytic, megaloblastic anaemia (raised MCV)
Blood film - Hypersegmented neutrophils and oval macrocytes (both b12 and folate deficiency)
Serum cobalamin (B12) - decreased
Schilling test (B12 absorption test)

GOLD: Parietal cell and intrinsic factor antibodies

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25
Q

What does blood film show in B12 or Folate deficiency

A

Hypersegmented neutrophils and oval macrocytes

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26
Q

What is the Schilling test

A

test for pernicious anaemia; radiolabelled B12 given and absorption measured. Later repeated with IF administration to see if B12 absorption increases

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27
Q

Signs and symptoms of pernicious anaemia and folate deficiency

A

Main clinical features same in megaloblastic anaemia, except severe neuropathy only in B12

Pallor, dyspnoea, headache, tachycardia, tachypnoea, weakness, lethargy, glossitis (inflammation of tongue),

Peripheral neuropathy: Personality changes, incontinence, paraesthesia, ataxia (loss of control of body movements), optic neuropathy.

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28
Q

Associated symptoms/conditions of pernicious anaemia

A

Myxoedema
Thyroid disorders
Addisons
Stomach cancer
Vitiligo

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29
Q

Management of pernicious anaemia

A

Treatment of underlying cause
B12 supplementation - Oral cyanocobalamin or IM hydroxycobalamin
Folic acid (should never be given without B12, prevent degeneration of spinal cord)

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30
Q

What can occur if a folate deficiency is corrected before a B12 deficiency?

A

Subacute combined degeneration of the spinal cord

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31
Q

What causes macrocytosis without anaemia?

A

Alcohol

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32
Q

Pathophysiology of sickle cell anaemia

A

Autosomal recessive gene mutation on beta globin chain (where valine replaces glutamic acid on 6th amino acid) causes “HbS” variant. (HBB gene on chromosome 11)

Under stress (infection, hypoxia, dehydration, acidosis, cold temperature), RBCs sickle, and HbS polymerises, leading to haemolysis or capillary obstruction (sickle cell crises).

initially, they can return to normal shape but eventually lose membrane flexibility and remain sickled.

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33
Q

Sickle cell disease’s relation to malaria

A

Sickle cell is more common in Africa, India, Middle East. Sickle cell trait (one copy of the gene) reduces severity of malaria. Selective advantage to having sickle cell trait in areas with malaria.

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34
Q

What are classic signs of any haemolytic anaemia?

A

Jaundice, Scleral icterus (yellow pigment of eyes), gallstones

(caused by haemolysis releasing bilirubin into the blood)

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35
Q

How is sickle cell screening conducted?

A

Guthrie heel prick test on newborns at 5 days of age

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36
Q

What does SCT screening screen for?

A

Sickle cell
Thalassaemia
Haemoglobin disorders

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37
Q

What are the 4 sickle cell crises

A
  1. Sequestration Crisis. RBCs sickle in spleen. Abdominal pain secondary to splenomegaly. Autosplenectomy.
  2. Aplastic crisis. Infection with parovirus B19 causes bone marrow suppression. causing sudden onset pallor, fatigue, anaemia. Reduced reticulocyte count.
  3. Haemolytic crisis - jaundice
  4. Vaso-occlusive crisis - seperate card
    (+Acute chest syndrome - acute cough, chest pain, dyspnoea)
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38
Q

Signs and symptoms of sickle cell anaemia and of its crises

A

Anaemia symptoms and jaundice (haemolytic!), worse after stressors
- Various crises, causing autosplenectomy/splenomegaly, bone and chest pain. (NB femoral head susceptible to avascular necrosis)
- Dactylitis
- Priapism

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39
Q

Signs of the vaso-occlusive crises in different areas in sickle cell anaemia.

Bone, ACS, Spleen, CNS, Genitalia

A

Bone - Dactylitis, Avascular necrosis, osteomyelitis
Lungs - Acute chest syndrome. Dyspnoea, chest pain, hypoxia. New chest infiltrates
Spleen - auto splenectomy, splenomegaly
CNS - Stroke
Genitalia - Priapism - prolonged, painful erection

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40
Q

Investigations for sickle cell anaemia

A

1st - Newborn screening - guthrie heel prick
- FBC - normocytic anaemia with reticulocytosis (young RBC)
- Blood film - Sickled RBCs, Howell-Jolly bodies
- GOLD: Hb Electrophoresis - HbS chains with absent HbA
- Sickle cell solubility test - HbS insoluble plasma goes cloudy

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41
Q

What investigations may be helpful in sickle cell crises

A

Sputum/ blood cultures
Arterial blood gas
FBC
Liver function test

Chest or bone X ray

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42
Q

Management of sickle cell crises

A

HYDRATION! (IV fluids to prevent sickling)
Analgesia
Oxygen
Antibiotics if infective crisis
Blood transfusion if severe anaemia

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43
Q

General management of sickle cell disease

A
  • Hydroxycarbamide (stimulates HbF (foetal haemoglobin), which does not sickle)
  • Prophylactic phenoxymethylpenicillin in children
  • Pneumococcal vaccine
  • Haematopoietic stem cell transplant Last resort
  • Blood transfusions (risk of iron overload so iron chellation must be done too)
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44
Q

Define thalassaemia and give it’s epidemiology

A

Autosomal recessive haemoglobinopathy that causes a microcytic anaemia. Prevalent in areas of malaria (Mediterranean, south Asian, African) as thalassaemia protective against it. (selective advantage)

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45
Q

Pathophysiology and subtypes of alpha thalassaemia

A

Autosomal recessive, leads to deletions of up to 4 alpha genes on chromosome 16 (2 on each)

1 deletion - Silent carrier

2 deletions - Alpha thalassemia minor/trait. Mild symptoms.

3 deletions - Haemoglobin H (HbH) disease. HbH has 4 beta chains (inability to produce alpha chains). Moderate anaemia, HbH cause

4 deletions - Hb Bart’s Hydrops Fetalis syndrome (Alpha thalassaemia major). Hb has high affinity for O2 so tissues not oxygenated. Cardiac failure and massive hepatosplenomegaly causes oedema all over (Hydrops fetalis). Fetus usually dies before birth or in first year.

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46
Q

How does severe hypoxia lead to splenomegaly

A

Hypoxia causes bone marrow, liver and spleen to increase RBC production. Causes enlargement of liver, spleen and bone marrow.

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47
Q

Pathophysiology of beta thalassaemia

A

Autosomal recessive point mutations on 2 beta genes on chromosome 11, causing impaired or absent beta chain synthesis.

1 partially or completely defective gene (Bᵀ B) - Beta Thalassaemia Minor (trait). Asymptomatic or mild/absent anaemia.

2 partially defective genes or 1 and 1 completely defective(Bᵀ Bᴼ). - Beta Thalassaemia intermedia. Moderate anaemia, splenomegaly

2 completely defective genes (Bᴼ Bᴼ) - Beta Thalassaemia Major. Complete absence of beta globin, severe anaemia and lifelong transfusion is needed. Hepatosplenomegaly.

Free alpha chains accumulate in RBCs and damage membrane -> Haemolysis, causing jaundice and secondary haemochromatosis

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48
Q

Why does thalassaemia sometimes not present at birth?

A

HbF is still in the circulation at first.

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49
Q

Signs/symptoms of thalassaemia

A
  • Chipmunk facies (more in beta) - enlarged forehead/cheeks due to extramedullary haematopoiesis
  • Hair on end appearance on X ray
  • Growth retardation
  • Hepatosplenomegaly
  • Jaundice
    (OEDEMA IN Hb Barts (Hydrops fetalis))

Anaemia symptoms: Pallor, palpitations, fatigue, failure to thrive

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50
Q

Investigations in Thalassaemia

A

FBC - Microcytic, hypochromic (less Hb=less oxygen) anaemia. High iron/ferritin

Blood film: Microcytic, hypochromic RBC. Target cells

Hb electrophoresis (GOLD): HbH (beta tetramers) in alpha, HbA2 in beta thalassaemia (+ low HbA)

Skull X ray: Hair-On-End appearance.

Genetic testing also diagnostic

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51
Q

Management of thalassaemia

A
  • Blood transfusions
  • Iron chellation (oral deferiprone)
  • Splenectomy may be needed
  • Stem cell transplantation only curative option
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52
Q

Complications of thalassaemia

A

GASH

Gallstones
Aplastic crisis (parovirus B19)
Secondary haemochromatosis
Hypersplenism

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53
Q

Microcytic anaemias

A

Iron deficiency
Alpha/beta thalassaemia
Sideroblastic anaemia

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54
Q

Normocytic anaemias

A

Haemolytic
- Sickle cell
- Hereditary spherocytosis
- G6PD Deficiency
- Malaria
- Autoimmune haemolysis

Non haemolytic
- CKD
- Aplastic

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55
Q

Macrocytic anaemias

A

Megaloblastic
- B12 and folate deficiency
Non megaloblastic
- Hypothyroid, Alcohol excess, liver disease

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56
Q

Sideroblastic anaemia definition, inheritance pattern and blood film result

A

Defective Hb synthesis causes defective RBCs that cant carry oxygen as well (sideroblasts). X linked recessive, or acquired.

Functional Fe deficiency (serum high but not used in Hb synthesis)

Blood film: Microcytic w/ Ringed sideroblasts and basophilic stippling.

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57
Q

Define G6PD deficiency

A

X linked deficiency of Glucose-6-Phosphate Dehydrogenase enzyme, making RBC more susceptible to damage by oxidation

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58
Q

Role of G6PD normally

A
  • Free radicals produced by body which can damage RBCs through DNA, protein and cell membrane damage.
  • Glutathione acts as an antioxidant, donating an electron to free radicals, turning them into water and oxygen, but becoming oxidised itself.
  • Glutathione reductase uses NADPH to donate an electron back to glutathione and NADP+ is formed.
  • G6PD reduces NADP+ back to NADPH using a G6P (which is a metabolite of glucose, so we have lots of it).
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59
Q

Pathophysiology of G6PD

A

Defective G6PD enzymes produced with shorter half lives, leading to reduced NADPH and glutathione so RBCs are unprotected from free radical damage. Damaged Hb precipitate in cell to form Heinz Bodies and when spleen tries to remove this, it takes a bite out of the RBC, forming bite cells.

Bilirubin from haemolysis is converted to urobilin, giving urine a dark tea-like colour

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60
Q

Epidemiology of G6PD (2)

A

X linked so more common in men
Found in areas with malaria (Africa, Mediterranean, SE Asia)

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61
Q

Common triggers of G6PD

A

Fava beans
Soy products
Red wine
Metabolic acidosis
Infections (pneumonia, sepsis)
Malaria drugs (chloroquines)

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62
Q

Signs and symptoms of G6PD

A

Asymptomatic until exposed to oxidative trigger

  • Jaundice
  • Dark Tea-coloured urine (urobilin)
  • Back pain (indicates kidney damage + urine)
  • Splenomegaly
  • Anaemia symptoms (Pallor, fatigue, tachycardia, dizziness, palpitation )
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63
Q

Investigations in G6PD

A

FBC: Low RBC, High reticulocyte
Blood film: Heinz bodies, bite and blister cells
Unconjugated bilirubin: high

GOLD: G6PD enzyme assay

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64
Q

Management of G6PD

A

Avoid triggers, transfusion if severe.

Epoetin alfa if kidneys damaged

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65
Q

Define hereditary spherocytosis

A

Autosomal dominant (can be recessive) haemolytic anaemia caused by a defect in spectrin and ankyrin (membrane proteins) causing RBCs to become spherical.

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66
Q

Key signs of hereditary spherocytosis

A

Neonatal jaundice
Splenomegaly
Anaemia symptoms

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67
Q

Investigations and diagnostic criteria in hereditary spherocytosis

A

FBC - Normocytic anaemia AND raised MCHC (mean corpuscular haemoglobin concentration)
Blood film - Spherocytes
High bilirubin and urobilinogen

Diagnostic criteria
- Family history
- Typical features
- Positive lab findings (Spherocytes, Raised MCHC)

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68
Q

Treatment of hereditary spherocytosis

A

Splenectomy
(Lifelong penicillin to prevent post-splenectomy sepsis)
Blood transfusion + Folic acid

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69
Q

Classifications (3 categories) of autoimmune haemolytic anaemia

A

Extrinsic - Immune system attacks RBCs
Intrinsic - RBCs have a defect

Extravascular - Destruction by spleen/liver (so normal haptoglobin)
Intravascular - RBC destruction within blood vessels

Warm - Haemolysis at 37C (IgG antibodies) (most common)
Cold - Haemolysis at 0-10C (IGM antibodies)

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70
Q

3 consequences of intravascular RBC destruction

A

1) Jaundice - Unconjugated bilirubin in blood
2) Tea-like urine - Unconjugated bilirubin in blood converted to urobilin by liver
3) Kidney disease - Hb broken down to Haemosiderin which is deposited in renal tubular cells

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71
Q

Signs and symptoms of AHA

A

Pallor
Jaundice
Fatigue
Shortness of breath
Hepatosplenomegaly (Extravascular)
Oliguria (Renal insufficiency - long term intravascular)

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72
Q

Investigation and treatment in AHA

A

Coombs test positive (agglutination test)
IgG and CD3 = Warm
CD3 alone = cold

Steroids/splenectomy

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73
Q

Patient presents with recent travel and fever what should you suspect?

A

Malaria

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74
Q

Define malaria

A

Notifiable protozoal parasitic infection of Plasmodium genus protozoa

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75
Q

5 protozoa species that cause malaria, and the one that causes complicated malaria

A

P. falciparum (most common and causes complicated)
P. ovale
P. vivax
P. malariae
P. knowlesi

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76
Q

Pathophysiology of malaria

A

Protozoal infection transmitted by female Anopheles mosquitos.

Sporozoite in mosquito’s salivary glands transmitted through bite into persons bloodstream, where they travel to the liver. They reproduce asexually here, killing hepatic cells and maturing into merozoites. They then enter the blood and invade RBCs, maturing into gametocytes, which reproduce sexually. Spleen detects most of these and destroys them, causing haemolytic anaemia.

P. falciparum generates a sticky protein that causes RBCs to clump together, occluding small vessels. This blocks blood flow, infected cells cannot reach spleen, and also causes organ failure.

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77
Q

Signs and symptoms of malaria

A

Signs:
- Anaemia
- Jaundice
- Hepatosplenomegaly
- Blackwater fever (malarial haemoglobinuria)

Symptoms:
- Fever
- Chills
- Headache
- Fatigue
- Diarrhoea
- Vomiting

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78
Q

Investigations in malaria

A

1st and GOLD: blood film
Thick - locates parasites (malaria?)
Thin - identifies Plasmodium species and identifies % of cells infected (species?)

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79
Q

Features of complicated malaria

A
  • Cerebral (vascular occlusion, coma etc)
  • Acute respiratory distress syndrome
  • Renal failure (proteinuria, haematuria)
  • Bleeding
  • Shock
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80
Q

What protozoa most likely to cause relapse in malaria and why?

A

P ovale and vivax

can form hypnozoites in liver, which emerge later

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81
Q

Preventative measures in malaria

A

Full body clothing
Insecticide treated bed nets
Prophylaxis (chloroquine) before travel to endemic areas
Indoor insecticide sprays
Empty stagnant collections of water

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82
Q

Treatment of malaria

A

Complicated: IV artesunate (quinine+doxycycline)

Uncomplicated: Fluids
- Chloroquine - treat acute infection
- Primiquine - kill hypnozoites

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83
Q

Define aplastic anaemia

A

Pancytopenia (deficiency of all 3 blood components, RBC, WBC, platelets) where bone marrow fails and hemopoietic stem cell production halts.

Leads to anaemia, leukopenia, thrombocytopenia

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84
Q

Give causes of aplastic anaemia

A

Idiopathic
Radiation
Infection (EBV, parovirus B19)

85
Q

investigations in aplastic anaemia

A

FBC - anaemia, thrombocytopenia, leukopenia
BM biopsy - low haematopoietic stem cells
Erythropoietin - raised

86
Q

Signs of aplastic anaemia

A

Anaemia symptoms +
Increased bleeding
Chest pain/SOB
Reccurent infections

87
Q

How does CKD cause anaemia

A

Reduced Erythropoietin production by kidneys

88
Q

Risk factors for folate deficiency

A
  • Elderly
  • Poverty
  • Alcohol
  • Pregnancy
  • Crohns or coealiac
  • Malnutrition
89
Q

Define folate deficiency

A

Deficiency in folate (vitamin B9) causing a macrocytic megaloblastic anaemia

90
Q

Pathophysiology of folate deficiency

A

Folate is a cofactor in amino acid metabolism and DNA/RNA synthesis

DNA impairment affects bone marrow a lot (as it divides most) leading to pancytopenia.

Folate also essential for foetal development, can lead to neural tube defects (Spina bifida)

91
Q

Signs/symptoms of folate deficiency

A

Pallor
Fatigue
Dyspnoea
Headache
Pancytopenia features
NO NEUROPATHY (There is in B12 deficiency)

92
Q

Differentials to rule out in folate deficiency

A

B12 deficiency
Aplastic anaemia

93
Q

Treatment of folate deficiency

A

Folic acid tablets
- Always give with B12 unless confirmed B12 normal. Correcting folate with low B12 can cause neurological disease

94
Q

Causes of folate deficiency

A

Poor intake (poor, alcoholic, elderly)
Increased demand (pregnancy, haemolysis)
Malabsorption disease (Crohns, coeliac)
Antifolate drugs (methotrexate, trimethoprim)

95
Q

Non megaloblastic, macrocytic causes of anaemia

A
  • Hypothyroidism
  • Alcohol excess (toxic to RBC, depletes folate)
  • Liver disease
96
Q

What is leukaemia

A

The uncontrolled proliferation of non functional blood blast cells. Leukaemia cells divide rapidly and take up space in the bone marrow, less energy and space available for normal cells. The lack of functioning blood cells leads to leukaemia symptoms, and increased infection and bleeding risk

97
Q

General leukaemia symptoms

A

Bone pain, bleeding, bruising, infections, anaemia
- Lymphadenopathy and lymph node pain
- Petechiae (red dots under skin) or petechial rash
- Hepatosplenomegaly
- Easy bruising
- Fatigue
- Weight loss
- Fever

98
Q

mnemonic to help remember ages of leukaemia onset

A

ALL CeLLmates have CoMmon AMbitions

ALL - under 5 and over 45
CLL - Over 55
CML - Over 65
AML - Over 75

99
Q

Define acute lymphoblastic leukaemia with epidemiology

A

Proliferation of lymphoblasts (mostly B cell). Associated with Down syndrome, radiation and t(12;21). Bimodal age distribution, first peak (75% of cases) at 5 years old, second at 50. In T cell ALL, thymus enlargement may be seen

100
Q

Investigations in ALL

A

FBC - anaemia, thromocytopenia, leukocytosis (High WBC, low everything else)
Blood film - Lymphoblasts
Nuclear TdT staining - positive

Bone marrow aspiration GOLD - At least 20% bone marrow infiltration

101
Q

Treatment of ALL

A

1 - Supportive with blood and platelet transfusions. IV fluids and a hickman line.
2 - Chemotherapy + Allopurinol (prevent tumour lysis syndrome)
First with prednisolone (4-8 weeks then high dose chemo)

102
Q

Complications and poor prognostic factors of ALL

A

Myelosuppression
Neutropenia/Neutropenic sepsis

Age <1 year or >10 years
t(9;22)
Hypodiploidy
Adult relapse

103
Q

Complications of chemotherapy

A

Stunted growth in children
Tumour lysis syndrome
Infertility
Neurotoxicity
Infections/immunodeficiency
Neutropenia

104
Q

Chronic lymphocytic leukaemia definition and epidemiology

A
  • Neoplastic proliferation of partially/ fully mature B lymphocytes.
  • Most common adult leukaemia
  • Can present asymptomatically due to gradual onset, noticed during FBC
  • Causes general leukaemia symptoms + non tender lymphadenopathy and splenomegaly
105
Q

Investigations in CLL

A
  • FBC - anaemia, thrombocytopenia, lymphocytosis
  • Blood film - Smudge cells (aged or fragile WBCs rupture to leave smudge) + spherocytes if active haemolysis
  • Flow cytometry - Positive markers for CLL e.g. CD5, CD19, CD20, CD23
  • Immunoglobulins - Low (B cells dont fully differentiate into plasma cells)
106
Q

Treatment of CLL

A

Early stage - Monitoring using FBC every 3-12 months

Late stage - Chemotherapy + allopurinol.
Radiotherapy may help lymphadenopathy
Stem cell transplant and Ig transplant
Blood transfusion

107
Q

Complications of CLL

A

Richter transformation - Transformation into a high grade non-Hodgkin lymphoma. (Rapid progressing lymphadenopathy, fever night sweat weight loss (B), raised LDH

Autoimmune haemolytic anaemia

Small lymphocytic lymphoma (Cells move to lymphatic system and settle at nodes)

Hypogammaglobulinaemia

108
Q

Signs and symptoms of leukaemia

A

Bone pain, bleeding, bruising, infections, anaemia
- Lymphadenopathy and lymph node pain
- Petechiae (red dots under skin) or petechial rash
- Hepatosplenomegaly
- Easy bruising
- Fatigue
- Weight loss
- Fever

109
Q

Acute myeloid leukaemia definition, subtypes and epidemiology

A
  • Neoplastic proliferation of myeloblasts, with important subtypes;
  • APML - t(15;17) promyelocyte accumulation with Auer rods. Can cause DIC.
  • Acute monocytic leukaemia - Monoblast accumulation without Auer rods. Gums infiltrated.
  • Affects older people, most common over 75s.
  • Associated with Pataus (trisomy 13), Downs (trisomy 21) syndrome, benzene + radiation exposure
110
Q

Symptoms specific to AML

A

Mouth ulcers
DIC (APML)
Gum infiltration/ hypertrophy

111
Q

Investigations in AML

A

FBC - Low RBC, platelets. High WBC
Blood film - Blasts and Auer Rods
Bone marrow aspiration - >20% infiltration into bone marrow
Immunophenotyping - checks cell lineage, confirms AML

112
Q

Management in AML

A
  • IV Fluid via hickman line
  • Chemotherapy + Allopurinol (prevent tumour lysis syndrome)
  • All-trans retinoic acid in APML, allows blasts to mature into neutrophils
  • BM transplant
113
Q

Define APML with pathophysiology

A

Acute ProMyelocytic Leukaemia (t15;17)

Disrupts retinoic acid receptor, promyelocytes can’t differentiate

114
Q

What are Auer rods

A

Aggregates of myeloperoxidase found in AML that increase risk of clotting (DIC)

115
Q

Patient with AML suddenly has lots of blood clots, what complication has occured

A

Disseminated Intravascular Clotting

116
Q

CML definition and pathophysiology

A

Uncontrolled proliferation of myeloid cells - usually granulocytes. Associated with t(9;22) - PHILADELPHIA CHROMOSOME.
- BCR-ABL genes fused, permanently activating Tyrosine Kinases, causing proliferation of myeloid cells. Rapid proliferation can lead to Acute Leukaemia (or Blast Crisis)

117
Q

Phases of CML

A

Chronic (asymptomatic) <10% blast cells
Accelerated (Further progression) 10-19% blast cells >20% basophils
Blast crisis (terminal phase, mimicks acute leukaemias) >20% blast cells, pancytopenia

118
Q

Signs of CML

A

Severe hepatosplenomegaly
Abdominal tenderness/fullness due to hepatosplenomegaly
May show features of gout due to purine breakdown

119
Q

Investigations in CML

A

FBC - Very high WCC across spectrum of myeloid cells, low Hb, high Urate
Blood film - Granulocytes
Cytogenetics - Philadelphia chromosome t(9;22)
LDH raised in leukaemia but unspecific

120
Q

Management of CML

A

Chemotherapy +- Allopurinol
Tyrosine kinase inhibitor (Imatinib)

Stem cell transplant if severe or if goes to blast phase

121
Q

Define myelodysplasia/ myelodysplastic syndrome

A

Dysplasia of myeloblasts in bone marrow but less than 20% infiltration. Causes cytopenia meaning death usually due to infection/bleeding. Increase in blast % causes progression to acute leukaemia

122
Q

Define lymphoma and give the two types with their differences

A

Neoplastic proliferation of lymphoid cells (B cells).
- Hodgkins (has Reed-Sternberg cells, spread is contiguous (one node to next) and effects rarely extra nodal)
- Non-Hodgkins (No RS cells, non contiguous spread and goes extra nodal (GI, skin, brain etc)

123
Q

Risk factors and epidemiology for Hodgkins lymphoma

A
  • EBV infection history
  • Family history of lymphoma
  • Post transplant
  • HIV
  • Bimodal (15-35 and >60)
124
Q

Subtypes of Hodgkins lymphoma

A
  • Nodular sclerosing: most common
  • Nodular lymphocyte predominant (popcorn cells - RS variant)
  • Lymphocyte rich
  • Lymphocyte depleted (worst prognosis)
  • Mixed cellularity
125
Q

Risk factors and epidemiology for Hodgkin’s lymphoma

A
  • EBV infection history
  • Family history of lymphoma
  • Post transplant
  • HIV
  • Bimodal (15-35 and >60)
126
Q

Signs/ symptoms of Hodgkin’s lymphoma

A

Lymphadenopathy (usually cervical, axillary, inguinal)
- Fixed, hard, rubbery, painless(!). Spread is contiguous
Splenomegaly
Alcohol induces lymph node pain

B symptoms
- Fever, night sweats, weight loss
Pruritus (itching)

127
Q

Staging/classification used for lymphoma

A

Ann-Arbor (1,2,3,4/A,B)
1 - 1 region of lymph nodes affected
2 - 2 or more, same side of diaphragm
3 - Involvement on both sides of diaphragm
4 - Widespread involvement including organs

A - No B symptoms
B - B symptoms

128
Q

Pathology associated with Classical and nodular sclerosing Hodgkin’s lymphoma

A

Classical - usually painless cervical lymphadenopathy
NS - Mediastinal lymphadenopathy, which may cause cough, chest pain and may compress superior vena cava, dilating neck veins and increaing JVP

129
Q

Investigations in Hodgkin’s lymphoma

A

FBC - Low Hb/platelets
CXR - Mediastinal lymphadenopathy and widened mediastinum can be used for Ann Arbor.
PET-CT Scan of thorax/abdomen/pelvis - Staging
Lymph node biopsy GOLD - Reed sternberg cells

130
Q

Differentials for lymphoma

A

Hodgkin’s/non hodgkin’s
Lymphadenopathy from other malignancies
Infectious Mononucleosis (glandular fever) - enlarged, tender lymph nodes, sore throat. Usually due to EBV

131
Q

Management of Hodgkin’s lymphoma

A

1A-2A - ABVD chemotherapy
- Adriamycin
- Bleomycin
- Vinblastine
- Dacarbazine

2A-4B - Longer courses of chemotherapy and radiotherapy

132
Q

Complications of radiotherapy and chemotherapy treatment

A

Radio - Hypothyroid, lung fibrosis, secondary malignancy
Chemo - Myelosuppression, Nausea, Alopecia, Infertility

133
Q

Define Non Hodgkin’s lymphoma

A

All lymphomas without Reed-Sternberg cells. Can spread extra nodally (skin, stomach, GI tract, bone marrow, spinal cord). Usually due to a genetic mutation in lymphocyte.

134
Q

Give 3 types of B cell origin Non Hodgkin’s lymphoma

A
  • Diffuse Large B cell Lymphoma (DLBCL) ⇒ Most common & High Grade (aggressive)
  • Follicular Lymphoma ⇒ Low grade (slow)
  • Burkitt Lymphoma ⇒ HIGHLY aggressive with starry sky appearance on microscope (usually associated with EBV in Africa, with extra nodal involvement including jaw. Outside of Africa, abdomen more common)
135
Q

Signs/symptoms of Non-Hodgkin’s lymphoma

A
  • Fixed, hard, rubbery, painless lymphadenopathy. Spread is non-contiguous
  • May have extra nodal manifestations
  • Hepatosplenomegaly (more common in NHL)

B symptoms
Fever, night sweats, weight loss

136
Q

Extra nodal manifestations in NHL

A

Skin - lesions and itching
GI tract - Bowel obstruction
Spinal cord - Compression, loss of sensation
BM - Pancytopenia

137
Q

Investigations in NHL

A

FBC - pancytopenia if BM affected
LDH - Increases as prognosis worsens (increased cell turnover/proliferation)
Lymph node biopsy GOLD - No reed-sternberg/popcorn cells
CXR, PET of chest, abdomen, pelvis - for staging
Lumbar puncture to check for CNS involvement

138
Q

Treatment of Non-Hodgkin’s lymphoma

A

Rituximab + Chemotherapy (R-CHVP)

Rituximab (mAB - targets CD20 on B cells)
C - cyclophosphamide
H - hydroxydaunorubicin
V - Vincristine
P - Prednisolone

Intrathecal Methotrexate for prophylaxis

Low grade may not need treatment

139
Q

Treatment of Non-Hodgkin’s lymphoma

A

Rituximab + Chemotherapy (R-CHVP)

Rituximab (mAB - targets CD20 on B cells)
C - cyclophosphamide
H - hydroxydaunorubicin
V - Vincristine
P - Prednisolone

Intrathecal Methotrexate for prophylaxis in CNS involvement

Low grade may not need treatment

140
Q

Define Multiple Myeloma with epidemiology

A

Cancer of differentiated B lymphocytes (plasma cells)
70+ years, Afro-Caribbeans

141
Q

Pathophysiology of Multiple Myeloma

A

Neoplastic plasma cells release abnormal antibodies consisting only of paraprotein light chains. Light chains can form amyloid proteins, causing amyloidosis. CRAB symptoms
C - Calcium - Hypercalcaemia caused by neoplastic cells releasing cytokines, activating osteoclasts via RANK receptor. Causes bone resorption.
R - Renal insufficiency - nephrocalcinosis and deposition of free light chains (Bence Jones proteins) in kidney tubules disrupt renal function. Results in Bence Jones proteins in urine.
A - Anaemia. Bone marrow infiltration causes reduced haematopoiesis. Pancytopenia
B - Bone pain. Bone lesions, fractures and pain caused by Osteoclast activation, inhibits osteoclast inhibition and suppresses osteoblasts. Common in skull, spine, long bones, ribs.

142
Q

Signs/symptoms of Multiple myeloma

A

OLD Crab
70 +
- hyperCalcaemia symptoms: Bones, stones, abdominal moans, psychiatric groans
- Renal insufficiency: Urinary frequency + Bence Jones in urine
- Anaemia - Fatigue, SOB, tachycardia
- B - Bone pain (especially back)

143
Q

Investigations in Multiple Myeloma

A
  • FBC normocytic, normochromic
  • Blood film - Rouleaux formation

Urine:
- Urine dipstick - Bence Jones protein
- Urine electrophoresis - Paraprotein band or “M” spike (IgG/IgA)

  • Bone Marrow Aspiration GOLD - >10% monoclonal plasma cells in BM

Imaging:
- Full body MRI to determine BM infiltration and find lesions
- Imaging using CXR - Skull/spine etc. Raindrop skull, Osteolytic lesions

144
Q

Diagnostic criteria in multiple myeloma

A

One or more biomarkers
- BM plasma cells >10%
- >1 focal lesion on MRI
- involved : uninvolved free light chain ratio >100

or
CRAB end organ damage

145
Q

Treatment of Multiple Myeloma

A

Supportive then. Chemotherapy +- stem cell transplant
- No NSAID (renal impairment)
- Bisphosphonate (suppress osteoclast activity, reduce fracture)
- Anaemia correction
- DVT prophylaxis - LMWH or aspirin

Chemotherapy:
<70 - bortezomib, thalidomide and dexamethasone
>70 - bortezomib, prednisolone and melphalan

146
Q

Complications of Multiple Myeloma

A
  • Fractures
  • Chronic pain
  • Hyper viscosity
  • Renal failure
  • Pancytopenia
  • Recurrent infections
147
Q

Risk factors for HIV

A
  • Regular unprotected sex
  • IV drug use/needle sharing
  • Blood transfusion
  • Parent with HIV (vertical transmission)
148
Q

Define HIV with types/epidemiology

A

HIV is a retrovirus (RNA virus) that infects cells of immune system (CD4+ cells; T helper cells, macrophages, dendritic cells). This causes immunodeficiency leading to AIDS (Acquired ImmunoDeficiency Syndrome)

Two main strains
HIV-1: Most common/virulent
HIV-2: West Africa, better outcomes

149
Q

What 3 ways is HIV transmitted?

A
  • Sexual (Male on male particular risk)
  • Parenteral (needlestick/ needle sharing)
  • Vertical (breastfeeding/vaginal delivery)
150
Q

Pathophysiology of HIV

A

HIV use gp120 to bind to CD4 on immune cells. It uses this and a coreceptor (e.g. CXCR4 on T cells or CCR5 on macrophages) to allow it to inject it’s single RNA strand into the cell.

The virion’s RNA is transcribed to dsDNA using reverse transcriptase which is integrated into the host DNA. As a result, the immune cell transcribes and translates new HIV viruses.

HIV replication is flawed, and makes many variants (e.g. R5 strain which binds to CCR5 on macrophages)

151
Q

Phases of HIV infection

A

Acute infection (12 weeks): rapid viral reproduction causing flu like symptoms. Viral load is high and antibodies are produced, causing viral load to drop and symptoms to subside.

Chronic (latent) phase (2-10 years): Virus increases slowly whilst T cells slowly decrease. Opportunistic infections can develop but CD4 count stays over 500 cells/mm³ so can be fought off. As this drops, more AIDS-like symptoms develop.

Late stage HIV/AIDS: CD4 count drops <200mm³, with dramatic increase in viral load and development of AIDS-defining illness.

152
Q

Symptoms of HIV/AIDS

A

Acute (CD4>500/mm³)
- Flu like (malaise, fever, sore throat, diarrhoea, maculopapular rash)

Chronic/latent (CD4 500-200 mm³)
- Fever
- Persistent lymphadenopathy
- Opportunistic infections such as EBV (causing hairy leukoplakia) or oral candidiasis (NON DEFINING)
- TB can reactivate

AIDS defining
- persistent fever, fatigue, weight loss, diarrhoea, visual loss
- Presence of AIDS defining conditions

153
Q

AIDS defining conditions

A

Infections body can normally fight off
- Recurrent bacterial pneumonia
- Pneumocystis pneumonia
- Fungal infection (candidiasis)
- Cytomegalovirus
- TB

Tumours
- Kaposi sarcoma (skin lesions!)
- Non Hodgkins lymphoma

154
Q

Investigations in HIV

A

Investigations must be confirmed

1st
- HIV antibody test (false negative for 3 months after initial exposure)
- p24 antigen test
Any negative testing requires repeat after 3 months

Confirmatory
- Repeat p24 or antibody test or use Western blot (detects p24, gp120, gp41)

155
Q

How is HIV screened for

A

Antibody tests in those who present with infectious disease

156
Q

How is HIV monitored

A
  • CD4 count (1200-500 normal, 500-200 latent, <200 AIDS). Lower = greater risk of opportunistic infection
  • Viral load (HIV RNA per ml of blood) Undetectable <50 copies per ml. Left untreated this number can reach 100,000s
157
Q

Treatment of HIV with additional prophylaxis

A

Antiretroviral - aim to increase CD4 count

  • 2 Nucleoside reverse-transcriptase inhibitors (NTRI) + protease inhibitor or non nucleoside reverse-transcriptase inhibitor

Additional prophylaxis:
- Co-trimoxazole prophylaxis against pneumocystis jirovecii pneumonia
- Vaccinations
- Condom usage
- C section and breastfeeding cessation in pregnancy

158
Q

Define polycythaemia

A

Erythrocytosis - A high concentration of Red Blood Cells in blood, causing an increase in PCV (Packed cell volume - proportion of cells in blood volume)

159
Q

Give secondary causes of polycythaemia

A
  • Obstructive sleep apnoea
  • COPD
  • Alcohol
  • Dehydration
  • Hypoxia
  • Increased Erythropoietin
160
Q

Define polycythaemia vera

A

JAK2 mutation causing increased numbers of RBCs in blood. PCV and haematocrit increase.

PCV - Packed cell volume: proportion of cells in blood volume
Haematocrit - Proportion of RBCs in haematocrit

161
Q

Pathophysiology of polycythaemia vera

A

Normally, kidneys release erythropoietin which binds to haematopoietic stem cells and activates the JAK2 (Janus Kinase 2) gene, causing division into RBC

In mutation, JAK2 always active, and division occurs even without erythropoietin. This causes increased RBCs most of all, but also increased neutrophils and platelets, causing hyper viscosity.

162
Q

What can polycythaemia develop into, and how does it do this?

A

Myelofibrosis
- In time, these haematopoietic cells start to die out and scar tissue forms, causing bone marrow failure. This causes pancytopenia (anaemia+ thrombocytopenia+ leukopenia)
- Extramedullary haematopoiesis (production of blood outside of BM) occurs and splenomegaly or hepatomegaly can occur.

163
Q

signs/symptoms of polycythaemia

A

Signs
- Excessive itching, especially after a bath (due to increased basophils and mast cells releasing histamine)
- Erythromelalgia: Pain redness swelling in hands and feet
- Plethoric appearance
- Conjunctival plethora
- Splenomegaly

Symptoms
- Blurred vision
- headache
- Dizziness
- Increased sweating

164
Q

Investigations in polycythaemia vera

A

FBC - High Hb, RBC, WBC, platelet, haematocrit, PCV

Erythropoietin - Low/normal in primary, possible high in secondary

Bone marrow biopsy - look for fibrosis

Abdominal USS - Check for splenomegaly

GOLD: Cytogenetics: JAK2 gene mutation

165
Q

Management of polycythaemia vera

A

1 - Venesection (regular removal of blood, aim to bring haematocrit to normal)
Aspirin to prevent blood clots
Hydroxycarbamide can be given to reduce RBC
Ruxolitinib JAK2 inhibitor

166
Q

Complications of Polycythaemia

A
  • Gout and kidney stones -Increased cell turnover causes buildup of uric acid
  • Splenomegaly
  • Myelofibrosis!!
  • Leukaemia

Clotting related:
- Stroke
- MI
- DVT
- Budd-Chiari syndrome (liver veins are blocked by blood clot)

(also paradoxically has a bleeding risk)

167
Q

Define thrombocytopenia, and the 2 conditions that cause it

A
  • Low platelet count
  • Immune Thrombocytopenic purpura (ITP)
  • Thrombotic thrombocytopenic purpura (TTP)
168
Q

Define ITP with epidemiology

A

Immune thrombocytopenic purpura

Antibodies created against platelets, which bind to them causing them to be destroyed in the spleen. Can be primary or secondary

More prevalent in children and elderly. Women>men

169
Q

Signs/symptoms of ITP

A

Mostly asymptomatic, but in severe cases causes:
- Purpura/purpuric rash (red/purple spots beneath skin caused by bleeding under skin)
- Petechiae
- Easy and long bleeding
- Menorrhagia/nose bleeds

170
Q

Investigations in ITP

A

FBC - isolated thrombocytopenia (Leukocyte/haematocrit normal)

Blood film - Megakaryocytes and large platelets (if concurrent AHA, spherocytes present)

Abdominal ultrasound check for splenomegaly

171
Q

Treatment of ITP

A

Prednisolone and IV IgG

Splenectomy if severe

172
Q

Define TTP

A

Thrombotic thrombocytopenic purpura.

Tiny blood clots develop throughout small vessels using up platelets and causing thrombocytopenia, bleeding under the skin and systemic issues.

173
Q

Pathophysiology of TTP

A

Problem with ADAMTS13 protein (deficiency or autoimmunity against) means it cannot inactivate von Willebrand factor, which enables platelet adhesion. These clot in small vessels and said clots break up RBCs, causing haemolytic anaemia.

As it affects small vessels, it is known as a microangiopathy

174
Q

Signs/symptoms of TTP

A

5 classical symptoms
- Thrombocytopenia
- Microangiopathic haemolytic anaemia
- Fever
- Renal insufficiency causing haematuria and reduced output.
- Neurological symptoms (headache, confusion, seizures, focal abnormalities, coma)

also
Purpuric rash, bleeding.

175
Q

TTP vs ITP symptoms and how you get it

A

ITP usually well systematically, rashes and bleeding main symptoms. Acquired

TTP has systematic effects. Inherited

176
Q

Investigations in TTP

A

ADAMTS13 decreased

FBC - Thrombocytopenia and normocytic, normochromic microangiopathic anaemia

Blood film - Schistocytes (fragmented blood cells)

Unconjugated bilirubin and LDH raised
PTT/APTT normal

177
Q

Management of TTP

A

Plasmapharesis/plasma exchange

Prednisolone + Rituximab (monoclonal antibody against B cells)

178
Q

Side effect of heparin treatment that causes thrombocytopenia

A

Heparin induced thrombocytopenia

Antibodies against heparin form, targeting platelet factor 4 protein on platelets.

179
Q

Define glandular fever with its cause and its other name

A

Infectious mononucleosis
Caused by EBV and associated with Hodgkin’s, Burkitt’s and nasopharyngeal carcinoma

180
Q

Presentation of glandular fever

A

Classic triad
Fever, pharyngitis, lymphadenopathy

Usually presents in adults and young children

Shows atypical lymphocytes on blood film

181
Q

How does glandular fever spread and what are its complications

A

Spread through saliva (kissing, sexual activity)

Lifelong latent infection, can cause chronic fatigue

182
Q

Define haemophilia and give its 2 subtypes

A

Inherited severe bleeding disorders, both affect intrinsic pathway (increase APTT), causing decrease in function or quantity of clotting factors.
A - Deficiency in factor 8
B (Christmas disease) - Deficiency in factor 9

Prolongs clotting time, causing bleeding to be more severe.

183
Q

What are the causes of haemophilia

A

Inherited
- X linked recessive (A- F8 gene, B- F9 gene) ∴ mostly affects males!

Acquired
- Liver failure (liver responsible for many clotting factors)
- Vit K deficiency
- Autoimmunity against a clotting factor
- DIC

184
Q

Signs and symptoms of haemophilia

A
  • Spontaneous, excessive, inappropriate bleeding
  • Nose, gum, GI, urinary, intracranial bleeding for example
  • Easy bruising
  • Haemarthrosis (bleeding into joints)
185
Q

Investigations of haemophilia

A

PT - normal
APTT - Prolonged (these conditions only affect intrinsic pathway!)
F8/F9 assay to show deficiency

186
Q

Treatment of haemophilia

A

A: IV factor 8 + desmopressin (releases F8 stored in vessel walls)
B: IV factor 9

187
Q

von Willebrand disease definition

A

Autosomal dominant mutation of vWF gene on chromosome 12 causing deficiency, absence or abnormal functioning of von Willebrand Factor. This causes excessive bleeding

188
Q

vWF normal function

A
  • Basis of platelet plug, attaches to collagen fibres and enables platelet adhesion
  • Needed as a carrier for Factor 8, protecting it from degradation
189
Q

von Willebrand disease types

A

1 reduced/defective vWF

2 Quantity fine but quality affected
2A - unable to bind platelets
2B - binds to platelets in blood, causing thrombocytopenia
2N - Cant bind to factor 8

3 No production

190
Q

Investigations in vW disease

A

PT normal
APTT high
Normal F8/F9 (rule out haemophilia)
vWF low
Platelets normal except 2B

191
Q

Management of vW disease

A
  • Desmopressin stimulates release of vWF from Weibelpalade bodies
  • vWF and factor 8 infusion
192
Q

Define Disseminated Intravascular Clotting with pathophysiology

A

Haemostasis is process of balancing fibrin breakdown and deposition. In severe disease (Sepsis, malignancy, trauma, haemolysis) procoagulants released which tip in favour of clotting, leading to increased clotting around the body, causing organ ischaemia.

The depletion of platelets in this way means less available for actual bleeds so small damage leads to severe bleeding.

Leads to a patient with too much and also too little clotting

193
Q

Investigations in DIC

A

PT - prolonged
APTT - prolonged
Platelets - low
Fibrinogen - low
D-Dimer - increased (fibrin degradation product when fibrin clots broken down)

194
Q

Symptoms of DIC

A

Widespread ecchymoses
Bleeding from mouth and nose
Confusion
Bruising
Acutely ill and shocked patient

195
Q

Treatment of DIC

A

Treat underlying cause
Fresh frozen plasma transfusion
Blood transfusion
Platelet transfusion

196
Q

Define tumour lysis syndrome

A

Complication of chemotherapy that entails the release of intracellular components of tumour cells into the blood stream

197
Q

What does Tumour Lysis syndrome cause to build up in blood

A
  • Hyperkalaemia
  • Hyperphosphataemia (which causes hypocalcaemia)
  • Also DNA components such as purines and pyrimidines. Purine converted into hypoxanthine, xanthine then uric acid, which builds up in blood and can cause kidney injury (Hyperuricaemia)

Overall,
- Hyperkalaemia
- Hyperphosphataemia
- Hypocalcaemia
- Hyperuricaemia (causing kidney injury and gout)

198
Q

Complications and treatment of Tumour Lysis Syndrome

A
  • AKI (uric acid causes crystal deposition)
  • Hypocalcaemia and hyperkalaemia can cause neurological dysfunction (Tetany seizures, numbness, tingling, spasms)
  • Arrhythmias
  • Heart failure

Treated with Allopurinol

199
Q

Give all the causes of possible bleeding dysfunctions

A

Inherited (Haemophilia A,B, VW Disease)
Acquired (DIC)
Over anticoagulation
- Heparin (binds to antithrombin 3 and inactivates factor 10)
- Aspirin (COX inhibitor)
- Clopidogrel (P2Y12 inhibtor)
- Thrombolytic (alteplase)

200
Q

What clotting factors rely on vitamin K

A

10, 9, 7, 2

(1972)

201
Q

Warfarin MoA

A

Vitamin K antagonist (affecting factors 10, 9, 7 and 2)

202
Q

How does myelofibrosis normally present? What does it show on blood film?

A

Pancytopenia and massive splenomegaly in a patient with Polycythaemia vera history

Teardrop poikilocytes

203
Q

What are the 4 steps of platelet plug formation?

A

endothelial injury, platelet
adhesion, platelet aggregation

  • Damage to a blood vessel causes exposure of collagen. Von Willebrand Factor (vWF) binds to collagen which acts as a molecular anchor for platelets to join.
  • Platelets adhere to the damaged endothelium via vWF. When platelets adhere, they activate and degranulate– their shape changes and they release chemicals that keep the vessel constricted and draw more platelets to the damaged area. This positive feedback loop continues.
  • The aggregation of platelets results in the formation of a plug that temporarily seals the break in the vessel wall.
  • Following formation of the platelet plug, coagulation is activated to form a fibrin mesh which stabilises the platelet plug.
204
Q

What are the healthy INR ranges in a normal person and a person on anticoagulants?

A

Normal - 0.8-1.2
Anticoagulant - 2.0-3.0

(increased value = increased bleeding risk, decreased value = thrombosis risk)

205
Q

What 2 treatments are usually used to raise/lower INR?

A

Raise - Warfarin
Lower - Vitamin K

206
Q

How should INR be lowered in patient on anticoagulants?

A

INR > 5
- Withhold 1-2 doses of anticoagulant
INR > 8
- Stop anticoagulant
- Administer IV or oral vitamin K
- Repeat INR after 24 hours

207
Q

How should INR be lowered in patient on anticoagulants and bleeding?

A

Minor bleed
- Stop anticoagulants
- Administer IV vitamin K
- Repeat INR after 24 hours

Major bleed
- Stop anticoagulants
- Administer IV vitamin K
- Fresh frozen plasma or prothrombin complex

208
Q

How should low INR be managed, for patient on warfarin?

A

Increase warfarin and give LMWH

(LMWH is faster acting - remove when INR normal)

209
Q

How should patient on warfarin be managed pre surgery?

A

Stop warfarin 5 days before

  • Bridging with LMWH if VTE in past 3 months, atrial fibrillation, stroke or TIA, which is stopped 24 hrs before surgery. (unless major bleed risk, then 48)
  • Vitamin K day before surgery

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