Lecture 13: Thrombotic disorders

Question 1

What are the three components of Virchow’s triad?

Answer 1

• Vascular injury: Surgery, atherosclerosis, trauma
• Stasis: Immobility, viscosity etc
• Blood hypercoagulability: Increased procoagulants, decrease in inhibitors,

Question 2

What are the classic signs of DVT?

Answer 2

• Leg swelling
• Leg pain
• Oedema

Question 3

Classic signs of PE?

Answer 3

• Shortness of breath
• chest pain
• tachycardia
• tachypnoea

Question 4

Diagnosis of DVT?

Answer 4

• Undertake risk factor test (oedema, cancer, immobilisation etc etc)
• Low risk: Undertake D-dimer test. If high/+ve U/S.
  
  • If D-dimer low, discharge
• High risk: Ultrasound

Question 5

What is a D dimer test?

Answer 5

• D dimer is a degradation product of fibrin

- Shows whether a clot has recently been dissolved

Question 6

Causes of VTE ** exam??

note VTE is a disease that encompasess DVT and PE

Answer 6

30-40% spontaneous: of these, likely thrombophilia
Remainder are provoked events (see virchows triad): surgery/trauma, immobility, hospitalisation, malignancy (up to 20%), HRT/pregnancy, OCP, myeloproliferative disease, antiphospholipid

remember multi hit

Question 7

Thrombophilia

Answer 7

Either acquired, hereditary or both
Tendency to clot
Manifests as VTE

Question 8

Causes of inherited thrombophilla?

Answer 8

• Abnormal inhibitor function: resistance to activated protein c (factor V leiden)
• Deficiency of inhibitors: antithrombin, proteins C and S. Rare REMEMBER DO NOT AFFECT APTT
• Increased factor levels: Prothrombin gene mutation 20210A*

Question 9

What is the genetic abnormality in Factor V Leiden?

Answer 9

• Point mutation of A to G
• Creates factor V resistant to protein C cleavage
• mutation means ＿ C cannot cleave, Xa lasts longer. Va layers will be higher.
• 4% of Northern Europeans *

Question 10

Why test for APCr?

Answer 10

Heterozygote 3-7 times increased risk of thrombosis.

Homozygotes: 50-100 fold risk

Question 11

Heparin as treatment for PE and DVT?

Answer 11

• Immediate effect
• Requires antithrombin: inactivation of Xa and IIa
• It is an inhibitor through increased antithrombin effect

Question 12

LMW heparin?

Answer 12

• used to treat venous thrombosis
• Similar to IV heparin
• Inhibits Xa rather than thrombin

Question 13

What are the 2 LMWHs used in clinical practice?

Answer 13

• Clexane

- Enoxaparin

Question 14

What would the treatment plan for a patient with DVT look like?

Answer 14

• LMW heparin

- Warfarin at same time : note risks of drug interactions

Question 15

How is warfarin monitored?

Answer 15

-INR

Question 16

How to reverse bleeding on warfarin

Answer 16

• Vitamin K - IV

- If immediately needed, prothrombinex containing I, IX, X

Question 17

New oral anticoagulants (DOAC’s)

Answer 17

Rivaroxaban: Inhibits Xa
Dabigatran: Inhibits thrombin/IIa

Same use as warfarin for VTE
Dabigatran superior to warfarin for A fib

Advantages: No monitoring needed, fixed dose, less intracranial haemorrhage.
Disadvantages: Renal excretion, so in renal impairment, retained

Question 18

Clotting tests and DOAC’s

Answer 18

Dabigartran: Prolonged TCT. APTT longer at therapeutic level. 1+1 longer. PR prolonged if very high
Rivaroxaban: PR longer to some extent, APTT less so.

Specific assay available for both

Question 19

Antidote for dabigatran

Answer 19

idarucizumab

Antibody that binds to dabigatran, immediate reversal