Haem 1 - Haemostasis and Thrombosis

Question 1

What makes the vessel wall normally antithrombotic

Answer 1

o	Expresses anticoagulant molecules
	Thrombomodulin
	Endothelial protein C receptor
	Tissue factor pathway inhibitor
	Heparans 

o Does not express tissue factor
 TF/FVIIa –> Primary cellular initiator of blood coagulation
 Found in the subendothelial tissue

o Secretes antiplatelet factors
 Prostacyclin
 NO

Question 2

what happens when blood vessels are injured

Answer 2

• Inflammation/injury makes the vessel wall prothrombotic  activates endothelial cells and neutrophils

o Effects
 Anticoagulant molecules (e.g. TM) are down-regulated
 TF may be expressed (pot-coagulant molecule)
 Prostacyclin production decreased
 Adhesion molecules upregulated
 VWF release

• Platelet and neutrophil capture

• Neutrophil extracellular traps (NETS) form
o Neutrophils can undergo netosis  under inflammatory stimuli they release the contents of their nucleus (DNA) – this captures things like vwf, releases things like histones (activate platelets), provides a surface for contact activation of the coagulation pathways, contains things like neutrophil elastase  will break down TFPI

Question 3

Where does each anticoagulant factor act

TFPI (tissue factor pathway inhibitor)
Protein C + S
Antithrombin

Answer 3

TFPI
inhibits FXa + TF/FVIIa (10, 7)

Protein C+S regulate/inactivate Va, VIIIa (5,8)

Antithombin inhibits Xa, IIa (thrombin) (10,2)

https://www.tekportal.net/wp-content/uploads/2018/11/thromboplastin.png

Question 4

List the anticoagulant factors deficiencies from highest to lowest risk of thrombosis

Answer 4

Antithrombin Deficiency
Protein C deficiency
Protein S deficiency
Factor V Leiden

Question 5

VTE risk assessment

patient

procedure

Answer 5

VTE risk assessment
Patient
•	Age >60
•	Previous VTE
•	Active cancer
•	Acute or chronic lung disease
•	Chorinc HF
•	Lower limb paralysis (excluding acute CVA)
•	Acute infection
•	BMI >30

Procedure 
•	Hip or knee replacement
•	Hip fracture
•	Other major orthopaedic surgery
•	Surgery >30 mins
•	Plaster cast immobilisation of lower limb

Question 6

Bleeding risk assessment

patient

procedure

Answer 6

Bleeding risk assessment
Patient
•	Bleeding diathesis (e.g. haemophilia, VWD)
•	Platelets <100
•	Acute CVA in previous month 
•	SBP >200 or DBP >120
•	Severe liver disease
•	Severe renal disease
•	Active bleeding
•	Anticoagulation of anti-platelet therapy

Procedure
• Neuro, spinal or eye surgery
• Other with high bleeding risk
• LP/spinal/epidural in previous 4 hours

Question 7

Immediate anticoagulant therapy options

Answer 7

• Immediate
o Heparin
 UFH  IV, monitored (APPT/ antiXa) - t1/2 1-2h
 LMWH  SC, no monitoring - t1/2 - 6h
 Pentasaccharide  SC, no monitoring
 Reversal - protamine
 All act by potentiating antithrombin – heparin directly activates antithrombin in the circulation
Activation of antithrombin (III) = inactivation of thrombin (II) + FXa

o DOAC – Direct acting anti-Xa and anti-IIa – direct enzyme inhibition
 Anti-Xa – Rivaroxaban, apixaban, edoxaban
 Anti-IIa – diabigatran
 Properties – oral administration, immediate acting (peak in 3-4h), short half-life, no monitoring, also useful in long-term
t/12 - 8-10h

Question 8

Delayed anticoagulant therapy options

Answer 8

o	Warfarin (vitamin K antagonist)
	Indirect effect – prevents recycling of vitamin K => delayed onset of action
t1/2= 2-3d

• Determined by the half life of the coagulation factors in the blood and not be the amount of vitamin K
 Levels of procoagulant factors II, VII, IX, X 2, 7, 9, 10 fall – delayed reduction in coagulation factors
 Levels of anticoagulant protein C + protein S also fall

• Reduction in procoagulant factors > reduction in anticoagulant factors
 Monitoring warfarin
• Always essential
o Measure of effect is INR (derived from PTT)
 reversal factor concentrates, vitamin K
 teratogenic

Question 9

Normal INR vs target on warfarin

Answer 9

Normal - 1

Target on warfarin 2.5 (2-3)

Question 10

Rate of reduction in coagulation factors after warfarin therapy starting with the factor that is decreases the fastest

Answer 10

7>9>10>2

Question 11

risk of recurrence

Which group of people are at higher risk
idiopathic
non-surgical risk (e.g. COCP, flight)
surgery

men
women

proximal
PE
distal

Answer 11

• idiopathic > non-surgical risk (e.g. COCP, flight) > surgery
• men>women
• proximal>PE>distal

Proximal thrombosis = thrombus from the popliteal vein and above – higher rates of recurrence than the distal veins (e.g. calf vein)

Question 12

Long term anticoagulation duration if VTE

after surgery
idiopathic
after precipitants

Answer 12

after surgery - no need
idiopathic - long term (esp. w DOAC)
after precipitants (usually 3 months adequate, longer duration if other thrombotic/haemorrhagic RF)