Haematology - Venous thrombosis

Question 1

what are the consequences of VTE?

Answer 1

• death
• recurrence
• thrombophlebitis syndrome
• pulmonary HTN (if PE isn’t cleared properly)

Question 2

what is thrombophlebitis syndrome?

Answer 2

• recurrent pain
• swelling
• ulcers

Question 3

what are the elements of Virchow’s triad?

Answer 3

• blood
• vessel wall
• blood flow

Question 4

what are the important factors in the blood that can affect VTE formation?

Answer 4

• viscosity (haematocrit, protein)
• platelet count
• coagulation system
  imbalance = thrombophilia or thrombosis

Question 5

what increases the risk of thrombosis?

Answer 5

• reduced prothrombin
• thrombocytopenia
• reduced protein C
• elevated anti-thrombin
• increased fibrinoylsis

Question 6

what are the procoagulant factors?

Answer 6

2, 5, 8, 9, 10, 11
fibrinogen
platelets
factor V Leiden

Question 7

what are the anticoagulant factors?

Answer 7

TFPI
Protein C
Protein S
Thrombomodulin
EPCR
Antithrombin
Fibrinolysis

Question 8

what is the normal state of the vessel wall?

Answer 8

• normally antithrombotic
• expresses anticoagulant molecules
• does not express tissue factor (is procoagulant so normally kept outside circulation)
• secretes antiplatelet factors (prostacyclin from vessel wall, NO)

Question 9

what anticoagulant molecules does the vessel wall express?

Answer 9

• thrombomodulin
• endothelial protein C receptor
• tissue factor pathway inhibitor
• heparans

Question 10

what happens to vessel wall in inflammation or injury?

Answer 10

makes it prothrombotic

Question 11

what stimuli can change the endothelium to make it prothrombotic?

Answer 11

• infection
• malignancy
• vasculitis
• trauma

Question 12

what are the effects of these stimuli on the vessel wall?

Answer 12

• anticoagulants downregulated
• adhesion molecules upregulated
• TF expressed (pro-coagulant)
• prostacyclin decreased
• release VWF (capture platelets and neutrophils)

Question 13

what is immunothrombosis?

Answer 13

inflammation triggers and drives thrombus formation

Question 14

how can blood flow affect VTE formation?

Answer 14

stasis promotes thrombosis

Question 15

what is the mechanism in which stasis promotes thrombosis?

Answer 15

• accumulation of activated factors
• promotes platelet adhesion
• promotes leukocyte adhesion and transmigration
• hypoxia = inflammatory effect on endothelium

Question 16

what are the causes of stasis?

Answer 16

• immobility (surgery, travel)
• viscosity (polycythaemia, paraprotein)
• compression (tumour, pregnancy)
• congenital (vascular abnormalities)

Question 17

which factor confers the highest risk of thrombosis?

Answer 17

antithrombin deficiency

Question 18

what are the different anticoagulant doses?

Answer 18

low dose = prophylactic

high dose = therapeutic

Question 19

what is the moa of heparin? how can it be given?

Answer 19

potentiates anti-thrombin activity
unfractionated - IV
LMWH - SC

Question 20

what other anti-coagulants are there?

Answer 20

directly acting anti-10a = Rivaroxaban, Apixaban

anti-2a/thrombin

Question 21

what are the long term disadvantages of anti-coagulation?

Answer 21

• injections
• risk of osteoporosis
• variable renal dependence

Question 22

how do you monitor LMWH?

Answer 22

• reliable pharmacokinetics so doesnt need to

- Monitoring: anti-Xa assay, renal failure (creatinine clearance <50), extremes or weight or risk

Question 23

how do you monitor unfractionated heparin?

Answer 23

• variable dose-response

- monitoring: APTT, Anti-Xa assay

Question 24

name the different DOACs

Answer 24

Anti-Xa: rivaroxaban, apixaban, edoxaban

Anti-2a: dabigatran

Question 25

what are the properties of DOACs?

Answer 25

• oral admin
• useful long term
• no monitoring
• immediate acting
• short half life

Question 26

what are the anti-coagulants that have a delayed effect? How do they work (which factors)?

Answer 26

• reduce procoagulant activity (2, 7, 9, 10)

- Vit K antagonists e.g. warfarin

Question 27

how does warfarin work?

Answer 27

• Vit K epoxide reductase inhibitor

- indirect effect on preventing recycling of Vit K

Question 28

what is a downside of warfarin?

Answer 28

onset of action is delayed

around 14 days to onset fully

Question 29

what procoagulants/ anticoagulants are affected by warfarin?

Answer 29

• procoagulants 2, 7, 9, 10 fall

- levels of anticoagulant protein C and S fall

Question 30

how do you reverse warfarin short and long term?

Answer 30

• Quickly (1 min): 2,7,9,10 infusion

- give vitamin K if high INR (12 hours)

Question 31

how do you monitor warfarin?

Answer 31

• INR (derived from PT)

Question 32

why is monitoring warfarin difficult?

Answer 32

• numerous interactions
• dietary Vit K
• variable absorption
• interactions with other drugs
• teratogenic

Question 33

what is important to start with warfarin? why?

Answer 33

LMWH

warfarin has immediate procoagulant that wears off after few days

Question 34

when is warfarin still indicated first line?

Answer 34

patients with prosthetic valves

Question 35

what are the 3 main goals of anticoagulant therapy?

Answer 35

1. prevent thrombosis
2. treat thrombosis
3. prevent recurring thrombosis

Question 36

how do you prevent thrombosis?

Answer 36

identify pt at increased risk of thrombosis

1. medical (infection, inflammation, immobility, age)
2. cancer pt (procoagulation, inflammation, flow obstruction)
3. surgical pt (immobility, trauma, inflammation)
4. previous vte, fhx, genetic traits
5. obese and elderly

Question 37

what are the methods for thromboprophylaxis?

Answer 37

• LMWH (tinzaparin, clexane, not monitored)
• TED stockings
• flowtron (increases flow)
• sometimes DOAC +/- aspirin

Question 38

which cases have a higher recurrence rate?

Answer 38

• men more than women

- proximal thrombosis higher recurrence

Question 39

how long is anticoagulation needed after a minor precipitant? what is idiopathic?

Answer 39

3 months

if idiopathic cause = long term anticoagulation needed