Haem - Thrombosis

Question 1

What are the complications of thrombosis

Answer 1

Death (mortality 5%)
Recurrent (20% in the first 2 years, 4% after)
Thrombophlebitis syndrome (recurrent pain, swelling, ulcers)
Pulmonary hypertension (if PE is not cleared properly)

Question 2

What is virchow’s triad

Answer 2

1. Blood
2. Vessel wall
3. Blood flow

Question 3

Describe how blood contributes thrombosis risk (Virchow’s triad)

Answer 3

Viscosity (high haematocrit, protein/paraprotein)
Platelet count
Coagulation system - imbalance of procoagulant and anticoagulant factors

Question 4

Which factors are procoagulant

Answer 4

F II,V, VIII, IX, X, XI
Fibrinogen
Platelets

Question 5

Which factors are anticoagulant

Answer 5

TFPI (tissue factor pathway inhibitor)
Protein C
Protein S
Thrombomodulin
EPCR
Antithrombin

Question 6

Which disorders increase risk of thrombosis

Answer 6

Factor V leiden
Protein S deficiency
Protein C deficiency
Antithrombin deficiency
Elevated FVIII and FXI

Question 7

Describe the coagulation cascade

Answer 7

1. Tissue Factor, exposed by vessel damage, forms a complex with FVII
   Formation of an active TF-VII complex
2. Activation of the extrinsic pathway via FX -> FXa
3. Activation of the intrinsic pathway via FIX -> FIXa
   Xa leads to conversion of prothrombin -> thrombin (IIa)
4. Activation of FV and FVIII by thrombin and platelets
5. Enhanced thrombin formation
6. Thrombin then converts fibrinogen to fibrin, which is cross-linked by the XIIIa
   enzyme (activated by thrombin) to form cross-linked fibrin

Question 8

Describe how vessel wall contributes thrombosis risk (Virchow’s triad)

Answer 8

The vessel wall is usually antithrombotic as it expresses anticoagulant molecules (thrombomodulin, protein C receptor, TFPI, heparans) and does not express tissue factor
Also secretes prostacyclin and NO (antiplatelets)

Inflammation will make the wall prothrombotic
- anticoagulatns downregulated
- Adhesion molecules upregulated
- Tissue factor expressed
- vWF release → platelet and neutrophil capture, (neutrophil extracellular traps)

Question 9

What stimuli will cause the vessel wall to become prothrombotic

Answer 9

Infection
Malignancy
Vasculitis
Trauma

Question 10

Describe how blood flow contributes thrombosis risk (Virchow’s triad)

Answer 10

Stasis will promote thrombosis
accumulation of activated factors → platelet adhesions → promotes leukocyte adhesion (NET) and transmigration

Question 11

What are the causes of blood stasis

Answer 11

Immobility: surgery, paraparesis, travel
Compression: tumour, pregnancy
Viscosity: polycythaemia, paraprotein
Congenital: vascular abnormalities

Question 12

What is the MOA for heparin and DOACs

Answer 12

Heparin: Potentiates anti-thrombin activity for an immediate anticoagulant activity

DOACs:
Anti-Xa: rivaroxaban, apixaban, edoxaban
Anti-IIa (antithrombin): dabigatran

Question 13

how is heparin therapy monitored

Answer 13

LMWH: not required
If renal failure, extremes weight or risk → Anti-Xa assay

Unfractionated heparin: APTT or anti-Xa assay

Question 14

What is the MOA for warfarin

Answer 14

Vitamin K epoxide reductase (VKER) inhibitor
Stops synthesis of factors 2, 7, 9 , 10 → delayed anticoagulant activity (14 days full onset)
FVII and protein C reduce first

Question 15

How do you reverse warfarin

Answer 15

Give vitamin K if high INR (12 hours)
Quickly (1 minute) – 2,7,9,10 infusion

Question 16

How do you monitor for warfarin

Answer 16

Measure of effect is INR– international normalised ratio derived from PT

Question 17

What are the following features for heparin (admin, action, onset, monitoring, half life effects, reversal, safety in pregnancy)

Answer 17

Admin: parenteral
Action: co-factor for antithrombin
Onset: immediate (SC 4h)
Monitor: none
Half life: 6h
Reversal: protamine
Pregnancy: safe

Question 18

What are the following features for warfarin (admin, action, onset, monitoring, half life effects, reversal, safety in pregnancy)

Answer 18

Admin: oral
Action: vit K antagonist
Onset: delayed
Monitor: INR
Half life: 2-3 days
Reversal: factor concentrate, vit K
Pregnancy: safe

Question 19

What are the following features for DOAC (admin, action, onset, monitoring, half life effects, reversal, safety in pregnancy)

Answer 19

Admin: oral
Action: direct enzyme inhibition
Onset: immediate, peak 4h
Monitor: none
Half life: 8-10h
Reversal: Ab to dabigatran, Xa
Pregnancy: avoid

Question 20

Which patients are at an increased risk of thrombosis

Answer 20

Medical inpatients: infection/inflammation, immobility, age
Cancer patients: procoagulation, inflammation, flow obstruction
Surgical patients: immobility, trauma, inflammation
Previous VTE, FHX, Genetic traits
Obese
Pregnant
Elderly

Question 21

What are the strategies for thromboprophylaxis

Answer 21

LMWH – Tinzaparin or Clexane, not monitored
TED stockings for surgery or if heparin CI
Intermittent pneumatic compression (Flowtron) – intermittent compression, increases flow
Sometimes DOAC +/- aspirin

Question 22

What factors should you consider when deciding whether to put a patient on long-term coagulation

Answer 22

What the circumstances were when the patient had thrombosis
Gender: M>F
Proximal or distal: proximal thrombosis is more likely to have DVT
Risk of bleeding

Question 23

Describe long-term anticoagulation therapy for the following features after a thrombotic event: post-surgery, COCP, flights, trauma, idiopathic

Answer 23

Surgery: none required
COCP: 3 months anticoagulation
Flights: 3 months anticoagulation
Trauma: 3 months anticoagulation
Idiopathic: long-term required

Question 24

Which patient factors increase risk of bleeding

Answer 24

Haemophilia, vWD
Platelets <100
Acute CVA in previous month
BP >200/120
Severe liver or renal disease
Active bleeding
Anticoagulant therapy

Question 25

What procedures increase risk of bleeding

Answer 25

Neuro, spinal, eye surgery
LP, spinal, epidural