Venous Thromboembolisms Flashcards
What are three main aspects of the blood that confer a thrombotic risk?
i) Viscosity
inc. Haematocrit - Polycythaemia
inc. protein/paraprotein - Myeloma
ii) Platelet Count
iii) Coagulation System
i. e. net excess of procoagulant activity.
How are vessel walls antithrombotic?
i) Expresses anticoagulant molecules such as;
- > Thrombomodulin
- > Endothelial Protein C Receptor
- > Tissue Factor Pathway Inhibitor
- > Heparans (blood vessel heparin)
ii) Does not express tissue factor
iii) Secretes antiplatelet factors
- > Prostacyclin
- > NO
What causes vessel walls to become prothrombotic?
Inflammation/Ijury can make the vessel wall prothrombotic Stimuli -> Infection i.e. COVID-19 -> Malignancy -> Vasculitis -> Trauma
Effect
-> Anticoagulant molecules i.e. Thrombomodulin are down regulated
-> Prostacyclin production decreased
-> Tissue factor may be express
-> Adhesion molecules up regulated
-> Von Willebrand Factor release
==> This can cause Neutrophil Extracellular Traps to form.
What is Neutrophil “netting”?
- > This involves releasing its PRO-COAGULANT DNA.
- > This captures vWf and platelets
- > The release of histones also go on to activate platelets.
Acts a surface for the activation of the thrombotic system.
How does Blood Flow increase the risk of thrombosis?
Stasis promotes thrombosis.
Mechanism involves
- > Accumulation of activated factors
- > Promotes platelet adhesion
- > Promotes leucocyte adhesion and transmigraion
- > Hypoxi produces an inflammatory effect on the VESSEL WALL. i.e. VwF release.
Causes of stasis include
- > Immobility ; Surgery, Travel
- > Compression ; Tumour, Pregnancy
- > Viscosity ; Polycythaemia, Paraprotein
- > Congenital ; Vascular Abnormalities.
What is antithrombotic therapy?
Immediate
-> Heparin
Unfractionated Heparin
Low Molecular Weight Heparin
-> Direct Acting Oral Anticoagulants DOACS
Fator Xa inhibitors
Factor IIa inhibitors
Delayed
-> Vitamin K Antagonists
Warfarin
MOA of Heparin?
The act by potentiating Anti-Thrombin and thus provide immediate effect.
What are the different types of heparin and and do they need monitoring?
Unfractionated Heparin (derived physiologically from pigs - HMWH + LMWH) - IV infusion – Monitored (aPTT) Low Molecular Weight Heparin - Sub Cutaneous - No Monitoring (does not affect thrombin) Pentasaccharide - Sub Cutaneous - No monitoring
What are the disadvantages of heparin?
However some disadvantages are that
- > Injections
- > Risk of osteoporosis
What are DOAC’s? And what is their MOA?
‘Direct Oral AntiCoagulant’
- > Oral administration
- > Immediate Acting, peaks within 3-4hours
- > Ueful for both long term and short term use
- > No monitoring
Anti-Xa
-> RivaroXaban, ApiXaban, EdoXaban
Anti-IIa
-> Dabigatran
What is MOA of warfarin?
NO Direct Anti-Coagulant Action
Oral tablets which prevent the recycling of Vitamin K.
-> As a result, levels of procoagulant factors which are Vitamin K dependent i.e. 2,7,9 and 10 also fall.
-> Levels of Protein C&S also fall.
What is the standard measuring unit for warfarin?
The standard measuring unit is the INR international normalised ratio, Derived from Pro-Thrombin Time
Why are Warfarin levels very variable and patient dependant?
Depends on:
- > Dietary Vitamin K
- > Variable Absorption
- > Interactions with other drugs
- > Teratogenic - NEVER USED in PREGNANT WOMEN
What are methods of thromboprophylaxis?
- > Low Molecular Weight Heparins
i. e. Tinzaparin 4500u/Enoxaparin 40mg OD - > TED Stockings
- > Intermittent Pneumatic Compression
- > ?DOAC+/-Aspirin
What are risk factors for thrombosis??
Patient ⚫ Age > 60yrs ⚫ Previous VTE ⚫ Active cancer ⚫ Acute or chronic lung disease ⚫ Chronic heart failure ⚫ Lower limb paralysis (excluding acute CVA) ⚫ Acute infection ⚫ BMI>30
Procedure ⚫ Hip or knee replacement ⚫ Hip fracture ⚫ Other major orthopaedic surgery ⚫ Surgery > 30mins ⚫ Plaster cast immobilisation of lower limb
What are bleeding risk factors?
Patient ⚫ Bleeding diathesis (eg haemophilia, VWD) ⚫ Platelets < 100 ⚫ Acute CVA in previous month (H’gge or thromb) ⚫ BP > 200 syst or 120 dias ⚫ Severe liver disease ⚫ Severe renal disease ⚫ Active bleeding ⚫ Anticoag or anti-platelet therapy
Procedure
⚫ Neuro, spinal or eye surgery
⚫ Other with high bleeding risk
⚫ Lumbar puncture/spinal/epidural in previous 4 hours
Describe the risk of recurrence of a thrombotic event
Post Surgical Precipitant
-> Very low recurrence risk. no need for long term anticoagulation
Post minor precipitants (COCP, Flights, Trauma)
-> Medium recurrence risk, usually 3 months of Anti-Thrombotic Therapy is adequate
Post idiopathic VTE
-> High Risk, 10-20% in 2 years, consider long term anticoagulants (especially with DOACS to reduce risk of bleeding).
