Haem: Thrombosis - aetiology and management Flashcards
What is the triad of symptoms in thrombophlebitic syndrome?
Recurrent pain
Swelling
Ulcers
also called post-thrombotic syndrome
Factors affecting blood which increase thrombosis risk
Viscosity
* high haematocrit
* raised protein/paraprotein
High platelets
coagulation factors
* excess pro-coagulant
* deficient anticoagulant
Virchow’s triad
3 contributing factors to thrombosis, disruptions in any of these increase thrombosis risk:
Blood
Vessel wall
Blood flow
Consequences following VTE
Death
Recurrence
Thrombophlebitic syndrome
Pulmonary HTN
Minimum length of anticoagulant treatment following VTE
3 months
What catalyses the conversion of fibrinogen to fibrin?
Thrombin
Which anticoagulant molecules are expressed on the blood vessel wall?
Thrombomodulin
Endothelial protein C receptor
Tissue factor pathway inhibitor
Heparans
NOTE: it does not normally produce tissue factor
Is blood vessel wall anti or pro thrombotic
normally antithrombotic
But infection (covid 19)/ vasculitis/ trauma/malignancy makes it very promthrombotic
Recall 5 effects of inflammation on the blood vessel wall
- Anticoagulant molecules (e.g. thrombomodulin) are downregulated
- TF expressed
- Prostacyclin decreased
- Adhesion molecules upregulated
- VWF released (leading to neutrophil capture, and formation of NETs)
Which coagulation pathway is mainly implicated in VTE
Extrinsic - via tissue factor being exposed
What are the anticoagulant proteins
What do they target
Tissue factor pathway inhibitor (TFPI) - degrades VIIa and Xa
Protein C and Protein S - degrades factor Va, and VIIIa
Antithrombin - degrades Xa and IIa (thrombin)
How do neutrophils contribute to immunothrombosis?
Neutrophils release DNA, which is procoagulant - Neutrophil Extracellular Traps (NETs)
low dose vs high dose anticoagulant indications
low dose - prevention
high dose - treatment
Give 4 ways in which blood stasis promotes thrombosis
- Accumulation of activated factors
- Promotes platelet adhesion
- Promotes leukocyte adhesion and transmigration
- Hypoxia produces inflammatory effect on endothelium
What is the broad mechanism of action of heparins?
Potentiate antithrombin - which binds to Xa
Give an example of an LMWH
Enoxaparin/ Tinzaparin
immediate vs delayed anticoagulants
delayed - warfarin –> reduces procagulants activity
immediate - Heparins, DOACs –> increases anticoagulant activity
heparin methods of administration
what monitoring required
unfractionated heparin - IV infusion - monitor
LMWH - subcut - no monitoring
pentasaccharide - subcut - no monitorinh
How is unfractionated heparin monitored?
What about LMWH?
Unfractionated heparin: it has variable pharmacokinetics and a variable dose-response
Must be monitored with APTT or anti-Xa levels
LMWH: reliable pharmacokinetics so monitoring usually not required
Monitor anti-Xa levels if there is renal failure, extreme weight or extreme risk
What are the disadvantages of heparin?
Administered by injection
Risk of osteoporosis
Variable renal dependence - renally excreted so monitor in CKD
Risk of heparin-induced thrombocytopaenia
How does warfarin affect vit K?
Warfarin inhibits vitamin K epoxide reductase
Prevents recycling of Vit K - factor 7 drops the first
delayed action
Which procoagulant factors fall as a result of warfarin medication?
II, VII, IX and X
*Also impairs Protein C and Protein S (which are natural anticoagulant molecules)*
benefits of DOACs
no monitoring required
less bleeding risk
no osteoporosis risk
no monitoring required
How can the action of warfarin be reversed?
Administering vitamin K – takes 12 hours
Giving factors 2, 7, 9 and 10 – immediate
if dietary vitamin K - difficult to anticoagualte
