Haem: Thrombosis - aetiology and management Flashcards
What is the triad of symptoms in thrombophlebitic syndrome?
Recurrent pain
Swelling
Ulcers
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
Recall 5 effects of inflammation on the blood vessel wall
- Anticoagulant molecules are downregulated
- TF expressed
- Prostacyclin decreased
- Adhesion molecules upregulated
- VWF released (leading to neutrophil capture, and formation of NETs)
How do neutrophils contribute to immunothrombosis?
Neutrophils release DNA, which is procoagulant
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 III
Which inactivates thrombin and factors 9, 10 and 11
Give an example of an LMWH
Enoxaparin/ Tinzaparin
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
Risk of heparin-induced thrombocytopaenia
How does warfarin affect vit K?
Warfarin inhibits vitamin K epoxide reductase
Prevents recycling of Vit K
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)*
How can the action of warfarin be reversed?
IV vitamin K – takes 6 hours
Prothrombin complex concentrate (factors 2, 7, 9 and 10) – takes 30 mins
How is warfarin monitored?
Pro-thrombin time/INR
What are the problems with warfarin?
Teratogenic so cannot give during pregnancy
Requires frequent monitoring (every 1 or 2 days when first start, and then every week, then once every 12 weeks really when everything is stable)
Initial hypercoagulable state due to inhibition of protein C and protein S - that’s why heparin is co-administered until INR stabilises
