Thrombotic disease Flashcards
what is thrombosis
formation of blood clot inside vessels –> blocking blood circulation
what does thrombosis cause
- ischaemia
- malfunction
- pain or swelling
what does arterial thrombosis
- MI
- AF
- Peripheral vascular disease (PVD)/ leg
- stroke
what does venous thrombosis cause
- DVT/arm,leg
- Pulmonary embolism/ lungs
what is Virchow’s traid for causes of thrombsis
- stasis
- hypercoagulability
- vessel wall injury
what is atrial thrombosis cause
- atherosclerosis
- inflammation of vessel wall
- infiltration of macrophages
- fat deposits
what are the phases of thrombotic response
- plaque fissure, rupture
- adhesion & activation of platelets
- activation of coagulation cascade
what is mural thrombi (arterial thrombosis)
- does not occlude vessel
- unstable angina
- transient ischaemia
what is occlusive thrombi (arterial thrombosis)
- occludes vessel
- MI
- cerebral infarction
what is thrombi driven by
uncontrolled platelet activation
what are the prothrombic stimulatory agonists
- ADP
- adrenaline
- colagne
- fibrinogen
- thrombin
- thromboxane A2
what are the antithrombic inhobitory agonists
- adenosine
- nitric oxide
- prostacyclin
what is the primary haemostatic response
- Platelets bind to collagen - Adhesion and activation - Release of pro-aggregatory substances ADP, TxA2 - Autocatalytic expansion of thrombus - Controlled by endothelial NO and PGI2
what is thrombotic response
- Platelets bind to collagen and exposed to oxidised lipids from plaques
- Activation
- Release of proaggregatory substances ADP, TxA2
- Autocatalytic expansion of thrombus
- Reduced bioavailability of endothelial NO and production of PGI2
- Occlusive thrombi
what do platelet derived soluble agonists do
drive expansion of the thrombus
how are ADP, TxA2 & Thrombin derived from platelets
- ADP: Released from platelet dense granules
- TxA2: Synthesised and release by platelet from arachidonic acid
- thrombin: generated on the platelet surface as the endpoint of the coagulation cascade
what does plaque content (oxidised lipids) do
- promote 2ry agonists
- reduce inhibitors’ actions (NO, PGI2)
how is atherothrombosis treated
1) Antiplatelets
- Aspirin (inhibition of COX-1 and thromboxane production)
- Anti aIIbb3 (receptor for fibrinogen and vWF)
- Anti P2Y (receptor for ADP induced platelet aggregation)
2) Fibrinolytics (tPA/uPA derivatives)
where is DVT most common
- area with low blood flow
- vulnerable around the valves
what is the most dangerous pathology associated with DVT
- pulmonary embolism
what are symptoms of DVT
- calf swelling
- pain
- lack of venous return
- associated odema
what increase the risk of DVT
- stasis: endothelial dyfunction hyercoaguable state
- immobilization
- surgery
- cancer
- pregnancy
- oral contraceptives
- genetic risk factors:
1) Deficiencies in coagulation inhibitors
2) Factor V Leiden mutation
what are the potential mechanisms for venous thrombosis
- circulatory stasis
- endothelial injury
- hypercoaguable state
describe circulatory stasis
- loss of laminar flow around valves, gaps between endo cells and minor platelet activation
describe Endothelial dysfunction
inflammation leads to activation and exposure of TF
describe Hypercoagulable state
- localised inflammation
- loss of inhibitor function – activity of thrombomodulin (TM) and protein C/S system leading to thrombin accumulation
- lupus anticoagulants (anti-phospholipid antibodies)
- impaired fibrinolysis
what is treatment for venous thrombosis
1) Immediate onset of anticoagulant effect:
- Unfractionated Heparin (intravenous – helps antithrombin to inhibit thrombin and Xa)
- Low Molecular Weight Heparin (LMWH; subcutaneous)
2) Slow onset:
- VKA, monitored by INR
3) Direct thrombin inhibitors (Dabigatran) promising in clinical trials
