15. Haemostasis and thrombosis Flashcards
What are the 3 stages of coagulation?
- Initiation
- Amplification
- Propagation
What happens in the initiation stage of coagulation?
Small-scale thrombin production
• Tissue factor bearing cells activate factors 10 and 5 => forms prothrombinase complex
• Prothrombinase complex activates factor 2 (prothrombin) creating factor 2a (thrombin)
• Antithrombin (AT-III) inactivates factors 2a and 10a
How do the following work as anticoagulants in the initiation stage: • Dabigatran (oral) • Rivaroxaban (oral) • Heparin (IV, SC) • Low-molecular weight heparins (SC) • Warfarin (oral)
- Dabigatran - factor 2a inhibitor (GI bleeding so not commonly used)
- Rivaroxaban - factor 10a inhibitor
- Heparin - activates AT-III
- Low-molecular weight heparins - activates AT-III, also thought to directly affect 10a
- Warfarin - vitamin K antagonist (required for the generations of factors 2, 7, 9, 10)
What does a positive D-dimer test suggest and what do you following this diagnosis?
- DVT
- Interim treatment with parenteral anticoagulant
- Dalteparin
What do you do following an ultrasound scan confirming a DVT/pulmonary embolism?
- Maintenance treatment with oral anticoagulant
* Rivaroxaban/warfarin
What treatment do you use following the confirmation of a pulmonary embolism with a CTPA (computed tomographic pulmonary angiography)?
- Dalteparin
* Heparin if more serious
What are the risk factors for DVT/pulmonary embolism (Virchow’s triad)?
- Rate of blood flow - blood flow is slow, no replenishment of anticoagulating factors
- Consistency of blood - natural imbalance between procoagulation and anticoagulation factors
- Blood vessel wall integrity - damaged endothelia, blood exposed to procoagulation factors
What happens in a non-ST elevated myocardial infarction (NSTEMI) and how is it treated?
- White thrombus (contains foam cells)
- Partially occluded coronary artery => ischaemia
- Antiplatelets
Where/when does a red thrombus form?
DVT
What happens in a ST elevated MI (STEMI)?
- White thrombus
- Fully occluded coronary artery
- Lack of oxygen
- Cell death and necrosis
- Antiplatelets and thrombolytics
What leads to a STEMI?
- Damage to endothelium
- Atheroma formation
- Platelet aggregation
What are the risk factors for a STEMI mainly associated with?
Diet - high fat/high LDL
Is the thrombosis in both an artery and vein subendothelial?
No, just artery
What happens in the amplification stage of coagulation?
- Thrombin binds to protease -activated receptors (PAR) on the platelet surface
- PAR activation - rise in intracellular Ca2+
- Exocytosis of ADP from dense granules
- ADP activates P2Y12 receptors - platelet activation/aggregation
- PAR/P2Y12 activation liberates arachidonic acid (AA)
- COX generates thromboxane A2 from AA
- This causes the expression of GPIIb/IIIa integrin receptor on platelet surface
- Activated platelets change shape, become sticky and attach other platelets
- Platelets themselves begin converting more thrombinase into thrombin
How do the following work as anticoagulants in the amplification stage:
• Clopidogrel (oral)
• Aspirin (oral)
• Abciximab (IV, SC)
- Clopidogrel - ADP (P2Y12) receptor antagonist
- Aspirin - irreversible COX-1 inhibitor, prevents TXA2 formation, lack of GPIIb expression
- Abciximab - monoclonal antibody inhibits GPIIb/IIIa receptor (limited, specialist use)
