Haemostasis and thrombosis Flashcards
What is interim treatment for DVT
interim treatment with parenteral anticoagulant (iv/sc Heparin or dalteparin)
What is given for when DVT has been diagnosd
given maintenance treatment with oral anticoagulant (changes from parenteral to oral)
Outline the molecular level of thrombus formation
- Tissue factor (TF)
TF bearing cells activate factors X & V, forming prothrombinase complex - Prothrombinase complex
This activates factor II (prothrombin) creating factor IIa (thrombin) - Antithrombin (AT-III)
AT-III….. inactivates fIIa & fXa
What is dabigatran
ORAL: factor IIa inhibitor
OAC/DOAC
(dabigaTran…. T for thrombin, which is factor 2)
What is rivaroxaban
ORAL: factor Xa inhibitor (think of 10 rivers)
Maintenance treatment
Apixaban also factor Xa inhibitor
Outline the 2 categories of heparin and their MAO
Panopto for subcutaneous
Heparin (IV, SC) - activates AT-III (reducing fIIa & fXa)
Low-molecular weight heparins (LMWHs, e.g.Dalteparin) - activate AT-III (reducing fXa)…. GIVEN AS INTERIM, PARENTERAL ANTICOAGULATNT
What is warfarin and mechanism of action
Vitamin K antagonist - vit K required for generation of factors II, VII, IX & X
ORAL
What is dalteparin
Low-molecular weight heparins (LMWHs, e.g.Dalteparin) - activate AT-III (fXa)
NOTE: the difference in MAO between heparin and LMWH is that the LMWH is also thought to directly inhibit factor Xa, not just increase AT-III
These are used for INTERIM, which is PARENTERAL (oral coagulants are used for maintenance)
What test might you do if you suspect PE
Multiple-detector computed tomographic pulmonary angiography (CTPA)
What is the difference between PE and DVT treatment
On cofnrimed diagnosis might give heparin as well as dalteparin for PE
but the same for maintenance
Outline the risk factors affecting DVT and PE
- Rate of blood flow
Blood flow is slow/stagnating –> no replenishment of anticoagulant factors & balance adjusted in favour of coagulation - Consistency of blood
Natural imbalance between procoagulation & anticoagulation factors (not viscosity!) - Blood vessel wall integrity
Damaged endothelia –> blood exposed to procoagulation factors
What would NSTEMI look like for tests
No changes on ECG & elevated troponin
What is NSTEMI
partially occluded coronary artery leading to ischaemia due to atheroma formation
Differentiate thrombotic lesion and an atherosclerotic lesion and where they occur
Red thrombus…. in a vein, not associated with atherosclerosis
White thrombis… in an artery with foam cells and macrophages/athersclerosis
What treatment would be offered for NSTEMI
Antiplatelet therapy: ASPIRIN & CLOPIDOGREL
Differentiate the cause of NSTEMI and STEMI
Non-ST elevated myocardial infarction (MI)
‘White’ thrombus –> partially occluded coronary artery
ST elevated myocardial infarction
‘White’ thrombus –> fully occluded coronary artery
Differentiate treatment for NSTEMI and STEMI
NSTEMI: antiplatelets
STEMI: antiplatelets & thrombolytics
What is NSTEMI/STEMI caused by
Damage to endothelium
Atheroma formation
Platelet aggregation
Different to VIRCHOW’S TRIAD (as it’s more to do with lifestyle… virchow’s is more to do with thrombus, whereas STEMI/NSTEMI more to do with atherosclerosis)
Outline difference between the thombus formation in vein and atherosclerosis
In atherosclerosis the thombosis is within the wall of the artery, in the plaque
In vein the thrombus is within the lumen
Outline the amplification stage of thrombosis formation on a cellular level
- Thrombin
Factor IIa –> activates platelets - Activated platelet
Changes shape
Becomes ‘sticky’ and attaches other platelets
What is PAR
Protease activated receptor
Outline the ampification stage of thrombosis on a molecular level
- Thrombin (IIa)- binds to protease-activated receptor (PAR) on platelet surface.
- PAR activation –> rise in intracellular Ca2+, and also liberates AA
- Ca2+ rise –> exocytosis of adenosine diphosphate (ADP) from dense granules (not the alpha granules, which contain growth factors)
What is the consequence of ADP exocytosis, PAR receptor activation and TXA2 activtation
- ADP receptors
ADP activates P2Y12 receptors –> platelet activation/ aggregation - PAR activation liberates arachidonic acid, COX generates TXA2 from the AA
- TXA2 activation leads to expression of GPIIbIIIa integrin receptor on platelet surface…. this is involved in platelet aggreation
State types of antiplatelet therapy
Clopidogrel (oral) - ADP (P2Y12) receptor antagonist
Aspirin (oral) - irreversible COX-1 Inhibitor (inhibits TXA2)
Abciximab (IV, SC)… inhibits GPIIbIIIa receptor (3rd line)
