Haemostasis and Thrombosis Flashcards
What is the difference between red and white thrombi?
Red: forms in veins, rich in fibrin + RBCs
White: forms in arteries, rich in platelets + macrophages (foam cells)
What are the 3 risk factors in Virchow’s triad?
Rate of blood flow: Slow/ stagnating flow means no replenishment of anticoagulant factors + balance tilts to procoagulant
Vessel wall integrity: damaged endothelia exposes blood to pro-coagulation factors
Consistency of blood: imbalance between procoagulants + anti-coagulants
What are the three stages in the cell based theory of coagulation? State which types of drugs target each of the different stages.
Initiation: small-scale production of thrombin: ANTI-COAGULANTS
Amplification: large-scale thrombin production on the surface of platelets: ANTI-PLATELETS
Propagation: thrombin mediated generation of fibrin strands: THROMBOLYTICS
What does the tissue factor-bearing cell contain?
Tissue Factor
Prothrombinase Complex = Factors 5a + 10a
Describe the process of initiation.
TF bearing cells activate factor 5 + 10 forming the prothrombinase complex (5a + 10a)
The prothrombinase complex converts prothrombin to thrombin
What is responsible for the inactivation of factors 2a and 10a?
Antithrombin (AT-III)
State 5 drugs that target the initiation stage of coagulation.
Dabigatran: factor 2a inhibitor (oral)
Rivaroxaban: factor 10a inhibitor (oral)
Heparin: activates antithrombin= less 2a + 10a (IV/SC)
Low Molecular Weight Heparin (e.g. Dalteparin): activates antithrombin: preferentially targets factor 10a
Warfarin (oral): vitamin K antagonist; inhibits production of factors 2, 7, 9 + 10
Describe the amplification stage of coagulation.
Thrombin activates platelets + makes them more sticky so that they aggregate
Explain, in detail, how thrombin causes platelet activation.
Thrombin binds to PAR (platelet activated receptor) on platelet membrane
Increase intracellular Ca2+
This stimulates ADP exocytosis from dense granules
ADP binds to P2Y12 receptors on the same platelet/ neighbouring platelets, which leads to platelet activation/aggregation
PAR activation also liberates arachidonic acid
AA is converted by COX to thromboxane A2
Thromboxane A2 increases expression of GpIIb/IIIa (involved in platelet aggregation)
State 3 drugs that target the amplification stage of coagulation and explain how they act.
Aspirin (Oral): irreversible COX1 inhibitor: stops production of thromboxane by platelets
Clopidogrel (Oral): irreversible ADP (P2Y12) receptor antagonist : prevents activation + aggregation
Abciximab (IV,SC): monoclonal antibodies directed at GpIIb/IIIa: prevent aggregation
What are the 2 main indications for anti platelets?
Arterial thrombosis: Acute coronary syndromes e.g. MI
Prophylaxis of atherosclerosis
Describe the propagation stage of coagulation.
Activated platelets cause large scale thrombin production
Thrombin converts fibrinogen to fibrin so fibrin strands are generated
Name an important thrombolytic and explain how it acts.
Alteplase: A recombinant tissue plasminogen activator (tPA)
Plasminogen is converted to plasmin, which is a protease that degrades fibrin, results in dissolution of clot
What are the 3 indications of thrombolytics?
Ischaemic stroke
STEMI
Rupture of an atherosclerotic plaque
How can DVT and PE be treated, either prophylactically and after it has happened?
Prophylactically: anticoagulants
After it happens: heparin or low MW heparin
