Haemostasis Flashcards
Platelet based pathways
Platelets form a primary haemostatic plug - platelet adhesion, activation and aggregation.
Coagulation makes a meshwork on the clot - enzyme cascade.
Vasoconstriction slows blood flow - vasoconstrictors and prothrombotic agents.
Virchows triad - risk factors for all 3
Haemostatic Plug
Adhesion to exposed collagen.
Activation: excytose dense granules, change shape and increase respiratory rate.
Aggregation: stimulated by ADP - blocked by prasugrel via fibrinogen.
Platelet Activation
Extracellular ADP -> activation by P2Y receptor -> cation flow.
Platelets release Thromboxane A2
ADP -> positive feedback on platelets
Coagulation
Initial activation factor is segregated.
Tissue factor is hidden behind endothelial cells.
If the basement membrane is exposed, tissue factor starts cascade
Extrinsic (tissue factor pathway - initiation of coagulation) OR Intrinsic (contact activation - positive feedback) Pathway -> common pathway -> clot
Prothrombin Group
Factors II, VII, IX, X enzymes need vitamin K for synthesis require Ca2+ for activation stable
Thrombin Group
Factors I, V, VIII activated by trhombin V and VIII are co-factors Factor I = fibrinogen Increased with inflammation, pregnancy and oral contraceptives
Coagulation info
based on a positive feedback loop
where thrombin activates clotting factors
clotting factors made by the liver - liver dysfunctions lead to clotting deficiency
Vitamin K
Fat soluble vitamins, required to synthesise enzyme coagulation factors.
made by bacteria of large intestine.
Essential for gamma carboxylating of clotting enzymes.
Deficiency: results in clotting insufficiency. caused by GI disease/no fat absorption. warfarin prevents recycling of vit K
Plasmin
Lyses fibrin - stops/destroys clots
Starts as inactive plasminogen - made by liver
Requires tissue plasminogen activator (tPA) to mature
tPA found on surface of endothelial cells
Protein C
Coagulation inhibitor
Starts as inactive enzyme made by liver
Activated on surface of endothelial cells
Works with Protein S to inactivate Factor Va & VIIIa
Antithrombin III
Peptide in the blood, made by liver
Blocks activity of thrombin, Xa and IXa
Heparin -> greater ATIII activity
Recombinant ATIII form used for thrombotic diseases
Lack of ATIII -> risk of thrombotic disease
Pharmacological Disease - Anti-platelet agents
prevents clots in arteries
Used in acute coronary syndromes
Aspirin - CoX inhibitor - blocks formation of thromboxane A2, lengthens bleeding time, doesn’t increase coagulation time, used for MI.
ADP receptor inhibitors - prasugrel/clopidogrel
Pharmacological Disease - Anti-coagulants
Prevents clotting in veins
Prophylactic for DVT and PE
Heparins inhibit coagulation by inhibiting factor Xa
DOACs - dabigatran/rivaroxaban
Warfarin - vit K antagonist - slow onset/requires monitoring
Pharmacological Disease - Fibrinolytics
Clot busting Thrombolytic drugs Prevents clots in arteries Used in acute coronary syndromes - AMI tPA Streptokinase Urokinase
Fibrinolysis and Inhibition of Coagulation
Imbalance of fibrinolysis -> leads to BV accumulating damage/haemorrhage.
Imbalance of clot formation -> leads to clot obstructing vessel lumen
Haemophilia A
Affects larger BVs, joints & muscles
Lack of factor VIII
X linked - only in males
Christmas disease
Haemophilia B
Lack of factor IX
Same symptoms as haemophilia A
Atherogenesis - A disease of inflammation
monocytes enter lesion and become macrophages - consume cholesterol esters - can become foam cells - which can die and release contents - attracts more leukocytes - inflammation haemostasis synergistic effects on atherogenesis
Atherogenesis - A disease of Lipids
LDL deposits lipids in lesion
cholesterol esters are non-aqueous, making them solid
cholesterol esters are oxidised - oxygen radicals
- this makes them immunogenic
oxidised lipids are consumed by macrophages
which become foam cells which explode
Atherogenesis - A disease of Endothelium
endothelium expresses chemo-attractants for monocytes to find and enter lesion
when endothelium is lost, collagen stimulates coagulation
endothelium normally covers collagen and basement membrane
endothelium lost -> vessel can’t control dilation
endothelium usually releases NO
