Haemostasis 270721 Flashcards
Pro-coagulation factors include
primary haemostasis (platelets, endothelium, vWF) Coagulation cascade
anti-coagulation factors
Natural inhibitors of thrombosis (anti-thrombin, protein C/protein S, Tissue factor pathway inhibitor), fibrinolysis
what 3 processes does vessel injury stimulate
vasoconstriction, platelet activation (formation of the primary haemostatic plug), activation of the coagulation cascade
what happens to the vascular endothelium in the first stage of blood clotting
damage to the endothelium leads to exposure of pro=coagulant subendothelial structures triggering a haemostatic response. Endothelial cells produce, prostaglandins, vWD, plasminogen activators, thrombomodulin. This then leads to platelet aggregation
what happens to platelet in the second stage of blood clotting
platelet adhesion directly via Glp1A and indirectly via vWF and Glp1B. This adhesion leads to release of ADP and thromboxane A2 -> platelet aggregation. Platelets attach to eachother via GlpIIB/IIA (fibronogen receptor)
What happens in the third step of blood clotting where a fibrin mesh is generated
Factor Xa is the rate limiting step for fibrin formation. Pathway is triggered by trace amounts of thrombin which is formed following activation of the platelet plug. Thrombin cleaves fibrinogen, activates platelets, activates FV and FVIII, FXI and FXIII this leads to more thrombin formation and thrombin creates more fibrin from fibrinogen
summarise the clotting cascade
Initiation phase: injury of vessel wall leads to blood and subendothelial cell collision leading to the EXTRINSIC pathway activation of factor 7 to F7a which activates factor 10 to 10a which binds to F5 which triggers the amplification phase by converting prothrombin to thrombin. This thrombin then activates F8,5,11. Starting up to intrinsic pathway eventually leading to more FX release converting more prothrombin to thrombin and thrombin converts fibrinogen to fibrin
How does vitimin K link to the clotting cascade
Vitamin K dependent factors 2,7,9,10 are produced in the liver and act as co-enzyme for the production of clotting factors
What is the most common cause of vitamin K deficiency
warfarin
what condition is the most thrombogenic condition
deficiency of antithrombin
how does thrombin start the anticoagulation pathway
thrombin activates thrombomodulin which opens up the receptor for thrombomodulin to bind protein C leading to activated protein C production. This then inactivates F5a and F8a
How is fibrinolysis stimulated
tPA is produced by endothelium this converts plasminogen to plasmin, plasmin then degrades fibrin. Thrombin activatable fibrinolysis inhibitor is stimulated by thrombin
what are the types of physiological anticoagulants
antithrombins, protein C and S, TFPI
Antithrombins
Heparin = AT-III potentiator (monitor levels with F Xa assay)
Antithrombins will bind to thrombin on a 1:1 ratio and it will then be excreted in the urine
There are FIVE types of antithrombin but the most active is AT-III
The lack or deficiency of antithrombin is the MOST THROMBOGENIC condition
antiplatelet disorders vs anticoagulatnts
o Platelet = petechiae, purpura Tx required when platelet count drops <30x109/L
o Coagulation = heamarthrosis