10 Haemostasis Flashcards
List the sequence of haemostasis
Stress: loss of blood
Vasoconstriction
Primary haemostasis: formation of unstable plaque by the interaction with GPIa and GPIb with collagen and vWF, respectively. Subsequently they release ADP, thromboxane and PGI2. This induces the activation of GPIIb/IIIa to bind fibrinogen for platelet aggregation
Secondary haemostasis: stabilisation of plaque with firbin
Fibrinolysis
State the condition where collagen or vWF is the substance for platelet adhesion
Small artery, high shear stress: GP1b/vWF
Large artery, low shear stress: GP1a/collagen
What are the features of activated platelet
Change shape
Change of membrane composition
Present new or activated protein on membrane
List the sites for the synthesis of coagulation factors
Liver
Megakaryocytes
Endothelial cells
What is the site of coagulation
The surface of activated platelets
Describe the process of fibrinolysis
Tissue plasminogen is converted to plasmin by the cleavage of tPA (synthesised from endothelial cells) and degrade fibrin clot into fibrin degradation product (FDP)
State a substance that has similar effect as tPA
Bacterial streptokinase
What is the direct coagulation inhibitory mechanism
Antithrombin which is a direct inhibitor or proteases such as XIa, IXa, Xa and thrombin
What is the therapeutic drug that targets this mechanism
Heparin which increases its action. Typically used in patients with venous thrombosis and pulmonary embolism
Describe the indirect coagulation inhibitory mechanism
Thrombin binds to thrombomodulin located on the endothelial cells. Upon binding, Protein C becomes activated. Activated Protein C and Protein S act to inhibit cofactors VIIIa and Va
Name the disease the is involved in indirect coagulation inhibitory mechanism and describe its defect
Factor 5 Leiden which the patient’s Factor Va is difficult to inhibit and so predispose patients to thrombosis
Arg506Gln