101 Flashcards
mechanisms that naturally keep blood thin
Nitric Oxide and PGI2 (prostacyclin)
Heparin sulphate binds anti thrombin 3 and activates - degrades CF 2,9,10
Thrombomodulin binds thrombin (2) and activates protein c - degades CF 5,8
Mechanisms of Haemostasis
Vascular spasm Platelet plug formation Coagulation clot retraction and repair Fibrinolysis
Effects in Vascular spasm
- Endothelin
- Myogenic mechanism
- Nociceptor activation
Platelet plug formation
vWF exposed and bind with platelets via Gp1b - platelets release chemicals ; ADP, TXA2, Serotonin.
Platelets activates and aggregate via binding to each other with fibrin via GPIIb/IIIa
Platelet chemicals
ADP - lead to activation of platelets to cause aggregation at injury site
Thromboxane A2 - lead to activation of platelets to cause aggregation at injury site
Bind to smooth muscle to cause contraction
Serotonin -Bind to smooth muscle to cause contraction
enhances vasco spasms
CF XIII
Fibrin cross linking to produce fibrin mesh network
Coagulation
Intrinsic Pathway (4-6 mins)
XII-XI-IX+VIII -X
X-Xa - Common pathway
Extrinsic Pathway (30 secs) III +VII (Stimulate activation of IX and also activation of common pathway X-Xa join active pathway
Factor III
produced by damaged tissue
Extrinsic pathway
Tries to drive IX-IXa or X-Xa
Clot retraction and repair
Platelet contraction
Release of PDGF (Platelet derived growth factor) - trigger proliferation of smooth muscle for repair
Vascular Endothelial Growth Factor (VEGF) - regenerate new endothelial area
Fibrinolysis
Plasminogen converted to Plasmin via TPA(Tissue Plasminogen Activator).
Break down Fibrin - release of fibrinogen and D-dimer
Heparin
Enhance Antithrombin 3 activity - Co factors disruptec
Clopidogrel
Inhibits ADP
Aspirin
Inhibits Thrombaxane A2
Abciximab
Inhibits the GpIIa/IIIb connection
Dabigatran (Prodaxa)
Inhibit activation of factor II
Warfarin
inhibits Vit K - limiting clotting factors
Diseases of platelet adhesion
Bernard-Soulier-Def GPIb
von Willebrand disease - def in vWF
Diseases of platelet aggregation
Glanzmann thrombasthenia - Def GPIIb/IIIa
Afibrinogemaenia - Def in Fibrinogen
Platelet abnormality condition
Grey platelet syndrome - deficiency in alfa granules
Wiskott-Aldrich syndrome - deficiency in dense granules
Alpha granules
Secrete - vWF and fibrinogen
Dense granules
Serotonin
ADP
Ca2+
Coagulation disorders
Haemophilia A - def VIII (Anti haemolytic factor A)
Haemophilia B - Def in IX
Anticoagulation molecules
TFPI - limits production of thrombin in initiation phase (extrinsic pathway)
Antithrombin - limits amplification (intrinsic and common pathway) 2,9,10
Protein C and S - limit cofactors VIII and V
Clot removal
Fibrinolysis
Plasminogen - plasmin via TFPI - Tissue Factor Protein Inhibitor
Bradykinin - a vasodilator. Reverses effect of serotonin and PG