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Haemostatics. Virchow’s Triad. Hypercoagulable state. Stasis/turbulence. Endothelial injury. Clotting Processes. 1) Vascular Phase (immediate): Transient vasoconstriction Exposure of underlying subendothelium Local factors. Clotting Processes (cont.). 2) Platelet Phase (15 sec):
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Virchow’s Triad Hypercoagulable state Stasis/turbulence Endothelial injury
Clotting Processes 1) Vascular Phase (immediate): • Transient vasoconstriction • Exposure of underlying subendothelium • Local factors
Clotting Processes (cont.) 2) Platelet Phase (15 sec): • Adhesion to subendothelium (mediated by von Willebrand factor) • Secretion of chemicals (5-TAPP) • 5HT: promotes vasoconstriction • Thromboxane A2: ↑ platelet aggregation • Adenosine diphosphate: activates GpIIb/IIIa to ↑ platelet binding • PAF (platelet activating factor): ↑ platelet aggregation • Plasminogen: localises clot formation at injury site *Aspirin, Dipyridamole *Clopidogrel, dipyridamole *Fibrinolytics (streptokinase, urokinase)
Clotting Processes (cont.) 3) Coagulation Phase: Extrinsic Pathway: Exposure to Tissue Factor Intrinsic Pathway: Exposure to collagen/glass XIIa XII VII VIIa + TF XI XIa IX IXa X Xa VIII VIIIa XIII XIIIa II IIa (thrombin) V Va I Ia (fibrin) • Warfarin blocks II, VII, IX, X (TV Channels) • Heparins activate III blocks Iia and Xa (low molecular weight heparins especially blocks Xa) • Dabigatran blocks II (thrombin). Is currently trialed as a less fussy (wrt interactions and monitoring) alternative to warfarin
Clotting Processes (cont.) • Coagulation Limiters: restricted to sites of exposed phospholipids • Antithrombin III: blocks IIa, Ixa, Xa, XIa and XIIa • Protein C: inactivates V, VIII • Protein S is a cofactor for Protein C • Protein C is activated by thrombin (IIa) • Tissue Factor Pathway Inhibitor (TFPI): blocks Xa, IIa
Haemostasis in Bruises • Types of bruises: • Damaged vessels (e.g. trauma, vasculitis) • Changes in blood (e.g. thrombocytopaenia) • Changes in dermis (e.g. senile purpura, scurvy) • Bruise = blood vessel damage that causes leaking into surrounding connective tissue • Petechiae are a type of bruising (a tiny red-purple spot; purpura and ecchymosesare similar but are larger) • Not to be confused with telangiectasia(capillary dilatation, e.g. from old age, steroid use, irradiation, liver failure)
Purpura – large red-purple spots (>10mm) Petechiae – tiny red-purple spots (<3mm) Telangiectasia – dilated capillary network Purpura – bigger red-purple spots (3-10mm)
Relevance to Dengue Fever • The patient had petechiae • The petechiae are possibly a result of thrombocytopaenia or platelet dysfunction makes it easier to break capillaries • Capillary vasodilationin critical phase could potentially worsen symptoms by increasing bleeding
References • Sherwood. Human Physiology 6th edition • Rang and Dale’s Pharmacology • Cross and Underwood. General Systemic Pathology • Kuma. Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed • AMH • Therapeutic Guidelines • Australian Prescriber: http://www.australianprescriber.com/magazine/32/2/51/5