Haemostasis Basics Flashcards
Haemostasis
The cessation of bleeding at a vascular injury site via the formation of a thrombus
Platelet Plug
Primary haemostasis
Circulating platelets form physical plug
Adhere to injury site + each other
Stop leak
Fibrin Clot
Secondary haemostasis
Assembly + activation of series of coagulation factor proteases
Cause thrombin production
Thrombin
Produces fibrin monomers
Can cross link together to form stabilised protein meshwork around plug
Platelets derivation
Megakaryocyte
1 megakaryocyte= over 1000 platelets
Platelets structure
no nucleus
1-4microm
Platelet circulation time
8.5-10 days
Platelet half life
4 days
Platelet production regulation
Thrombopoietin
Platelet level normal
150-400 x10(9) per litre
Thrombocytopenia
Platelets below 150x10(9) per litre
Thrombocytosis
Platelet above 400x10(9) per litre
Platelet adhesion prevention
NO and PGI2 (prostacyclin) release
What happens when endothelium exposed
NO production stops
Collagen under endothelium exposed
VWF
Protein in blood
Binds to exposed collagen
Receptor which helps bind platelets to VWF
Platelet GP1b receptor
Platelet GP2b/3a receptor
Expressed by adherent platelets
Binds to fibrinogen
Fibrinogen binds to more platelets to form meshwork
Platelet aggregation pathway
Endothelium exposed NO production stops Collagen under endothelium exposed VWF binds to collagen Platelets bind to VWF via GP1b receptors Platelets express GP2b/3a receptor Receptor binds to fibrinogen Meshwork formed
Bound platelet changes
Become spiky + change shape
Release ADP, TXA2 and 5HT
ADP + TAX2 effect
Attract more platelets to the site
Aggregate to form platelet plug
5HT effect
Acts on local smooth muscle
Vasoconstriction
Bleeding time test
Normally stops 1-9mins
Children 1-13 mins
F>M
Plug spread prevention
Healthy endothelium next to damaged site releases NO
Extrinsic pathway
Triggers coagulation after vessel injury
Factor VII
Plasma protein
Factor III + Factor VII
Factor III exposed when blood vessel injured
Factor III converts VII–> VIIa
Factor III (tissue factor)
Intracellular in endothelium and smooth muscle
Factor VIIa
Reacts with Ca and Factor X to form Xa
Xa and Ca
Prothrombin –> thrombin
Common pathway
Prothrombin –> thrombin
prothrombin time
Assesses extrinsic + common pathway
Activate partial prothrombin time
assesses intrinsic and common pathway
INR
Number derived from PT
0.8-1.2
Used to assess coagulability of patients on heparin or warfarin
haemophilia A
Deficiency factor VIII
Haemophilia B
Deficiency factor IX
Plasmin
removal of clots when damaged tissue healed
Plasminogen inactive form
Held by alpha-2 antiplasmin
tPA
Released from endothelial cells
Catalyses plasminogen –> plasmin
D-dimer
production of fibrin breakdown
Low D-dimer levels
indication thrombosis not present
Vitamin K deficiency
Increased INR
Unstable clots
Heparin
Activates anti-thrombin
AT inhibits thrombin + factor Xa
IV as not absorbed by gut
Short half life
Warfarin
Competes with sites that bind Vit K
Reduces effectiveness of clotting factors especially Factors VII, IX and X
Increases prothrombin time
Daibigatran
Direct thrombin inhibitor
Rivaroxaban, apixaban, edoxaban
factor Xa inhibitors
