13. Haemostasis 1 Flashcards
(48 cards)
What is the role of Coagulation factors?
Help form clots to plug holes in vasculature
What is the role of Regulatory factors in haemostasis?
Stop coagulation system firing off prematurely
which would cause thrombosis
What prevents coagulation factors being triggered unnecessarily?
Triggers are outside the circulation in the sub endothelial tissue (Collagen and Tissue factor)
What is Von Willebrand Factor (vWF)?
A giant adhesive plasma protein
Has multiple binding sites for platelets, collagen and factor 8
How is Von Willebrand Factor found in blood normally?
In a rolled up form
Many of its binding sites are hidden
What happens when vWF binds to collagen?
Blood flow pushes it along and stretches it
vWF becomes long and thin
Describe platelets
Fragments of megakaryocytes Much smaller than RBCs No nucleus Granular Half life ~10 days
List 3 stimulatory receptors on platelets and what they bind to
P receptors: bind ADP
Thromboxane receptors: bind thromboxane
PGI2: binds prostacyclin
List 2 adhesive receptors on platelets and what they bind to
Integrin alpha-II-b-beta-3
GPIb-alpha
Both bind to vWF
What is exposed when the endothelial layer is damaged?
Collagen and tissue factor
What is required in primary haemostasis?
Collagen
Platelets
Von Willebrand Factor
(+ fibrin in larger vessels for stabilisation)
Describe the formation of a platelet plug in primary haemostasis
Rolled up vWF binds to exposed collagen and gets stretched out Exposes vWF binding sites for platelets Platelets bind as they flow by Platelets become activated Granules discharge, release more vWF vWF captures more platelets
What do platelets bind to other platelets in a platelet plug with?
Fibrinogen
What is platelet activation?
Conversion from a passive to an interactive cell
How are activated platelets different?
Change shape
Expose phospholipid
Present new or activated proteins on their surface
What happens inside platelets when they’re activated?
Ca2+ flux causes granules to degranulate
Release ADP, Fibrinogen and vWF
Takes phospholipid from its surface and makes thromboxane
What is coagulation?
Formation of a fibrin mesh (occurs in secondary haemostasis)
List the Sites of Synthesis of Clotting Factors, Fibrinolytic Factors and Inhibitors
Liver (primarily)
Endothelial cells (Factor VIII and vWF)
Megakaryocytes (to platelets) (vWF and factor V)
What is the co-factor needed to activate factor VII?
Tissue factor
When factor VII and tissue factor form a complex what happens?
Becomes activated (VIIa) Turns inactive proteins (factors IX and X) into active forms (IXa and Xa)
What is the dampening mechanism that turns off coagulation almost immediately?
TFPI
Binds to FVIIa and FXa
What can FXa make before the coagulation process is dampened by TFPI?
Thrombin
What does thrombin do if there is enough made before the dampening process?
Forms 2 complexes:
IXa enzyme, VIIIa cofactor, PL (phospholipid that platelets are providing)
+
Xa enzyme, Va cofactor on surface of PL with Ca2+
These make a lot more thrombin
What extra feedback can make more FIX if needed?
XI activated to XIa
Converted to IX
