Haemostasis Flashcards
What are the 2 main functions of haemostasis?
Maintenance of:
- vascular integrity
- blood fluidity
What factors are involved in haemostasis?
- Blood vessels
- Platelets
- Von Willebrand Factor
- Coagulation cascade
- Fibrinolytic mechanisms
What is primary haemostasis?
Formation of the primary plug
What are the first steps involved when there is vascular endothelial damage?
- Exposure of sub-endothelial collagen
- Release of P-selectin inducing ‘rolling’ of platelets and leucocytes
- Release of von Willebrand factors which bind to collagen and platelets
How does platelet-endothelium adhesion occur?
Via GPI receptor who binds to von Willebrand factor or collagen, enabling platelets to adhere to the damaged endothelium
How does platelet aggregation occur?
Platelet-platelet via GPIIb/IIIa receptor through fibrinogen of vWF bridges
What can platelets secrete following activation?
- Thromboxan
- Serotonin
- factorV
- ADP
- ATP
- Plasminogen
How does clot retraction occur?
Activated platelet, interplatelet bridging via fibrinogen and platelet myosin+actin undergo a contractile process that cause clot retraction which facilitates wound closure
What is the von Willebrand structure, and what is it involved in?
- Large multimeric plasma protein produced by endothelial cells
- Involved in platelet adhesion and aggregation
von Willebrand structure is secreted as a carrier of which factor?
Factor VIII
What is secondary haemostasis?
Formation of the definitive clot - coagulation
How is the definitive clot formed?
Conversion of soluble fibrinogen to insoluble fibrin mediated by thrombin (activation sustained by the coagulation cascade)
Fibrin cross linkage forms a mesh that makes the platelet plug more stable
Define the role of the coagulation cascade
Interconnected series of enzyme activated steps resulting in the formation of thrombin (factor IIa) and insoluble fibrin
The factors of the coagulation cascade are in the order of?
When they were discovered
Which of the factors is fibrinogen, and which is fibrin?
Factor I
Activated form Factor 1a
Which of the factors are the following:
- Free Ca ions
- Prothrombin
- Tissue factor
- Thrombin
- IV
- II
- III
- IIa
Most steps of the coagulation cascade involve?
- an enzyme, substrate and cofactor
- assembled and localised on a phospholipid surface
- with free calcium ions
Which factors are involved in the intrinsic and extrinsic pathways?
Extrinsic = Factor VII + tissue factor as an activator Intrinsic = XII, XI, IX, VIII
Describe the common pathway and the factors involved
- Xa, Va and free calcium on a phospholipid surface form the prothrombinase complex
- Converts II into IIa (prothrombin into thrombin)
- This converts I into Ia (fibrinogen into fibrin)
- Amplifies coagulation
- The common pathway is the end of both the intrinsic and extrinsic pathway
The PTT tests for which pathways?
Intrinsic and common
The PT tests for which pathways?
Extrinsic and common
Where are the coagulation factors produced?
In the liver
Which factors are vitamin K dependant?
II, VII, IX, X
Which factors are non-enzymatic?
Factor III - tissue factor
Factor I (fibrinogen)
Factor V
Factor VIII
What do the vitamin K dependant factors rely on for activity?
Carboxylation in the liver - need to bind to free calcium ions
Why don’t we turn into a big clot?
- Dissolution of the clot, fibrinolysis
- Natural anticoagulants
Describe tertiary haemostasis
- Fibrinolytic pathway
- Starts when coagulation starts
- Lysis of platelet-fibrin network
- Degrades fibrin to fibrin degradation products including D-dimers
Tertiary haemostasis is mediated by?
Plasmin
What is the major anticoagulant?
Antithrombin III
Which molecule enhances the action of antithrombin III?
Heparin
What are other natural anticoagulants?
- Intact endothelium
- Protein C
- Tissue factor pathway coagulation inhibitor
Which factor starts the intrinsic pathway?
Factor XII
What is the end product of secondary haemostasis?
Cross-linked fibrin
Which factor is activated by the intrinsic and extrinsic pathways?
Factor X
Haemophilia A is a deficiency of factor VIII, which test result would be altered?
PTT
In severe liver insufficiency, which test results can be altered?
PT, PTT, fibrinogen conc
