Principles Of Haemostasis Flashcards
What are the components of haemostatic response?
Platelets
Von Willebrand factor
Clotting factors= proteases/cofactors/fibrinogen
White cells
Clotting factors can be divided into 3 different categories. What are these 3 categories and which factors are included?
Which factors are vitamin K dependent?
Proteases: FVII FX FXI FIX Prothrombin (FII)
Cofactors:
FV-> works with FX
FVIII-> works with FIX
Fibrinogen + FXIII
Vit K dependent:
- FVIII
- FX
- FIX
- prothrombin
What factors does normal haemostatis depend on?
Vessel wall integrity Adequate numbers of platelets Properly functioning platelets Adequate levels of clotting factors Proper function of fibrinolytic pathway
What is the sequence of events following injury to blood vessel wall to lead to vessel repair?
Local vasoconstriction at injury site
Release of TF
2 pathways occur simultaneously:
1.
-platelet adhesion to subendothelium of damaged vessel due to exposed collagen
i.e. starts with primary haemostasis
-platelet aggregation + activation occurs
- Activation of the coagulation cascade
- formation of fibrin to act as scafold for blood clot
Pathways converge to form thrombus
What is the starting point for the intrinsic pathway?
What factors form part of the intrinsic pathway?
What is used to measure the function of the intrinsic pathway?
Starts with factor XII (i.e. vitamin K dependent protease)
FXI FXI FVIII
I.e. 7, 8, 9, 11,12
APTT is used to measure intrinsic pathway
What is the starting point for the extrinsic pathway?
What is key to activating the extrinsic pathway?
Which factors are involved in extrinsic pathway?
What test measures the function of the extrinsic pathway?
FVII
Tissue factor is key because it cleaves VII to VIIa which is the activated form
What marks the start of the common pathway?
What is the function of this factor?
Factor Xa
Intrinsic pathway:
-FX converted to FXa by FVIII
Extrinsic
-FX converted to FXa by VIIa
Function of FXa:
-convert prothrombin to thrombin
What is the function of FXIII?
Not directly involved in intrinsic and extrinsic pathways
Activated by thrombin to form FXIIIa
FXIIIa= part of formation of stable fibrin clot by helping to crosslink fibrin
What are the key features of platelets?
Anucleated
Alpha granules:
-contain secondary mediators i.e. chemokines and cytokines
Dense granules:
-contain secondary mediators
Actin myosin
-involved in platelet contraction to help in platelet aggregation
GPIIb/IIIa
-upregulated into order to form platelet aggregates i.e. used to bind to other platelets and cross link collagen
GPIb
-binds to VWF
Glycogen
-energy source for platelets
What is Von Willebrand factor?
What precipitates it binding to exposed collagen?
How is it involved with thrombosis?
Circular globular protein
Shear forces in small BV precipiate VWF to change shape and become more open
-leads to increase in surface area to bind platelets
Binds to exposed collagen and acts to bind platelets via GPIb to precipitate platelet aggregation
What are the components involved in platelet activation and aggregation?
GPIb on platelet surface binds to VWF which stimulates the release of secondary mediators involved in platelet signalling and aggregation: (secondary mediators released)
-ADP
-thrombin
-Collagen
-TXA2
I.e. involved in formation of stable clot by signallying other platelets to aggregate
What occurs in platelet granular release?
Alpha granules release:
- FGN
- FVIII
- vWF
- FV
- PDGF
Dense granules release:
- ADP
- 5HT
- Ca2+
Induces change in platelet shape which acts to increase the platelet surface area to interact with other platelets and clotting factors
What is important ask about in the history of someone suspected of bleeding disorder?
F= menorrhagia
Epistaxis (nose bleeds)
Easy bruising
Prolonged bleeding after shaving cuts
FH or personal HX of heavy bleeding after surgery or dental extraction
Medications which might affect clotting:
- antiplatelets
- anticoagulants
What are important area to exam when someone is suspected of a bleeding disorder?
Oral cavity= might have evidence of mucosal bleeding
Conjunctivae for pallor
Hepatosplenomegaly
Evidence of collagen disorder on skin + joints i.e. scars etc
-bleeding disorders can occur in association with collagen disorders
Peticia on skin
-small bleeds in dermis of skin associated with low platelets (non-blanching)
What are the 2 functiona of thrombin?
Can be prothrombotic:
-acts to convert fibrinogen to fibrin
Can by thrombolytic:
- when thrombin binds to thrombomodulin receptors on endothelium it is converted to have anticoagulent properties
- thrombin-thrombomodolin complex acts to convert protein C to activated protein C as part of the process of thrombolysis
