Haemostasis Flashcards
What is haemostasis?
The arrest of bleeding and the maintenance of vascular patency.
What are the requirements of haemostasis
Permanent state of readiness
Prompt response
Localised response
Protection against unwanted thrombosis
What are the components of haemostasis?
Formation of platelet plug
Fibrin clot formation
Fibrinolysis
What is primary haemostasis?
Formation of platelet plug
What prevents primary haemostasis in undamaged blood vessels?
Negative charge
Vasodilation (NO and prostocyclins- also inhibit platelet aggregation)
Plasminogen activators.
How are platelets formed?
Budding off megakaryocytes
Describe platelets
Small anucleate discs
How long to platelets last for?
7-10 days
How do platelets stop bleeding?
Adhere to collagen in damaged endothelium (vessel walls).
Damaged walls causes release of Von Willebrand Factor (VWF) which attaches to exposed collagen and platelets have receptors for.
What can cause failure of platelets/primary haemostasis?
Vascular
Platelets
vWF
What is a reduced number of platelets called?
Thrombocytopenia
What are the consequences of platelet failure?
Spontaneous Bruising and Purpura
Mucosal Bleeding
Intracranial haemorrhage
Retinal haemorrhages
What are common locations of mucosal bleeding?
Epistaxes
Gastrointestinal
Conjunctival
Menorrhagia
How do you investigate primary haemostasis?
Platelet count
No simple screening tests for other components of primary haemostasis
What is secondary haemostasis?
Fibrin clot formation
Describe fibrin clot formation
1) VII from circulation combines with tissue factor (TF) (III) on platelets.
2) Tf/VII converts X to Xa (initiation)
3) Xa and cofactor V (V/Xa) convert prothrombin (II) to thrombin (propagation)
4) Thrombin converts fibrinogen (I) to fibrin.
5) Thrombin activates VIII/IXa which further induces V/Xa (amplification)
What is extrinsic coagulation?
Factor VII and TF -> Fibrinogen to fibrin
Propogation
What is intrinsic coagulation?
Thrombin activates VIII/IXa which further induces V/Xa (amplification)
How do you measure extrinsic coagulation?
Prothrombin time
How do you measure intrinsic coaguation?
Activated partial thromboplastin time
What are the fibrinogen receptors on platelets called?
Glycoprotein IIb-IIIa
What additional molecule is needed for GPIIb-IIIa to bind fibriongen and aggregate platelets?
ADP
What can cause secondary haemostasis failure?
Single clotting factor deficiency
Multiple clotting factor deficiencies
Increased fibrinolysis
Are single clotting factor deficiencies usually hereditary or acquired?
Hereditary
What can cause increased fibrinolysis?
Complex coagulopathies
What are the consequences of secondary haemostasis failure?
No characteristic clinical syndrome
May be combined primary/secondary haemostatic failure
Pattern of bleeding depends on: Single/multiple abnormalities, the clotting factors involved
What is fibrinolysis?
Breakdown of fibrin
Describe fibrinolysis
Fibrin converted to fibrin degradation products (FDP) by plamsmin.
What does plasmin do?
Breakdown fibrin
Describe production of plasmin
Plasminogen converted to plasmin by Tissue Plasminogen Activator (tPA) (released from endothelial cells).
Why do we have natural anticoagulant defences?
To control coagulation
What are three natural anticoagulats we have?
Antithrombin
Protein C
Protein S
What does antithrombin block?
Thrombin
Tf/VIIa
V/Xa
VIII/IXa
What does Protein C block?
Blocks VIII/IXa
What does Protein S block?
Blocks V/Xa
What can a failure of natural anticoagulation cause?
Thrombophilia
What activated Protein C and S?
Thrombin
