Introduction to Haemostasis Flashcards
What is haemostasis?
Arrest of bleeding and maintenance of vascular patency
What is required of haemostasis so that it may be an effective response?
Must be in permanent state of readiness
Prompt and localised response
Give protection against unwanted thromboses
What are the stages of normal haemostasis?
Formation of platelet plug = primary haemostasis Formation of fibrin clot on top of platelets = secondary haemostasis Fibrinolysis and anticoagulant defences
Where are platelets formed?
In the bone marrow by budding from megakaryocytes
What are platelets?
Small anucleated discs with a lifespan of 7-10 days
What causes platelet adhesion to the site of an injury?
Endothelial damage exposes collagen and releases VWF and other proteins to which platelets have receptors
What causes platelet aggregation at the site of the injury?
Platelets already adhered to the injury secret various chemicals that attract other platelets
What are the causes of failure to form a platelet plug?
Vascular = lack of collagen in vessel wall
Thrombocytopenia, reduced platelet function and VWF deficiency
What does failure of platelet plug formation cause?
Spontaneous bruising and bleeding
Mucosal bleeding and retinal haemorrhage = epistaxis, GI/conjunctival bleeding, menorrhagia
Intracranial haemorrhage if severe
How are disorders in primary haemostasis screened for?
Using platelet count
Why are clotting factors attracted to platelets?
Platelets contain positively charged phospholipids = attracts negatively charged clotting factors
What causes release of tissue factor?
Endothelial damage
What is the first step in fibrin clot formation?
Tissue factor binds to clotting factor VIIa = this then activates factors V and Xa
What does the activation of factors V and Xa in the clotting cascade cause?
Activate prothrombin to form thrombin = this causes fibrinogen to form fibrin
Why is an alternative simultaneous pathway needed to produce fibrin?
Only limited amount of tissue factor released which wouldn’t produce enough fibrin by the main pathway to stop bleeding
What is the alternative pathway that produces fibrin via a positive feedback loop?
Thrombin activates factors VIII and IXa = these activate further factors V and Xa
What are the different phases of fibrin clot formation?
Initiation = tissue factor release Amplification = activation of factors VIII and IXa Propagation = fibrin formation
What are some causes of failure to form fibrin clot?
Single clotting factor deficiency = usually hereditary
Multiple clotting factor deficiencies = usually acquired
Increased fibrinolysis = usually part of complex coagulopathy
What occurs in fibrinolysis?
tPA activates plasminogen to form plasmin
Plasmin causes fibrin to break down to form FDPs
What can be measured to show excessive fibrinolysis?
D-dimers = formed by cross-linkage of FDPs
What can be used to screen for fibrin clot formation abnormalities?
Prothrombin time and activated partial thromboplastin time
What is the initial step in both prothrombin time and activated partial thromboplastin time?
Blood is added to citrate and centrifuged to separate platelets
How is prothrombin time measured?
Add tissue factor and phospholipid = measure time taken for blood to clot
How is activated partial thromboplastin time measured?
Add phospholipid and contact activator and measure clotting time = tests factors VIII and IXa
