Haemostasis and bleeding disorders Flashcards
(32 cards)
What is haemostasis?
The arrest of bleeding and the maintenance of vascular patency
What is needed for haemeostasis?
Permanent state of readiness, prompt response, localised response, protection against unwanted thrombosis
What are the components of a normal haemostatic system?
- Formation of platelet plug - primary haemostasis
- Formation of fibrin clot - secondary haemostasis
- Fibrinolysis
- Anticoagulant defences
How are platelets formed?
Formed in the bone marrow by budding from megakaryocytes
Describe the structure of platelets
Small anucleate discs with a mean life span of 7-10 days
What is the function of platelets and what is the mechanism behind this function?
Endothelial damage exposes collagen and releases Von Willebrand Factor (VWF) and other proteins to which platelets have receptors - platelet adhesion at the site of injury
There is then secretion of various chemicals from the platelets, which leads to aggregation of platelets at the site of injury
Name some causes of failure of the platelet plug
- Vascular e.g. age, steroids, Henoch-Schonlein purpura, scurvy, Marfan’s syndrome
- Thrombocytopenia - reduced production e.g. marrow problem or increased destruction
- Reduced function of platelets - drugs e.g. aspirin, renal failure
- Von Willebrand factor deficiency
What can happen as a consequence of failure of platelet plug formation?
Spontaneous bruising and purpura, mucosal bleeding (epistaxes, GI, conjunctival, menorrhagia), intracranial haemorrhage, retinal haemorrhages
How is primary haemostasis screened for?
Platelet count
No simple screening tests for other components of primary haemostasis
What are some causes of failure of fibrin clot formation?
- Single clotting factor deficiency - usually hereditary e.g. haemophilia A and B - isolated prolonged APTT
- Multiple clotting factor deficiencies - usually acquired e.g. disseminated intravascular coagulation (DIC), liver disease, vitamin K deficiency - multiple screening tests prolonged
- Increased fibrinolysis - usually part of complex coagulopathy
What are the possible consequences of failure of fibrin clot formation?
- No characteristic clinical syndrome
- May be combined primary/secondary haemostatic failure
- Pattern of bleeding depends on single/multiple abnormalities and the clotting factors involved
What are some screening tests for fibrin clot formation?
- Prothrombin time
- Activated partial thromboplastin time
Name some naturally occurring anticoagulants
Serine protease inhibitors, protein C and protein S
What is thrombophilia?
Deficiency of naturally occurring anticoagulants, may be hereditary
Increased tendency to develop venous thrombosis (DVT/PE)
How is a fibrin clot formed in terms of clotting factors?
- Endothelial damage -> Tissue Factor forms a complex with factor VIIa -> Va/Xa are activated as a result
- Factor Va/Xa allows the conversion of prothrombin into thrombin
- Thrombin then stimulates factor VIII/IXa to activate more V/Xa and thus convert more prothrombin into thrombin
- Thrombin allows fibrinogen to be converted into fibrin
What are some causes of peripheral platelet destruction?
- Coagulopathy e.g. disseminated intravascular coagulation (DIC)
- Autoimmune e.g. immune thrombocytopenic purpura (ITP)
- Hypersplenism
What are the causes of Von Willebrand deficiency?
Acquired
Hereditary - autosomal dominant, common, variable severity (generally mild)
What is the most common cause of primary haemostatic failure?
Thrombocytopenia - usually acquired, due to either marrow failure or peripheral destruction
What can cause multiple clotting factor deficiencies which then lead to failure of fibrin clot formation?
- Liver failure
- Vitamin K deficiency/warfarin therapy
- Complex coagulopathy - DIC
What is used to investigate cause of failure of fibrin clot formation?
- APTT - activated partial thrombplastin time
- PT - prothrombin time
- Both will be prolonged in clotting factor deficiencies
Where are coagulation/clotting factors synthesised?
In hepatocytes - thus reduced in liver disease/failure
Why is vitamin K important in coagulation?
Factors II, VII, IX and X are carboxylated by vitamin K, which is essential for function
Where do we get vitamin K from, where is it absorbed and what does it need for absorption?
- Sources - diet and intestinal synthesis
- Abosrbed in upper intestine
- Requires bile salts from gall bladder for absorption
What can cause vitamin K deficiency?
- Poor dietary intake - typically patients in ICU with parenteral feeding
- Malabsorption
- Obstructive jaudive i.e. gall stones block bile salts from travelling from the liver to the intestine for vitamin K absorption
- Vitamin K antagonists - warfarin
- Haemorrhagic disease of the newborn
