Haemostasis Flashcards
What is haemostasis?
the arrest of bleeding WHILST maintaining vascular patency
What qualities must haemostasis have to be effective?
- ready to act quickly
- localised response (prevent clots everywhere)
- must protect against unwanted thrombosis
How are platelets formed and how long do they last in the circulation?
- budding off of megakaryocyte cytoplasm
- anucleate cells => only live for 7-10 days
What is formed during Primary Haemostasis?
Platelet plug at injury site
- can stop bleeding in minor injuries, but often overcome in larger wounds
How is the platelet plug formed?
- Endothelial (vessel wall) damage
- exposes collagen/ releases Von Willebrand Factor (VWF) and other proteins
- platelets have receptors to these => adhesion at site of injury
- platelets secrete chemicals to aggregate other platelets at site
WHat is the role of vWF in the platelet plug?
Allows platelets to stick to collagen and to each other
How long before a procedure must aspirin be stopped to allow for enough platelet formation to clot the blood?
1 week
- gives body time to make platelets but doesn’t overexpose patients to risk of clot
Why may the platelet plug fail to form?
- lack of collagen in vessels (due to increasing age or conditions e.g. scurvy [need Vit C to make collagen])
- platelet dysfunction (reduced no. [thrombocytopenia] or reduced function [due to drugs e.g. NSAIDs])
- vWF deficiency disorder (familial disorder)
What are the clinical consequences or symptoms patients will experience if they fail to make a platelet plug?
- spontaneous bruising and purpura (wont blanche)
- usually in lower limb (Thighs)
- mucosal bleeding
=> Nose, GI tract, conjunctival, retinal, menorrhagia, blood blisters in mouth
In severe cases:
- intracranial haemorrhage (v. low platelet function)
Why do more female patients present with bleeding disorders than men?
- many female patients present with menorrhagia which warrants referral
WHat screening tests can be used for Primary Haemostasis?
- FBC and make sure to check platelet count
What is formed in secondary haemostasis and where does this take place?
- fibrin clot formation
- occurs on surface of platelet plug
How are various clotting factors attracted to the surface of the platelet plug?
- Platelet plug surface = phospholipid (-ve charge)
- Ca2+ released and is attracted to -ve surface
- Ca2+ forms positive layer over platelet plug
=> -ve charged clotting factors are attracted to +ve Ca2+ layer
What clotting factors are involved in the initiation of the clotting cascade?
Tissue Factor(TF) and Factor VII complex => TF/VIIa
Describe the activation of each complex in the coagulation cascade
EXTRINSIC
- TF/VIIa activates V/Xa
- These then cleave Prothrombin (Factor II) to active Thrombin (Factor IIa)
- active Thrombin (IIa) can then change Fibrinogen to Fibrin (to make clot)
INTRINSIC
- Thrombin also causes activation of VIII/IXa complex
- this activates V/Xa again, causing further amplification of the cascade
What clotting factor complex is involved in the amplification of the coagulation cascade?
VIII/IXa
What stage of the coagulation cascade is known as propagation?
Prothrombin -> thrombin
as thrombin is most important to go on and activate fibrinogen and intrinsic pathway
What can cause failure of a fibrin clot?
- Single clotting factor deficiency (hereditary)
eg Haemophilia - Multiple clotting factor deficiencies (acquired)
eg Disseminated Intravascular Coagulation (DIC) - Increased fibrinolysis (=> more clot breakdown)
e. g. in complex coagulopathy
What clotting factor can be lost in haemophilia?
Problem with VIII/IX complex
=> Haemophilia A = Factor VIII deficiency
=> Haemophilia B = Factor IX deficiency
Why does DIC tend to occur?
lots of inflammation and tissue damage in body causes high release of Tissue Factor (TF)
=> clots appear throughout the body
What is the usual aim of fibrinolysis when the body has had to clot blood?
Breaks down the EDGE of the blood clot to allow blood to still flow past it
=> maintains blood vessel patency
Describe the fibrinolysis cascade
Tissue plasminogen activator (tPA) activates plasminogen -> plasmin
Plasmin changes fibrin (in clots) to fibrin degradation products
If patients cant form fibrin clots, how do they clinically present?
- No characteristic clinical picture
- May be combined primary/secondary haemostatic failure => may have low platelets
- bleeding into joints (ankles, knees, elbows) and muscle common in haemophilias
- massive bruising due to internal bleeding
What can tPA be used for clinically if it has the ability to breakdown clots?
- Stroke
- PE
