8. Haemostasis Flashcards
How does a clot form?
Clot initiation: platelet aggregation, activation of coagulation
Clot formation: thrombin converts fibrinogen to fibrin, fibrin fibres, causes retraction
Fibrinolysis: clot breaks up into fibrin fragments
Describe platelets
Megakaryocytes produce platelets in the bone marrow
Platelets bud from cytoplasm
Normal life span 7-10 days
What is platelet adhesion?
Damage to vessel wall
Exposure of underlying tissues
Platelets adhere to collagen via vWF receptor
What is platelet activation?
Secrete ADP, thromboxane and other substances to become activated and citrate other platelets
Involved in activation of clotting cascade
Revise some coagulation factors by secretion from internal stores
What is platelet aggregation?
Cross linking of platelets to form a platelet plug
What are the mediating factors?
Plt receptors - glycoprotein complexes Von willebrands factor Fibrinogen Collagen ADP Thromboxane/arachidonic acid Thrombin
What is the clotting cascade?
Amplification system activation of precursor proteins to generate thrombin (IIa)
Thrombin coverts soluble fibrinogen into insoluble fibrin
Enmeshes initial platelet plug to make stable clot
How is the clotting cascade controlled?
Natural anticoagulants to inhibit activation
Clot destroying proteins which are activated by the clotting cascade
What are the coagulation factors?
Fibrinogen
Prothrombin
Factor 5,7,8,9,10,11,12,13
Tissue factor
What are the natural anticoagulants?
Protein C
Protein S
Antithrombin
Tissue factor pathway inhibitor
Where are coagulation factors and natural anticoagulants made?
Liver
How do you measure extrinsic factors?
PT (prothrombin time)
If PT is prolonged, factor VII either not working or not making enough
How do you measure intrinsic factors?
APTT (activated partial thromboplastin time)
If APTT is prolonged, VIII, IX, XI or XII are not working or not making enough
What does it indicate if both PT and APTT are prolonged?
V, X, prothrombin or fibrinogen are not being made enough
What is Von willebrand factor?
Involved in platelet adhesion to the vessel wall, platelet aggregation and also carries FVIII (stabilises it)
What happens to the vessel wall when it is damaged and a clot is forming?
Vasoconstriction
Reduction of vWF - essential for plt adhesion
Exposure of collagen and tissue factor which initiates activation of clotting factors
What are natural anticoagulants?
Stop further coagulation Protein C Protein S Anti-thrombin If deficient, clot more easily
What are D-dimers?
Fibrin degeneration product present in blood after blood clot is degraded in fibrinolysis
What happens in fibrinolysis?
Plasminogen is converted to plasmin by plasminogen activator
Plasmin then causes clot to break up into D-dimers
What are the congenital coagulation factor disorders?
Haemophilia A (factor 8) Haemophilia B (factor 9) Etc.
What are the acquired coagulation factor disorders?
Liver disease
Vit K deficiency
Anticoagulants including warfarin (inhibits vit K) or direct oral anticoagulants (DOACs)
Why can a vitamin K deficiency cause coagulation factor disorder?
Natural anticoagulants need vitamin K
What are the possible signs and symptoms of coagulation factor disorders?
Muscle haematomas
Recurrent haemarthroses - bleeds in joints
Joint pain and deformity
Prolonged bleeding post dental extraction
Life threatening post op and post traumatic bleeding
Intracerebral haemorrhage
How is haemophilia A inherited?
X-linked recessive
