Disorders Of Blood Coagulation Flashcards
Why is blood clotting a good thing?
Stops bleeding at the site of injury
Keeps blood in and pathogens out
What activates clotting?
Endothelium in blood vessels normally maintains an anticoagulant surface- when this is broken, collagen is exposed which activates clotting
What is involved in primary haemostasis?
Platelet adhesion, aggregation, activation
What is involved in secondary haemostasis?
Activation of fibrin formation through the clotting cascade
What happens in primary haemostasis?
If collagen becomes exposed to blood, von willebrand factors bind to it
Von willebrand factors bind to platelets from blood and activate them
Activated platelets express functional fibrinogen receptors
What happens in secondary haemostasis?
Tissue factor activates the coagulation cascade to initiate a minor burst of thrombin
Factor VIIa binds to tissue factor -> FXa -> conversion of prothrombin to thrombin
Thrombin activates receptors on platelets and endothelium -> inc in platelet aggregation and release of von willebrand factors
Thrombin also activates FVIIa and FVa which then form tenase complex and prothrombinase complex with platelets
What does the tenase complex do?
Accelerate production of factor Xa
What does the prothrombinase complex do?
Activate thrombin
What happens in fibrinolysis?
Plasminogen -> plasmin by tissue plasminogen activator
Plasmin then degrades the fibrin mesh -> fibrin degredation products
What is an example of fibrin degredation products?
D-dimer
Where is tissue plasminogen activator found?
Endothelial cells
What does antithrombin inhibit?
Serine protease
What is antithrombin activity enhanced by?
Binding heparan binding sites on endothelial cells
What does antithrombin inhibit?
Coagulation - thrombin, IXa and Xa
What is heparan binding domain?
Basis of the anticoagulant activity of heparin
What does heparin do?
Increases the activity of ATIII
What are protein C and S?
Natural anticoagulant plasma proteins
What is protein C activated by?
Thrombin bound to thrombomodulin on endothelial cells
What is protein S?
APC cofactor which helps with binding to cell surfaces
What does APC do?
Degrades cofactors FVa and FVIIIa
What are three blood clotting disorders?
Haemophilia
Thrombophilia
Disseminated intravascular coagulation
What are haemophilia A and B?
Mutations in coagulation factors
What is von willebrand disease?
Platelet disorder
What do collagen abnormalities cause?
Fragile blood vessels and bruising
What is haemophilia?
Failure to clot -> haemorrhage
What is thrombophilia?
Excessive clotting -> thrombosis
What causes inherited thrombophilia?
Mutations in coagulation factors
What causes acquired thrombophilia?
Malignancy increases clotting factors
What is disseminated intravascular coagulation?
Whole body clots
What causes haemophilia A?
Mutated FVIII
What causes haemophilia B?
Mutated FIX
What does haemophilia look like clinically?
Bleeding into joints
What does von willebrand disease look like clinically?
Bleeding in the mucous membrane
What happens when there is a factor V leiden mutation?
Resistance to APC -> FVa not activated -> increased risk of DVT
What happens in an antithrombin deficiency?
Thrombin, IXa and FXa are not inactivated -> increased risk of DVT
What are some causes of excessive clotting?
Factor V leiden mutation
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
What does DVT development depend on?
Alterations in the blood constituents
Changes in normal blood flow
Damage to the endothelial layer
What are the symptoms of DVT?
Pain and tenderness of veins Limb swelling Superficial venous distension Increased skin temperature Skin discolouration
What are the risks with DVT?
If the clot is above the knee it is significantly more likely to embolise
What is disseminated intravascular coagulation seen in?
Sepsis
What happens in disseminated intravascular coagulation?
Depletion of clotting factors and platelets leading to bleeding
What do anticoagulants do?
Prevent more clotting
What do thrombolytics/ fibrinolytics do?
Reverse clotting
Give some examples of anticoagulants
Warfarin
Heparin
Direct oral anticoagulants (DOACs)
Give examples of thrombolytics/fibrinolytics
Plasminogen activators : EPA, streptokinase
What does VTE stand for?
Venous thrombus embolism
What pre-treatment investigations can you give for VTE?
Clotting screen
FBC
Renal screen
Liver function tests
What does the clotting screen show?
Prothrombin time
Partial thromboplastin time
Thrombin time
What are the treatments for DVT?
Anticoagulants
What are examples of DOACs?
Rivaroxaban and apixaban
Dabigatran
What are some bleeding complications from anticoagulants?
Anything from nosebleed -> intercranial haemorrhage
