Haemostasis Flashcards
What are the principles of haemostasis?
To prevent bleeding and unnecessary coagulation, allowing blood to flow
What things are essential for haemostasis?
1) To keep blood moving
2) Platelets
3) Coagulation factors
4) Anticoagulant factors
What are the precursors to platelets?
Megakaryocytes
What is the normal platelet count?
150-400 x 109/L
What is the normal life span of platelets?
7-10 days
What are the three major steps of haemostasis?
1) Vasoconstriction
2) Temporary blockage of a break by a platelet plug
3) Blood coagulation, formationof a fibrin clot which stabilises the friable platelet plug into a stable clot
What is the end result of the activation of the clotting system?
Production of thrombin which acts on fibrinogen to produce fibrin filaments, which are then deposited and trap red blood cells
What are the only cells that can be in contact with blood and not clot it?
Endothelial cells, white blood cells, unactivated platelets and red blood cells
What are platelets activated by?
Collagen surfaces, ADP (released by activated platelets for amplication purposes), thromboxane A2 and thrombin
What do platelets do when they are activated?
1) Stick to the exposed subendothelium, specifically to von Willebrand factor which is concentrated on the subendothelial basement membrane
2) Aggregate with other platelets to form a plug (fibrinogen binds to the platelets and sticks them together)
3) Swell and change shape into sticky spheres
4) Secrete factors from platelet granules that help the platelet plug to grow and aid clotting
How does aspirin decrease platelet aggregation?
Irreversibly inactivates cyclooxygenase - one of the enzymes responsible for the production of thomboxane A2
What is the endpoint of the clotting cascade?
Fibrin is produced
What is the enzyme that cleaves the circulating plasma protein fibrinogen into fibrin?
Thrombin
What do many of the clotting factors (including Factors II, VII, IX and X) require for their synthesis?
Vitamin K
What are some examples of co-factors for the enzymes of the clotting cascade?
Phospholipids and calcium
What are the two clotting pathways?
Intrinsic (factors all contained within blood, triggered by negatively charged surface, no vessel needs to be broken for it to occur)
Extrinsic (needs a tissue factor - thromboplastin. Triggered by thromboplastin released from damaged cells adjacent to the area of haemorrhage)
What is the role of the vascular wall in clotting?
Arterial media contracts when an artery is damaged
Subendothelium traps platelets
Endothelium secrete substances such as tissue plasminogen activaator, thrombomodulin, vwf, tissue factor
What factors oppose clotting?
Antithrombin III, protein C and protein S
What is the enzyme responsible for fibrinolysis?
Plasmin
What is the inactive precursor of plasmin?
Plasminogen
What is plasminogen activated by?
Tissue plasminogen activator
What is streptokinase?
Plasminogen activator - obtained from streptococci
What is urokinase?
A plasminogen activator found in urine
What is haemophilia A a deficiency in?
Factor VIII
How is haemophilia A inherited?
X-linked recessive
What would be the results of a blood test of a patient with haemophilia?
Normal platelet count Normal bleeding time Normal prothrombin time Prolonged APTT (measures the intrinsic pathway of which factor VIII is a part) Low factor VIII assay
What is haemophilia B?
Factor IX deficiency
What is Von Willebrand Disease caused by?
Deficiency or abnormality in von willebrand factor
What are the functions of von Willebrand factor?
Assists in platelet plug formation by attracting circulating platelets to sites of vessel damage and stabilises factor VIII, protecting it from premature destruction
How could a patient with von Willebrand disease be diagnosed?
Raised bleeding time and APTT
Common pattern of bleeding is mucosal bleeding reflecting the inadequate platelet function and adhesion
How could a patient with thrombocytopenia be diagnosed?
Prolonged bleeding time
Normal PT and APTT (as these assess clotting cascade, not platelet function)
What are the causes of thrombocytopenia?
1) Decreased platelet production (eg bone marrow malignancy, drugs, infections, B12 and folate deficiency)
2) Decreased platelet survival (immunologic destruction)
3) Sequestration - in an englarged spleen
4) Dilutional - due to massive blood transfusions (blood stored for more that 24 hours do not contain platelets)
What is disseminated intravascular coagulation?
Thrombohaemorrhagic disorder occurring as a secondary complication in a variety of conditions
What are thrombophilias?
Inherited or acquired defects of haemostasis resulting in a predisposition to thrombosis
eg factor V leiden, antithrombin deficiency, protein C or protein S deficiency
What is bleeding time?
Bleeding time is a medical test done on someone to assess their platelets function
What are some diseases that prolong bleeding time?
Thrombocytopenia, von willebrands disease, disseminated intravascular coagulation
What is prothrombin time?
Prothrombin time (PT) is a blood test that measures how long it takes blood to clot.
