Haemostasis Flashcards
What do endothelial cells do to prevent thrombus formation in the absence of injury?
Secrete prostacyclin Secrete nitric oxide Express heparin sulphate Express thrombomodulin Express tissue factor pathway inhibitor
What two processes constitute primary haemostasis?
Vasoconstriction
Platelet activation
What does secretion of prostacyclin do?
Inhibits platelet activation and aggregation
What does expression of heparin sulphate do?
Activates antithrombin
What does thrombomodulin do?
Changes thrombin’s affinity away from activation of proclotting factors towards activation of anticoagulant factors
What is the earliest response to vascular injury?
Vasospasm
What is the normal lifespan of a platelet?
10 days
What does the glycoprotein receptor, GP IIb/IIIb, on platelets bind to?
Free fibrinogen and von Willebrand factor
What is the normal activation of platelets dependant on?
Von Willebrand factor
What does von Willebrand factor bind to, causing an increase in the substances half-life?
Factor VIII (8)
What are the four primary compounds that activate platelets?
Collagen
ADP
Thromboxane A2
Thrombin
What are contained in alpha granules in platelets?
Fibrinogen
Von Willebrand factor
Factor V (5)
What do platelets release on activation to cause further platelet activation?
ADP
Thromboxane A2
What causes shape change in platelets when they are activated?
Increase in intracellular calcium
What is factor I?
Fibrinogen
What is activated factor II?
Thrombin
What is also known as Christmas factor?
Factor IX (9)
What is factor III also known as?
Tissue factor
What is specific to the extrinsic pathway?
Tissue factor Factor VII (7)
What is specific to the intrinsic pathway?
Factor VIII (8) Factor IX (9) Factor XI (11) Factor XII (12)
What is part of the common pathway?
Factor X (10)
Thrombin
Fibrin
What are the three main antithrombotic control mechanisms?
Antithrombin
Protein C pathway
Tissue factor pathway inhibitor
What does antithrombin inactivate?
Thrombin Factor VIIa Factor IXa Factor Xa Factor XIa
What does protein C and it’s cofactor, protein S, inactivate?
Factor Va
Factor VIIIa
What cleaves fibrin in fibrinolysis?
Plasmin
What activates conversion of plasminogen to plasmin?
Tissue-type plasminogen activator
Urinary-type plasminogen activator
What does plasmin cleaving fibrin produce that can be tested?
D dimer
What are the three inhibitors of fibrinolysis?
Plasminogen activator inhibitor 1
Alpha 2 antiplasmin
Thrombin activatable fibrinolysis inhibitor
What vitamin is important to the coagulation cascade?
Vitamin K
What factors is vitamin K involved (needed) in the formation of?
Prothrombin Factor VII Factor IX Factor X Protein C Protein S
What is bleeding from mucous membranes and purpura characteristic of?
Bleeding due to thrombocytopenia or abnormal platelet function
What three things can cause thrombocytopenia?
Reduced platelet production in bone marrow
Excessive peripheral destruction of platelets
Sequestration in enlarged spleen
What are the common features of immune thrombocytopenia purpura?
Easy bruising
Purpura
Epistaxis
Menorrhagia
What are the characteristic features of thrombotic thrombocytopenia purpura?
Florid purpura Fever Fluctuating cerebral dysfunction Haemolytic anaemia Sometimes accompanied with renal failure
What commonly precedes ITP in children?
Viral infection, eg varicella zoster or measles
What is there a lack of in haemophilia A?
Factor VIII (8)
How is haemophilia A inherited?
X-linked
What does the severity of bleeding in haemophilia A depend on?
Amount of residual coagulation factor activity
What are common symptoms of severe haemophilia A?
Bleeding into joints - recurrent bleeding can lead to joint deformity and crippling
Bleeding into muscles
What are the main laboratory features of haemophilia A?
Prolonged APTT Reduced level of factor VIII Normal bleeding time Normal PT Normal VWF
What is haemophilia B also known as?
Christmas disease
What is haemophilia B a deficiency in?
Factor IX (9)
What does von Willebrand factor have a role in?
Platelet adhesion to damaged subendothelium
Stabilising factor VIII in plasma
What is the abnormal in Von Willebrand disease?
Deficiency or abnormal von Willebrand factor causing:
Defective platelet function
Factor VIII deficiency
What are the typical clinical features of von Willebrand disease?
Bleeding following minor trauma or surgery
Epistaxis
Menorrhagia
Haemarthroses are rare
What are the main laboratory features of von Willebrand disease?
Prolonged bleeding time Prolonged APTT Normal prothrombin time Reduced von Willebrand factor levels Reduced factor VIII levels
What 3 things may cause vitamin K deficiency?
Inadequate stores
Malabsorption of vitamin K
Oral anticoagulant drugs
What may cause inadequate stores of vitamin K?
Haemorrhagic disease of newborn
Severe malnutrition
What are the clinical features of vitamin K deficiency?
Bruising
Haematuria
Gastrointestinal or cerebral bleeding
What are the laboratory features of vitamin K deficiency?
Prolonged prothrombin time Prolonged APTT Normal bleeding time Normal factor VIII levels Normal von Willebrand factor levels
What is disseminated intravascular coagulation?
Widespread initial thrombosis followed by a tendency to bleed
Why does bleeding occur in DIC?
Consumption of platelets and coagulation factors
Activation of fibrinolysis
Name some causes of DIC.
Malignant disease Septicaemia Haemolytic transfusion reactions Obstetric causes Trauma, burns, surgery Other infections eg malaria Liver disease Snake bite
What is the treatment for DIC?
Treat underlying cause
Maintain blood volume and tissue perfusion
Transfuse platelets, plasma, red cell concentrates in patients who are bleeding
How does the mutation in Factor V Leiden affect factor V?
Factor V is less likely to be cleaved by activated protein C
What does Factor V Leiden cause?
A tendency to thrombosis, particularly if individual has other thrombosis risk factors, eg oral contraceptive pill, pregnancy
What type of genetic conditions are protein S and C deficiency?
Autosomal dominant
