PSC1002/L03 Haemostasis Flashcards
Define haemostasis.
The arrest of bleeding from a broken blood vessel from arterioles, venules and capillaries
Describe platelets.
Small cell fragments (anuclear) budded of edge of large bone marrow cells (megakaryocytes)
What is platelet and megakaryocyte production mediated by?
Thrombopoietin - hormone produced in liver and kidneys
Describe the process of thrombopoiesis. (3)
Haematopoietic stem cell differentiates into myeloid cell line
Megakaryoblast into megakaryocyte
Thrombopoietin stimulates MKC to extend arms through bone marrow sinusoids into blood vessels
How many platelets are produced each day?
10^11
How many platelets can a megakaryocyte produce in its lifetime?
1000-3000
Where are platelets stored and how are they released?
Spleen
Released by contraction of the spleen activated by SNS
How are platelets disposed of?
After 7-10 days, apoptosis and phagocytosed in liver and spleen
What is the role of the exterior platelet coat?
Rich in glycoproteins
Adhesion, aggregation and activation
What is the role of the platelet tubular system?
Site of thromboxane A2 synthesis and release
What is the role of alpha granules in platelets?
Contain clotting mediators
Including von Willebrand factor, V, VIII and fibrinogen
What is the role of delta (dense bodies) in platelets?
Contain ADP, Ca2+ and serotonin for activation and clotting
Name the 3 steps in haemostasis.
Vascular spasm
Formation of platelet plug
Blood coagulation
Describe vascular spasm (step 1 of haemostasis). (4)
Cut or tear in blood vessel
Damaged cells and platelets release vasoconstrictors
Constriction of smooth muscle layer
Minimises blood loss and pushes broken epithelium together
Describe platelet plug formation (step 2 of haemostasis). (2)
Adhesion, activation and aggregation
Platelets stick together using vWF
Where is von Willebrand’s factor synthesised?
Endothelial cells and platelets
Give 3 functions of the platelet plug.
Compaction/strengthening
Further vasoconstriction
Stimulation of the clotting cascade
What is the role of prostaglandin 2? Where is it synthesised?
Limits platelet plug to damaged region
Inhibits platelet aggregation
In normal blood vessel lining
Describe blood clotting (step 3 of haemostasis). (2)
Conversion of fibrinogen into fibrin
RBCs enmeshed in fibrin plug
Describe formation of fibrin polymers. (2)
Fibrinogen into fibrin monomers stimulated by thrombin (factor IIa, protease)
Fibrin monomers into fibrin polymers stimulated by factor XIIIa
Describe the intrinsic pathway of thrombin stimulation.
Initial stimulus is exposed collagen (through damage to endothelium wall)
Describe the extrinsic pathway of thrombin stimulation.
Initial stimulus is blood contact with damaged tissue outside of blood vessel that exposes tissue factor (factor III, tissue thromboplastin)
Describe the initiation phase of blood clotting. (3)
Tissue exposure triggers extrinsic pathway
Thrombin production
Amounts produced too small for sustained coagulation
Describe the amplification phase of blood clotting. (2)
Thrombin produced by extrinsic pathway feeds back
Activates intrinsic pathway
What is the role of anti-thrombin? (2)
Inhibits many clotting factors (inc. thrombin)
Enhanced by heparin
Describe the tissue factor pathway inhibitor. (3)
Binds to factor III/VIIa complex
Prevents activation of its substrates factor IX and X
Binds factor Xa directly
What is stimulated by thrombin binding to its receptor?
Production of prostaglandins (PGI), nitric oxide and ADP to inhibit further platelet aggregation
What is the role of thrombomodulin? (4)
Expressed by endothelial cells
Binds thrombin
Eliminates its coagulant effects
Inactivates factors Va and VIIIa
What do aggregated platelets secrete and what is the function?
Platelet derived growth factor B (PDGF-B)
Recruits fibroblasts from surrounding tissue
What dissolves clots?
Fibrinolytic enzyme - plasmin
What activates plasmin?
Tissue plasminogen activator (t-PA), secreted by endothelial cells
What does tissue plasminogen factor (t-PA) need to become activated?
Binding of fibrin
(Only works on clot)
Which clotting factors are proteases?
All other than III, V, VIII and XIII
Which clotting factors are glycoproteins? (3)
III, V and VIII
Which clotting factor is a transglutaminase?
XIII
What is coagulopathy?
Deficiency or dysfunction of coagulation factors
What is thrombocytopaenia or thrombopathy?
Quantitative or qualitative defects of platelets respectively
Give 3 causes of acquired disorders of haemostasis.
Renal disease - lack of thrombopoeitin
Hepatic disease - lack of fibrinogen
Vitamin K deficiency - lack of II, VII, IX and X
Drug-induced disorders
Give 3 examples of inherited disorders of haemostasis.
Structural defects to vascular system
Thrombotic disorder
Quantitative or qualitative platelet defects
Coagulopathy
What is Virchow’s Triad of risk factors for thrombosis?
Blood stasis
Changes in vessel wall
Thrombogenic changes in blood
What effect does a thromboembolism have on blood flow and blood pressure?
Decreases volume flow from around 60% blockage
Increases velocity exponentially to 85% then drops
When would anticoagulants be prescribed? (3)
Atrial fibrillation
Aortic valve replacement
Recent surgery
Autoimmune disease attacking fat and protein components of blood vessel walls
Describe thrombocytopenia. (3)
Low platelet count
Presents as petechiae, easy bruising or excessive bleeding
Caused by autoimmune disease or drug induced
What is thrombotic thrombocytopenic purpera? (2)
Caused by formation of small clots in circulation
Low platelet numbers
Describe von Willebrand’s Disease. (4)
Lack of vWF
Poor platelet aggregation
Excessive gum bleeding
Autosomal dominant
Describe haemophilia A. (2)
Factor VIII deficiency
X-linked recessive
Describe haemophilia B. (1)
Deficiency in factor IX
