Haemostasis & Haematopoeisis Flashcards
(44 cards)
Haemostasis =
What’re its 3 components?
A series of regulatory processes that culminate in the formation of a blood clot to limit bleeding from an injured vessel
3 components: platelets, vascular wall and coagulation cascade
Haemorrhage =
Extravasation of blood into extravascular spaces
What’s the role of the endothelium and platelets in haemostasis?
Endothelium: has antiplatelet, anticoagulant and fibrinolytic properties to act as a barrier expressing factors which limit clotting to site of injury (prevent thrombosis)
Platelets: form the initial haemostatic plug, providing a surface for recognition of coagulation factors
What’re the 3 ways platelets form the initial plug and recruit coagulation factors?
Adhesion to ECM at sites of vascular injury
Activation by secretion of granules
Aggregation of platelets
What’s the coagulation cascade?
Two pathways extrinsic and intrinsic lead to final common pathway of FXa + FVa + Ca2+>prothrombin>thrombin>fibrinogen>fibrin which stabilises the clot
Intrinsic: FXIIa>FXIa>FIXa>FVIIIa> FXIa + FVIIIa + Ca2+
Extrinsic: TF>FVIIa> TF + FVIIa + Ca2+
What are the 3 stages of haemostasis?
1: Vasoconstriction - minimises blood loss and activated by endothelin release and neurogenic reflex
2: Primary haemostasis - initial platelet plug formed as vWF expressed on endothelial cells to recruit platelets, change platelet shape to enhance platelet-platelet interactions by secretory granules released
3: Secondary haemostasis - platelet plug consolidation by TF expression on subendothelial cells which binds to and activates factor VII and thrombin to initiate coagulation cascade. Thrombin cleaves circulating fribinogen to fibrin.
What drugs interfere with the coagulation cascade?
Heparin - binds to antithrombin III to inactivate thrombin and FXa
Warfarin - affects metabolism of vitamin K therefore affecting production of prothrombin, factors VII, X, IX
New oral anticoagulant: Dabigatran, reversible inhibitor of Thrombin
Step 4: clot stabilisation, resorption and role of fibrinolytic system
Fibrin and platelet aggregates undergo contraction to form permanent plug
Counterregulatory mechanisms limit clot to site of injury
Involves fibrinolytic system: inactive circulating plasminogen converted to plasmin which breaks down fibrin to reduce size of clot and contribute to later dissolution
How is coagulation controlled? Why is it important?
Needs to be restricted to the site of injury
Fibrinolytic cascade
Requires negatively charged surface (platelets)
Anticoagulation factors are expressed on adjacent intact endothelium
Circulating inhibitors eg antithrombin III
Dilution
Thrombosis =
Formation of a sold mass of blood products in a vessel lumen (thrombus)
Pathological process leading to vascular occlusion/ischaemia/infarct
What is Virchow’s triad? What are its 3 features?
Predisposition to thrombosis
Endothelial injury, abnormal blood flow, hypercoagulability
What are the fates of thrombi?
Propagation
Embolisation
Resolution/dissolution
Organisation
Embolism =
A detached intravascular solid/liquid/gas that is carried by the blood to a site distant from origin
What are common embolisation sites?
Lower extremities - limb ischaemia
CNS - stroke
Intestines - bowel ischaemia
Kidney/spleen - may be asymptomatic
Infarction =
Area of ischaemic necrosis caused by inadequate blood supply
What’s haematopoiesis?
The production of all types of mature blood cells
What causes megaloblastic anaemia?
Folic acid (vitamin B9) and cobalamin (vitamin B12) deficiency
What causes pernicious anaemia?
Intrinsic factor deficiency (maybe by autoimmune destruction of parietal cells) meaning reduced vitamin B12 absorption in the terminal ileum
What’s the composition of blood? Plasma?
Cells + plasma = blood
Plasma: h20, small organic compounds, electrolytes, proteins (globulins, albumin, fibrinogen)
Where are haematopoietic stem cells located? How do they give rise to cell lineages?
Bone marrow
Stem cells proliferate -> differentiate -> mature
What are the 5 different types of stem cell in order of their potency?
Totipotent - any cell type
Pluripotent - any cell type of the embryo
Multipotent - several related cell types
Oligopotent - small number of very closely related cells
Unipotent - can produce more of the identical cell type
What are the 2 common progenitor cells from a multipoint haematopoietic stem cell that starts the 2 lineages?
Common myeloid progenitor -> erythrocytes, thrombocytes, granulocytes, macrophages
Common lymphoid progenitor -> lymphocytes
Outline Erythropoiesis, including what’s needed for it
Proerythroblast -> erythroblast -> reticulocyte -> erythrocyte
Controlled by EPO, requires Iron, folic acid and vitamin B12
What are the 4 changes in erythrocyte maturation?
Acquisition of biconcave disc shape
Loss of organelles, including nucleus
Decrease in cell size
Haemoglobin production
