Blood clotting pathways Flashcards
haemostasis is the arrest of bleeding. what are the 3 major steps
- vascular spasm
- formation of platelet plug
- blood coagulation
haemostasis is controlled to ensure what things happen/don’t happen?
- inappropriate blood clotting
- temporary blood clots
- blood clots must be eventually degraded
what is vascular spasm
- vasoconstriction of blood
- less blood lost
- process mediated by platelet-derived products such as serotonin and thromboxane A2
what are platelets
they are fragments of bone marrow cells called megakaryocytes. they contain the granules and cytoplasm of the cell but not the nuclei. it contains organelles that secrete and generate energy. they have a high conc of myosin and actin so are able to contract like muscle cells they are also called thrombocytes.
what are platelets activated by
- platelets are activated by ADP, platelet activation factor, collagen and thrombin.
what are the effects of activation of platelets?
- change shape from disc to sphere
- generate compounds involved in haemostasis such as thromboxin A2
- aggregate
- adhere to vessel walls at the site of injury to form a haemostatic plug (washed away by blood when vasoconstriction eases)
- synthesise thromboxane, which is involved in platelet activation and vasoconstriction.
what is the most common platelet bleeding disorder
- von Willebrand disease
- vW Factors help platelets to stick to each other
- vW disease is an autoimmune disease affecting vWF so platelets cannot stick together as much so clots can’t form.
what are antiplatelet drugs used for and name some examples
used to treat arterial thrombosis (blood clots within vessels), they decrease platelet aggregation. Examples include:
- aspirin (thromboxane A2)
- platelet receptor antagonist (targets vWF)
- platelet ADP receptor antagonist
explain the importance of collagen in bleeding disorders
- important role in the structure and function of small blood vessels
- vascular causes of excessive bleeding include congenital or acquired deficiencies in collagen synthesis
what is blood coagulation
blood coagulation factors interact to form secondary fibrin-rich haemostatic plugs in small vessels and the secondary fibrin thrombus in arteries and veins. there’s an intrinsic and extrinsic pathway.
describe the intrinsic and extrinsic pathways of blood coagulation.
- intrinsic pathway: activated by exposure of flowing blood to endothelial collagen
- extrinsic pathway: activated by tissue damage which exposes the flowing blood to a protein called tissue factor.
- both pathways result in the conversion of fibrinogen to fibrin.
what is fibrin
- insoluble, thread-like material
- forms a loose mesh that traps blood
- generated from fibrinogen which is synthesised in the liver
what is thrombin
- enzyme which catalyses the conversion of fibrinogen to fibrin
- also activates factor XIII
what is factor XIII
- strengths and stabilises the loose mesh of fibrin
explain the blood clotting cascade (intrinsic pathway)
- collagen activates factor xiii
- aggregated platelets secrete platelet factors (PF3) which is essential for the cascade and platelet aggregation.
- results in activation of factor X, which converts prothrombin into thrombin
explain the blood clotting cascade (extrinsic pathway)
- requires contact with tissue factors
- tissue factors activate factor X
how does thrombin convert fibrinogen into fibrin
thrombin cleaves 4 peptide bonds in fibrinogen, releasing fibrinopeptide. the cleaved molecule is called fibrin monomers. the monomers assemble into a mesh called fibrin. fibrin is then cross-linked by factor xiii.
explain the regulation of the clotting process
- must form rapidly, but at the site of injury
- thrombin has a dual function, as well as activating fibrin, it also initiates the cascade reactions which eventually deactivate the clot.
- clotting factors are easily altered and are short-lived due to ti dilution by blood or removal by the liver.
what stops blood from clotting?
- absence of thrombin
- exists as prothrombin
what are the roles of vitamin k?
the liver requires vitamin K to synthesise prothrombin.
what are the roles of calcium?
calcium binds prothrombin to the site of injury where the clotting factors are, which is required for conversion to thrombin.
what is warfarin?
warfarin is a rat poison which is used as an anti-coagulant medically as it produces prothrombin w/o the need for enzymes in the liver. the prothrombin doesn’t bind to ca2+ therefore it’s an anticoagulant.
what prevents inappropriate clotting?
- anti-thrombin produced by the liver
- heparin: synthesised by mast cells - activates anti-thrombin
- protein S and C degrade clotting factors
- tissue factor pathway inhibitors (TFPH)
explain fibrinolysis
fibrinolysis is the process of dissolving the clot. Plasminogen is a protein synthesised by the liver. factor xii converts it to plasmin which breaks down fibrin slowly then the phagocytic WBC remove the debris.
what is thromboembolism
inappropriate clots forming in vessels.
- Thrombosis: abnormal clots attached to the walls of the vessels, can narrow or close the vessel.
- embolus (embolism): freely floating clots or mass, can completely block a small vessel
what are the 4 continuous, overlapping and precisely programmed phases
- rapid haemostasis
- appropriate inflammation
- proliferation
- tissue remodelling
