Pathophysiology of Haemostasis and coagulation Flashcards
what is clotting/coagulation?
the formation of a thrombus/clot which can occur before and after death
what is the final product of coagulation?
a platelet fibrin thrombus
what is haemostasis?
the process of repairing damaged blood vessels to maintain their integrity to keep blood within the vessel.
what is primary haemostasis?
- mediated by platelets
- platelets adhere together forming a weak ‘platelet plug’
what is secondary haemostasis?
a coagulation cascade occurs stabilising the platelet plug
what happens when there’s disruption to endothelial cells?
- transient vasoconstriction of the endothelial cells
- this is mediated by neural stimulation and release of endothelin from endothelial cells in response to thrombin and shearing forces. - von Willebrand Factors bind to the exposed collagen on the basement membrane via GPIb found on platelets. This is called ADHESION which causes the platelets to change shape.
- platelets degranulate RELEASING ADP and TXA2 and Ca
- ADP induces the expression of GP2b and GP3a for AGGREGATION, and the expression of fibrinogen(FNG) as a linker molecule.
- TXA2 promotes platelet AGGREGATION by enhancing linking b/w FNG and GP2b/GP3a
what lab tests are carried out for primary haemostatic disorders?
- platelet count (quantitative)
- blood smear (qualitative)
- bone marrow biopsy (as the precursors of platelets-megakaryocytes-are in bone marrows)
- test for VWF (von Willebrand Factor) levels
what is the aim of the coagulation cascade in the secondary haemostasis action?
- to stabilise the weak platelet plug by generating thrombin converting the platelet linker molecule (fibrinogen) into cross linked fibrin.
- this forms platelet fibrin thrombus
where are most coagulant factors and inhibitors synthesised?
in the liver
what is required for clotting factors 2, 7, 9 and 10 to work?
vitamin K
what three things are required to carry out the secondary haemostasis coagulation cascade?
- exposure of activating substance i.e. tissue factor (factor 7)
- phospholipid surface of platelets
- calcium from dense core of granules of platelets
what systems is the coagulation cascade divided into?
- extrinsic
2. intrinsic
what coagulation factors are required in the extrinsic system?
factor 7
what coagulation factors are required in the intrinsic system?
factors 8,9,11,12
what coagulation factors are required in the final common pathway?
factors 1, 2, 5 and 10
what coagulation factor is used to cause the cross-link of fibrin monomers?
factor 13
what is the function of thrombin?
- makes fibrin monomers from fibrinogen
- also activates the fibrin stabilising factor 13 to strengthen the fibrin clot
what switches off thrombin?
- the anticoagulant ‘antithrombin3’
- this limits clot formation where appropriate
what factors does antithrombin3 inactivate?
factors 10a, 9a, 11a, 12a and 7a
what is tissue plasminogen activator?
a protein found on endothelial cells which activates plasminogen to form plasmin
-used to breakdown a clot
what is the role of plasmin?
- it cleaves fibrin and fibrinogen into fibrinogen degradation products (FDPs).
- blocks platelet aggregation
what is used to inactivate plasmin?
alpha2-antiplasmin
what does the clotting test for prothrombin time (PT) evaluate?
the extrinsic coagulation system (plus final common pathway) down to the formation of the fibrin clot - factors that are evaluated are 7, 10, 5, 2, 1
what is the normal prothrombin time?
11 to 15 seconds
what is the prothrombin time used for?
- monitor people taking warfarin for anticoagulation
- evaluate liver function (if PT is increased, can mean liver disease etc)
- used to detect factor 7 deficiency if aPTT is normal
what does the activated partial thromboplastin time evaluate?
the intrinsic coagulation system down to formation of a fibrin clot.
-Factors that are evaluated include 1, 2, 5, 9, 8, 10, 11, 12 (basically not 7)
what is the normal activated partial thromboplastin time?
30 to 40 seconds
what is the use of activated partial thromboplastin time?
- to monitor heparin anticoagulation therapy. (Heparin enhances antithrombin III activity)
- to detect factor deficiencies in the intrinsic system if the PT is normal.
