Haemostasis Flashcards
define haemostasis and when does it happen?
- the stopping of blood flow
- it is the normal haemolytic response to vascular damage and is immensely linked to interactions between blood vessel walls, circulating platelets and blood coagulation factors
- it is an efficient and rapid mechanism for stopping bleeding from sites of blood vessel injury
- response needs to be tightly controlled to prevent extensive clots form forming and to be able to break down clots once damage is repaired
what are the major components of haemostats?
platelets, coagulation factors, coagulation inhibitors, fibrinolysis, blood vessels
what are platelets and what is their function?
- they are produced in the BM by fragmentation of the cytoplasm of megakaryocytes
- they circulate for 7-10 days
- thrombopoietin (TPO) is the major regulator of platelet formation, 90% produced int he liver
-the main function is for the formation of the mechanical plugs during haemostatic response to vascular injury
state the overview of haemostatic plug formation
1) response to injury: vessel constriction
2) formation of insatiable platelet plug
3) stabilisation of platelet plug w fibrin blood coagulation
4) dissolution of clot and vessel repair fibrinolysis
what happens in the first step of the haemostatic plug formation?
- vasoconstriction
- immediate vasoconstriction of the injured blood vessel and reflex constriction of adjacent small arteries responsible for slowing blood flow to area of injury
- reduced blood flow allows activation of platelets and coagulation factors
describe the second stage of the haemostatic plug formation
- primary haemostatic plug formation
- initial adherence of platelets exposed to connective tissue mediated by von willebrand factor (VWF)
- collagen exposure and thrombin generated by activation of tissue factor produced at site of injury
- this causes the platelets to release granule contents which activates platelet prostaglandin synthesis
- this forms thromboxane A2 (TXA2)
- additional platelets from circulating blood drawn to area of injury
- platelet aggregation promotes the growth of haemostatic plug which covers exposed connective tissue
- unstable primary plus produced within 1 minute and is not sufficient
what is the van willebrand factor?
- involved int he shear-dependent platelet adhesion to vessel wall and other platelets
- also carries factor VII which is a large glycoprotein w multimess made of 2-50 dimeric subunits
- synthesised in endothelial cells and megakaryocytes
what is TXA2?
secondary amplification of platelet activation to form stable platelet aggregate
what happens in the third stage of haemostatic plug formation?
- also known as secondary haemostasis
- biochemical reactions of coagulation
- there is a coagulation cascade where soluble fibrinogen is converted into a meshwork of insoluble fibrin
- this stage is tightly regulated by coagulation factors, cofactors and inhibitors
- that results in the controlled formation of thrombin which initiates fibrin formation
what are the physiological limitations of blood coagulation?
- if unchecked, can lead to dangerous occlusion of blood vessels (thrombosis)
- protective mechanisms- coagulation factor inhibitors, blood flow and fibrinolysis
- important that the effect of thrombin is limited to the site of injury
- first inhibitor is tissue factor pathway inhibitor (TFPI), which is synthesised in endothelial cells and present in plasma and platelets, accumulates at site of injury caused by local platelet activation
- TFPI inhibits XA and VIIa and tissue factor to limit main in vitro pathway
- direct inactivation of thrombin and serine protease factors by circulating inhibitors (antithrombin)
- heparin potentiates its action significantly
what happens in the last stage of haemostatic plug formation?
- fibrinolysis
- where fibrin is degraded by plasmin
- main mechanism is the clot limiting mechanism and repair and healing mechanism
what is thrombosis?
the pathological process where platelets nfs fibrin interact w vessel wall to form a haemostatic plus to cause vascular obstruction
what are the different types of thrombosis?
ishcaema (arterial) or stasis (venous)
this can underlie diseases such as ischaemic heart, cerebrovascular or peripheral vascular diseases, venous occlusion, pulmonary embolism
what is the relationship between haemostasis and thrombosis?
haemostasis ⇌ thrombosis
- eqm shifts to the left when coagulation factors and platelets decrease and fibrinolytic factors and anticoagulant proteins increase
- eqm shifts to the right when coagulation factors and platelets increase and fibrinolytic factors and anticoagulant proteins decrease
why do you need to test haemostatic function?
-defective haemostasis w abnormal bleeding can be due to a vascular disorder, thrombocytopenia (platelet dysfunction) or defective blood coagulation
-simple tests can assess platelet, vessel wall and coagulation components of haemostasis
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