5 Haemostasis and thrombosis Flashcards
Haemostasis definition ?
complex process that stops bleeding
In the hemostatic balance , there is the need for a balance between …
anticoagulants and procoagulants
In hemostatic balance if balance tips in favour of :
1. anticoagulants = …..
2. procoagulants = ….
- excessive bleeding e.g. hemophilia
- thrombosis occurs
skin , fracture, childbirth (think why ?)
Why do we need a hemostatic balance in the body ? Explain from pro-thrombotic (pro-clotting/ pro-coagulation) perspective
- stops skin cuts from bleeding excessively
- heals bone fractures
- prevents fatal hemorrhage during childbirth (placenta detaches from uterus after childbirth )
Why do we need a hemostatic balance in the body ? Explain from anti-thrombotic (anti-clotting/ anti-coagulation ) perspective
- prevents arteries / capillaries being constantly blocked
- prevents strokes, heart attacks, pulmonary thrombo-emboli
3 stages of haemostasis following vessel injury ?
- Primary haemostasis - formation of unstable platelet plug
- secondary haemostasis - stabilisation of plug with fibrin (blood coagulation system)
- dissolution of clot and vessel repair (fibrinolysis & recanalisation)
recanalisation = process of
restoring flow to or reuniting an interrupted channel of a bodily tube (e.g. blood vessel)
Successful hemostasis depends on 4 factors, what are they ?
- vessel wall
- platelets
- coagulation system
- fibrinolytic system
Defects in any of the 4 core components of haemostasis (vessel wall, platelets, coagulation system, fibrinolytic system) leads to what ?
too much clotting - or too little
3 stages of events following arterial injury
- vascular spasm
- platelet plug formation
- coagulation fibrin forms a mesh
Explain vascular spasm stage following arterial injury
smooth contraction, vasoconstriction
Explain platelet plug formation stage following arterial injury
- injury to lining of vessel exposes collagen fibers; platelets adhere
- platelets release chemicals that make nearby platelets sticky - formation of platelet plug
what happens in the coagulation fibrin stage following arterial injury to result in formation of clot?
mesh network traps RBC and platelets
Features of platelets:
1. nucleus presence ?
2. µm in diameter ?
3. in bone marrow present as ?
4. function = maintain … & prevent / ……
- anucleate
- 2-4
- megakaryote progenitors
- maintain vascular integrity & prevent/ stop bleeding
how a platelets activated ?
blood vessel injury - which makes them travel to the injured area
3 ways in which platelets facilitate the formation of the primary hemostat plug (primary hemostasis) ?
- adhere to subendothelial structures via von Willebrand factor
- adhere to each other (aggregation)
- form platelet plug which is held together by the insoluble fibrin mesh
Normally in blood vessel walls the
endothelilal cells of ..1… vessels produce:
- ….2…. (heparin-like molecule and ..3..) which prevent clotting
- …4.. and ….5…. which prevent platelet aggregation
- intact
- coagulation inhibitors
- thrombomodulin
- NO
- prostacyclin
Coagulation system is a “cascade” where each activated factor serves as a ….. that ….. the next reaction
catalyst that amplifies the next reaction
Coagulation system converts what to form fibrin ?
prothrombin -> thrombin enzyme
which cleaves fibrinogen -> insoluble fibrin
Intrinsic pathway of coagulation cascade:
1. activated how ?
2. promotes binding of which factor ? which does what ?
- exposed collage, endothelial damage
- XII (12), activates factor Xa
Extrinsic pathway:
1. what leads to release of tissue factor …?
2. activates which factor ?
- trauma, III
- Xa
What’s the common pathway of coagulation in the coagulation cascade ? resulting in what ?
- Activated X pathway
- set of reactions resulting in prothrombin -> thrombin enzyme, then soluble fibrinogen -> insoluble fibrin strands which form the clot
The clotting cascade contains several feedback loops which can PREVENT the cascade at different levels.
What are the main anti-thrombin factors?
- anti-thrombin III
- protein C
- protein S
How many clotting factors are Involved in the coagulation cascade ?
12
VI doesn’t exist, I - XIII
What factors regulate clotting in the coagulation cascade (prevent excessive clotting & subsequent disease) ?
mediators such as protein C & protein S provide negative feedback on the clotting cascade
Name two factors which contribute to turning OFF the coagulation system (coagulation inhibitors)
- Anti-thrombin III
- protein C
How does anti-thrombin III contribute as a coagulation inhibitors ?
serine protease inhibitor which inhibits (degrades) thrombin and factor 10a
How does protein C contribute as a coagulation inhibitor?
Inhibits factors Va and VIIIa
Protein C:
* …1… dependent zymogen
* activated into an active …2… enzyme
* following contact by …3.. (which is activated by …4..)
- vitamin K
- serine protease
- thrombomodulin
- thrombin
Why is tight regulation of the coagulation system required ?
1ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin
Deficiency of anti-thrombin factors can be observed in what inherited condition ?
Inherited thrombophilia
Inherited thrombophilia is a condition that leads to a …
predisposition to form clots (at times/places when they shouldn’t form)
- What is fibrinolysis ?
- what is this an example of ?
- breakdown and removal of a clot
- homeostatic process conducted by the body
What are the 3 classes of fibrinolytic drugs which can be used in fibrinolytic therapy ?
- t-PA
- streptokinase
- urokinase
what is hemophilia ?
spontaneous internal bleeding
3 Laboratory blood tests of haemostasis ? & what they each measure
- full blood count (platelets)
- prothrombin time - INR test = measures the extrinsic pathway
- activated partial thromboplastin time (APTT) - measures intrinsic pathway and final common pathway
The combination of long PT and APTT might point to defects either ..1.. or ..2.. ?
- defect in final common pathway of coagulation
- multiple defects across both intrinsic and extrinsic pathways
Diseases of platelets result from what ?
abnormal numbers or function or combination of both
what is warfarin ?
1. …. antagonist
2. to …. and prevent ….
3. inhibits….
- vitamin K antagonist
- to thin the blood and prevent thromboses
- hepatic synthesis of clotting factors II, VII, IX , X
4 problems with warfarin ?
- difficulties in determining dose
- narrow therapeutic window
- drug/diet interactions
- delay in efficacy as pre-existing factors is still available for use
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Management involved when bleeding whilst on warfarin ? & reason with each
- Vitamin K to overcome the vitamin k antagonism and allow synthesis of vitamin k dependent clotting factors
- prothrombin complex concentrate if immediate reversal needed
Although warfarin is ..1… it isn’t always ..2… to use. More recent oral ….3… do not require ….4.. monitoring by are more ..5..
- cheap
- easy
- anticoagulants
- therapeutic
- expensive
thrombosis = formation of…
solid mass of blood clot within the circulatory system
What are the 3 main factors which cause thrombosis (Virchow’s triad) ?
- Abnormal blood flow
- Abnormal vessel wall
- Abnormal blood components
do venous or arterial clots have a higher cell content ?
venous clots have a higher cell content
are venous or arterial clots darker ?
venous clots are darker because they are de-oxygenated
some key histological features of arterial thrombi
- pale/read
- granular
- lines of zahn = alternating lines of red blood cells and thrombus strands
some key histological features of venous thrombi ?
- soft
- gelatinous
- deep red= de-oxygenated
- higher cell content
Effects of arterial vs venous thrombosis
arterial
* ischemia
* infarction (depending on site/collateral circulation)
venous
* congestion
* oedema
* ischemia
5 outcomes of thrombosis ?
- propagation
- organisation
- re-canalisation
- fibrinolysis
- embolisation
- Propagation is when the clot ….
- occurs …. in arteries
- occurs … in veins
- extends in length along the blood vessels (progressive spread of the thrombosis)
- distally
- proximally
Organisation as an outcome of thrombosis , occurs when the clot..1.. and can lead to .2..
- embeds (attaches to vessel wall)
- long-term blockage of a vessel
Organisation as an outcome of thrombosis happens within …1…. days of clot formation this is the growth of ..2…. results in the attachement of the ..3.. to the vessel wall
- 2 days
- fibroblasts & capillary proliferation
- thrombus
In the organisation outcome of thrombosis gradually results in what ?
the thrombus is dissolved and fibrovascular tissue replaces it, which impedes blood flow
Recanalisation outcome of thrombosis occurs when …1… and may be converted into ..2… of vessel in the thrombus which may restore the vessel’s ..3…
However this usually results in ….4…. of bloodflow
- capillaries infiltrate the thrombus (clot)
- one or two channels
- circulation
- incomplete restoration
fibrinolysis outcome of thrombosis…
occurs when there is …1…. = ..2.. of the clot
fibrinolytic system is …3.., clot is busted and blood flow is ..4..
- complete dissolution of the thrombus
- breakdown
- active
- re-established
embolisation outcome of thrombosis…
..1.. breaks off in the arterial or ….2… system and travels through the ..3.. and ..4… e.g. in a pulmonary embolism (..5…)
- part of the thrombus (clot)
- venous
- bloodstream
- lodges at a distant site
- PE
Embolsisms can consist of ..1.., ..2.., …3.. , where > 90% of emobli are ….4…
- solid
- liquid
- gas
- thrombo-emboli
there are many causes of embolism, apart from the fact that embolsism can consist of solid, liquid or gas.
Name some other types of embolism
- air
- fat
- amniotic fluid (in pregnancy only)
- nitrogen
- medical equipment
- tumour cells
the effect of a thrombi-emobli depend on two factors - what are they ?
- thromboemboli venous or arterial
- what is the site of origin
