Haemeostasis Flashcards
what is haemostasis?
tightly regulated process which maintains fluid state in normal vessels
allows for rapid formation of clot in vascular injury (thrombosis)
what are the 3 components of haemostasis?
- vascular wall
- platelets
- process of blood clotting
what is the process of haemostasis?
- contraction of vessel wall
- formation of a platelet plug at site
- formation of fibrin clot to stabalise platelet plug
what are the basic principles of platelets?
- disc shaped an anucleate
- made from cytoplasm of megakaryocytes
- normal lifespan = 7-10 days
what is the role of platelets when vessels are damaged?
Platelet Adhesion: seconds
* damage to endothelium in vessel wall
* exposure of underlying tissue
* platelets adhere to collagen via vWF (von willebrand factor)
Platelet activation/secretion:
* platelets secrete granules - contain ADP, ATP, fibrin
* the release of ADP stimulates the recruitment of other platelets (activating the coagulation cascade)
Platelet aggregation:
* fibrinogen allows platelets to cross link forming platelet plug
* provides some stability but is still open to damage
what are some mediating factors involved in a platelet plug formation?
- platelet receptors
- vWF allow for platelet adherance
- fibrinogen - links platelets together
- collagen
- thrombin - converts fibrinogen to fibrin
what happens in the coagulation/clotting cascade?
- multiple steps occur - at each step a zymogen is converted to an active enzyme
- there are 2 pathways, an intrinsic and extrinsic pathway - which meet at factor X to form a common pathway
- amplification system generates thrombin
- thrombin is super important because it converts soluble fibrinogen to insoluble fibrin
- converts platelet plug into a stable clot
(tightly regulated process)
what coagulation factors are involved in the extrinsic pathway?
factor VII
what coagulation factors are involved in the intrinsic pathway?
factor VIII
factor IX
factor XI
factor XII
what drugs can be given to stop clotting and where in the coagulation process do they act?
antithrombin - stops clotting at factor X
TFPI (tissue factor plasminogen inactivator) - stops clotting at factor VII
what are some different coagulation factors and where are they made?
made in the liver:
* fibrinogen
* prothrombin
* factor 5
* factor 7
* tissue factor
what are some different natural anticoagulants and where are they made?
made in the liver:
* Protein C
* Protein S
* Antithrombin
* Tissue factor pathway inhibitor (TFPI)
what tests can be done to determine if a patient has clotting defects?
- activated partial thromboplastin time (APTT) - measures intrinsic pathway time
- prothrombin time (PT) - measures extrinsic pathway time
- thrombin time (TT) - measures time taken for conversion of fibrinogen to fibrin
what would a prolonged APTT + PT indicate?
indicates error in common pathway
how is clot broken down once vessel wall is repaired?
- antithrombin III prevents conversion of fibrinogen to fibrin
Activated Protein C (APC):
* thrombin binds to endothelial cell receptor called thrombomodulin
* resulting complex activates protein C
* which inactivates factor VIIIa and Va
Tissue factor pathway inhibitor:
* acts in initiation phase of clotting
* binds to factor VIIa complex and inhibits factor Xa formation
Fibrinolysis:
* breaks down fibrin clot by activating plasminogen
* plasminogen is converted to plasmin which breaks down fibrin
* this forms D dimers
what may bleeding disorders be caused by?
abnormalities in vessel wall, platelets or coagulation factors
what is thrombocytopenia?
deficiency in platelets causes:
* excessive bleeding
* brusing
* slow blood clotting
what are common symptoms of thrombocytopenia?
patients present with:
* purpura
* petechiae
* mucosal bleeding
* epistaxis
* menorrhagia
what are the different bleeding disorders which cause thrombocytopenia?
decreased platelet production:
* megloblastic anaemia
* sepsis
increased consumption of platelets: Immune
* immune thrombocytopenic purpura
* thrombotic thrombocytopenic purpura
increased consumption of platelets: non-immune
* haemolytic-uraemic syndrome
* hypersplenism
what is immune thrombocytopenic syndrome?
- isolated low platelet count with normal bone marrow
- this diagnosis is given if the patient is normal for every other thing which could cause low thrombocytopenia
what is thrombotic thrombocytopenic purpura?
- blood disorder which causes too many clots to form in small blood vessels
- this uses up all platelets present
what is haemolytic-uraemic syndrome?
- low RBC, acute kidney injury + low platelets
- associated with infection by E.Coli
- patients present with bloody diarrhoea, fever and vomitting
what is hypersplenism?
- spleen is functioning too much
- removing too many blood cells including platelets
- treated by splenctomy
what are the different coagulation factor disorders which cause thrombocytopenia?
Congenital: Inherited disorders
* Haemophilia A or B
* Von Willebrands disease
Acquired disorders of coagulation:
* Liver disease
what is haemophilia A?
- X linked recessive
- lack of factor VIII (intrinsic pathway affected so prolonged APTT + normal PT)
- ranges from mild/moderate/severe
- easily bruise
- risk of haemorrhage
what is haemophilia B?
X-linked recessive
reduction of factor IX (intrinsic pathway affected so prolonged APTT + normal PT)
what is Von Willebrand disease?
- lack of vWF so platelets cant adhere to collagen
- prolonged bleeding time
- results in excessive bleeding from wounds
- spontaneous bleeding from mucous membranes
what is Disseminated intravascular coagulpathy (DIC)?
- type of microangiopathic haemolytic anaemia
- triggers coagulation - lots of microthrombi form in circulation
- results in consomption of clotting factors so cant stop bleeding if they are injured - results in haemorrhage
- prolonged PT time + APTT time
- low fibrinogen
- raised D dimers
what are thrombophilias?
congenital or acquired defects of haemostasis which increase patients risk of thrombosis
congenital causes:
* deficiency in natural anticoagulants
* abnormal factor V
acquired causes:
* antiphospholipid syndrome
what are the different anticoagulant drugs?
warfarin - vitamin K inhibitor:
* affects vitamin K dependent factors (e.g. factor II, VII, IX + X)
direct oral anticoagulants
heparin
aspirin
what are the complications of using anticoagulants?
bleeding
how would you deal with complications associated with warfarin?
- stop giving warfarin
- give vitamin K
- if severe give prothrombin complex concentrate
how would you deal with complications associated with heparin?
- stop giving heparin
- give protamine sulphate (if needed)
