Intro to Haemostasis Flashcards
what is Haemostasis
the arrest of bleeding and maintenance of vascular patency
what is needed for homeostasis
a permanent state of readiness
a prompt response
a localised response
protection against unwanted thrombosis
what happens in the normal homeostatic system
formation of a platelet plug
formation of a fibrin clot
fibrinolysis
anticoagulant defences
how and where are platelets formed
in the bone marrow by ‘budding’ from megakaryocytes
what is the structure of a platelet
small anucleate discs
what is the lifespan of a platelet
7-10 days
how are platelets activated
endothelial (vessel wall) damage exposed collagen to the blood and also releases Von Willebrand Factor (VWF)
this causes passing platelets to stick to the side of injury as they have VWF receptors (glycoprotein IB)
platelets then secrete chemicals causing aggregation of platelets at the site of injury (attract more and make them all stick together)
this forms a platelet pug
what causes the failure of platelet plug formation
Vascular problems
Platelet problems
- reduced number (thrombocytopenia)
- reduced function
Von Willebrand Factor problems (low or absent)
what happens if a platelet plug is not formed (presentation in failure of primary haemostasis)
spontaneous bleeding and purpura
mucosal bleeding
- epistaxes
- gastrointestinal
- conjunctival
- menorrhagia
intracranial haemorrhage
retinal haemorrhages
how do you screen for primary Haemostasis problems
platelet count
-no other simple screening test
what is primary haemostats
formation of a platelet plug
what is secondary Haemostasis
formation of a fibrin clot (more stable than platelet plug)
how are fibrin clots formed (v basic)
conversion of prothrombin to thrombin
thrombin causes the conversion of fibrinogen to fibrin
fibrin forms a mesh for proteins to stick to
where are the clotting factors used for secondary Haemostasis produced
liver
what clotting factors are vitamin K dependent
II, VII, VIII, X
what two pathways lead to fibrin production
Extrinsic pathway
Intrinsic pathway
what is the extrinsic pathway
Tissue factor released from damaged vessels
tissue factor binds to and activated factor 7
TF-factor 7 complex caused factor X to become Xa
X-Xa leads onto the common pathway
what is the intrinsic pathway
not as important in fibrin production but amplifies response
exposed collagen at damaged side activates factor XII which starts a cascade
XII-XIIa
XI-XIa
IX-IXa
IXa binds to factor VIIIa
Activates factor X
this triggers the common pathway
what happens if the intrinsic pathway doesn’t work
bleeding into muscles and joints
what is the common pathway
the pathway that actually produced the thrombin
IXa-XIIa (intrinsic) and TF-7a complexes both activated factor X starting the cascade
X-Xa - this activates factor II
Prothrombin - thrombin (II-IIA)
fibrinogen - fibrin
II also activated IIX in the intrinsic pathway to help stabilise the clot
what does prothrombin time measure
the time for the extrinsic pathway to go from TF to TF-7 complex
what does activated partial prothrombin time measure
the time for the intrinsic pathway to go from facts 12 to IXa-VIIIa
what does thrombin time measure
time for the common pathway to go from factor 10 to the production of fibrin
what causes a failure in fibrin clot formation
Single clotting factor deficiency eg. haemophilia (hereditary)
Multiple clotting factor deficiencies (disseminated intravascular coagulation - acquired)
Increased fibrinolysis (complex coagulopathy)
how is fibrin broken down in fibrinolysis
Tissue plasminogen activator converts plasminogen to plasmin
plasmin caused fibrin to be broken down into fibrin degradation products
what happens if secondary haemostats (fibrin clot formation) does not work
no characteristic syndrome
may be combined primary/secondary failure
bleeding depends on:
- single/multiple abnormalities
- what factors are involved
questions to ask in bleeding disorders history
bleeding/bruising duration previous surgery/dental extractions drug history family history examination
what do anticoagulants do
interrupt fibrin clot formation
what do anti-platelets do
interrupt platelet plug formation
what are some naturally occurring anticoagulants
Serine protease inhibitors (anti-thrombin)
Protein C and protein S
what is a thrombophilia
deficiency of naturally occurring anticoagulants
increased tendency to develop venous thrombosis
