haemostasis Flashcards
what is haemostasis
about keeping the blood flowing to provide organs with blood
describe the appearance of platelets
- very small
- no nucleus
- lifespan = 10 days
- stored in spleen
- little blueish/purple dots in btwn RBCs
describe thrombopoeisis
- platelets are made in bone marrow
- need thrombopoietin (TPO) which is platelet growth factor
- TPO produced primarily in the liver (and kidney)
- produced based on negative feedback loop = platelets bind TPO removing TPO from circulation to prevent over production
list key features of platelets
- membrane bound fragments of cytoplasm from megakaryocytes
- surface glycoproteins
- phophatidyl serine
- rich in microfilaments and microtubules to allow contraction
- have organelles (alpha and gamma granules)
what do alpha granules have in platelets
- growth factors (insulin -like growth factor, platelet derived growth factor, transforming growth factor beta)
- von willebrand factor
- P-selectin, thrombospondin, fibronectin
- platelet factor 4
explain the overall process of haemostasis
primary haemostasis:
- initial repsonse to endothelial damage
- local vasoconstriction
- formation of the platelet plug
secondary:
- strengthening and reinforcement of the platelet plug
- formation of a stable fibrin clot
tertiary:
- removal of fibril by fibrinolysis
- restore vessel patency (open/unblock)
explain the process of primary haemostasis
initial response:
- damage to blood vessel endothelium leads to local neural reflexes (pain receptors) and muscle contraction (vasoconstriction to reduce blood flow). platelets activate
platelet adhesion:
- platelets bind to von Willebrand factor on exposed sub-endothelium via GP Ib-IX-V
platelet activation:
- platelets change shape (become spike to grab)
- receptors activate and bind collagen
- produce thromboxane A2 (makes sticky)
- release granule contents (ADP, serotonin, platelet activating factor)
platelet aggregation:
- primarily mediated by fibrinogen binding to GP IIb/IIIa on adjacent platelets
- enhanced by generation of thrombin (links with secondary hemostasis
- forms the platelet plug (not firm, easy to wipe away. needs to be consolidated)
explain the process of secondary haemostasis
- strengthening and reinforcement of the platelet plug
- involves coagulation factors (factor 7)
- formation of a stable fibrin clot
cell-based coagulation model
-initiation (extrinsic pathway) = injury exposes TF-bearing cell to flowing blood and small amount of FIXa and thrombin generated
- Amplification = thrombin activates platelets (exposing PS). vWF released (tethers platelets to site of site of injury by binding GPIb/FIX receptor on one hand and sub-endothelial on the other leading to activation of factor 11, 7 and 5
- propogation = factors assemble on the activated platelet to form intrinsic tenase resulting in FXa generation on the platelet surface and prothrombinase complex forms and results in a burst of thrombin generation directly on the platelet
explain tertiary hemostasis
fibrin clot removal:
- tissue plasminogen activator activates plasminogen to form plasmin
- plasmin breaks down fibrin fibres to fibrin degradation products
- fibrin degradation products act as anticoagulants by interfering with platelet aggregation and fribrin polymerisation
- smallest = D-dimer
list (describe) disorders of haemostasis
- thrombocytopenia (abnormally low platelet count caused by either decreased production or increased destruction
- thrombocytopathy (abnormal platelet function von willebrands disease
- vascular defects
what is buccal mucosal bleeding time
- time taken for bleeding to stop after making a small incision
- a quick test to perform in practice
- healthy dog should stop bleeding in 1.7-4.2 mins and cat 1-2.4 mins
- prolonged if disorder of primary haemostasis
how can you count platelets
- take EDTA sample
- counts should be performed ASAP to avoid clotting
- can use haemocytometer, automated cell count or smear
estiomated count on smear = no. x 15 x 10^9/L healthy dog/cat should have more than 10 platelets per 100x oil immersion field
check for clumping in feathered region
explain group coagulation tests
anticoagulant = sodium citrate = binds Ca ions so blood cant clot
prothrombin time = add thromboplastin and Ca ions to activate the extrinsic pathway
activated partial thromboplastin time = add reagent to activate the intrinsic pathway and Ca ions
time to clot formation prolonged by alterations of factors
thrombin clot time assesses ability of added thrombin to convert fibrinogen to fibrin
what is the anticoagulant factor in EDTA tubes and how does it work
sodium citrate - temporarily binds calcium inons so that the blood cant clot
what is the difference between the intrinsic and extrinsic coagulation pathways
intrinsic: response to internal damage to vessel wall. very fast
Extrinsic: response to external trauma which has caused the blood to excape circulation. takes longer, more steps
