Flashcards in Platelets and Coagulopathy Deck (41)
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1
4 components of haemostasis?
- endothelium
- platlets
- coagulation factos
- fibrinolytic factors
2
What are endothelial cells? What action do they have ?
- flattened cells lining blood vessels
- pro and anticoagulant properties
- normally anticoagulant - inhibit coagulation and platelet aggregation
- act as barrier to subendothelial collagen which is procoagulant
3
What is vWF produced by? Function?
- endothelial cells and platelets
- stored in Weibel Palade bodies
- Released early in haemostatic process
- responsible for platelet adhesion to collagen
4
Which reticular lines have the shortest half life? CLinical impliations?
- Neutrophils 6hrs
- Platelets ~1week
- RBC ~120d
> if BM affected, neutrophil numbers will be affected first, then platelets, then anaemia
5
What are platelets?
- small, discoid, ANUCLEAR cells
- megalokaryocyte (precursor in BM) breaks off to form platelets = thrombopoiesis
- mediated by thrombopoietin
- 3-5um pale basophilic with small red granules
- circulate for 5-9d most species
6
With generalised BM destruction what will be lost first?
- Neutrophils 6hrs t1/2
7
What is present on the outer membrane of platleets?
- receptors for ahesion and aggregation
> glycoproteins
- GP1b binds vWF
- GP IIbIIIa binds fibrinogen on adjacent platelets allwing aggregaion
* defects in receptors -> abnormal platelet function and clot formation*
8
What is contained within the platelets?
- cytoskeleton (actin and myosin allows for shape change)
- membrane bound granules
> alpha granules (red) - contain vWF, finbrinogen and factors V and VIII
> dense granules - contain ADP and calcium
9
What is primary hemostasis? 2*? What follows these?
1* = formation of 1* platlet plug
2* = activation of coagulation cascade and generation of insoluble fibrin which sabilises platlet plug
> Fibrinolysis - breakdown of fibrin and platelet plug
10
Outline steps of 1* haemosasis.
- damage endothelium exposes subendohelial collagen
- vWF released from damaged endothelium
- platelet adhesion occours
- platelets bind to collagen via receptor GPib and vWF from the endothelium
- once platelets adhered to collagen, undergo shape change and become spherical with filipodia
- additional receptors for vWF (GPIb) and fibrinogen (GPIIbIIIa) exposed
11
How does platelet aggregation occour?
- platelets bind fibrinogen via GPIIbIIIa
- fibrinogen generated from coagulation cascade
- released from platelets and found in plasma
12
What do platelets secrete?
- aggregating platelets degranulate
- ADP, fibrinogen, vWF
- TXA2 also released from platelet membrane
> increase platelet adhesion and aggregation
- also release factors V and VIII -> coagulation
13
What happens to the whole blood vessel whe damaged?
- vasoconstriction to v blood pressure and blood flow past the area
14
2* haemostasis
- involves activation of the coagulation cascade
- happens simultaneously with formation of platelet plug
- damage to endothelium releases tissue factor activating EXTRINSIC clotting pathway
15
What is the first and most important coagulation factors?
Tissue factor
16
What is the end point of the coagulation cascape?
- activate thrombin tha causes fibrinogen -> fibrin
17
What are coagulation factors?
- soluble enzymes (serine proteases) found in circulation
- each step of coagulation cascade converts one of these factors from inactive state (proenzyme) to its active state
- each step amplifies system
- > insoluble fibrin aim
- fibrin stablises 1* platelet plug
18
Do the intrinsic, extrinsic and common pathways exist in vivo?
no only in vitro
19
What is the intrsinc and extrinsic link -> common apthway factor?
factor 10 -> 10a
20
What is extrinsic system also known as? What does it do?
= Initiation
- most important in vivo
- tissue factor (TF) released from damaged tissue binds to and activates FVII in presence of calcium
- TF-FVII complex activates FX of common pathway and FIX of intrinsic pathway
21
What is he intrinsic pathway?
= Amplification pathway
- FXII activated by contat with negatively charged surface (cofactor HMWK)
- activated FXII cleaves and activates FXI which in turn activates FIX(calcium required)
- activated FIX activates FX of common pathway (calcium required)
22
Outline common pathway
- activation of factor X
- activated FX binds activated FV and calcium on platelet surface
- this converts prothrombin (FII) to thrombin (FIIa)
- thrombin converts fibrinogen (FI) to fibrin (FIa)
- fibrin crosslinked by activated FXIII
23
What are inhibitors of coagulation?
> antithrombin III
- inhibits thrombin and activated FX
- activity increased by heparin from endothelium
- protein C inactivates factors V and VIII
> fibrinolysis
24
Outline fibrinolysis
- enzymatic breakdown of fibrin by plasmin
- plasmin from plasminogen found in the platelet membrane and plasma
- plasmin degrades fibrinogen and fibrin to produce fibrin degradation products (FDPs)
25
What is coagulation?
2* haemostasis
26
How can platelets be evaluated in the lab?
> platelet conc (automated counts on EDTA)
- good accuracy for all species except cat, sheep and goat d/t overlap between RBC and platelet size
- platelet clumps can affect accuracy of counts d/t uneven distribution and overlap of size of clumps and RBCs
* very common in cats!!*
27
Which species must have a platelet count carried out from blood smear?
- cats
- CKC spaniels, often thrombocytopenic with giant platelets which may be counted as RBCs
28
What is thrombocytopenia? At what level may spontaneous haemorrhage occour?
29
What is thrombocytosis? Clinical relevance?
> 1000x10^9/L
^ risk thrombotic activity
30
