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Flashcards in Platelets and Coagulopathy Deck (41):

4 components of haemostasis?

- endothelium
- platlets
- coagulation factos
- fibrinolytic factors


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


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


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


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


With generalised BM destruction what will be lost first?

- Neutrophils 6hrs t1/2


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*


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


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


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


How does platelet aggregation occour?

- platelets bind fibrinogen via GPIIbIIIa
- fibrinogen generated from coagulation cascade
- released from platelets and found in plasma


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


What happens to the whole blood vessel whe damaged?

- vasoconstriction to v blood pressure and blood flow past the area


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


What is the first and most important coagulation factors?

Tissue factor


What is the end point of the coagulation cascape?

- activate thrombin tha causes fibrinogen -> fibrin


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


Do the intrinsic, extrinsic and common pathways exist in vivo?

no only in vitro


What is the intrsinc and extrinsic link -> common apthway factor?

factor 10 -> 10a


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


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)


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


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


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)


What is coagulation?

2* haemostasis


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!!*


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


What is thrombocytopenia? At what level may spontaneous haemorrhage occour?


What is thrombocytosis? Clinical relevance?

> 1000x10^9/L
^ risk thrombotic activity


What practical way can clotting times be evaluated?

> Buccal mucosal bleeding time (minutes)
- 1* haemostasis (evaluates platelet FUNCTION more than number and doesn't look at coagulation [2* clotting])
- spring loaded cassette


Is buccal mucosal bleeding time a good test? When would it be increased?

- very low sensitivy
- ^ thrombocytopenic
- ^ vW disase and disorders of platlet function
- will NOT be ^ with coagulation deficiecny (2* hemostasis)


3 main dioders of platelets?

> thrombocytopenia
> thrombocytoisis
> disorders of functon


What clinical signs may be seen with 1* clotting dz and 2*?

1* petichae and echymoses
2* haematoma


Mechanisms of thrombocytopenia?

> ^ platelet desruction or consumption
- immune mediated destruction
- haemorrhage (wont massively lower numbers)
- sequestration (transient)
> decreased production
- look BM
- other lines likely affected aswell
> infectious
- numerous causes
- machanism unknown


Most common casue of most severe thrombocytopenia?

> immune mediated
- platelet number v low often concurrent decreased production
> Evan's syndrome = concurrent immune mediated thrombocytopenia and anaemia


What is Evan's syndrome?

- concurrent immune mediated thrombocytopenia and anaemia
- rare but bad!


2 forms of immune-mediated thrombocytopenia?

> 1* ab against platelet ag
> 2* - many causes
- other immune dz (SLE)
- drugs/vaccine/injection
- neoplasia
- infectious


Clinical findings of immune-mediated thrombocytopenia

> clinical findings
> profound thrombocytopenia (NB: always recheck numbers and look for clumps on smear and lcots in tube!!!)
> peticheal or ecchymotic haemorrhage
> Hx bleeding from gums, mucosal surfaces, prolonged bleedig from wounds etc.


Dx of IMT?

- hard to confrm, r/o other causes
- response to tx most common
- may see mehgakaryocyte hyperplasia (BM)
- BM examination poss even if platelet nos low - rarely bleed from site
- antiplatelet Abs (need large volume of blood as platlet numbers will be low)


What is haemostasis?

- interaction between BVs, platelets and coag factors that normally maintains blood in a fluid state and allows for formaion of platelet plugs and clots when vessels injured


2 mechanisms of thrombocytopenia? What will be seen on coag tests?

> ^ consumption
- haemorrhage (numbers should stay above 100x10^9)
- DIC numbers may be v low (but should also see other signs of coagulation defects)
- PT, PTT will be prolonged
- FDPs will be increased
> sequestration
- rare but may occour with splenomegaly or large cavitated mass
> decreased production
- BM disease
- neoplasia
- drugs
> infectious
- many causes including immune mediated and v production
- FeLV, BVD, Ehrlichia, Leishmania