Flashcards in Platelets and Coagulopathy Deck (41):
4 components of haemostasis?
- 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
- 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
- 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?
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?
- 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
- 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?
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?
- 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?
^ 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?
> disorders of functon
What clinical signs may be seen with 1* clotting dz and 2*?
1* petichae and echymoses
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
- 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)
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