Platelets and Coagulopathy Flashcards
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) - DIC - 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
