Platelets and Coagulopathy Flashcards
(41 cards)
1
Q
4 components of haemostasis?
A
- endothelium
- platlets
- coagulation factos
- fibrinolytic factors
2
Q
What are endothelial cells? What action do they have ?
A
- 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
Q
What is vWF produced by? Function?
A
- endothelial cells and platelets
- stored in Weibel Palade bodies
- Released early in haemostatic process
- responsible for platelet adhesion to collagen
4
Q
Which reticular lines have the shortest half life? CLinical impliations?
A
- Neutrophils 6hrs
- Platelets ~1week
- RBC ~120d
> if BM affected, neutrophil numbers will be affected first, then platelets, then anaemia
5
Q
What are platelets?
A
- 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
Q
With generalised BM destruction what will be lost first?
A
- Neutrophils 6hrs t1/2
7
Q
What is present on the outer membrane of platleets?
A
- 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
Q
What is contained within the platelets?
A
- 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
Q
What is primary hemostasis? 2*? What follows these?
A
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
Q
Outline steps of 1* haemosasis.
A
- 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
Q
How does platelet aggregation occour?
A
- platelets bind fibrinogen via GPIIbIIIa
- fibrinogen generated from coagulation cascade
- released from platelets and found in plasma
12
Q
What do platelets secrete?
A
- 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
Q
What happens to the whole blood vessel whe damaged?
A
- vasoconstriction to v blood pressure and blood flow past the area
14
Q
2* haemostasis
A
- involves activation of the coagulation cascade
- happens simultaneously with formation of platelet plug
- damage to endothelium releases tissue factor activating EXTRINSIC clotting pathway
15
Q
What is the first and most important coagulation factors?
A
Tissue factor
16
Q
What is the end point of the coagulation cascape?
A
- activate thrombin tha causes fibrinogen -> fibrin
17
Q
What are coagulation factors?
A
- 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
Q
Do the intrinsic, extrinsic and common pathways exist in vivo?
A
no only in vitro
19
Q
What is the intrsinc and extrinsic link -> common apthway factor?
A
factor 10 -> 10a
20
Q
What is extrinsic system also known as? What does it do?
A
= 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
Q
What is he intrinsic pathway?
A
= 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
Q
Outline common pathway
A
- 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
Q
What are inhibitors of coagulation?
A
> antithrombin III
- inhibits thrombin and activated FX
- activity increased by heparin from endothelium
- protein C inactivates factors V and VIII
fibrinolysis
24
Q
Outline fibrinolysis
A
- 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
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
31
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)
32
3 main dioders of platelets?
> thrombocytopenia
> thrombocytoisis
> disorders of functon
33
What clinical signs may be seen with 1* clotting dz and 2*?
1* petichae and echymoses
| 2* haematoma
34
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
```
35
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
36
What is Evan's syndrome?
- concurrent immune mediated thrombocytopenia and anaemia
| - rare but bad!
37
2 forms of immune-mediated thrombocytopenia?
```
> 1* ab against platelet ag
> 2* - many causes
- other immune dz (SLE)
- drugs/vaccine/injection
- neoplasia
- infectious
```
38
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.
39
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)
40
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
41
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
