LEC 8 Pletelets & Hemostasis

8/10/2019 LEC 8 Pletelets & Hemostasis

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Dr S.BashirDr S.Bashir ##

PlateletsPlatelets ::(thrombocytes)(thrombocytes)

Flattened, disk-like cellFlattened, disk-like cellfra ments .fra ments .

!ssential for "emostasis.!ssential for "emostasis.!ac" #latelet circulates for !ac" #latelet circulates for

$-%2 da s$-%2 da s

'emo(ed ) s#lenic'emo(ed ) s#lenicmacro#"a es.macro#"a es.*"ere are + 3 , uL of *"ere are + 3 , uL of )lood.)lood.


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Dr S.BashirDr S.Bashir $$

SynthesisSynthesis

Produced in t"e )one marro/.Produced in t"e )one marro/.Lar e cells called me akar oc tes releaseLar e cells called me akar oc tes releasefra ments 0#latelets1 into t"e circulation.fra ments 0#latelets1 into t"e circulation.


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Dr S.BashirDr S.Bashir %%

Platelet function:Platelet function:

platelet plug platelet plug


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Dr S.BashirDr S.Bashir ''

11- - Vascular PhaseVascular Phase

*"e smoot" muscle cells in t"e*"e smoot" muscle cells in t"e)lood (essel /all res#ond to)lood (essel /all res#ond todama e. *"edama e. *"e 46N*' 4*46N*' 4* . *"e. *"e

)lood (essel diameter decreases)lood (essel diameter decreasesreduction in )lood loss.reduction in )lood loss.

*"e refle8 is immediate )ut*"e refle8 is immediate )uttransient.transient.9n:ur9n:ur e8#ose t"e rou " & sticke8#ose t"e rou " & stickcolla en fi)ers in t"e )asementcolla en fi)ers in t"e )asementmem)rane of (esselsmem)rane of (essels 0 !8tra 4ell.0 !8tra 4ell.Matri81.Matri81.


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Dr S.BashirDr S.Bashir ((

2 2 - - Platelet plug phasePlatelet plug phase


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Dr S.BashirDr S.Bashir 1*1*

3- oagulation Phase3- oagulation Phase

se


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Dr S.BashirDr S.Bashir 1111

!echanism of oagulation!echanism of oagulation

PhasePhase9n:ured tissues release t"rom)o#lastin,9n:ured tissues release t"rom)o#lastin, PF PF 33 0a #"os#"oli#id10a #"os#"oli#id1

PF PF 33 interacts /it" )lood #rotein clottin factors,interacts /it" )lood #rotein clottin factors,and calcium ions to tri er a clottin cascade.and calcium ions to tri er a clottin cascade.

4lottin factors are4lottin factors are #roen> mes#roen> mes 0inacti(e0inacti(een> mes1 t"at "a(e to )e con(erted to acti(een> mes1 t"at "a(e to )e con(erted to acti(een> mes.en> mes.


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!echanism of oagulation!echanism of oagulation

PhasePhase?urin t"e coa ulation?urin t"e coa ulation#"ase en> mes and#"ase en> mes and#roen> mes interact.#roen> mes interact.*"e acti(ation of one*"e acti(ation of one#roen> me#roen> me creates ancreates anacti(e en> me t"at acti(atesacti(e en> me t"at acti(atesanot"eranot"er #roen> me#roen> me t"at /illt"at /illt"en acti(ate a t"ird and sot"en acti(ate a t"ird and soon ieldin a c"ain reactionon ieldin a c"ain reactionoror cascadecascade ..


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Dr S.BashirDr S.Bashir 1#1#

!echanisms of oagulation!echanisms of oagulation

PhasePhase+oagulation can be acti!ate by either+oagulation can be acti!ate by either

-ntrinsic pathway-ntrinsic pathway

Extrinsic pathwayExtrinsic pathway he intrinsic pathway/ all factors foun he intrinsic pathway/ all factors founin bloo .in bloo .

he extrinsic pathway/ re0uires tissue he extrinsic pathway/ re0uires tissuefactors resulting from tissue in ury.factors resulting from tissue in ury.


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E +34 -"5 6E+ 7"-S6

E9 8-"S-+

P'6*H'6M=9N *H'6M=9N

F9='9N6@!N

F9='9N0II1 0III1

0I1V

X

*issue *"rom)o#lastin

VII


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Fi)rino en Fi)rin

*"rom)in

Prot"rom)in

Aaa

99a

*F

!8trinsic Pat"/a


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Fi)rino en Fi)rin*"rom)in

Prot"rom)in

Aaa

99a

*F

!8trinsic Pat"/a

9Aa

999a

A9a

A99a

9ntrinsic #at"/a

A999a

Soft clot

Fi)rin

Hard clot


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Dr S.BashirDr S.Bashir 2*2*

%ntrinsic Path$ay %ntrinsic Path$ay

Begins with the exposure of Begins with the exposure of collagencollagen which starts thewhich starts theactivation cascade of severalactivation cascade of severalproen$ymes eventuallyproen$ymes eventuallyresulting in the production ofresulting in the production ofprothrombin activator ( !)prothrombin activator ( !) ..

Because there are severalBecause there are severalsteps, the intrinsic path doessteps, the intrinsic path does

not ma#enot ma#e ( !)( !) as fast as theas fast as theextrinsic path. %owever,extrinsic path. %owever,multiple steps allows for moremultiple steps allows for moreamplification which meansamplification which meansmoremore ( !)( !) will be madewill be made moremorefibrinfibrin


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'-(ibrinolysis'-(ibrinolysis

&s repairs proceeds, the clot gradually dissolves. This&s repairs proceeds, the clot gradually dissolves. Thisdissolution is #nown asdissolution is #nown as fibrinolysis.fibrinolysis. ibrinolysis begins with the activation of the proen$ymeibrinolysis begins with the activation of the proen$yme

plasminogen into plasminplasminogen into plasmin'lasmin digests the fibrin strands and erodes the'lasmin digests the fibrin strands and erodes thefoundation of the clotfoundation of the clot ..


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Dr S.BashirDr S.Bashir 2#2#

HemostasisHemostasis :: summary summary


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Dr S.BashirDr S.Bashir 2$2$

)hy *oesn+t bloo* clot in normal)hy *oesn+t bloo* clot in normalvessels, vessels, "n*ogenous %nhibitors of Hemostasis"n*ogenous %nhibitors of Hemostasis%-%-*"e normal endot"elium*"e normal endot"elium intact & smoot"intact & smoot" ..

2-2- Flo/ of )lood.Flo/ of )lood. StasisStasis clottin tendenc B clottin tendenc B

3-3- !ndot"elium also secretes #roducts /"ic"!ndot"elium also secretes #roducts /"ic"in"i)it #latelet a re ationin"i)it #latelet a re ation nitric o8idenitric o8ide andand#rostac clin.#rostac clin. (antagonists for thromboxane A(antagonists for thromboxane A 2 2 11

5-5- ntit"rom)in 0 *1 0also called ntit"rom)in 0 *1 0also called antit"rom)inantit"rom)in999 ,999 ,from t"e li(er from t"e li(er ,, in"i)itsin"i)its t"rom)in 0factort"rom)in 0factor99a1 .99a1 .-- He#arinHe#arin from mast cells en"ances *from mast cells en"ances * ..


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Dr S.BashirDr S.Bashir 2%2%

)hy *oesn+t bloo* clot in)hy *oesn+t bloo* clot in

normal vesselsnormal vessels

, ,


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Bleeding Disorders & Coagulopath Bleeding Disorders & Coagulopath


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Dr S.BashirDr S.Bashir 2(2(

Vitamin 0 *ef Vitamin 0 *ef ::

S nt"esi>ed ) )acterial flora in lar eS nt"esi>ed ) )acterial flora in lar eintestine.intestine.

Stimulates li(er s nt"esis of factorsStimulates li(er s nt"esis of factors 99, ,99, ,99 , A.99 , A.?eficienc in?eficienc in

C Ne/)orns, s#eciall #remature ones.Ne/)orns, s#eciall #remature ones.;" B;" B

C Prolon ed use of anti)iotics.Prolon ed use of anti)iotics. ;" B;" B


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Dr S.BashirDr S.Bashir #1#1

hrombushrombus

lar e t"rom)us ma lar e t"rom)us ma)lock a (ein)lock a (ein

.. eepeep V V einein hrombosishrombosis=lood stasis increase risk of=lood stasis increase risk of? *? * ..4auses of stasisB4auses of stasisB C 9mmo)ili>ation after9mmo)ili>ation after

fractures sur er ,fractures sur er ,deli(er , Lon fli "ts.deli(er , Lon fli "ts.


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Dr S.BashirDr S.Bashir ####

"mbolus"mbolus

9f t"e t"rom)us )reaks9f t"e t"rom)us )reaksoff & tra(els in t"eoff & tra(els in t"e

)loodstream, itEs called)loodstream, itEs calledanan em)olus.em)olus.!m)olus )locks an!m)olus )locks anarterarter C =rain stroke.=rain stroke. C Pulmonar em)olism.Pulmonar em)olism. C M ocardial infarctionM ocardial infarction


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Dr S.BashirDr S.Bashir #$#$

reatment of coagulopathiesreatment of coagulopathies


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Dr S.BashirDr S.Bashir #%#%

"#ogenous anti-coagulants"#ogenous anti-coagulants

HeparinHeparin /"ic" /orks ) inacti(atin t"rom)in./"ic" /orks ) inacti(atin t"rom)in.4annt )e taken orall & "as to )e in:ected.4annt )e taken orall & "as to )e in:ected.

ouma*in $arfarinouma*in $arfarin ## /"ic" #re(ents t"e li(er/"ic" #re(ents t"e li(erfrom utili>in (itamin D 0necessar for t"efrom utili>in (itamin D 0necessar for t"e#roduction of clottin factors1. *aken orall .#roduction of clottin factors1. *aken orall .

spirin spirin , /"ic" in"i)its #latelet a re ation and, /"ic" in"i)its #latelet a re ation and#rosta landins s nt"esis#rosta landins s nt"esis 0*"rom)o8ane 2 )ut0*"rom)o8ane 2 )utalso #rostac cline.1also #rostac cline.1


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Dr S.BashirDr S.Bashir #'#'

Prevention of clotting in the labPrevention of clotting in the lab::

He#arini>ed containers.He#arini>ed containers.

7 +a7 +a :::: chelating agentschelating agents // ED 7,ED 7,citratescitrates ..


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Dr S.BashirDr S.Bashir #)#)

han4 5ou han4 5ou

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LEC 8 Pletelets & Hemostasis