Hemostasis

Hemostasis
Bloodmustbefluid
Mustcoagulate(clot)atappropriatetime
Rapid
Localized
Reversible

NormalHemostasis
Awellregulatedprocess
Maintainsbloodinafluid,clotfree
stateinnormalvessels
Inducestherapidformationofa
localizedhemostaticplugatthesiteof
vascularinjury

NormalsequenceofHemostasis
(4steps)

1.Arteriolarvasoconstriction
1.Arteriolarvasoconstriction (transient)
Reflexneurogenicmechanisms
Bleedingwouldresumeaftervasoconstrictionif
itwerentfortheactivationofplateletsor
coagulationsystems

 2.ExposureofsubendothelialECMwhen
thereisendothelialinjury
ECM,especiallycollagen,ishighly
thrombogenic
Plateletsadhereandbecomeactivated
Changeinshape
Releaseofsecretoryproducts

Aggregationofplateletsformshemostatic
plug
Thisisprimaryhemostasis

Firsttwosteps
ofnormal
hemostasis

Normalhemostasiscontinued

3.Tissuefactorreleasedatthesiteof
injury(byendothelialcells)
injury
Workswithsecretedplateletfactors
Activatescoagulationcascade
Aseriesofproteinswherethrombinis
thrombin
activated
Inducesfurtherplateletrecruitmentand
granulerelease

Endsinfibrindeposition
Calledsecondaryhemostasis

Normalhemostasiscontinued

4.Formationofpermanentplug
Preventsfurtherhemorrhage
Polymerizedfibrinandplatelet
aggregation
Counterregulatorymechanisms(tPA)
limittheplugtothesiteoftheinjury

Steps3and4

TheMainPlayersinHemostasis

Endothelialcells
Platelets
Coagulationcascade

EndothelialCells
ProducevWF(vonWillebrandfactor)
vWF
Aproductofnormalendothelium
foundintheplasma
essentialforplateletbindingtocollagenandother
surfaces

SecreteTissuefactor
inducedbycytokines(TNF,IL1)
activatestheextrinsicclottingpathway

EndothelialCellshave
ProthromboticEffect
ViavWFandtissue
factor
factorsthatdepress
fibrinolysis
factorsneededforthe
clotarenotdestroyed
beforeclotforms

Collagenishighly
thrombogenic

Platelets
Expressglycoproteinreceptorson
glycoproteinreceptors
membranes.GpIb,IIb/IIIa
Havethreetypesofgranules
Alphagranules
Fibrinogen,fibronectin,factorVandVIII,
PDGF,TGF

Densebodiesordeltagranules
ATP/ADP,ionizedcalcium,histamine,
serotonin,epinephrine

Lysosomalgranules

Platelets

Hyalomereandgranulomere

Plateletscontinued

UponencounteringtheECM,platelets
undergothreegeneralreactions:
three
1.Adhesionandshapechange
Adhesionandshapechange
mediatedbyvWFandglycoproteinIb
2.Secretion(releasereaction)
Secretion
calciumrequiredincoagulationcascade
ADPasmediatorofplateletaggregation
Surfaceexpressionofphospholipidcomplex
Bindingsiteforcalciumionsandcoagulation
factors

Plateletscontinued

3.Aggregation
ADPandTXA2(vasoconstrictorthromboxaneA2)
arethestimulifortheformationoftheprimary
hemostaticplug
AspirininhibitssynthesisofTXA2

Fusedmassofplatelets
Createdbycoagulationcascadethatproduces
thrombin
thrombin
Thrombinalsoconvertsfibrinogento
fibrinogen fibrincementing
fibrin
plateletsinplace

PEMBEKUAN DARAH /SISTEM KOAGULASI

Proses koagulasi merupakan rangkaian reaksi

enzimatik yg melibatkan :
protein plasma sbg faktor koagulasi
fosfolipid
Ca 2+
Produk akhir jendalan fibrin

Faktor koagulasi

Factor

Common name(s)

Fibrinogen

II

Prothrombin

III

Tissue Factor, Tissue Thromboplastin

IV

Calsium Ion

Labile Factor, Proaccelerin

VI
VII

Stable Factor, Proconvertin

VIII

Hemophilia A factor

IX

Christmas Factor, Hemophilia B Factor, Plasma Thromboplastin

Component

Stuart Prower Factor

XI

Hemophilia C factor, Plasma Thromboplastin Antecedent (PTA)

XII

Hageman Factor, Contact Factor

XIII

Fibrin Stabilizing Factor, Laki-Lorand Factor

PK

Prekallekrein, Fletcher Factor

HMWK

High Molecular Weight Kininogen, Fitzgerald Factor

JalurIntrinsik JalurEkstrinsik

XIIVII
Kontak
XIIa Ca++
HMWKPKKTromboplastinjaringan
XIXIa
IXIxaVIIa
PF3
VIIITenaseComplex
Ca++

JalurBersama

XXa
V
PF3ProthrombinConvertingComplex
Ca++
Fibrinogen

ProtrombinTrombin

FibrinMonomer

FibrinPolimerSoluble
XIIIXIIIa
Ca++
FibrinPolimerInsoluble

Intrinsic pathway
XIIa
Extrinsic Pathway
XIa

TF
Prothrombin

VIII

IXa
VIIIa

Fibrinogen

VIIa
Xa
Va
Thrombin

V
Soft clot

Fibrin

XIIIa

Hard clot

Fibrin

Fibrinogen

Fibrin

Fibrinogen

Thrombin

Fibrin

Prothrombin
Xa
Va
Thrombin
Fibrinogen

Fibrin

Extrinsic Pathway
TF
Prothrombin
VIIa
Xa
Va
Thrombin
Fibrinogen

Fibrin

Intrinsic pathway
XIIa
Extrinsic Pathway
XIa

TF
Prothrombin

IXa
VIIIa

Fibrinogen

VIIa
Xa
Va
Thrombin

Soft clot

Fibrin

XIIIa

Hard clot

Fibrin

Intrinsic pathway
XIIa
Extrinsic Pathway
XIa

TF
Prothrombin

VIII

IXa
VIIIa

Fibrinogen

VIIa
Xa
Va
Thrombin

V
Soft clot

Fibrin

XIIIa

Hard clot

Fibrin

Hemophilia A
Deficiency of/nonfunctional VIII

Hemophilia B
Deficiency of /nonfunctional IX
Why do they bleed?

Intrinsic pathway
XIIa
Extrinsic Pathway
XIa

TF
Prothrombin

VIII

IXa
VIIIa

Fibrinogen

VIIa
Xa
Va
Thrombin

V
Soft clot

Fibrin

XIIIa

Hard clot

Fibrin

FIBRINOLISIS
Proses penghancuran deposit fibrin oleh sistem fibrinolitik
aliran darah terbuka kembali
Sistem Fibrinolitik, td :
- Plasminogen
- Aktifaktor Plasminogen
- Inhibitor Plasmin
Sistem Fibrinolitik dicetuskan oleh adanya aktivator plasminogen
memecah plasminogen plasmin
Aktivasi plasminogen : jalur intrinsik
jalur ekstrinsik
jalur eksogen

Fibrinolysis

Fibrin

Plasmin

Fibrin Split Products (FSP)

Fibrinolysis
Plasminogen
tPA

Fibrin

Plasmin

Fibrin Split Products (FSP)

SkemaFibrinolisis

IntrinsikEkstrinsikEksogen
(XIIa,Kalikrein)(tPA)(UrokinaseStreptokinase)

AktivatorPlasminogen

PlasminogenTerikatPlasminTerikatFibrin

FDP
PlasminogenBebasPlasminBebasFibrinogen
V
VIII
AntiPlasmin

Inhibitorsoffibrinolysis
Plasminogenactivatorinhibitors(PAIs)
2antiplasmin(serpin)

PEMERIKSAAN LABORATORIUM HEMOSTASIS

1. Rumple Leed (RL)

2. Bleeding time / masa perdarahan
3. Clotting time / masa penjendalan
4. Jumlah trombosit
5. Protrombin Time (PT) / Plasma Protrombin Time (PPT)
6. Activated Partial Tromboplastin Time (APTT)
7. Trombin Time

2. BLEEDING TIME/MASA PERDARAHAN

Tujuan :
menilai faktor hemostasis yg letaknya ekstravaskuler
Metoda :
Ivy
- voler lengan bawah (T 40 mmHg) tusuk lancet
sedalam 3 mm isap dg kertas saring tiap 30 detik
- N : 1 6 menit
Duke
- telinga
- N : 1 3 menit

3. CLOTTTING TIME / MASA PENJENDALAN

Tujuan :
Mendeteksi kualitas dan kuantitas faktor koagulasi scr
keseluruhan
Nilai normal :
9 15 menit
Gelas arloji : 2 6 menit

4. JUMLAH TROMBOSIT
Tujuan :
mengetahui kuantitas trombosit
Cara :
Langsung
Manual : Brecher
Herweden
Semi otomatik
Otomatik
Tak langsung Fonio
Nilai normal : 150.000 400.000 / mm 3

5. PROTROMBIN TIME (PT) / PLASMA PROTROMBIN

TIME (PPT)
Tujuan :
- Menguji faktor koagulasi jalur ekstrinsik (VII) & jalur
bersama (V, X)
- Memonitor terapi anti koagulan oral

Cara :
Plasma + Ca 2+ + tromboplastin jaringan terbentuk jendalan
dideteksi dgn fotodetektor (37 0C)
Waktu yg diperlukan utk pembentukan jendalan PT

Nilai normal :
11 -15 detik ( atau beda dgn kontrol 2 detik )

6. ACTIVATED PARTIAL TROMBOPLASTIN TIME (APTT)

Tujuan :
- Menguji faktor koagulasi jalur intrinsik (VIII, IX, XI, XII) &
bersama (V, X)
- Memonitor terapi heparin
Cara :
Plasma + Ca 2+ + tromboplastin jaringan terbentuk jendalan
dideteksi dgn fotodetektor (37 0C)
Waktu yg diperlukan utk pembentukan jendalan APTT
Nilai normal :
20 - 40 detik

7. THROMBIN TIME (TT)

Tujuan :
menguji perubahan fibrinogen menjadi fibrin
Cara :
plasma + reagen trombin bekuan (370 C)
Nilai normal :
16 20 detik

ConditionsCausing
Bleeding
Incompletehemostasisismost
commoncauseofbleeding.
VitaminKdeficiency
severecoagulationdefect
Requiredforsynthesisofprothrombin
andfactorsVII,IXandX

Parenchymaldiseasesoftheliver
Liversynthesizesseveralcoagulation
factors

Hereditarydeficiencies
HemophiliaAfactor
VIIIdeficiency

Sexlinkedrecessive
30%duetonewmutations
anddonthavefamilylink
Hemarthrosescommon
Hemarthroses
(spontaneousbleedingin
joints)
Infusepatientwithfactor
VIIIfromhumanbloodor
cryoprecipitate.
Need100%levelspreop,
keepat30%postop.

HemophiliaBfactorIX
deficiency
Clinicallyindistinguishable
fromHemophiliaA
Sexlinkedrecessive
Need50%preoperatively
ProlongedPTT,normalPT
TX:FactorIXorFFP

Von
Von Willebrands
Willebrands Disease
VonWillebrands
DiseaseMostcommon

congenitalbleedingdisorder.
TypesI,II,andIII.
PTnormalPTTnormalor
elevated
Prolongedbleedingtime
TypeImostcommon(70%)
withmildsx.
TypeIIIcausesmost
bleeding

TypeIandIII
reducedquantityof
vWF
TX:Cryo,DDAVP
TypeIIdefectinvWF
molecule,enoughofit
butdoesntworkwell.
TX:Cryo

Platelet
Platelet Disorders
AcquiredH2
Acquired
blockers,heparin.
BernardSoulier,a
Soulier
Gp1breceptor
deficiency(cantbind
toeachother)
UremiaInhibitsGp1b,
Uremia
vWF.TX:dialysis,
DDAVP,cryo,plts.

Ticlopidinedecreases

ADPinplatelets,prevents
exposureofGp1b/IIIa
receptors.
Dipyramidole
decreasesADPinducedplt
aggregation.
PlavixADPreceptor
antagonist.
Pentoxifyllininhibits
pltaggregation

Platelet
Platelet Disorders
Heparininduced
thrombocytopenia
(HIT)

DIC
Decreasedplts,
prolongedPT,PTT.
Antiplateletantibodies
Lowfibrinogen,high
resultsinplatelet
fibrinsplitproducts,
destruction.
highDdimers
Alsocausesaggregation
andthrombosis.
Ofteninitiatedby
Lowdosesofheparin.
tissuefactor.
LMWHmayhavelessrisk.
Treatunderlyingcause

Thrombi
Plateletaggregates
Fibrin
Trappederythrocytes
andleucocytes
Notpartofthis
hemostaticprocess

Thisisadeepvein
thrombosis
Postoperativepatients
confinedtobed

Endothelialinjuryisdominant
influence
Heartandarterialcirculation
Hypercholesteremia,cigarettesmoke
products
Radiation,bacterialendotoxins
Resultsinexposureofsubendothelial
collagen,adherenceofplatelets,releaseof
tissuefactorandlocaldepletionof
prostacyclin(antithrombin)

Alterationsinnormalbloodflow
Turbulence
injuresendothelium
Atheroscleroticplaques

Stasis
Stasis
Cancreatevenousthrombi
Aneurysmscauselocalstasis
DeformedcellsofSicklecellanemiacause
vascularocclusions

StasisandTurbulence
Disruptlaminarflow(cellsinmiddle)
Bringplateletsintocontactwith
endothelium
Preventdilutionofactivatedclotting
factorsbyfreshflowingblood
Retardinflowofclottingfactorinhibitors

Hypercoagulability
LeidenFactor30%spontaneousvenous
LeidenFactor
thrombosis.
Mostcommoncongenitaldisorder.
ResistancetoProteinC,defectonfactorV
TX:heparin,warfarin.
ProteinC,Sdeficiency5%venous
ProteinC,Sdeficiency
thromboses.TX:heparin,warfarin.

Hypercoagulability
AntithrombinIIIdeficiency23%
AntithrombinIII
thrombosis.Heparindoesntwork.Can
developafterpreviousheparinexposure.
TX:ATIIIconcentrate,FFP(highestconc)
followedbyheparin.
Polycythemiadefectinplateletfunction,
Polycythemia
usuallythrombotic,butcanbleed.Keep
HCT<48,PLTS<400beforeSX.TX:ASA.

Hypercoagulability
LupusAnticoagulantantiphospholipid
LupusAnticoagulant
antibodies.NotallpatientshaveSLE.A
procoagulant(prolongedPTTbut
hypercoagulable).
DiagnosebyseeingprolongedPTT,false
positiveRPRtestforsyphilis.
TX:heparin,warfarin.

Hypercoagulability
CardiopulmonaryBypassfactorXII
CardiopulmonaryBypass
activated,resultsinhypercoagulablestate.
TX:heparin,warfarin.
Warfarininducedskin
Warfarininducedskin necrosisOccurs
necrosis
whencoumadinstartedbeforeheparin.Due
toadecreaseinproteinS,Cmakingpatient
transientlyhypercoagulable.Patientswith
ProtienCdeficiencyhighlysusceptible.

Hypercoagulability
Maybegeneticor
acquired
Geneticmutationsin
thefactorVgene
MutantfactorVis
resistantto
anticoagulanteffectof
activatedproteinC

Smoking,obesityand
age

Latepregnancyand
postpartum
amnioticfluidinfusion
intocirculation

Disseminatedcancers
tumorsrelease
procoagulants

Advancedage,bed
restand
immobilization

Hematologic
Hematologic Drugs
WarfarinpreventsVitKdependent

decarboxylationofglutamicresiduesonVit
Kdependentfactors.
Dextraninhibitsplateletsandcoagulation
factors.
Sequentialcompressiondevicesimprove
Sequentialcompression
venousreturnbutalsoinducefibrinolysis
withcompression(releaseoftPA).

Hematologic
Hematologic Drugs
HeparinactivatesantithrombinIII.
Heparin
Reversedwithprotamine(11.5protamine
per100uofheparin).
Halflife6090min.
Longtermheparinusecausesosteoporosis,
alopecia.DoesnotcrossBBB.
Protaminesideeffectsarehypotension,
Protamine
bradycardia,decreasedheartfunction.

Hematologic
Hematologic Drugs
Hirudinleeches,thrombininhibitor.
AncrodMalayanpitvipervenom,stimulates
tPArelease.

Amicarantifibrinolytic,procoagulant,inhibits
plasmin.UsedinDIC,persistentbleeding
followingCABG,thrombolyticoverdoses.

Streptokinase,tPAneedtofollowfibrinogen

levels,levels<100associatedwithseverebleeding.

Fateofthrombus
Propagation
Accumulatemore
plateletsandfibrinand
obstructacritical
vessel

Embolization
Dislodgethrombiand
transportedtoother
sitesinvasculature

Fateofthrombus,
continued

Dissolution/resolution
Removedby
fibrinolyticactivity

Organization
Organization
Induceinflammation
andfibrosisandmay
reopenandallowblood
flow

Fatescontinued
Recanalization
Openingsandeven
bloodvesselscreated
inthrombus