hemostasis & coagulation disorders(ringkas ii) - dicky [compatibility mode]

8/11/2019 Hemostasis & Coagulation Disorders(Ringkas II) - Dicky [Compatibility Mode]

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What isWhat is haemostasishaemostasis??

A body mechanism to stop traumatic bleeding spontaneousA body mechanism to stop traumatic bleeding spontaneousand localized, and to keep the fluidity of blood in vascular.and localized, and to keep the fluidity of blood in vascular.

BalanceBalance haemostasishaemostasis require:require: Bloodvessel

orma oo vesse sorma oo vesse s

Normal plateletsNormal platelets

Normal coagulation factorsNormal coagulation factors

Inhibitors Platelet

ormaorma r no ys sr no ys s an o eran o er

regulating proteins/inhibitorsregulating proteins/inhibitorsHemostasis

FibrinolysisCoagulation

factors


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HemostasisMx NORMAL HEMOSTASIS & KOAGULASI:

1. Spasme dinding pembuluh darah (fase vaskularmis: Carbazochrome

2. Peranan fungsi platelet (fase platelet)

3. Faktor Koagulasi (fase koagulasi)

mis: Vit. K

. s em an oagu an an an r no s s

mis: Asam traneksamat ( anti fibrinolisis )


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Hemostasis

1. Vascular Phase - Vasoconstriction


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Senile PurpuraSenile Purpura


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Petechiae inPetechiae in

VasculitisVasculitis

(Rocky Mountain Spotted Fever)(Rocky Mountain Spotted Fever)


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-- ImmuneImmune

disorderdisorder ChildrenChildren

FollowsFollows

infectioninfection PetechiaePetechiae withwith

edema andedema and

itching.itching.


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--

20y Male, fever, painful symmetric polyarthritis for a day. During the next two days, edema and palpable purpura developed.


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2. Platelet Phase ( Platelet Plug )


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ROMBOSITROMBOSITJumlahnya adalah 150 450 x 10 / mmDiameter 2.5

Fungsi : adhesi, sekresi, agregasi pembentukan

Diproduksi di sumsum tulang melalui fragmentasisitoplasma

megakariosit (1 megakariosit 4000 trombosit)Produksi trombosit dikendalikan oleh mekanisme

umora ya u ormon rom opo e n

Trombopoietin disintesis oleh hati (>>>) dan ginjal


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--

PetechiaePetechiae && PurpuraPurpura

spontaneous bleeding afterspontaneous bleeding after

CNS bleeding (CNS bleeding (severesevere pltplt))

Prolonged bleeding time (BT)Prolonged bleeding time (BT)


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Platelet count < 100,000/LPlatelet count < 100,000/L

Spontaneous bleeding if < 20,000 /LSpontaneous bleeding if < 20,000 /L

If BMP shows increased ofIf BMP shows increased of megakaryocytesmegakaryocytes

If vice versa means disorders of plateletIf vice versa means disorders of platelet

PseudothrombocytopeniaPseudothrombocytopenia: platelet clumping: platelet clumpingsecondary to collection of blood in EDTAsecondary to collection of blood in EDTA


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..

marrow injury (drug, irradiation), marrowmarrow injury (drug, irradiation), marrow, , ,, , ,

failure (failure (e.ge.g aplasticaplastic anemia)anemia)

2. Sequestration due to2. Sequestration due to splenomegalysplenomegaly

3. Accelerated destruction3. Accelerated destruction


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Causes of Accelerated DestructionCauses of Accelerated Destruction Drugs:Drugs:

ChemoChemo txtx,, thiazidethiazide, ethanol, estrogen, sulfonamides,, ethanol, estrogen, sulfonamides,

quinidinequinidine, quinine, methyldopa, quinine, methyldopa Heparin Induced ThrombocytopeniaHeparin Induced Thrombocytopenia

Autoimmune DestructionAutoimmune Destruction

Idiopathic ThrombocytopenicIdiopathic Thrombocytopenic PurpuraPurpura ( ITP )( ITP )

Thrombotic ThrombocytopenicThrombotic Thrombocytopenic PurpuraPurpura ( TTP )( TTP )

Hemorrhage with extensive transfusionHemorrhage with extensive transfusion


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PlateletPlatelet dysfunctiondysfunction

n er e sor ers:n er e sor ers:

BernardBernard--SoulierSoulier diseasedisease

large platelets, failure oflarge platelets, failure of adhesionadhesion

GlanzmannsGlanzmanns thrombastheniathrombasthenia normal size, failure ofnormal size, failure of aggregationaggregation

DrugsDrugs -- Aspirin, Alcohol, Uremia,Aspirin, Alcohol, Uremia,


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Platelet deficiency..


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3. Blood Clot


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PEMBEKUAN DARAHPEMBEKUAN DARAH(KOAGULASI)(KOAGULASI)

Meru akan sistem am lifikasi biolo isMeru akan sistem am lifikasi biolo is

ProkoagulanProkoagulan aktivasi oleh proteolisisaktivasi oleh proteolisis faktor koagulasifaktor koagulasiaktif (bersifat enzim)aktif (bersifat enzim) mengaktifkan prokoagulanmengaktifkan prokoagulan

er u nyaer u nya

CASCADE KOAGULASICASCADE KOAGULASI

em en u an r nem en u an r n


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NomorNomor NamaNama

II FibrinogenFibrinogenSemua faktor koagulasi mrpk

IIIIII TromboplastinTromboplastin / Tissue Factor/ Tissue Factor

IVIV CalciumCalcium

Semua enzim mrpk serine protease

a e ac ora e ac or roacce er nroacce er n

VIIVII ProconvertinProconvertin / Serum/ Serum ProthrombinProthrombinConversion Accelerator (SPCA ) / StableConversion Accelerator (SPCA ) / Stable

kecuali Faktor XIII

VIIIVIII AHF (AntiAHF (Anti HemofilicHemofilic Factor)Factor)

IXIX PlasmaPlasma ThromboplastinThromboplastin ComponentComponent

(Faktor Jaringan) terdapat pada

permukaan jar perivaskuler,

berikatan dengan Faktor VII (TF-

XX StuartStuart ProwerPrower FactorFactor

XIXI PTA (PlasmaPTA (Plasma ThromboplastinThromboplastin

FVII)

Istilah faktor VI tdk lg digunakan,

n ece enn ece enXIIXII Hageman Factor (Contact Factor)Hageman Factor (Contact Factor)

XIIIXIII Fibrin Stabilizing FactorFibrin Stabilizing Factor

sebab apa yang semula dianggapfaktor VI yg terpisah, sekarangdiketahui adalah bentuk aktif

-- PrekallikreinPrekallikrein (Fletcher Factor)(Fletcher Factor)

-- HMWK (High Molecular WeightHMWK (High Molecular WeightKininogenKininogen))


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Blood Coagulation & TestsBlood Coagulation & Tests


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Inisiator koagulasi


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..misalnyamisalnya dengandengan obatobat asamasam tranexamattranexamat


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.. rnoyssrnoyss


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Fibrinol sisFibrinol sis Normal body process to breakdown fibrin/clotsNormal body process to breakdown fibrin/clots


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PG

t-PAt-PA

PG

PlasminogenPlasminogen

PlasminPlasmin

-

PG PL

-

PG PLFDPsFDPs

FibrinFibrinFibrin


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Faktor XIa, XIIa,HMWK, Kallikrein

tPA (tissue plasminogenActivator), Urokinase

Plasminogen Plasmin

Fibrin / Fibrinogen Fragmen X

Fragmen Y + D

Fragmen E + D

Sistem FibrinolitikSistem Fibrinolitik


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Primary and SecondaryPrimary and Secondary HemostasisHemostasisInjury to vessel wall ( exposure of subendothelium )

Adhesion of platelets

Vasoconstriction

Activation and aggregation of platelets

Primary hemostatic thrombus (white thrombus)

Activation of coagulation cascade

Activation of thrombin and formation of fibrin

Intrinsic (F XII/F XI) and extrinsic pathways (tissue factor)

Secondary hemostatic thrombus (red thrombus)


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Coagulation & fibrinolysis should be in balanceCoagulation & fibrinolysis should be in balance


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IMBALANCESIMBALANCES


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HaemostasisHaemostasis estingsestings


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HaemostasisHaemostasis TestingsTestings Abnormalities are notnormall detectable b

laboratory tests

vessel

, ,

plateletaggregometry

Inhibitors Platelet

Hemostasis

Coagulation

PT, APTT, TT, vWF, coagulation factors,

Protein C, Protein S, AT-III, LA1, LA2, D-Dimer

C diti fC diti fC diti fC diti f


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Conditions ofConditions ofConditions ofConditions of

coagu opat ycoagu opat ycoagu opat ycoagu opat y

Hemophilia Liver disease

DIC

Anticoagulant treatment


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OnsetOnset -- delayed after traumadelayed after trauma

Deep bleedingDeep bleeding

--

Into deep tissuesInto deep tissues HematomaHematoma

arge s n eearge s n ee cc ymosescc ymoses


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Acute bleedingAcute bleeding

Diseases with potentialDiseases with potential hemostasishemostasis disorders: liverdisorders: liver

disease se sis DICdisease se sis DIC thrombo hiliathrombo hilia.. Screening preScreening pre--operative/invasiveoperative/invasive

Patient that are havin or will have anticoa ulantPatient that are havin or will have anticoa ulant

therapytherapy


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Platelet countPlatelet count

Activated Partial Thromboplastin timeActivated Partial Thromboplastin time

Thrombin Time (TT)Thrombin Time (TT)


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PTPT APTTAPTT DeficiencyDeficiency

NN>>

>>NN

XII, XI, IX, VIIIXII, XI, IX, VIIIVIIVII

>> >> X, V, II, IX, V, II, I

Mixing Study:To distinguish deficiency from inhibitor


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Normal bleeding time & Platelet countNormal bleeding time & Platelet count

ProlongedProlonged prothrombinprothrombin time (PT)time (PT)

deficiencies of II, V, VII, Xdeficiencies of II, V, VII, X Prolonged time (Prolonged time (aPTTaPTT))

all factors exce t VII XIIIall factors exce t VII XIII

Mixing studiesMixing studies -- normal plasma correctsnormal plasma corrects


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Classic hemo hilia hemo hilia AClassic hemo hilia hemo hilia A

XX--linkedlinked receciverececive (affects 1 males)(affects 1 males) Most commonMost common -- severe bleedinsevere bleedin

Spontaneous hematomasSpontaneous hematomas < 1, 5, 75%< 1, 5, 75%

AbnormalAbnormal aPTTaPTT Intrinsic path.Intrinsic path. Diagnosis:Diagnosis:

Immunoassay: factorImmunoassay: factor VIIIVIII ( N: 52( N: 52--100% )100% )

Po ymorp c DNA pro esPo ymorp c DNA pro es TreatmentTreatment -- factor VIIIfactor VIII concentrate, Cryoprecipitateconcentrate, Cryoprecipitate


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Factor IX DeficiencyFactor IX Deficiency

Christmas disease (Hemophilia B)Christmas disease (Hemophilia B)

--

Indistinguishable from classic hemophilia (FIndistinguishable from classic hemophilia (FVIIIVIII

AbnormalAbnormal aPTTaPTT Intrinsic pathIntrinsic path

Dia nosis:Dia nosis: factor IXfactor IX ( N: 52( N: 52--100% )100% )

Re uires evaluation of factor VIII and IXRe uires evaluation of factor VIII and IX

activity levels to diagnoseactivity levels to diagnose TreatmentTreatment -- factor IX concentratefactor IX concentrate

Cryoprecipitate if factor IX unavailableCryoprecipitate if factor IX unavailable


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VonVon WillebrandWillebrand DiseaseDisease

PenyakitPenyakit perdarahanperdarahan kongenitalkongenital (( autosomalautosomal dominantdominant

melekatkanmelekatkan trombosittrombosit keke endotelendotel ,,

diperlukandiperlukan pdpd adesiadesi trombosittrombosit && berperanberperan sbgsbg

pembawapembawa fcfc VIIIVIII DefisiensiDefisiensi//abnormalitasabnormalitas fcfc VWVW tjdtjd abNabN hemostasishemostasis

primerprimer

RiwRiw PenyakitPenyakit:: EpistaksisEpistaksis,, ptekieptekie,, hematomhematom,, menoragimenoragi,, perdarahanperdarahan gusigusi //

salsal.. CernaCerna (( spontanspontan // tdktdk ))

TandaTanda && GxGx KlinikKlinik::


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TandaTanda && GxGx KlinikKlinik::

Rin anRin an:: erdarahanerdarahan mukokutanmukokutan GIBGIB e istaksise istaksismenoragimenoragi ))

BeratBerat hemartrosishemartrosis,, hematomhematom intraintra muskularmuskular

Lab: BTLab: BT , APTT N/ , F VIII ,, APTT N/ , F VIII , vWFvWF N/N/

TipeTipe I (70%) :I (70%) : defekdefek kuantitatifkuantitatif DDAVPDDAVP

pepe :: e ee e ua aua a onsen raonsen ra

F VIII (F VIII ( tergantungtergantung tipetipe ))

Platelet type (pseudoPlatelet type (pseudo--VWD) :VWD) : defekdefek glikoproteinglikoprotein IbIb

Cryoprecipitate ( f VIII, fibrinogen,Cryoprecipitate ( f VIII, fibrinogen, vWFvWF ))


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Acquired coagulation disorderAcquired coagulation disorder::

Vitamin K deficiencyVitamin K deficiency

-- neonatesneonates -- decreased intestinaldecreased intestinal

flora and dietary intakeflora and dietary intake-- oral anticoagulants (oral anticoagulants (coumadincoumadin))

-- fatfat malabsorptionmalabsorption syndromessyndromes

, , ,, , ,

Prolonged PT andProlonged PT and aPTTaPTT


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Combined Primar and SecondarCombined Primar and SecondarHemostaticHemostatic DisordersDisorders

..

CoagulationCoagulation Major pathologic processesMajor pathologic processes --

obstetric complications,obstetric complications, neoplasmsneoplasms,,

n ec on seps s , ma or rauman ec on seps s , ma or rauma

PrimaryPrimary -- platelet consumptionplatelet consumption

ee ng me,ee ng me, p a e e sp a e e s SecondarySecondary -- factor consumptionfactor consumption

,,

DDi i t di i t d II t lt l CC l til ti


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DDisseminatedisseminated IIntravascularntravascular CCoagulationoagulation

A complex systemic thrombohemorrhagic disorder involving the generation ofintravascular fibrin and the consumption of procoagulants and platelets. The resultantclinical condition is characterized by intravascular coagulation and hemorrhage.

Common Causes of DICCommon Causes of DIC


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Common Causes of DICCommon Causes of DICInfections*Infections*

-- , ,, ,EnterobacteriaceaeEnterobacteriaceae GramGram--positive bacteria:positive bacteria: PneumococcusPneumococcus, Staphylococcus, Hemolytic Streptococcus, Staphylococcus, Hemolytic Streptococcus Viral: Hepatitis,Viral: Hepatitis, varicellavaricella, cytomegalovirus, hemolytic streptococcus, cytomegalovirus, hemolytic streptococcus

CancerCancer--related*related*

Leukemia: AcuteLeukemia: Acute promyelocyticpromyelocytic, acute, acute myelogenousmyelogenous, chronic, chronic myelogenousmyelogenous, acute, acutelymphoblasticlymphoblastic Solid tumors: Lun breast stomach rostate ancreas ovarianSolid tumors: Lun breast stomach rostate ancreas ovarian biliarbiliar tracttract Blood transfusion reactions: Acute hemolytic transfusion reactions, massiveBlood transfusion reactions: Acute hemolytic transfusion reactions, massive

transfusion of whole bloodtransfusion of whole blood Liver disease: Liver failure secondary to primary liver disease or metastasisLiver disease: Liver failure secondary to primary liver disease or metastasis

Prosthetic devices:Prosthetic devices: PeritoneovenousPeritoneovenous shuntsshuntsObstetric complicationsObstetric complications

Amniotic fluid embolismAmniotic fluid embolism Premature separation of placentaPremature separation of placenta EclampsiaEclampsia; retained placenta; retained placenta

Septic a ortionSeptic a ortion

Widespread tissue damageWidespread tissue damage Following surgery or traumaFollowing surgery or trauma After severe burnsAfter severe burns

Vascu ar a norma itiesVascu ar a norma ities KasabachKasabach Merritt syndromeMerritt syndrome

Leaking prosthetic valvesLeaking prosthetic valves Cardiac bypass surgeryCardiac bypass surgery

Test Res lts in DICTest Res lts in DIC


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Test Results in DICTest Results in DICenera Testsenera Tests

Platelet count: DecreasedPlatelet count: Decreased Fibrino en level: DecreasedFibrino en level: Decreased Peripheral blood smear:Peripheral blood smear: SchistocytesSchistocytes DD--dimerdimer assay: Elevatedassay: Elevated

Tests to Determine Accelerated CoagulationTests to Determine Accelerated Coagulationrr : r: r FibrinopeptideFibrinopeptide A: ElevatedA: Elevated ProthrombinProthrombin activation peptides (F1 & F2): Elevatedactivation peptides (F1 & F2): Elevated

hrombinhrombin--antithrombinantithrombin complexes: Elevatedcomplexes: Elevated

PlasminogenPlasminogen: Decreased: Decreased

AlphaAlpha--22--antiplasmin: Decreasedantiplasmin: Decreased


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..

PrimaryPrimary -- dysfunctional platelets and/ordysfunctional platelets and/or

thrombocytopenia (thrombocytopenia ( BT)BT)

SecondarySecondary -- decrease in all coagulationdecrease in all coagulation

factors exce tfactors exce t vWFvWF PTPT aPTTaPTT Vitamin K will promote synthesis ofVitamin K will promote synthesis of


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BTBT PltPlt PTPT PTTPTT

Vascular DisVascular Dis -- -- -- --

PLT DisorderPLT Disorder -- -- -- --

*Congenital*Congenital -- -- --

Vit K / LiverVit K / Liver*Acquired*Acquired -- -- --

Combined (DIC)Combined (DIC) --

SummarySummary


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SummarySummary

Symptom Platelet Coagulation

Petechiae Yes No

ites kin &

Mucosa

Deep Tissue

Time Immediate Delayed

cc ymoses/Hematomas es es


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hemostasis & coagulation disorders(ringkas ii) - dicky [compatibility mode]

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