Koagulasi intravaskular diseminata (DIC) adalah suatu sindroma yg timbul sbg suatu komplikasi penyakit/kelainan serius yg mengancam jiwa

DIC akut : kel hemoragik yg ditandai dgn ekimosis multipel, perdarahan mukosa & berkurangnya jumlah trombosit serta faktor koagulasi dlm darah

DIC kronik : jarang diketahui sampai akhirnya berlanjut pada keadaan tromboemboli yg ditandai dgn aktivasi faktor sistem koagulasi

Coagulation cascade Vascular Endothelium Anticlotting Mechanisms Fibrinolytic System Platelets Blood Flow Dynamics

Subendothelial matrix

Platelets

Hemostatic plug

Fibrin

Endothelial cell

RBCWBC

WBC

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Vascular endothelium expresses: ◦ Thrombomodulin◦ TissuePlasminogen

Activator◦ Tissue

thromboplastin/ Tissue factor

Subendothelial matrix

Platelets

Hemostatic plug

Fibrin

Endothelial cell

RBCWBC

WBC

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Intrinsic Pathway Extrinsic Pathway Common Pathway Contact Pathway Tissue Factor Pathway

◦Primary factor in DIC

Contact Tissue Factor + VII

XIIIa

XIII

Thrombin

Fibrin(strong)

Fibrinogen Fibrin(weak)

IX

XI

XIa

IXa

XaVa

XIIa

Prothrombin

TF-VIIa

(Prothrombinase)

PL

PL

(Tenase)

VIIIa

PL

X

Intrinsic Pathway

HKa

Extrinsic Pathway

Common Pathway

TF Pathway

Protein C, Protein S, Antithrombin III

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Antithrombin III (ATIII): ◦ The major inhibitor of

the coagulation cascade. Inhibits Thrombin Inhibits activated

Factors IX, X, XI, and XII.

◦ Activity is enhanced by heparin.

Tissue factor pathway inhibitor TFPI

Contact Tissue Factor + VII

XIIIa

XIII

Thrombin

Fibrin(strong)

Fibrinogen Fibrin(weak)

IX

XI

XIa

IXa

XaVa

XIIa

Prothrombin

TF-VIIa

(Prothrombinase)

PL

PL

(Tenase)

VIIIa

PL

X

Intrinsic Pathway

HKa

Extrinsic Pathway

Common Pathway

TF Pathway

Protein C, Protein S, Antithrombin III

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Protein C◦ Activated by

Thrombin/Thrombomodulin

◦ Anticoagulant and fibrinolytic activity.

◦ Vitamin K and Protein S are cofactors

Protein S

Contact Tissue Factor + VII

XIIIa

XIII

Thrombin

Fibrin(strong)

Fibrinogen Fibrin(weak)

IX

XI

XIa

IXa

XaVa

XIIa

Prothrombin

TF-VIIa

(Prothrombinase)

PL

PL

(Tenase)

VIIIa

PL

X

Intrinsic Pathway

HKa

Extrinsic Pathway

Common Pathway

TF Pathway

Protein C, Protein S, Antithrombin III

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Plasmin◦ Produced from

Plasminogen by Tissue Plasminogen activator (TPA)

◦ Degrades Fibrin and Fibrinogen (Fibrin degradation products, FDP)

◦ Degrades Factors V, VIII, IX, XI, and XII.

◦ Activity is inhibited by Antiplasmin.

FibrinolysisPlasminogen

Plasmin

Fibrin, fibrinogen

ActivationExtrinsic: t-PA, urokinase

Intrinsic: factor XIIa, HMWK, kallikrein

Exogenous: streptokinase

Fibrin, fibrinogendegradation products

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Antiplasmin◦ Inactivates plasmin

rapidly. Acts slowly on plasmin

sequestered in the fibrin clot.

◦ Inactivates factors XI and XII slowly.

Plasminogen -Activator Inhibitor-1(PAI-1)◦ Inhibits the function of TPA◦ Also has some inhibitory

activity against urokinase, plasmin, thrombin, activated Protein C, factors and XII, and kallikrein

FibrinolysisPlasminogen

Plasmin

Fibrin, fibrinogen

ActivationExtrinsic: t-PA, urokinase

Intrinsic: factor XIIa, HMWK, kallikrein

Exogenous: streptokinase

Fibrin, fibrinogendegradation products

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ATIII

Clotting Factors

Tissue factor*

PAI-1

Antiplasmin TFPI

Prot. C

Prot. S

ProcoagulantProcoagulant AnticoagulantAnticoagulant

Fibrinolytic System

An acquired syndrome characterized by systemic intravascular coagulation

Coagulation is always the initial event

SYSTEMIC ACTIVATION OF COAGULATION

Intravascular deposition of

fibrin

Depletion of platelets and coagulation

factors

Thrombosis of small and midsize

vesselsBleeding

Organ failure DEATHDEATH

DIC timbul ketika monosit & sel endotelial diaktivasi atau trauma oleh substansi toksik dari penyebab penyakit dasar. Respon monosit & sel endotel terhadap trauma ialah dgn mengeluarkan faktor jaringan pd permukaan sel dgn mengaktivasi kaskade koagulasi.

Pd DIC akut pengeluaran trombin yg cepat & banyak meyebabkan kurangnya faktor pembekuan & trombosit serta aktivasi sistem fibrinolisis.

Perdarahan jaringan subkutaneus, kulit & mukosa membran timbul disertai dgn oklusi pembuluh darah yg menyebabkan terbentuknya fibrin dlm mikrosirkulasi.

Pd DIC kronik proses terjadinya sama dgn akut, tapi lebih lambat & ringan. Biasanya membutuhkan waktu yg lama u/ merespons dengan berkurangnya perdarahan tapi dpt meyebabkan hiperkoagulasi state.

Epidemiologi :Insiden → AS 1994 : 18.000 30 - 50 dgn sepsis

Mortalitas/morbiditas → tergantung penyakit dasar & beratnya koagulopati : - purpura idiopatik fulminan angka mortalitas : 18%- sepsis akibat aborsi dgn kuman klostridium & syok dgn DIC berat : 50% - trauma berat dgn infeksi : dua kali lipat

Laki-laki : wanita

Usia : semua umur

Kelainan yg menimbulkan DIC

Infeksi : Akut : bakteri dgn toksinnya, jamur, virus,riketsia Kronik : beberapa penyakit kronik seprti TBC, abses & osteomielitis

Penyakit inflamasi non-infeksi : IBS : crohn’s disease, kolitis ulseratif

Komplikasi obgyn : Akut : abrupsio plasenta, aborsi (aborsi terapeutik), emboli cairan amnion, syok hemoragik Kronik : dead fetus syndrome

Keganasan : Akut : akut promielositik leukemia, akut mielomonositik atau monositik leukemia, Ca prostatika diseminata Kronik : Ca paru, payudara, GIT

Penyakit pembuluh darah : Akut : infark atau perdarahan otak Kronik : aneurisma aorta, giant hemangioma

Bisa : Akut : ular, laba-laba (jarang)

Trauma : Akut : destruksi jaringan masif, kerusakan otak

Lain-lain : Akut : Heparin-induced thrombocytopenia with thrombosis (HITT), purpura fulminan pd bayi (homozygous protein C defisiensi)

Pemeriksaan fisik

• sirkulasi : perdarahan spontan, perdarahan sub akut & trombosis lokal & difus

• CNS : penurunan kesadaran/stupor, defisit neurologi lokal

• CV : hipotensi, takikardia, kolaps sirkulasi

• Sistem respirasi : friction rub pleura, tanda-tanda

ARDS

Overt DIC Scoring SystemOvert DIC Scoring System

Taylor, FB, et al. Thromb Haemost 2001;86:1327

D-dimer elevation is the classic lab – these reflect degradation of cross linked fibrin. ELISA is the method of choice.

PT (INR) elevation reflects reduction in factors VII, X, V, and prothrombin – members of the extrinsic and common pathways, and the most commonly affected factors in DIC.

PTT elevation reflects deficiencies in factors XII, XI, IX, and VIII (intrinsic) – less sensitive than PT

Fibrinogen reduction – due to consumption. Relative reduction is a useful finding – in a patient with malignancy who should have a level of 800, 200 is low.

Thrombocytopenia◦ plat count <100,000 or rapidly declining

Prolonged clotting times (PT, APTT) Presence of Fibrin degradation products or

positive D-dimer Low levels of coagulation inhibitors

◦ AT III, protein C Low levels of coagulation factors

◦ Factors V,VIII,X,XIII Fibrinogen levels not useful diagnostically

Radiologi : - peny dasar u/ menetukan trombosis perdarahan - torak foto : densitas pd perihiler → injuri pd paru

Diagnosis Banding :- Hemolityc-uremic syndrome- Immune thrombocytopenia purpura (ITP- Thrombocytopenia thrombotic purpura- lain-lain : kelainan hemostatis lainnya

Stop the triggering process .◦ The only proven treatment!

Supportive therapy No specific treatments

◦ Plasma and platelet substitution therapy◦ Anticoagulants◦ Physiologic coagulation inhibitors

Penatalaksaan

Terapi peny dasar :- terapi segera dilakukan- atasi syok, sepsis, ggn kehamilan

Terapi DIC akut : - Tanpa perdarahan atau adanya iskemia (-)- Dgn perdarahan Transfusi darah jika diperlukan FFP Kriopresipitat Tranfusi trombosit

Dgn iskemia Antikoagulan stlh resiko perdarahan dikoreksi

Kronik- Tanpa tromboemboli Tdk ada terapi spesifik, terapi profilaksis : low- dose heparin, LMWH pada penderita dengan resiko tinggi trombosis

- Dengan tromboemboli Heparin atau LMWH, trial dgn warfarin

Komplikasi :

- GGA- Trombosis yg mengancam jiwa & perdarahan- Tamponade jantung- Hemotorak- Hematoma intraserebral- Gangren & amputasi jari-jari- Kematian

Prognosis :Tergantung pd penyakit yg mendasari & beratnya DIC