dic
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dic.pptTRANSCRIPT
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