SISTEM HEMOSTASISSISTEM HEMOSTASIS = SUATU SISTEM YANG MEMPERTAHANKAN PBL = SUATU SISTEM YANG MEMPERTAHANKAN PBL DARAH DAN ISINYA DALAM KEADAAN NORMAL DARAH DAN ISINYA DALAM KEADAAN NORMAL

TUJUAN SISTEM :

1. MENGHENTIKAN PERDARAHAN

2. MEMPERTAHANKAN SUPAYA DARAH TETAP CAIR ( BILA ADA TROMBUS ).

KULIAH HEMOSTASIS 2011

Gambar : Gangguan Hemostasis.

• GANGGUAN HEMOSTASIS:

- PERDARAHAN, - TROMBOSIS

1. HEMOSTASIS PRIMER : PBL DARAH, TROMBOSIT, ENDOTEL, AGREGASI DAN PELEPASAN FAKTOR TROMBOSIT. 3-5 MENIT BERHENTI DNG PMBTKN PLATELET PLAG ( SUMBAT TROMBOSIT).2. HEMOSTASIS SEKUNDER - KOAGULASI, 3-10 MENIT TERBENTUK FIBRIN . - MEMPERKUAT SUMBAT TROMBOSIT. 3. HEMOSTASIS TERSIER FIBRINOLISIS, SBG TAHAP AKHIR, WAKTU 24 -72 JAM , FIBRIN LARUT, LUKA SEMBUH.

PROSES HEMOSTASIS ADA 3 TAHAPPROSES HEMOSTASIS ADA 3 TAHAP

PERDARAHAN .

PADA PERDARAHAN ADA 3 KOMPONEN PENTING:1. EKSTRAVASKULER: - BESAR JARINGAN - JENIS JARINGAN - BESAR TEK. JAR.(USIA MUDA > TUA

2. VASKULER: * LAPISAN ENDOTEL DAN OTOT POLOS . LAP. ENDOTEL BERPERAN SINTESIS: - TISSUE FACTORS, PROSTASIKLIN, FAKTOR VON WILLEBRAND, AKTIVATOR PLASMINOGEN, ANTI TROMBIN III DAN TROMBOMODULIN. * JAR. IKAT SUBENDOTEL: - MEMBRANA BASALIS, KOLAGEN, ELASTIN DAN FIBRONEKTIN

3. INTRAVASKULER : TROMBOSIT, PROKOAGULAN, AKTIVATOR DAN INHIBITOR : KOAGULASI DAN FIBRINOLISIS.

Manning, JE. (2004) American College of Surgeons' Advanced Trauma Life Support (ATLS): Hemorrhaging is broken down into 4 classes:

1. Class I Hemorrhage involves up to 15% of blood volume. - change in vital signs, fluid resuscitation not usually necessary.2. Class II Hemorrhage involves 15-30% blood volume. .Tachycardic, narrowing of the difference between the systolic and diastolic. .Peripheral vasoconstriction. . Skin pale and be cool. .The patient start acting differently. . Volume resuscitation with crystalloids (Saline solution or Lactated Ringer's). Blood transfusion is not typically required.3. Class III Hemorrhage involves loss of 30-40% of circulating blood volume. . Blood pressure drops. . Heart rate increases . Peripheral perfusion worsens. . Mental status worsens. . Fluid resus.with crystalloid, blood transfusion usually necessary.4. Class IV Hemorrhage involves loss of >40% blood volume. The limit of the body's compensation is reached and aggressive resuscitation is required to prevent death.

* KOMPONEN HEMOSTASIS

PEMBULUH DARAHTROMBOSITKASKADE FAKTOR KOAGULASIINHIBITOR KOAGULASIFIBRINOLISIS

1. KELAIANAN PEMBULUH DARAH : * KELAINAN STRUKTUR PBL DARAH * AKIBAT INFEKSI/ IMUN.

** DIDAPAT: - PURPURA SIMPLEK RINGAN , USIA SUBUR GANGGUAN FRAGILITAS PBL DARAH KULIT. - PURPURA SENILIS MANULA , OK. ATROFI JAR. KOLAGEN. - AKIBAT INEKSI: DHF, DEMAM TIFOID, ENDOKARDITIS BAKTERIEL, SEPSIS. - AKIBAT OBAT2-AN : PINISILIN, ISONIACIDE, ASPIRIN, TIAZID, OKSITETRASIKLIN.

** DITURUNKAN : - HEMORHAGIS TELEANGIECTASIS. 2. FIBRINOLISIS BERLEBIHAN

3.TROMBOTIC THROMBOCYTOPENIC PURPURA:

-Dimulai kerusakan jaringan dan pelepasan vWF dari endotel sering pada: Kehamilan, ca metastase, HIV, ticlopidin, kemoterapi.

-Anemia Hemolitik, trombositopeni, renal failur, demam, gangguan neurologi.

-Prothrombin time, partial thromboplastin time,

fibrinogen hampir normal.

* Sebab : deff. aktifitas ADAMTS 13 (enzim pemecah vWF) -> agregasi trombosit.

Terapi : plasmaparesis dan tranfusi plasma

4. HEMOLITIK UREMIC SYNDROME:

* PEMBULUH DARAH

LAPISAN ENDOTEL, TERDAPAT : - VASOKONSTRIKTOR :

1. ENDOTELIN

2. WEIBEL-PALADE , BERISI :

- FAKTOR VON WILLEBRAND (VW)

- ANTIGEN .VW.

- P-SELEKTIN

3. INTEGRIN

4. TROMBOPLASTIN

PEMBULUH DARAH RUSAK: Endotel rusak : ENDOTEL KELUARKAN ENDOTELIN UNTUK : - VASOKONTRIKSI - ENDOTELIN BERSAMA TROMBIN MENGIDUKSI ENDOTEL MENGELUARKAN SUBSTANSI ADESI: INTEGRIN DAN SELEKTIN - ENDOTELIN MENARIK LEUKOSIT DAN TROMBOSIT KE DAERAH PEMBULUH DARAH YANG RUSAK.

- VASODILATATOR :

. NITRIC OXIDE (NO). NITRIC OXIDE (NO). AKTIVATOR PLASMINOGEN . AKTIVATOR PLASMINOGEN . ADP – ASE. ADP – ASE. PROSTAGLANDIN (PG12) / PROSTASIKLIN . PROSTAGLANDIN (PG12) / PROSTASIKLIN . AT III (ANTI THROMNIN III). AT III (ANTI THROMNIN III). TROMBOMODULIN. TROMBOMODULIN. PROTEIN C. PROTEIN C

PEMBULUH DARAH :

SEL ENNDOTEL RUSAK / TERKELUPAS BILA :ASIDOSISHIPOKSIATERPAPAR ENDOTOKSINTERPAPAR KOMPLEK ANTIGEN ANTIBODI

SIRKULASI

TROMBOSIT/ PLATELET :UMUR 7-10 HARIPRODUKSINYA DIATUR TROMBOPOITINTROMBOPOITIN DIBUAT HATI & GINJAL

Platelet clumps may appear as large structures in the aspirate or the blood smear. The structure of individual platelets are evident on careful examination.(Peter Maslak).

Signaling mechanisms linking platelet receptors to integrin activation. GPVI ligation activates the ITAM-signaling pathway, whereas stimulation of G protein–coupled receptors triggers pathways involving Gq, Gi/z, and G12/13, adenylyl cyclase. DAG indicates diacyl glycerol; IP3, inositol-1,4,5-

trisphosphate; PI-3-Kβ/; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-3,4,5-trisphos-phate; PKC, protein kinase C; PLCβ2/3,

phospholipase C-β2/3; RhoGEF, Rho-specific guanine nucleotide exchange factor.

3. KELAINAN TROMBOSIT : KUANTITATIF & KUALITATIF.* KUANTITATIF :

TROMBOSITOPENIA - GANGGUAN PRODUKSI (MEGAKARIOSIT TURUN , MEGAKARIOSIT NORMAL) - DISTRUKSI PERIFER BERLEBIHAN ITP. . PRIMER (IDIOPATIK) . SEKUNDER : SLE, LMH, CLL. - DISTRIBUSI ABNORMAL (POOLING). SPLENOMEGALI (SEKUESTRASI) / HIPERSPLENISME .

* KUALITATIF: GANGGUAN FUNGSI TROMBOSIT - DIDAPAT : GAGAL GINJAL, OBAT-OBATAN , HIPERGAMAGLOBULINEMIA. - DITURUNKAN: VON WILLEBRAND DISASE, SINDROMA BERNARD – SOULIER, STORAGE POOL DISEASE, GLANZMANN THROMBOCYTOPENIA (DEFF. GP.IIb-IIIa)

* TROMBOSIT :BILA ENDOTEL RUSAK ENDOTELIN AKAN MENARIK

TROMBOSIT ADESI PADA KOLAGEN PEMBULUH DARAH.

TROMBOSIT AKTIF AKAN MEMBENTUK PSEUDOPODIA SEHINGGA :

- MELEPAS SUBSTASI ADP, SEROTONIN, DLL - MUDAH MELEKAT KE KOLAGEN ENDOTEL - MUDAH MELEKAT KE TROMBOSIT LAIN (AGREGASI TROMBOSIT).TROMBIN MENGHAMBAT SINTESA AMP SIKLIK

PENINGKATAN ION KALSIUM HIPERAGREGASI TROMBOSIT.

PADA SIKRESI ADP YANG BERLEBIH AKAN MENGAKTIFKAN MEMBRAN FOSFOLIPID (FAKTOR TROMBOSIT 3) SEHINGGA TERJADI AKTIFASI SISTIM KOAGULASI.

TROMBOSITOPENI:Produksi yg terganggu Aplasia, infiltrasi sel yg mglami keganasan,

fibrosis.Squestrasi trombosit oleh lien yang membesar. Hipertensi portal(SH), infiltrasi lien oleh sel

lekemia,limfoma dan penyakit limfoproliferasi.Perusakan diluar lien yang meningkat. Imunologi : infeksi bakteri dan virus, obat, ITP.

PENYAKIT DG TROMBOSITOPENIDrug induced thrombocytopenia - Obat kemoterapi - Antibiotik : Sufonamis, penisilin,cephalosporin - Heparin - Tiazid, ACE-IITP - karena antibodi terhadap trombosit.Gangguan trombosit fungsional - Von willebrand disease .

PENYAKIT DG TROMBOSITOPENI:(lanj.)

Defek membran trombosit :Defek release trombosit - Pemakaian Aspilet dan NSAID .Defek pada penyimpanan granula - Lekemia, SLE, penyakit hati kronis .

PROTEIN PLASMA :Protein koagulasiEnzim fibrinolitisInhibitor KomplemenKinin

* PROTEIN KOAGULASI* PROTEIN KOAGULASIPEMBENTUKAN FIBRIN- Pembentukan faktor IX a (sistim kontak)- Pembentukan faktor Xa- Pentukan trombin (faktor IIa)- Pembentukan fibrin

PEMBENTUKAN F IXa :Aktifasi F XII jadi XIIa oleh :Fosfolipid, kolagen subendotel, F XIIa (protein serin) mengaktifkan F XI->FXIa.F XIa bersama Ion Ca mengubah F IX-> F IXaF IXa Mengubah F X -> F Xa

PEMBENTUKAN F Xa:

* PENGAKTIFAN F Xa MELALUI : Jalur intrinsik Jalur ekstrinsik - JALUR INTRINSIK:.Tissue faktor, F VII, ion Ca ->komplek TF/fVIIa.TF/F VIIa mengaktifkan F IX -> F IX.TF/F VIIa & IXa mengatifkan F X -> F Xa.

* JALUR EKSTRINSIK : - Faktor jaringan (TF), F VII, Ion Ca, TFPI - Sitokin (IL-1, TNFa), komplemen, komplek imun

-> merangsang endotel, makrofag, sel tumor mengeluarkan TF.

- TF -> TF/VIIa -> aktifan F X-> F Xa

* PEMBENTUKAN TROMBIN:* PEMBENTUKAN TROMBIN:-F II (protrombin), F Xa, F v, faktor trombosit 3, Ca membentuk komplek menjadi Trombin

Catatan : F II, VII, IX, X dibuat di hepar tergantung Vit K.

PEMBENTUKAN FIBRIN :

TROMBIN MENGUBAH F XIII -> F XIIIaF I (fibrinogen) menjadi Fibrin monomerFibrin monomer diubah menjadi fibrin stabil

oleh F XIIIa

MEKANISME PEMBEKUAN DARAH

Gambar . Hemostasis lengkap )

The human hemostatic system can be defined as consisting of multiple independent yet integrally related cellular and protein components that function to maintain blood fluidity under normal conditions and to promote localized, temporary thrombus formation at sites of vascular injury. The six major components of this hemostatic system are vascular endothelium, platelets, plasma coagulation proteins or "factors," natural anticoagulant proteins, fibrinolytic proteins, and antifibrinolytic proteins. In the presence of an intact endothelium, there is no "clot" formation taking place inside the blood vessels, even though a low, basal physiologic level of coagulation factor activation is occurring continuously. This highly regulated hemostatic system maintains a delicate balance between a prohemorrhagic state and a prothrombotic state. This balance is maintained by the concomitant actions of platelets, coagulation factors, and fibrinolytic inhibitors (on one side of the "hemostatic scale"), and of natural anticoagulants and fibrinolytic proteins (on the other side of the scale). (7)

PENYAKIT PERDARAHAN:

Hemofili AHemofili BKekurangan vit K (II,VII, IX, XI) Ganggan fungsi

hatiDIC : – Ada tissue factor (endotoxin, jar.rusak dll). - TF aktivasi koagulasi diikuti aktifasi fibrinolitik bergantian. -Trombositopeni, APTT, PPT, TT memanjang, fibrinogen turun, FDP > . ANTI KOAGULAN SIRKULASI (IgG): AIDS, SLE.PENYAKIT HATI : Sintesis: fibrinogen, protrombin, V, VII, IX, X, XI,

Gangguan absorbsi dan metabolisme vit K, Splenomegali -> squestrasi (Hb.Al,At )

Figure 3. Role of TF in thrombus formation after rupture of an atherosclerotic plaque. TF expressed by foam cells (orange) and in the necrotic core (yellow) of the plaque would be exposed to clotting factors in the blood and initiate clotting after plaque rupture. In addition, blood-borne TF may contribute to thrombus propagation. TF is constitutively expressed by adventitial cells (blue). EC, endothelial cells; SMC, smooth muscle cells.

 

Immediately after endothelial cell injury, endothelial cells and platelets are activated promoting the expression of cell adhesion molecules. This vascular response promotes leukocyte rolling and tethering onto the endothelium that initiates an inflammatory event which can lead to thrombosis.

Treatment. - Desmospressin (DDAVP) . vasopressin analog whose pressor effects are substantially less than its antidiuretic effects . Is useful by causing the release of VWF from tissue stores, predominantly endothelial cells. . DDAVP has been reported to shorten the bleeding time in 50%– 75% of patients with uremia.

- Recombinant factor VIIa (rFVIIa) . Used effectively in this setting. In fact, rFVIIa appears to have a wide spectrum of clinical uses in a variety of different hemorrhagic disorders due to both platelet dysfunction and coagulopathy.

Hemostatic drugs.

Indication Dose Onset Duration Caveat

Desmopressin Acute bleeding before biopsy or emergency surgery

0.3 µg/kg (IV, SC) 30–60 min

6–12 hours Tachyphylaxis

300 µg (Intranasal) 60–90 min

6–12 hours

q 12–24 hour x 4–5 doses

Conjugated estrogens

Chronic, recurrent bleeding or before elective surgery, esp. from uremia

0.6 mg/kg IV infusion or 50 mg po q day x 5–7 days

7 days 2 weeks Use for < 7 days

DrugIntractactable mennorhagia, oral bleeding or GI bleeding

Aminocaproic acid: 5 g IV over 1 hour *f/b

1 g/h infusion for 8 hours

30 min 2–4 hours after discontinuation

Enters the extravascular or GI bleeding compartments;

or 5 g po x 1 f/b 1 gm po hourly for 8 hours

1.5 hours Renal clearance; contraindicated in DIC and with

Tranexamic acid (TA): 10–15 mg/kg body weight po or IV q 8 hours

30–60 min

hematuria; TA not available in US

Recombinant activated factor VII

Hemophilia-related inhibitors; other uses are off-label

90 (50–100) µg/kg IV bolus every 2 hours or as needed

Immediately

2 hours Monitor for thrombosis

* f/b, "followed by"

TERIMA KASIH