KULIAH HEMOSTASIS 2011

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

TUJUAN SISTEM :
1. MENGHENTIKAN PERDARAHAN
2. MEMPERTAHANKAN SUPAYA DARAH TETAP
CAIR ( BILA ADA TROMBUS ).
Gambar : Gangguan Hemostasis.
 GANGGUAN HEMOSTASIS:

-PERDARAHAN
PERDARAHAN, . - TROMBOSIS

PROSES HEMOSTASIS ADA 3 TAHAP

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.
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 DARAH
TROMBOSIT
KASKADE FAKTOR KOAGULASI
INHIBITOR KOAGULASI
FIBRINOLISIS
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)

. AKTIVATOR PLASMINOGEN
. ADP ASE
. PROSTAGLANDIN (PG12) / PROSTASIKLIN
. AT III (ANTI THROMNIN III)
. TROMBOMODULIN
. PROTEIN C
PEMBULUH DARAH :
SEL ENNDOTEL RUSAK / TERKELUPAS BILA :
ASIDOSIS
HIPOKSIA
TERPAPAR ENDOTOKSIN
TERPAPAR KOMPLEK ANTIGEN ANTIBODI
SIRKULASI
TROMBOSIT/ PLATELET :
UMUR 7-10 HARI
PRODUKSINYA DIATUR TROMBOPOITIN
TROMBOPOITIN 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 proteincoupled receptors triggers pathways
involving Gq, Gi/z, and G12/13, adenylyl cyclase. DAG indicates diacyl glycerol; IP 3, inositol-1,4,5-
trisphosphate; PI-3-K/; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-3,4,5-
trisphos-phate; PKC, protein kinase C; PLC2/3, phospholipase C-2/3; 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 TROMBOSITOPENI
Drug induced thrombocytopenia
- Obat kemoterapi
- Antibiotik : Sufonamis, penisilin,cephalosporin
- Heparin
- Tiazid, ACE-I
ITP
- 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 koagulasi
Enzim fibrinolitis
Inhibitor
Komplemen
Kinin

* PROTEIN KOAGULASI
PEMBENTUKAN 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 IXa
F 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:
-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 XIIIa
F I (fibrinogen) menjadi Fibrin monomer
Fibrin 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 A
Hemofili B
Kekurangan vit K (II,VII, IX, XI) Ganggan fungsi hati
DIC : 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 0.3 g/kg (IV, SC) 3060 612 hours Tachyp
emergency surgery min hylaxis

300 g (Intranasal) 6090 612 hours

min

q 1224 hour x 45 doses

Conjugated Chronic, recurrent bleeding or before 0.6 mg/kg IV infusion or 50 7 days 2 weeks Use for
elective surgery, esp. from uremia mg po q day x 57 days < 7 days
estrogens
Intractactable mennorhagia, oral bleeding or Aminocaproic acid: 5 g IV over 1 30 min 24 hours after Enters
GI bleeding hour *f/b discontinuation the
Drug 1 g/h infusion for 8 hours extravasc
ular or
GI
bleeding
compart
ments;

or 5 g po x 1 f/b 1 gm po hourly for 1.5 hours Renal

8 hours clearance
;
contraind
icated in
DIC and
with

Tranexamic acid (TA): 1015 mg/kg 3060 hematuri

body weight po or IV q 8 hours min a; TA not
available
in US

Hemophilia-related inhibitors; other uses are 90 (50100) g/kg IV bolus every 2 Immedia 2 hours Monitor
Recombinant off-label hours or as needed tely for
activated factor thrombos
is
VII
TERIMA KASIH