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ligand receptor
adhesion vWF GP Ib/IX/V
collagen GP Ia/IIa
aggregation fibrinogen GP IIb/IIIa
Normal Hemostasis
Platelet
Factor X Factor Xa
Factor X
Factor Va
Prothrombin
Normal Hemostasis
Factor XII
HMWK/PK Extrinsic pathway
Factor XI Factor XIa
Factor X
Intrinsic pathway Factor Xa
Factor X
Factor Va
Factor X Factor Xa
Factor X
Factor Va
Prothrombin
Normal Hemostasis
Factor XII
HMWK/PK Natural anticoagulant
Factor XI Factor XIa
ProteinC Prothrombin
Normal Hemostasis
Fibrinolytic system
High Molecular Weight
Kininogen (HMWK)
Tissue plasminogen act
Prekallekrein (PK)
F.XII UrokinaseFibrin polymer
Plasminogen Plasmin
“New concept !”
1. Initiation
Hemostasis occurs on two surfaces:
TF- bearing cells and platelet
2. 3. Propagation
Amplification
IIa
X prothrombin
VIII/vWF VIIIa
TF VIIa X V
a a
TF-expressing cell thrombinV Va
VIIa TF
I XI XIa
thrombin
X
prothrombin
IXa
platelet
I X
X
XIa IXa VIII X V
a a a
Activated platelet
Hoffman M et al. Blood Coagul Fibrinolysis.
1998; 9(suppl 1): S61-S65.
X prothrombin
VIII/vWF VIIIa
TF VIIa X V
a a
TF-expressing cell thrombinV Va
VIIa TF
I XI XIa
X
prothrombin thrombin
IXa
platelet
I X
X
XIa IXa VIII X V
a a a
Activated platelet
Bernard-Soulier Syndrome
Etiology of Thrombocytopenia
Decreased Production
• Hypoproliferation • Aplastic Anemia, Amegakaryocytic
thrombocytopenia, infection, toxins, drugs
Infiltrative marrow disease, TAR
• Ineffective Thrombopoiesis • Megaloblastic anemia
Increased Destruction
• Immune • Alloimmune, Autoimmune: ITP, SLE
BT N or ↑ ↑↑ N or ↑ ↑↑ N ↑↑↑↑
vWF:Ag ↓ ↓ ↓ ↓ or N ↓ or N ↓↓↓↓
vWFR:Co ↓ ↓↓↓ ↓↓ ↓ ↓ or N ↓↓↓↓
LD-RIPA - - ↑ - - -
FVIII N or ↓ N or ↓ N or ↓ N ↓↓↓ ↓↓↓
Multimer N but ↓ abnormal abnormal N but ↓ N but ↓ absent
vWF Multimer Analysis
XII TF
XIIa
HK/PK
HMWK VIIa VII
XI XIa
XIa Tenase
IX IXa/ VIIa/TF
IX IXa
VIIIa/PL
VIIIa
XX Xa
Xa
Ca++++
Ca
IIII Ca++++
Ca IIa
IIa
Va/PL
Va/PL
Fibrinogen
Fibrinogen Fibrin
Fibrin
XIIIa
Common Pathway X-linkedFibrin
Prothrombin Time (PT)
Uncorrectable
Inhibitor
prolonged
0% 100% coagulation
time
Prolonged PT or aPTT occurs when
coagulation factor < 35-40% <35%
Interpretation of Abnormal
Coagulogram
Isolated prolonged PT
Mixing study
Correctable Uncorrectable
Deficiency Inhibitor
Bleeding No bleeding
Mixing study
Correctable Uncorrectable
Fibrinogen
D-dimer
Fibrin(ogen) degradtion product
Thrombin time
Reptilase time
Euglobulin lysis time
Tes lain untuk Hemostasis
sekunder
• fibrinogen
• D - dimer
• Fibrin ( Ogen ) produk degradtion
• waktu trombin
• waktu Reptilase
• Euglobulin lisis waktu
Fibrinogen
Functional level (200-400 mg/dl)
↓ Fibrinogen (esp. < 100 )
DIC
Fibrinolytic therapy
Primary fibrinolytic state
Congenital afibrinogenemia
Acquired/congenital dysfibrinogenemia
↑ Fibrinogen
Inflammatory states/acute illness
May associated with shortened PT/aPTT
Fibrinogen
• tingkat fungsional ( 200-400 mg / dl )
• ↓ Fibrinogen ( esp . < 100 )
• DIC
• terapi fibrinolitik
• negara fibrinolitik utama
• afibrinogenemia kongenital
• Diakuisisi / bawaan dysfibrinogenemia
• ↑ Fibrinogen
• keadaan inflamasi / penyakit akut
• Mungkin terkait dengan dipersingkat PT / aPTT
D-Dimer
Measured cross-linked fibrin degradation
product by plasmin
More sensitive and specific for fibrinolysis than
Fibrin(ogen) Degradatioin Product (FDP)
↑ D-dimer:
DIC
Acute thromboembolic episodes
Post-trauma or surgery
Malignancy
D-Dimer
• Diukur cross-linked fibrin degradasi produk
oleh plasmin
• Lebih sensitif dan spesifik untuk fibrinolisis
dari fibrin ( Ogen ) Degradatioin Produk (
FDP )
• ↑ D - dimer :
• DIC
• episode tromboemboli akut
• Pasca - trauma atau operasi
• Keganasan
Fibrin(ogen) Degradation Product
↑ levels in
Primary fibrinolytic syndromes
DIC
After lytic therapy
Acute thromboembolic episodes
After injury/surgery
Fibrin ( Ogen ) Degradasi
Produk
• ↑ tingkat di
• sindrom fibrinolitik utama
• DIC
• Setelah terapi litik episode tromboemboli
akut
• Setelah cedera / operasi
Thrombin Time
Thrombin Time (TT)
Assess the ability to convert fibrinogen fibrin by
adding thrombin to plasma
Prolonged TT:
Inhibitor of thrombin: heparin, anti-thrombin antibody
Hypofibrinogenemia or dysfibrinogenemia
Inhibitor of fibrin polymerization: fibrin degradation
product, paraprotein
trombin Waktu
• Trombin Waktu ( TT ) Menilai kemampuan
untuk mengkonversi fibrinogen fibrin
dengan menambahkan trombin untuk
plasma
• TT berkepanjangan : Inhibitor trombin :
heparin , anti - trombin antibodi
Hipofibrinogenemia atau
dysfibrinogenemia Inhibitor polimerisasi
fibrin : produk degradasi fibrin ,
paraprotein
Euglobulin Lysis Time
Euglobulin fraction of plasma is precipitated by
acetic acid and thrombin added.
Lysis of clot is observed.
Normal : > 120 min
Shortened ELT:
DIC
Liver disease
Primary fibrinogenolysis: malignancy, e.g. prostate
carcinoma
Euglobulin Lisis Waktu
• Euglobulin fraksi plasma diendapkan oleh
asam asetat dan trombin menambahkan .
• Lisis bekuan diamati .
• Yang normal : > 120 min
• ELT disingkat :
• DIC
• Penyakit hati
• fibrinogenolysis utama : keganasan , misalnya karsinoma prostat
Management of
Bleeding Patients
Manajemen Perdarahan Pasien
Yingyong Chinthammitr
27 June 2007
Objectives
• Efficient practice of replacement therapy
• Management of common bleeding
problems
tujuan
• Praktek efisien dari terapi penggantian
• Manajemen masalah perdarahan umum
Goal of replacement Rx
• Treatment of bleeding
• Prevention of bleeding before procedure
TF
TF
TF
IX VIIa X
II
IXa
IX
IIa
XI a Xa
VIIIa
VaVa
Activated
Activated
platelet
X II VIII/vWF VIIIa + free vWF
TFPI Xa
Xa VIIa VIIa XI
TF
TF TF
TF Va IIa
Platelet
V XIa
V
Tissue factor--bearing cell
Va
TF
TF
TF
VIIa X
II
IIa
Xa
VaVa
Activated
Activated
platelet
Fibrin Glue
- มี 2 ขวด คือ
1. Thrombin
2. Fibrinogen, F XIII (cryoprecipitate)
Thrombin XIIIa
Fibrinogen ------------->Fibrin ------> Cross-linked
Fibrin
เติม Calcium ใน Thrombin
อาจเติม Tranexamic acid ใน Fibrinogen
ใช้ อุปกรณ์ two syringes with one
air-line
Tranexamic acid
- anti-fibrinolysis
- adjunctive Rx in areas with
high fibrinolysis (Oral cavity,
GI tract, GU tract)
- Contraindication : DIC,
Thrombosis, Renal bleeding
(obstructive uropathy)
- IV : 10 mg/kg/dose q 8 h
- Oral : 25 mg/kg/dose q 8 hr
- Oral wash in dental bleeding
• asam traneksamat
• - Anti – fibrinolisis
• - Ajuvan Rx di daerah dengan fibrinolisis tinggi (
Rongga mulut , saluran pencernaan , GU
saluran )
• - Kontraindikasi : DIC , Thrombosis , ginjal
perdarahan ( uropati obstruktif )
• - IV : 10 mg / kg / dosis q 8 h
• - Oral : 25 mg / kg / dosis q 8 jam
• - Mencuci Oral pendarahan gigi
Bleeding
Berdarah
• Thrombocytopenia
• Coagulopathy
• Combined
• trombositopenia
• koagulopati
• bergabung
Platelet level & Bleeding
• Platelet level
• Platelet function
• Anemia
• Local problem
• Coexisting coagulopathy
Trombositopenia & Pendarahan
• tingkat platelet
• fungsi trombosit
• Anemia
• masalah lokal
• hidup bersama koagulopati
Platelet transfusion
• Symptomatic Rx , not Rx cause
• Dose: 1 unit per 10 kg BW
• Indication
– Bleeding associated with thrombocytopenia
– Prophylaxis, before invasive procedure/surgery
• Contra-indication
– TTP (Thrombotic thrombocytopenic purpura)
/HUS (Hemolytic uremic syndrome), HIT
(Heparin-induced thrombocytopenia)
transfusi trombosit
• Gejala Rx , tidak Rx penyebab
• Dosis : 1 unit per 10 kg BW
• Indikasi Perdarahan yang berhubungan
dengan trombositopenia Profilaksis ,
sebelum prosedur invasif / operasi
• Kontra - indikasi TTP ( trombotik purpura
thrombocytopenic ) / HUS ( uremik
hemolitik sindrom ) , HIT ( Heparin
diinduksi trombositopenia )
Prophylaxis in thrombocytopenia
Condition Threshold
Chronic stable thrombocytopenia <5,000 or
(underproduction e.g. aplastic anemia) No
• No medications added
• Return to blood bank if not use within 30 min
• Most adverse transfusion reactions occur in the
first 15 min.
• Time of transfusion – not exceed 4 hr
• Rate in adult (good cardiac condition)
: 200 - 300 mL/hr
• NOT for: volume expansion, protein (alb, glob)
nutrient
turunan plasma : FFP , Cryo .
• Tidak ada obat ditambahkan
• Kembali ke bank darah jika tidak menggunakan
dalam waktu 30 menit
• Kebanyakan reaksi transfusi yang merugikan
terjadi dalam 15 menit .
• Waktu transfusi - tidak melebihi 4 jam
• Tingkat pada orang dewasa ( kondisi jantung
yang baik ) : 200-300 mL / jam
• TIDAK untuk : ekspansi volume , protein ( alb ,
gumpal ) nutrisi
Cirrhosis
• FFP 10-15 ml/kg
• Vitamin K 10 mg IV
• Pitfalls
– Uncorrected localized bleeding problem e.g. varice,
mucosal lesion
– Overdependence on PT
– Goal: to correct or prevent bleeding, Not to achieve a
normal PT
– Timing of FFP therapy before an invasive procedure
Cirrhosis
• FFP 10-15 ml / kg
• Vitamin K 10 mg IV
• perangkap
• Dikoreksi masalah perdarahan lokal mis varice ,
lesi mukosa
• Overdependence di PT
• Tujuan : untuk memperbaiki atau mencegah
perdarahan , Tidak untuk mencapai normal PT
• Waktu terapi FFP sebelum prosedur invasif
Vitamin K deficiency
• Vit. K 10 mg IV slowly, sc
• FFP
• Prothrombin complex concentrate (PCC)
• Vit . K 10 mg IV perlahan-lahan , sc
• FFP
• Protrombin kompleks konsentrat ( PCC )
HEMARTHROSIS AND HEMOPHILIC ARTHROPATHY
Hemophilia A
• Cryoprecipitate
• Factor VIII concentrates
• FFP
• DDAVP
Hemophilia B
vWD
• DDAVP • FFP
• Cryoprecipitate • Cryo. Removed Plasma
• F IX concentrates
• F VIII concentrates
• FFP
Hemophilia A
• Kriopresipitat
• konsentrat faktor VIII
• FFP
• DDAVP
Hemophilia B
vWD
• DDAVP • FFP
• kriopresipitat • Cryo . dihapus
• konsentrat F VIII Plasma
• FFP • konsentrat F IX
Rx of Bleeding episodes
in Hemophilia
Site Level (%) Rx Length
Joint 30-40 1 dose
Muscle 30-40 1-3 doses
Hematuria 30-40 1 dose
Retroperitoneal 50 5-7 d
GI 50 5-7 d
Neck 100 7-10 d
Intracranial 100 10-14 d
Hemophilia A with hemarthrosis
• 60 kg.
• Raise F VIII to 30 %
• 1 u/kg raise 2%
• F VIII half life = 12 hr
– Raise 30% -> 15 u/kg = 15x60 = 900 u
– Cryo. 9 bags ( cont. ~5 bags q 12 hr)
Hemofilia A dengan
hemarthrosis
• 60 kg .
• Naikkan F VIII sampai 30 %
• 1 u / kg menaikkan 2 %
• F VIII paruh = 12 jam
• Angkat 30 % - > 15 u / kg = 15x60 = 900 u
• Cryo . 9 tas ( cont. ~ 5 tas q 12 jam )
Hemophilia B with hemarthrosis
• 60 kg.
• Raise F IX to 30 %
• 1 u/kg raise 1%
• F IX half life = 24 hr
– Raise 30% -> 30 u/kg = 30x60 = 1800 u
– FFP 1800 ml. ( cont. 900 ml. q 24 hr)
Hemofilia A dengan
hemarthrosis
• 60 kg .
• Naikkan F VIII sampai 30 % 1 u / kg
menaikkan 2 %
• F VIII paruh = 12 jam
• Angkat 30 % - > 15 u / kg = 15x60 = 900 u
• Cryo . 9 tas ( cont. ~ 5 tas q 12 jam )
Warfarin-associated
coagulopathy & bleeding
• Life-threatening Bleeding
– withhold warfarin, FFP/PCCs, vit. K 5-10 mg.
i.v., provide medical support (e.g. PRC)
• Major, non-life-threatening Bleeding
– withhold warfarin, FFP/PCCs, vit. K 1-10 mg.
i.v., provide medical support (e.g. PRC)
Question…