Pemeriksaan Laboratorium

pada Gangguan Pembekuan

dan Trombosis
Dr. Zubir, M. Biomed, SpPK

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 HEMOSTASIS
??? Yang baik

10-03-2013 Juli S Hemostasis 2013

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 VASKULER

TROMBOSIT
HEMOSTASIS
PRIMER

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 VASKULER

TROMBOSIT
HEMOSTASIS
SEKUNDER
KOAGULASI

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 VASKULER

TROMBOSIT
HEMOSTASIS
TERTIER
KOAGULASI

FIBRINOLISIS

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INDIKASI PEMERIKSAAN HEMOSTASIS

1. Gejala-gejala/kecurigaan adanya
- Hemorrhagic diathesis
- Thrombotic diathesis

2. Pemantauan Pengobatan
- Fraksi-fraksi darah
- Antikoagulan : - oral : PPT-INR
- parenteral : APTT

3. Persiapan tindakan pembedahan

4. Membantu menegakkan diagnosis gangguan

fungsi hati

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JENIS PEMERIKSAAN HEMOSTASIS

1. PEMERIKSAAN PENYARING

A. Pemeriksaan “Bed-Side”
- tes resistensi kapiler (Rumpel Leede)
- waktu pendarahan (bleeding time)
- waktu pembekuan (clotting time)
- waktu retraksi bekuan (clot retraction)
- waktu lisis bekuan (clot lysis)

B.Pemeriksaan di laboratorium
- waktu rekalsifikasi plasma (PRT)
- waktu protrombin plasma (PPT)
- waktu tromboplastin partial teraktivasi (APTT)
- waktu protrombin serum (SPT)
- waktu trombin (TT)

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JENIS PEMERIKSAAN HEMOSTASIS

2. PEMERIKSAAN LANJUTAN
- jumlah trombosit
- fungsi trombosit
- titer / kadar fibrinogen
- waktu pembentukan tromboplastin (TGT)
- tes parakoagulasi
- waktu lisis euglobulin
- fibrinogen/fibrin degradation product (FDP)
- D-dimer
- assai faktor koagulasi
- protein-C
- protein S
- AT III
- dll.

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VASKULER TROMBOSIT KOAGULASI PLASMIN

RL RL CT Clot lysis
BT BT PRT Euglob.lysis
CR PPT Parakoag.
Adesi APTT FDP
TAT SPT D-dimer
PF3 TT
 Thr TGT
Titer FI
Assai F

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 Laboratory Evaluation of Bleeding
Overview

CBC and smear Platelet count Thrombocytopenia

RBC and platelet morphology TTP, DIC, etc.

Coagulation Prothrombin time Extrinsic/common

pathways
Partial thromboplastin time Intrinsic/common
pathways
Coagulation factor assays Specific factor deficiencies
50:50 mix Inhibitors (e.g., antibodies)
Fibrinogen assay Decreased fibrinogen
Thrombin time Qualitative/quantitative
fibrinogen defects
FDPs or D-dimer Fibrinolysis (DIC)

Platelet function von Willebrand factor vWD

Bleeding time In vivo test (non-specific)
Platelet function analyzer (PFA) Qualitative platelet
disorders and vWD
Platelet function tests Qualitative platelet
disorders
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FAKTOR KOAGULASI
I. FIBRINOGEN
II. PROTHROMBIN
III. TISSUE THROMBOPLASTIN, THROMBOKINASE
IV. CALCIUM
V. PROACCELERIN, LABILE FACTOR
VII. PROCONVERTIN, STABILE FACTOR
VIII. ANTIHEMOPHILIC A FACTOR (AHF)
ANTIHEMOPHILIC GLOBULIN (AHG)
IX. ANTIHEMOPHILIC B FACTOR (AHB)
PLASMA THROMBOPLASTIN COMPONENT (PTC)
CHRISTMAS FACTOR
X. STUART FACTOR, STUART PROWER FACTOR
XI. PLASMA THROMBOPLASTIN ANTECEDENT (PTA)
XII. HAGEMAN FACTOR, CONTACT FACTOR
XIII.FIBRIN STABILIZING FACTOR, FIBRINASE
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 HMWK
KALIKREIN III
XII
VII
XI

CT IX

PRT SPT VIII PPT

APTT

X
V
II
I TT

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 gangguan hemostasis

normal :
C
plasmin

V t

abnormal :
vtc plasmin

N
Hemorrhagic diathesis
N

N
Thrombotic diathesis
N
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Laboratory Evaluation of the
Coagulation Pathways
Partial thromboplastin time Prothrombin time
(PTT) (PT)
Surface activating agent Thromboplastin
(Ellagic acid, kaolin) Tissue factor
Phospholipid Phospholipid
Calcium Calcium

Intrinsic pathway Extrinsic pathway

Thrombin time Common pathway

Thrombin

Fibrin clot 14
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Activation of Fibrinolytic System
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 / D-DIMER

A scheme of the fibrinolytic system.

t-PA, tissue plasminogen activator, UK, urokinase; pro-UK, pro-urokinase;
SK, streptokinase; PAI-1, plasminogen activator inhibitor1;
a2-PI, a2-plasmin inhibitor.FDP, fibrin degradation products.
The dotted line indicates inhibition

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The balance between the formation & degradation of fibrinolysis
APTT : normal
PPT: normal

Normal
???

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 Evaluation of a Bleeding Patient

Normal PT
Normal aPTT

Abnormal
Urea
Factor XIII
solubility deficiency

Normal

Consider evaluating for:

Mild factor deficiency
Abnormal fibrinolysis
(a2 anti-plasmin def)
Elevated FDPs
Monoclonal gammopathy
Platelet disorder
Vascular disorder
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 Evaluation of a Bleeding Patient

Normal PT
Abnormal aPTT

50:50 mix is
Repeat abnormal
with
Test for inhibitor activity:
50:50 Specific factors: VIII,IX, XI
mix Non-specific
(anti-phospholipid Ab)

50:50 mix is
normal

Test for factor deficiency:

Isolated deficiency in intrinsic pathway
(factors VIII, IX, XI)
Multiple factor deficiencies (rare)
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 Evaluation of a Bleeding Patient

Abnormal PT
Normal aPTT

50:50 mix is
abnormal
Repeat
with Test for inhibitor activity:
50:50 Specific: Factor VII (rare)
mix Non-specific: Anti-phospholipid
(rare)

50:50 mix is
normal

Test for factor deficiency:

Isolated deficiency of factor VII (rare)
Multiple factor deficiencies (common)
(Liver disease, vitamin K deficiency,
warfarin, DIC)
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 Evaluation of a Bleeding Patient

Abnormal PT
Abnormal aPTT

50:50 mix is
Repeat abnormal
with Test for inhibitor activity:
50:50 Specific : Factors V, X,
mix Prothrombin,
fibrinogen (rare)
Non-specific: anti-phospholipid
(common)
50:50 mix is
normal
Test for factor deficiency:
Isolated deficiency in common pathway:
-Factors V,X, Prothrombin, Fibrinogen
Multiple factor deficiencies (common)
-(Liver disease, vitamin K deficiency, warfarin, DIC)
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 APTT : n
PPT: abn

gangguan jalur extr.

Def.f. VII

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THROMBASTHENIA

Glanzmann’s disease

Heriditer recessive autosomal

Defisiensi glikoprotein IIb IIIa
 F 1 tak dapat berikatan dg
- trombosit
- actomyosin membran trombosit

Akibat : - agregasi primer 

- retraksi bekuan 
- B.T.

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 PLATELET ROLE ON HAEMOSTASIS

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THROMBASTHENIA Glanzmann

PERUBAHAN LAB.
Thrombosit :  & morph : normal
B.T.
R.L. N
C.R. 
APTT, PPT, SPT : N
Agregasi primer (dg ADP,Adr,Collagen): ( - )
Agregasi Ristocetin : 
Tes Retensi Trombosit : (homo)
PF 3 : (homo)

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 Von WILLEBRAND’s disease

Heriditer autosomal dominant

Defisiensi F VIII vW (VIII R : Ag)
Perdarahan superficial

TIPE :

1. PARTIAL QUANTITATIVE
2. QUALITATIVE
3. COMPLETE DEFICIENCY

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31
 Von WILLEBRAND’s disease …
LABORATORIUM :

Trombosit :
- Jml. & morfologi normal
- PF 3 normal
- Agregasi : normal, kecuali
dengan RISTOCETIN : 
- Tes RETENSI :
BT :
CR : N
PPT : N
APTT : N / +
F. VIII related activities  +

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 HEMOPHILIA
Heriditer Sex linked (x linked)
xx1 xy

x1 y xy xx xx1
% F VIII IX PERDARAHAN

1 Spontan di persendian,
otot
1-5 Post trauma, kadang-
kadang spontan
5 - 20 Post trauma

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 HEMOPHILIA…

LABORATORIUM :

BT : normal
CT : normal
 in severe cases
PPT : normal
APTT :
F VIII : C :  hemophilia A
F IX : C :  hemophilia B

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Main clinical and laboratory findings in haemophilia
A, factor IX deficiency (haemophilia B, Christmas
disease) and von Willebrand’s disease

Haemoph A Factor IX Von

deficiency Willebrand's
disease

Bleeding time Normal Normal Prolonged

Prothrombin
time Normal Normal Normal
Partial thrombo- Prolonged Prolonged Prolonged or
plastin time normal
Factor VIII : C Low Normal Normal / Low
Factor VIII R : AG Normal Normal Low

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 DIC
DISSEMINATED INTRAVASC. COAG.

 Deposisi fibrin intravasc. yang luas

 Konsumsi  faktor koagulasi
 trombosit
 Sebagai akibat dari :
 bahan-bahan prokoag.
 kerusakan endotel yang luas
 agregasi trombosit

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PATOGENESIS

1. MASUKNYA BAHAN2 PROKOAGULAN

- emboli cairan amnion

- solutio placentae
- adeno Ca penghasil mucin
- leukemia promyelocytic
- malaria falciparum
- reaksi transfusi hemolitik
- bisa ular

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PATOGENESIS

2. KERUSAKAN ENDOTEL YANG LUAS &

PEMAPARAN KOLAGEN

- endotoxaemia
- septicaemia : - gram negatif
- meningococcus

- septic abortion
- infeksi virus ttt
- luka bakar yang luas
- hipotermia

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3. AGREGASI TROMBOSIT INTRA VASC.

- infeksi bakteri, virus

- immune-complex

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 INFECTION THERMAL CHANGES TRAUMA/SURGERY
ANOXEMIA AUTOIMMUNE OBSTETRIC PROBLEMS
ACIDOSIS EXTRACORP. CIRC HEMOLYSIS,
NEOPLASIA

STIMULUS

SURFACE ACTIVATION TISSUE

PLATELET ACTIVATION THROMBO PLASTIN

INTRINSIC PATHWAY EXTRINSIC PATHWAY

INTRAVASCULAR COAGULATION
FIBRINOLYSIS

CONSUMPTION OF COAG. THROMBOSIS OF

FACTORS, PLATELETS MICROCIRCULATION

DECOMP. COMP. OVER COMP. ORGAN DAMAGE

Juli S Hemostasis 2013 40

 Gram- Negative Sepsis
Endotoxin

Vascular Endothelial cell Injury

Tissue Platelets XIIa TPA

Thromboplastin activation activation Release
release
Activated Plasminogen
Hypotension Clotting factors Release
Shock

Dilution Thrombin Plasmin

Inactivation
Hepatic Clearance

Figure Gram-negative sepsis.

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 PERUBAHAN LAB PD BERBAGAI STADIUM DIC

DECOMP. COMP. OVER OMP.

 TROMBO  N N

T.T + + /N
F.I  N
FDP/D-DIMER ++ + +
PPT N N
APTT N 
PARAKOAG + + +

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LABORATORIUM

I. PALING SPESIFIK & SENSITIF

• Parakoagulasi/Solubel fibrin complex
• FDP/ D-dimer
• Fibrinopeptide A
• Konsentrasi Fibrinogen serial

II. KURANG SPESIFIK & KURANG SENSITIF

• PPT
• APTT
• TT
•  Trombo serial

III. PALING KURANG SPESIFIK & SENSITIF

• Euglobulin clot lysis
• Assay faktor koag. (selain F l)
• HDT

IV. AT III

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Renal Disease

Qualitative platelet defect

Thrombocytopenia due to suppressed

bone marrow function

Abnormal factors VIII

Low von Willebrand factor activity

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Liver Disease

(1) Synthesis of coagulation factors :

prothrombin, fibrinogen, factors V, VII,
IX and X.
High molecular weight kininogen
Prekallikrein, ATIII, Protein C.
Vitamin K dependent (II,VII,IX,X)
Protein C

 Reduced in amount
Product is abnormal

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Liver Disease

(2) Clearance of factors by RES

Activated coagulation factors IXa,
Xa, etc.
FDPs and fibrin monomers
Activated plasminogen

(3) Increased protein loss or catabolism

? Turnover of clotting factors
? Loss into ascitic fluid
Protein losing enteropathy (PLE).

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Liver Disease

(4) Thrombocytopenia
Pooling
Alcohol
Folic acid deficiency
DIC

(5) Qualitative platelet defect

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Post-operative bleeding

Unsecured bleeding point

Disseminated intravascular coagulation (DIC)
Shock
Sepsis
Incompatible transfusin
Massive transfusion
Deficient coagulation factors: fibrinogen, V, VIII
Thrombocytopenia
Incompatible transfusion
Citrate toxicity
Liver disease
Renal disease
Drugs
Heparin
Antibiotics

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TERIMA KASIH

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