Tes Fungsi pembekuan darah dan

penyakit koagulasi

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1. Hemostasis

Trauma
pembuluh
darah
Faktor
jaringan

Saraf

Konstriksi
pembuluh darah
Aliran darah
menurun

Aktivasi
Platelet
Sumbatan hemostatik
primer
(Primary hemostatic plug)
Platelet-Fusion

Aktivasi
Koagulasi

Trombin,
Fibrin

Sumbatan hemostatik stabil

( Stable
Hemostatic
Plug)
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Medicine School
of Shandong University

2. Proses Koagulasi Process

12 faktor pembekuan yang terlibat pada

proses pembekuan darah.
Sebagian besar faktor pembekuan disintesis
di hepar.
Vitamin K mempengaruhi kerja faktor : II,
VII, IX, X .

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Faktor I

Fibrinogen

Faktor VIII

Antihemophilic
globulin

Faktor II

Prothrombin

Faktor IX

Partial
thromboplastin
component

Faktor III

Thromboplastin Faktor X

Stuart-Prower
factor

Faktor IV

Calcium

Faktor XI

Plasma
thromboplastin
antecedent

Faktor V

Labile or
proaccelerin

Faktor XII

Hageman factor

Faktor VII

Stable factor
atau
proconvertin

Faktor XIII

Fibrin-stabilizing
factor

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 Proses koagulasi terbagi atas 2 jalur proses

Proses koagulasi berlangsung 4 tahap.
Tahap I : pelepasan faktor platelet/trombosit
Tahap II: pembentukan thromboplastin
Tahap III: konversi prothrombin menjadi
thrombin

Tahap IV: pembentukan fibrin dari

fbrinogen
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Intrinsik 12,11,9,8
(aPTT-)

Ekstrinsik-7
(PT)

Jalur bersama (TT)

FX FXa

Prothrombin Thrombin

Fibrinogen Fibrin
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Coagulation Pathways
Intrinsic Pathway

Extrinsic Pathway

IX

Tissue Factor + VII

X

Contact

XI

TF Pathway

TF-VII a
PL

XIIa HKa

Common Pathway

Prothrombin

XIa
IXa

PL

(Tenase)

VIIIa

Xa

(Prothrombinase)
Protein C, Protein
S, Antithrombin III

PL
XIII

Va
Thrombin

Fibrinogen

Fibrin
(weak)

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XIIIa

Fibrin

(strong)
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Klasifikasi gangguan pembekuan

darah :

Kelainan /penyakit pembuluh

darah

Kelainan /penyakit Platelet

Kelainan /penyakit koagulasi

Kelainan /penyakit lain

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1.Capillary Fragility (Tourniquet Test;

Rumpel-Leede Capillary-Fragility Test)
Tujuan tes :
Menilai kekuatan dinding pembuluh darah.
Mengevaluasi tendensi perdarahan.
Identifikasi adanya trombositopenia*.

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Description of test

Operator applies a blood-pressure cuff to the upper

arm and inflates it to a point midway between
diastolic and systolic pressure. For example, if your
blood pressure is 120/80, the cuff is inflated to 100
mmHg.
Pressure is maintained for 5 minutes then released.
The number of petechiae are counted, and their size
is recorded. Petechiae are small red spots of blood
under the skin caused by leakage of blood cells
through an abnormally fragile capillary.
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TEST RESULTS
Test values:
The size and number of petechiae are observed.
Normal values:
A few petechiae may normally be present before
the test. Less than 10 on the forearm after the test is
considered normal.
Scale for reporting number of petechiae: 0 to 10 =
1+ 10 to 20 = 2+ 20 to 50 = 3+ 50 or more = 4+

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What HIGH or INCREASED may indicate:

Conditions unrelated to bleeding defects, such as scarlet fever*,

measles, influenza*, chronic kidney disease, hypertension* and
diabetes* can increase capillary fragility.
DIC*.
Dysproteinemia*.
Fibrinogen*.
Polycythemia vera*.
Prothrombin*.
Purpura senilis*.
Scurvy*.
Severe factor-VII deficiency*.
Thrombasthenia*.
Thrombocytopenia*.
Vitamin-K deficiency.
Von Willebrand's disease*.

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2.Bleeding Time
This is a test that measures the speed at
which small blood vessels close off to stop
bleeding (the condition of the blood vessels)
and platelet function

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13

Perform the Test

A blood pressure cuff is
placed on the upper arm
and inflated. Two incisions
are made on the lower arm.
These are about 10 mm
(less than 1/2 inch) long
and 1 mm deep (just deep
enough to cause minimal
bleeding).
The blood pressure cuff is
immediately deflated.
Blotting paper is touched to
the cuts every 30 seconds
until the bleeding stops.
The length of time it takes
for the cuts to stop bleeding
is recorded.

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14

Normal Values

The bleeding stops within 1 to 9 minutes

(what is considered normal varies from lab
to lab, depending on how the test is
measured).

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abnormal results mean

A vascular (blood vessel) defect

A platelet function defect
Thrombocytopenia (low platelets)
Primary thrombocythemia
Von Willebrand's disease
Drugs that may increase bleeding times
include dextran, indomethacin, and
salicylates (including aspirin).

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3. Prothrombin Time
PT measure the factors in Extrinsic way
such as VII, X, II.
II, VII , IX, X, are manufactured by liver
and required Vitamin K.
PT alse used to measure the effectiveness of
the coumarin type of anticoagulation drugs,
such as warfarin.

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 Measurement

Reference values : 12~15 seconds, over the

control 3 seconds make sense.
Percentages : 60~140% . ( It means the
prothrombin activity)
PT ratio : the ratio of the PT to control.
International Normalized Ratio (INR)
INR : PT ratio convert to INR according ISI
(International Sensitivity Index) .
Recommendations value: INR 2.0~3.0

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Clincal Significance of PT
Increased PT :
liver diease or damage such as cirrhosis of
liver.
Unable to absorb Vitamin K from
gastrointestinal tract.
True deficiency of Vitamin K.
DIC
Decreased PT
No diagnostical significance

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4. Partial Thromboplastin Time

PTT demonstrate the lack of factors, except

factor VII.
PTT test the function of Instrinsic clotting
system.
PTT is useful to screen for general plasma
deficiencies.

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 The purpose of PTT is to monitor heparin

therapy.
If the PTT is abnormal, further test are
needed to pinpoint exactly which factors is
defective or deficient
Reference value: 22~34 seconds

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Clinical Significance in PTT

Increase PTT
Lack of factor VIII Hemophilia A
Lack of factor IX Hemophilia B
Taking heparin: PTT is kept about 1.5~2.5
times the control value.
DIC
Decrease PTT
No diagnostical significance
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3. Activated Clotting Time

The ACT is used to monitor intrinic system
.
The reference value is different from PTT.
There is the same clinical significance
between ACT and PTT.
ACT can measured at the bedside.

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5. Platelet Count

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 Platelets are manufactured in bone marrow

by megakarocyte.
Platelets are only fragments of ctyoplasma.
They are removed by spleen when they are
old or damage.
Reference value
150,000~350,000/ 3

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Clinical Significance of Platelet

Count
Increase Platelet Count (Trombocytosis)
Malignant tumor
Polycythemia vera
Splenecytomy

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Low Platelet Count (Thrombocytopenia)

ITP ( idiopathic thrombocytopenic purpura)
Acute mass loss of blood
AIDS
Hemolytic Disorders
Hypersplenism ( overactive spleen )
Administration of Heparin

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6.Disseminated Intravascular
Coagulation (DIC)
DIC is characterized by
the systemic activation of the coagulation
system followed by activation of fibrinolytic
system
high thrombin and plasmin generation

DIC is not a disease itself, but is a

manifestation of a serious underlying
disorder.

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Causes of DIC

Infection

- bacterial sepsis, viral

infections

Neoplasm
- AML, adenocarcinoma
Obstetrical disorders - retained dead fetus,
abruption, etc

Trauma/surgery
Others

- brain injury, crush, burns, etc.

- acute hemolytic transfusion

reaction, etc.

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Hemostatic Balance

PAI-1
Antiplasmin
Tissue factor*
Clotting Factors

Procoagulant

Prot. S

Prot. C
TFPI
Fibrinolytic System

ATIII

Anticoagulant

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DIC
An acquired syndrome
characterized by
systemic
intravascular
coagulation
Coagulation is always
the initial event

SYSTEMIC
ACTIVATION OF
COAGULATION

Intravascular
deposition of
fibrin

Thrombosis of
small and
midsize vessels

Organ failure

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Depletion of
platelets and
coagulation
factors

Bleeding

DEATH
31

Pathophysiology of DIC
Activation of Blood Coagulation
Tissue factor/factor VIIa mediated thrombin
generation via the extrinsic pathway
complex activates factor IX and X

TF
endothelial cells
monocytes
Extravascular:
lung
kidney
epithelial cells

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32

Pathophysiology of DIC
PATHOPHYSIOLOGIC
EVENTS

LABORATORY
MANIFESTATIONS

CLINICAL
MANIFESTATIONS

underlying disorder

tissue factor release

depletion of clotting factors

prolonged PT, PTT

thromboctyopenia (consumption)
activation of intrinsic
pathway of coagulation
(systemic thrombin
generation)

hemorrhage
depletion of physiologic anticoagulants

decreased fibrinogen
generalized intravascular
fibrin deposition

microangiopathic hemolytic anemia

thrombosis/infarction

activation of
fibrinolytic system
(systemic plasmin
generation)

increased FDP and D-dimer

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Laboratory Tests Used in DIC

D-dimer*
Antithrombin III*
F. 1+2*
Fibrinopeptide A*
Platelet factor 4*
Fibrin Degradation
Prod
Platelet count
Protamine test

Thrombin time
Fibrinogen
Prothrombin time
Activated PTT
Protamine test
Reptilase time
Coagulation factor
levels

*Most reliable test

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Occult Blood Test

Occult Blood (OB) means Hidden blood
that cant easily been found the presence of
blood.
Sometimes it is called Guaiac Test
Gastroccult is specifically designed to test
for occult blood.
This test always is used to test the feces
(stool).
Healthy person is negative
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Clinical Significance of OB
Positive:
UGB : upper gastrointestinal bleeding
Such as:
Bleeding esophageal varices
Colon polyp or colon cancer
Esophagitis
Gastritis
GI (gastrointestinal) trauma
GI tumor
Hemorrhoids
Fissures
Inflammatory bowel disease
Peptic ulcer
Complications of recent GI surgery
Angiodysplasia of the colon

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False-Positive
Red meat
High-fiber diet

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Clinical Features of Bleeding Disorders

disorders
Site of bleeding

Platelet
factor disorders

Coagulation

Skin
Mucous membranes

Deep in soft tissues

(joints, muscles)

(epistaxis, gum,
vaginal, GI tract)

Petechiae

Yes

No

Ecchymoses (bruises)

Small, superficial

Large, deep

Hemarthrosis / muscle bleeding

Extremely rare

Common

Bleeding after cuts & scratches

Yes

No

Bleeding after surgery or trauma

Immediate,

Delayed (1-2

days),
usually mild

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often severe

38

Petechiae
(typical of platelet disorders)

Do not blanch with pressure

(cf. angiomas)
Not palpable
(cf. vasculitis)
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Ecchymoses
(typical of
coagulation factor
disorders)

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Coagulation factor disorders

Inherited bleeding
disorders
Hemophilia A and B
vonWillebrands
disease
Other factor
deficiencies

Acquired bleeding
disorders
Liver disease
Vitamin K
deficiency/warfarin
overdose
DIC

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Hemophilia A and B
Hemophilia A

Hemophilia B

Coagulation factor deficiency

Factor VIII

Factor IX

Inheritance

X-linked
recessive

X-linked
recessive

Incidence

1/10,000 males

1/50,000 males

Severity

Complications

Related to factor level

<1% - Severe - spontaneous bleeding

1-5% - Moderate - bleeding with mild injury
5-25% - Mild - bleeding with surgery or trauma

Soft tissue bleeding

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Hemophilia
Clinical manifestations (hemophilia A & B
are indistinguishable)
Hemarthrosis (most common)
Fixed joints

Soft tissue hematomas (e.g., muscle)

Muscle atrophy
Shortened tendons

Other sites of bleeding

Urinary tract
CNS, neck (may be life-threatening)

Prolonged bleeding after surgery or dental

extractions
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Hemarthrosis (acute)

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Treatment of hemophilia A

Intermediate purity plasma products

Virucidally treated
May contain von Willebrand factor

High purity (monoclonal) plasma

products
Virucidally treated
No functional von Willebrand factor

Recombinant factor VIII

Virus free/No apparent risk

No functional von Willebrand factor

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Dosing guidelines for hemophilia A

Mild bleeding

Target: 30% dosing q8-12h; 1-2 days (15U/kg)

Hemarthrosis, oropharyngeal or dental, epistaxis,
hematuria

Major bleeding

Target: 80-100% q8-12h; 7-14 days (50U/kg)

CNS trauma, hemorrhage, lumbar puncture

Surgery
Retroperitoneal hemorrhage
GI bleeding

Adjunctive therapy

-aminocaproic acid (Amicar) or DDAVP (for mild

disease only)
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Copyright 2004, Medicine School of Shandong University

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Treatment of hemophilia B
Agent

High purity factor IX

Recombinant human factor IX

Dose

Initial dose: 100U/kg

Subsequent: 50U/kg every 24 hours

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