HAEMORRHAGIC

HAEMORRHAGIC
DISEASE
DISEASE

Suspected
Suspected of
of hemorrhagic
hemorrhagic disease
disease ::
1.
1. Spontaneous
Spontaneous bleeding
bleeding
2.
2. Prolonged
Prolonged bleeding/massive
bleeding/massive
3.
3. More
More than
than one
one site
site bleeding
bleeding

PATHOGENESIS
PATHOGENESIS
Hemostasis process :
- maintaining blood in a state of dilution
- maintaining blood in vascular
- to stop bleeding vascular damage

HEMOSTASIS

G
IN
TT

VA
SC
U

O
CL

LA
R

3 components of hemostasis:

THROMBOCYTE

Disturbance one of components homeostas

bleeding

TRAUMA/INJURY
VASOCONSTRICTION

+
BLOOD

CLOTTING

ADHESION OF THROMBCYTE

THROMBINE

ADP/SEROTONINE

FIBRINE

AGREGATION OF THROMBOCYTE

STABILE HAEMOSTATIC BLOCKAGE

DETECTION
DETECTION OF
OF HAEMORRAGIC
HAEMORRAGIC DISEASE
DISEASE
Step
Step II

-- good
good history
history taking
taking
-- physical
physical examination
examination

-- Trauma:
Trauma: -- History
History of
of trauma
trauma chronologically
chronologically
-- Mild
Mild
trauma
trauma
bleeding
bleeding
-- Severe
Severe
spontaneous
spontaneous bleeding
bleeding
-- Quantity
Quantity and
and duration
duration of
of bleeding
bleeding
-- Recurrent
Recurrent bleeding
bleeding

-- trauma
trauma
always
always bleeding
bleeding

Congenital
Congenital hemorrhagic
hemorrhagic disease
disease
-- Deep
Deep tissue
tissue bleeding
bleeding
(( large
large hematom
hematom or
or hemarthrosis)
hemarthrosis)

Congenital
Congenital hemorrhagic
hemorrhagic disease
disease
-- Petechie
Petechie
not
not congenital
congenital hemorrhagic
hemorrhagic dise
dise
-- Congenital
Congenital hemorrhagic
hemorrhagic disease
disease usually
usually
coagulation
coagulation disorder
disorder

Laboratory
Laboratory examination
examination ::
-- Screening
Screening examination
examination
-- Specific
Specific examination
examination

Screening
Screening examination
examination ::

1.
1. Platelet
Platelet count
count
2.
2. Bleeding
Bleeding time
time (( thrombocyte
thrombocyte function)
function)
3.
3. Prothombine
Prothombine time
time (PT)
(PT)
4.
4. Activated
Activated partial
partial tromboplastin
tromboplastin time
time (APT
(APT
5.
5. Clotting
Clotting observation
observation // clotting
clotting retraction
retraction

Specific
Specific examination
examination ::

1.
1. Coagulation
Coagulation factor
factor (factor
(factor assay)
assay)
2.
2. Thrombocyte
Thrombocyte function
function ::
aggregation,
aggregation, release
release reaction
reaction etc.
etc.

VASCULAR
VASCULAR DISORDER
DISORDER
Mostly : secondary vascular pupura :
-

Immunology: Schenlein-Henoch syndr

Infection: Virus, Rickets, Bacteria
Drugs
Deficiency of Vit. C
Uremia

Congenital:

- Hereditary hemorrhagic telangiectasia

(Osler-Weber-Rendu)
- Cutis hyperelastica (Ehler-danlos)

Clinical :

- usually petechiae skin & mucosa

spontaneous
- Tourniquet test

positive

- symptoms & signs of primary disease

Laboratory:
- platelet count normal
- bleeding time normal
- PT & APTT normal

SCHENLEIN-HENOCH
SCHENLEIN-HENOCH SYNDROME
SYNDROME
- Allergic Purpura
- Anaphylactic Purpura
Incidence :
- 3 -7 years of age
- Male : female = 3 : 2

Etiology:
Immunologic Reaction:
-

Infection: beta hemolytic Streptococcal, V

Food : milk, egg, tomato, fish etc.
Drug : erythromycin, sulfa, penicillin, ect.
Insect bite

-Hemolytic Streptococcal Infection importa

- 75% cases History of respiratory tract

infection 1-3 weeks before

- 50% cases positive throat swab culture

- 30% cases titer ASO

PATHOGENESIS
PATHOGENESIS
Immune complex :
- vasculitis increase permeability
- perivasculer inflammation

CLINICAL
CLINICAL MANIFESTATION
MANIFESTATION
1. Skin involvement:
- erytema, maculopapuler
- petechie & echymosis
Distribution of lesion: symmetric:
- extensor lower extremity
- gluteus, hip
- extensor arm elbow

2.Articular involvement:

- 75% case
- polyarthralgia/polyarthritis non-mi
- periarthriculer swelling
- especially knee & ankle
- full recovery

3. Stomach involvement:
Colic (50%) with : vomiting, diarrhea,

melena
- mild to severe umbilicus
- cause : edema & bleeding intestinal
mucosa

4. Kidney involvement:
- 25-50% case 2-3 weeks

- proteinuria & hematuria (micro/macrosco

- often in male
- 5 -10% chronic

MANAGEMENT
MANAGEMENT

self limiting symptomatic treatment

- Corticosteroid:
- intestinal mucosa edema colic & invaginat
- arthricular involvement
- Bed rest avoid intracranial bleeding

PROGNOSTIC
PROGNOSTIC
Good if no complication
- Full recovery in 4 weeks
- Residive
-

- Complication rare:
- invagination, intestinal perforat
- intracranial bleeding
- renal failure

THROMBOCYTE
THROMBOCYTE DISORDER
DISORDER

A. QUANTITATIVE DISORDER
1. Thrombocytopenia bleeding
2. Thrombocytosis thrombus formation
Normal:
platelet count 150.000 - 400.000/mm3
< 50.000/mm3 spontaneous
bleeding

THROMBOCYTOPENIA:
THROMBOCYTOPENIA:
a. Production disorder:

- Hypoproliferation: aplastic anemia, ATP

- Ineffective thrombopoesis :
- Megaloblastic anemia
- ANLL M7

b. Distribution disturbance:

- Splenomegali: pooling thrombocyte

- Lymphoma

c. Dilution:
- Massive blood transfusion

d. Abnormal destruction
- Non-immune: - DIC
- Infection: DHF, sepsis

- Immune:
- Idiopathic Thrombocytopenic Purpura (IT
- Drugs: Kina, kinidin, sulfa, dilantin, ect.
- Neonatal thrombocytopenia
- Purpura post-transfusion

e. Abnormal consumption:
- DIC, DHF

B. QUALITATIVE DISORDER
= Trombastenia or thrombopati
1. Adhesion disturbance
2. Aggregation anomaly
Diphenydramin:
- prevent platelet aggregation

3. Disturbance of platelet release reactio

Asetil salisilic ac.:
- distrub release of ADP
- asetilasi platelet membrane

IDIOPATHIC/IMMUNE
IDIOPATHIC/IMMUNE
THROMBOCYTOPENIC
THROMBOCYTOPENIC PURPURA
PURPURA (ITP)
(ITP

Destruction of platelet shorter age

immunologic mechanism:
- antibody (IgG) platelet
- C3 complement
- cellular immunity activation:
macrophage & cytotoxic cell

KLASIFIKASI
KLASIFIKASI

1. Acute ITP (85-90%): self limiting anak-ana

2. Chronic ITP (10-15%): dewasa

ITP
ITP Akut
Akut
- Umur : 2 - 8 tahun
- 50% kasus : 1 - 6 minggu sebelumnya
viral infection: ARTI, hepatitis, mumps,
mononucleosus infectiosa,
cytomegaloviral etc.)

Gejala
Gejala klinis:
klinis:

- perdarahan kulit dan selaput lender pete

dan ekimosis melena, hematuri
- peradarahan alat dalam jarang

- thrombositopeni berat perdarahan otak

- tourniquet test is positive

Gambaran
Gambaran darah:
darah:
- thrombositopeni
- hapusan darah:
bentuk trombosit abnormal,
ukuran besar, terpisah-pisah
- retraksi bekuan berkurang
- waktu perdarahan memanjang
- PT & APTT normal

Sum-sum
Sum-sum tulang:
tulang:
Penting menyingkirkan:
- aplastic anemia
- leukemia
Megakariosit:
- Jumlah normal atau meningkat
- Morfologi:
- immatur
- sitoplasma lebih basofil
- kurang granulasi

Pengobatan
Pengobatan ITP
ITP akut
akut
- Istirehat dan hindari trauma
- Kasus ringan tidak perlu pengobatan

- Kasus berat perdarahan luas/berat:

- kortikosteroid
- suspense trombosit tidak dianjurkan
- blood transfusion (PRC): atas indikasi

Prognosis:
Prognosis:
- Sebahagian besar (85 - 90 %) sembuh
- 10 - 15% kronis

ITP
ITP Kronik
Kronik

- Thrombositopeni (< 100.000/mm3) 6 bulan

- Remisi spontan sangat jarang
- Umur > 10 tahun , Pr > Lk

Pengobatan:
1. Kortikosteroid
2. imunosupresif bila 1 tidak berhasil
3. IgG or Danazol
3. Sphlenektomy bila 1, 2 dan 3 tidak
berhasil

GANGGUAN
PEMBEKUAN
Komponen pembekuan:
pembekuan:
Komponen
1. sistem
sistem Pembekuan
Pembekuan Darah
Darah
1.
mekanisme
mekanisme pembekuan
pembekuan darah
darah

2. Sistem
Sistem Pencegahan
Pencegahan Pembekuan
Pembekuan
2.
mencegah
mencegah pembekuan
pembekuan intravascular
intravascular

darah tetap
tetap cair
cair
darah

3. Sistem
Sistem Fibrinolytic
Fibrinolytic
3.
melisiskan
melisiskan fibrin
fibrin
lumen
lumen pembuluh
pembuluh dar
dar

tetap terbuka
terbuka
tetap

SISTEM
SISTEM PEMBEKUAN
PEMBEKUAN DARAH
DARAH
Faktor-faktor pembekuan darah:
International Name Synonym
I

Fibrinogen

II

Prothrombin

III

Tissue factor,
Tissue thromboplastin

IV

Calcium (Ca)

Proacelerin, Labile Factor

VII

Proconvertin, Stable factor

VIII

Antihemophilic Factor, AHF-A

SISTEM
SISTEM PEMBEKUAN
PEMBEKUAN DARAH
DARAH
IX

Plasma Thromboplastin Compon

(PTC), Christmas Factor, AHF-B

Stuart Prower Factor

XI

Plasma Thromboplastin Anteced

(PTA), AHF-C

XII

Hageman Factor, AHF-D

XIII

Fibrin Stabilizing factor (FSF)

Prekalikrein

Fletcher Factor

Kininogen

Fitzgerald factor

SISTEM
SISTEM PENCEGAH
PENCEGAH PEMBEKUAN:
PEMBEKUAN:
Inhibitor
Inhibitor pembekuan:
pembekuan:
-- Antithrombin
Antithrombin III
III
-- C
C Protein
Protein &
& SS Protein
Protein
-- Alpha-2
Alpha-2 macroglobulin
macroglobulin

SISTEM
SISTEM FIBRINOLITIK:
FIBRINOLITIK:
Plasminogen
Plasminogen systemsystem- plasmin:
plasmin:
-- Plasminogen
Plasminogen
-- Plasminogen
Plasminogen activator
activator
-- Anti
Anti plasmin
plasmin

Proses
Proses pembekuan
pembekuan darah:
darah:
1.Pembentukan
1.Pembentukan activator
activator protrombin
protrombin
(Protrombinase):
(Protrombinase):
-- Intrinsic
Intrinsic
-- Ekstrinsic
Ekstrinsic
2.
2. Prothrombin
Prothrombin
trombin
trombin
3.
3. Fibrinogen
Fibrinogen
fibrin
fibrin

Kerusakan jaringan

Kontak permukaan
XII
I
N
T
R
I
N
SI
C

XIIa
XI

III
+
VII

XIa
IX

IXa
VIII
X

Xa

Ca++

PROTHROMBINASE

Ca++

V
F.Tr-3

Prothrombin

Ca

++

Thrombin

Fibrinogen

Fibrin
XIII
Fibrin polymer

E
x
T
R
I
N
S
I
C

GANGGUAN
GANGGUAN PEMBEKUAN
PEMBEKUAN
1. Sistem pembekuan
2. Sistem pencegah pembekuan
3. Sistem fibrinolitik

Gangguan sistem/mekanisme pembekuan

defisiensi satu atau lebih :
faktor pembekuan

1.
1. Pembentukan
Pembentukan berkurang:
berkurang:
---

genetik/kongenital
genetik/kongenital :: hemophilia
hemophilia
Vit.
Vit. K
K deficiency
deficiency II,
II, VII,
VII, IX
IX &
& X,
X, C
C Prote
Prote

-- penyakit
penyakit hati
hati berat
berat

2.
2. PEMAKAIAN
PEMAKAIAN BERTAMBAH
BERTAMBAH

-- Consumption
Consumption coagulopathy
coagulopathy
Disseminated
Disseminated Intravascular
Intravascular Coagulation
Coagulation
(DIC)
(DIC)

Sifat-sifat
Sifat-sifat gangguan
gangguan pembekuan:
pembekuan:

1. Perdarahan trauma ringan, jarang spontan

2. Jarang petechie
3. Perdarahan sendi dan jaringan dalam
hematoma besar, ekimosis besar
4. Perdarahan dari luka:
- tidak segera timbul
- sering berulang
- berlangsung lama (>48 jam)
- merembes ( oozing )
Laboratorium:
- PT & PTT: salah satu atau
keduanya
- waktu perdarahan normal

HEMOFILIA
HEMOFILIA

HEMOFILIA
HEMOFILIA
Penyakit perdarahn:

- Gangguan pembekuan
Coagulation factors deficiency
- congenital, herediter

Hemophilia:
Hemophilia A factor VIII deficien

Hemophilia B factor IX deficiency

INSIDEN
INSIDEN
1 : 10.000
Hemofilia paling banyak
GENETIKA
GENETIKA DAN
DAN PATOFISIOLOGI
PATOFISIOLOGI
- Factor VIII Gen X chromosome
- Mutasi gen (substitusi dan delesi)
gangguan sintesis faktor VIII
Penyakit diturunkan secara resesif
Kromosom seks : X-linked

GENETICS
GENETICS AND
AND PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
Male (Xh Y) affected
female (Xh X) carrier
Usually by marriage:
Normal father (X Y)
Carrier mother (Xh X)
Hemophilia almost entirely in boys

GENETICS
GENETICS AND
AND PATOPHYSIOLOGY
PATOPHYSIOLOGY

Women could be affected:

- father = (Xh Y) & mother = (Xh X)
- Inactive gene of VIII factor
- Spontaneous mutation gene of VIII facto
F VIII: protein plasma are needed in
prothrombin activator synthesis process
F VIII deficiency coagulation cascade
disturbance

CLINICAL
CLINICAL MANIFESTATION:
MANIFESTATION:
Depends on F VIII levels

Severe Hemophilia : F VIII < 1%

spontaneous bleeding
hemarthrosis, muscle bleeding,
gastrointestinal, hematuria & brai
Moderate Hemophilia : F VIII 1 5 %
bleeding after minor trauma
Mild Hemophilia : F VIII 6 25 %
bleeding after major trauma,
surgery

DIAGNOSIS
DIAGNOSIS

History:
- History of repeated bleeding joints
- Brothers with the same illness
- Brothers from mother with the same illn
Physical examination:
- hemarthrosis, hematoma, etc
Laboratory:
- normal platelet & bleeding time
- Prolonged PTT & normal PT
- TGT & AHF assay F VIII deficiency

COMPLICATION
COMPLICATION
Because of the disease:
hemophilia arthropathy
contracture and paresis/paralysis
of muscle
hemophilic pseudotumor
Because of treatment:
Formation antibody against F VIII
thrombosis
ITP
Viral hepatitis

TREATMENT
TREATMENT
1. Stop the bleeding:
Administration of F VIII:
- cryoprecipitate
- F VIII concentrate (KOATE)
Bed rest
Immobilizes bleeding area:
cold compress, tampon

2. Correction of bleeding consequenc

- Treatment of anemia & shock
- synovectomy
- joints & muscles rehabilitation

TREATMENT
TREATMENT
3. Bleeding prevention:
- prevention of trauma
- addition of F VIII before surgery
- contraindication: aspirin

VITAMIN
VITAMIN K
K DEFICIENCY
DEFICIENCY

Is found in:

1. Hemorrhagic disease of the newborn (HD

2. Disorder of Vit. K absorption:
- Biliary tract obstruction
- Chronic diarrhea
- Severe liver disease
3. Intestinal sterilization by antibiotics

HEMORRHAGIC
HEMORRHAGIC DISEASE
DISEASE OF
OF THE
THE NEWBORN
NEWBORN
(HDN)
(HDN)

Hemorrhagic disease in newborn baby due to:

Deficiencies of factor II, VII, IX & X vitamin K

Physiology
Physiology (normal):
(normal):
Coagulation
Coagulation factor
factor II,VII,IX
II,VII,IX &
& X:
X:
-- decrease
decrease in
in newborn
newborn

the
the lowest
lowest rate
rate at
at 22 -- 55 days
days of
of age
age
-- increase
increase at
at 77 14
14 days
days of
of age
age

Etiology:
Etiology:

-- Uncomplete
Uncomplete colonization
colonization of
of intestinal
intestinal fl
fl

the
the synthesis
synthesis of
of vit
vit K
K in
in gut
gut is
is still
still low
low
-- decrease
decrease of
of vit
vit K
K in
in placenta
placenta

If decreasing of coagulation factor excessiv

HDN

May
May result
result from
from ::
1.Very
1.Very low
low amounts
amounts of
of vitamin
vitamin K
K storage
storage
2.No
2.No synthesis
synthesis of
of vit.
vit. K
K in
in gut
gut

sterile
sterile intestinal
intestinal flora
flora
3.
3. Absorption
Absorption of
of vit
vit K
K in
in gut
gut very
very low
low

4.
4. Disorder
Disorder of
of vitamin
vitamin K
K metabolism:
metabolism:
-- Damaging
Damaging of
of vit.
vit. K
K ::
barbiturat,
barbiturat, phenytoin,
phenytoin, diazepam,
diazepam, INH,
INH
Rifampisin
Rifampisin
-- disturbance
disturbance of
of vit.K
vit.K usage
usage by
by liver:
liver:
dicumarol,
dicumarol, salicylat
salicylat

FUNCTION OF VITAMIN K
Protein (II, VII, IX & X)

Vitamin K

Carboxylation

Functional of coagulation factor

(II, VII, IX & X)

The process were done in liver

Incidence:
- Age: 2 - 5 days

Clinical
Clinical manifestations:
manifestations:
Bleeding
Bleeding in
in various
various location:
location:
-- gastrointestinal
gastrointestinal tract:
tract: melena
melena
-- umbilical
umbilical cord,
cord, skin,
skin, mucosa
mucosa
-- cephalhematom,
cephalhematom, brain
brain bleeding
bleeding

BLOOD
BLOOD HEMOSTASIS
HEMOSTASIS
ABNORMAL/PROLONGED

NORMAL

PT (Factor II, VII, X)

Thrombin time (TT)

APTT (Factor II, IX, X)

Fibrinogen

Thrombotest,
Normotest (F. II, VII, X)

Activity F. V, VIII, XI

Activity F. II, VII, IX, X

Antigen F. II,VII,IX,X

There are PIVKA II

Platelet count & BT

Practical:
HDN: bleeding manifestation in baby <12 weeks with :
- Prolonged of PT & APTT
- Normal platelet and BT

TREATMENT
TREATMENT
HDN self limited
Bleeding can stop spontaneously
but needs long time
- Massive hemorrhagic
- Continuous hemorrhagic
- intracranial hemorrhagic
Threaten the newborns life

Needs immediate & the right treatme

HDN
Vit.
Vit. KK 1-2
1-2 mg
mg im/times
im/times
--Continous
Continousbleeding
bleedingor
or
recurrent
recurrent
-Prolonged
-ProlongedPTT
PTT

Severe
Severehemorrhagic
hemorrhagic

shock
shock

Repeat
RepeatVit.
Vit.KK
(3
(3times,
times,every
every66hours)
hours)
--Continous
Continousbleeding
bleedingor
or
recurrent
recurrent
--Prolonged
ProlongedPTT
PTT

Anemia
Anemia

Plasma
PRC
Plasmaor
or
PRCtransf
transf
Fresh
Freshfrozen
frozenplasma
plasma(FFP)
(FFP)

Plasma
Plasmaor
or
fresh
freshfrozen
frozenplasma
plasma(FFP
(FF
20 ml/kgBW

PROPHYLAXIS
PROPHYLAXIS
Vitamin K 1 mg

High risk newborn :

- Premature
- Twins
- Assisted labor
- Asphyxia

DIC
DIC

== DISSEMINATED
DISSEMINATED INTRAVASCULAR
INTRAVASCULAR
COAGULATION
COAGULATION
- Intravascular coagulation spread
everywhere in blood vessel (systemic)
pathologic activation of
haemostatic mechanism

DIC:
Defibrination syndrome = Consumption coagulopat
complication: many condition / disease
initiate DIC

--WIDE
WIDEENDOTHEL
ENDOTHELDAMAGE
DAMAGE
--
TISSUE
TISSUETHROMBOPLASTIN
THROMBOPLASTIN
CIRCULATION
CIRCULATION
WIDE
WIDEACTIVATION
ACTIVATIONOF
OF
COAGULATION
COAGULATIONPROCESS
PROCESS
BLOOD
BLOODVESSEL
VESSEL
OCLUTION
OCLUTION

MAHA
MAHA

INTRAVASCULAR
INTRAVASCULAR
TROMBI-FIBRIN
TROMBI-FIBRIN

USAGE:
USAGE:
--COAGULATION
COAGULATIONFACTOR
FACTOR
--PLATELET
PLATELET

FIBRINOLISIS
FIBRINOLISIS

DEFICIENCY
DEFICIENCY
--COAGULATION
COAGULATIONFACTOR
FACTOR
--PLATELET
PLATELET

FDP
FDP

COAGULATION
COAGULATION
DISORDER
DISORDER

ISCHEMIA
ISCHEMIA

HEMORAGE
HEMORAGE

ETIOLOGY:
ETIOLOGY:
- Massive vascular endothel damage
- Tissue Factor (tromboplastin) circulation

1.
1. Trauma:
Trauma:
-- burn,
burn, crush
crush injury,
injury, heat
heat stroke
stroke

2.
2. Infection:
Infection:
-- Viral:
Viral: DHF,
DHF, Variola
Variola
-- Bacterial:
Bacterial: sepsis
sepsis
-- Fungus:
Fungus: candidiasis
candidiasis

3.
3. Metabolic:
Metabolic:
-- Acidosis,
Acidosis, alkalosis,
alkalosis, ketosis
ketosis
-- Hyperthermia,
Hyperthermia, hypothermia
hypothermia

4.
4. Immunologic:
Immunologic:

-- Blood
Blood transfusion
transfusion reaction
reaction (massive
(massive hemol
hemo
-- Anaphylactic,
Anaphylactic, Immune
Immune complex
complex diseases.
diseases.

5.
5. Malignancy:
Malignancy:
-- Leukemia
Leukemia (ANLL-M
(ANLL-M33))

6.
6. Others:
Others:
-- Shock
Shock
-- Anoxia
Anoxia

DIAGNOSIS
DIAGNOSIS
CLINICAL:
Primary
Primary Severe
Severe Disease
Disease

Duration
Duration of
of illness
illness
with:
with:
-- hemorrhage
hemorrhage
-- tissue/organ
tissue/organ ischemia
ischemia ::
acral
acral necrosis
necrosis
renal
renal failure
failure

LABORATORY
-- Blood
Blood smear
smear
microangiopathy:
microangiopathy:
burr
burr cells,
cells, helmet
helmet cells
cells
-- Thrombocytopenia
Thrombocytopenia &
& prolonged
prolonged bleeding
bleeding
time
time
-- PT,
PT, PTT
PTT &
& prolonged
prolonged thrombin
thrombin time
time
-- coagulation
coagulation factor
factor

Fibrinogen
Fibrinogen
-- FDP
FDP (FSP)
(FSP)

THERAPY
THERAPY
1.
1. Treat
Treat etiology
etiology factor
factor
2.
2. Blockade
Blockade
process
process

3.
3. Blood/plasma
Blood/plasma component
component substitution
substitutio