HEMOSTASIS

Dr ELSYE SOUVRIYANTI , MKes, SpA

Hemostasis
Proses fisiologis penghentian perdarahan di tempat
terjadinya injuri

Faktor yang berperan :
1) pembuluh darah
2) trombosit
3) proses koagulasi dan enzim fibrinolitik
4) jaringan
Platelet activation
1. Adhesion
Vascular damage
Contact with collagen
(Endothelial damage)
2. Loose aggregation
3. Firm ggregation
4. Fibrin formation
5. Clot retraction
ADP Release
Thrombin formation
on platelet plug surface
Coagulation
Platelet retraction
Thrombin formation
Coagulation cascade, the traditional concept
H E M O P H I L I A
CLINICAL PICTURE, TREATMENT
AND ITS PROBLEMS
Introduction
Hemophilia is the most common inherited
bleeding disorder.
There are:
Hemophilia A : deficiency of factor VIII
Hemophilia B : deficiency of factor IX
Both hemophilia A and B are inherited as
X-linked recessive disorders
Symptoms could occur since the patient
begin to crawl

Epidemiology
Incidence:
hemophilia A ( 85%) 1 : 5,000 10,000 males
(or 1 : 10,000 of male life birth)
hemophilia B ( 15%) 1 : 23,000 30,000 males
(or 1 : 50,000 of male life birth)
Approximately 70% had family history of
bleeding problems

Genetic
Inherited as sex (X)-linked recessive
Genes of factor VIII/IX are located on
the distal part of the long arm (q) of X
chromosome
Female (women) are carriers
Hemophilia
Clinical Classification*
Severe Moderate Mild

Coagulation factor level <1% 1 - 5% >5%
Bleeding spontaneous mild trauma moderate trauma
Episodes 1-2 x/wk 1 x/mo none
Hemarthrosis common occasionally rare


* Hemophilia A or B
Clinical manifestation
Bleeding:
usually deep (hematoma, hemarthrosis)
spontaneous or following mild trauma
Type:
hemarthrosis
hematoma
intracranial hemorrhage
hematuria
epistaxis
bleeding of the frenulum (baby)


Hemarthrosis
Most common type of bleeding
Frequently affected joints in this order:
knee
elbow
ankle
shoulder
wrist
hip
etc.
8%
25%
44%
15%
5%
lain-lain 3%
Diagnosis
history of abnormal bleeding in a boy
normal platelet count
bleeding time usually normal
clotting time normal
prothrombin time usually normal
partial thromboplastin time prolonged
decreased antihemophilic factor
Antenatal diagnosis
antihemophilic factor level
F-VIII/F-IX gene identification (DNA analysis)

Carrier assessment
A woman is an obligate carrier of hemophilia
if one of the following condition is met:
her father is a hemophiliac
she has given birth to 2 or more hemophiliac sons
she has given birth to 1 hemophiliac son and there is a
well documented family history of hemophilia on the
maternal side of her pedigree

Confirmed by laboratory test:
ratio F-VIII:C / F-VIII:Ag < 1
chromosome analysis


1. Prompt intervention
Rest
Ice
Compression
Elevation

2. Definitive treatment
replacement therapy
Treatment
Management of bleeding episode
Stop bleeding with clotting factor within 2
hours of onset
Veins should be well reserved
Avoid the use of anti-aggregation drugs
Home therapy

Followed by comprehensive treatment
Comprehensive care
To be governed through multidiscipline
approach involving experts in the field of:
hematology occupational therapy
orthopedics vocational therapy
infectious disease psychology
nutrition nursing
dentistry genetics



Blood component replacement therapy

factor-VIII factor-IX
(unit/ml) (ml)
fresh-frozen plasma ~ 0,5 ~ 0,6 200
cryoprecipitate ~ 4,0 - 20
factor-VIII concentrate 25 - 100 - 10
factor-IX concentrate - 25 - 35 20


source of F-VIII: - monoclonal antibody purified;
- intermediate- and high-purity;
- recombinant

Dosage


F-VIII : 20 - 25 U/kgBW/12 hrs
F-IX : 40 - 50 U/kgBW/24 hr

Loading dose: 2 x
Dosage regulation:

F-VIII demand = BW (kg) x F-VIII desired(%)
(units) 1,5

Desired F-VIII for:
hemarthrosis 15%
minor surgery 30%
major surgery 60%
intracranial hemorrhage 100%

Other aim of treatment:
DDAVP
Genetic engineering
Supportive: antifibrinolytic agent
analgesics
Physiotherapy (rehabilitation)

Prophylaxis
Complications
development of factor-VIII inhibitor
(about 20%)
treatment of inhibitor:
increase dose of F-VIII
shortcut coagulation pathway
use of F-VIII from other species

Complications
In the past there were several diseases
transmitted by transfusion such as:
Malaria
Syphilis
Hepatitis
HIV/AIDS
With adequate screening and storage the
TTD can be diminished
There are still risk of transmission with:
Parvovirus B 19
Creutzfeld-Jacob disease

Sports for hemophiliacs
Permitted: Not permitted:
swimming soccer
table-tennis self defense
tennis boxing
golf wrestling
squash racing
rowing hockey
diving
Hemophilia Camp
Teach self infusion
Enhance interaction amongst patients
and parents
Conduct seminars (medical or social)
Evaluation of orthopedic status
Discuss join activities (sports, etc.)
Hemophilia patients are as good as normal
human resources in productivity, but because of
expensive and limited source of F-VIII/F-IX

could not optimally treated

risk of being crippled/handicapped

function

productivity

society burden
Purpura Trombositopenik
Imun
CLINICAL PICTURE, TREATMENT
AND ITS PROBLEMS
DEFINISI
Purpura trombositopenia idiopatik pada
anak adalah penyakit perdarahan akibat
penghancuran trombosit yang berlebihan,
dapat timbul dalam bentuk akut dan bersifat
sementara, maupun rekuren yang disertai
masa remisi (kronis).
EPIDEMIOLOGI
Anak > dewasa
Perempuan : laki-laki 1 : 1
Puncak usia 3-5 tahun
Amerika serikat 100 tiap 1 juta orang/tahun



IKA FKUI Juli 2001-Juni 2003 79 kasus
perempuan : laki-laki 1,8 : 1


PATOGENESIS
Antigen virus berikatan dengan Fab antibodi
(kompleks imun)

Beredar dalam sirkulasi

Menempel pada permukaan trombosit

Bagian Fc antibodi berikatan dengan reseptor Fc
makrofag sehingga terjadi fagositosis di limpa dan
hati




Faktor pencetus belum diketahui




MANIFESTASI KLINIS
Perdarahan Mendadak
Perdarahan kulit
petekie sampai ekimosis
subkonjungtiva
Perdarahan mukosa
Epistaksis dan perdarahan gusi (30%), melena dan
hematuri masif (5-10%)
Perdarahan intrakranial
1%,Trombosit < 10.000/uL, 4 minggu pertama sakit



MANIFESTASI KLINIS
Dikutip dari Cines dkk
7
2002
Dikutip dari Cines dkk7 2002
PEMERIKSAAN PENUNJANG
Darah perifer lengkap
Hemoglobin normal atau sedikit
menurun
Lekosit normal
Trombosit < 100.000/uL
Hapusan darah tepi : morfologi eritrosit
dan lekosit normal, trombosit normal
atau sedikit lebih besar

Hapusan darah tepi
Diunduh dari http://rds.yahoo.com/S=96062883/K=thrombocytopenia/v=2/SID=w/TID=I030_86/

PEMERIKSAAN PENUNJANG
Aspirasi sumsum tulang
Kontroversi
Tidak rutin untuk menegakkan diagnosis
Dilakukan bila gambaran hematologi
khusus : sel imatur, netropenia persisten,
anemia yang tidak dapat dijelaskan,
morfologi eritrosit dan lekosit abnormal



PEMERIKSAAN PENUNJANG
Antibodi antitrombosit
kurang sensitif dan kurang spesifik

Anti HIV atau HIV DNA
jika ditemukan faktor risiko
DIAGNOSIS
Anamnesis
Pemeriksaan fisis
Darah perifer lengkap yang sesuai
dan konsisten dengan gambaran PTI
akut

Tabel 1. Prinsip dasar anamnesis dan pemeriksaan
fisis pada anak tersangka PTI
Anamnesis
Gejala perdarahan:
Jenis, derajat dan lama perdarahan. Didahului tindakan invasif atau tidak
Gejala sistemik:
terutama yang terjadi dalam 6 minggu terakhir, infeksi virus seperti varicella,
atau
infeksi berulang seperti pada penyakit defisiensi imun
Imunisasi virus hidup beberapa saat sebelum sakit
Penggunaan obat-obatan seperti heparin, kinin, sulfonamide atau aspirin
Faktor risiko HIV
Riwayat trombositopenia atau kelainan darah dalam keluarga
Riwayat trauma
Pemeriksaan Fisis
Gejala perdarahan (jenis dan derajat beratnya)
Hati, limpa dan kelenjar getah bening
Tanda infeksi
Gambaran dismorfik yang menunjukkan kelainan kongenital
Gambaran sindrom kongenital
Dikutip dari George JN dkk
3

Tabel 2. Diagnosis banding trombositopenia akut
Purpura trombositopenia akut
DIC
Sepsis
Sindrom hemolisis uremik
Leukemia akut
Anemia aplastik
Dikutip dari Buchanan GR
2

TATA LAKSANA
Terapi ? kontroversi
80-90% sembuh spontan, < 6 bln
Tujuan terapi :
menghentikan perdarahan
meningkatkan jumlah trombosit sampai
kadar aman
mencegah perdarahan intrakranial
TATA LAKSANA
American Society of Hematology
3
dan British
Pediatric Hematology Group
16

Tr 30.000/uL, tanpa gejala/ringan (-)
Tr < 20.000/uL, perdarahan mukosa bermakna
atau Tr < 10.000/uL, purpura ringan kortikosteroid
atau imunoglobulin iv
Perdarahan berat yang mengancam jiwa
kortikosteroid dosis tinggi iv, imunoglobulin iv,
transfusi trombosit
TATA LAKSANA
British Pediatric Hematology Group
16

Imunoglobulin G hanya pada :
1. Terapi gawat darurat, tidak remisi dengan
kortikosteroid atau perdarahan aktif
2. Persiapan operasi yang tidak dapat ditunda
atau ekstraksi gigi darurat

Fujisawa
17
Gejala klinis ringan, trombosit > 10.000/uL
tanpa terapi
PROGNOSIS
Baik
morbiditas dan mortalitas rendah
80-90% sembuh spontan
10-20% menjadi PTI kronik