HEMOPHILIA

Introduction
X

linked recessive disorders

HEMOPHILIA. A
Is a bleeding disorder that results from a
deficiency in coagulation factor VIII (FVIII).
HEMOPHILIA B
Is a bleeding disorder that result from a
deficiency in coagulation factor IX (F IX)

FAMILY HISTORY

FATHER
MOTHER

: HEMOPHILIA
: NORMAL

FATHER : NORMAL
MOTHER
: CARIER

FATHER : HEMOPHILIA
MOTHER
: KARIER

PREVALENCE OF HEMOPHILIA
Indonesia

Population
Expected Prevalence
Known cases
Characterised

209 million
13,000*
850 (6.5%)
234

Annual Health Expenditure per Capita

-India:
US $15
-Indonesia
US $110
-USA
US $4,108
-G7 Average US $2107

Based on 133/Million male Population

Countries with Similar

Population Number
Country
U.S.A.
Brazil
Indonesia

GNI

Prevalence

FVIII p.c.

35,400

51

3.4

2,830

37

0.93

710

0.008

CLINICAL MANIFESTATION :
Bleeding

on muscle

and joint
Severe pain
recurrent
Continous bleeding
Life threatining

Laboratory finding
Reduce

level of factor VIII or IX

APTT is two to three times
Platelet count
Bleeding time
Normal
Prothrombin time
Thrombin time

Genetics and classification

No apparent racial and ethnic group

X-Linked traits.
Severe hemophilia < 1% U/dl clotting factor
Bleeding spontaneous
1 5% U/dl
Mild trauma induce bleeding
Mild hemophilia > 5% U/dl
Significant trauma bleeding

Treatment
guideline therapy for hemorrhage
in hemophilia (1)
Site bleed

Hemostatic factor
level

Factor dosing
hemophilia A

Comment

Joint

40-80%

20-40 u/kgBW
qd as needed

-rest/immobilization
-physical/rehabilitation
following bleed

muscle

40-80%

20-40 u/kgBW
Qd as needed

-calf/forearm bleed is limb

threatening
-significant blood loss with
femoral/retroperitoneal

Oral mucosa

Initially 50% then

antifibrinolytic
coverage usually
suffices

25 u/kgBW

gastrointestinal

Initially 100% then

30% until healing
occurs

40-50 u/kg then

30-40 u/kg qd

Antifibrinolytic therapy
maybe usefull

Treatment
guideline therapy for hemorrhage
in hemophilia(2)
Site bleed

Hemostatic factor
level

Factor dosing
hemophilia A

Comment

Epistaxis

Initially 80-100%
then 30% until
healing occurs

40-50 u/kg then

30-40 u/kg

Pressure/pack/cautery
usefull for severe or
recurrent bleed

Genitourinary

Initially 100% then

30% until healing
occurs

40-50 u/kg then

30-40 u/kg

Evaluate for stone or

urinary tract infection
antifibrinolytic
contraindicated

Central nervous
system

Initially 100% then

50-100% for 10-14
days

50 u/kg then
25u/kg q12 hours
or continous
infusion

Anticonvulsant frequently
used preventively

Trauma or surgery

Initially 100% than

50% until wound
healing begins then
30% until healing
complete usually 714 days

50 u/kg then doses Perioperative management

q 12 hours or by
plan must be in place pre
continous infusion op evaluation for inhibitor
crucial prior to elective
surgery

Factor XI Deficiency
( Hemophilia C )
An

autosomal deficiency
Mild and moderate bleeding symptoms
In Israel 1-3/1000 are homozygous
The bleeding not correlated with the amount of
Factor XI
Severe deficiency minimal or no symptoms

Treatment
There

is no concentrate factor XI
Fresh Frozen Plasma (FFP)
Minor surgery local pressure
Plasma infusion 1U/kg increase
plasma
concentration by 2 U/dl
The infusion of 10 -15ml/kg plasma
sufficient to control moderate
hemorrhage

von Willebrand Disease

Hereditary

bleeding disorder
1 2% of general population
Inherited autosomal
Women > men
Classified : type 1, 2 and 3

Clinical manifestations
Mucocutaneous
-

hemorrhage
Excessive bruising, epistaxis, menorrhagia
Post op hemorrhage

Laboratory findings
Bleeding time
PTT
Platelet count was normal

Treatment
Increasing
Factor

the plasma level of VWF and

VIII
Desmopressin (DDAVP)
Plasma derived VWF : 1 U/kg 1.5
U/dl
Purified VWF concentrate future
- presurgical management or
prophylaxis

Protokol pemberian FVIIIK

Basic principles of bleeding treatment

episodes in hemophilia A
1. Treat bleed early with factor
replacement therapy within 2 hours of the onset
symptoms
2. Treat veins with care. A hemophiliacs veins are
his lifeline
3. Avoid products that cause platelet dysfunction
4. Home therapy with clotting factor is usually
begun when a child is 3-5 years old.
5. The concept of comprehensive care at a
hemophilia treatment center is state of the art
approach to hemophilia treatment

Specific hemorrhage
Joint hemorrhage

Raise FVIII level to 40%. For more

joint bleeding raise the level to 6080 %.

X ray or may not be indicated.

2nd infusion to raise factor level to
40% may required in 12 24
hours.3rd infusion in 72 hours if
symptom persist

Immobilize the joint as soon as

possible until pain subsides. A
cryocuff is most helpful.

Adjunctive care : ice,rest, and

elevation
Pain control : aspirin free medication

specific hemorrhage

Muscle hemorrhage

First give patients the

appropriate dose of FVIIIK
and then evaluate

Raise FVIII level to 40% first

symptom/trauma.

A second infusion to rise fctor

level 40 % often required
within 24 hours.

Should be monitored
neurovascular compromise

specific hemorrhage

Iliopsoas hemorrhage

Problem often presents as an

acute abdomen or as hip pain.

Sign may include pain in lower

abdomen,groin,and/or lower
back,and pain on extension,
paresthesia
Immediately raise FVIII 80100%.maintain VIII >50%.

Hospitalize for
observation,treat anemia
CT scan for confirm the
diagnosis.
Limit activity until pain
resolves,physical therapy

This is a form of muscle hemorrhage

with unique presentation

specific hemorrhage

CNS hemorrhage/head trauma

This is a true medical

emergency.

Treat all post traumatic head

injuries and significant
headaches as head bleed.

Immediately raise FVIII level

to 80-100%,maintain FVIII at
least 50% until the
hemorrhage improves (usually
2-3 weeks).

CT scan or MRI should be

performed

Case of suspected head

trauma treat with FVIIIk and
then evaluate

specific hemorrhage

Throat and neck hemorrhage and

severe tosillitis

This is true medical

emergency, immediately raise
FVIII level 80-100% when
symptom or significant
trauma occur.

Maintain FVIII at least 50%

for 1-2 weeks until
hemorrhage resolves.

CT scan or MRI should be

performed.

To prevent hemorrhage with

severe tonsillitis may be
indicate to give antibiotic

specific hemorrhage

Acute abdomen /Acute

gastrointestinal hemorrhage

Give appropriate dose of

FVIIIK and evaluate.

Immediately raise FVIII level

to 80-100%. Maintain FVIII at
least a 50% until etiology is
defined.

Treat anemia or shock as

needed.

Treat origin of hemorrhages .

EACA or tranexamic acid may

use as adjunctive therapy as
long as the possibility of renal
bleeding has been eliminated

specific hemorrhage

Opthalmic trauma or hemorrhage

Give the patient the

appropriate dose of factor
VIIIK and then evaluate.

Immediately raise FVIII

level 80-100%. Maintain a
factor level at least 50%.

Evaluation by
ophtalmologist and
hematologist is required

specific hemorrhage

Renal hemorrhage

Avoid use of anti-fibrinolytic

agent.

Painless hematuria should be

treated with complete bedrest and
vigorous hydration (1-1/2 x
maintenance) for 48 hours.

If there is pain or persistent gross

hematuria, give FVIII raise to 50
%.

Prednison , if hematuria (gross or

microscopic) persist or if there
are repeated episode

specific hemorrhage

Oral hemorrhage

Bleding may be controlled with

use of EACA or tranexamic acid
alone or with the use of FVIIIK
and either EACA or tranexamic ac.

Evaluate and treat for anemia as

indicated.

The application of topical such as

thrombin on the bleeding mucous
membran may be effective and
also ice.

A soft, cold diet for 24 hours is

recommended.

Consult to the dentist or

otolaryngologist

specific hemorrhage

Epistaxis

Factor replacement usually

not required because the
formation of a platelet plug
often adequate.

Place his head forward to

avoid swallowing blood and
have him gently blow out
weak clots. Apply firm
pressure to the fleshy part of
the nose for at least 10-20
minutes.
For bleed related allergy URI
efinefrin drop 5%-1%, 2
drop/nostril b.i.d for 5 days

Watch for anemia if bleeding

is prolonged
EACA or tranexamic acid may
be helpful as well as normal
saline solution or gel

specific hemorrhage

Soft tissue hemorrhage

Most superficial soft tissue bleed

does not required replacement
therapy. The application of firm
pressure and ice.

Evaluate for severity and possible

muscular or neurovascular
involvement.If this suspected
treat with factor to 80-100%
immediately

A young,active child with

hemophilia commonly has
numerous bruises. Parents are
sometimes wrongfully accused
of child abuse

specific hemorrhage

Lacerations and Abrasions

Deep laceration required raising

FVIII level to 50%, then
suturing. Removal of sutures
usually requires another
infusion of FVIII.

Superficial laceration can be

treated by cleaning the wound
followed by application of
pressure and steri-strips.

Aberation require cleaning

and pressure

Treament regimen guidelines for

therapy of hemophilic bleeding
Bleeding site

optimal factor
dosage(iu/kg)
level (%)
------------------------------------------------------------------Hematoma
20-30
10-15
Hemarthrosis 30-50
15-25
GI tract
40-60
20-30
Retropharyng/tongue 60-100
30-50
Intracranial
80-100
30-50
Retroperitonial
60-100
30-50
Hematuria
30-50
15-25
Minor bleeding
20-30
10-15

Factor concentrate in developing

country

Problems with hemophilia care are immence

-

only 10-60% hemophilia have been identified

diagnostic facilities are limited
factor concentrates for treatment are scarce
government support is few, crucial for succesful
programme including purified factor concentrate
- most individual have to pay factor concentrate
- essential to establish a good transfusion service
to provide plasma for making factor concentrate
or may be imported

Therapy should be administered as

promptly as possible when the bleeding
episode begins or is recognized.
early use of replacement therapy, even in
minimal amount, produces better
hemostasis than delayed use