HEMOPHILIA

Dr. Rini Andriani, Sp.A

FKIK UNTAN
8 Juni 2011

Bleeding/ Easy Bruisability

Low Platelet count
Platelet Morphology

Normal Platelet Count

PT/aPTT

Small Platelet
Large Platelet
Anemia
No anemia
Dec retics
Normal retics
Aplastic anemia
ITP
Leukemia
Megaloblastic anemia

PT/aPTT

Normal PT
Normal PTT

Normal PT
Prolonged PTT

Prolonged PT
Prolonged PT
Normal PTT
Prolonged PTT

Platelet
1:1 mixing studies Vit K Deficiency Liver Disease
Dysfunction vWB Disease
Factor VII Def
Vit K Def
vWB Dse
DIC

1:1 Mixing Studies

Normal PTT

Prolonged PTT

Factor VIII/IX Deficiency

Specific Factor Assay

Inhibitors

FINDINGS

HEMOPHILIA
A
B

Bleeding Time
PT
aPTT

Normal

Normal

Normal
Normal

Prolonged

Factor VIII

Low

Factor IX

Normal

vWB Factor

HEMOPHILIA
DISESASE

Normal

vWB
Prolonged

Normal

Prolonged
Normal

Prolonged
Low/Normal

Low
Normal

Normal
Low

FINDINGS

Symptoms

HEMOPHILIA

Joint & muscle

bleeding
Gender dist. Males>Females
Frequency
1:6000
Abn CHON Factor VIII
Bleeding time Normal
PTT
Prolonged
Factor VIII
Dec to absent

vWB DISEASE

Bruising, epistaxis &

mucosal bleed
Male=Female
1:200-500
vWB Factor
Prolonged
Normal/Prolonged
Borderline to dec

What is Hemophilia?
It is an inherited disorder
of blood clotting

HEMOSTASIS
PRIMARY HEMOSTASIS = primary clot
(platelet)

SECONDARY HEMOSTASIS
factors

coagulation

CLOTTING CASCADE

Intrinsic Pathway

Extrinsic Pathway

Contact
XII

XIIa
XI

XIa

Tissue Factor

IX

IXa

VIIa

VIIIa+Pl

X
II

Xa
Va+Pl
IIa

Fibrinogen

Fibrin Clot

VII

Clotting is a
complex process
in which the
activated form of
one coagulation
factor activates the
next factor in a
clotting sequence

How does bleeding stop?

Vasoconstriction
Platelet plug
formation
Fibrin clot
In a person with
hemophilia, the clot
does not form
properly due to lack
of clotting factor

Hemophilia
A person with hemophilia has less clotting factor than
usual.
Hemophilia A deficiency of factor VIII
Hemophilia B deficiency of factor IX
Normal range of factor activity: 50 200%
Hemophilia
Severe: less than 1%
Moderate:
1 5%
Mild:
6 30%

FACTOR LEVEL AND SEVERITY OF

CLINICAL MANIFESTATIONS
TYPE PERCENT MANIFESTATION
Factor VIII
Severe
Moderate

<1%
1-5%

Spontaneous; hemarthrosis; hemorrhage

Gross bleed after mild to mod trauma

Mild

5-25%

Bleed after a moderate to severe trauma

Carrier

30-50%

Gynecologic & Obstetric Hemorrhage

HISTORY
2nd century AD: Talmud (collection of jewish
rabbinical writings)
Male babies exempted from circumcision if with hx of
2 brothers who died from the procedure

12th century: Albacusis (Arab physician)

Wrote family of whose males died of bleeding after
minor injuries

1803: Dr. John Otto (Philadelphia MD)

hereditary and affecting males

1828: Hopff (University of Zurich)

hemophilia first appear

Inheritance of Hemophilia

Inheritance of Hemophilia

How common is hemophilia?

Factor VIII deficiency- 1:10,000 male

births
Factor IX deficiency - 1:30,000 to 50,000
male births
All races and socioeconomic groups are
equally affected

Clinical Manifestations
Major Bleeding
CNS

Hip/Iliopsoas/
retroperitoneal

Neck/Throat
GIT
Advanced joint/muscle Forearm compartment

May cause death or crippling

Start appropriate factor replacement urgently
Hospitalization usually required
Bruising may be absent in deep muscle bleed
Muscle compartment bleed (calf, forearm) may cause
nerve damage or vascular compromise

Clinical Manifestations
Minor Bleeding
Joint/early/

Mouth/gums

Muscle/soft tissue
hematuria

epistaxis

Complications may arise

Treat early to avoid long term complications

Clinical Manifestations
Hemarthrosis is the hallmark of hemophilia.
Joints become swollen, red, hot and painful
with diminished range of motion.
Muscles become tense, swollen, re, hot and
painfull usually with bruising overlying the
affected area.

TREATMENT
1950s 1960s: FWB or FFP
Late 1960: Cryoprecipitate
(Dr. Judith Pool)

1970s:
1990s:
2000:

Factor 8 and 9
Safer Factor Conc.
Ultra recombinant

Factor VIII Treatment Guidelines

Dose depends on bleeding severity

Expected Response: 1 iu/kg = 2% rise
Half-life: 8-12 hours
For serious bleeding, Factor 8 assay may
be required to monitor the response to
transfusion/infusion.
Surgical cases:
Continuous infusion is a better option
If there is no response to appropriate
Treatment - test for INHIBITORS

Factor IX Treatment Guidelines

Dose depends on bleeding severity

Expected Response: 1 iu/kg = 1-1.5% rise
Half-life: 16-24 hours
For serious bleeding, Factor 9 assay may
be required to monitor the response to
transfusion/infusion.
Surgical cases: Continuous infusion is a
better option
If there is no response to appropriate
Treatment - test for INHIBITORS

Acute Bleeding in hemophilia: Guidelines in Treatment

Bleeding site

Optimal
Level %

Dosage IU/kg
F VIII

Joints

40

20

Muscles

40

20

GIT

80-100

Tongue/Retropharyngeal

80-100

F IX
40

Frequency
24 hrs Days
1-2

1-2

40

1-2

1-2

40-50

60-80

1-2

2-3

40-50

60-80

1-2

3-4

-F. Hernandez, MD.,et al,

Treatment Manual for Hemohilia, 2003

Acute Bleeding in hemophilia: Guidelines in Treatment

Bleeding site

Optimal
Level %

Dosage IU/kg
F VIII

Retroperitoneal

80-100

40-50

Intracranial

80-100

40-50

Hematuria

50

Minor bleeding

50

F IX
80

Frequency
24 hrs Days
1-2

3-4

80

1-3

7-10

25

40

1-2

1-2

25

30-40

1-2

1-2

-F. Hernandez, MD.,et al,

Treatment Manual for Hemophilia,
2003

Computations:
Factor VIII
Wt (kg) x desired percent activity
2

= No. of IU

Factor IX
Wt (kg) x desired percent activity = No. of IU
Cryoprecipitate: 1u = 80IU Factor VIII

Treatment Guidelines
Do not give ASA
Aspirin impairs platelet function, which may
compound existing bleed
Cyclokapron/Tranexmic acid: 15-25mkd
Antifibrinolytic prevent clot breakdown
agents that inhibit plasminogen activity in the
saliva
Indicated for mucous membrane bleeding;
contraindicated in patients with hematuria

Treatment Guidelines
Childhood immunization
Following the injections, press on area >5 minutes
Apply ice

Avoid IM injections unless administered under

replacement
Venipuncture or superficial vein is safe if
pressure is applied for several minutes
Femoral or jugular venipuncture should not be
attempted.

General Care
Exercise
Encourage participation in sensible,
physical exercise because strong
muscles help support joints.
Ideal exercises: swimming & bicycling
- strengthen muscles and preserve
normal joint motion
Avoid jogging and contact sports.

Advances in Management

Factor Concentrates
Home Treatment
Prophylactic Care/Port-a-cath
Continuous Infusion
Products Used to treat patients with
Inhibitors/Immunosuppression
Comprehensive Hemophilia Care

Thank You!

CLOTTING CASCADE
PTT

PT

Contact Factors
TF
T
E

VIIa

N
E
T

IIa
Fibrinogen

XIII
Fibrin

XL FIBRIN