What is Haemophilia?
Haemophilia is an x-linked recessive hemorrhagic
There are two main types of Haemophilia:
Haemophilia A or classic Haemophilia that represnts
80% of cases and it's due to mutation in F8 gene that
Haemophilia B or Christmas disease which mutation
happens in F9 gene which affects FIX.
The disease affects 1 in 10,000 males in all ethnics.
CLASSIFICATION OF HAEMOPHILIA
CLASSIFICATION LEVEL OF FACTOR VIII
OR IX IN THE BLOOD
SEVERE less than 1% of normal
MODERATE 1% to 5% of normal
MILD 5% to 30% of normal
In the severe or moderate forms is characterized by
bleeding into the joints(hemarthrosis), soft tissue, and
muscles after minor trauma or even spontaneously.
In mild forms patient experience infrequent bleedings
which usually secondary to trauma.
In those with residual FVIII or FIX >25% the disease
discovered only bleeding after major trauma or
In early life, bleeding may present by circumcise and
more evident when children begin to crawl or walk.
in severe cases the most frequent manifestation is
recurrent hemarthroses which mainly affects knee,
ankle, hips, shoulder and elbow, recurrent bleeding
can cause "target joint" resulting in progressive joint
hematomas in muscles of limbs can cause
Bleeding into oropharyngeal spaces and CNS and
retroperitoneal are life threatening and requires
hematuria is frequent and mostly is self-limited.
1. Factor replacement therapy:
1.Response to a bleeding episode
2.Prophylactic therapy(maintain factors >1%)
Mostly severe forms and younger than 6
Haemophilic boys that receive infusions of VIII (3days/week)
or IX (2days/week) can reach puberty without detectible joint
FVIII(100ng/ml) or FIX(5 µg/ml) is 1IU
1IU/kg of FVIII can increase 2% of its plasma level
FVIII (IU)= (Target FVIII – FVIII Baselines)×BW×0.5unit/kg
1IU/kg of FIX increases 1% of its plasma level
FIX (IU)= (Target FIX- baselines FIX)×BW×1unit/kg
Exp: dose of FVIII needed to increase plasma level to 100% in
70kg person with severe haemophilia : (100-1)×70×0.5=3500IU
Half lifes: FVIII 8-12h / FIX 24h
FFP: in a 70 kg person 1 Unit Plasma increases most
Can cause transient rise in FVIII and VWF but not FIX
Dose not increase FVIII level in severe haemophilia
EACA(ε-amino caproic acid)
Uses in gum and gastrointestinal bleedings and oral surgeries
The formation of alloantibodies to FVIII or FIX is
currently the major complication.
Usually appears early in life median 2 years old.
In these patients a 1:1 mix with normal plasma, aPTT
is abnormally prolonged.
The results expressed in Bethesda Unit(1 BU is amount
of antibody that neutralizes 50% of FVIII or FXI which
presents in normal plasma after 2h incubation 37°C)
BU<5 50-100U/kg FVIII or FIX
BU>10 can use PCC(prothrombin,VII,IX,X)
Infectious Disease & Aging
HCV is the major cause of morbidity and second cause of
mortality in patients exposed to older clotting factors.
Co-infection of HCV and HIV present almost 50% of
Elderly patients have higher rate of severe arthrophaty,
HCV and HIV infections and malignancies related to
HIV&HCV like HCC.
Mortality from coronary artery disease is lower in
haemophilic patients due to hypocoagulability;however it
does not prevent athrogenesis.
Hypertension and chronic renal disease are common