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Hemophilia & von willibrand disease
Dr.Padmashini
objectives
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History
Introduction
Definition
Clinical Features
Diagnosis
Available treatment modalities
History
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Best known of the
hereditary bleeding
disorders.
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First coined by Schonlein in
1820s.
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Originally termed
“Haemorraphilia” i.e. love
for haemorrhages but over
time contracted to
Hemophilia.
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Hemophilia is often called the disease of kings because it was
carried by many members of Europe’s royal family.
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Queen Victoria of England was a carrier of hemophilia
Introduction
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Hemophilia are bleeding disorders due to deficiency or defect
in one of the factor present in clotting cascade,
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X – linked recessive disorder,
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Disease of men with women being asymtomatic carrier
Definition
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Hemophilia A (classic) : deficiency or dysfunction of factor
VIII
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It is a large single chain protein that regulates the activation of
factor X by proteases generated in intrinsic coagulation
pathway
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Incidence : 1 in 10,000males
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Hemophilia B (Christmas) : deficiency or dysfunction of factor
IX
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Incidence : 1 in 25,000-35,000 males
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Von willibrand disease : It is a hereditary deficiency a defect
in portion of factor VIII complex
Types
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Factor level < 1% - severe disease
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Factor level 1-5% - moderate disease
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Factor level 5-20 % - mild disease
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Factor level 20-50% - unaware that they have hemophilia
Clinical features
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Easy bruising & recurrent
bleeding in to joints &
muscles
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Bleeding occurs hrs or days
after injury if untreated
continue for days or weeks
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Large collection of clotted
blood putting pressure on
adjacent normal tissuenecrosis of muscle –
compartment syndrome
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Pseudophlebitis : venous
congestion
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Pseudotumour : bone cysts
result from unresolved
hematoma
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CNS : SDH occur
spontaneously or with
minimal trauma
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Hematuria : common
usually not serious
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Femoral neuropathy due to
pressure from unsuspected
retroperitoneal hematoma
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Mucocutaneous bleeding:
spontaneous bleeding in to
orophraynx , GI tract,
epistaxsis ,hemoptysis,
delayed bleeding after dental
extraction
Hemophilic Arthropathy:
 chronic inflammation.
 Chronic proliferative synovitis
 characterised by progressive and erosive destruction of joint
cartilage, narrowing of joint space
scenario
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A one yr old male baby brought to ER at around 4 pm with
bleeding continously after a small cut in the knee joint while
playing at around 11am on the same day
Lab Investigation
COAGULATION PROFILE
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PT – normal
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aPTT – prolonged
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Factor assay
factor VIII deficiency – hemophilia A
factor IX deficiency – hemophilia B
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Bleeding time - normal
Prenatal diagnosis
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Obtain chorionic villi samples in 10th-11th gestational week
and perform direct genotype testing.
Initial assesment
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Early & complete factor replacement before or at the same
time as other resuscitative & diagnostic maneuvers
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Bleeding in to neck,tongue,retropharynx – airway compromise
– intubation
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Bleeding in to CNS – immediate factor replacement fallowed
by CT scan
Cont..
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Neurologic defecit localize to region with in spinal cord – MRI
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Hemophilic pt with back, thigh, groin, abdominal pain-factor
replacement with imaging
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Hemarthrosis – consult orthopedist for splinting &
rehabilitation
Special attention
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Adequate pain relief with opiods
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Avoid aspirin & NSAID
DONTS
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Central lines should not be placed with out factor replacement
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ABG/ arterial line
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IM injections
Treatment
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Factor replacement therapy
Two different options :
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Plasma derived & purified factor
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Recombinant factor replacement
Hemophilia A
 Human plasma derived factor VIII products
 Human plasma derived factor VII
 Recombinant factor VIII products
 Porcine factor VIII products
Hemophilia B
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Factor IX complex product
Activated factor IX complex product
Purified factor IX product
Recombinant factor IX product
DOSAGE
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Dosing regimen based on clotting factor volume of distribution,
half life of factor & hemostatic level of factor required to control
the bleeding
Hemophilia A
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One unit of factor VIII per Kg of body weight raises plasma
level by approximately0.02U/ml
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Half life – 8-12 hrs
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Dose of FVIII (units) = (percent desired rise in plasma FVIII)
x (body wt) x 0.5
Hemophilia B
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One unit of factor IX per Kg of body weight raise the plasma
level by0.01u/ml
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Half life – 16 hrs
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Dose of factor IX(units)=(percent desired rise in factor IX) X
body weight
FACTOR REPLACEMENT GUIDELINES
Minimum initial factor levels
40-50%
80-100%
50%
100%
30-50%
100%
Undiagnosed bleeding disorder
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FFP or cryoprecipitate
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Each bag cryoprecipitate:
100 units of factor VIII
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FFP – all plasma clotting
factor ,concentration of
1u/ml
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One unit FFP – raise factor
level 3-5 %
Cryoprecipitate
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Prepared by slowly thawing fresh frozen plasma at 2-4`C, then
harvesting the precipitate by centrifugation.
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Cryo prepared from 200ml of FFP contains 80-100 U of FVIII,
~250mg fibrinogen and useful amounts of FXIII and vWF per
10-15ml of precipitate.
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Use thawed cryo within 4hr.
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Can be stored at -18`C for 1yr.
scenario
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A 10 yr old girl weighing 20kg a known case of haemophilia B
came to ER with complaints of profuse gum bleeding after
brushing her teeth
Specific problems
Oral & mucosal bleeding :
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Area identified, cleaned of
inadequate clot & dry
topical thrombin placed at
bleeding site
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Factor replacement should
be 80-100 %
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Antifibrinolytic agent( epsolin aminocarporic acid &
tranexamic acid)
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Dose of EACA – 75-100 mg/kg q 6 h (children)
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1-6 g q 6 h for adults
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Given PO /IV
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Tranexamic acid
 oral- 25 mg/kg/dose
every 6-8hr.
 iv - 10 mg/kg/dose
every 6-8hr
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Topical hemostatic agent –
microfibrillar collagen
hemostat,thrombin &
absorbable gelatin sponges
scenario
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A 25 yr old gentleman who is diagnosed as having
haemophilic A 10 yrs ago, with factor level of 25% admited in
the hospital for severe AGE,while securing I.V cannula pt had
continous bleeding from the vene puncture site
Mild hemophilia A
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Treated with desmopressin
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Desmopressin cause release
of Vwf from endothelial site
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Inc amount of Vwf capable
of carrying additional
amount of factor VIII in
plasma
Dose
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Intravenous: 0.3 ug/kg ( max 20 ug) over 30 min
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Intra nasal : children > 5 yrs single spray in single nostril (150
ug total dose)
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Adults & adolescent 300 ug total dose
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Third dose – inc factor by 2-3 times
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Repeated 8-12 hrs
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Pts stores of factor VIII will be depleted & subsequently effect
will be less
Scenario
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A 7yr old boy who is an haemophilic came to ER with
complains of tooth ache O/E pt was having caries tooth,for
which dentist has adviced tooth extraction
Dental procedure
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Filling carries tooth : single
infusion of factor VIII with
administration of 4-6 g of
EACA q6h for 3-4 days
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Major oral & periodontal
surgery , extraction of
permanent teeth – factor
replacement begin before
surgery & continue for 2-3
days
Inhibitors
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Usually IgG antibodies that rapidly neutralize factor VIII
activity
Two types :
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Type 1 – raise their antibody fallowing exposure to factor VIII
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Type 2 – low antibody titre not stimulated by factor VIII
infusion
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Type 1 – should not receive factor VIII
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Control of bleeding – porcine factor VIII
-prothrombin complex concentrate
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Type 2 – respond to higher doses of factor VIII
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Gene therapy –Involves transfer of genes that express a
particular gene product into human cells
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studies in human under trial
Complication
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Multiple episodes of hepatitis
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Elevated hepatocellular enzyme level
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Hepatospleenomegaly
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End stage liver disease
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Iv drug abusers & long term hemophilia – high risk for AIDS
Von willibrand disease
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It is a hereditary deficiency a defect in portion of factor VIII
complex
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vWF is a glycoprotien ,synthesized, stored & then secreted by
vascular endothelial cells
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Co factor for platelet adhesion & carrier protien for factor VIII
Major three groups
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Type 1 : common & partial quantitiative disease
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Type 2 : qualitative ( abnormal function)
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Type 3 : severe & almost compelete defeciency of vWF
Clinical features
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Skin & mucosal bleeding
Recurrent epistaxsis,gingival bleeding
Unusual bruising
GI bleeding
Menorrhagia in young women
Laboratory test
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Prolonged bleeding time
Low or normal vWF antigen
Low vWF activity
Mildly prolonged aPTT
Pt with O bld group – 30 % reduction in vWF level compared
to other bld groups
Treatment
Non transfusional therapy :
 Desmopressin – mainstay of treatment with type 1 vWF
 It induces release of vWF from storage site with in the
endothelium
 Dose
Transfusional therapies
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Plasma derivatives
Cryoprecipitate
Humate p
Platlelet transfusion
Prevention of bleeding
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Avoid trauma by adjusting
their lifestyle.
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Contact sports should be
avoided, but swimming and
cycling with appropriate
gear should be encouraged.
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Avoid use of drugs that
affect platelet function viz.
NSAIDs.
What medical information should be carried by a
hemophiliac ?
A person with hemophilia should carry
information about his health, including
the type of hemophilia, treatment
needed, and allergies.
An international medical card is
available free through the World
Federation of Hemophilia. Tags called
Medic-Alert and Talisman are sold in
some countries
World Hemophilia Day 2009
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Since 1989, patient groups and treatment centres have been
coming together on April 17 to celebrate World Hemophilia
Day.
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The theme for World Hemophilia Day 2009 is “Together, we
care,” which emphasizes the importance of comprehensive
care in hemophilia healthcare delivery.
Take home message
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Early & complete factor replacement
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Do not waste time in imaging studies
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Prevention of bleeding
The Sun is Rising for Patients with Hemophilia
The Future is Bright
Thank you