Hemophilia

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Hemophilia von willibrand disease

• Dr.Padmashini

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objectives

• History
• Introduction
• Definition
• Clinical Features
• Diagnosis
• Available treatment modalities

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History

• Best known of the hereditary bleeding disorders.
• First coined by Schonlein in 1820s.
• 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
  Europes royal family.
• Queen Victoria of England was a carrier of
  hemophilia

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Introduction

• Hemophilia are bleeding disorders due to
  deficiency or defect in one of the factor present
  in clotting cascade,
• X linked recessive disorder,
• Disease of men with women being asymtomatic
  carrier

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Definition

• Hemophilia A (classic) deficiency or
  dysfunction of factor VIII
• It is a large single chain protein that regulates
  the activation of factor X by proteases generated
  in intrinsic coagulation pathway
• Incidence 1 in 10,000males

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• Hemophilia B (Christmas) deficiency or
  dysfunction of factor IX
• Incidence 1 in 25,000-35,000 males
• Von willibrand disease It is a hereditary
  deficiency a defect in portion of factor VIII
  complex

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Types

• Factor level lt 1 - severe disease
• Factor level 1-5 - moderate disease
• Factor level 5-20 - mild disease
• Factor level 20-50 - unaware that they have
  hemophilia

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Clinical features

• Easy bruising recurrent bleeding in to joints
  muscles
• 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 tissue-necrosis of
  muscle compartment syndrome

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• Pseudophlebitis venous congestion
• Pseudotumour bone cysts result from unresolved
  hematoma

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• CNS SDH occur spontaneously or with minimal
  trauma
• Hematuria common usually not serious
• 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

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• Hemophilic Arthropathy
• chronic inflammation.
• Chronic proliferative synovitis
• characterised by progressive and erosive
  destruction of joint cartilage, narrowing of
  joint space

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scenario

• 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

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Lab Investigation

• COAGULATION PROFILE
• PT normal
• aPTT prolonged
• Factor assay
• factor VIII deficiency hemophilia A
• factor IX deficiency hemophilia B
• Bleeding time - normal

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Prenatal diagnosis

• Obtain chorionic villi samples in 10th-11th
  gestational week and perform direct genotype
  testing.

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Initial assesment

• Early complete factor replacement before or at
  the same time as other resuscitative diagnostic
  maneuvers
• Bleeding in to neck,tongue,retropharynx airway
  compromise intubation
• Bleeding in to CNS immediate factor replacement
  fallowed by CT scan

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Cont..

• Neurologic defecit localize to region with in
  spinal cord MRI
• Hemophilic pt with back, thigh, groin, abdominal
  pain-factor replacement with imaging
• Hemarthrosis consult orthopedist for splinting
  rehabilitation

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Special attention

• Adequate pain relief with opiods
• Avoid aspirin NSAID
• DONTS
• Central lines should not be placed with out
  factor replacement
• ABG/ arterial line
• IM injections

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Treatment

• Factor replacement therapy
• Two different options
• Plasma derived purified factor
• Recombinant factor replacement

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• Hemophilia A
• Human plasma derived factor VIII products
• Human plasma derived factor VII
• Recombinant factor VIII products
• Porcine factor VIII products

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Hemophilia B

• Factor IX complex product
• Activated factor IX complex product
• Purified factor IX product
• Recombinant factor IX product

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DOSAGE

• Dosing regimen based on clotting factor volume of
  distribution,
• half life of factor hemostatic level of
  factor required to control
• the bleeding

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Hemophilia A

• One unit of factor VIII per Kg of body weight
  raises plasma level by approximately0.02U/ml
• Half life 8-12 hrs
• Dose of FVIII (units) (percent desired rise in
  plasma FVIII) x (body wt) x 0.5

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Hemophilia B

• One unit of factor IX per Kg of body weight raise
  the plasma level by0.01u/ml
• Half life 16 hrs
• Dose of factor IX(units)(percent desired rise in
  factor IX) X body weight

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• FACTOR REPLACEMENT GUIDELINES

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Minimum initial factor levels

• 40-50
  80-100
• 50
  100
• 30-50
  100

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Undiagnosed bleeding disorder

• FFP or cryoprecipitate
• Each bag cryoprecipitate
• 100 units of factor VIII
• FFP all plasma clotting factor ,concentration
  of 1u/ml
• One unit FFP raise factor level 3-5

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Cryoprecipitate

• Prepared by slowly thawing fresh frozen plasma at
  2-4C, then harvesting the precipitate by
  centrifugation.
• 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.
• Use thawed cryo within 4hr.
• Can be stored at -18C for 1yr.

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scenario

• 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

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Specific problems

• Oral mucosal bleeding
• Area identified, cleaned of inadequate clot dry
  topical thrombin placed at bleeding site
• Factor replacement should be 80-100

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• Antifibrinolytic agent( epsolin aminocarporic
  acid tranexamic acid)
• Dose of EACA 75-100 mg/kg q 6 h (children)
• 1-6 g q 6 h for adults
• 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
• Topical hemostatic agent microfibrillar
  collagen hemostat,thrombin absorbable gelatin
  sponges

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scenario

• 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

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Mild hemophilia A

• Treated with desmopressin
• Desmopressin cause release of Vwf from
  endothelial site
• Inc amount of Vwf capable of carrying additional
  amount of factor VIII in plasma

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Dose

• Intravenous 0.3 ug/kg ( max 20 ug) over 30 min
• Intra nasal children gt 5 yrs single spray in
  single nostril (150 ug total dose)
• Adults adolescent 300 ug total dose

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• Third dose inc factor by 2-3 times
• Repeated 8-12 hrs
• Pts stores of factor VIII will be depleted
  subsequently effect will be less

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Scenario

• 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

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Dental procedure

• Filling carries tooth single infusion of factor
  VIII with administration of 4-6 g of EACA q6h
  for 3-4 days
• Major oral periodontal surgery , extraction of
  permanent teeth factor replacement begin before
  surgery continue for 2-3 days

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Inhibitors

• Usually IgG antibodies that rapidly neutralize
  factor VIII activity
• Two types
• Type 1 raise their antibody fallowing exposure
  to factor VIII
• Type 2 low antibody titre not stimulated by
  factor VIII infusion

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• Type 1 should not receive factor VIII
• Control of bleeding porcine factor VIII
• -prothrombin complex concentrate
• 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
• studies in human under trial

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Complication

• Multiple episodes of hepatitis
• Elevated hepatocellular enzyme level
• Hepatospleenomegaly
• End stage liver disease
• Iv drug abusers long term hemophilia high
  risk for AIDS

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Von willibrand disease

• It is a hereditary deficiency a defect in portion
  of factor VIII complex
• vWF is a glycoprotien ,synthesized, stored then
  secreted by vascular endothelial cells
• Co factor for platelet adhesion carrier protien
  for factor VIII

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Major three groups

• Type 1 common partial quantitiative disease
• Type 2 qualitative ( abnormal function)
• Type 3 severe almost compelete defeciency of
  vWF

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Clinical features

• Skin mucosal bleeding
• Recurrent epistaxsis,gingival bleeding
• Unusual bruising
• GI bleeding
• Menorrhagia in young women

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Laboratory test

• 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

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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

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Transfusional therapies

• Plasma derivatives
• Cryoprecipitate
• Humate p
• Platlelet transfusion

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Prevention of bleeding

• Avoid trauma by adjusting their lifestyle.
• Contact sports should be avoided, but swimming
  and cycling with appropriate gear should be
  encouraged.
• Avoid use of drugs that affect platelet function
  viz. NSAIDs.

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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

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World Hemophilia Day 2009 

• Since 1989, patient groups and treatment
  centres have been coming together on April 17 to
  celebrate World Hemophilia Day.
• The theme for World Hemophilia Day 2009 is
  Together, we care, which emphasizes the
  importance of comprehensive care in hemophilia
  healthcare delivery.

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Take home message

• Early complete factor replacement
• Do not waste time in imaging studies
• Prevention of bleeding

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The Sun is Rising for Patients with Hemophilia

The Future is Bright
you
Thank