Factor XIII Case Studies

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Factor XIIICase Studies

• Mary Edgar
• Haemophilia Nurse Specialist
• Bristol Haemophilia Centre, UK

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Factor XIII Deficiency

• Last enzyme to be activated in clotting process
• Clots formed but not stabilised
• Autosomal recessive inheritance
• Very rare 11-3 million people
• More prevalent in countries where consanguineous
  marriages are common

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The global distribution of consanguineous marriage
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Clinical Manifestations

• Severe bleeding tendency
• Soft tissue bleeding umbilical cord and CNS
• Mucosal bleeding
• Miscarriages
• Delayed bleeding after trauma

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J Thromb Haem 2004
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Bristol Haemophilia Centre

• Cohort of 5 patients (44 in UK)
• Patient care provided by multidisciplinary team
• Laboratory FXIII assays record levels as
• lt or gt 2 and lt or gt 10
• No data available to inform best practice

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Case Study 1

• Married woman aged 53
• No family history
• History of profuse umbilical cord and post
  tonsillectomy bleeding
• Diagnosed aged 11
• Miscarriages and 2 stillbirths
• 2 daughters not affected

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Clinical Presentation and Management

• 1987 Intracerebral bleed (aged 34 years)
• L sided weakness, parasthesia and epilepsy
• Commenced 2 weekly FFP prophylaxis
• 1988 CNS rebleed (had FFP week before)
• Physiotherapy
• July 1988 Commenced 4 weekly factor XIII
  prophylaxis

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• FACTOR XIII CONCENTRATE
• Plasma derived
• Virally inactivated
• Dose 10 U/Kg
• Half life 7- 10 days
• Re-treat when clot lysis assay shows FXIII
  activity lt10

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Current Condition and Management

• Small residual hemiplegia/dysarthria but no
  epilepsy
• Prone to tiredness and migraines
• Otherwise well
• Reviewed and monitored 6 monthly
• FXIII dose adjusted as necessary
• Stable on FXIII prophylaxis for 17 years
• FXIII given by family doctor

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Case Study 2

• 22 year old girl. 3 brothers, 2 sisters
• 1 brother and 1 sister also affected
• Diagnosed soon after birth with umbilical stump
  bleeding
• 1st patient in UK to be treated with FXIII
  concentrate
• Commenced monthly FXIII prophylaxis

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Challenge Faced by Centre

• Age 19 years became pregnant
• Thought she couldnt get pregnant because FXIII
  deficiency associated with poor implantation!
• Transferred to Adult Centre
• On 4 weekly FXIII prophylaxis 750iu
• No data available re pharmacokinetics and
  pregnancy

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Prophylaxis Regime

• FXIII levels monitored weekly
• Aim to keep FXIII above 10
• At 20 weeks FXIII increased to 1000iu every 4
  weeks
• At 24 weeks FXIII increased to 1000iu every 3
  weeks

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Maternal Management Plan

• Anticipate vaginal delivery
• Use Fentanyl PCA if Entonox not enough
• Avoid epidural analgesia and forceps delivery
• Caesarian section if necessary
• To be given bolus infusion FXIII if no
  prophylaxis in previous 5 days

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Outcome!

• February 04 - normal delivery 2 weeks before EDD
• Healthy baby boy not affected
• No post partum bleeding
• October 05 FXIII prophylaxis increased to
  1250iu 4 weekly because of weight gain
• Now self- treating at home

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Case Study 3

• 7 year old boy
• 23rd March 05
  Fell onto back while playing on
  patio
• 27th March 05
  Difficulty walking/passing urine
• Poor bowel control
• Evidence of UTI
• Prescribed oral antibiotics by family doctor

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28th March 2005

• Assessed at District Hospital
• Urinary retention
• Neurological signs in legs
• Transferred to specialist neurology unit
• ? Non accidental injury
• Referred to Social Services
• Urgent MRI scan

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Clinical Management

• Extradural haematoma found
• 1st April 2005
  Surgical drainage of
  extradural haematoma
• 4th April 2005
  Surgical exploration because
  re-accumulation of haematoma
• 6th April 2005
  Second surgical exploration
  
  

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3 Weeks Post Injury

• Faecal and urinary incontinence
• Catheterisation
• Supra-pubic catheter inserted
• Abnormal wound bleeding noted
• Referred to Haematologist
• FXIII assay performed

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Haemostasis Assessment and Management

• FXIII lt 2
• No family history
• Easy bruising
• 18th April 2005 (26 days post injury)
• First infusion Factor XIII 750 iu given
• 4 weekly FXIII prophylaxis regime commenced

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1 Year Later

• Monthly FXIII prophylaxis 750iu
• Regular haemophilia/neurology review
• Self-catheterises daily
• Uses laxatives and suppositories to control
  faecal incontinence
• Walks on toes when he is tired
• Condition stable
• Coming to terms with diagnosis

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What have we learnt?

• Importance of early diagnosis, monitoring and
  regular review
• Importance of FXIII prophylaxis to prevent
  bleeding
• Need for data and research to inform best
  practice
• Need to share experience and expertise