Paediatric Coagulopathy

Haemophilia

• Haemophilia A and B are X-linked recessive disorders in 70% and spontaneous gene mutations in 30% of cases
• Haemophilia A = Factor VIII deficiency
• Haemophilia B = Factor IX deficiency (Christmas disease)
• Bleeding may be spontaneous or traumatic
• Most neonates are born without significant bleeding
• Typically bleeding into joints and soft tissues vs. mucosal (platelets)

• Presentation
  • Mild disease: >5% factor levels. Bleeding with major trauma/surgery
  • Moderate: 1-5% factor levels. Bleed after minor injury. May have joint bleeds. 
  • Severe: <1% factor levels. Frequent bleeding into joints/muscles. Spontaneous or minor trauma
• Consider ICH, retroperitoneal haemorrhage (may mimic appendicitis) and soft tissue haemorrhage in head/neck can occlude airway due to swelling
• GI bleeding is uncommon
• Investigations
  • Prolonged APTT, Normal PT and normal platelets

• Treatment
  • Do not delay clotting factor replacement for imaging
  • Recombinant factor concentrates are preferred to plasma-derived concentrates
  • May be prophylactic or therapeutic
  • Prophylactic factor replacement 2-3x/week with topups for any breakthrough bleeds have dramatically reduced bleeding episodes
  • Factor VIII half-life: 8-12 hours (more regular dosing schedule)
  • Factor IX half-life: 24 hours 
  • Dosing depends on weight, severity, location of bleed, previous bleeds at site and presence of inhibitors
  • Desmopressin can be used for mild Haemophilia A (raises Factor VIII levels for several hours)
  • FFP or cryoprecipitate can be used in emergencies if no concentrates available

• Inhibitors
  • Alloantibodies that develop against clotting factors
  • Present in 10-20% of Haemophilia A and 3-5% of Haemophilia B
    • Up to 50% of Haemophilia B patients with inhibitors can suffer anaphylaxis in response to Factor IX delivery
  • Means more concentrate required
  • Alternatives include FEIBA-NF (II and Xa), prothrombin complex and Factor VIIa
  • Immune tolerance therapy may reduce inhibitors through development of neutralising anti-inhibitor antibodies

• Bleeds requiring admission
  • Suspected ICH
  • Bleeding into neck/throat
  • Forearm/calf bleed with suspicion of compartment syndrome
  • Bleeding into hip or inguinal area, suspected iliopsoas haemorrhage
  • Undiagnosed abdominal pain
  • Persistent haematuria
  • Bleeds causing severe pain
• General measures (PRICE)
  • Protection of area: Splint, immobilise
  • RICE

• Venous access
  • Major fear and stressor for children and families with haemophilia
  • Distraction, relaxation techniques and nitrous sedation
  • Ask parents re: preferred methods
  • Remember at risk of venepuncture bleeding
  • Apply pressure for at least 3 minutes post-venepuncture
• Analgesia
  • Avoid NSAID’s
• Tranexamic acid
  • Used for treating and preventing mouth bleeds and epistaxis
  • Contraindicated for haematuria
  • 25mg/kg/dose TDS PO for 5-7 days
• Follow-up
  • Haemophilia clinic and physio post-joint/muscle bleed is mandatory
  • Immobilise for 48 hours

Von Willebrand disease

• Commonest inherited disorder of coagulation
• 1% of population though only a minority will present with significant bleeding
• Autosomal dominant in most cases
• vWF
  • Facilitates platelet adherence to vascular endothelium by enabling a platelet plug to form
  • Carrier protein for factor VIII
• Presentation
  • Mucosal and cutaneous bleeding
  • Prolonged bleeding after trauma/surgery
  • Bruising and bleeding out of proportion to injury
  • 10-20% of adolescents with menorrhagia and 15% of children with recurrent epistaxis

• Type 1:
  • 60-80% of cases
  • Partial quantitative deficiency of vWF
• Type 2 (A, B, M and N)
  • Qualitative defects in vWF
  • Moderate to severe bleeding
  • Desmopressin fails due to qualitative defect and contraindicated in type 2B as may cause thrombocytopaenia and worsened bleeding
• Type 3
  • Quantiative deficiency of vWF and decreased factor VIII activity
  • Desmopressin causes no rise in vWF

• Investigations
  • Coag screen may be normal
  • vWF assay
• Treatment
  • Desmopressin
    • Releases Factor VIII from endothelium
    • Will increase vWF 3-5x baseline within 30-60 minutes
    • Contraindicated in Type 2B as may cause thrombocytopaenia and worsened bleeding
  • Plasma-derived Factor VIII contains both vWF and Factor VIII
    • Treatment of choice for Type 2A, 2B and Type 3 vWD
    • Recombinant Factor VIII does not contain vWF and is ineffective
  • Tranexamic acid

Platelet disorders

• Normal 150-400
• Lifespan 5-7 days
• Thrombocytopaenia
  • Significant thrombocytopaenia presents with petechiae, epistaxis, spontaneous bruising and mucosal bleeding
  • Usually bleeding complications only if <50
  • Spontaneous <10
• Qualitative dysfunction
  • Can occur in hepatic failure, renal failure, myeloproliferative disorders, aspirin and rare inherited syndromes
• Thrombocytosis
  • Inflammatory reactions, Kawasaki, malignancy and polycythaemia rubra vera
  • >1000 associated with acute thrombosis or haemorrhage

Idiopathic thrombocytopaenic purpura (ITP)

• Most common platelet disorder in children
• Autoimmune condition with anti-platelet autoantibodies leading to reduced platelet survival (often antibodies absent on testing)
• Peaks in winter with viral infections
• Usually acute in children with <6mo duration (90% – RCH)
• Up to 10-30% will have chronic form >6mo duration
• Presentation
  • Bruising and petechiae (rare oral bleeding, epistaxis, rectal bleeding, haematuria)
  • 3 weeks following viral illness or vaccination
  • No hepatosplenomegaly or lymphadenopathy or pallor
  • Normal blood count and film apart from thrombocytopaenia

• DDx
  • If limp, hepatosplemegaly or lymphadenopathy consider lymphoproliferative disorder or aplastic anaemia
  • Exclude NAI
• Outpatient Management
  • If platelets >20, no bleeding and some patients with platelets <20
  • Need good social situation, unequivocal diagnosis, Paediatric agreement and follow-up guaranteed
  • Avoid contact sports, head injuries, aspirin and other possible interfering drugs until better
  • Weekly platelet count extended to 2-4 weekly once improving
  • School return once platelets >20
  • If >150, d/c from follow-up but warn that recurrence can occur
  • Admit most if platelets <20 (ICH <1% of these patients though)

Treatment

• Consider treatment if bleeding or thrombocytopaenia is severe
• If <20 and asymptomatic – monitor with Paediatric input
• If <20 and significant purpura, mucosal bleeding or other haemorrhage – IVIG (fastest response) and high-dose glucocorticoids (oral prednisolone 2-4mg/kg/day for 2 weeks then taper)
  • Steroids first-line usually
• Can give Anti-D to Rhesus positive children but platelet rise is slower
• Splenectomy if life-threatening haemorrhage or significant bleeding with failure to respond to above
• Consider ICH if ITP and severe headache
• Platelet transfusion only to be used if life-threatening haemorrhage

Chronic ITP

• 10-30% have failure to remit by 6 months
• Spontaneous remission occurs in 2/3 of these
• Chronic course mostly seen in older children, esp. adolescent girls
• Consider rare congenital thrombocytopaenia
• Splenectomy required rarely (70-80% success rate)
• Acute, relapsing ITP
  • Usually precipitated by viral infection
  • Manage as for acute ITP (as long as first episode was uncomplicated)

Last Updated on November 20, 2021 by Andrew Crofton