Known patients with inherited bleeding disorder

• Ask patient for medical card identifying their condition and severity
• Contact haematology immediately even if no treatment deemed necessary
• Unless major trauma/head injury, send patient to haematology emergency admissions

Inherited bleeding disorders

• Factor VIII deficiency (Haemophilia A)
• Factor IX deficiency (Haemophilia B)
• Factor XI deficiency (Haemophilia C)
• von Willebrand factor deficiency (vW disease)
• Hereditary intrinsic platelet defects (rare)
• Deficiency of other coagulation factors (rare)

Haemophilia A and B

Severity

• Baseline plasma concentration of Factor VIII/IX as % of normal:
• mild (6-40%): muscle and joint bleeds, usually following trauma
• moderate (1-5%): muscle and joint bleeds, usually following trauma
• severe (<1%): spontaneous joint and muscle bleeds

Presentation

• X-linked inheritance occurring almost exclusively in men
• rarely female haemophilia carrier may have mild bleeding
• Most patients present with muscle or joint bleeds
• Minor bleeds usually present with
• pain and slight restriction of movement
• minimal or no joint swelling
• Major bleeds present with:
• severe pain/tenderness
• marked swelling and restriction of movements of the joint
• Head injury or suspected intracranial bleed
• administer appropriate factor concentrate immediately
• arrange urgent CT scan of head
• Do not wait for scan before starting treatment
• Other bleeding manifestations (e.g. GI bleeding, haematuria) usually associated with an underlying pathology
• Be alert for a major bleed into psoas muscle
• symptoms include pain in groin, abdomen or lower spine, hip in flexion, inability to sit, stand, weight bear or lie straight, numbness, paraesthesia over thigh region

von Willebrand's disease

• Affects men and women
• Usually presents with:
• mucocutaneous bleeding
• frequent and prolonged epistaxis
• menorrhagia
• easy bruising

• Treat all bleeds without delay
• call blood bank for factor preparations
• ask to process urgently
• Treatment of significant bleeds usually involves administration of clotting factors/desmopressin:
• in Haemophilia A: recombinant Factor VIII (Advate® or Elocta®) given as slow IV bolus or desmopressin given SC or IV infusion over 20 min
• in Haemophilia B: recombinant Factor IX (Benefix® or Alprolix®) given as slow IV bolus
• in von Willebrand’s disease: Desmopressin or vW factor concentrate (Voncento® or Veyvondi®) given as slow IV bolus
• Avoid aspirin or non-steroidal anti-inflammatory drugs for analgesia

Haemophilia A

Minor muscle or joint bleed

• In mild/moderate Haemophilia A, consider desmopressin
  
  • if patient has baseline Factor VIII >10% and is aged 2-65 yr with no history of hypertension or ischaemic heart disease, give desmopressin 0.3 microgram/kg either SC (preferable as no need for cannulation) or IV in 50 mL sodium chloride 0.9% over 20 min (warn patient that flushing and headache may occur and advise to restrict fluid intake to 1 L during next 24 hr) 
    
    
    

    Desmopressin is available in 15 microgram/mL vials for SC administration
  • if patient does not meet these criteria, give Factor VIII concentrate to raise Factor VIII to 30–50%
• In severe Haemophilia A, give Factor VIII concentrate to raise factor percentage to 30–50%, usually by single injection, not suitable for desmopressin

Major muscle/joint bleed

• Admit patient and inform on-call haematology consultant/SpR
• In Haemophilia A of any severity, give Factor VIII concentrate to raise factor level to 80-100%
• Rest joint for at least 1 day, prescribe appropriate analgesia
• Do not administer IM injections
• Check for neurological deficit
• femoral nerve in a psoas bleed
• median nerve compression in carpal tunnel with a forearm bleed

Head injury or suspected intracranial bleed

• Admit patient and inform on-call haematology consultant/SpR
• In Haemophilia A of any severity, give Factor VIII concentrate immediately to raise factor level to 80-100%
• administer appropriate Factor VIII concentrate immediately
• arrange urgent CT scan of head
• Do not wait for scan before starting treatment

Further therapy

• Monitor factor level with advice from haematology team
• Repeated doses of Factor VIII concentrate may be required at 12-24 hrly intervals

Haemophilia B

• Desmopressin has no role in treating Haemophilia B

Minor muscle or joint bleeds

• Give Factor IX concentrate to raise level to 30-50%

Major muscle/joint bleeds or head injuries

• Admit patient and inform on-call haematology consultant/SpR
• In Haemophilia B of any severity, give Factor IX concentrate (Benefix® or Alprolix®) to raise level to 50-80%
• factor IX level higher than 80% is a risk for venous thrombosis
• Rest joint for at least 1 day and prescribe appropriate analgesia
• Check for neurological deficit
• femoral nerve in a psoas bleed
• median nerve compression in carpal tunnel with a forearm bleed

Head injury or suspected intracranial bleed

• Admit patient and inform on-call haematology consultant/SpR
• In Haemophilia B of any severity, give Factor IX concentrate immediately to raise level to 50-80%,
  • factor IX level higher than 80% is a risk for venous thrombosis
• Arrange urgent CT scan of head
• Do not wait for scan before starting treatment

Further therapy

• Monitor factor level with advice from haematology team
• Repeated doses of Factor IX concentrate may be required once daily

Patients with von Willebrand’s disease or hereditary platelet disorders

• Discuss with on-call haematology consultant/SpR
• Use local measures to stop bleeding (e.g. nasal packing, etc)
• Give tranexamic acid 1 g oral 8-hrly

Other treatment

• Patients with type 1 disease usually respond well to desmopressin but non-responders will require treatment with von Willebrand’s factor concentrate 
• Consider desmopressin. If patient aged 2-65 yr with no history of hypertension or ischaemic heart disease, give desmopressin 0.3 microgram/kg SC (preferable to IV as no need to cannulate) or IV in 50 mL sodium chloride 0.9% over 20 min (see warning box above)
• Warn patient that flushing and headache may occur and advise to restrict fluid intake to 1 L during next 24 hr
• Patients with type 2 and 3 disease require vW factor concentrate

Patients with other coagulation factor deficiencies or other bleeding manifestations

• Contact on-call haematology consultant/SpR

• Coagulation factor concentrates are available from hospital blood bank
• Before initiating treatment, discuss management with on-call haematology consultant/SpR to decide:
• factor concentrate required, dose, frequency and duration of treatment
• monitoring of pre- and post-infusion percentages (if required)
• Document use of any factor concentrate (including dose and time given) on treatment chart
• If patient admitted, monitor carefully to ensure bleeding has stopped

Calculation of factor dose

• Give individual patient same brand of concentrate each time treatment is required
• information in medical record or in blood bank

Step 1: calculate factor increment required (%)

• Factor increment required = desired factor level - baseline factor level of patient

Step 2: calculate dose of specific factor required

• For Factor VIII concentrates (Advate^® or Elocta^®)
• dose required (in units) = body weight (kg) × factor increment required × 0.5
• For Factor IX concentrate (Benefix^®, Alprolix^®)
• dose required (in units) = body weight (kg) × factor increment increase required x 1.2
• For vW Factor concentrate (Voncento^®, Veyvondi^®)
• Dose required (in RIC units) = 40-80 units (RIC activity) × body weight (kg)
• RIC = Ristocetin co-factor activity

Administration

Reconstitution of factor concentrate

• Check dosage of factor to be given
• order appropriate factor concentrate from main blood bank
• Most factor concentrates are provided in packs with:
• concentrate powder
• diluent in syringe
• vial adapter for transfer of diluent
• infusion set
• Read instructions carefully before reconstituting factor
• a clear step by step guide is in each package
• incorrect reconstitution may result in wastage of expensive concentrate
• If in doubt, seek advice from haematology nurses or haemophilia nurse specialist

Drawing up

• Transfer diluent into dried concentrate vial via a needleless adapter
• Ensure no concentrate remains undissolved
• Draw up concentrate into a syringe

Administering

• Administer concentrate via IV cannula as a slow bolus, flush cannula with normal saline
• remove cannula at the time of discharge
• Record dose administered and date and time in patient notes and treatment chart
• Return any unused concentrate (even if pack opened) to hospital blood bank

Post administration

• Observe patient after administration for 30 min
• Discard all used bottles and needles into sharps bin
• Record dose administered and date and time in patient notes and treatment chart
• Return any unused concentrate (even if pack opened) to hospital blood bank

Allergic reactions

• Uncommon
• more common to react to factor IX
• If reaction occurs, treat with chlorphenamine +/- hydrocortisone

• Inform haemophilia nurse specialist
• all bleeding disorder patients admitted with a bleed will be reviewed by haematology team the following working day
• Remove cannula