Haemophilia protocol

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Objectives

The Royal Hospital for Children is the regional centre (West of Scotland) for the management of children with inherited bleeding disorders. The purpose of this protocol is to provide information of the appropriate use of blood products for this patient group.

Scope

Children with haemophilia and other clotting factor deficiencies.

Audience

Clinicians involved in the treatment of children with these conditions, including acute bleeding and surgery.

This SOP will cover:

  • Administrating Factor VII & IX Replacement Products
  • Treatment of Haemophilia A
  • Haemophilia A Patients with a FVIII Inhibitor
  • Treatment of Haemophilia B
  • Treatment of von Willebrand’s Disease
  • Factor XIII Deficiency
  • Factor VII Deficiency
  • Specific Bleeding Situations
  • Products – Sourced from Blood Bank via Trakcare
  • How to Order Factor Replacement Products from Trakcare (Appendix 1)
  • Blood Product Collection (Appendix 2)
Authorised personnel / specific staff competencies

The management of haemophilia patients will be directed by the Consultant or a senior member of the medical team.

the Medical/Nursing team will be responsible for admitting, assessing, investigating and administering treatment, and monitoring response. 

Treatment Products

1. Factor Concentrate:

  • Various products – see individual disorders & products.
  • Extended half life (EHL) factor FVIII and FIX products are now allocated for some patients

 

2. DDAVP (Desmopressin): 

Vials contain 4mcg/ml OR 15mcg/ml (Octim)

  • Administration - subcutaneously or intravenously.
  • Intravenous administration- prescribed amount is added to 50mls 0.9% NaCl and given intravenously over 45-60 mins via butterfly or cannula.
  • Subcutaneous injection - give required amount.

If DDAVP is required on two or more consecutive days, U&E’s and fluid balance should be monitored.

 

3. Anti-fibrinolytic Agents

Tranexamic Acid

Orally 25mg/kg TID

Intravenously 10mg/kg TID 

  • Can be used with factor concentrate/DDAVP
  • Most useful for mucosal bleeding
  • Contraindicated in the presence of haematuria
Haemophilia A

1. Severe/Moderate Haemophilia A:

FVIII replacement with allocated product, ordered via Trakcare (see Appendix 1)

 

2. Mild Haemophilia A:

FVIII replacement with allocated product, ordered via Trakcare (see Appendix 1)

OR

DDAVP - (where a response has been demonstrated)

 

NOTE

Children <2yrs should not receive DDAVP, because of the risk of fluid overload and hyponatraemia. Use allocated factor concentrate.

Children 2-3yrs who require treatment with DDAVP, should be admitted and have their electrolyte and fluid balance monitored for at least 24 hours following DDAVP. Excess fluid intake should be avoided.

 

FVIII Dosing Guidelines:

Factor VIII increase is 2 iu/dl for every iu/kg of FVIII infused.

Required units = body weight (kg) x desired factor VIII:
C rise (iu/dl) x 0.5

(can be less in young children)

DDAVP – 3-5 fold increase of baseline FVIII can be expected

(Individual DDAVP response should be available in or Trakcare)

 

Guidance for patients with Severe/Moderate Haemophilia A

Bleed Site (target)

Haemophilia A

Minor injuries/accidents; (target 40iu/dl)
Soft tissue injuries; Early joint bleeds;
Small muscle bleeds; Lacerations;
Mouth bleeds/dental work

20iu/Kg
(round total to nearest vial size)
Repeat infusions every 12 to 24 hours)
for 1-3 days

Moderate injuries/accidents;
(target 60iu/dl)
Major muscle bleeds; joint bleeds; long
bone #; Haematuria

30iu/Kg
(round total to nearest vial size)
Repeat infusions every 12 to 24 hours)
for 1-3 days

Major bleeds;
(target 80-100iu)
Head injuries or intracranial
haemorrhage; GI tract bleeds;
emergency surgery; naso-pharyngeal
bleeding

40-50iu/Kg
(round total to nearest vial size)
Repeat dose 40-50 iu/kg every 8 to 24
hours

Factor VIII levels should be monitored in the presence of severe bleeding and/or following surgery, (pre dose administration and 15 mins post dose, using coag bottle)

All significant injuries/major bleeds; bleeds that do not settle and any surgical interventions should be discussed with the Consultant in Charge or on-call Consultant Haematologist

Extended half life FVIII (Elocta)

  • First infusion should raise FVIII levels appropriate to the bleed as above
  • Subsequent dosing with EHL products should take into account previous half life studies (see Trakcare care plan & discuss with consultant on call as required)

All significant injuries/major bleeds; bleeds that do not settle and any surgical interventions should be discussed with the Consultant in Charge or on-call Consultant Haematologist

Guidance for Mild Haemophilia A

DDAVP 0.3mcg/KG (Max dose to be given 20mcg/dose)

Bleed Site (target)

Haemophilia A

Minor injuries/accidents; (target 40-50iu/dl)
Soft tissue injuries; Small muscle bleeds; Lacerations; Mouth
bleeds/dental work

0.3mcg/kg either IV or 
Subcutaneously

Moderate injuries/accidents; (target 60-80iu/dl)
major muscle bleeds; joint bleeds; long bone #; Haematuria

0.3mcg/kg either IV or
Subcutaneously
(patients with a poor DDAVP
response may require FVIII)

Major bleeds; (target 80-100iu)
head injuries or intracranial haemorrhage; GI tract bleeds;
emergency surgery; naso-pharyngeal bleeding

Use allocated factor product

For patients requiring FVIII calculate dose based on the baseline FVIII level and target FVIII

Haemophilia A patient with a FVIII Inhibitor

Patients with inhibitors are likely to respond poorly to standard FVIII replacement therapy. Options for treatment are:

  • High dose FVIII or Recombinant FVIIa (Novoseven)
  • Inhibitor patients will have an individual treatment on Trakcare.

Dosing Novoseven (RFVIIA):

1mg, 2mg and 5mg vials are available, doses should be rounded to the nearest whole vial size, where appropriate.

Mild-moderate bleeding/injuries

  • 2-3 injections of 90 mcg per kg administered at 2 hourly intervals
  • If further treatment is required, one additional dose of 90 mcg per kg can be administered

Haemarthrosis/ significant bleeds/injuries

  • One single injection of 270 mcg per kg body weight
  • Subsequent dosing will vary according to the type and severity of bleeding.

Major/unresolved bleeding episodes

  • 90 mcg per kg every 2 hours and should continue until clinical improvement is observed. Dosing can then be extended to 3hourly for 24 hrs, 4hourly for 24 hours.

Invasive procedure/surgery

  • An initial dose of 270 mcg per kg should be given immediately before the intervention.
  • 2 hourly dosing of 90mcg/kg should then proceed for the first 24 - 48 hours depending on the intervention performed and the clinical status of the patient.

All significant injuries/major bleeds; bleeds that do not settle and any surgical interventions should be discussed with the Consultant in Charge or On-call Consultant Haematologist

Haemophilia B

Product: Recombinant FIX as per allocated product

FIX Dosing Guidelines:

Factor IX increase is approximately 1 iu/dl for every 1 iu/kg FIX infused

(often less in young children)

Required units = body weight (kg) x desired factor IX rise (iu/dl)

 

Guidance for Patients with Severe/Moderate Haemophilia B

Bleed Site (target)

Haemophilia B

Minor injuries/accidents;
(target 40iu/dl)
Soft tissue injuries; Small muscle bleeds; Early joint
bleeds; Lacerations; Mouth
bleeds/dental work

40iu/Kg
(round total to nearest vial size)
Repeat every 24 hrs for 1-3 days
until resolved

Moderate injuries/accidents;
(target 60iu/dl)
major muscle bleeds;
established joint bleeds; long bone #; Haematuria

60iu/Kg
(round total to nearest vial size)
Repeat every 24 hrs for 1-3 days
until resolved

Major bleeds;
(target 80-100iu)
head injuries or intracranial haemorrhage; GI tract bleeds;
emergency surgery;
naso-pharyngeal bleeding

80-100iu/Kg
(round total to nearest vial size)
Repeat at least every 24 hrs until
bleeding has resolved

Factor IX levels should be monitored in the presence of severe bleeding and/or following surgery, (pre dose administration and 15 mins post dose, using coag bottle)

All significant injuries/major bleeds; bleeds that do not settle and any surgical interventions should be discussed with the Consultant in Charge or on-call Consultant Haematologist

Extended half life FIX (Alprolix, Idelvion)

First infusion should raise FIX levels appropriate to the bleed as above.

Subsequent dosing with FIX EHL products should take into account previous half life studies (see Trakcare care plan & discuss with consultant as required)

All significant injuries/major bleeds; bleeds that do not settle and any surgical interventions should be discussed with the Consultant in Charge or on-call Consultant Haematologist

Guidance for Mild Haemophilia B

  • Calculate dose based on the baseline FIX level and target FIX

 

Side Effects of FIX Administration

  • Anaphylaxis – which can be an indication of inhibitor development
Treatment of von Willebrand’s Disease

Type I vWD:

  • DDAVP - where a response has been demonstrated
    (see previous dosing guidelines)

Type II vWD:

  • DDAVP - where a response has been demonstrated
  • Patients <2yrs should not be given DDAVP, because of the associated risk of fluid overload and hyponatraemia. These patients should receive
    • FVIII/vWF Voncento.
  • Patients 2-3yrs who require treatment with DDAVP (where a response has been demonstrated), should be admitted and have their electrolyte and fluid balance monitored for at least 24 hours following DDAVP. Excess fluid intake should be avoided.

Type IIB vWD:

  • Voncento (pdFVIII/vWF) (DDAVP is usually contraindicated in this sub-type of vWD)

Type III von Willebrand’s Disease:

  • Voncento (pdFVIII/vWF)

Voncento (pdFVIII/vWF) dosing for Type I, II & III vWD

Dosing will depend on the baseline FVIII & vWF levels and the desired increase (see Trakcare for baseline levels)

Generally, 1 IU/kg VWF:RCo raises the circulating level of VWF:RCo by 0.02 IU/ml (2 %).
Levels of VWF:RCo of > 0.6 IU/ml (60 %) and of FVIII:C of > 0.4 IU/ml (40 %) should be achieved

On-demand treatment

Usually 40 - 80 IU/kg of von Willebrand factor (VWF:RCo) corresponding to 20 - 40 IU FVIII:C/kg of body weight (BW) are recommended to achieve haemostasis.

An initial dose of 80 IU/kg VWF:RCo may be required, especially in patients with type 3 VWD where maintenance of adequate levels may require greater doses than in other types of VWD.
Repeat dosing may be administered every 12-24 hours.

Voncento should be clearly prescribed in vWF:RCo units

FVIII & vWF activity levels should be monitored in the presence of severe bleeding and/or following surgery, (pre dose administration and 15 mins post dose, using coag sample).

All significant injuries/major bleeds; bleeds that do not settle and any surgical interventions should be discussed with the Consultant in Charge or on-call Consultant Haematologist

Factor XIII Deficiency

Fibrogammin 250/1250 IU

Dosage

The dosing regimen should be individualised based on body weight, laboratory values, and the patient's clinical condition.

Routine prophylaxis dosing schedule for treatment of congenital FXIII deficiency

Initial dose

40 International Units (IU) per kg body weight

Subsequent dosing

  • Dosing should be guided by the most recent trough FXIII activity level, with dosing every 28 days (4 weeks) to maintain a trough FXIII activity level of approximately 5 to 20%.
  • Recommended dosing adjustments of ± 5 IU per kg should be based on trough FXIII activity levels as shown in Table 1 and the patient's clinical condition.
  • Dosing adjustments should be made on the basis of a specific, sensitive assay used to determine FXIII levels.

An example of dose adjustment using the standard Berichrom® FXIII activity assay is outlined in Table 1 below.

Table 1: Dose adjustment using the Berichrom® FXIII activity assay

Factor XIII Activity Trough Level (%)

Dosage Change

One trough level of <5%

Increase by 5 units per kg

Trough level of 5% to 20%

No change

Two trough levels of >20%

Decrease by 5 units per kg

One trough level of >25%

Decrease by 5 units per kg

Prophylaxis prior to surgery

After the patient's last routine prophylactic dose, if a surgery is scheduled:

  • Between 21 and 28 days later – administer the patient's full prophylaxis dose immediately prior to surgery and the next prophylactic dose should be given 28 days later.
  • Between 8 and 21 days later – an additional dose (full or partial) may be administered prior to surgery. The dose should be guided by the patient's FXIII activity levels and clinical condition and should be adjusted according to the half-life of Fibrogammin.
  • Within 7 days of last dose – additional dosing may not be needed.
Factor VII Deficiency

Recombinant FVIIa (Novoseven):

Dose, dose range and dose interval

The recommended dose range in adults and children for treatment of bleeding episodes and for the prevention of bleeding in patients undergoing surgery or invasive procedures is 15 – 30 µg per kg body weight every 4 – 6 hours until haemostasis is achieved. Dose and frequency of injections should be adapted to each individual.

1mg 2mg 5mg vials available

  • Doses for FVII deficient patients should be prescribed as per dosing recommendations and NOT rounded to nearest whole vial size.
  • Novoseven can be kept refrigerated following re-constitution and be used for multi dosing from a single vial for 24 hours.
  • Novoseven is given by slow intravenous bolus injection either via butterfly, cannula or port-a-cath.

Patients with major/severe bleeds and head injuries should be admitted to hospital for factor level monitoring and subsequent factor dosing.

Following severe bleeds/injuries/some surgical interventions factor level monitoring is necessary; immediately Pre & 15mins post dose, factor levels are required (coag sample).

Specific Bleeding Situations

Haemarthrosis

IF IN DOUBT TREAT

  • FVIII replacement may be required 12 hourly in a major joint bleed for first 24-48 hrs.
  • Rest/elevate, where possible, the affected joint.
  • Joint bleeds can be painful, analgesia should be advised/prescribed (aspirin containing products and NSAID's should not be prescribed)
  • Physio referral for assessment should be made via Trakcare

Head Bumps/Knocks/Head Injuries

IF IN DOUBT TREAT 

  • Often relatively minor with small bumps/swelling on the head/forehead with some bruising, require only 1-2 doses of factor replacement.
  • Children should be admitted for observation if the degree of trauma is significant or uncertain.
  • Skull x-rays, CT scans etc. are not routinely required for minor injuries, but should be arranged promptly in the event of significant trauma or in the presence of symptoms or signs suggestive of intracranial bleeding.
  • Factor levels should be monitored following major head trauma.
  • Head injury guidelines are available in the haemophilia room or A&E dept to give to parents/carers, for those not requiring admission.
  • Small scalp lacerations are usually best sutured or steri-striped, along with a dose of the appropriate factor product +/- tranexamic acid for 3-5 days. This can be carried out in A&E following appropriate factor replacement.

Mouth Bleeds

  • Torn frenulum, bites/cuts to the tongue, can result in the loss of significant amount of blood.
  • Those presenting with an oral bleed >4 hours should have haemoglobin checked.
  • In addition to factor replacement a prescription for Tranexamic acid should be given for 3-5 days for all mouth bleeds for all patient groups.
  • Ensure parents/carers are advised to complete the treatment programme prescribed even if the bleeding has stopped.

Musculoskeletal Bleeds

IF IN DOUBT TREAT

  • Factor replacement is usually required daily for 24-48 hrs.
  • Factor replacement may be required 12 hourly in a major muscle bleed, e.g. Iliopsoas bleed for 24-48hrs, followed by daily treatment for further 2-3 days. 

Soft Tissue Bleeds/Injuries

  • Factor replacement 1-2 days is usually sufficient.

Bleeding at Other Sites

  • Deep cuts/lacerations should be treated as for musculo skeletal bleeds. If suturing is required they should be referred to A&E dept. or surgeons as appropriate following factor replacement.
  • Fractures will require high dose factor replacement prior to any surgical management of the fracture by the orthopaedic team.

Review of Injuries/Bleeds

  • Minor injuries/bleeds do not need to be reviewed the following day if parents/carers are happy that previous similar bleeding episodes have settled with single dose injections.
Products - sourced from Blood bank via Trakcare (see Appendix 1)
  • Kogenate Bayer (rFVIII)
  • Advate (rFVIII)
  • RefactoAF (rFVIII)
  • NovoEight (rFVIII)
  • Elocta (extended half life rFVIII)
  • Fandhi (plasma derived FVIII)
  • FEIBA (Bypassing agent)
  • Novoseven (rFVIIa)
  • Benefix (rFIX)
  • Alprolix (extended half life rFIX)
  • Idelvion (extended half life rFIX)
  • Voncento (pd FVIII/vWF)
  • Fibrogammin (pdFXIII)
  • DDAVP (IV/SC) Ward Fridges/pharmacy
  • Tranexamic Acid Ward level/pharmacy

Reconstituting Factor Products

Most factor replacement products are packaged in 4 sizes:

250 IU          500 IU          1000IU          2000IU

  • Doses are normally prescribed to allow complete vials to be administered.
  • Differing batch numbers and vials sizes can be mixed in the same syringe.
  • Reconstituted factor products should be given within three hours of reconstitution, unless a continuous infusion is being used.
  • Factor products are given by slow intravenous bolus injection either via butterfly, cannula or port-a-cath.
  • Factor products are obtained from blood bank, via the Trakcare system.

Please follow individual product insert/instructions for specific re-constitution guidance

Further Information / Exceptions

For further information contact:

Medical staff (day time only):

Consultants:

Dr E Chalmers
Dr F Pinto

85644
85646

Haematology Registrar:

Page/deg phone

18437
or deg 85645

Out of hours:

On call consultant or registrar

(as per rota)

Nursing Staff (day time only):

Advanced Nurse Practitioner
(Benign Haematology):

Lyn Docherty

84701

Haematology Nurse Specialist: 

Ruth Bissell

84474

 

For Patient Information on Portal/Trakcare - see under care plans:

  • Factor deficiency and level
  • Treatment plan
Appendix 1: How to Order Factor Replacement Products from Trakcare
  1. Select patient from Trakcare
  2. Know which product you need (see care plan)
  3. Select NEW REQUEST
  4. Select Labs Child
  5. Tick Specimen Collection Box
  6. Sub Category- Delete VIROLOGY SPEC and enter BT in box, click on spy glass
  7. Select Blood Transfusion
  8. Item Box - enter OT, click on spy glass
  9. Select Other Products
  10. Add to list
  11. PRIORITY BOX- hit spy glass Select URGENT
  12. Update
  13. Complete the boxes, mandatory where question in bold
  14. Products required- enter name of product and how many units/vials needed, bearing in mind vial sizes
  15. Enter the location that you want factor delivered to
  16. Complete with personnel password.

 

  • The TrakCare request form will print in the lab but you will also have to alert the lab by phone and send a collection card (see Appendix 2)
  • If pod ‘down’ use emergency porter.
  • All requests to treat a bleeding episode/injury should be treated as urgent.
  • To have order delivered YOU MUST page the MLA pg 17262, to request delivery of the product, (you will need the patient CHI number to confirm identity). 
Appendix 2: Blood Product Collection form

If the Blood Product Collection Card is unable to be printed in blood bank then this will have to be completed and sent to the lab.

References

Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia: (4th edition).  Peter W Collins, Elizabeth Chalmers (et al).  British Journal of Haematology (BJH), 2013, 160, 153-170

Guideline for the diagnosis and management of the rare coagulation disorders.  A United Kingdom Haemophilia Centre Doctors’ Organisation guideline on behalf of the British Committee for Standards in Haematology.  Andrew D Mumford, Writing Group Chair & BCSH Task Force Member, Sam Ackroyd, Raza Alikhan, Louise Bowles, Pratima Chowdary, John Grainger, Jason Mainwaring, Mary Mathias and Niamh O’Connell on behalf of the BCSH Committee.  BJH 2014, 167, 304-3326

The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors’ Organisation guideline approved by the British Committee for Standards in Haematology.  Mike A Laffan, Will Lester, James S O’Donnell, Andrew Will, Robert Campbell Tait, Anne Goodeve, Carolyn M Millar and David M Keeling.  BJH 2014, 167, 453-465

The use of enhanced half-life coagulation factor concentrates in routine clinical practice:  guidance from UKHCDO.  P Collins, E Chalmers (et al).  Haemophilia 2016, 22, 487-498

Editorial Information

Last reviewed: 24 April 2018

Next review: 30 April 2020

Author(s): Dr E Chalmers

Version: 5

Approved By: Schiehallion Clinical Governance Group