Management of Haemophilia and Other Inherited Bleeding ...

Author: Dr Jeanette Payne , Consultant Haematologist H&O/11/1871 Created April 2020 Next review: April 2023 (Do not use after this date) Version number 2 © SC(NHS)FT 2020. Not for use outside the Trust. of 15

Management of Haemophilia and Other Inherited Bleeding Disorders

Reference: CG1871

Written by: Dr Jeanette Payne

Peer reviewer Dr Emma Astwood

Approved: 2020

Approved by D&TC: 10th January 2020

Review Due: 2023

Intended Audience This document contains information and clinical guidelines for management of children under the care of the Haematology department. It is to be used by staff within the Trust whenever they are caring for these children either in hospital or at home.

Purpose This document contains information and clinical guidelines for the management of children with haemophilia and other inherited bleeding disorders.

Table of contents

1. General Information

2. Treatment of bleeds

a) Mild/moderate haemophilia

b) Severe haemophilia

c) Rare congenital clotting factor deficiencies

d) von Willebrand disease

e) Inherited platelet disorders

3. Management of procedures

a) Immunisations

b) Dental work

c) Surgery

4. Factor concentrates

5. Management of severe haemophilia

a) Prophylaxis

b) Home treatment

c) Port-a-caths

d) Inhibitors

6. Musculoskeletal health

a) Physiotherapy

b) Target joints and synovitis

7. References

8. Consent forms and information Sheets

CG1871 Sheffield Children’s NHS Foundation Trust



1. General Information This guideline covers the management of all children with congenital bleeding disorders who are under the care of Sheffield Children’s Hospital (SCH) Haemophilia Centre. Aspects specific to individual conditions are highlighted. Detailed guidance on the management of children with haemophilia and FVIII or IX inhibitors is covered in a separate guideline (Diagnosis and Management of Congenital Haemophilia with Inhibitors – H&O/11/1892) Children with inherited bleeding disorders (IBDs) are registered both locally with the SCH Haemophilia Centre and nationally with the National Haemophilia Database. Parents are provided with a bleeding disorder card stating their child’s diagnosis and contact details for the centre. All registered children should have an information record in the alert section of their EDMS notes stating their diagnosis and usual treatment. The records are also kept on the shared info area on H drive INFOAREA\haematology\CLINIC LETTERS\Haematology Patient Information\ Haemostasis Thrombosis\Patient Folders Arrangements for advice/review including out of hours During working hours, parents of children with bleeding disorders who are registered at SCH are advised to contact one of the haematology nurse specialists on ext 17329, bleep 123 or bleep 142 for advice. If the nurses are not available and the query is clinically urgent parents are advised to contact Ward 6. Outside of routine working hours parents requiring urgent clinical advice are advised to call Ward 6. The call will be taken by a qualified staff nurse or doctor who will collect the relevant information and record it on the specifically designed telephone advice record( see section 7). If the caller is unable to answer the query or if the child needs to be seen they will then call the SpR or consultant haematologist and pass on the information recorded and if necessary the doctor will then call the parent/patient to give specific advice. For children with severe bleeding disorders, parents are asked to always consult with the haemophilia centre if acute advice/treatment is needed even if the problem is not obviously related to haemophilia since specialist assessment is often needed to exclude a bleed or a problem related to haemophilia treatment e.g port infection. For less severe conditions the parents are told to only contact the haematology team for bleeding related problems and injuries. If a review is advised the patient will generally be asked to come directly to The Haematology & Oncology Unit (Ward 6) but in some circumstances the SpR or consultant may advise going to the emergency department or calling an ambulance. In these circumstances the SpR or consultant will phone the relevant emergency department ahead of arrival to pass on relevant information and ask to be called once the child has been initially assessed. If a child arrives without prior notice, the on-call haematology consultant can be contacted to direct management which is usually best delayed until the initial assessment is completed by a junior doctor. Contact details and access information is provided to all parents (Haemophilia Centre Information Sheet – see section 7).

http://nww.sch.nhs.uk/documents/3-clinical-guidelines/2200-diagnosis-and-management-of-congenital-haemophilia-with-inhibitors




If a child with an inherited bleeding disorder is seen in the emergency department at Sheffield Children’s Hospital the medical staff are asked to contact the haematology consultant on-call to discuss the child’s management if there is trauma, bleeding symptoms or need for an invasive procedure. 2. Treatment of bleeding episodes. The assessment of a child with a bleeding disorder must be directed to look specifically for symptoms and signs of bleeding. A bleed may not be obvious, or even necessarily cause swelling, so a high index of suspicion is needed even if there are not many physical signs. The initial symptoms of a joint or muscle bleed may be pain (in the early stages may be described as a tingling sensation or feeling of fullness) or in a younger child the only pointer may be a limp or decreased use of a limb. Examination may reveal increased warmth over the area, swelling and decreased range of movement. Note with some deeper joints e.g hip/shoulder swelling may not be visible. Any presentation in a child with severe haemophilia should be discussed with the haematology SpR or consultant. If a bleed is suspected, prompt treatment with factor concentrate is required. Table 1. Guidance for factor VIII and IX levels required to treat bleeds6

Type of bleed

Target level iu/ml (% level with 100% defined as 1.00 iu/ml)

Duration of treatment

Joint 0.5-0.6iu/ml (50-60%) x1-2 doses may sufficient for early bleeds Larger bleeds -treat until resolution of pain.

Muscle (except ileopsoas)

0.4-0.6 iu/ml (40-60%) 2-3 days but may need longer if inadequate response. Treat until resolution of pain

Ileopsoas and hip bleed

initial 0.8-1.0 iu/ml (80-100%) maintenance 0.3-0.6 iu/ml (30-60%)

Initial phase 1-2days Maintenance phase at least 3-5 days or until resolution of pain

CNS bleed Initial 0.8-1.0 iu/ml (80-100%) then 0.5 iu/ml (50%)

7 days 7-14 days

Mouth or nose

Factor may not be needed unless severe/recurrent bleeding. Use local measures and tranexamic acid (TXA) as first line treatment

Until bleed stops then continue TXA for 5-7 days

Haematuria Spontaneous haematuria is not an infrequent occurrence in severe haemophilia. Apart from increased oral hydration additional treatment is generally not required and bleeding stops within a few days. Replacement therapy may become necessary if haematuria persists or is profuse.




Suggested management of haematuria:

1. Encourage increased oral fluid intake.

2. If haematuria persists and/or is severe, consider admitting for intravenous hydration followed by factor concentrate administration to raise levels to at least 0.50 IU/mL. A second dose may be required 8-12 hours later.

3. Antifibrinolytic therapy with tranexamic acid is specifically contraindicated as this can lead to clot colic.

a) Mild or moderate haemophilia A: Individuals with mild and moderate disease do not tend to bleed spontaneously but are more likely to bleed after surgery including dental extractions and after trauma. First line treatment, particularly for mucosal bleeding, is tranexamic acid. Treatment is generally only needed to correct the factor deficiency following trauma and prior to surgery or invasive dental work or for bleeding when tranexamic acid alone is ineffective. Admission should be arranged for mouth/tongue bleeds that pose a risk to the airway and also for psoas bleeds. Usual treatment to raise FVIII levels in mild haemophilia A is with desmopressin (DDAVP). A single dose generally leads to a 3 to 5 times rise in factor VIII which is often sufficient in mild disease to provide adequate haemostasis. An adequate response is not guaranteed so FVIII level 1 hr after administration is recommended to determine the level of response on the first occasion DDAVP is used.

Desmopressin (DDAVP) (caution <2 years old*)

Subcut

0.3 microgram/kg neat (use 15 microgram/ml concentration preparation)

IV 0.3 microgram/kg in 30-50mls 0.9% sodium chloride over 20-30 minutes

Tranexamic acid Oral 15-25mg/kg 2-3 times a day (max 1.5g/dose)

IV 10mg/kg every 8 hours slow bolus over 10 minutes (max 1g)

* DDAVP is relatively contraindicated in children under 2 years old. DDAVP should ONLY be administered to this age group with consultant approval as young children are at greater risk of hyponatraemia and fluid restriction is more difficult to enforce. Fluid restriction is advised in the 24hrs following a dose of DDAVP to minimise the risk of hyponatraemia and fits.




The following is suggested as a guide to fluid restriction which must include oral and intravenous fluids

Age Maximal fluid/24hrs

2-4yrs <750mls

5-10yrs <1litre

>10yrs <1.5litres

If more than one dose of DDAVP is planned U&Es must be checked prior to each subsequent dose to check for hyponatraemia. If hyponatraemia occurs further doses of DDAVP must NOT be given. For those in whom DDAVP does not provide an adequate rise in FVIII or where a sustained rise is required (e.g major surgery), clotting factor concentrates may be required. Factor concentrates should only be used in patients with mild/moderate haemophilia with authorisation of a consultant haematologist. b) Severe haemophilia: Patients with severe haemophilia often have spontaneous bleeding usually involving the large weight bearing joints, muscles or soft tissues. These bleeds classically start when a child begins to be mobile but iatrogenic or traumatic bleeding can occur before then. Many of these episodes can be treated as outpatients, but admission should be considered for mouth/tongue bleeds that could compromise the airway, psoas bleeds or serious joint bleeds. Bleeds at other locations may require inpatient care e.g. head injuries, lacerations and post-operative management. Intracranial bleeds are rare but can occur spontaneously as well as after trauma. The incidence in severe haemophilia in the UK is highest in the first 2 years of life at a median age of 4months. Most cases occur without a history of trauma so a high index of suspicion is required for a child presenting with compatible symptoms/signs. Children who require factor concentrates will be given a recombinant product in all but exceptional cases. The specific factor given will be decided by a consultant haematologist. Changes from the use of one factor concentrate to another in an individual patient should only be instigated by a consultant haematologist. Tranexamic acid may be useful alone or in combination with factor concentrate particularly for mucosal bleeds. For children on home treatment parents will usually bring some of their own home supply of factor concentrate into hospital with them. Otherwise contact the on-call haematology laboratory staff to obtain the product from blood bank. If the child is on a clinical trial this will be clearly recorded in their notes. There is a small supply of trial products held in blood bank for named patients for emergency use. Use of these products must be directed by a consultant haematologist. The main supply of trial product is held in pharmacy and can be obtained in routine hours by request from a trial investigator using a study specific prescription




In general patients will be given the specific product that they have previously been allocated. A record of this will be on the information record in the notes and also on the haematology (blood bank) computer. A guide to dosing of factor concentrate( in the absence of a FVIII or IX inhibitor): Haemophilia A

FVlll = Desired rise (%) x body weight (kg) 2

The desired increase is determined by the nature and location of the bleed. For example, a joint bleed or muscle bleed will usually respond to a factor level of 40-60%, whereas a psoas bleed should be treated to 80-100%. If a CNS/intracranial bleed is suspected immediate treatment to 100% is required without waiting for imaging to confirm/exclude a bleed. 100% is defined as a FVIII or IX of 1.00iu/ml See table 1. Haemophilia B

Haemophilia B is less common than haemophilia A. The clinical presentation and features of each are indistinguishable and the classification of severity is as for haemophilia A. Haemophilia B is treated in a similar way but with Factor IX concentrate if local measures and tranexamic acid alone is not sufficient. DDAVP is ineffective. The half-life of FlX is longer at 16-22 hours so once daily treatment is usually sufficient when using a standard half-life FIX product

F lX (for Benefix dosing) = Desired rise (%) x body weight (kg) x1.4

Since there is a risk of anaphylaxis to factor IX in patients with inhibitors, the first 20 FIX infusions must be given in hospital in an area where full resuscitation facilities are available. Patients should be monitored for any signs of a reaction for 1hr after infusion. Previous levels attained after a specified dose of FVIII/FIX may be available on ICE reporting to guide dosing. Laboratory confirmation of the FVIII/FIX level achieved should be considered for serious bleeds requiring multiple doses of factor and is required for peri-operative management of haemostasis.

c) Rare Congenital Clotting Factor Deficiencies Congenital deficiencies of other clotting factors e.g fibrinogen, II, V, VII, X , XI and XIII can result in a bleeding phenotype. The risk of bleeding is not always related to the degree of factor deficiency. The management of these children in relation to bleeding and any surgical procedures including dental extractions should be discussed with a consultant haematologist. The general information in section 1 applies to these patients. Factor XII deficiency cause a prolonged APTT but is not associated with a bleeding tendency and is therefore not of clinical significance.




d) von Willebrand Disease. Whilst more common than haemophilia, von Willebrand disease is usually less severe. Mucosal bleeding, especially epistaxis and menorrhagia are common symptoms. Most patients can be treated similarly to those with mild haemophilia A with tranexamic acid +/- DDAVP (See section for mild/moderate haemophilia A above). There are some variants of von Willebrand disease where DDAVP is ineffective and the use is occasionally contraindicated. When a child with VWD is given DDAVP for the first time, their response can be determined by taking a citrated sample (purple top bottle) for VIII, VWF antigen and activity 1hr after administration. A later 4hr level gives additional information on the duration of response and will be requested in selected cases to guide treatment. In cases where DDAVP is contraindicated or when the combination of tranexamic acid and DDAVP is ineffective, intermediate purity FVlll which contains von Willebrand factor may be required. This is a plasma derived clotting factor concentrate so carries with it the theoretical but minimal risk of blood borne pathogens so use is avoided if other measures are effective. Measurement of VWD parameters (VIII, VWF Antigen and RiCoF) following administration can be used to guide the dosing regime

e) Inherited Platelet Disorders There are a variety of inherited platelet disorders which result in a reduction in platelet number and/or function. These disorders present with symptoms of thrombocytopenia. Severity varies greatly between disorders and individuals. Treatment varies depending on the severity of bleeding and may include tranexamic acid, DDAVP, platelet transfusions or novoseven (recombinant VIIa). Always discuss management with the on-call haematology consultant. 3. Management of procedures a) Immunisations

It is advised that children with disorders that significantly increase the risk of bleeding avoid intramuscular injections as there is a risk of haematoma formation which can lead to compartment syndrome. In these cases vaccinations should be given subcutaneously and GPs are advised of this by letter when the diagnosis is made. Since there is a small risk of infection from exposure to blood products it is advised that individuals with bleeding disorders who are likely to be exposed to plasma derived products are vaccinated against hepatitis A and B5

If a child is going to receive recombinant products, it is worth waiting until they are one year of age to give the combined “Twinrix or Ambirix” formulation. In the case of children receiving plasma preparations from infancy, vaccination against hepatitis B should be commenced shortly after birth and then separate vaccination against hepatitis A may be given once they are a year old.




b) Dental work Good dental hygiene and regular checks are recommended to reduce the need for invasive dental work. Check-ups can be performed by a community dentist who should be made aware of the diagnosis by the parents via the bleeding disorder card. All invasive dental procedures e.g extractions and the use of an inferior nerve block should be referred by the local dentist to the Charles Clifford Dental Hospital so that haemostatic management can easily provided by our department. See Management of surgery and dental work in patients with bleeding disorders – H&O/11/1896 guideline for more information. c) Management of surgery If a child with a bleeding disorder presents with symptoms of a bleed or requires an invasive surgical procedure, management should be discussed in advance with a consultant haematologist so that a treatment plan can be made. Surgery should be planned ideally for late morning or early afternoon. This will allow sufficient time for transport of blood samples and performing factor assays if required. See Management of surgery and dental work in patients with bleeding disorders guideline – H&O/11/1896 4. Factor concentrates

Single factor concentrates are commercially available for replacement of fibrinogen, factors VII, VIII, IX, X, XI and XIII. Not all products are stocked routinely at SCH but can be ordered in for a patient if required electively. If a product is needed urgently and is not available at SCH (e.g fibrinogen, FXI) these can usually be obtained from STH haemophilia centre. The trust will be invoiced from STH for any product used. If a recombinant product is available and funded by NHSE then this will usually be given in preference to a plasma derived product. There are some circumstances where a plasma derived product may have benefits over a recombinant one but this will always be decided by a consultant haematologist. There are a range of recombinant FVIII and IX products commercially available. The UK follows a national procurement process for tendering of factor concentrates for the purchase of factor concentrates. The NHS contract is determined after a national tendering process in order to maximise cost savings for the NHS. Data of usage of factor concentrates is submitted from the centre upon request to commissioners and NHSE and analysed alongside other centres to ensure that usage will meet the contract agreed. Sometimes patients are required to switch from one product to another. If this is the case an inhibitor screen will be taken pre and post switch. After the national contracts are agreed and if any new information is available the consultant haematologists will be informed by the lead clinician for haemophilia (currently Dr Jeanette Payne) which products should be used for a new patient starting treatment. Otherwise unless there is a planned switch of product patients should be given the same product that they have previously received whenever possible.

http://nww.sch.nhs.uk/documents/3-clinical-guidelines/2201-management-of-surgery-and-dental-work-in-patients-with-bleeding-disorders

http://nww.sch.nhs.uk/documents/3-clinical-guidelines/2201-management-of-surgery-and-dental-work-in-patients-with-bleeding-disorders




5. Severe Haemophilia

a) Prophylaxis The majority of children with severe haemophilia receive regular prophylactic factor infusions at home administered by a parent or themselves. The decision for starting prophylaxis and the regime used will be based on the recommendations of the latest UKHCDO guideline2. SCH practice is to usually start prophylaxis after the first joint bleed, or if there are other significant bleeds requiring treatment, especially if spontaneous bleeds are occurring as this history confirms a severe bleeding phenotype If possible, prophylaxis will be given via peripheral venepuncture with the aim of teaching parents to administer treatment. If venous access is very difficult then a port-a-cath may be required which the parents are often taught to access using an aseptic technique. If a port is inserted it should be considered a temporary measure with conversion to peripheral venepuncture as soon as the child’s veins allow. The minimum dose of factor that prevents breakthrough bleeds should be used rounding up to the nearest vial size. A starting dose of 25-50units/kg is recommended. A standard prophylaxis regime for severe haemophilia A is three times weekly using a standard half-life product but some children do not have breakthrough bleeds on twice weekly treatment and others need escalation to alternate days or rarely daily treatment to prevent bleeds. As the half-life of factor IX is longer, a twice weekly schedule for prophylaxis using a standard half-life product is usually sufficient in severe haemophilia B. Prophylaxis may be introduced by initially administering factor concentrate once weekly but treatment should be escalated rapidly to more frequent administration as soon as venous access permits in order to prevent the occurrence of any joint or soft tissue bleeds. The prophylaxis regime will be guided by clinical and laboratory monitoring which includes: 1. Occurrence of breakthrough bleeds 2. Trough and peak levels (“pre and post” factor concentrate) - trough levels should be

taken immediately before a dose at the usual interval between prophylactic doses. Peak levels should be taken 20mins-1hr after administration. Each requires a venous 1ml or 2.5ml citrated sample (filled strictly to the mark on the purple bottle). Bottles should be clearly labelled and the request form should state the timing of the last dose, amount of factor given and type of factor used. This information is required to ensure the laboratory testing is accurate and that results can be interpreted correctly.

The prophylaxis regime, together the decision regarding when levels are required will be agreed between a haematology consultant and haemophilia specialist nurse. Prophylactic doses should be tailored to provide maximum cover for particular physical activities, e.g. school, PE, sports. Prophylaxis should be administered ideally in the morning to optimise factor levels Enhanced half-life (EHL) products There are several FVIII and FIX enhanced half-life clotting factor concentrates (EHL-CFCs) that are currently either in clinical trial or have recently come into clinical use. These products use a variety of techniques (i.e. pegylation, fusion to Fc fragments or fusion to albumin) to extend the half-life of either clotting factor.




In general, EHL factor VIII concentrates extend the plasma half-life of FVIII by 1.5 times (i.e. approx. 18 hours in adults). The half-life for factor IX is extended, on average, by 3 –5 times (i.e. approx. 72-96 hours in adults). The potential benefits of EHL-CFCs include the ability to reduce injection frequency for patients as well as giving the option for maintaining a higher trough level. However, the published PK data on EHL-CFCs demonstrates a shorter half-life than in adults with an increase in recovery and half-life across age bands together with a large degree of interpatient variability. The half-life of EHL FVIII is approximately 13hrs for <6yrs and 15 hrs for 6-12yrs. The half- life of an EHL FVIII in young children therefore is often not sufficient to allow a reduction in frequency to less than their regime on a standard half-life product. For FIX the extension of half-life is much greater than for FVIII even in younger children (66-89hrs for <6yrs and 70-93 hrs 6-12yrs) and use of a EHL FIX generally allows a once weekly for adequate prophylaxis. Currently the use of EHL-CFCs outside of a clinical trial is NOT recommended for previously untreated patients (PUPs). When considering a switch to an EHL-CFC for previously treated patients, the UKHCDO guidance on EHL-CFC use together with criteria set out by NHSE should be followed4. Patients may be offered a switch of product if the following criteria are met

1. Compliance and ongoing adherence with recording of home treatment using haemtrack

2. Willingness to complete blood tests for PK studies and inhibitor screening pre and post switch

3. Patient considered able to adhere to prescribed regime after any necessary training and education

4. The patient has received at least 50 exposure days of factor concentrate and not had an inhibitor requiring tolerisation in the previous year

A consultation with patients/parents should cover options for regimens and it should be made clear to patients that use of an EHL-CFC may not reduce infusion frequency for all individuals. Patients or their responsible carer must provide written consent of the acceptance of the conditions and clinical criteria for the use of an EHL-CFC. Copies of the consent form can be found on the H drive (H:\INFOAREA\haematology\CLINIC LETTERS\Haematology Patient Information\Haemostasis Thrombosis\General Haemophilia Information\EHL) Once a trial switch is agreed the haemophilia nurse specialist will discuss with parents the practicalities of using up existing supplies of clotting factor concentrate and agreeing a suitable date for the first dose of the EHL-CFCs. Blood tests will be arranged on the current product to include an inhibitor screen (within the past 3months) and levels at the following time points following an infusion of factor concentrate to determine recovery and an approximate half-life.




FVIII- 15mins-1hr, 6-12hrs, 24hrs, 2 days, 3 days. A 3 day level is not required if the child is on an alternate day prophylaxis regime FIX- 15mins-1hr, 6-12hrs, 24hrs, 3 days, 4 days. The starting dose of the EHL-CFC will be decided by the lead haemophilia consultant based on a current weight, previous prophylaxis regime and PK results. The first dose of EHL-CFC will be given in the centre and blood tests taken to determine recovery and an approximate half-life. Samples will be taken at the following timepoints FVIII- 15mins-1hr, 6-12hrs, 24hrs, 2 days, 3 days. FIX - 15mins-1hr, 6-12hrs, 24hrs, 3 days, 5 days, 7 days The prophylaxis regime will be informed by these results and parents will also be given guidance on the dose of factor to give for treatment of a bleed. If a bleed does not respond to a single dose of treatment parents are asked to phone for advice. Subsequent doses and frequency will be decided by a consultant haematologist who will take into account the PK results which are recorded on ICE. A summary of PK results pre and post switch together with the prophylaxis regime will be recorded in EDMS as a summary clinical note. After approximately 10 exposure days a repeat inhibitor screen and trough level will be taken and the prophylaxis regime adjusted if necessary. Patients will be regularly assessed for frequency of bleeding and for repeat trough levels as indicated No later than 3months after the switch, a decision will be made whether to continue the EHL-CFC or switch back to a standard half-life product based on clinical and laboratory criteria Patients should be switched back to a standard half-life product if any of the following occur

a. The anticipated clinical benefits do not materialise after 3 months of using an EHL regimen e.g neither a reduction of frequency of injections or reduction in frequency of bleeds

b. Increase in the rate, frequency or severity of bleeding episodes

c. Trough level is reduced

d. There is evidence that the patient is not adherent to the prescribed regimen

e. The patient, or their responsible carer, is not compliant with maintaining home treatment records

b) Home treatment This is given either via peripheral venepuncture using a “butterfly needle” or through port-a-cath. Having control over their treatment allows parents and older children to become “expert patients”. Their knowledge and experience of managing the condition should not be under estimated. If they are concerned enough to ring for advice it usually means that they are worried. In general parents are asked to phone to ask for advice if their child’s symptoms are not improving after 1-2 extra doses of factor concentrate.




Children on home treatment have their factor concentrate delivered to them directly. Prescriptions are generated in the centre and are sent to the home delivery company to instruct on delivery. Any changes to the prophylaxis regime needs to be followed by a change in the prescription. Prescriptions are verified by a haematology consultant or a haemophilia specialist nurse (provided they have a non-medical prescribing qualification). The prescriptions have a clinical check by a specialist pharmacist. Treatment records must be completed and kept up to date in time for clinic reviews for children on home treatment. Parents and children who are old enough to do so are encouraged to record treatment electronically using the haemtrack website (https://apps.mdsas.nhs.uk/haemtrack) or app. Use of haemtrack avoids the need for paper records and allows live information to be viewed by the centre. If parents are unable or do not wish to keep electronic records are permitted to make paper records. The haemtrack home records sheet should be used which is available to provide copies to the parent. The template can be found on the H drive under general haemophilia information (H:\INFOAREA\haematology\CLINIC LETTERS\Haematology Patient Information\ Haemostasis Thrombosis\General Haemophilia Information\Haemtrack c) Port-a-caths

Children with port-a-caths are at risk of the same complications as other children with central lines. The same principles apply to this patient group with regard to central line care CG924 - Guidelines For Caring For Patients With Central Lines The most common serious port complication in this patient group is of line infection. Parents should be made aware of the risk and of the signs of an infection and the need to consult immediately if the child becomes febrile, vomits or feels unwell in the period after the line is used. Often symptoms will be transient and by the time the child is reviewed may appear to be back to normal. Blood cultures should be taken from the port if there is any suspicion of infection. Children presenting with a possible port infection should be discussed with the consultant on-call. The consultant will decide if intravenous antibiotics are required pending the result of blood cultures and whether these are to be given via the port or peripherally. In most cases ceftazidime and teicoplanin would be an appropriate first choice of antibiotics. If there is haemodynamic compromise or if the suspicion of port infection is high, a peripheral cannula should be inserted for administration of antibiotics and factor concentrate pending blood culture results. Even in the presence of a serious bacterial port infection it is quite normal for the child to appear very well and fevers to not recur whilst the port is not being used. If blood cultures are positive subsequent management will be guided by the organism identified. Antibiotics should be given as advised by microbiology. If either a Gram-negative organism or a Staphylococcus Aureus is identified arrangements should be made for the line to be removed as experience shows that these infections are virtually never cleared in this patient group with antibiotics alone. Even where blood cultures are negative at the end of treatment there is a very high recurrence rate of bacteraemia often with cardiovascular compromise at the time of recurrence.




d) Inhibitors Up to 30% of children with severe haemophilia A will develop allo-antibodies which are more commonly termed an “inhibitor” against FVII. An inhibitor frequently leads to ineffectiveness of FVIII replacement. Inhibitors are less common in haemophilia B and in mild/moderate haemophilia A but still can occur and are difficult to manage. The greatest risk period is early in treatment in the first 20 days of exposure to factor but can occur at any time. During this early exposure period it is good practice to send a sample for an inhibitor screen when the child needs a venepuncture for treatment. An inhibitor should be suspected and tested for if a child has repeated or recurrent bleeding despite factor replacement or if they have a suboptimal clinical or laboratory response. In severe and moderately severe haemophilia, patients should be screened for inhibitors by sending a 2.5ml citrated sample to haematology at the following times:

1. For previously untreated patients every 5th exposure day until the 20th exposure day.

2. For patients between 20 and 150 exposure days 3-6 monthly

3. For patients beyond 150 exposure days once yearly

4. If there is concern from clinical symptoms e.g frequent bleeds or bleeds not responding to factor or from laboratory tests i.e response to factor significantly less than predicted.

5. Prior to surgical procedures Inhibitors can also occur in those with mild haemophilia and it is good practice for such patients to be screened after receiving an intensive period of factor concentrate. Testing is also required pre-surgery if they have been exposed to factor concentrate since the last inhibitor screen Inhibitor screens must be taken prior to administration of factor concentrate. The management of haemophilia in the presence of inhibitors is complex and should always be discussed with a consultant haematologist. More detailed information can be found in the guideline Diagnosis and management of haemophilia with inhibitors – H&O/11/1892

http://nww.sch.nhs.uk/documents/3-clinical-guidelines/2200-diagnosis-and-management-of-congenital-haemophilia-with-inhibitors




5. Musculoskeletal health

Management of a suspected joint or muscle bleed should be discussed with a consultant haematologist. Specific management will depend on the underlying bleeding disorder (see sections 2-7 for diagnosis specific information) Physiotherapy

Physiotherapy input is an important aspect of haemophilia care for the assessment and management of musculoskeletal complications. Physiotherapy input is especially indicated for the following situations

A joint bleed which requires multiple doses of factor concentrate and/or is slow to settle

Rehabilitation from a psoas bleed

A child who is experiencing difficulty recovering despite adequate factor concentrate

A joint with chronic synovitis and recurrent bleeding

When orthopaedic intervention is required All children with severe haemophilia and those with moderate haemophilia who are on prophylaxis will have routine physiotherapy assessments annually. For those over 4yrs the assessment will include an annual Haemophilia Joint Health Score. All referrals for physiotherapy should be made via the lead haemophilia physiotherapist Matt Denton (ext 17227). If Matt is unavailable for acute bleeds then inpatients can be referred to the inpatient orthopaedic physiotherapy team for solely for mobility assessments or to the outpatient team in the physiotherapy gym for all other indications Target Joints and synovitis Recurrent bleeding into a joint leads to the development of synovitis which is characterised by a painless chronic swelling of the affected joint. An inflamed synovium is more prone to bleeding and may lead to the joint becoming a target joint. A target joint is defined by the PEDNET group as having 3 or more bleeds in a 6 month period. Recognition, imaging and intervention to minimise synovitis in any target joints should be based on an individualised approach which includes optimisation of factor replacement therapy, exclusion of an inhibitor, use of appropriate orthoses and early consideration of radioactive synovectomy. Radioactive synovectomy for children is currently available by referral to the haemophilia team in Newcastle or Great Ormond Street Hospitals. Steroid injections may be considered on an individual basis in consultation with rheumatology team. Some reports of short term symptomatic benefit but no firm evidence base to support use in haemophilia




6. References 1. http://www.medicines.org.uk/emc/medicine/20491/SPC/Ambirix+suspension+for+injection/

2. Richards M, Williams M, Chalmers E, Liesner R, Collins P, Vidler V, Hanley J; Paediatric Working Party of the United Kingdom Haemophilia Doctors’ Organisation. Br J Haematol A United Kingdom Haemophilia Centre Doctors’ Organization guideline approved by the British Committee for Standards in Haematology: guideline on the use of prophylactic factor VIII concentrate in children and adults with severe haemophilia A.. 2010 May;149(4):498-507.

3. Hay CR, Brown S, Collins PW, Keeling DM, Liesner R. Br J Haematol. The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation.. 2006 Jun;133(6):591-605

4. Collins P, Chalmers E, Chowdary P, Keeling D, Mathias M, O’Donnell J, Pasi KJ,

Rangarajan S, Thomas A. The use of enhanced half-life coagulation factor concentrates

in routine clinical practice: guidance from UKHCDO. Haemophilia. 2016 Jul;22(4):487-

98

5. Watson HG, Wilde JT, Dolan G, Millar C, Yee TT, Makris M. Update to UKHCDO

guidance on vaccination against hepatitis A and B viruses in patients with

inherited coagulation factor deficiencies and von Willebrand

disease.Haemophilia. 2013 May;19(3):e191-2.

6. Guideline for the management of hemophilia ( World Federation of Hemophilia)

http://www1.wfh.org/publications/files/pdf-1472.pdf

7. Consent Forms & Information Sheets H&O/11/1871 pis – Managing Bleeding Episodes at Home Patient Information Sheet

H:\INFOAREA\haematology\CLINIC LETTERS\Haematology Patient Information\Haemostasis Thrombosis\ General Haemophilia Information

H&O/11/1871 Form – Bleeding Disorders Telephone Advice Record Located on Ward 6 in white folder above nurses station

H&O/11/1871 contact – Contacting the Haemophilia Centre Patient Information Sheet H:\INFOAREA\haematology\CLINIC LETTERS\Haematology Patient Information\Haemostasis Thrombosis\ General Haemophilia Information H&O/Form/019 – Consent form Enhanced Half Life (EHL) Factors

H:\INFOAREA\haematology\CLINIC LETTERS\Haematology Patient Information\Haemostasis Thrombosis\General Haemophilia Information\EHL\EHL consent

http://www.medicines.org.uk/emc/medicine/20491/SPC/Ambirix+suspension+for+injection/

https://www.ncbi.nlm.nih.gov/pubmed/27311929

https://www.ncbi.nlm.nih.gov/pubmed/?term=Watson%20HG%5BAuthor%5D&cauthor=true&cauthor_uid=23600911

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wilde%20JT%5BAuthor%5D&cauthor=true&cauthor_uid=23600911

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dolan%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23600911

https://www.ncbi.nlm.nih.gov/pubmed/?term=Millar%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23600911

https://www.ncbi.nlm.nih.gov/pubmed/?term=Yee%20TT%5BAuthor%5D&cauthor=true&cauthor_uid=23600911

https://www.ncbi.nlm.nih.gov/pubmed/?term=Makris%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23600911

https://www.ncbi.nlm.nih.gov/pubmed/23600911

http://www1.wfh.org/publications/files/pdf-1472.pdf

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