Introduction to Haemophilia

and Related Bleeding

Disorders

Brid Booth Fleming

Clinical Nurse Specialist

CUH

How does bleeding start and

stop?

Blood vessel injury

The capillary contracts to help

slow the bleeding

Platelets make a plug to

patch the hole

Clotting factors in plasma

work together to form a clot

over the plug

Bleeding Disorders

Haemophilia

von Willebrand Disease

Platelet Function Defect

von Willebrand Disease

Up to 1% of the

population

125 / million have a

clinically significant

bleeding disorder

Autosomal inheritance

von Willebrand Factor

Large glycoprotein produced by endothelial cells

and megakaryocytes

Carrier protein for Factor VIII

vWF Related antigen - quantitative assay

vWF Ristocetin cofactor - functional assay

Six subtypes – Type 1, 2A, 2B, 2M, 2N, 3

von Willebrand Disease

Usually mild to moderate bleeding tendency

Mucocutaneous bleeding

Easy bruising

Epistaxis

Menorrhagia

TREATMENTS:

Tranexamic acid

DDAVP - Desmopressin

Wilate – plasma derived - FVIII & vWF

Platelet Function Disorders

Quantitative and Qualitative

Platelets - engaged in sequential responses

at site of bleeding – activation, adhesion,

spreading, aggregation vital that they

function

Glanzmann Thrombasthenia, Bernard-

Soulier syndrome

Tx with Cyclokapron and Platelets

2000 years of Haemophilia

Haemophilia Most common: Haemophilia A

VIII deficiency

x-linked recessive

1:20,000 births

Haemophilia B

IX deficiency

x-linked recessive

1:100,000 births

Clinically indistinguishable

Others k/a rare bleeding disorders

Clinical Presentation of

Haemophilia A and B

Severity of bleeding is inversely proportional to level

Severe : <0.01 IU/dl (<1%)

(Can have spontaneous bleeding – joint,

muscle and intracerebral bleeds)

Moderate : 0.01-0.05 IU/dl (1-5%)

(Prolonged bleeding with trauma and surgery)

Mild : >0.05-0.50 IU/dl (5-50%)

(Bleed with trauma and surgery)

Inheritance Haemophilia gene - carried

on X chromosome

Male with haemophilia passes the gene to all of his daughters, not sons. Daughters - obligate carriers

Carriers have a 1 in 2 chance of passing the gene to offspring. If affected X passed to a son, he will have haemophilia. If passed to a daughter, she will be a carrier - like her mother

2/3 will have family history, 1/3 can be Spontaneous Mutation

Is Haemophilia lifelong?

A person born with haemophilia will have it for life

The level of factor (VIII or IX) usually stays the same throughout life

Joint / Muscle Bleeds

Most common joint bleeds – weight bearing joints -ankles, knees, and elbows

Bleeds in other joints can also happen, including the toes, shoulders, and hips

Hands are not usually affected except after injury

Muscle bleeds also – ileopsoas – compartment syndrome

Treatment

2 forms:

1. Acute: treatment of bleeding episodes - once a bleed has

started - important to raise factor level promptly to stop

haemorrhage. Continue until bleeding stops

1. Prophylaxis: - to prevent spontaneous bleeding

- pre surgery/sporting activity

- venous access vs implanted device – eg

Portacath, Hickmann – involves teaching

Treatment

A BLEED or POTENTIAL BLEED REQUIRES IMMEDIATE TREATMENT - within 2 hours is optimal time

Identify site of suspected bleed and assess for compression of vital structures

If in doubt manage as a bleed, then consider alternative diagnosis and investigate accordingly - check HgB

Avoid unnecessary investigations – eg. X-rays, coagulation profiles – unless clinically indicated

Analgesia as needed

Avoid IM injections, NSAIDs and Aspirin RICE

Physiotherapy referral for joint or muscle bleeds

CHRONIC JOINT BLEEDING

Potential Outcomes Repeated delay or untreated bleeding more pain

immobility muscle wasting and weakened joint more susceptible to bleeding

Synovial tissue thickens with repeated bleeds - even more friable blood vessels develop

Vicious cycle of bleeding and re-bleeding - “TARGET JOINT”

CHRONIC ARTHRITIS – occurs with repeated bleeding and inadequate or DELAYED factor replacement

Destruction of cartilage and eventual destruction of bone can occur, resulting in decreased joint function and pain JOINT REPLACEMENTS . . . . . .

Haemarthrosis

Recombinant CFCs

Coagulation Factor Concentrates (CFCs) are fractionated & freeze-dried preparations of individual clotting factors or groups of factors

They provide convenient high doses of clotting factor for prophylaxis and treatment of bleeding (World Federation of Haemophilia 1997)

Elocta, Alprolix, Novoseven - Genetically engineered

FEIBA – plasma derived

Recombinant CFCs introduced into Ireland in late 1990’s

Ireland first European Country to offer patients with haemophilia recombinant treatment (Holmquist 1997)

Treatments incl Factor Concentrates

TREATMENT INDICATION HALF - LIFE

Elocta

Recombinant

FVIII Deficiency 19 hours

Alprolix

Recombinant

FIX Deficiency 72 Hours

Novoseven

Recombinant or

FEIBA

Plasma Derived

Patients with inhibitors to

FVIII or FIX

+/-2.7 Hours

6 Hours

DDAVP

Desmopressin

Minor bleeding for some

mild to moderate FVIII

deficiency patients (Trial)

12 – 24 Hours

Calculating a Dose of

FVIII or FIX Concentrate

Confirm:

Factor Deficiency – Bleeding Disorder Alert card

Baseline Factor Level

Site and severity of bleed

Rise Required

Inhibitor History

Weight

Dosing Formula:

% Rise Required x Weight (kg)

K

Rise Required = desired level (%) – baseline level (%)

K factor for FVIII = 2

K factor for FIX = 0.6 for 0-6yrs and 0.8 for 6-12yrs, 12yrs and up the k factor is 1

Always round up dose to nearest vial size for all

Mild Haemophilia - Treatment

Consider DDAVP (Desmopressin) - mild FVIII

DDAVP stimulates the release of vWF,

vWF carrier protein for FVIII, thereby FVIII

Use appropriate factor concentrate dosing for severe bleeding/some surgery/head injury

Tranexamic acid (anti-fibrinolytic) useful in mucosal bleeding

Treatment - considerations

Record in Blood product prescription and in patient’s notes

Apply pressure to veni-puncture site for 5 min

Consider concurrent treatment eg. anti-fibrinolytic agent

Give factor prior to suturing and removal of sutures

Reconstitute immediately prior to use - Use filter

needle/device supplied

Separate filter needle for each vial

Glass syringes not compatible with cannula – separate

connector or use plastic syringe

Add solvent to powder and gently rotate to dissolve

- do not shake

Inspect solution for particulate matter - clear and colourless

DDAVP Synthetic Vasopressin Analogue

Indication: Mild Factor VIII Deficiency (not FIX or

severe FVIII) for Trauma or undergoing minor surgery

Mode of Action: Stimulates release of stores of FVIII

and vWF from the endothelial cells into circulating blood

Dosage: I.V: 0.3 mcg/kg diluted in 100mls of Nacl 0.9% over 30-60mins, then 50ml flush

Caution: DDAVP Trial – to ensure it increases levels

Fluid restriction to 50-75% of maintenance in the next 24 hrs

DDAVP Nasal spray - 150 mcg (125/nostril)

DDAVP

Contraindications:

Child < 2 years

History of epilepsy /

seizures

Renal impairment

Cardiac Failure

Hypertension

Head Injury

Side Effects:

Headaches

Facial Flushing

Nausea

Abdominal pain

Fluid Retention

Hyponatraemia Always check sodium level prior to

DDAVP infusion and remember to

fluid restrict to 50% - 75% of

maintenance fluids post infusion

Tranexamic Acid (Cyklokapron)

An anti-fibrinolytic agent

Uses: alone or in combination with DDAVP or CFCs for treatment and prophylaxis of mucosal membrane bleeding

Dosage: Oral (tablets only) 15 - 20mgs/kg q.i.d.

I.V. 0.5 - 1 gram 3 times daily

Mouthwash 2.5mls-10mls of a 5% solution 3-4 times daily

Adverse Effects: Nausea, vomiting & diarrhoea

Caution: Rapid IV injection causes dizziness &

hypotension give as infusion

Contraindications: Thromboembolic Disease, DIC or

Haematuria

INHIBITORS

Anti-Factor Antibodies - IgG

Incidence: 10-20%

Familial incidence (x6)

Majority occur <10yrs of age

Occur within first 25 tx days

Bleeding

Treat bleeding with by-pass agent

Novoseven, FEIBA, Hemlibra (Emicuzimab)

Eradicate with Immune Tolerance Therapy ITT

Recognition of Bleeds

General Haemophilia Care Encourage normal active life - Exercise - avoid major

contact sports

Prophylactic Factor VIII or IX

– 2/3 times/week previously - vein or implanted device

– Education of parents and child

– Factor delivered directly to patient’s homes

Treatment of acute bleeds ASAP

Patient - best person to recognise a bleed – tingling, heat, swelling, then pain

Factor concentrate prescribed on Transfusion prescription

(Form 15 CUH) - ordered from Blood Bank

Injected IV some slow bolus others >2/3 mls/min

Avoid NSAIDS, Aspirin and IM injections

General Haemophilia Care

Physiotherapy

Management of arthropathy

Education for teachers and other carers

Dental review / dental hygiene

Bi-annual / Annual clinic review

Vaccinations s/c

Obstetric Care

Mum

Obstetrician

Haematologist

Anaesthetist

Paediatrician

Baby

The Pregnancy Plan

Haemophilia Nurse

GP

Pregnancy Plan - Mum

Planned delivery with plan written in chart

Some clotting factors rise in pregnancy

Haematology review in first trimester

Repeat factor levels at 28 and 36 weeks if known carrier with low levels

If assays normal at 36 - no intervention required

Epidural not contraindicated if levels above 50%

Avoid IM injections, NSAIDs and Aspirin

Management of Neonates

with suspected Haemophilia

Scan to ascertain male/female foetus

Counselling on Inheritance and possibility of having a child with haemophilia – preferably in advance – seen at combined haem/obs clinic

Plan for Management of neonate in mum’s obstetric notes

Vaginal delivery – optimum choice

C-section for obstetric reasons only

Management of Neonates with

suspected Haemophilia N.B. Avoid instrumentation, ie forceps, vacuum,

scalp electrodes

CONTACT HAEMATOLOGY TEAM AND LAB WHEN

MUM IN LABOUR / ON INDUCTION / PLANNED

SECTION

Sample of Cord blood for factor level – repeat

peripheral sample will be required later

PO Vitamin K as IM injections contraindicated

Management of Neonates with

suspected Haemophilia If no instrumentation used, risk of intracranial or

extracranial bleed is rare

Incidence with instrumentation - 3.5%

Kulkarni et al, 1999

Heel prick for Guthrie card analysis and BCG

(subcutaneous) can be carried out without

haemostatic support

Apply pressure for at least 5 minutes following all

venipunctures and heel prick

Management of Neonates with

suspected Haemophilia

If factor level < 0.01iu/ml - cranial U/S

If cranial U/S normal, and suspect ICH, consider CT/MRI

If instrumentation needed to deliver a baby with 1:2 chance of severe factor def (<1%) - Consultant Haematologist may consider factor replacement before results or U/S esp if delay – Always discuss with consultant haematologist

Haemostasis Guidelines

The National Haemophilia Guidelines are available on the Staff directory

A quick two page reference guide is also available in the same location

Also available on www. nationalhaemophiliacouncil.ie

Questions????

Contact Details

Hereditary Bleeding Disorders Nurse Specialists:

Bríd Booth Fleming, Norma Collins, AnnMarie Ryan Hall & Brid Firtéar

Monday – Friday 8.30am – 5pm Office: 021-4922278 / 4920482, Mobile: 087-9683246 (Emergency)

After 5pm and at weekends: Contact CUH switchboard and ask for Haematology registrar on call

Email: hcd@hse.ie

Haematologist:

Dr. Cleona Duggan - Adult service

Dr. Clodagh Ryan - Paediatric service Secretary 021-4546400