introduction to haemophilia and related bleeding disorders · bleeding disorders haemophilia von...
TRANSCRIPT
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: [email protected]
Haematologist:
Dr. Cleona Duggan - Adult service
Dr. Clodagh Ryan - Paediatric service Secretary 021-4546400