Prophylactic Anti-D choices –
one dose or two? / who
decides?
Claire Harrison
Guy’s and St Thomas’ NHS Foundation Trust
Prevention – anti-D
1.4
1.2
%
1
0.8
0.6
0.4
0.2
0
Nothing
Conventional Prophylactic
% rhesus negative women with rhesus positive fetus sensitised / pregnancy
Cost per year of HDN due to anti-D
• Currently 625 sensitisations per year
• At least 30 fetal deaths, stillbirths, neonatal and
post-neonatal deaths.
• 15 children will have major permanent
developmental problems, a further 30 will have
minor developmental problems
• Number needed to treat to avoid a fetal or neonatal
loss in a subsequent pregnancy estimated as
5,790.
1
RAADP Guidelines
• Nov 2002 NICE
– Technology Appraisal
• May 2002 RCOG ‘Green Top Guidelines’
– Refer to NICE only, with link to website
• June 2006 BCSH
– “..takes account of the publication of the NICE
guidance..”
• 2008 NICE review
Implementation of routine antenatal anti-D
prophylaxis: a survey of UK maternity units
• A postal survey of 324 UK maternity units 2005.
• Responses were received from 91% of units
(294 of 324).
• RAADP was offered by 220 of 294 (75%)
– England and Wales 19% of those offered a singledose regime.
– 12% routine paternal blood group testing was offered.
– Written patient information was provided at 97%
– 147 of 217 (69%) returned a copy. ( 60 different
(Harkness 2007)
leaflets)..
Prophylactic Anti-D choices –
one dose or two? / who decides?
2
Considerations in choice of regime:
•
Reduce the incidence of HDN
•
Compliance with NICE guidance
•
Overcome poor compliance/uptake
•
Donor exposure
•
Optimal use of midwifery time
•
Improve record keeping/audit trail
•
Optimal use of financial resources
Antenatal anti-D prophylaxis:
One dose or two ?
“Two doses of anti-D immunoglobulin 500 IU at
28 and 34 weeks into pregnancy appear to be
as effective as one 1500 IU dose at 28 weeks”
NICE Technology Appraisal Guidance – No 41. Routine anti-D prophylaxis for rhesus negative
women
Antenatal anti-D prophylaxis:
One dose or two ?
• Trent Institute for Health Services
Research conducted 3 meta-analyses as
part of the NICE review
“No evidence of any significant difference
between the regimens in terms of Rh
sensitisation”
Chilcott J et al. Health Technol Assess. 2003; 7 (4)
3
Antenatal anti-D prophylaxis:
One dose or two ?
• “A single dose of 1500 iu anti-D may be an
effective alternative regimen that
potentially offers cost and logistic benefits.
However more evidence is required to
establish its comparative efficacy”
BCSH 2006
Pharmacokinetics
• Calculated residual anti-D at 12 weeks
– 2 x 500iu
– 1 x 1500iu
= 31.75ug
= 18.75ug
• Measured residual
– 2x500iu
• MacKenzie 2005 - 30% detectable anti-D at 12 weeks
– 1x1500iu
• Bowman 1987 - 0% detectable at 11 weeks
• Bichler - 60% detectable (higher sensitivity) at 11 weeks
• Witter - 44% (at 20ug) at 8 weeks
Theoretical concern:
Pharmacokinetics of single dose anti-D
Assumes elimination t 1/2
21 days for BPL 500IU
17 days for Rhophylac
Graph adapted from Mackenzie IZ. Br J Midwifery. 2004; 12: 13-19
4
Antenatal anti-D prophylaxis:
One dose or two ?
• RAADP is recommended as a treatment option
for all pregnant women who are RhD negative
and not known to be sensitised to the D antigen
• …the preparation with the lowest associated
cost should be used. This cost should take into
account the lowest acquisition cost available
locally and costs associated with administration
NICE 2008
Considerations in choice of regime:
•
Reduce the incidence of HDN
•
Compliance with NICE guidance
•
Overcome poor compliance/uptake
•
Donor exposure
•
Optimal use of midwifery time
•
Improve record keeping/audit trail
•
Optimal use of financial resources
√
√
Compliance with RAADP
• MacKenzie 2006
– Oxford, John Radcliffe
– RAADP given for past 14 years
– 2x500iu
– 1992-96
• 89% had first injection
• 81% had second injection
• 74% had both
– 1997-2003
• 90% had first
• 87% had second
• 79% had both
• RHH
– 12% (50/413) did not get second dose
• Chaffe (Kent)
– 87.0 and 86.0% receive 1st + 2nd doses respectively).
5
Considerations in choice of regime:
•
Reduce the incidence of HDN
•
Compliance with NICE guidance
•
Overcome poor compliance/uptake
•
Donor exposure
•
Optimal use of midwifery time
•
Optimal use of financial resources
•
Improve record keeping/audit trail
√
√
√….?
Anti-D products and donor exposure
Product
Dose of antiD/ vial or ≡t
Donations/batch* Vial or ≡t of
* many repeat donors
anti-D/ batch
D-gam (BPL) 500 IU
620
25-33,000
vials
Partoglobin
1250IU
SDF (Baxter)
Mean 12,500
Max 25,000
17-31,000
syringes
Rhophylac
(ZLB
Behring)
375
26-44,000
vials
1500IU
Adapted from Regan etal 2007
Financial Considerations (Trent analysis)
~ 6000 deliveries 2004/5
15% Rh Neg = 897
Laboratory
Costs
AntiAnti-D per Cost per year
woman
immunoglobulin
Additional:
- Consumables
- Midwifery time
- Clerical staff
Total to
implement
Prophylaxis
500iu
13143.4
19.50 x
2 doses
34,944.00
22,623.00
70,710.40
1250iu
13143.4
19.50 x
2 doses
34,944.00
22,623.00
70,710.40
1500iu
13143.4
30.00
26,688.00
11,565.00
51,396.40
6
• Current costings (excl VAT):
– D-Gam (BPL) (500iu x 2)
– Partobulin (Baxter) (1250 x 2)
– Rhophylac (CSL Behring) (1500 x 1)
£54
£70
£46.50
– WinRho (Baxter) (1500iu x 1)
£313.50
Considerations in choice of regime:
•
Reduce the incidence of HDN
•
Compliance with NICE guidance
•
Overcome poor compliance/uptake
•
Donor exposure
•
Optimal use of midwifery time
•
Optimal use of financial resources
•
Improve record keeping/audit trail
√
√
√
√
√
√
?
Personal experience:
7
2002:
Decision implement NICE guidance
Written into business plan 2003
RAADP implemented 2 x 500iu anti-D
Review of situation 2004
• Clinic functioning
• Good audit trail
• But
– Clinic overloaded some women delayed in
getting first dose
– Poor compliance 22% not attending for second
dose
• And
– On-going problems with Kleihauer results
8
Review
• Clinic organisation could be improved
• But local population issues
– Highly multicultural and migrant
– ? Needle phobic and fail to attend for 2nd dose
• Investigate possibility of using single dose
1500 anti-D
• Also consider how many different doses
are stocked
Decision:
• Implement single dose 1500iu @ 28
weeks
AND
• Use the same dose for all sensitizing
events and post partum dose
9
Weeks gestation
Action
Less than 12 weeks
Only give if surgical intervention,
excess bleeding, abdo pain,
termination
Sensitizing events >12/40
1.
2.
3.
4.
Request 1500iu anti-D
Do Kleihauer if had amnio
or >20/40
Give anti D even if had
prophylaxis
Repeat anti-D + kleihauer
6/52 if on-going
28-30 weeks
Routine antenatal prophylaxis
42 weeks
Consider further dose
Post natal
Give 1500iu anti D when baby is
RhD positive
Dosing equivalence?
Effects on RAADP
Absorption
Extracellular volume
Post partum
41% of women had a RCV >
1800 mL 500 IU of anti-D may
not adequately cover a 4 ml FMH
Propose:
D-negative women >100 kg
should receive an additional
dose of 500iu anti-D
Regan et al 2008
Outcome:
• Midwives happy
• Currently assessing proportion of women
appropriately receiving RAADP (99% 2007)
Current focus:
• Quality of patient information & consent
• How to deliver effective education and training in a
cost and time pressured environment
10
Transfusion Update Meeting
anti-D
Day
Royal Society of Medicine
Saturday, 6th December 2008
11