Plasma for fractionation

Autosufficienza in plasma e plasmaderivati:
situazione attuale e scenari futuri
Seminario AVIS, Roma 21 gennaio 2012
Appropriatezza e impiego clinico:
situazione italiana
e panorama internazionale
Claudio Velati
Società Italiana di Medicina Trasfusionale e Immunoematologia
1
The main topics
• The actual plasma donation situation
• The use of plasma:
– clinical use
– plasma for fractionation
• The needs in the future
• Some ethical aspects
2
The main topics
• The actual plasma donation situation
• The use of plasma:
– clinical use
– plasma for fractionation
• The needs in the future
• Some ethical aspects
3
Number of plasma donations by apheresis
350000
331231
330000
321287
300000
250000
218000
197400
200000
144118
150000
100000
45739
50000
0
0
AUT
BEL
0
DNK
2870
FIN
FRA
DEU
0
0
GRC
IRL
5264
ITA
LUX
3257
NLD
NOR
Blood Transfusion in Europe, The White Book 2005.
3300
0
PRT
ESP
CHE
2300
SWE
GBR
4
Self-sufficiency in plasma for clinical use
From USA
Yes
No
From USA
From Austria
Blood Transfusion in Europe, The White Book 2005.
5
Percentage of self-sufficiency
in plasma derivatives
100 %
80 %
70 %
60 %
20 %
0%
Blood Transfusion in Europe, The White Book 2005.
6
Plasmapheresis collections provide source plasma, including plasma
with specific antibodies, for fractionation into medicinal products.
In some Countries plasma for transfusion referred to as Fresh Frozen
Plasma (FFP) is also collected by apheresis donation.
The volume of plasma collection by apheresis per 1,000 inhabitants
reflects the volume of the national plasmapheresis programs.
In 30 reporting Countries on average 2.5 litres (range 0-14) of plasma
per 1,000 inhabitants is collected by plasmapheresis.
Apparently Austria, Bulgaria, Germany and The Netherlands stand out
as Countries with a considerbly more extensive plasmapheresis
programmes, with about 10 L or more of plasmapheresis plasma per
1,000 inhabitants/year.
Modified from: “The Collection, Testing and Use of Blood and Blood Components in Europe
(2006 Report EDQM-Council of Europe. C.L. vd Poel, M.P. Janssen, M.-E. Behr-Gross
7
Plasma collected by apheresis
(L/x1000 inhabitants)
7
7
Modified from: “The Collection, Testing and Use of Blood and Blood Components in Europe
(2006 Report EDQM-Council of Europe.
Europe) C.L. vd Poel, M.P. Janssen, M.-E. Behr-Gross
8
Plasma collected by apheresis
(L/x103)
Modified from: “The Collection, Testing and Use of Blood and Blood Components in Europe
(2006 Report EDQM-Council of Europe.
Europe) C.L. vd Poel, M.P. Janssen, M.-E. Behr-Gross
9
The main topics
• The actual plasma donation situation
• The use of plasma:
– clinical use
– plasma for fractionation
• The needs in the future
• Some ethical aspects
10
Fresh Frozen Plasma (FFP) has been available
since 1941 and at first was used as volume
replacement.
After the introduction of plasmaderivatives
and hydroxyethyl starch the use of FFP has
been reconsidered and its use was indicated in
case of bleeding, or to prevent bleeding, in
patients with altered coagulation tests.
11
12
13
14
15
Number of transfused plasma units
(apheresis and separation units)
1000000
942007
900000
800000
700000
600000
498724
500000
400000
330000
300000
247409
200000
100000
169900
103000 95500
39607
BEL
DNK
FIN
FRA
DEU
GRC
IRL
73000
99327
3135
0
AUT
50690
36386
25000
ITA
LUX
NLD
Blood Transfusion in Europe, The White Book 2005.
NOR
PRT
ESP
CHE
SWE
GBR
16
Plasma units transfused / 1000 inhabitants
17
18
17
16
16
12
14
11
12
10
8
6
10
8
7
6
8
4
6
1
4
2
0
N
FI
A
FR
RC
U
DE
G
A
IT
X
LU
D
NL
R
NO
P
ES
Blood Transfusion in Europe, The White Book 2005.
E
SW
BR
E
CH
G
L
PO
17
Plasma units transfused / 1000 inhabitants
31
35
28
30
20
25
15
20
15
10
9
13
8
5
10
9
6
6
7
5
0
Modified from: “The Collection, Testing and Use of Blood and Blood Components in Europe
(2006 Report EDQM-Council of Europe
Europe) C.L. vd Poel, M.P. Janssen, M.-E. Behr-Gross
18
IL PLASMA FRESCO CONGELATO E’ INDICATO
– Nella fase acuta della coagulazione intravascolare disseminata
(DIC), in presenza di diatesi emorragica. In assenza di emorragia
l’impiego del plasma non è indicato. Non esiste evidenza che l’uso
profilattico possa prevenire la DIC o ridurre il fabbisogno trasfusionale.
– Nel trattamento della porpora trombotica trombocitopenica (P.T.T.) come liquido
sostitutivo nelle procedure di plasma-exchange e/o per infusione endovenosa.
– Nei deficit congeniti o acquisiti di singoli fattori della coagulazione, in presenza di
emorragia, quando non siano disponibili i concentrati dei singoli fattori.
– Come antagonista degli anticoagulanti orali, in presenza di manifestazioni
emorragiche o in previsione di un intervento chirurgico urgente o manovre invasive ad
alto rischio emorragico, una volta espletati gli altri provvedimenti terapeutici necessari
(ad esempio, la somministrazione di vitamina K)
Raccomandazioni per il buon uso del sangue
Comitato Ospedaliero per il Buon Uso del Sangue AOVV - 2007
Total quantity of plasma used for fractionation
(litres)
1600000
1400000
1200000
584744
1000000
800000
60944
600000
33317
891636
400000
20000
TOTAL
0
2200
TOTAL
470160
200000
336000
0
5500
70000
62300
DNK
FIN
434456
0
217800
0
0
AUT
BEL
270000
7300
FRA
DEU
GRC
0
IRL
From fresh frozen plasma
ITA
LUX
NLD
280000
1361
37463
NOR
TOTAL
219000
80000
0
PRT
0
ESP
CHE
SWE
GBR
Part from other plasma
Blood Transfusion in Europe, The White Book 2005.
20
Plasma for fractionation
• In 31 reporting Countries, an average yield of 7.2 L (range
0-26 L) per 1,000 inhabitants is found of plasma for
fractionation into medicinal products.
• However, 6 of 31 (19%) reporting Countries deliver 15 L or
more plasma per 1,000 inhabitants.
• In Europe, the main supply of plasma for fractionation is
recovered plasma: in 18 reporting MS, on average 70% of
the plasma for fractionation is from recovered plasma
(range 0-100%).
Modified from: “The Collection, Testing and Use of Blood and Blood Components in Europe
(2006 Report EDQM-Council of Europe. C.L. vd Poel, M.P. Janssen, M.-E. Behr-Gross)
21
Plasma for fractionation
(L/x103)
Modified from: “The Collection, Testing and Use of Blood and Blood Components in Europe
(2006 Report EDQM-Council of Europe.
Europe) C.L. vd Poel, M.P. Janssen, M.-E. Behr-Gross
22
23
The main topics
• The actual plasma donation situation
• The use of plasma:
– clinical use
– plasma for fractionation
• The needs in the future
• Some ethical aspects
24
Future demand for plasmaderivatives will
be influenced by:
• Demographics and health services improvements
in emerging countries, growing acceptance,
awareness and funding
• New therapeutic indications
• Pricing pressure
• Increased competition from new manufacturers,
promotional and educational activities
• Plasma procurement and processing capacity
25
Projected Albumin demand
based on the results of several studies
Marketing Research Bureau
26
The main topics
• The actual plasma donation situation
• The use of plasma:
– clinical use
– plasma for fractionation
• The needs in the future
• Some ethical aspects
27
28
29
The EBA-IPFA position
Section 2.11 must continue to make explicit reference to agreed international
definitions for VNRBD (eg CoE, WHO, FDA, ISBT). i.e.CoE
• ‘Voluntary unpaid donation shall mean the donation of blood or blood
components by a person of his/her free will and without receiving payment in
cash or in kind in return which could be considered a substitute for money.
This also includes time off work other than that reasonably required for
donation and travel. Small tokens, gratuities, refreshments and the
reimbursement of direct costs and direct travel expenses are compatible with
the voluntary and unpaid donation of blood.’
• FDA Status of monetary incentives’
• ‘Cash or cash equivalent Tickets or events where markets for resale exists;
• transferable discounts-coupons convertible to cash; music media where
market for resale exists; vouchers for free medical tests; Scholarships paid
directly to students.’
31
Final considerations (1)
Homogeneous assessment of clinical needs is not yet reached: is patient
under-transfused in Spain or over-transfused in Germany, Greece
and Poland?
EU has not yet achieved self-sufficiency in plasma and plasma
derivatives.
About plasmaderivatives, demand, use and needs for patients should be
distinguished (WHO 2010)
Wide variations in per capita use of PDMP in developed countries eg
IVIg use are observed: former EU excluding UK 2007: 55 g/1000,
North America: 120 g/1000.
No evidence that clinical needs are not fulfilled in countries which have
developed robust therapeutic evidence based systems to optimal use
(eg Germany: 36 g per 1000).
32
Final considerations (2)
Europe is close to self reliance with VNRBD plasma:
IVIg use 2007 for 13 countries of the former EU with a total of 3.6
million L of plasma collected from European VNRBD, the level of
sufficiency achieved is in the range of 80 to 86%. Getting closer to 100%
sufficiency from VNRBD plasma should be further developed.
Potential negative impact of paid donations are to be considered:
On the donor health: plasma pools from paid US high-frequency, highvolume plasmapheresis donors showed significantly lower protein
content (eg total IgG: - 24%), than pools from unpaid EU or US WB or
plasmapheresis donors (R Laub et al Vox Sang 2010).
On the blood system: paying donors has been shown as a potential threat
to the wider supply of blood products, as many patients need both labile
blood products and PDMPs.
33
Final considerations (3)
EBA and IPFA continue their advocacy for developing VNRBD
with coordinated blood and plasma programmes which would
better meet all patients’ needs and comply with the donor health
requirements and the European commitment on ethical issues
and unpaid donations.
Some ethical issues have to be clarified: the anti-D paradox.
The USA – EU challenge is open!
34