1. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Strengthening voluntary non-remunerated plasma
collection capacity in Europe (SUPPLY)
Evaluating the evidence basis of plasma donor protection practices (WP 5.2):
A scoping review and a systematic review
European Conference on Donor Health & Management 2023

2. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
• To facilitate evidence-based plasma donor protection practices
 5.1 Collect information on current plasma donor protection practices
 5.2 Evaluate the available scientific evidence on plasma donation & health
 5.3 Support tool on standardized donor vigilance data to be collected
 5.4 Develop recommendations
Objective SUPPLY – WP5

3. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
4. Data extraction & synthesis
3. Selection of articles
2. Developing a search strategy
1. Defining PICO question (focused)
5. Quality assessment
6. Evidence conclusions
4. Data charting & mapping
3. Selection of articles
2. Developing a search strategy
1. Defining PCC question (broad)
Scoping review Systematic review
Aim: to explore a new theme; to identify
available study designs; to identify gaps in
a body of literature
Aim: to formulate a conclusion about a
focused research question

4. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review: PCC question
?
Which studies are
available that
investigated
the safety or health of
plasmapheresis (C),
in healthy donors (P),
in any setting or
geographical location
(C)?
Population
Concept
Healthy donors who underwent plasmapheresis
Safety of plasmapheresis (adverse events and other health effects)
Design Systematic reviews, (non-)randomized controlled trials, (un-)controlled observational studies
Language No restrictions
Search date 10th of October 2022
Context Any setting or geographical location

5. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review versus Systematic review
4. Data extraction & synthesis
3. Selection of articles
2. Developing a search strategy
1. Defining PICO question (focused)
5. Quality assessment
6. Evidence conclusions
4. Data charting & mapping
3. Selection of articles
2. Developing a search strategy
1. Defining PCC question (broad)
Scoping review Systematic review
Aim: to explore a new theme; to identify
available study designs; to identify gaps in
a body of literature
Aim: to formulate a conclusion about a
focused research question
Finally included:
 90 observational studies (57 controlled –
33 uncontrolled)
 16 controlled experimental studies

6. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review versus Systematic review
4. Data extraction & synthesis
3. Selection of articles
2. Developing a search strategy
1. Defining PICO question (focused)
5. Quality assessment
6. Evidence conclusions
4. Data charting & mapping
3. Selection of articles
2. Developing a search strategy
1. Defining PCC question (broad)
Scoping review Systematic review
Aim: to explore a new theme; to identify
available study designs; to identify gaps in
a body of literature
Aim: to formulate a conclusion about a
focused research question

7. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review: data charting
study setting
location
population
convalescent plasma (y/n)
time of outcome assessment
duration of follow-up
number and frequency of donations within the study period
outcomes (adverse events - health effects)
associated factors
publication type
publication language
study design

8. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review: data mapping – evidence (gap) map
Filters:

9. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review - Take home messages?
Research gaps Future directions
Preventive measures
Factors potentially affecting the occurrence of
adverse events
Long-term health effects of plasma donation
Different donation frequencies and the effect on
donor safety
More high-quality controlled ((quasi-)experimental)
studies

10. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review versus Systematic review
4. Data extraction & synthesis
3. Selection of articles
2. Developing a search strategy
1. Defining PICO question
5. Quality assessment
6. Evidence conclusions
4. Data charting & mapping
3. Selection of articles
2. Developing a search strategy
1. Defining PCC question (broad)
Scoping review Systematic review
Aim: to explore a new theme; to identify
available study designs; to identify gaps in
a body of literature
Aim: to formulate a conclusion about a
focused research question

11. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
PICO question + eligibility criteria
?
What is the impact
of
plasmapheresis
frequency (I),
on safety or health
(O),
of healthy donors
(P)?
Population
Intervention
Comparator
Healthy adults who donated plasma via plasmapheresis
Higher frequency of plasmapheresis; plasmapheresis frequency of longer duration
Lower frequency of plasmapheresis, placebo, no plasmapheresis; plasmapheresis
frequency of shorter duration
Outcome Primary: Adverse events (ISBT grading tool)
Secondary: Cardiovascular health, protein levels
Design Controlled experimental/observational studies
Language English, Dutch, French, or German
Search date 23rd of May 2023

12. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review versus Systematic review
4. Data extraction & synthesis
3. Selection of articles
2. Developing a search strategy
1. Defining PICO question
5. Quality assessment
6. Evidence conclusions
4. Data charting & mapping
3. Selection of articles
2. Developing a search strategy
1. Defining PCC question (broad)
Scoping review Systematic review
Aim: to explore a new theme; to identify
available study designs; to identify gaps in
a body of literature
Aim: to formulate a conclusion about a
focused research question
Finally included:
 4 observational studies (cohort)
 2 experimental studies (1 RCT and 1
non-RCT)
 1 ongoing experimental study (RCT)

13. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Scoping review versus Systematic review
4. Data extraction & synthesis
3. Selection of articles
2. Developing a search strategy
1. Defining PICO question
5. Quality assessment
6. Evidence conclusions
4. Data charting & mapping
3. Selection of articles
2. Developing a search strategy
1. Defining PCC question (broad)
Scoping review Systematic review
Aim: to explore a new theme; to identify
available study designs; to identify gaps in
a body of literature
Aim: to formulate a conclusion about a
focused research question

14. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Certainty assessment body of evidence ( 4 observational studies)
Downgrading with 1 level due to
• methodological limitations
• imprecision of results (due to limited sample sizes)
Final certainty of evidence:
VERY LOW
Initial certainty of evidence: LOW

15. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Certainty of
evidence
Definition
HIGH
We are very confident that the true effect lies close to that of the estimate of the effect
Further research is very unlikely to change our confidence in the estimate of effect
MODERATE
We are moderately confident in the estimate of effect: the true effect is likely to be close to the
estimate of effect, but possibility to be substantially different.
Further research is likely to have an important impact on our confidence in the estimate of
effect
LOW
Our confidence in the effect is limited: the true effect may be substantially different from the
estimate of the effect.
Further research is very likely to have an important impact on our confidence in the estimate
of effect and is likely to change the estimate.
VERY LOW
We have very little confidence in the effect estimate: the true effect is likely to be substantially
different from the estimate of effect.
Any estimate of effect is very uncertain

16. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Included experimental studies (1 non-RCT & 1 RCT)
Author, year, country
(study design)
Population Intervention Comparator Outcomes
Ciszewski, 1993, Canada
(non-RCT)
61 currently active, voluntary
plasmapheresis donors
Donor status: repeated
Frequency: once per week
Volume (per donation): 500mL (<80kg)
or 600mL (>80kg)
Duration: 6 months
Frequency: once every 2 weeks (or
longer)
Volume (per donation): 500mL (<80kg)
or 600mL (>80kg)
Duration: 6 months
Protein levels: total protein, IgG, IgA,
IgM
Mortier, 2023, Belgium
(RCT)
72 voluntary plasmapheresis donors
Donor status: 1 new and 71 regular
donors who had not donated for at
least 2 weeks
Very high-frequency
Frequency: twice per week
Volume (per donation): 650 mL
Duration: 12 weeks
High-frequency
Frequency: 3 donations per month
Volume (per donation): 650 mL
Duration: 12 weeks
Low-frequency
Frequency: 1 donation per month
Volume (per donation): 650 mL
Duration: 12 weeks
Placebo
Frequency: once per month
Volume (per donation): 0mL (sensation
of undergoing a plasma donation)
Duration: 12 weeks
Adverse events (ISBT grading tool,
except citrate reactions)
Cardiovascular health: glycemia,
insulinemia, HbA1c, total cholesterol,
SBP, DBP, BMI, %Fat, FM, FFM, lactate
190W, lactate post, HRmax, VO2peak,
oxygen pulse
Protein levels: Ferritin, albumin, IgG,
IgA, IgM

17. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Mortier et al., 2023
RESULTS
• Five haematomas were present in HF (3 events in 3 donors, adverse event rate (per 50
donations): 1.08) and VHF (2 events in 1 donor, adverse event rate: 0.28).
• A total amount of 5 vasovagal reactions were reported, 1 in HF (1 donor, adverse event
rate: 0.36) and 4 in VHF (3 donors, adverse event rate: 0.57).
• Six anaemic events (in 5 donors, adverse event rate: 0.85) were detected in VHF.
CONCLUSIONS
Few (minor) adverse events were reported in (very) high frequency plasmapheresis.
No other (major) events were reported.
Primary outcome: adverse events

18. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Secondary outcome: protein levels
Normal range
30-80 g/L
6,0 – 16,0 g/L
0,8-3,0 g/L
0,4-2,5 g/L

19. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
RESULTS
Secondary outcome: protein levels
13
14
15
16
D0 D42 D84
Haemoglobin
(g/dl)
0
20
40
60
80
100
120
D0 D42
Ferritin
(µg/l)
D0 D42 D84
0
20
40
60
80
100
120
D0 D42 D84
Ferritin
(µg/l)
* *
* * * *
Mortier et al., 2023

20. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
RESULTS
Secondary outcome: protein levels
5
6
7
8
9
10
11
12
D0 D42 D84
IgG
(g/l)
1,0
1,5
2,0
2,5
3,0
D0 D42 D84
IgA
(g/l)
0,4
0,6
0,8
1,0
1,2
D0
IgM
(g/l)
1,0
1,5
2,0
2,5
3,0
D0 D42 D84
IgA
(g/l)
0,4
0,6
0,8
1,0
1,2
D0 D42 D84
IgM
(g/l)
5
6
7
8
9
10
11
12
D0 D42 D84
IgG
(g/l)
1,0
1,5
2,0
2,5
3,0
D0 D42 D84
IgA
(g/l)
0,4
0,6
0,8
1,0
1,2
D0
IgM
(g/l)
* *
*
Mortier et al., 2023

21. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
RESULTS
Secondary outcome: protein levels
35
40
45
50
55
D0 D42 D84
Albumin
(g/l)
* *
Mortier et al., 2023

22. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Seconday outcome: protein levels
CONCLUSIONS
Very high frequency plasmapheresis (twice per week) may result in a large reduction
in ferritin and IgG levels
(Very) high frequency plasmapheresis may result in little to no difference in other
protein levels (haemoglobin, IgA, IgM, albumin, CK)
Mortier et al., 2023

23. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Mortier, 2023, Belgium Higher plasmapheresis
frequency
(intervention)
Lower
plasmapheresis
frequency (control)
Statistically
significant
(p<0.05)
effect?
Magnitude of effect? (clinically)
Glycaemia 3 times a month
2 times a week
once per month yes Trivial, small unimportant, no effect
HbA1c 2 times a week once per month yes Trivial, small unimportant, no effect
Insulinaemia, total cholesterol, blood
pressure, body composition, exercise-
related parameters
3 times a month
2 times a week
once per month no Trivial, small unimportant, no effect
RESULTS + CONCLUSIONS
Secondary outcome: cardiovascular health
 (Very) high frequency plasmapheresis may result in little to no difference in cardiovascular health markers
Mortier et al., 2023

24. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Certainty assessment body of evidence (experimental studies)
Initial certainty of evidence: HIGH
Downgrading with 2 levels due to
• methodological limitations
• imprecision of results (due to limited sample sizes)
Final certainty of evidence:
LOW

25. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
Certainty of
evidence
Definition
HIGH
We are very confident that the true effect lies close to that of the estimate of the effect
Further research is very unlikely to change our confidence in the estimate of effect
MODERATE
We are moderately confident in the estimate of effect: the true effect is likely to be close to the
estimate of effect, but possibility to be substantially different.
Further research is likely to have an important impact on our confidence in the estimate of
effect
LOW
Our confidence in the effect is limited: the true effect may be substantially different from the
estimate of the effect.
Further research is very likely to have an important impact on our confidence in the estimate
of effect and is likely to change the estimate.
VERY LOW
We have very little confidence in the effect estimate: the true effect is likely to be substantially
different from the estimate of effect.
Any estimate of effect is very uncertain

26. This report is part of the project “101056988/SUPPLY” which has received funding from the European Union’s EU4Health Programme (2021-2027). The content of this report represents the
views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency
(HaDEA) or any other body of the European Union.
The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
• Tine D’aes
• Natalie Schroyens
• Emmy De Buck
• Veerle Compernolle
• Christian Erikstrup
• Susan Mikkelsen
• Katja van den Hurk
• Marloes Spekman
Acknowledgments – EBA/WP5 SUPPLY members
• Elodie Pouchol
• Pascale Richard
• Torsten Tonn
• Thomas Burkhardt
• Pierre Tiberghien
• Peter O’Leary
• Petar Kos
• Gaia Mori