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Evidence basis of plasma donor protection
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
Editor's Notes
The general objective of SUPPLY WP5 is to facilitate evidence-based plasma donor protection practices
Project 1, collecting information on current plasma donor protection practices will be presented by Marloes Spekman
I will present the results and conclusions of task 2, evaluating the available scientific evidence on plasma donation & donor health
In a first stage, we conducted a scoping review. A scoping review aims to explore a new theme (in this case plasma donation & donor health), to identify available study designs and/or to identify evidence gaps.
The first step is to define a broad PCC question, describing the population, concept, and context.
Our question was, which studies are available that investigated the safety or health of plasmapheresis (concept) in healthy donors (population), in any setting or geographial location (context), the search date for this review was October 2022.
After searching 5 databases and 3 registers, 2 reviewers independently conducted the study selection which finally resulted in 90 observational studies (57 controlled and 33 uncontrolled) and 16 controlled experimental studies
Fourth and final step in the scoping review, charting important study characteristics, and translate this information into an evidence gap map.
Information on the following characterics were charted:
Publication type (research article or trial registry)
Publication language
Study design
Population
Convalescent plasma
Time of outcome assessment
Duration of follow-up
Number and frequency of plasma donations within the study period
Study setting and location
The 2 main axes in our data charting table were
the outcomes (which were divided in different adverse events categories and categories related to health effects)
Studies factors that were potentially associated with these outcomes.
We used EPPI mapper software to translate this information from the 106 included studies into an interactive evidence map, which you can download via the QR code at the right upper corner.
In this screenshot, you can see the 2 main axes, outcomes in red and the associated factors in yellow
Both adverse events and health effect outcomes have further subcategories, which I will not show into detail given the limited time available.
Also associated factors were subdivided into donor characteristics, plasma donation characteristics, preventive measures or ‘none’ (meaning that prevalence or incidence of adverse events/health effects was assessed).
The coloured squares in the map indicate the study design, dark blue represents uncontrolled observational studies, light blue controlled observational and green indicate experimental studies.
If you access the map, you will see that different filters (related to the charted characteristics) can be used.
Four important research gaps were identified, namely limited or a lack of evidence regarding
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
Therefore, more future high-quality research studies, especially experimental/quasi-experimental studies, are needed.
The latter topic, different donation frequencies, was selected to further explore into detail in the second stage of our WP, the systematic review
The aim of a systematic review is to formulate a conclusion about a specific PICO question, describing the population –intervention – comparator and outcomes of interest
Our PICO question was: what is the impact of plasmapheresis frequency on safety or health of healthy donors.
We included controlled experimental/observational studies investigating higher frequency of plasmapheresis or plasmapheresis frequency of longer duration compared to a lower frequency of plasmapheresis, placebo, no plasmapheresis or plasmapheresis frequency of shorter duration.
Population of interest were healthy donors, primary outcomes were adverse events, secondary outcomes: cardiovascular health and protein levels.
The search date of this review was May 2023.
We excluded studies comparing first-time versus repeated donors were excluded, as well as studies comparing different (cumulative) numbers of plasma donations without specifying the exact donation frequency
After searching databases/trial registers and screening the literature, we finally included 4 observational studies, and 3 experimental studies (of which 1 is ongoing).
In contrast to a scoping review, a detailed synthesis and quality assessment of the included studies is executed, together with the formulation of evidence conclusions.
The 4 observational studies (3 old studies from the seventies/eighties and 1 from 2013) can be shortly presented due to the very-low quality. According to the GRADE approach, the initial quality of observational studies is considered as low, the quality of these 4 studies was further downgraded to very low due to methodological limitations (risk of bias) and due to limited sample sizes.
The 4 observational studies (3 old studies from the seventies/eighties and 1 from 2013) can be shortly presented due to the very-low quality. According to the GRADE approach, the initial quality of observational studies is considered as low, the quality of these 4 studies was further downgraded to very low due to methodological limitations (risk of bias) and due to limited sample sizes.
Very low quality evidence means that any estimate of effect is very uncertain (we don’t know actually)
We also included 2 experimental studies:
1 Canadian non-RCT from 1993 where repeated, voluntary donors received plasmapheresis once per week for 6 months compated to plasmapheresis once every 2 weeks for 6 months and were total protein, IgG, IgA and IgM were assessed
1 recent Belgian RCT where 72 voluntary plasmapheresis donors were randomly assigned to the following groups: very high frequency donation (donating plasma twice per week for 12 weeks), high frequency group (3 donations per month for 12 weeks), a low-frequency group (1 donation per month for 12 weeks) and a placebo group where participant had a sensation of undergoing a plasma donation, once per month for 12 weeks). Adverse events (according to the ISBT tool), (non-)biochemical cardiovascular health markers and different protein levels were assessed
In terms of our primary outcome,the adverse events, this RCT found that
5 haematomas were present, 3 in the high frequency group and 2 in the very high-frequency group, looking to the adverse event rate for haematoma (expressed per 50 donations): rates were very low, about 1 haematoma per 50 donations in HF group and 0,28 in VHF
A total amount of 5 vasovagal reactions were reported, which resulted in an adverse event rate of 0,36 (per 50 donations) in HF and 0,57 (per 50 donations) inVHF
Finally, 6 anaemic events were detected in VHF (with a rate of 0,85 per 50 donations).
Conclusion is that few minor adverse events were reported in the high/very high frequency group and no other (major) events were reported.
In the Canadian study, total protein, IgG, IgA, IgM were assessed during 6 months and compared between the weekly and bi-weekly donation group, the mean difference, visualized at the right panel, indicate that all these protein levels were reduced in the weekly donation group, but none of these differences were statistically significant or clinically meaningful (given the normal ranges of these protein levels)
The Belgian RCT found that haemoglobin levels were reduced in the very high frequency group compared to the low frequency and placebo group, this difference was statistically significant but not clinically meanigful given the normal range, expressed by the red dotted line.
Ferritin levels were reduced in both high and very high frequency group compared to the low frequency and placebo group and this statistical significant difference was considered as clinically relevant since ferritin levels of 20 micorgram/L were below the lower limit of normal (22 micorgram/L)
An important finding was that, compared to the placebo group, a small reduction in IgG levels in the low and high frequency was present (IgG values are within normal range), the reduction in IgG levels was more pronounced in the very high frequency group, and this reduction is considered to be clinically relevant since the IgG levels dropped below the lower limit of normal, this is 6 g/L
No differences were observed in IgA/IgM levels
Finally, albumin levels were reduced in the very high frequency group, but were within the normal range.
Therefore, we concluded that
Finally, several cardiovascular health markers were assessed (glycaemia, HbA1c, insulinaemia, total cholesterol, blood pressuren body composition and exercise-related parameters, although some markers were statistically signifcantly reduced in high/very high frequent donors (glycaemia/HbA1c), all observed differences were considered to be clinically irrelevant
Therefore, we concluded that …
The initial quality of the evidence of experimental studies starts at high (because this type of trials are considered as the gold standard to assess causality)
The quality of the 2 included trials was further downgraded due to methodological limitations and limited sample sizes, which finally resulted in low-certainty evidence
Which means that further research is needed because future research studies will very likely have an important impact in our confidence in the estimate of effect and will likely change the estimate.
Finally, I would like to thank the different EBA and WP5 SUPPLY members, especially Tine D’aes and Natalie Schroyens which served as excellent reviewers in both the scoping/systematic review, and Christian Erikstrup and Katja van den Hurk to coordinate WP5 and facilitated the discussions during the completion of this work.
Thank you for your attention.
