This research line mainly deals with donor base analysis, donor health care and donor eligibility assessment. The primary research questions are:
1. How is donor selection shaped best, while assuring that the demands for blood products are met, regarding both quantity and quality?
2. How is donor health care shaped best?
Donor eligibility assessment, or selection is done at the recruitment stage and/or at the point where donors are invited to make a donation. Donor selection is based on many factors or donor characteristics. For instance when new donors register, their blood type is assessed. Donors whose blood type is more frequently needed will generally be asked to donate more often. One of the challenges is to find out which donors have these frequently needed blood types, especially when extensively phenotyped red blood cell concentrates are needed for alloimmunized patients. Moreover, donor selection should be risk assessment based.
Furthermore donors are screened before making a donation by assessing characteristics including hemoglobin levels, prevalent disease, and certain risky (sexual) behaviors. In about 10% of all donation attempts, a donor is deferred at this stage. A decision of deferral is made when proceeding with the donation may either harm the donor’s health (e.g. because of iron depletion), or that of the recipient of blood product(s), e.g. because of infectious disease. Since deferral is a proven reason of donor lapse, reducing these percentages is paramount. The main reason for donor deferral is low hemoglobin (Hb);2-3% of male donors and 5-7% of female donors are being deferred for low Hb. Therefore prediction and prevention of low Hb-levels and depleted iron status are important targets of this research line.
Although blood donation is generally safe, some short and long term side effects may occur. Mostly, these effects are not serious; examples are local reactions, such as bruises, vasovagal reactions and iron depletion. Nonetheless donors are a healthy group of individuals who donate voluntarily and any harm should be prevented. Positive side effects have also been hypothesized; therefore long term effects on chronic diseases are studied as well. An ultimate task would be to find factors that distinguish donors who benefit from (frequent) donations from those to whom it does harm.
- Donor InSight
- Prediction models for hemoglobin deferral in whole blood donors
- Heterogenic donors
Donor InSight, Part 1
Donor InSight (DIS) is a large-scale, longitudinal survey based study, conducted among a random sample of 50,000 whole blood and plasma donors in 2007-2009. The aim of DIS is to understand the characteristics of donors (socio-demographic, lifestyle), their experiences with donation, reasons and motivation for donor return or lapse, their medical history and physical and psychological effects of donation. 31,338 (63%) donors participated and the majority gave permission for linking their DIS data to donation records and medical records and to be contacted for future studies. Some examples of publications that resulted from the DIS study are:
- Atsma F, Veldhuizen I, de Vegt F, Doggen C, de Kort W. Cardiovascular and demographic characteristics in whole blood and plasma donors: results from the Donor InSight study. Transfusion 2011; 51(2):412-20.
- Atsma F, Veldhuizen I, Verbeek A, de Kort W, de Vegt F. Healthy donor effect: its magnitude in health research among blood donors. Transfusion 2011; 51(8):1820-8.
- Veldhuizen I1, Atsma F, van Dongen A, de Kort W. Adverse reactions, psychological factors, and their effect on donor retention in men and women. Transfusion. 2012; 52(9):1871-9.
Furthermore, the DIS results are an important source of information for improvements to the blood supply. A better understanding of donor characteristics and motivation contribute to a more efficient and focused strategy regarding donor recruitment and retention. Knowledge of donation experience and health effects of donation contributes to keeping donors healthy and reducing the number of deferred and lapsing.
Donor InSight, Part 2 (follow up)
In order to investigate changes in donor behaviour and motivation, lifestyle, health, etc., again 50,000 questionnaires were sent out in 2012-2013. All still eligible participants from DIS-1 (n=29,532) and a new random sample of 20,468 donors were contacted. In total, 34,823 (69.7%) donors participated. The questionnaires have been processed and the data will be available to use after data cleaning.
Blood donation generally is seen as a safe, voluntary and socially useful activity, based on the altruism of donors. A number of positive effects of blood donation are described in scientific literature, such as feelings of satisfaction, feelings of being more alert and feeling better in general. However, the majority of the literature concerning blood donation describes negative experiences, such as fatigue, vasovagal symptoms, fainting, bruises or hematomas. Besides the pain, anxiety or fear exhibited by the donor, this might also impede people from donating blood in the future. Also, it might trigger a stress reaction.
Stress reactions are quite common phenomena. When someone is confronted with a stressful situation, a stress reaction occurs. Factors inducing such a stress reaction, known as stressors or stress stimuli, are thought to be diverse, meaning that every situation or every object might elicit a stress reaction, whereas the stress experience might differ between individuals and circumstances. Recent research has also shown that even anticipatory stress (worrying about what is to come) causes physiological arousal, thereby inducing stress reactions in blood. Reaction include increases in heart rate, blood pressure and cortisol, but also relate to changes in blood clotting, platelet activation and increases in clotting factors. Therefore, acute psychological stress in voluntary blood donors may have an effect on the quality of donated whole blood and the derived blood products, such as platelets, plasma and red blood cells.
Unfortunately, up till now it remains largely unclear if there is a relation between blood donation and stress. Therefore, we will investigate the effects of blood donation related stress for the donor, by combining physiological (heart rate, heart rate variability, blood pressure), hormonal (cortisol), and psychological measurements (stress, anxiety) in immediate conjunction with the bloodletting procedure. In addition we want to study the possible effects of donation stress in donors by measuring coagulation and platelet activity. If donation stress does indeed affect hemostasis in the donor, we will also investigate the effect of donation stress on the collected blood product(s).
Each year, a relevant proportion of the invited blood donors is eventually deferred from donation because of low hemoglobin (Hb) levels. Deferrals are meant to protect donors from developing iron deficiency anemia after a blood donation, however, they may increase the risk of donor lapse, even though the donor may actually meet the Hb criterion at the time of the next donation invitation. Early estimation of the risk of Hb deferral on the next visit to the blood collection center could be helpful in the management of the blood donation program.
As a PhD student, Mireille Baart developed prediction models for Hb deferral risk in whole blood donors. The prediction models were developed in Dutch whole blood donors. Predictive factors in the models are Hb level measured at the previous visit, age, seasonality, difference in Hb levels between the previous two visits, time since the previous visit, deferral at the previous visit, and the total number of whole blood donations in the past two years. The models were externally validated in a cohort of Irish donors. After updating the models to the Irish situation the performance of the models was satisfactory. Subsequently, the added value of zinc protoporphyrin (ZPP) levels to the prediction models was investigated. Results showed that addition of ZPP improved the model performance.
Results from studies on the prediction models show that with a limited number of easy-to-measure characteristics the risk of Hb deferral in whole blood donors can be reliably predicted. The model predictions could be helpful in the management of the donation program by applying them in the invitation process of blood donors. Donors with a low predicted risk of Hb deferral can be invited for a donation with preference, whereas for donors with a high risk of Hb deferral interventions such as postponement of the invitation for donation or a dietary advice are warranted.
As a postdoc, Mireille Baart is working on an impact study of the prediction models. In this study, the effectiveness of using the models for the selective invitation of donors with a low risk of Hb deferral will be evaluated in terms of the number of Hb deferrals, donor lapse and costs. Results of this study will show whether implementation of the prediction models in practice would be valuable.
There is little knowledge about the response of the body to iron loss caused by blood donation. The kinetics of iron after whole blood donation will be investigated by comparing new whole blood donors with frequent whole blood donors. The effect of whole blood donation on iron kinetics, iron absorption and iron incorporation in erythrocytes will be studied. Therefore, donors will be followed for a period of six months after whole blood donation. Furthermore, it will be investigated what is the most adequate parameter to detect iron deficiency in whole blood donors. With the results of this study we want to determine the donation interval for whole blood donors on a more personalized level and thereby reduce the number of deferrals due to low hemoglobin levels.
Frequent whole blood donations may carry the risk of iron depletion and subsequent hemoglobin (Hb) level decrease. A low Hb level may lead to deferral for donation, which results in unnecessary costs for the blood bank and an increased risk of donor lapse. There are large differences in Hb levels and Hb recovery after donation between donors. Several factors are known to influence Hb, for example sex, age and season. However, genetic loci associated with red cell parameters may also play a role, but this has never been studied. Therefore, the aim of this study is to investigate genetic factors associated with declining versus stable Hb levels in blood donors. Furthermore, it will be assessed whether genetic factors can improve existing prediction models. Last, health effects of iron deficiency in blood donors will be examined.
Blood donors with a known Hb level of their first donor screening, who have already participated in Donor InSight 2 and gave permission to be recontacted will be eligible to participate in this study. From this group we will select donors who represent the extreme ends of four groups of donors with different Hb trajectories:
1. Donors with high naïve Hb levels that decline over time
2. Donors with high naïve Hb levels that remain stable over time
3. Donors with low naïve Hb levels that decline over time
4. Donors with low naïve Hb levels that remain stable over time
This list of potential participants will be complemented with a group randomly selected donors, in order to also enable analyses on a representative sample of the donor population. We expect that 3,000 blood donors will participate in this study.
Increased knowledge on genetic factors that distinguish between donors with different Hb trajectories after repeated blood donations will help to select donors and tailor their donation intervals in order to prevent iron deficiency, deferral for donation and unnecessary costs.