The Effect of Plasma Donation Frequency on Plasma Protein Composition, Inflammation Markers and Psychological Distress - a Randomized Controlled Trial

Plasma is the largest single component of blood and makes up about 55% of the total blood volume. It carries the cellular parts of the blood and consists of 90% water, more than 1000 different proteins, and other substances such as minerals, hormones, lipids, and vitamins. The plasma is important for osmotic pressure, intravascular volume, and circulation of hormones, electrolytes, and proteins.

Collected plasma may be used as fresh frozen plasma for transfusion or as plasma for fractionation. Plasma sent for fractionation is further processed into purified therapeutic proteins called plasma-derived medicinal products (PDMPs). Examples of PDMPs are albumin, immunoglobulins, blood coagulation factors like prothrombin complex, and protease inhibitors like α1-antitrypsin. PDMPs are used to treat patients with a wide variety of diseases, for example, congenital diseases like severe combined immunodeficiency, α1-antitrypsin deficiency, or hemophilia. Treatment with PDMPs is often lifelong. Plasma used in transfusion and PDMPs were recently added to the World Health Organization (WHO) Model List of Essential Medicines, underscoring the importance of these products. The demand for plasma and PDMPs is increasing worldwide.

USA is responsible for 70% of the world's source plasma supply. The commercial plasma industry often relies on paid, high-frequency plasma donors, which raises several ethical questions and concerns about donor health. Norway's blood supply is based on voluntary non-remunerated blood donors (VNRBD), which means that a person gives blood, plasma, or cellular components of his/her own free will and receives no payment for it, and this is considered as the safest and most sustainable blood supply.

Current recommendations allow a maximum of 33 plasma donations per year with a minimum 96-hour interval. The collection volume for each plasmapheresis is based on an estimation of the total blood volume calculated according to the International Committee for Standardization in Haematology (ICSH) formula and must never exceed 880 mL plasma. The donation interval is adjusted after measurement of total serum protein (TSP), which is required at the first donation and measured at least annually, as well as serum immunoglobulin G (IgG), which has to be measured at least annually in addition to at every fifth donation. TSP must not be less than 60 g/L, and IgG must not be less than 6.0 g/L. The earlier national guidelines in Norway allowed plasma donations of 650 ml plasma each donation, up to 15 L of plasma every year, and minimum 2 weeks donation interval. At Innlandet Hospital Trust, currently apheresis donors donate every 4 weeks or rarer, and only 324 plasmaphereses were performed in 2019.

The impact of high-frequency plasma donations on plasma protein composition and donor health has not been thoroughly examined. Although high-frequency plasma donation is associated with lower plasma protein levels, donor safety has been ensured by monitoring concentrations of TSP and IgG to adjust donation frequency. A cross-sectional study argued for the safety of long-term intensive donor plasmapheresis of up to 45 l of plasma per year in terms of immunity, red cell and iron metabolism, and cardiovascular risk markers. Another cross-sectional study used pooled plasma samples from different countries with different sampling frequencies and sampling volumes. In this study, however, they found that high-frequency and high-volume plasma donations were associated with a limited ability for plasma proteins, especially immunoglobulins, to return to normal physiological levels. Furthermore, levels of plasma proteins were substantially lower in donors undergoing frequent plasmapheresis than in controls. How these differences in protein concentrations are related to the health of the donors is uncertain.