Plasma separation is a medical and industrial process that isolates the liquid component of blood (plasma) from its cellular elements. Plasma makes up about 55% of total blood volume and is roughly 92% water. The remaining portion consists of dissolved proteins, including albumin, antibodies (immunoglobulins), and clotting factors, along with salts, hormones, and nutrients. The objective is to extract this protein-rich fluid from red blood cells, white blood cells, and platelets. This separation allows for therapeutic use in patients or for manufacturing life-saving medicines, maximizing the utility of every donation.
How Plasma is Separated
Centrifugation
Plasma separation relies on differences in density and particle size between the liquid plasma and the cellular components. The most widely used technique for high-volume separation is centrifugation, which uses a powerful spinning motion to apply centrifugal force to the blood sample. Because red blood cells, white blood cells, and platelets are denser than plasma, they are rapidly pushed to the bottom of the container. This results in the layering of components, with the least dense plasma forming the top, straw-colored layer. This highly efficient process often takes less than ten minutes and yields high-purity plasma.
Membrane Filtration
In automated donation or therapeutic devices, centrifugation is performed continuously in a sealed apheresis machine. The machine draws blood, separates the plasma in a spinning chamber, and then returns the remaining cells to the donor or patient. An alternative method is membrane filtration, which relies on particle size exclusion. Whole blood is passed across a semi-permeable membrane with microscopic pores that allow smaller plasma proteins and fluid to pass through, while retaining larger cellular components.
Membrane filtration is often used in certain therapeutic devices and point-of-care settings due to its simpler, more portable setup. While filtration avoids the need for high-speed spinning equipment, it can be slower for processing large volumes of blood. Continuous blood flow can also lead to the clogging of the filter membrane, limiting its throughput. Centrifugation remains the standard method for large-scale collection and rapid clinical procedures.
Plasma Collection for Supply
Most collected plasma is used as a raw material for manufacturing complex pharmaceutical products. This source plasma is collected from healthy donors primarily through automated plasmapheresis. During this donation, a machine continuously separates and collects the plasma while returning the red blood cells and other components to the donor. Plasma can also be recovered from traditional whole blood donations, though this yields a smaller volume.
Once collected, thousands of individual plasma donations are pooled and subjected to fractionation, a complex industrial process. Fractionation involves carefully controlled changes in temperature, acidity (pH), and alcohol concentrations to separate and purify specific therapeutic proteins. This multi-step purification isolates valuable components such as albumin, immunoglobulins (antibodies), and various clotting factors. These purified proteins are then formulated into life-saving medicines.
These separated proteins are formulated into medicines used to treat rare, chronic, and life-threatening conditions. For example, immunoglobulins treat primary immune deficiencies, and clotting factors manage hemophilia. Separated plasma samples are also routinely used in diagnostic testing and biomedical research to study disease markers and biological processes.
Clinical Application: Therapeutic Exchange
Plasma separation is also used directly in a clinical setting through Therapeutic Plasma Exchange (TPE). TPE involves removing a patient’s plasma and replacing it with a substitute fluid, such as albumin and saline or donor plasma. The primary purpose of this exchange is to rapidly eliminate large molecular weight substances causing disease that cannot be easily removed by standard dialysis.
Many conditions treated with TPE are autoimmune disorders where harmful autoantibodies circulate in the plasma and attack the body’s own tissues. Removing the plasma clears a significant portion of these pathological antibodies from the bloodstream. TPE is a standard treatment for conditions including Guillain-Barré Syndrome, Myasthenia Gravis, and Thrombotic Thrombocytopenic Purpura (TTP). For instance, TPE quickly reduces autoantibodies in Myasthenia Gravis, particularly during a severe crisis.
The TPE procedure typically lasts a few hours, cycling the patient’s blood through an apheresis machine. The machine separates the harmful plasma using centrifugation or membrane filtration, and the cellular components are immediately returned to the patient with the replacement fluid. A typical session can remove 65% to 70% of the disease-causing proteins from the plasma. This rapid removal provides clinical benefit when conventional therapies are too slow or ineffective.