Therapeutic apheresis: history, clinical application, and lingering uncertainties

Undertaking a review article to commemorate a 50th anniversary engenders an appreciation of history. Since therapeutic apheresis (TA) is a field that is completely dependent on an underlying technology, it seems appropriate to begin this article with a brief overview of the history of apheresis technology. As it happens, many seminal events occurred within a 20-year period that nicely brackets the publication of the first issue of TRANSFUSION. One line of development began in Boston in the early 1950s. Dr Edwin Cohn, a Harvard biochemist, had devised a large-scale method for purification of albumin from pooled human plasma. Albumin would tolerate pasteurization and was expected to be a safer agent for resuscitation of wounded soldiers than lyophilized pooled plasma, which had proven in World War II to carry an appalling risk of hepatitis transmission. As an offshoot of this effort, Dr Cohn envisioned a device that would separate donor plasma—the desired component—immediately and “online” during the whole blood donation process. The resulting “Cohn centrifuge,” a huge apparatus with a “reusable” metal centrifugal element, was never really practical for its intended purpose, although it proved useful for deglycerolizing frozen red blood cells (RBCs). Fortunately a young engineer named Alan Latham was commissioned to improve it. When others’ enthusiasm for the instrument flagged, he obtained control of the relevant patents, improved the design of the centrifugal element, and found a way to fabricate a single-use version from plastic at a modest cost. The resulting “Latham bowl” was first marketed in a device for washing or deglycerolizing RBCs (Haemonetics Model 10). It was later adapted for “intermittent-flow” platelet (PLT) donation and TA procedures in the Haemonetics Model 30, which was the first apheresis instrument to be widely available on a commercial basis. A second “bloodline” of technology for TA had its inception at the National Cancer Institute (NCI) in the mid-1960s. George Judson, an IBM engineer whose son was being treated for chronic myelocytic leukemia (CML), asked Dr Emil Freireich if he could use his engineering skills to enhance his son’s treatment. Dr Freireich envisioned a device that would remove some of the excess white blood cells (WBCs) from the blood of CML patients for transfusion to neutropenic patients. A cooperative effort ensued, supported jointly by Mr Judson’s employer and the NCI. The result was a continuous-flow centrifugal blood separator, also with a “reusable” metal bowl and capable not only of meaningful WBC collection and depletion but also of exchanging plasma or RBCs. Subsequent refinements by IBM and by Cobe Laboratories, a dialysis equipment manufacturer that eventually bought IBM’s blood processor division, led to the versatile and more automated Cobe Spectra that became a mainstay of TA in the United States after its introduction in the late 1980s. A third family of apheresis instruments originated at Fenwal in the 1970s. These devices were the first to employ a sealless centrifuge mechanism devised independently by both Herbert Cullis at Fenwal and Yoichiro Ito at the National Institutes of Health. The sealless system ABBREVIATIONS: AQP-4 = aquaporin-4; ASFA = American Society for Apheresis; CML = chronic myelocytic leukemia; CNS = central nervous system; DSA = donor-specific antibody; HUS = hemolytic uremic syndrome; LDL(s) = low-density lipoprotein(s); MAHA = microangiopathic hemolytic anemia; MS = multiple sclerosis; NCI = National Cancer Institute; NMO = neuromyelitis optica; RBCX = red blood cell exchange; SLE = systemic lupus erythematosus; TA = therapeutic apheresis; TPE = therapeutic plasma exchange; TTP = thrombotic thrombocytopenic purpura; XM = crossmatch.