In 1922, the practice of blood collection and transfusion medicine looked very different from that to which it would evolve a century later. While the ABO blood group had been discovered by Karl Landsteiner (although not yet Rh),1 compatibility testing between donors and patients had been published,2 and anticoagulants were available to store blood,3 none of these were in widespread use.4 There were no blood centers (first established in 1937) and no testing of transfusion-transmitted diseases (syphilis would be the first in the 1950s). If a surgeon wanted to perform a procedure, or a patient required a transfusion, it would need to wait until the donor presented.
In 1922, the effective transfer of blood from one person to another remained a formidable task.4 Clotting, remaining uncontrolled, quickly occluded transfusion devices and frustrated most efforts.4 An intermediate step was needed before the importance of the ABO blood group and compatibility testing could be perceived and the appropriate changes could be incorporated into practice.4 One process was initiated by Alexis Carrel who developed a surgical procedure that allowed for direct transfusion.4 Carrel5 introduced the technique of end-to-end vascular anastomosis with triple-threaded suture material. This procedure brought the ends of vessels in close apposition and preserved luminal continuity, thus avoiding leakage or thrombosis.4 This technique was adapted by others for the performance of transfusion.6 Because all these procedures usually culminated in the sacrifice of the two vessels, they were not performed frequently.5 Direct transfusion was also fraught with danger.4 In a passage written two decades later, the procedure was recalled in the following manner:7 “The direct artery to vein anastomosis was the best method available but was often very difficult or even unsuccessful. And, what was almost as bad, one never knew how much blood one had transfused at any moment or when to stop (unless the donor collapsed). (I remember one such collapse in which the donor almost died—and the surgeon needed to be revived.)” Despite these many difficulties, direct transfusion through an arteriovenous anastomosis for the first time efficiently transferred blood from one person to another.4 The process also disclosed fatal hemolytic reactions that were undeniably caused by transfusion.8 However, transfusions did not become commonplace until anticoagulants were widely available and direct methods of transfusion were rendered obsolete.4 After the introduction of anticoagulants, blood transfusions using stored blood products (indirect transfusion) were given in progressively increasing numbers.4 At Mount Sinai Hospital in New York, the number of blood transfusions administered between 1923 and 1953 increased 20-fold.9,10
Blood banking disparities
In 2022, blood banking practices around the world vary greatly. In high-income countries, no cost has usually been spared in meeting public demands for blood safety.4 In middle- and particularly low-income countries, the picture is quite different.4 The greatest blood need is for women hemorrhaging during childbirth, infants and children with anemia caused by malaria, and victims of trauma.4 In Sub-Saharan Africa, fewer than three million units of blood are collected annually for a population of more than 700 million.4 Of the 148 countries reporting data to the World Health Organization (WHO), 41 are unable to screen for minimum safety (human immunodeficiency virus [HIV], hepatitis B [HBV] and C viruses [HCV], as well as syphilis).4 WHO estimates that unsafe blood in these countries results in 16 million new infections with HBV, five million with HCV, and 160,000 with HIV each year (accounting for 5% to 10% of the world's HIV infections).4 Fortunately, there is progress in some nations in achieving an all-volunteer supply and minimum screening.4 Thus, there are two drastically different pictures of blood safety and availability worldwide.11,12
Another approach to maintain adequate availability is to control usage by ensuring that blood is used appropriately.4 Some U.S. blood centers have been successful in bringing their transfusion medicine expertise into the patient care setting by providing transfusion services to hospitals.4 In the United Kingdom, liaison systems for blood centers to hospitals employing web-based technology for supply chain management have been introduced.13,14 In Denmark, success has been reported using the Thromboelastograph (Haemoscope, Niles, IL) hemostatic system to manage coagulopathy in conjunction with treating physicians—something also done in many U.S. hospitals.15 Other point-of-care tests to assess the state of the coagulation system and tissue oxygenation could also result in more accurately targeted component transfusion.4
The development of the board-certified blood banking and transfusion medicine specialists being deployed in blood centers and hospitals was critical to the successful use of blood transfusion in patient care.4 Today, patient blood management, defined as, “an evidenced-based multidisciplinary approach to optimizing the care of patients who need a transfusion.”16 has become a new standard for assuring transfusion is indicated based on best evidence.4 This has significantly reduced blood utilization in high-income countries and has been supported by indications that a restrictive blood transfusion strategy does not impair outcomes in most cases and that more is not better.17 At the same time, the treatment of trauma is returning to what is in effect whole blood for those massive bleeding by administering plasma and platelets in proportion to red cells early in the care of victims.18
Blood beyond the next 100 years
What does the future hold? There will be continued developments in stem cell technology, biotherapies, and cord blood banking.4 In addition, board-certified transfusion medicine specialists will increasingly function in collaboration with surgeons, oncologists, and hematologists in treating the acutely ill patient with complex medical problems.4 The clearest trend has been away from autologous transfusion, with some medical centers seeking bloodless medicine and surgery by combining pharmacotherapy (mainly erythrocyte stimulating agents and iron infusion), blood recovery and reinfusion, and use of conservative thresholds and endpoints.19
The big question is whether blood from donors will be completely replaced? Recent advancements in the past decade for in vitro generation of red blood cells (RBCs) seems to suggest great promise for efficient high-density erythroid bioprocesses despite the challenges faced.20 The applications for RBCs from human induced pluripotent stem cells make them very attractive options to pursue as eventual substitutes to donor blood.20
So hold onto your hats! If the last 100 years were any indication, the next 100 holds big challenges as well as significant advances.
1. Landsteiner K. Ueber Agglutinationserscheinungen normalen menschlichen Blutes. Wien Klin Wochenschr 1901;14:1132–4.
2. Ottenberg R, Kaliski DJ. Accidents in transfusion: their prevention by preliminary blood examination: based on an experience of 128 transfusions. JAMA 1913;61:2138–40
3. Lewisohn R. A new and greatly simplified method of blood transfusion. Med Rec 1915;87:141–2.
4. Rossi EC, Simon TL, Transfusion in the new millennium. In. Simon TL, McCullough J, Snyder E, Solheim, BJ, Strauss RG. eds. Principles of transfusion medicine.5th ed. Hoboken, NJ: John Wiley and Sons, Ltd. 2015:1-10.
5. Carrel A. The transplantation of organs: a preliminary communication. JAMA 1905;45:1645–6
6. Walker LG Jr. Carrel’s direct transfusion of a five day old infant. Surg Gynecol Obstet 1973;137:494–6.
7. Ottenberg R. Reminiscences of the history of blood transfusion. J Mt Sinai Hosp 1937;4:264–71.
8. Pepper W, Nisbet V. A case of fatal hemolysis following direct transfusion of blood by arteriovenous anastomosis. JAMA 1907;49:385–9.
9. Lewisohn R. Blood transfusion: 50 years ago and today. Surg Gynecol Obstet 1955;101:362–8.
10. Rosenfeld RE. Early twentieth century origins of modern blood transfusion therapy. Mt Sinai J Med 1974;41:626–35.
11. Improving blood safety worldwide [editorial]. The Lancet 2007;370:361.
12. Riley W, Schwei M, McCullough J. The United States potential blood donor pool: estimating the prevalence of donor exclusion factors on the pool of potential donors. Transfusion 2007;47:1180–8
13. Allen T. Blood center and hospital relationships in England and North Wales: their impact on the declining demand for red blood cells? Transfusion 2007;47 (Aug Suppl): 158S–63S.
14. Chapman J. Unlocking the essentials of effective blood inventory management. Transfusion 2007: 47 (Aug Suppl): 190S–6S.
15. Johansson PI. The blood bank: from provider to partner in treatment of massively bleeding patients. Transfusion 2007: 47 (Aug Suppl): 176S–81S.
16. Frank SM, Guinn NR. Patient Blood Management. In. Cohn C. et al, eds. Technical Manual. 20th ed. Bethesda, MD. AABB Press; 2020: 583-612.
17. Carson JL, Guyatt G, Heddle NM, et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316(19):2025–2035. doi:10.1001/jama.2016.9185.
18. O’Reilly K. Massive transfusion: a question of timing, detail, a golden ratio. CAP Today December 1, 2014.
19. Klein HG, Spahn DR, Carson JL. Red blood cell transfusion in clinical practice. Lancet 2007;370:415–26.
Lim ZR, Vassilev S, Leong YW, Hang JW, Rénia L, Malleret B, Oh SK-W. Industrially Compatible Transfusable i
Lim ZR, Vassilev S, Leong YW, Hang JW, Rénia L, Malleret B, Oh SK-W. Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions. International Journal of Molecular Sciences. 2021; 22(18):9808. https://doi.org/10.3390/ijms22189808.