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“It was the best of times,

It was the worst of times,

It was the age of wisdom,

It was the age of foolishness.”

 Charles Dickens

 A Tale of Two Cities, 1859

In 1978 our apheresis activities began using an AMINCO (continuous flow) machine to provide 238 units of neutrophils to profoundly leukopenic patients, and we exchanged our first patient with thrombotic thrombocytopenic purpura (TTP). By my retirement in 2003 we had completed 11 499 apheresis procedures: 4373 plasma exchanges (PE), 2875 stem cell collections, 288 therapeutic leukapheresis for malignant leukocytosis, 190 RBC exchanges for sickle cell crisis, and 97 therapeutic plateletpheresis procedures for extreme thrombocytemia. We have now exchanged nearly 300 patients with TTP, most probably the largest single institution experience. My experience was gained by treating these patients nearly daily for 33 years. Consequently, I witnessed many innovations and changes in this challenging now nearly global treatment.

A major positive impact of providing apheresis from Transfusion Services has forced, or allowed, many transfusion physicians and technologists to become more patient-attentive and clinically oriented. They are obligated to be aware of patients' problems and concerns as they not only became genuine experts in understanding and operating the various collection machines but also in acquiring consummate venipuncture techniques as well as appropriate care for venous access sites. Therapeutic apheresis has provided an entirely new field of knowledge and career path for many originally trained in Blood Bank serology, testing, and component preparation. Such exposure dramatically changed my focus from laboratory hematology to this new field as I found how very much I enjoyed direct patient contact and providing this life enhancing/saving primary treatment.

Unfortunately, during the early years its popularity and acceptance was undoubtedly slowed by the intense focus on the global AIDS epidemic and the concomitant widespread fear of receiving any type of blood products. Nonetheless, it slowly increased in popularity, but sadly many PEs were commonly performed on patients with rheumatoid arthritis, lupus erythematosis, multiple sclerosis, etc. Randomized controlled trials (RCT) subsequently revealed PE was either not efficacious for these diseases and several others or was restricted to only subgroups of patients with particular manifestations of these maladies. Sadly, even today many unnecessary procedures are still performed for diseases or conditions that are not recommended by published guidelines nor supported by RCTs' conclusions. The numbers of such unwarranted procedures varies greatly but is thought to be between 5% and 20%. Such procedures are expensive, time consuming, and in the United States not reimbursable. Moreover, they pose risks/dangers to patients without demonstrable benefits. Nonetheless, such unwarranted procedures are still undertaken, and usually supported by citing only an abstract or small case series or many times accompanied by the all too familiar phrase “can't hurt, might help”. The lack of utilizing Evidence-Based Medicine (EBM)/best evidence available remains a serious global problem. Some clinicians do not believe in or base their proposed treatments on EBM, and this is especially common for hematologic disorders. The overwhelming majority of US medical schools provide only two hours of dedicated teaching of transfusion medicine (TM) , usually in the second year of pathology. The indications, complications, and cost of apheresis are seldom, if ever, mentioned in these lectures. Consequently, this lack of education in TM/apheresis remains the “root cause” of the problem faced daily by most clinicians and is especially common when ordering therapeutic apheresis.

The Food and Drug Administration's chronic reticence to allow novel medical devices, either off- or online, to be used for patients' treatments has been well publicized. The review time for drugs during 2003–07 increased by 28% while the clearance time for medical devices slowed 43%, and approval times for new technologies lengthened by 75% (California Health Care Institute and the Boston Consulting Group). Therefore, few if any RCTs involving such devices have been undertaken although such devices and their apheresis applications are common in other countries. Consequently, there is usually no credible evidence that such devices are at all efficacious or even safe! This remains a critical problem. However, the therapeutic benefit of appropriate apheresis is now unquestioned and has been life saving and health enhancing for innumerable patients.

Empedocles of Sicily (490–430 BC) originated the concept of the four elements, which was modified by Hippocrates to include the four bodily humors, the Humoral Theory. Galen of Pergamon (129–201 AD) believed the balance of these humors was essential for good health. Conversely, their imbalance caused illness/disease, and he believed that many diseases might be corrected by bloodletting, which would reduce or remove the causative bad humor(s). Thanks to the pioneering work of George Judson and Emil Freireich in the late 1960s we can now selectively remove the “bad humors” residing in patients whose RBCs (sickle cells), WBCs (leukemias), platelets (thrombocytosis), and plasma (TTP, etc.) are responsible for or mediate their illnesses.

I feel privileged to have actively participated as PE became widely accepted as the primary treatment for many illnesses, most notably TTP. It remains the primary treatment of choice although TTP's specific defect, ADAMTS13 protease, has been identified. It remains to be seen whether the recombinant ADAMTS13 protease will be clinically effective and subsequently widely available. The growing popularity of no longer requiring the classic diagnostic pentad for TTP to requiring only a few fragmented RBCs in anemic and thrombocytopenic patients is problematic and may, in fact, be imprudent. Several diseases are well documented to present with similar signs/symptoms and laboratory values, most notably systemic lupus erythematosis.

“Two roads diverged in a yellow wood,

And sorry I could not travel both,

I took the one less traveled by,

And that has made all the difference.”

 Robert Frost

 The Road Not Taken, 1920

Biosketch

Leo McCarthy is Emeritus Professor of Pathology, Medicine, and Pediatrics at Indiana University after 32 years as director of Transfusion Medicine. He earned undergraduate and medical degrees from the University of Nebraska and completed a Pathology residency at Stanford University after serving in the U.S. Navy as a Marine surgeon in Vietnam. He has authored more than 300 publications, presented at numerous national/international meetings, initiated a fellowship as well as an annual lectureship in TM, was elected to Alpha Omega Alpha Honor Medical Society, was elected as a Fellow in the both the prestigious Royal Colleges of Physicians of Edinburgh and Ireland. He received many other honors including Indiana's highest distinction, awarded by the governor, Sagamore of the Wabash.