Bloodletting on prescription
Yfke Prins, BSc Medicine
Much to my surprise, an internist mentioned that the treatment of choice for a patient with polycythemia vera (PV) was bloodletting. I thought I had misunderstood her for a second, but then she repeated her sentence, probably after seeing my puzzled face. She was serious, and, as I discovered that day, bloodletting (also known as phlebotomy) is still applied in the clinic; although, much less frequent than, e.g. during the Middle Ages. In this brief message, we will discuss the history of phlebotomies and the current clinical applications.
Most of you are probably familiar with bloodletting or phlebotomies. The procedure consists of retrieving around 350-500 millilitres of blood from the body [1]. The treatment has been used throughout history, dating back to 3.000 years ago [2]. Around 2.500 years ago, bloodletting rose in popularity. The commonly accepted theory of disease was Hippocrates’ theory: he believed that life consisted of the four elements, which were represented in the body by so-called humours, namely blood, phlegm, black bile, and yellow bile [2]. Disbalance between these humours could cause disease, meaning that the cure of diseases consisted of restoring the balance by removing one of the four humours, e.g. blood [2]. Since then, bloodletting had been accepted as a treatment for almost any illness. Bloodletting was even taken to extremes. For example, in 1799, George Washington died after a total of 1.7 litres of his blood was retrieved in an attempt to cure his (retrospectively diagnosed) acute epiglottis [1, 2]. However, gradually phlebotomies became discredited, eventually leading to its sporadic application today [2].
One of the diseases in which phlebotomies are still applied is PV, a myeloproliferative disease characterised by erythrocytosis (an increase in erythrocytes) and a high haemoglobin level [2, 3]. White blood cells and thrombocytes can also be increased, although the disease predominantly targets erythroid cells [2, 3]. As a result, the blood becomes viscous, leading to an increased risk of thrombosis [1, 3]. Treatment consists of phlebotomies and prophylactic platelet aggregation inhibitors [4]. In some cases, depending upon the risk profile, cytoreductive therapy, most often Hydrea (a form of oral chemotherapy), can be started [4]. In this case, the phlebotomy’s goal is to lower the viscosity of the blood by removing the excess of erythrocytes and haemoglobin [3]. The frequency and volume of the phlebotomies are guided by the haemoglobin and erythrocytes levels [1, 3].
However, PV is not the only disease in which bloodletting is used as a treatment – hereditary hemochromatosis is another example. This illness is most often caused by a mutation in the HFE gene, although in rare cases, other mutations can occur [5]. This mutation leads to an excess of iron, which, as the body cannot get rid of this efficiently, is stored in other organs [5]. Thus, hemochromatosis leads to organ damage, such as liver failure, diabetes, and heart failure [5]. Treatment consists of regular phlebotomies, of which the frequency and volume are adjusted based upon the ferritin levels [5]. If phlebotomies are applied in the early stages of the disease, the iron build-up and subsequent organ damage can be prevented [5].
Bear in mind that this is not an exhaustive list of indications. Porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia, amongst others, are also indications for phlebotomies [3]. This shows us we can learn from the past. Although the idea of applying phlebotomies as a treatment for any disease is odd, it is rooted in truth, and it still does have its clinical applications today. For patients with e.g. hemochromatosis and PV, science in the Middle Ages was (accidentally) quite far ahead!
References
- Assi, T. B., Baz, E. Current applications of therapeutic phlebotomy. Blood Transfus 12, 75-83 (2014).
- Greenstone, G. The history of bloodletting. BCMJ 52, 12-14 (2010).
- Kim, K., Oh, K. Clinical applications of therapeutic phlebotomy. J Blood Med 7, 139-144 (2016).
- Boekhorst, P., Kevin, M-D., Raymakers, R., Schutgens, R. Van Wijk, R., Jie, K.-S et al. Guidelines for diagnosis and treatment of essential thrombocytosis, polycythaemia vera and primary myelofibrosis. Ned Tijdschr Hematol 8, 64-79 (2011).
- Murphree, C., Nguyen, N., Raghunathan, V., Olson, S., DeLoughery, T. et al. Diagnosis and management of hereditary haemochromatosis. Vox Sanguinis 115(4), 255-262 (2020).
