A bloody battle.

Since the first blood transfusion in 1628, blood donations have saved the lives of countless patients suffering severe trauma, disease or blood clotting illnesses. An entire industry has evolved and diversified towards the implementation of perfusion devices, separation and isolation of cells, monitoring the health of transfusions and isolating valuable products such as clotting factors or immunoglobulins. In recent years, improvements to the management of blood bank resources have led to some significant changes in the work of the administration to the technical staff.

For blood transfusions, time and storage of blood has a significiant effect on the survival of erythrocytes (Luten et al., 2008). Critical care patients are often administered fresh batches to reduce the likelihood of transfusion reactions and improved oxygen delivery in the patient (McLellan, Walsh, & McClellan, 2002). Furthermore, improved mapping of Rhesus Kell (K), Duffy, Cellano, Kidd and MNS erythrocyte antigens have also contributed to the improved specificity of blood group matching (Benahadi et al., 2014).

Accumulated stores of old blood are also becoming a problem. Long term >40 day storage of packed red blood ceslls (pRBC’s) have been associated with increased likelihood of hemolysis and exposure to plasma free Hb. Pretransfusion washing of allogenic RBC’s to remove the accumulation of dead cells and stabilise K+, Lactate, Glucose and pH levels before administering to patients may circumvent the issue of unused red blood cells (Bennett-Guerrero et al., 2014).

Screening for blood bourne diseases have eliminated the likelihood of contracting viral hepatitus and HIV-1. However many risks are still associated with the advent of unconventional infectious agents such as prions. Prions are ‘infectious’ misfolded aggregated proteins responsible for neurological wasting disorders such as Creutzfeldt-Jakob-Disease (CJD), Bovine spongiform encephalitus (BSE) and Kuru. It is now clearly established that transfusion of blood can transmit the disease and that this presents a major public health concern due to its difficulty to detect and the symptomatic latency of the disease (Andréoletti et al., 2012).  PrPSc ELISA – the gold standard bioassay is most sensitive to known isoforms transmitted within species. This is a critical shortfall because outbreaks such as BSE in the food chain are likely to have led to the spread of countless chimeric inter-species prion isotypes. The restriction of blood services in the UK has been justified by these findings (Hunter et al., 2002). Inevitably, in 2004 two transfusion-associated cases of vCJD were reported in individuals with a variety of pathological findings approximately 6-6.5 years after transfusion (Llewelyn et al., 2004; Peden, Head, Diane, Jeanne, & James, 2004). With the later reporting of a third prion infection the transfusion-transmission infection rate has been estimated at between 1/15,000 to 1/30,000 (Wroe et al., 2006).

Despite all efforts to improve the quality and efficiency of transfusion, transfusion medicine succumbs to perenial shortages. In Australia, this may be due to an ageing population and falling birth rate limiting the supply. Demand is also increased by a growing number of hematological, orthopedic and cardiovascular diseases among the elderly populations. A large study (n ~ 240,000) from the United States (Ottowa), found that these factors combined constitute 45.7% of blood products and approx 43.6 % total RBCs (Shehata et al., 2014). To address these shortages some countries like Japan have discussed insurance schemes that aim to promote the autologous donation (Makino, 2014). Private blood banks in the US have existed for a while where the donor is renumerated. However many aid organisations such as World Health Organisation and Red Cross remain in favour of non-renumerated blood donations as it support a safe blood supply. In Australia the emergence of private cord blood banks for emerging stem cell therapies have also attracted condemnation for their ‘fee for service’ approach (http://www.abc.net.au/news/2011-06-06/questions-raised-over-private-blood-banks/2748544).

The reprogramming (or induction) of pluripotent stem cells iPSC from adult ‘stem cells’ promises new applications towards regenerative tissue, transplant and transfusion.  The induction of stem cell factors by retroviral delivery can direct a distinct progression of cell fate more effectively than somatic cell nuclear transfer (Okita, Ichisaka, & Yamanaka, 2007).  Fibroblasts may even be directed towards multipotency in absence of Myc (Nakagawa et al., 2008) and utilising the micro-RNAse mIR-19a/b (He et al., 2014). These developments have piqued the interest of popular science writers (http://www.the-scientist.com/?articles.view/articleNo/39718/title/Artificial-Blood-Is-Patient-Ready/) and health technologists. It is now possible to impute specific human leukocyte antigen (HLA) types and strive towards the generation of thousands of specific blood lines. However significant shortcomings in infrastructure and the industry may pose a risk to the equitable and timely supply of this technology.

 

Andréoletti, O., Litaise, C., Simmons, H., Corbière, F., Lugan, S., Costes, P., . . . Lacroux, C. (2012). Highly efficient prion transmission by blood transfusion. PLoS pathogens, 8(6), e1002782.

Benahadi, A., Boulahdid, S., Adouani, B., Laouina, A., Mokhtari, A., Soulaymani, A., . . . Alami, R. (2014). Mapping Rare Erythrocyte Phenotypes in Morocco: A Tool to Overcome Transfusion Challenges. Journal of Blood Transfusion, 2014.

Bennett-Guerrero, E., Kirby, B. S., Zhu, H., Herman, A. E., Bandarenko, N., & McMahon, T. J. (2014). Randomized study of washing 40- to 42-day-stored red blood cells. Transfusion, n/a-n/a. doi: 10.1111/trf.12660

He, X., Cao, Y., Wang, L., Han, Y., Zhong, X., Zhou, G., . . . Gao, P. (2014). Human Fibroblast Reprogramming to Pluripotent Stem Cells Regulated by the miR19a/b-PTEN Axis. PloS one, 9(4), e95213. doi: 10.1371/journal.pone.0095213

Hunter, N., Foster, J., Chong, A., McCutcheon, S., Parnham, D., Eaton, S., . . . Houston, F. (2002). Transmission of prion diseases by blood transfusion. Journal of General Virology, 83(11), 2897-2905.

Llewelyn, C., Hewitt, P., Knight, R., Amar, K., Cousens, S., Mackenzie, J., & Will, R. (2004). Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. The Lancet, 363(9407), 417-421.

Luten, M., Roerdinkholder‐Stoelwinder, B., Schaap, N. P., De Grip, W. J., Bos, H. J., & Bosman, G. J. (2008). Survival of red blood cells after transfusion: a comparison between red cells concentrates of different storage periods. Transfusion, 48(7), 1478-1485.

Makino, S. (2014). [The current state of transfusion medicine in Japan]. Gan To Kagaku Ryoho, 41(4), 410-415.

McLellan, S., Walsh, T., & McClellan, D. (2002). Editorial II Should we demand fresh red blood cells for perioperative and critically ill patients? British journal of anaesthesia, 89(4), 537-540.

Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., . . . Yamanaka, S. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature biotechnology, 26(1), 101-106.

Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313-317.

Peden, A. H., Head, M. W., Diane, L. R., Jeanne, E. B., & James, W. I. (2004). Preclinical vCJD after blood transfusion in a< i> PRNP</i> codon 129 heterozygous patient. The Lancet, 364(9433), 527-529.

Shehata, N., Forster, A., Lawrence, N., Rothwell, D. M., Fergusson, D., Tinmouth, A., & Wilson, K. (2014). Changing trends in blood transfusion: an analysis of 244,013 hospitalizations. Transfusion.

Wroe, S. J., Pal, S., Siddique, D., Hyare, H., Macfarlane, R., Joiner, S., . . . Hewitt, P. (2006). Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. The Lancet, 368(9552), 2061-2067.

 

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