A piece of equipment developed at the Ribeirão Preto School of Medicine of the University of São Paulo is capable of ensuring the quality of the blood used in transfusions for immunodeficient persons, who may show incompatibility with the donor’s immune defense cells. The equipment is the result of the postdoctoral study by biophysicist Evamberto Garcia de Góes, under the supervision of Professor Dimas Tadeu Covas. The prototype that is installed in the Ribeirão Preto Hemocenter Foundation (FHRP) protects the blood from the room temperature (it needs to remain under refrigeration) and provides for a better exposure of the product, when coupled to the apparatuses that carry out the irradiation of gamma or X-rays. At the moment, the ideal procedure is to use specific irradiators, created for this purpose, which use sources of cesium 137 to produce gamma rays. It so happens that they cost over US$ 100,000.
As the majority of blood banks cannot acquire the apparatus, irradiation is done with cobalt therapy equipment, which uses cobalt 60 to emit gamma rays, or with linear accelerators, which emit X-rays – both originally planned to irradiate patients with cancer. “The problem is that, in both cases, the irradiation takes from 30 minutes to two hours to be concluded, and, in this period, the blood stays exposed to the room temperature, which can jeopardize its quality”, explains Góes, since 2001 a professor at the Franciscan University Center, in Santa Maria, in Rio Grande do Sul. “The main function of our prototype is to allow the use of the two types of equipment with the same efficiency as the specific irradiator, but free from exposure to room temperature. All this at a cost of R$ 10,000 (an amount financed by the FHRP)”, says the researcher.
The prototype developed by Góes is a thermal container with two compartments: one for platelet bags, with a temperature of 22°C, and the other for red blood cells, with a temperature between 2°C and 4°C A computer-driven motor makes the container rotate in front of the radiation beam, allowing a uniform distribution of the rays and guaranteeing adequate doses for each bag. This is important, according to Evamberto, because insufficient doses and excessive ones can jeopardize the efficiency of the process.
The rotation is also intended to keep the blood plasma products agitated, a condition that is indispensable for the platelets. “We did a series of physical and biological studies to find a frequency of rotation of the containers that was capable of homogenizing the doses of radiation on the blood bags and of offering an ideal degree of agitation for the platelets, without jeopardizing the quality of the red blood tytes”, Professor Goés says.
“Irradiation of the blood is necessary for preventing a rare but fatal reaction, known as transfusion-associated graft-versus-host disease (TA-GVHD), which occurs in patients with an immune deficiency, as in the case of people who have been given a transplant or who have some kind of leukemia”, Goés says. The agents of the reaction are the T-lymphocytes, which act in organic defense. When these cells, present in the donor’s blood, identify a possible incompatibility with the patient’s blood, they start to multiply and to attack, directly or indirectly, some systems in the receiver’s organism. In a few days, they cause necrosis of the tissues and failure of the bone marrow.
In patients with a normal organic defense, a possible attack would be neutralized by the efficient action of their immune system, but this does not happen with immunodeficient patients”, Goés explains. The professor clarifies that this kind of incompatibility that unleashes the attack does not derive from the differences in blood group of RH factor, but from a gene disparity associated with the histocompatibility system (the genetic capacity of a tissue or an organ to be accepted by a receiver).
Break up of the molecule
TA-GVHD can be devastating, because it does not respond to any kind of treatment and is fatal in the majority of cases. According to Góes, it is the safest way of avoiding the disease, because it breaks up the DNA molecule of the T-lymphocyte, preventing it from splitting and eliminating its capacity for proliferating in the patient’s organism. According to Goés, what is ideal is for the blood to be used in patients with an immunological deficiency not to have even one of these cells in a condition to set off an immune response against the patient. But, according to current medical literature, blood that has up to 10,000 T-lymphocytes per kilo of the patient is regarded as safe. If the patient weighs 70 kilos, for example, there can only be 700,000 T-lymphocytes in the total volume of blood that he is going to be given.
In their research for a doctorate, carried out at the Alberto Luiz de Coimbra Engineering Postgraduation and Research Institute (Coppe), of the Federal University of Rio de Janeiro (UFRJ), before developing the prototype, Góes, Covas and biologist Maristela Delgado Orellano implemented a technique at the Ribeirão Preto Hemocenter Foundation that makes it possible to identify a viable T cell in a universe of 1 million cells, which increases the patient’s safety significantly. This is the technique that is also part of the methodology used in the prototype developed in the postdoctoral project.
The importance of improving the quality of the irradiation of the blood in equipment not specific for this purpose, according to Góes, is the corroboration, by means of surveys, that the majority of Brazilian institutions irradiate blood with radiotherapy equipment. In Brazil, a survey carried out by Goés himself and by José Carlos Borges, from UFRJ, who supervised his doctorate, in 1996, showed that only 10% of the country’s blood banks have a specific irradiator. The situation is not so different in the United States, where, according to an article published in the Blood magazine, in 1991, a survey carried out with 99 blood banks, 397 hospital blood banks, and 948 transfusion services indicated that 87.7% of these institutions did not enjoy facilities on site for irradiating blood by means of the use of a specific irradiator and used, like the Brazilian ones, radiotherapy equipment.
The prototype attracted the interest of MGM Indústria e Comércio de Equipamentos Médicos, of Ribeirão Preto. According to the company’s commercial director, Marcos Rocha, his team has now found that the apparatus is technically viable. MGM is now analyzing the adaptation of the prototype to the standards of the National Health Surveillance Agency (Anvisa), and its viability in terms of economics and of production. Should they decide to produce the equipment, the intention is to put it onto the market within a period of from six months to a year. According to Rocha, the analyses should be concluded in the next few months, and everything indicates that the company will decide to produce the apparatus. “We have every interest in industrializing a prototype developed at the university”, he says, recalling that MGM?s tradition is to produce equipment developed by Brazilian researchers. The company went into the market ten years ago, launching a low cost colposcope that brought down the price for diagnosing cervical cancer.
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