Cómo administrar el 'oro rojo' de los hospitales

http://www.elpais.es/articulo/elpsalpor/20050510elpepisal_1/Tes/Cómo%20administrar%20el
Mientras llega la sangre artificial, los especialistas buscan métodos para ahorrar hemoderivados
Mientras las empresas de biotecnología tratan de poner a punto un tipo de sangre artificial que sustituya a la humana, especialistas de diversas sociedades científicas relacionadas con el uso de hemoderivados buscan procedimientos para ahorrar sangre. Se trata de hacer más eficiente y seguro el uso del llamado 'oro rojo' de los hospitales, un bien muy escaso.
JOAQUÍN MAYORDOMO - Sevilla
EL PAÍS - 10-05-2005

Sobre la sangre hay tres axiomas que ningún experto discute: el primero es que siempre será un bien escaso que necesitará de la donación; el segundo, que el riesgo cero no existe para quienes reciben una transfusión, y el tercero, que la sangre, al ser un producto biológico, nunca estará libre del todo de ser contaminada por bacterias o virus desconocidos, con lo que se hace imposible, a priori, su detección.
Tratándose de un producto que el organismo humano genera y regenera con facilidad, parece que no debería haber problemas de abastecimiento. Pero la población envejece, la cirugía es cada día más compleja, los donantes disminuyen y cada vez han de estar más controlados. ¿Consecuencia? La sangre escasea. Y, por consiguiente, las empresas farmacéuticas libran una batalla contra reloj para encontrar un sustituto mediante procedimientos de biotecnología. Los especialistas reciben información de que la tan ansiada sangre artificial está a punto de conseguirse, pero todo apunta a que "sólo va a servir, en principio, para solventar problemas de urgencia en catástrofes o en periodos de guerra", explica Elvira Bisbe, anestesista del conjunto hospitalario Mar-Esperanza de Barcelona.
Lo que sí parece cierto es que israelíes y norteamericanos están ya utilizando esta "sangre sintética" con éxito en los heridos de los atentados palestinos y con los soldados de la guerra de Irak. Si así fuera, la ansiada molécula de hemoglobina sintética, capaz de captar gran cantidad de oxígeno en los pulmones, transportarlo y soltarlo rápidamente en los tejidos sin causar daño, podría llegar al mercado en cualquier momento. Pero la mayoría de los especialistas no lo consideran algo inmediato. "Lo que parece que ocurre es que se ha conseguido eliminar de esta sangre artificial la toxicidad que tenía, y eso podría ser un paso definitivo", dice Elvira Bisbe.
Las guerras siempre producen grandes daños y algunos de los saltos de la medicina se han producido para hacerles frente: "En la Primera Guerra Mundial se perfeccionaron las transfusiones sanguíneas, y en la Guerra Civil española se creó el primer banco de sangre...", explica Juan Vicente Llau, anestesista en el hospital Clínico de Valencia. Como Bisbe, Llau tampoco cree que la sangre artificial vaya a llegar tan pronto a los hospitales. Para él, como para la mayoría de anestesistas, hematólogos, intensivistas y otros profesionales relacionados con la sangre, el principal problema que se plantea es la disparidad de criterios entre los sanitarios a la hora de practicar transfusiones: "La verdadera revolución", insiste Llau, "sería que los profesionales tomaran conciencia de la necesidad de ahorrar sangre y establecer protocolos que permitan un uso racional y seguro en las transfusiones".
En una reciente reunión sobre Alternativas a las Transfusiones Sanguíneas, celebrada en Sevilla, en la que participaron cinco sociedades científicas relacionadas con el llamado oro rojo de los hospitales, se acordó elaborar un documento de consenso capaz de fijar unas pautas, "siempre basadas en la evidencia científica, que avalen las técnicas y fármacos que emplear en cada paciente que precise una transfusión", explica Ramón Leal, intensivista del hospital Virgen del Rocío y secretario de esta reunión. Leal, que es también asesor europeo en sangrados críticos y coordinador nacional del Grupo de Sangre de Cuidados Intensivos: "Contamos con varias técnicas para la recuperación de la sangre durante o en el posoperatorio, disponemos de más de una docena de fármacos que nos permiten reducir el sangrado o estimular la producción de sangre... Pero no tenemos protocolos comunes", dice. Si se aplicase siempre la pauta más adecuada, el ahorro de sangre en las transfusiones podría llegar al 20%. "Pero para ello tenemos que sensibilizar a nuestros médicos de que la sangre es, y lo será cada vez más, un bien escaso", sostiene Enric Contreras, hematólogo del hospital Joan XXIII de Tarragona.
Las estrategias de ahorro de sangre son varias y conocidas, pero no siempre se aplican bien. Una de ellas consiste en reducir el umbral 10 de hemoglobina hasta 8, con lo que se puede llegar a ahorrar hasta 1,5 litros de sangre por transfusión. "Es la forma más barata y resulta muy eficaz en personas jóvenes", recuerda Elvira Bisbe. También se puede mejorar la anemia en el preoperatorio o, lo que es lo mismo, estimular al paciente para que fabrique más sangre. Y la eritropoyetina (la famosa EPO que usan algunos deportistas para doparse) es "un fármaco fundamental para muchos pacientes que han de ser operados porque les ayuda a mejorar la calidad de su sangre", explica Llau. Reducir el sangrando es otra estrategia de ahorro de hemoderivados a tener en cuenta. Fármacos como el factor VII activado, utilizado por primera vez en Israel, en 1999, con un soldado que había perdido un brazo, reducen la pérdida de sangre en más de un 50%. En cirugía cardiaca, en la que el sangrado es muy abundante, el empleo de estos fármacos es fundamental. Y en cirugía ortopédica, también. Un estudio realizado por Elvira Bisbe sobre cirugía ortopédica programada concluye que, aplicando la estrategia adecuada, puede ahorrarse hasta el 70% de sangre.
Hay otras formas de ahorro en los hospitales. La utilización de la propia sangre (autotransfusión) es uno de ellos. Puede extraerse antes de la operación pero también puede hacerse durante o después del proceso quirúrgico. En ambos casos, tras un proceso de filtrado, la sangre queda en condiciones de volver a ser transfundida.
En cualquier caso, la sangre, como producto biológico que es, exige rigor y cuidado en su manipulación: no debe olvidarse que una transfusión es siempre un trasplante. Eso no quiere decir que la sangre no sea hoy segura. "Al contrario, es más segura que nunca", dice, rotundo, Leal. Pero una transfusión jamás está exenta de riesgo. "El riesgo cero, en medicina, no existe", recalca Enric Contreras.
Las técnicas disponibles permiten hoy descubrir los agentes patógenos que se conocen (virus del sida, de la hepatitis C, mal de las vacas locas, etcétera). Pero "¿quién puede asegurar que no haya algún virus, retrovirus o bacteria, ahora desconocidos, que podrían aparecer dentro de un tiempo, como ocurrió con el sida?", se pregunta Llau. Por eso se insiste tanto en la necesidad de consensuar actuaciones entre los profesionales. El documento de consenso, cuya publicación se prevé para finales de año, será pionero en su género en Europa, según Leal, y va a suponer "un antes y un después" en las transfusiones sanguíneas porque se pretende que Administración, hospitales y médicos tengan un marco de referencia.
La próxima década propiciará grandes cambios en lo referente a hemoderivados. El primero ya se ha iniciado con los llamados hospitales sin sangre, "un concepto que, en la práctica, no significa otra cosa que ahorro de sangre y de costes, además de máxima seguridad para los pacientes", indica Juan Manuel Flores, subdirector médico de rehabilitación y traumatología del hospital Virgen del Rocío. "Lo ideal sería que cualquier hospital, con las técnicas ya existentes, fuese, en materia de sangre, autosuficiente", concluye.
Alternativas a la transfusión
En el mundo desarrollado hay cada día más personas (se habla ya de una de cada tres) que sugieren que no se les haga transfusión sanguínea cuando la necesitan o no la admiten. No sólo los Testigos de Jehová (en España unos 150.000) se niegan, sino también ciudadanos que, bien informados de riesgos y alternativas existentes a la transfusión, piden una autotransfusión, o bien someterse a una de esas técnicas de ahorro antes descritas. Según Javier Bárcenas, médico de familia, y asesor de los Testigos de Jehová en su relación con los hospitales, "hoy, prácticamente, todo el mundo entiende que, de acuerdo con nuestras creencias, no queramos sangre de otros". Los Testigos de Jehová, en general, ya no tienen problemas cuando se trata de una operación programada; cuentan con una red de más de 100 hospitales sin sangre. Bárcenas "se congratula" de que la ciencia y sus creencias por fin "confluyan". Y cita el hospital del Espíritu Santo de Barcelona en el que se han hecho ya más de 4.000 intervenciones de cirugía ortopédica sin necesidad de transfusión sanguínea.
Mientras tanto, las donaciones de sangre se estancan. En España, en 2003, la sangre aportada por 1.650.000 españoles que donaron (38 de cada 1.000 habitantes) no fue suficiente ni para llegar a la media europea (por encima de 40 por 1.000), ni para alcanzar la cifra que establece la OMS como "ideal" (45 donantes por 1.000 habitantes). Esta cifra es la que garantiza el autoabastecimiento de un país.
Por comunidades autónomas, Navarra y Euskadi, con 54,7 y 47,1 donaciones por millar están a la cabeza. Por abajo, Andalucía y Canarias con 33,8 y 31,8, respectivamente, son las dos últimas. Con estos datos, no es de extrañar que se busquen alternativas en el ahorro y en la biotecnología.

Infections Related To Red Cell Transfusions
Including Variant Creutzfeld-Jacob Disease

http://www.nataonline.com/Art.php3?NumArticle=482

Summary

Currently in the developed world, the risks of infection by the transfusion of blood components is very low. Improved methods of selection of all voluntary donors as well as highly sensitive screening techniques to detect the most important agents known to be transmissible by blood transfusion have greatly improved the safety of the blood supply. Nevertheless, there is still the risk of transmitting viruses (mainly HBV, HCV, HIV, CMV, etc.), bacteria (e.g. staphylococci, Pseudomonas, Yersinia) and parasites (e.g. malaria and T. Cruzi).Transmissions occur because donors gave blood during the "window period", because of error, or because no screening test is available for that agent. No cases of new variant Creutzfeldt-Jakob disease (or CJD) nor of any transmissible spongiform encephalopathy have been shown to be transmitted by blood transfusion. However, because bovine spongiform encephalopathy (BSE) ("mad cow disease") acquired epidemic proportions only in the U.K. (with the exception of one out of 45 cases), the British Department of Health has decided to introduce several prophylactic measures that might reduce the hypothetical risk of transmission by blood transfusion, such as universal leukodepletion and disposal of all volunteer U.K. plasma for fractionation with its replacement by imported non-volunteer plasma from the U.S.A

Key words:


Allogeneic Blood Transfusion

Risks

Infection

Screening

Virus

Prion

Creutzfeldt-Jacob Disease

Transmissible Spongiform Encephalopathies

Bacteria

Parasites

Leukodepletion

Currently in the developed world, the risks of blood transfusion to recipients are very low, and it is therefore difficult to assess new methods for improving blood safety. Unfortunately, although allogeneic blood transfusion has never been safer, the perception of the public, fed by the media, is that blood is becoming increasingly unsafe. Hence, when new infectious agents are discovered which "might "pose a risk to the blood supply, health care policy makers are compelled to introduce all sorts of measures and procedures, regardless of their cost, to avoid the theoretical risk of transfusion-transmitted infection. Though infrequent, there are numerous known risks of transfusion, the most serious being (1) the risk for acquiring hepatitis or HIV infection, (2) ABO hemolytic transfusion reactions, mostly due to procedural errors such as identification mistakes, and (3) bacterial contamination. Most of the major risks of transfusion are preventable, such as identification mistakes or failures to test, yet scarce resources are being spent by health services in these areas which would give a high return for a relatively small expenditure.

Blood transfusion has never been safer in countries with adequate resources. Hence, if any additional measures to prevent hazards of transfusion are contemplated, they must have demonstrable benefit. The risk of transfusion-transmitted infection for known agents can be quantified by (a) calculating the frequency of infectious markers in the donor population; (b) establishing the number of new cases of transfusion-transmitted infection and (c) extrapolating from case reports.

The first and most important step in maintaining a safe blood supply will always be a rigorous process of selection of prospective voluntary, unpaid blood donors. The second is the use of specific microbiological screening tests.Agents transmissible by transfusion can be either cell associated -for example, cytomegalovirus (CMV)and human T cell leukemia virus type I (HTLVI), associated with white cells; malaria, associated with red cells -or plasma associated -for example, hepatitis B virus -or both -for example, HIV. If they are plasma associated, pooling large numbers of units of plasma (for example, 15, 000 to 20, 000 as in the production of factor VIII) greatly increases the chances of disseminating such contaminants. Even without pooling, transfusion with blood components may result in up to four or five patients being infected by a single contaminated donation. All red cell transfusions carry the risk of transmitting cell-and plasma-associated microbial agents. Transmission of white cell-associated viruses such as CMV or HTLV can be prevented by leukodepletion of red cell concentrates but transmission of plasma-associated viruses cannot be avoided if the red cells are washed o thawed after freezing. Currently, the means used to reduce the risk of transfusion-transmitted infection are donor selection, promotion of self-exclusion and screening of blood donations for microbiological agents such as HBV, HCV and HIV with assays of increasing sensitivity in order to reduce the window period of infectivity.In addition, procedures to inactivate microbial agents in plasma, platelet concentrates and even red cells are being used or are undergoing clinical trials. The treatment of red cells with FRALES looks promising. Because the current risk of blood transfusion is so low, it is difficult to quantify the risk, and it is therefore difficult to measure increased safety of the blood supply. The problem is how to assess the cost-benefit equation, an impossible task with regards to vCJD in the U.K..

The risk of transfusion-transmitted infections for unknown or new agents such as pathological prions cannot be estimated since we do not know the frequency of infectious prions in the U.K. population, and no cases of transfusion-transmitted prion disease have ever been reported. Moreover, at present there are no screening tests available that would allow us to assess the prevalence of abnormal prion carriers in the population.

Properties of infections transmissible by transfusion

Agents transmitted by blood transfusion often possess a combination of some or all of the following properties:

- They are present in the blood for long periods, sometimes in high titers.

- They can cause subclinical infections or only mild symptoms.

- They have long incubation periods (sometimes years) before clinical signs appear.

- They may exist in a latent or carrier state, or both.

- They are stable in blood stored at 4° C.

Screening tests for blood donations [Table 1]

Screening tests are usually directed at antibody to the agent rather than antigens, except in the case of hepatitis B virus. Antibody screening tests are markers for certain persistent or chronic infections and therefore indicate a potential for infectivity, especially when the innoculum is as large as a unit of blood or blood component.

Various agents may be transmitted by transfusion. In the United Kingdom only four screening tests for blood donations are currently mandatory. They are HBV surface antigen (HBsAg) for hepatitis B virus, antibody to HIV-1 and 2, antibody to hepatitis C virus (HCV), and antibody to Treponema pallidum (syphilis). A proportion of the blood supply is screened for CMV antibodies, and some donors are screened for malaria antibodies. Tests for several other agents are available, but it has not yet been considered necessary to extend the present range.

For a test to be suitable for screening blood for transfusion, several conflicting demands have to be met. The test must be sensitive, specific, rapid, amenable to automation and process control and preferably economical. In addition, in microbiological screening tests most donor serum samples are negative. Great vigilance is therefore required in carrying out the routine screening tests. In low prevalence populations even an apparently low rate of false positive results from a screening test implies that a positive reaction has little predictive value. If, for example, an agent has an incidence of 1/10, 000 donations, then a test with a specificity of 99%, will produce a false positive reaction once in every 100 donations, or 100 false positive reactions for every true positive. It is therefore imperative that any donor samples that give a positive reaction to any of the mandatory screening tests be sent to a reference laboratory for confirmation before the donor is informed of the results. Transfusion centers in the United Kingdom, and in other countries, use assays for HIV antibody that have low false positive rates, and they all have access to reference laboratories that carry out a battery of confirmatory tests, which virtually eliminates the possibility of mislabeling uninfected donors.

Specificity is vital if the confidence of donors is to be maintained, and it must not be forgotten in the search for increased sensitivity. Fortunately recombinant and synthetic antigens as well as modern molecular biological methods have produced remarkable improvements in the sensitivity and specificity of assays for HIV antibody.

Bacterial complications of transfusion [Table 2]

Bacteria normally present in skin flora, such as staphylococci, can contaminate some blood donations at the time of collection; the blood's own bactericidal powers, citrate, and cold storage will, however, destroy most such contaminants.

Bacterial complications of transfusion are relatively rare in developed countries because of the use of sterile, disposable, collection sets and clean phlebotomy techniques. When they do occur, however, they can rapidly be fatal, principally as a result of endotoxic shock. Exogenous contaminants can be introduced into the blood mainly during collection or (rarely) during processing or the preparation and storage of platelets. At present, most blood components are prepared in closed systems; blood is collected in multiple packs and the possibility of microbes entering the packs is negligible. On the other hand, those components prepared in an open system (such as washed cells) should be processed in sterile rooms and given a limited (24 hours) shelf life. Most serious and fatal complications of blood transfusion caused by bacteria are due to skin contaminants such as staphylococci, diphtheroids and micrococci which enter the blood with the skin plug caused by the venesection needle. In addition, common environmental contaminants reported as causing serious (and often fatal) bacterial infections include Pseudomonas, Achromobacter, and coliform organisms - that is, Gram negative bacteria that grow preferentially at 4-8° C or at room temperature, but not at 37° C. Such bacteria use citrate as a source of energy, and this leads to the clot-ting of stored blood.

Reactions to the transfusion of contaminated blood are due to septicemia or, more often, to endotoxins; they usually develop within minutes, with alarming signs and symptoms: chills, rigors, fever, nausea, vomiting, bloody diarrhea, abdominal and muscle pains, hypotension (often leading to shock with flushing and dry skin), renal failure, hemoglobinuria, and disseminated intravascular coagulation. It is very difficult to distinguish these symptoms from those caused by an ABO incompatible transfusion reaction.

Bacteria that may cause low grade or a symptomatic infections in the donor (such as Salmonella or Yersinia species) are sometimes an endogenous source of contamination. Y. enterocolitica can be a particular problem as it grows in red cell concentrates stored at 4° C without causing haemolysis and producing a powerful endotoxin. Bacteria that do not grow well in blood stored at 4° C will grow rapidly in platelet concentrates that are routinely stored for five days at 20-22° C. Fatal salmonella, E. coli, and staphylococcal septicemia have been caused by contaminated platelet concentrates.

As soon as it is suspected that a contaminated unit has been or is being transfused, the transfusion should be stopped and blood samples as well as the packs of any units transfused should be sent to the blood bank and microbiology laboratory for investigation. The patient should be treated as if he or she has septic shock before the results of laboratory investigations are available. Broad spectrum antibiotics and hydrocortisone should be given intravenously, together with adequate fluid replacement and vasopressive drugs.

Treponema pallidum (syphilis)

T. pallidum can be transmitted only by fresh blood and platelet concentrates because it is only inactivated by refrigeration for 72 hours. It is not transmitted by products fractionated from pooled plasma such as factor VIII. The incubation period varies from four weeks to four and a half months, the average being nine to 10 weeks. It is only rarely transmitted by transfusion, but when it is, it presents as a secondary eruption. It responds to treatment with antibiotics, usually a course of benzylpenicillin (two megaunits).

Screening for the antibody is mandatory, for example, by the cardiolipin assay or, increasingly in the U.K., by the more specific T. pallidum hemagglutination assay or ELISA. In early primary syphilis, at the height of infectivity, screening tests may be negative. The detection rate is low because most positive donors have had the infection and been treated. Donors with acute or latent infection are rare. The value of screening is mainly to identify donors who may have contracted other sexually transmitted diseases.

Parasitic complications of blood transfusion

Malaria

Plasmodium falciparum is the most dangerous of the human malarial parasites; the others are Plasmodium vivax, Plasmodium ovale and Plasmodium malariae. The organisms are absolutely restricted to red blood cells which may contaminate components such as platelets. Freezing plasma will lyze any contaminated red cells and is therefore safe, but malaria parasites can survive storage of blood at 4º C for more than a week. The incubation period is from one week to one month, but for P. malariae it may be several months. Special note should be taken of unexplained fevers after transfusion.

Occasional transmissions still occur in the United Kingdom despite the careful taking of histories. Of 18, 374 cases of malaria in Britain reported to the Malaria Reference Laboratory between 1977 and 1986, only four were caused by blood transfusion. However, recently a case of fatal transfusion-transmitted malaria was reported. Most countries exclude donors who may have been exposed to malarial infections on the basis of their clinical and travel history. In the U.K. a recently approved ELISA test to detect antibody to P. falciparum has allowed the acceptance of donors with a history of possible malarial exposure provided that this exposure was more than six months previously and that they are seronegative and free of symptoms. If a diagnosis of malaria after transfusion is made, conventional treatment should be started. Primaquine should not be used, however, as the parasite will be restricted to the red cells.

Viruses transmissible by blood transfusion [Table 3]

Most of the transfusion-transmitted diseases are caused by viral infections, several of which are currently arousing considerable public and medical interest. Effective antiviral agents are still not available to treat most viral infections, so the safety of blood and blood components has to rely solely on "self-exclusion" by potential donors who are at risk of contracting viruses that are transmissible by transfusion (often transmitted sexually or by intravenous drug misuse) and on laboratory screening for evidence of microbial infection. So far inactivation methods are routinely available only for fractionated products made from pooled plasma and, in some countries, also for fresh frozen plasma (FFP). This is a brief review of the range of viruses that are transmitted by transfusion and of their properties.

Hepatitis B virus (HBV)

HBV is 42 mm in diameter and contains DNA. Reports of the isolation of cross-reacting variants of HBV have been published. The virus is plasma borne and easily transmitted by all blood components and most blood products (for example, factor VIII). It is not transmitted by pasteurized albumin. The chance of transmission is enhanced when plasma is pooled for the manufacture of blood products. However, the risk is removed with current viral inactivation procedures of fractionated blood components. The incubation period ranges from two to six months but is usually about four. Although it is extremely infectious parenterally and is resistant to both chemical and heat inactivation, the number of transfusion-transmitted cases has been drastically reduced by screening of blood donations, and the few that do occur are due to carriers with subliminal levels of HBsAg in blood donations or seronegative donors undergoing acute infection.

Screening for hepatitis B surface antigen (HBsAg) is mandatory. Assays for antibody to hepatitis core (HBc total antibody or IgM) are available for diagnosing acute HBV infection. Assays for hepatitis B core antibody should not replace that for HBsAg screening of donors; however in several countries, such as the USA and France, both tests are done routinely on all blood units. Screening for the delta agent is unnecessary as delta depends on HBV to provide its surface antigen. Screening for antibody to HBsAg can be used to identify donors whose plasma is suitable for the preparation of hepatitis B immunoglobulin. In the United Kingdom hepatitis B virus is detected in approximately 1 in 20, 000 donations overall, a lower rate than in the general population, because individuals at high risk of having HIV and, concomitantly, HBV are now excluding themselves from donation. Vaccine is available for protecting HBV negative recipients of the products of pooled plasma (for example, previously untreated hemophiliac patients) and for patients who need regular transfusions (for example, those with thalassemia). Vaccine-escape mutants of HBV have been reported. This necessitates careful validation of HBsAg assays.

HCV and non-A, non-B hepatitis

Assays have been developed in which cloned antigens or synthetic peptides can react with antibody to HCV, the agent that is the cause of most of the non-A, non-B hepatitis transmissible as a result of transfusion. The virus is plasma borne and has some routes of transmission in common with hepatitis B virus. The incubation period for non-A, non-B hepatitis is from two to 26 weeks, which may reflect different agents. HCV, a flavivirus, seems to be of the longer incubation type.

Some countries (including the United States) require screening of blood donors for antibody to hepatitis B core (anti-HBc) and measurement of alanine aminotransferase (ALT) activity as surrogate markers for non A, non-B hepatitis. Most donations exhibiting only one of these abnormal markers, however, do not transmit non-A non-B hepatitis, so "surrogate" screening leads to unnecessary wastage of blood donations. The main causes of increased alanine aminotransferase activity in British blood donors are obesity and alcohol consumption; some donations may transmit the disease despite having normal markers. Assays for hepatitis C antibody are used routinely to screen blood donations in all industrialized countries, including the United Kingdom. Improved screening assays based on recombinant or synthetic antigens including viral core protein have been developed.

In the United States, before screening for HIV antibody was introduced, about 10% of transfusions caused significant increases in transaminase activity in recipients, and there were occasional cases of symptomatic hepatitis; this figure has now been reduced to 0.15% after the introduction of screening for anti-HCV. There are, however, large geographical variations and rates have come down since the exclusion of donors at risk of HIV infection and the introduction of surrogate screening tests. Acute infection is usually mild, but a proportion of patients do develop chronic liver disease. Large prospective studies on the chronicity of non-A, non-B hepatitis that has been transmitted by transfusion are needed, particularly in the United Kingdom, where roughly 0-5% of recipients of blood transfusions experience significantly increased transaminase activities. Confirmed rates of positivity for anti-HCV (and thus carrier rates) in the United Kingdom range from 1 in 1, 000 to 1 in 3, 000. Screening assays still generate a proportion of false positive results, as shown by recombinant immunoblot assays and the polymerase chain reaction. Modern methods of viral inactivation of factors VIII and IX will prevent transmission. Hemophiliacs who have received effectively inactivated factor VIII have proved negative for antibody to hepatitis C virus, in contrast to those who received uninactivated concentrate, with a worldwide anti-HCV prevalence greater than 70%, a prevalence similar to that in intravenous drug users.

Recently another flavivirus distantly related to HCV has been cloned and named hepatitis G virus. However, it does not appear to be hepatotropic and the alternative name 'GB virus C' or GBV-C is more appropriate. Viremia is present in 1 to 2% of blood donors, and the virus has been shown to be transmissible by transfusion. It is generally non-pathogenic (in the majority of reported studies) and is not causatively or predictively associated with elevated alanine aminotransferase (ALT) levels in infected individuals.

HIV

HIV-1 was transmitted by transfusion before screening for anti-HIV was introduced and before donors at high risk started excluding themselves from giving blood. HIV-2 occurs mainly in west Africa. Both are retroviruses, 100 nm in diameter, that carry their own RNA-dependent DNA polymerase (reverse transcriptase). Before screening was introduced, HIV had been transmitted by whole blood, red cell components, platelet concentrates, and fresh frozen plasma. It can contaminate factor VIII and factor IX concentrates, but it can readily be inactivated chemically or by heat, and modern concentrates do not transmit it. It has not been transmitted by albumin, immunoglobulins, or antithrombin III. With current anti-HIV assays, the seroconversion period is rarely longer than one month, and a primary illness similar to glandular fever may occur during this time. The incubation period for AIDS is variable, with a likely median time of at least seven years in adults (though the period is shorter for infants).

Screening for HIV antibody is by an "antiglobulin" or "sandwich" enzyme-linked immunosorbent assay (ELISA), or a gelatin particle assay. "Competitive" assays specifically for anti-HIV-1 are available, although most countries use assays that can detect both anti-HIV-1 and 2. Screening for HIV antigen is not indicated in a country with such a low HIV prevalence as Britain; donors with confirmable HIV antigen in the absence of HIV antibody are vanishingly rare. More than a million blood donations have been screened for HIV antigen in the United States and Europe and none was positive for HIV antigen in the absence of anti-HIV. Nevertheless, blood donations are now routinely screened for HIV antigen in the USA, and only 1 donor per 6 million units tested has confirmable HIV antigen, without HIV anti-bodies. This low prevalence of "window-period" infections is not the case in countries with high rates of HIV infection, such as Thailand where donation screening for HIV antigen has detected several positive donors who had not yet developed anti-HIV.

Transmission of HIV by transfusion has been extremely rare since the introduction of screening. HIV antibody is found in 1 in 108, 000 donations overall in the United Kingdom. The incidence is significantly higher in new donors (1 in 23, 000) than in known donors (1 in 217, 000). "Seroconverting" donations (those negative for HIV antibody but infectious because of recent infection) are therefore extremely rare. On only 2 occasions has a donation from a seronegative donor been known to have transmitted HIV infection in the United Kingdom since screening started in 1985, i.e. 2 in more than 22 million blood donations. The virus can be inactivated in blood products by treatment with heat or chemicals, but blood and blood components (for example, platelets) cannot be treated in either of these ways. Methods for inactivating such cellular components are however being assessed.

Adult T cell leukemia; human T cell leukemia virus

Human T cell leukemia virus (HTLV-I) is a pathogenic retrovirus. The clinical importance of HTLV-II is not clear; in the West it is associated with intravenous drug use and world wide has been found in a few cases of hairy cell leukemia. Much of what has been reported as antibody to HTLV in the U.S.A. is likely to be antibody to HTLV-II. Both agents are associated with white cells and not transmitted in plasma. The incubation period for adult T cell leukemia is about 20 years, but even then only about 1% of patients who are seropositive develop the disease. HTLV-I can also (rarely) cause tropical spastic paraparesis (also known as HTLV-I associated myelopathy), which seems to have a shorter incubation period than adult T cell leukemia. HTLV-I infection is endemic in the Caribbean, parts of Africa, and Japan where 34% of the population are seropositive and where, before mandatory screening, transmission by transfusion was quite common.

In the United Kingdom, the prevalence of anti-HTLV in blood donors varies from 1 in 20, 000 to 1 in 80, 000 or less, depending on the region. Routine screening of blood donations for HTLV antibodies is not mandatory in the U.K., although it is mandatory in the U.S.A., Japan and some European countries.

Cytomegalovirus (CMV)

Cytomegalovirus is a member of the herpes group of viruses, and latent infection of white cells in seropositive subjects may allow recrudescence of the virus. Viremia in healthy donors is rare. The incubation period is up to 12 weeks, and blood transfusion can cause primary infection, reactivation of an endogenous latent infection, or reinfection with a different strain of the virus.

ELISA or particle agglutination tests are used for screening. Because severe (and sometimes fatal) CMV disease may occur only after transmission to immunosuppressed patients, selective screening of donors is sufficient to fulfil the demands for CMV-negative units for CMV negative recipients of bone marrow transplants, low birth weight premature infants and intrauterine transfusions. About half of all donors in the United Kingdom are seropositive, and the rate increases with age. Seropostivity also depends on the socioeconomic background of the subject and the geographical location. However, only between 3% and 12% of donor units have the potential for transmitting the virus (especially, but not exclusively, if IgM CMV antibody is detectable), but there is no screening test to identify specifically those seropositive donors who are likely to be infectious. Components from which the white cells have been removed (for example, by leukodepletion filters) and frozen-thawed red cells have been shown not to transmit CMV. IgG given intravenously with antiviral agents helps to ameliorate the effects of infection in immunosuppressed patients.

Parvovirus B19

Although serum parvovirus is not usually pathogenic when transmitted by transfusion, it can lead to an aplastic crisis in a patient with chronic hemolytic anemia (such as sickle cell anemia) because of its inhibitory effect on red cell precursors. The risk of transmission by transfusion of non-pooled components is small because, as for hepatitis A, there is no carrier state and the period of viremia is short in immunocompetent individuals. The titer of virus during the period of viremia, however, is high, and infectious units of plasma can contaminate batches of factor VIII; over 90% of recipients of untreated factor VIII are likely to be seropositive. Heat treatment of freeze dried factor VIII at 80º C for 72 hours seems to inactivate most, if not all, of the virus.

Prion diseases and variant CJD

Transmissible spongiform encephalopathies (TSE) are fatal and untreatable diseases in which the pathological and clinical changes are essentially of the central nervous system (CNS). TSE, in the form of scrapie, has been known to affect sheep and goats since the 18th century; in 1936 scrapie was shown to be transmissible. Scrapie is epidemic in some countries such as the U.K. where 1/3 of flocks are affected. Bovine spongiform encephalopathy (BSE) ("mad cow disease"), appeared in cattle in the U.K. in 1995, with a mean incubation period of 5-6 years. The only country in the world where BSE acquired epidemic proportions is the U.K., with over 3, 000 cases/month in 1992 and more than 170, 000 affected cattle reported. There are still some residual cases of BSE being reported in the U.K. every month. It is now accepted that BSE resulted from feeding cattle with meat and bone meal contaminated with sheep scrapie at a time when the rendering techniques changed.

Several forms of human TSEs are known (I) Creutzfeld-Jakob disease (CJD), first described in 1921, which can present as: classical/sporadic, familial or iatrogenic, (ii) Gertsmann-Sträussler-Sheinker syndrome (GSS); (iii) fatal familial insomnia (FFI); (iv) kuru; and (v) the recently reported new variant CJD (nvCJD). In 1968, classical CJD was shown to be transmissible in the laboratory to a chimpanzee. The first cluster of 10 cases of the new clinico-pathological variant of CJD, named new variant or nvCJD, was reported in 1996. As of September 1999, 43 cases of nvCJD had been identified in the U.K., and a single case in France. No confirmed cases have been reported in other countries. There are differences between classical/sporadic CJD and nvCJD: the former is a disease of relatively short duration, affecting people who are middle aged or elderly, whilst the latter affects young adults and is of longer duration. CJD has a world-wide distribution with an incidence of about 1 case/million population/year, whilst nvCJD has so far been confined to the U.K.. Classical CJD presents as a rapidly progressive dementia or ataxia, whilst nvCJD tends to present as a psychiatric illness with or without sensory symptoms and it may take months for neurological disease to develop. Both CJD and nvCJD are very similar in their terminal stages.

TSEs are caused by an accumulation in the CNS of an abnormal protein PrPRES or PrPSC. In humans, a gene PRNP encodes for a normal membrane protein PrPC, of unknown function. In TSEs the normal PrPC undergoes a post translational modification and is converted to the pathological isoform PrPRES which does not elicit antibody formation in the host. Both normal and abnormal prion proteins have the same primary structure (same gene) but the abnormal PrPRES has a different conformation with significant ß sheet structure as opposed to the predominantly á structure seen in normal PrPC. This new confor- mation makes PrPRES insoluble in detergents, protease resistant, with a tendency to aggregate and form amyloid structures. The abnormal prion would be able to replicate without the need for nucleic acid; its accumulation in the CNS is associated with disease and infectivity. Abnormal prion protein is more abundant in nvCJD than in classical CJD.

It is now clearly established that nvCJD is BSE in humans: (i) there is sufficient evidence that the prion strain is the same; (ii) it is highly probable that the agent spread from cattle to humans; (iii) both BSE and nvCJD have the highest prevalence in the U.K.; (iv) it is reasonable to believe that transmission was via contaminated food. So far, there is no epidemiological evidence of transmission of any form of TSE by routine, therapeutic blood transfusion in humans or animals. In fact, the mechanism of infectivity is unknown for all of the TSEs. However, absence of evidence of risk is not necessarily evidence of absence of risk. Prions can be demonstrated in the blood of experimental animals only when blood or fractions therefrom are directly inoculated into the brains of other animals. This indicates that, if abnormal prion is present in blood of infected animals or humans, its amount must be very low.

Postmortem investigations have shown that nvCJD has a greater association with lymphoid tissue, since it has been found in tonsils and the appendix of infected humans. It is likely that sub-populations of white cells, possibly the follicular dendritic cells and/or B lymphocytes are a prerequisite for CNS infection, hence the decision for universal leukodepletion of the U.K. blood supply.

It is not known how many people could be infected with the abnormal prion of nvCJD in the U.K.. Furthermore, it is not known whether all infected subjects will acquire the disease. So far, all the cases investigated show the same genotype i.e. methionine homozygosity in codon 129 of the infected patient's prion protein. This suggests an increased susceptibility to nvCJD in the 1/3 of the U.K. population who have this genotype.

It is still early days to know whether or not nvCJD is transmissible by transfusion. Of the 43 people who have died of nvCJD in the U.K., 4 are known to have been blood donors, leading to world-wide recalls of fractionated blood products made from their plasma. This led to the U.K. government decision to stop fractionating British plasma. As a result, plasma for fractionation in the U.K. is being imported from countries where there have been no cases of nvCJD reported, mainly, the USA; 450 tonnes of U.K. volunteer donor plasma are being discarded in England every year.

In January 1998, the Spongiform Encephalopathy Advisory Committee (SEAC), commissioned a study to investigate the risk of exposure to nvCJD infectivity in transfused blood or blood products as a result of donations from people unknowingly carrying the abnormal prions. The study group concluded that blood from people with nvCJD may contain infectivity that could be transmitted through blood transfusion, although this has never been proved conclusively. The recommendations are based on the assumption that infectivity is present in blood. The implementation of precautionary measures recognizes the potential for blood transfusion to act as a vehicle for dissemination of the abnormal prion. Leukodepletion, elimination of U.K.-sourced plasma, prevention of transfusion recipients from giving blood, prophylactic treatment using pentosan polysulphate were all evaluated. The risk assessment concluded that, with our current level of knowledge, it is not possible to draw any firm conclusions as to whether or not prion infectivity can be transmitted through the transfusion of blood or plasma derivatives and, in addition, the number of people who may have been infected with nvCJD is not known. For these reasons, it is not possible to estimate the absolute level of risk, if any. The only evidence for infectivity in blood is based on experiments with animal models that have shown that blood from an animal artificially infected with a form of TSE can be infectious when inoculated intracerebrally into another animal of the same species. There has been only one report of TSE transmission by blood transfusion in an animal model, but this has not been verified by others.

The risk assessment study concluded that no measures have been identified that can eliminate all the hypothetical risk of nvCJD by transfusion, but several preventive measures provide significant risk reduction, in particular;

Leukodepletion: the group recommended universal leukodepletion justified by the collateral clinical benefits (e.g. reduction of the immunomodulatory effects, HLA alloimmunisation). U.K. Blood Transfusion Services have implemented universal leukodepletion of all labile blood components, as from November 1999.

- Elimination of U.K. plasma productswill eliminate any risk of transmission by fractionated products, assuming there is no nvCJD in the source country from where plasma is imported.

- Reduction in any inappropriate use of blood components would certainly decrease the risk in recipients.

- Maximizing autologous blood transfusion.

- Use of high purity Factor VIII for hemophiliacs under 16 years old.

- Investigation of prophylactic treatment against nvCJD; it has been shown, in animal models, that polysulphonated polyglycosides such as pentosan polysulphate can reduce the susceptibility to infection from TSEs.

- Extensive surveillance and monitoring of nvCJDoccurrence and transmission at a national level.

Despite so many unknowns and despite the fact that prion diseases have never been shown to be transmitted by blood transfusion, the U.K. government has decided to introduce the above precautionary measures at a considerably high cost, following the premise that "it is better to be safe than sorry".

Conclusion

The number of infections that are potentially transmissible by blood transfusion seems daunting. In developed countries, however, the incidence of most of these infections in the general population is low. Most potential donors who are at high risk of transmitting infectious agents have voluntarily stopped giving blood, and blood that is given is carefully screened, so the absolute numbers of infectious complications of blood transfusion are minute. Patients are at much greater risk if they do not have transfusions when they genuinely need them than they are from the possible complications of transfusion, particularly as physicians are now more aware of the risks and more discerning in their prescription of blood or its components.

References

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3 Almond J, Pattison J.Human BSE. Nature 1997; 389(6650):437-8.
4 Azzi A, Morfini M, Mannucci PM.The transfusion- associated transmission of parvovirus B19. Transfus Med Rev 1999; 13(3):194-204.
5 Barbara JA.Does GB virus C ('hepatitis G virus') threaten the safety of our blood supply? Transfus Med 1997; 7(2):75-6.
6 Barbara JA.Prevention of infections transmissible by blood derivatives. Transfus Sci 1998; 19(1):3-7.
7 Barbara JA.Microbiological safety of blood transfusion. Vox Sang 1998; 74 Suppl 2:11-3.
8 Barbara J, Flanagan P.Blood transfusion risk: protecting against the unknown. BMJ 1998; 316(7133):717-8.
9 Brown P.Can Creutzfeldt-Jakob disease be transmitted by transfusion? Curr Opin Hematol 1995; 2(6):472-7.
10 Brown P, Bradley R.1755 and all that: a historical primer of transmissible spongiform encephalopathy. BMJ 1998; 317(7174):1688-92.
11 Brown P, Rohwer RG, Dunstan BC, MacAuley C, Gajdusek DC, Drohan WN.The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy. Transfusion 1998; 38( 9):810-6.
12 Busch MP, Alter HJ.Will human immunodeficiency virus p24 antigen screening increase the safety of the blood supply and, if so, at what cost? Transfusion 1995; 35(7):536-9.
13 Busch M, Chamberland M, Epstein J, Kleinman S , Khabbaz R, Nemo G.Oversight and monitoring of blood safety in the United States. Vox Sang 1999; 77(2):67-76.
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15 Debeir J, Noel L, Aullen J, Frette C, Sari F, Mai MP et al.The French haemovigilance system. Vox Sang 1999; 77(2):77-81.
16 Engelfriet CP, Reesink HW, Brand B, Levy G, Williamson LM, Menitove JE et al.Haemovigilance systems. Vox Sang 1999; 77(2):110-20.
17 Kleinman S, Busch MP, Hall L, Thomson R, Glynn S, Gallahan D et al.False-positive HIV-1 test results in a low-risk screening setting of voluntary blood donation. Retrovirus Epidemiology Donor Study. JAMA 1998; 280(12):1080-5.
18 Knight R.The relationship between new variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Vox Sang 1999; 76(4):203-8.
19 Lackritz EM, Satten GA, Aberle-Grasse J, Dodd RY, Raimondi VP, Janssen RS et al.Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med 1995; 333(26):1721-5.
20 McDonald CP, Hartley S, Orchard K, Hughes G, Brett MM, Hewitt PE et al.Fatal Clostridium perfringens sepsis from a pooled platelet transfusion. Transfus Med 1998; 8(1):19-22.
21 Mollison PL, Engelfriet CP, Contreras MC.Blood Transfusion in Clinical Medicine. 10th edition. Oxford: Blackwell Science; 1997.
22 Pamphilon DH, Rider JR, Barbara JA, Williamson LM.Prevention of transfusion-transmitted cytomegalovirus infection. Transfus Med 1999; 9(2):115-23.
23 Patterson WJ, Painter MJ.Bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease: an overview. Commun Dis Public Health 1999; 2(1):5-13.
24 Pawson R, Rajan S, Hazlehurst G, Dusheiko G, Miller R, Hewitt P et al.. Hepatitis C lookback programme: a single hospital experience. Transfus Med 1999; 9(3):189-93.
25 Regan FA, Hewitt PE, Barbara JA, Contreras MC.Prospective investigation of transfusion transmitted infection in the recipients of over 20.000 units of blood. BMJ 1999 (in Press).
26 Sazama K.Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 1990; 30(7):583-90.
27 Shulman IA.Intervention strategies to reduce the risk of transfusion-transmitted Trypanosoma cruzi infection in the United States. Transfus Med Rev 1999; 13(3):227-34.
28 Voak D, Caffrey EA, Barbara JA, Pollock A, Scott M, Contreras MC.Affordable safety for the blood supply in developed and developing countries. Transfus Med 1998; 8(2):73-6.
29 Will RG, Kimberlin RH.Creutzfeldt-Jakob disease and the risk from blood or blood products. Vox Sang 1998; 75(3):178-80.
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Marcela Contreras & John A. Barbara

Executive Director,
National Blood Service,
London, UK

Brief History of Bloodless Medicine and Surgery

INTRODUCTION

Although the term “bloodless medicine and surgery” is relatively new, the desire to restrict blood loss and transfusion need is not. In fact, medicine has searched for alternatives to allogeneic blood ever since transfusion became a practical reality. The history of transfusion can be followed by tracking the convergence of the growth of knowledge in anatomy and physiology with the development of technology and the maturation of our rationale for using blood. Underlying and anchoring these themes is the persistent bass note of risk, that prompted the search for alternatives. This brief review highlights the reasons for and the results of the changes in transfusion medicine that ultimately led to the current state of bloodless medicine and surgery. Although the focus may seem weighted toward the United States, particularly in recent developments, I have attempted to include worldwide milestones, especially those of true pioneers in the field.

DEVELOPMENT OF ALLOGENEIC TRANSFUSION

It is generally accepted that the first human transfusions were performed in France and England in 1667. Although there are apocryphal reports of blood being transfused to Pope Innocent VIII in the 15th century, the lack of means to transfuse blood makes this unlikely. As is true in much of medicine, 17th century transfusions were the direct result of the development of technology coinciding with a knowledge of anatomy and physiology, no matter how crude, that made an idea a reality. The sentinel events were the description of the venous circulation in De Motu Cordis by William Harvey in 1628 and Sir Christopher Wren’s creation in 1658 of the first “syringe” made by fastening an animal bladder to a sharpened goose quill. Wren was actually preceded in 1652 in the use of this device by Francis Potter, a British rector, whose choice of pullets as an experimental animal doomed his experiments to failure. Using larger animals, Wren was able to inject a variety of substances into veins. Building on these early experiments, Richard Lower performed the first animal to animal blood transfusions in a dog in 1665 in London. Similar experiments were conducted by Jean Baptiste Denis and a group of collaborators in Paris at the same time. This group is credited as the first to transfuse animal blood into a human subject when they gave lamb’s blood to a young man “possessed of an incredible stupidity” on June 15, 1667 [1]. Lower quickly followed with a similar transfusion given to Arthur Coga in London on November 23, 1967.

The transfusions were technically successful, but no clinical benefit was achieved. The latter is not unexpected since the physicians’goal was to treat the patient’s mental problems through the infusion of animal humors from the blood. This medical fad continued for only a short period of time until a French patient, Antoine Mauroy, died after two transfusions of calf’s blood given by Denis in December, 1667. In the investigation that ensued, Dr. Denis and colleagues were acquitted of the patient’s death when the French courts determined that Mauroy had been poisoned by his wife. However, the civil action dealt a death blow to transfusion experimentation. The procedure was quickly banned as dangerous by medical and legislative bodies throughout Europe and it disappeared from sight expect for sporadic cases. Since transfusion had not been shown to have any measurable benefit, there was no movement to find a replacement.

Only sporadic reports of transfusion can be found from the 1660’s until the early 1800’s, a period of 150 years. During this time medical science had made significant advances with the further elucidation of oxygen physiology and red cell function. In 1774, Priestley described the function of red blood cells as oxygen carriers. In the same year, Lavoisier clarified the role of oxygen in respiration. The stage was set for a new era of transfusion medicine. The credit for the rebirth of interest in transfusion belongs to James Blundell, a physician-surgeon practicing in London in the early 19th century. Alarmed by the unacceptably high number of deaths in his practice caused by post-partum hemorrhage, Blundell looked for a means to replace this shed blood. Blundell’s interest prompted him to experiment first in the animal laboratory with interspecies transfusion, which led him to the conclusion that transfusing animal blood into humans was inherently unsafe [2]. When faced with the daunting task of obtaining human blood for transfusion, he developed two approaches : 1) obtaining capillary blood from volunteer donors with a rather monstrous device, and 2) salvaging shed blood. He stirred or agitated the blood to “defibrinate” it, then infused it through an impeller device that included one of the first uses of a three-way stopcock. Four of his first eight attempts at human to human transfusion were successful.

Blundell is considered to be the Father of Autotransfusion for his work in this field [3]. He justly deserves credit as the first to use autologous blood for transfusion. However, I believe he warrants even greater recognition as the Father of Modern Surgical Transfusion Science for being the first to make the connection between the potential benefit of transfusion in preventing death from hemorrhage. This philosophy was a departure from the traditional view of blood transfusion based on Galenic principles of blood as a humor rather than as a physiological substance. Remember that Blundell practiced medicine at a time when blood letting to the extreme was widely accepted as appropriate therapy for most illnesses. Little regard was paid to the deaths caused by this iatrogenic hemorrhage. Battlefield approaches to bleeding were based on quick action and vessel ligation. Surgeons had made the connection between blood loss and death, but Blundell was the first to show that transfusion could be therapeutic [4]. In addition, Blundell’s rejection of animal blood as incompatible with human’s predated Landsteiner’s discovery of blood groups by almost 100 years.

Blundell’s pioneering work reawakened the medical world to the therapeutic potential of transfused blood. Others modified and improved on his clinical experiments, to the extent that Jennings was able to compile and publish a bibliography and review of 243 transfusions performed before 1873 [5] (Figure 1). His findings pointed out the problems with transfusion that prompted the search for an alternative. Although 114 patients (46.9 %) were reported to have had a “complete recovery” following transfusion, others did not fare so well. During this period, our understanding of physiology and the effects of blood loss advanced rapidly. Claude Bernard established the concept of an internal milieu of checks and balances in the body and the need to maintain a steady intravascular volume to prevent death. In 1854, Le Dran defined metabolic derangement as the clinical entity of shock. The use of blood transfusion now had a firmer physiological foundation for use in clinical practice as a means of restoring blood volume.

However, multiple problems with blood hindered its regular use. Lethal transfusion reactions were not understood. Blood was difficult to handle because of its rapid clotting time, which effectively eliminated even temporary storage and indirect transfusion. As a result, the field of clinical transfusion medicine was dominated by surgical specialists who created direct, surgical communications between donor and recipient by connecting artery to vein (Figure 2) (Figure 3). Unfortunately, this approach required considerable skill, was cumbersome, and permitted only one-time transfusions. Early syringe and roller devices using two syringes improved direct transfusion practices, but the problems of reactions, sterility, and volume overload remained. These problems prompted physicians to look for easier more universal solutions.

As early as 1876, Barnes and Little described the use of saline solutions in the restoration of “equilibrium in the circulatory system” [1]. Further experiments with this first “blood substitute” established a firm role for crystalloid infusions in the treatment of hemorrhage. Hamlin tried infusions of milk as a blood replacement, reasoning that the white corpuscles of blood came from the same source as milk [29].

Fortunately, this approach was short-lived. Saline provided some advantages and was used in conjunction with the newly developed general anesthesia that permitted more involved surgery. Evidence produced by Rudolph Virchow that malignancies traveled via the lymphatic system led to the radical excision of cancers and their lymph node groups, e.g., radical mastectomy and abdominoperineal resection. Excessive hemorrhage as a cause of death now moved from the battlefield into the elective surgical suite. Halsted’s description of uncontrolled bleeding as the only defense of the unconscious patient against the incompetent surgeon epitomized the new era of surgical training aimed at controlling blood loss [6] (Figure 4). Surgeons trained by Halsted at Johns Hopkins spread the bible of gentle tissue handling, anatomic surgical approaches and meticulous hemostasis that remain with us today as a mainstay of bloodless medicine and surg e r y. Halsted was a true innovator in bloodless medicine and surgery both in his insistence on careful technique and in his introduction of the “German hemostat”, an instrument used today by surgeons around the world. His refusal to accept preventable blood loss in the operating theater is a major tenet of modern transfusion alternative philosophy. He also understood that the use of patient and procedure-directed anesthesia permitted the surgeon the time necessary to perform s u rgery without hemorrhage. Even with these advances, blood loss remained an obstacle to the further development of surg e r y.

As the 20th century approached, some investigators tackled the problem of transfusion reactions, some searched for ways to store blood, while others improved our knowledge of when to transfuse. Landsteiner’s description of the ABO red cell antigen system led to early forms of testing that dramatically reduced the risk of death from transfusion reactions [7]. Weil added citrate salts to blood, proving that this would retard coagulation. Lewisohn was the first to devise a safe combination of citrate that permitted blood to be stored temporarily. Rous and Turner, working at the Rockefeller Institute in New York, added dextrose to the citrated blood, thereby allowing storage for up to 21 days [8]. Crile consolidated our understanding of anemia, hemorrhage and transfusion as battlefield transfusions. Work presented at the American Human Serum Association meeting in 1941 focused on the need for the United States and Canada to prepare a wartime supply of blood and blood products. This work is summarized in the monograph entitled Blood Substitutes and Blood Transfusion edited by Stuart Mudd and William Thalhimer [11]. The book contains state of the art chapters on preparation of dried human plasma, early work on hemoglobin-saline solutions by Amberson, and the use of casein infusions by Whipple. Substitutes saw little use during the war. Thirteen million units a means of restoring blood loss [1].

This landmark work was completed just in time for blood to be used at the front in World War I. However, it created a whole, new set of problems of the need for a donor supply and how, where and for how long to store blood (Figure 5). Russian physicians, led by Filatov, Depp and Yudin pioneered the collection and storage of cadaver blood [9]. This approach met with great disfavor in the West, but it formed the basis for the development in 1934 of the first blood bank in Chicago by Seed and Fantus that were under investigation were described as well as protein hydrolysates, the clinical precursors of hyperalimentation solutions. None of these were ready for extensive clinical use. For example, Amberson’s hemoglobin solutions produced significant renal damage and were rapidly eliminated from the circulation [13].

[10]. Their unique contribution was twofold : development of a facility to store blood and the use of live human donors.

The onset of World War II created the need for modernization in transfusion delivery as well the need for a suitable substitute (Figure 6). British blood services responded with both direct and indirect of blood and blood products were contributed by United States citizens for use by the Armed Forces between 1941 and 1945. The realization that the United States now collects the same number of units in one year reflects how much the business of blood banking has grown.

Lessons learned in World War II were described by White and Weinstein in their book on current transfusion practices [12]. Topics in the book included the use of human plasma in treating shock on the battlefield and plans for the adaptation of its use to civilian settings. A variety of gelatin-based and animal derivative substitutes

The general opinion based on this huge wartime experience was that blood and blood products were safe for widespread human use. No one wished to return to the “bad old days” of animal products for transfusion when human plasma and albumin were readily available, effective and safe. Physicians returning home after the war demanded that blood transfusion be available, so transfusion medicine entered an era of rapid growth secure in the belief that the benefits of transfused blood far outweighed the risks.

THE RISE OF ALTERNATIVES TO ALLOGENEIC BLOOD

Several major forces played pivotal roles in the development of transfusion alternatives and bloodless medicine and surgery, including our increasing knowledge of the risks of allogeneic blood, the desire of Jehovah’s Witnesses to have advanced medical care without transfusion, explosions in medical technology and steady progress in our understanding of oxygen transport physiology. The problem of lethal transfusion reactions had been solved with the introduction of routine typing and cross-matching. The ability to identify the Rh complex and multiple, isolated red cell antigens reduced the incidence of hemolytic and antibody-based reactions. It had been known for some time that blood transfusion transmitted syphilis, malaria, smallpox and what was known as passive anaphylaxis. The only disease thought to be a public health concern in the United States was syphilis. Transmission could be prevented by mandatory testing for spirochetes using the Venereal Disease Research Laboratory, or VDRL, test. As a result, physicians were complacent about the use of blood. Water began to seep through the dam as early as 1943 with reports of jaundice following the administration of blood products [14, 15]. These isolated reports raised little concern among the surgeons, most frequent users of blood, primarily because they rarely saw the consequences of transfusion-transmitted hepatitis. Patients who developed this disease after surgical transfusion were long gone from the surgeon’s practice. Milles, Langston and D’Alessandro raised concerns about this problem in their visionary monograph on autologous transfusion published in 1971 [9]. They reported not only on the relationship between transfusion and hepatitis but also on their experience with the use of both predonated autologous blood and autotransfusion to avoid allogeneic transfusion.

Several major forces played pivotal roles in the development of transfusion alternatives and bloodless medicine and surgery, including our increasing knowledge of the risks of allogeneic blood, the desire of Jehovah’s Witnesses to have advanced medical care without transfusion, explosions in medical technology and steady progress in our understanding of oxygen transport physiology. The problem of lethal transfusion reactions had been solved with the introduction of routine typing and cross-matching. The ability to identify the Rh complex and multiple, isolated red cell antigens reduced the incidence of hemolytic and antibody-based reactions. It had been known for some time that blood transfusion transmitted syphilis, malaria, smallpox and what was known as passive anaphylaxis. The only disease thought to be a public health concern in the United States was syphilis. Transmission could be prevented by mandatory testing for spirochetes using the Venereal Disease Research Laboratory, or VDRL, test. As a result, physicians were complacent about the use of blood. Water began to seep through the dam as early as 1943 with reports of jaundice following the administration of blood products [14, 15]. These isolated reports raised little concern among the surgeons, most frequent users of blood, primarily because they rarely saw the consequences of transfusion-transmitted hepatitis. Patients who developed this disease after surgical transfusion were long gone from the surgeon’s practice. Milles, Langston and D’Alessandro raised concerns about this problem in their visionary monograph on autologous transfusion published in 1971 [9]. They reported not only on the relationship between transfusion and hepatitis but also on their experience with the use of both predonated autologous blood and autotransfusion to avoid allogeneic transfusion.

Milles and Langston’s pioneering work in autologous predonation and autotransfusion was prompted by their concerns about transfusion-transmitted hepatitis and medicine’s inability to prevent its spread. Unfortunately, their work fell on deaf ears in most operating rooms in the United States, in part because of the need for allogeneic blood to support advances in surgical technology and treatment. Some others saw the wisdom of using the patient’s own blood. Investigation of another approach to using autologous blood through hemodilution has been part of the life’s work of Konrad Messmer of Germany, who has provided us with the understanding of hemodilution and the physiologic basis for its current clinical use. The ready availability of blood in the 1950’s and 1960’s led to the development of what I have chosen to call transfusion-based surgical technologies and operations. These include cardiac, vascular, oncologic and joint replacement surgery amongst others. Gibbon’s invention of the first heart-lung machine in 1953 provided the means for surgery on the heart and great vessels. Blood was used to prime the pump in early machines. I personally remember routinely typing and crossmatching 25 units of blood for single-vessel cardiac bypass operations in the 1970’s. This extensive use of blood prompted surgeons and anesthesiologists to find ways of salvaging any left over cells [20].

Autotransfusion, or salvage and reinfusion of shed blood, had been used sporadically since 1914 when Theis, a German obstetrician, successfully returned blood lost from ruptured ectopic pregnancies through a gauze filter in three women [17]. Loyal Davis and Harvey Cushing reported on its usefulness in neurosurgery in 1925 [18]. Stager’s review of the literature in 1951 showed that autotransfusion had been used in close to 500 patients with great success [19]. Although Cohn had conceived of the idea of a cell separation device for autotransfusion as early as 1953, the first prototype was built by Taswell and Wilson at the Mayo Clinic in 1968. At the same time, Dyer and Klebanoff developed a cell salvage device through Bentley Laboratories. Blood collected by this first “Bentley” machine was contaminated with impurities that often lead to coagulopathy and it was known to produce lethal air embolism. Improvements in separation technology and circuit design helped combat these problems. Latham at Haemonetics Corporation devised a differential centrifugation bowl coupled with a collection reservoir containing anticoagulant that created a practical means for recovery of shed blood in the operating room during a variety of surgical procedures [20]. Improvements in these devices over the years have led to the current range of cell salvage devices that are used in both the operative and postoperative periods.

One group of patients, the Jehovah’s Witnesses, were unable to take advantage of these transfusion-based surgical technologies and operations, because of their religious beliefs that forbade them from accepting blood transfusions [21]. Their desire to obtain the best possible medical care without the use of blood was met with scorn and derision by many in the medical community. Most physicians misunderstood the Witnesses position and labeled them as radicals who refused all medical treatment for themselves and their children. Few surgeons who did understand were willing to take on the problems of major surgery without transfusion. One of these few, Denton Cooley, was the earliest of the modern pioneers in bloodless medicine and surgery. His demonstration that open heart surgery could be safely performed without blood, first published in 1977, encompassed a twenty year experience including 542 patients ranging in age from one day to 89 years [22]. This work provided a stimulus for others to provide surgical treatment to Jehovah’s Witnesses. The most notable among these was Ron Lapin, a California surgeon, who operated on several thousand Witness patients during his surgical career. Moreover, he was the first to recognize bloodless medicine and surgery as a “speciality” or discipline. Based on this belief, he created the first bloodless medicine and surgery center in Bellflower Hospital in California in the late 1970’s – early 1980’s in response to the demand for his services. He also published the first journal in the field and made the first efforts at training and credentialing physicians. The Watchtower Bible and Tract Society, the parent organization of the Jehovah’s Witness religion, recognized the importance of providing educational assistance to physicians who were willing to treat their members. Early. Informal efforts at education and communication were given structure in 1988 with the introduction of the Hospital Information Services branch of the watchtower in Brooklyn. This group of individuals has become one of the primary sources of information regarding transfusion alternatives to the medical community.

Technological developments also played a significant role during this time, particularly in the field of blood substitutes. Gerald Moss and Stephen Gould in Chicago and Tom Chang in Montreal were among those who worked diligently on the production of a safe, human hemoglobin-derived substitute for blood [23, 24]. Moss and Gould’s systematic approach to solving the toxicity problems of these products has led to their polymerized hemoglobin, Polyheme® which is in clinical trials today [25]. Tom Chang’s continued quest for a liposome encapsulated hemoglobin substitute has produced two, significant side benefits. He has provided us with much needed information on oxygen transport physiology as well as a venue for discussion of blood substitute through both his biannual conferences and the journal Artificial Cells, Blood Substitutes and Immobilization Biotechnology. Perfluorocarbon-based blood substitutes saw the light of day in the early 1980’s in the form of Fluosol DA20%, a product produced by Green Cross of Osaka, Japan. It was the genius of Ryochi Naito, the company’s founder, that coupled Leland Clark’s work with raw perflourocarbons with Robert Geyer’s development of intravenous lipid emulsions to produce this first artificial blood substitute [26].

Clinical trials of Fluosol in the anemic Jehovah’s Witness patient in the early 1980’s led to a myriad of advances in bloodless medicine and surgery. Although Fluosol was not proven to be of significant benefit in treating surgical anemia, its failings helped us to redefine the role of temporary oxygen carriers and to focus on their correct potential use as transfusion alternatives. Duane Roth, Peter Keipert and Simon Faithfull of Alliance Pharmaceuticals have built on this early experience to produce Oxygent® , the modern perfluorocarbon oxygen carrier now in clinical trials [27]. Experiences with Fluosol had a much greater impact on those involved in the 1980’s clinical trials, myself included [28]. These were the stimulus for many to question longstanding teachings about the transfusion trigger and to begin to reassess our use of allogeneic blood. Experience with treating Jehovah’s Witnesses prompted us to develop one of the first bloodless medicine and surgery centers at Cooper Hospital in Camden, New Jersey. Others sprang up in Chicago, Cleveland and in Europe as time progressed. To date there are close to 200 such centers throughout the world. A look at the world’s literature on bloodless medicine and surgery topics shows how much work has been published in this field.

Without question, the realization in the early 1980’s that the HIV virus was transmissible by blood transfusion opened the eyes of both physicians and the public to the inherent risks of allogeneic blood. This reawakening coincided with many of the technological and scientific advances that allowed us not only to analyze blood in a more sophisticated and complete way but also to take measures to ensure increased safety. The reader is undoubtedly familiar with the worldwide efforts and successes in this area. Physicians and scientists throughout the world have modified surgical procedures, investigated and improved autologous strategies, explored the role of drugs, blood substitutes and sealants in minimizing blood loss and the need for transfusion. Alternatives are widely accepted as typified by predonation, which has become a standard in joint replacement surgery. Arguments have shifted from whether or not these alternatives reduce allogeneic blood use concerns over appropriate and cost-effective use. Consensus conferences transfusion policies have been held in a variety of countries and by all major societies. Organizations such as NATA, the Network for Advancement of Transfusion Alternatives, and the driving force behind this textbook are now in place.

Although bloodless medicine and surgery has come a long way, there is still much to be done. Our understanding of the benefit of allogeneic blood in a clinical settings is now under scrutiny and will help redefine when and whom we transfuse. Although most physicians understand the risks of blood, education is still needed in the correct use of alternatives. Blood substitutes, or oxygen carriers, are finally on the clinical horizon and will revolutionize the way we understand and treat oxygen transport. The future is bright for the field of transfusion alternatives.

References

1. Diamond L. A History of Blood Transfusion, in Blood, Pure and Eloquent. W. MM, (Ed). McGraw-Hill: New York , New York, 1980: 659-683.

2. Blundell J. Experiments on the Transfusion of Blood by the Syringe. Medicochir Transactions, 1818; IX: 56-92.

3. Tawes R, Duvall T. Autotransfusion in Cardiac and Vascular Surgery: Overview of a 25-Year Experience with Intraoperative Autotransfusion. In: Autotransfusion: Therapeutic Principles and Trends. R. Tawes (Ed). Gregory Appleton: Detroit, 1997: 147-148.

4. Bell J. The Principles of Surgery. Philadelphia, 1810; PA.

5. Jennings C. Transfusion: It’s History, Indications, and Modes of Application . Leonard & Co. New York, 1883: 108.

6. Surgical Papers by William Stewart Halsted. Baltimore , MD: Johns Hopkins Press, 1924.

7. Landsteiner K. Wein Klin Wschr, 1901; 14: 113 2 – 1136.

8. Rous P, Turner J. Preservation of living RBC in vitro. J Exp Med, 1916; 232: 219-225.

9. Milles G, Langston H, D’Allessandr W. Autologous Transfusion. The John Alexander Monograph series. Maier H (Ed). C.C. Thomas. Springfield, 1971; 127.

10. Fantus B. Therapy of the Cook County Hospital (blood preservation). JAMA, 1937; 109: 128-132.

11. Mudd S, Thalhimer W. Blood Substitutes and Blood Transfusion. Vol. 1: C.C. Thomas. Springfield, 1942: 407.

12. White C, Weinstein J. Blood Derivatives and Substitutes. Preparation, Storage, Adminsitration and Clinical Results including a Discussion of Shock. Etiology, Physiology, Pathology and Treatment. Vol. 1: Williams and Wilkins. Baltimore, 1947: 484.

13. Amberson W, Jacobs J, Hisey A. Hemoglobin Solutions as Transfusion Media, in Blood Substitutes and Blood Transfusion. S. Mudd and W. Thalheimer (Eds). Chas. C. Thomas Springfield, 1942: 156-172.

14. Morgan H, Williamson D. Jaundice following administration of human blood products. Brit Med J, 1943: 1: 750- 752.

15. Lehane D et al. Homologous Serum Jaundice. B M J , 1949: 2: 572-574.

16. Grant F. Autotransfusion. Ann Surg, 1921; 74: 253-255.

17. Theis J. Zur Behandling der extrauterine Gravidataet. Zbl Gynaek, 1914; 38: 1191 - 1194.

18. Davis L, Cushing L. Experiences with blood replacement during and after major intracranial operations. Surg Gynec Onstet, 1925; 40: 310-316.

19. Stager W. Blood conservation by autotransfusion. Arch Surg, 1951; 63: 78-83.

20. Tawes R Jr., DuVall T B. The basic concepts of an autotransfusor: the Cell-Saver. Semin Vasc Surg, 1994; 7 (2): 93- 9 4 .

21. Jehovah’s Witnesses and the Question of Blood. Watchtower Bible and Tract Society. New York, 1977: 38-49.

22. Ott DA, Cooley DA. Cardiovascular surgery in Jehovah’s Witnesses. JAMA, 1977; 238: 1256-1258.

23. Moss G, Gould S, Sehgal L. Polyhemoglobin and Flurocarbon as Blood Substitutes. Biomat Art Cells Art Org , 1981; 15 (2): 333-336.

24. Chang T M. Blood substitutes based on modified hemoglobin prepared by encapsulation or crosslinking: an overview. Biomater Artif Cells Immobilization Biotechnol, 1992; 20 (2-4) 159-179.

25. Gould SA et al. The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery [see comments]. J Am Coll Surg , 1998; 187 (2): 113-120 (discussion: 120-122).

26. Spence RK. Perfluorocarbons in the twenty-first century: clinical applications as transfusion alternatives. Artif Cells Blood Substit Immobil Biotechnol, 1995; 23 (3): 367-380.

27. Keipert P. Perfluorochemical Emulsions: Future Alternatives for Transfusion, in Blood Substitutes: Principles, Methods, Products and Clinical Trials. T. Chang, (Ed). Montreal, 1998: 127-156.

28. Spence RK et al. Fluosol DA-20 in the treatment of severe anemia: randomized controlled study of 46 patients. Crit Care Med, 1990; 18 (11): 1227-1230.

29. Spence RK. Blood substitutes. In Clinical Practice of Transfusion Medicine, 3rd Ed. Petz, Swisher, Kleinman, Strauss, Spence (eds.). Churchill-Livingston, New-York, 1996: 967-984.

http://www.nataonline.com/Art.php3?NumArticle=71

Richard K. Spence, MD, FACS Director, Department of Surgical Education Baptist Health System, Inc. 701 Princeton Avenue, SW 4 East Birmingham, Alabama 35211-1399 USA

Cirugía sin sangre

Existe una técnica avanzada que reduce al mínimo la pérdida de este fluido antes, durante y después del tratamiento

Debido a la escasez de sangre se están empezando a desarrollar técnicas en la que no se tenga que recurrir a la transfusión. (EFE)

08 de octubre de 2005La primera transfusión de sangre de la que se tiene noticia se hizo hacia 1440 al papa Inocencio VIII, según señala la enciclopedia cibernética Wikipedia. Cuando el Pontífice entró en coma, a sugerencia de su médico se le hizo una transfusión de la sangre de tres niños. Los menores tenían 10 años de edad y se les había prometido un ducado a cada uno a cambio de su sangre. Aunque los tres fallecieron, los historiadores de la medicina destacan este evento como el primer intento histórico de transfusión de sangre.
Desde entonces, el mundo ha dado muchas vueltas y las transfusiones han llegado a convertirse en cosa de todos los días. En efecto, cada año más de cuatro millones de niños y adultos en Estados Unidos reciben alrededor de 10 millones de unidades de sangre. En realidad, éstas ayudan a salvar miles de vidas cada día. En algunos países no se concibe una operación sin la correspondiente transfusión.
Por otro lado, el peligro de contaminación con la sangre administrada ha llevado a buscar otros métodos o técnicas, entre ellos la de evitar completamente la transfusión.
Una de éstas técnicas es la “medicina sin sangre” que, a pesar de no ser muy popular aún, puede ayudar a evitar el contagio de enfermedades transmitidas por este vital líquido o evitar su escasez cuando se produzcan emergencias.
¿En qué consiste?
La medicina o cirugía sin sangre es una forma avanzada de ofrecer atención médica quirúrgica sin recurrir a donantes. Este tipo de medicina utiliza técnicas modernas para reducir al mínimo la pérdida de sangre del paciente antes, durante y después del tratamiento. El enfoque permite a los doctores brindar atención a los pacientes sin usar productos adicionales de sangre porque cada paciente retiene una cantidad suficiente de la suya.
“La mayoría de nuestros pacientes [testigos de Jehová] no acepta sangre. En vista de esto, a algunos médicos se nos ocurrió desarrollar técnicas que pudiéramos emplear para hacer intervenciones quirúrgicas y tratamientos médicos en los que no se tuviera que recurrir a la transfusión sino a otras alternativas médicas. Como consecuencia de la escasez de sangre estamos empezando a tomar conciencia de las estrategias de conservación de este vital líquido”, señaló en entrevista con La Opinión el doctor Vinod Malhotra, especialista en este tipo de intervenciones con práctica en el condado de Orange.
“Muchas veces hacemos transfusiones en los hospitales simplemente porque ya se ha ordenado la sangre”, continúa diciendo Malhotra. “El recuento de sangre de un hombre adulto es de aproximadamente 15 unidades, algunas veces, por diferentes motivos o accidentes, éste baja, pero aun así encontramos que no es necesario hacer transfusiones en ciertos niveles. Esas unidades que usamos innecesariamente podrían ser utilizadas en un centro de tratamiento de traumas o en otros lugares”, señala este especialista.
“Calculo que el 60% de la sangre que se usa en este país se aplica en intervenciones quirúrgicas electivas. Es decir, en operaciones que uno tiene tiempo de planear y en las que se sabe con anticipación que se producirá una pérdida de sangre. Si uno es un buen cirujano, no se debería perder esa sangre y se debería preparar al paciente adecuadamente. Esto significa, asegurarse de que el recuento sanguíneo se encuentra en su nivel más elevado posible, tomar todas las precauciones, usar técnicas durante la intervención que puedan ‘salvar’ la sangre del mismo paciente o usar métodos o aparatos [como el Cell Saver, que limpia y regenera la sangre y luego la bombea de regreso al cuerpo] para ‘reciclar’ la sangre del mismo paciente y devolvérsela, entonces no necesitará recurrir al banco de sangre”.
“Si pudiéramos reducir el uso y ahorrar un 10% adicional, sería de mucha ayuda. Por ejemplo, la cantidad de sangre que usamos anualmente en este país es de alrededor de 10 millones de unidades, si pudiéramos ahorrar la mitad o más de cinco millones de unidades, podríamos cubrir las necesidades verdaderas cuando realmente se necesita”.
Motivos religiosos
Si bien una de las razones principales para recurrir a esta práctica es evitar el contagio y la propagación de enfermedades (como el VIH, sida, hepatitis, etc.), también hay otras de carácter religioso.
La prensa nacional ha reportado de casos en que los padres y los médicos han chocado por el uso o no uso de la transfusión de sangre y han terminado en los tribunales.
“Recibo muchas llamadas de médicos que brindan tratamiento a personas que siguen la fe de los testigos de Jehová y que no están familiarizados con este método de tratamiento sin sangre. Me llaman porque no saben qué tratamiento aplicar, sólo saben una manera de tratar al paciente, y ésta es con transfusión de sangre. Nunca se les enseñó en las escuelas [de medicina] y no se sienten cómodos ni quieren correr el riesgo, por lo que me dicen: ‘Encárgate tú de esto’“, afirma Malhotra.
Recuperación de pacientes
Además del poco conocimiento de este tipo de procedimiento, también es grande el desconocimiento de su seguridad. Muchos de nosotros, que venimos de países donde asociamos las intervenciones quirúrgicas con la donación de sangre, podemos sentirnos “inseguros” de someternos a una operación si sabemos que no vamos a disponer de este líquido que se nos pueda transfundir en caso de ser necesario.
“Según nuestra experiencia, y hacemos muchas operaciones con este método, no vemos ninguna diferencia en la permanencia de pacientes que reciben y los que no reciben transfusiones de sangre. Sin embargo, algunos estudios sostienen que cuanto más reciben transfusiones, más prolongada es la permanencia de los pacientes en el hospital”, señaló Malhotra.
La razón probablemente sean las complicaciones que suscita la sangre recibida en el organismo del paciente, dice el doctor.
Para todo tipo de operaciones
Según Malhotra, se puede recurrir a la intervención quirúrgica sin transfusión de sangre para cualquier tratamiento, a corazón abierto, cirugía al cerebro o de otro tipo. No hay ningún tipo de intervención que no se pueda realizar.
“Por ejemplo, digamos que una mujer se tiene que someter a una histerectomía. Si se la prepara con anticipación aumentando su consumo de hierro, vitaminas y ácido fólico para elevar su recuento sanguíneo, entonces debería haber poca pérdida de sangre durante la intervención. Esto también puede funcionar en casos de emergencia”, afirma este especialista.
“Lo que hacen algunos doctores es internar a la paciente en el hospital, conseguir algo de sangre y proceder a intervenirla. Creo que si tuvieran en mente: ‘Voy a tratar de ahorrar sangre para emergencias verdaderas’, y si la paciente dijera: ‘No quiero que me apliquen cuatro unidades de sangre’, si todos trabajáramos juntos, si los pacientes estuvieran más informados, los beneficios serían para todos”.
Cambio de mentalidad
“Todo lo que se piensa sobre la sangre tiene que cambiar y este proceso requiere años, a menos que se dicten ciertas normas o algo así y es difícil conseguir la aplicación de normas en temas médicos. Debería ser una decisión voluntaria de los doctores”.
Desde hace muchos años se vienen haciendo predicciones de que Estados Unidos pronto padecerá una escasez de sangre disponible para transfusiones. Este pronóstico se basa en una reducción proyectada debido a un aumento en la edad de la población, reducción del número de donantes y de personas que no son donantes regulares, pero que pueden serlo en caso de emergencia, mientras la demanda aumenta debido al envejecimiento de la población y al creciente número de intervenciones quirúrgicas llamadas “mayores”.
“Va a llegar el día en que experimentaremos una escasez crítica. Necesitamos una política nacional de conservación de sangre, educar a la gente y a los médicos para que busquen técnicas alternativas”, señala Malhotra.
Más informados
Gracias a la facilidad actual de conseguir información a través de internet, por ejemplo, los pacientes pueden cuestionar a su médico: “¿Puede hacer algo diferente?”. La gente está más informada, pero debería hacer más preguntas.
“En otros países [no desarrollados] se tiene que aprender cómo tratar a los pacientes cuando no se puede conseguir sangre, mientras que aquí el médico la pide y se la dan en un minuto. Entonces, en este país nunca se ha aprendido a enfrentar la situación cuando se produce una escasez porque sólo se enseña que hay una sola manera: si se pierde sangre, se la reemplaza con sangre. En otros países no se tiene esta facilidad”, concluye Malhotra.

Ana Labrin-García

mailto:ana.labringarcia@laopinion.com