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Is directed blood transfusion a good idea?

The appearance of transfusion-transmitted HIV infection has heightened awareness of dangers that have always been present. Directed donation, while no panacea, may provide one alternative.

DURING THE LAST three decades the medical establishment and general public have grown increasingly aware of the risks of transfusion-transmitted diseases. While risks associated with transfusion therapy have always been present, the occurrence of transfusion-transmitted HIV infection greatly heightened this awareness. Some patients have refused regular blood transfusion, demanding "safer" blood. Thus began the search for alternatives to traditional blood bank practices.|1~ The best alternative, widely endorsed, is autologous transfusion.

In appropriate clinical situations, such as major orthopedic or cardiovascular surgery, autologous transfusion has been documented to reduce the patient's exposure to homologous blood significantly. At the same time another modality, directed blood transfusion (also referred to as designated or recipient-selected transfusion), has gained in popularity and practice. In this mode, the patient or the patient's family recruits donors from among family and friends. Since these individuals are often donating for the first time, one potentially positive effect is to increase the donor base.

The concept of donor-specific transfusion is not new. It has been used in the setting of solid organ transplantation, for single-donor platelet apheresis transfusion support, for persons belonging to very rare blood groups, and for patients requiring ongoing plasma transfusion therapy.|2~ In the setting of solid organ transplantation from a living related donor, pretransplant transfusions from the organ donor may significantly reduce the risk of subsequent graft rejection.|3~

* Chemotherapy. Patients undergoing intense chemotherapeutic regimens, possibly including bone marrow transplantation, for hematologic malignancies frequently require a period of intense and/or ongoing platelet transfusion support. Using single-donor apheresis platelets from family members or friends commonly provides a readily available source of platelets, helps reduce the total number of donor exposures and the incidence of febrile transfusion reactions,|4~ and may, in the case of family members--where there is at least partial human leukocyte antigen (HLA) compatibility--reduce or delay the incidence or onset of platelet alloimmunization. Patients with erythrocyte antibodies to high-frequency antigens often depend for their red blood cell transfusion needs on the generosity of a limited number of donors, often including family members, who lack the corresponding red blood cell antigen. Such blood is often frozen and stockpiled locally or in rare-donor repositories.

* Coagulation disorders. Finally, the number of donor exposures can be reduced substantially for patients, especially children, who require ongoing plasma transfusions for inherited coagulation disorders such as Christmas disease (factor IX deficiency). The key is to supply transfusions from a limited number of donors who regularly donate plasma specifically for the individual patient, optimally by automated plasmapheresis.

The popularity of directed red blood cell transfusions has grown not out of medical necessity but out of fear of traditional blood transfusion therapy. Today, directed red blood cell transfusion practice is one of the most emotional and controversial facets of transfusion medicine. What follows is an effort to balance the pros and cons of directed red blood cell transfusion practice so that decisions regarding its use can be based on rational choice rather than irrational fear.

* Making the right comparisons. In attempting to evaluate the safety and efficacy of directed blood transfusion practice, it is important to define and understand the parameters being evaluated. Key questions to consider include the following:

* Are all directed donors being compared as a group with the agglomerate of volunteer homologous donors?

* Are all directed donors who have a previous history of homologous donation being compared as a group with the agglomerate of volunteer homologous donors?

* Are all first-time directed donors being compared as a group with the agglomerate of first-time homologous donors?

* Infectious disease markers. In a recent comprehensive study by Starkey and coworkers,|5~ five infectious disease markers--hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), anti-HIV-1, alanine aminotransferase (ALT), and rapid plasma reagin (RPR)--were evaluated in 466,667 blood donors presenting to 20 Council of Community Blood Centers (CCBC) facilities from September 1987 to March 1988. The hypothesis was that the prevalence of markers for infectious disease in units from different donor groups--homologous volunteer, autologous, and homologous directed--could be used to compare the risks presented by these donations to the non-self-transfusion recipient. Most important, data are provided that allow various comparisons between the donor groups.

Thus, analysis of the data provided on directed donors allows comparisons between total directed and total volunteer homologous groups, between previous volunteer directed donors and repeat volunteer donor groups, and between first-time-directed and first-time-volunteer homologous groups. The data emphasize the value of a history of prior volunteer homologous blood donation as a predictor in the safety of the directed blood.

Grindon has reported his experience with infectious disease markers in directed donors in the Atlanta area.|6~ No significant difference in infectious disease markers was shown between directed donor and volunteer donor groups even though the frequency of first-time donors in the former was twice that of the latter. Grindon's total population of donors was about 25% that of Starkey and coworkers. Furthermore, there were clearly regional differences. Grindon concluded that decisions affecting the utilization of directed donor blood should be based on locally acquired data.

* Pressure to donate. There are ample reasons to be cautious in evaluating the medical efficacy of red blood cells from directed donors. At a 1986 meeting of the American Association of Blood Banks (AABB), Newman reported these results of a confidential questionnaire administered to 133 consecutive directed blood donors|7~:

* Three percent of donors indicated that they had been strongly urged ("pressured") to donate blood.

* Twenty-two percent stated their belief that some or many donors would modify their answers to donor questions in order to be allowed to donate.

Data of this type led Parsons and Miller to suggest emphatically at the same AABB meeting that directed red blood cells be classified as nonvoluntary, since "whether due to anxiety or coercion, it is clear that self-deferral and medical history as means of protecting the blood supply have been seriously compromised . . . ."|8~

* Impeding autologous transfusion. A further concern with directed red blood cell transfusion programs is their potential interference with autologous blood transfusion practice. Indeed, in an abstract presented at the AABB meeting in 1988 by Chambers and coworkers, "Directed Donor Program May Adversely Affect Autologous Donor Participation," 100 active autologous donors were surveyed.|9~ Of 95 respondents, 75 understood that autologous blood is safer than directed blood; 21 felt that autologous and directed blood were equally safe; and 19 of 100 active autologous donors indicated that they would have preferred directed donation if it had been made available.

* GVHD risk. Another topical issue regarding the safety of directed donor blood relates to the risk of graft-versus-host disease when patients who receive blood share an HLA haplotype with an HLA-homozygous blood donor.|10,11~ In the United States, this situation is most likely to arise when a relative, especially a first-degree relative, serves as the directed blood donor. In this setting, where the donor blood is not recognized by the recipient as foreign, the recipient need not be immunocompromised to be at risk for this complication. Since transfusion-associated GVHD is almost uniformly fatal, and rapidly so, the AABB states (emphasis added): "Blood and cellular components should be irradiated with a minimum of 1500 cGy |proposed revision for 15th edition of AABB Standards manual: 2500 cGy~ in order to reduce the risk of graft-versus-host disease in fetuses receiving intrauterine transfusions, and in selected immunoincompetent or immunocompromised recipients, and when the donor is known to be a first-degree relative |proposed revision: any relative~ of the recipient. The blood bank or transfusion service should participate in the development of the protocols for this procedure . . . ."|12~

* Suitable donors. Yet another concern about directed blood programs relates to the probability of finding a sufficient number of suitable donors. Kanter and coworkers provide ample data showing that unrelated donors who do not know their blood types are an inefficient source of directed donations.|13~ For example, if an O-positive white patient needs three units of blood for surgery, and type-compatible blood is used, 12 unrelated donors are needed in order to be 95% confident of obtaining three type-compatible units. This calculation is based on the 45% probability of random white donors' being type-compatible (O+ or O-). Different results will be obtained with blacks, Hispanics, Asians, and other racial groups since the distribution of blood groups varies by race. For Asians, 16 donors would be required; for blacks, 11 donors; for Hispanics, 8 donors. Kanter provides helpful tables to assist with similar calculations at various confidence levels with any antigen of known distribution.

* Cost. The inefficiency just discussed contributes to the increased costs associated with the procurement of directed donor blood. In a recent multicenter study by Forbes et al, the acquisition costs for autologous blood and directed blood were found, on average, to be 50% greater than those for standard volunteer homologous blood.|14~

It is apparent that greater efficiency in obtaining suitable donors is provided when first-degree relatives are the source of the directed donor blood. More distant relatives are less likely to be helpful. In another study by Kanter and Hodge, for example, directed donations from a recipient's husband and other relatives were evaluated for their potential risk in the occurrence of subsequent hemolytic disease of the newborn (HDN).|15~ In essence, this study provides data showing that with respect to HDN, the father and paternal relatives are riskier donors, while the maternal relatives are safer donors. Thus, the risk for HDN in a subsequent pregnancy of an Rh-negative white or black female transfused with a single unit of the baby's father's blood is approximately fourfold greater than the risk for HDN in the general population.

* Minimal exposure. One approach to directed transfusion practice, popularized by Brecher and coworkers at the Mayo Clinic, is known as minimal-exposure transfusion. This is defined as "the acquisition of all the projected blood needs of a specific patient from one donor, including erythrocytes, plasma, cryoprecipitate, fibrin glue, and platelets."|16~ In accordance with the hypothesis that using a single donor would minimize the risks of transfusion-transmitted disease and alloimmunization, the AABB Standards for Blood Banks and Transfusion Services allows a single donor to donate for a specific patient. To be allowed to donate at a frequency equivalent to that of autologous donors, the donor must meet all volunteer homologous blood standards, including the one for hemoglobin.

In summary, the recent rapid growth of interest in directed red blood cell transfusion practice has been generated not, as in the past, by medical necessity--such as for transplantation, plateletpheresis, rare blood groups, and plasmapheresis--but largely from fear of traditional blood transfusion therapy. This change has largely been propelled by concern about potential litigation from patients who experience transfusion complications after being denied the opportunity to use directed-donor blood. At least three states, California, Illinois, and New Jersey, now require that patients be offered not only autologous transfusion but also directed transfusion.

Depending on the approach used in setting up a program, directed-donor blood may be as safe as volunteer homologous blood (from directed donors who have previously served as volunteer donors) or less safe than volunteer homologous blood (from first-time directed donors). Although the utilization of minimal-exposure transfusion programs should theoretically lead to improved safety in blood transfusion, data indicating this outcome are not yet available.

In our institution, we give interested patients and their families information detailing potential risks of directed red blood cell transfusion therapy. We also require a clinician's order before providing the service. An informed consent mechanism such as this may prevent paradoxical litigation if the directed blood transfusion should unfortunately lead to a bad outcome.


1. Garner RJ, Silvergleid AJ, eds. Autologous and Directed Blood Programs. Bethesda, Md: American Association of Blood Banks; 1987.

2. AuBuchon JB. Autologous transfusion and directed donations: Current controversies and future directions. Transfusion Med Rev. 1989; 3: 290-306.

3. Ratner LE, Hadley GA, Hanto DW, Mohanakumar T. Immunology of renal allograft rejection. Arch Pathol Lab Med. 1991; 115: 283-287.

4. Chambers LA, Kruskall MS, Pacini DG, Donovan LM. Febrile reactions following platelet transfusion: Effect of single versus multiple donors. Transfusion. 1990; 30: 219-221.

5. Starkey JM, MacPherson JL, Bolgiano DC, et al. Markers for transfusion-transmitted disease in different groups of blood donors. JAMA. 1989; 262: 3452-3454.

6. Grindon AJ. Infectious disease markers in directed donors in the Atlanta region. Transfusion. 1991; 31: 872-873. Letter.

7. Newman B. Directed donations: A look at various issues. Transfusion. 1987; 27: 574. Abstract.

8. Parsons DR, Miller DT. A proposal to classify directed donors as non-voluntary. Transfusion. 1987; 27: 575. Abstract.

9. Chambers LA, Kruskall MS, Leonard SS, Ellis AM. Directed donor programs may adversely affect autologous donor participation. Transfusion. 1988; 28: 64S. Abstract.

10. Anderson KC, Weinstein HJ. Transfusion-associated graft-versus-host disease. N Engl J Med. 1990; 323: 315-321.

11. Anderson KC, Goodnough LT, Sayers M, et al. Variation in blood component irradiation practice: Implications for prevention of transfusion-associated graft-versus-host disease. Blood. 1991; 77: 2096-2102.

12. American Association of Blood Banks. Standards for Blood Banks and Transfusion Services, |Sec~J3.500. 14th ed. Bethesda, Md: AABB, 1991; 39-40.

13. Kanter M, Selvin S, Myhre BA. The probability of finding suitable directed donors. Arch Pathol Lab Med. 1989; 113: 174-176.

14. Forbes J, Anderson M, Anderson G, et al. Blood transfusion costs: A multicenter study. Transfusion. 1991; 31: 318-323.

15. Kanter MH, Hodge SE. Risk of hemolytic disease of the newborn as a result of directed donations from relatives. Transfusion. 1989; 29: 620-625.

16. Brecher ME, Moore SB, Taswell HF. Minimal-exposure transfusion: A new approach to homologous blood transfusion. Mayo Clin Proc. 1988; 63: 903-905.

Roslyn Yomtovian is director, blood bank-transfusion medicine service, department of pathology, University Hospitals of Cleveland.

Pros and cons of directed blood transfusion practice


Increased blood supply

Positive psychological effects

Possible decreased litigation

Decreased risk of fetal-maternal alloimmunization (with maternal donors)

Possible decreased risk of disease transmission (minimal-exposure porgram)


Possible increased risk of disease transmission

Increased risk of graft-versus-host disease

Increased risk of fetal-maternal alloimmunization (with paternal donors)

Increased cost

Possible increased litigation

Recent lawsuit highlights risk of directed donation

Should wavering hospitals capitulate when patients demand directed donations? Not necessarily. A recently settled court case provides a cautionary tale for the 1990s.

On Aug. 29, 1992, after three weeks of testimony in New York State Supreme Court, Brooklyn, a man who had developed AIDS after receiving blood transfusions for emergency surgery in 1986 was granted approximately $200,000 from the hospital and $100,000 from the surgeon. The patient--Gregory Scarpa, reputedly a top-ranking member of the Columbo crime family--had refused blood from the hospital blood bank, insisting on donations from friends, relatives, and associates. One of those associates, a weight lifter now said to have injected steroids, later died of AIDS.

Defense lawyers say Scarpa was told that in an emergency, directed donations cannot always be screened. Scarpa counters that a nurse told him it was safer to use the blood of friends and relations than that of strangers. Furthermore, he now says he should not have had a choice.

"I wasn't given ample warning," The New York Times quotes him as stating at a news conference after the settlement was announced.|1~ "It was never something that should have been left to the prerogative of the patient."


1. Tabor MBW. Settlement in suit on H.I.V.-tainted transfusion. The New York Times. August 30, 1992, section L, p. 35.
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Title Annotation:includes related article
Author:Yomtovian, Roslyn
Publication:Medical Laboratory Observer
Date:Nov 1, 1992
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