The New York Times - November 18, 1984
Lawrence K. Altman M.D.

A HEMOPHILiac, Tom Kincer could not keep a job. Any move he made might touch off an alarming surge of bleeding, then debilitating stiffness and pain.

In the late 1960's, an important medical advance in the understanding and use of donated blood helped hemophiliacs to begin to lead normal lives. A new laboratory technique enabled researchers to extract from blood a component known as Factor VIII, the lack of which causes hemophilia. Hemophiliacs could simply inject themselves with Factor VIII periodically, when they felt they were bleeding or about to bleed, and their highly dangerous condition would be stabilized, as it was for Tom Kincer. By injecting himself at home, in Kentucky, he was able to fish, boat, travel.

In 1980, however, Tom Kincer began experiencing extreme fatigue. He often perspired heavily for no apparent reason. His wife found that his personality had changed, his moods swinging to extremes. In the summer of 1981, the lymph glands in his neck began to swell; he rapidly lost about 15 pounds. In 1983, he developed an ear infection that his doctors found was due to an unusual fungus called aspergillus.

Soon Tom learned that he had AIDS, acquired immune deficiency syndrome, an incurable disease that fatally attacks the body's immune system, destroying its ability to ward off disease. Six months after the diagnosis, at the age of 49, he was dead. Some of the Factor VIII he had injected was contaminated with the virus that causes AIDS.

What happened to Tom Kincer and now about one in 200 severe hemophiliacs, all of whom are dependent on Factor VIII therapy, illustrates in part what has become one of the great paradoxes in the annals of modern medicine. The use of donated blood in treatment and research has become central to the practice of medicine. (Current blood-research projects, page 154.) It is crucial for, among others, children in anemia clinics, cancer patients and victims of burns and other accidents. Through donated blood, red cells are quickly harnessed to carry needed oxygen, white cells are thrown into battle against infections; proteins with preformed antibodies help susceptible individuals against certain diseases, and platelets gather to form clots to stop bleeding.

But at the same time, the use of donated blood has become dangerous for some people in a limited and disturbing new set of circumstances. There is confusion and fear about who is at risk and the extent of the threat. In addition, AIDS has further complicated the already complicated field of blood research.

Though there was at first strong reluctance on the part of many blood-bank officials across the nation to accept the conclusion, they now generally agree with epidemiologists that AIDS can be directly transmitted through donated blood. That is the conclusion drawn from current medical case studies at the Pasteur Institute in Paris, where the virus believed to cause AIDS was first isolated in 1983, and at the National Cancer Institute in Bethesda, Md., where scientists have successfully grown in test tubes large amounts of the retrovirus involved.

In a widely publicized news conference last April, Health and Human Services Secretary Margaret Heckler predicted that a blood test for AIDS would be available within six months. The six months have passed and the blood test still is being developed. As Dr. Aaron Kellner, president of the New York Blood Center, said right after the prediction had been made: "Margaret Heckler's rosy estimate of four to six months is going to be doubled and a little more. Realistically, it will take about a year before the test is validated . . . before one can tool up to make enough tests so that we can do 12 million every year" - the number of units of blood collected from Americans for 3.5 million recipients each year by the 3 main blood-collecting agencies in the United States - the American Red Cross, the American Association of Blood Banks and the Council of Community Blood Centers.

In short, doctors are now working to develop a test that would both tell a person whether he has AIDS and that would help blood bankers prevent AIDS victims from donating blood and thus contaminating the general supply. If not accurate, such a test has the potential for disaster. Over the next few months, a chief objective of AIDS and blood-bank researchers will be to determine the AIDS test's accuracy - how often it might misidentify specimens.

Each time a new test is developed, scientists have to determine how accurately it detects what it is supposed to detect. In the case of what scientists call a "false positive," test results indicate evidence of infection when, in fact, the specimen is from someone who is infection-free or who has been infected with an agent biologically similar to the one being studied. Conversely, a "false negative" occurs when a test fails to detect the presence of an agent. Obviously, each type of error can be extremely harmful, both for the person falsely labeled as having a disease such as AIDS and for the person who receives infected blood.

The overall risk to the total population of blood recipients is extremely small; but risk is there, nevertheless. A donor today may be unaware that he has AIDS or is an asymptomatic carrier. Moreover, the threat persists for several years after the transfusion.

What of the victims of diseases now treated with various blood components, or accident victims needing a transfusion? Indeed, how dependent has the practice of medicine become on donated blood? Could patients now do without it? Should they resort to an autologous transfusion, employing their own blood stored for use later if needed? How great are the risks? Are current precautions adequate?

Only a few months ago, virtually all the answers to these questions would have been pessimistic. Now, however, in addition to the AIDS test that researchers are checking out, medical laboratories have produced other reasons for optimism: Scientists last month reported the discovery of a virus that they believe causes non-A non-B hepatitis, which is the most common form of hepatitis that has been traced to blood transfusions. They seek now to develop a blood test that will identify blood contaminated with that virus. Through genetic engineering, contaminant-free Factor VIII has recently been produced artificially by researchers at Genentech, a California biotechnology company. The largest, most complex protein ever cloned in the laboratory, it will not be marketed for at least five years, after additional animal experiments and human trials. Even then, there is no guarantee that it will prove lastingly effective in humans or that its cost will prove competitive with Factor VIII derived from human blood. Some scientists now predict that a vaccine against AIDS itself will be available within the decade.

Right now, the number of transfusions given in American hospitals has never been higher. Experts say that there is a greater risk for those who need blood but refuse transfusions for fear of AIDS than there is for those who accept the transfusions. But the realization that AIDS can be transmitted through transfusions has made some patients reluctant to agree to the procedure. Blood-bank officials tell unconfirmed stories of people who nearly bled to death because they refused to accept the blood of strangers.

Moreover, documented transfusion-associated AIDS cases have even discouraged some potential donors from giving blood because they were mistakenly frightened that the needles used might be contaminated. Donations at the New York Blood Center, for example, dropped temporarily by 6 percent last year, and this was so despite the fact that a blood donor runs no risk of contracting AIDS. The needles are used just once, then are disposed of. Nevertheless, the drop in donations led to serious blood shortages - almost a panic - in New York and elsewhere in the country in mid-1983.

MOST PEOPLE DO not think of blood transfusions as transplants. They are. Indeed, they are the most successful. Normal red cells have a lifespan of 120 days. Platelets, the tiny fragments that help blood clot, live 9 to 11 days. Red cells and platelets from donated blood simply join those of the recipients and continue for their normal lifespans with amazing vigor.

Mismatches of blood types do occur, but only at a rate of about one in 10,000 transfusions, experts say, and these are often because of errors by technicians at blood banks or hospitals. As a result, preventive steps have been taken. Some regional blood banks have adopted the bar-coding technique that supermarkets use to label food products to mark each bag of blood as soon as it is collected at a mobile unit or blood center; then, automated blood typing and processing techniques ready it for shipment to a hospital.

The success of transfusions in general was made possible by the substitution of plastic bags for glass bottles. Several sterile plastic bags can be attached by tubing so that blood can be collected in one bag and spun in a centrifuge to separate the platelets from red cells and other blood components. Aside from being less fragile than bottles, plastic bags also cost less and pose less risk of infection.

A key problem throughout the history of blood transfusions has been infection. Hepatitis B was the plague of the 1960's; the virus causing the disease contaminated many times more units of the donated-blood supply than are now believed tainted with the AIDS virus. However, the incidence of Hepatitis B dropped drastically after a test was developed to screen it out. Now, aside from AIDS, the chief causes of infection are non-A non-B hepatitis and cytomegalic virus infections, both of which can follow a transfusion by weeks or even months. The non-A non-B hepatitis threat will continue until the new test to detect that disease's presence is available.

In March 1983, blood-bank officials, feeling pressure from the United States Public Health Service, strengthened measures to screen out potentially infectious donors. Blood officials asked members of the homosexual community and other high-risk groups not to donate blood. Blood centers asked prospective donors even more questions about symptoms of AIDS, such as coughing, night sweats, swollen lymph glands and diarrhea. The New York Blood Center distributed pictures of Kaposi's sarcoma to nurses who screen prospective donors to make them familiar with the skin nodules that characterize this cancer. Kaposi's sarcoma is rare and has tended to be limited to men 60 and older. Now it is occurring with unusual frequency among AIDS patients, most of whom are under 40.

Some high-risk donors - members of groups most susceptible to AIDS, such as homosexuals, Haitians living in the United States and intravenous drug abusers - want to donate blood. Others respond to social pressure from, say, fellow workers, and give blood because they do not want to appear conspicuous by declining. For both of these groups, the New York Blood Center and others have created a new option - designating their blood for research purposes in the laboratory instead of for transfusion. To do so, donors check off a box in the unsigned form that they fill out privately, with no one else around; the blood is then excluded from use in transfusions. Only designated blood-center employees can read the information and the data is not entered in the blood center's central computer. Only the blood of people whose donation has been approved for transfusions is sent to hospitals for that purpose.

At latest tally, about 2 percent of all donors either designate their blood for research studies or do not fill out the form, in which case the blood is not used for transfusion.

Concern over AIDS has also led more surgeons to use devices to siphon off blood during operations. Instead of discarding it as usual, the blood is saved and, if necessary, returned to the patient rather than transfusing someone else's blood.

Blood-bank officials believe that the new measures have reduced and perhaps eliminated donations contaminated by the AIDS agent. Based on 1983 data, the risk of AIDS to a person receiving a transfusion of blood or blood products is estimated as one in 100,000. This is the estimate of Dr. James W. Curran, the chief of the AIDS branch at the Centers for Disease Control in Atlanta, and Dr. Lewellys F. Barker of the American Red Cross, published this year in the Annals of Internal Medicine. (Though a crude figure, it contrasts with the one-in- a-million figure that some vested-interest blood bankers were citing only a few months earlier.) The threat seems greatest to those who receive more than 5 to 10 units of blood, although cases of AIDS have been reported among individuals who received only 2 units.

As of Oct. 1, 1984, of the 6,251 reported AIDS cases, 130 were believed to have been acquired through transfusions of blood or blood products such as Factor VIII, according to the Federal epidemiologists at the Centers for Disease Control. Of the 130 transfused, 45 were hemophiliacs and the remainder nonhemophiliac recipients. Because the incubation period of AIDS can be up to five years, many doctors believe the toll in each category will increase before the situation improves. The 45 hemophiliac-AIDS cases occurred in 24 states.

Why so few of the estimated 20,000 hemophiliacs in the United States using Factor VIII therapy have developed the syndrome is not known. Some epidemiologists suspect that hemophiliacs contract AIDS because of contamination of an entire lot of Factor VIII that may have been used by more than 100 individuals, but no lot of Factor VIII has yet been proved to have infected more than one victim. Another possibility is that some hemophiliacs have developed asymptomatic AIDS infections, or an early, unmanifested form of the disease. AIDS is not like measles, in which virtually every susceptible person who comes in contact with the measles virus gets the disease. In fact, as with polio, only a tiny percentage of those who get infected with AIDS go on to develop the severe form of the disease.

The situation breeds confusion. For example, some patients living in large cities have gone elsewhere for transfusions in the mistaken belief that blood received there would be safer than blood donated near home. But much of the blood collected in one area of the United States is transfused elsewhere. In several transfusion-associated AIDS cases, the donated blood came from more than one city. In one case in the Middle West, for example, the 22 units of blood a patient received came from 6 states. THE NEWS OF A LINK between Factor VIII and AIDS led some hemophiliacs to stop taking the component, despite the urging of National Hemophilia Foundation officials that the risk of not taking the therapy outweighed the risk of getting AIDS. Avoiding Factor VIII injections could lead to uncontrolled bleeding as well as pain and swelling of the joints.

Hemophilia is passed on in a sex-linked hereditary pattern: males are the victims; females are the carriers, being affected only rarely. Although hemophilia can be traced through families for generations, sometimes it arises for the first time due to a spontaneous mutant gene. Any family could be affected.

The introduction of Factor VIII therapy in the 1960's reduced deaths among hemophiliacs sharply. Still, accidents frequently occur before the injections are begun. Then the disease's prolonged bleeding can affect the brain or other vital organs. Moreover, the therapy has remained full of risks, chiefly infection, the nemesis of all transfusions.

Factor VIII is generally prepared from large pools of plasma obtained from 2,000 to 22,000 people, most of them paid donors. Studies show that the risk of hepatitis and other infection is increased in blood products obtained from paid donors. Because Factor VIII extraction techniques are so imperfect, the currently marketed product is impure, full of extraneous proteins, containing only trace amounts of the vital component.

The great advantage of today's voluntary donation system is that - because people have been willing to give blood freely for all patients rather than for a particular individual - it is possible for anyone in any community using the system to get blood at any given time. Thus, the community blood-bank system we know today differs drastically from the individually centered one of a generation or so ago, when the custom was to call on friends to come suddenly to the hospital to donate when the need arose.

Because that could not always be done, blood banks turned to paid donors. By 1962, about 65 percent of the blood transfused in New York came from doctors and paid donors, often a euphemism for derelicts. Hepatitis B was the frequent complication.

As a result, the New York Blood Center was formed along the lines of recommendations made by a committee of the New York Academy of Medicine in 1958. In the words of Dr. Kellner, "We had to take the collection of blood out of the hands of social workers and businessmen and bring it back into the realm of medicine and science." In general, the New York Blood Center now sets worldwide standards in transfusion practice and blood research.

Today, 98 percent of the blood used for transfusions in the Greater New York Area comes from volunteer donors. But there are not enough of them. The New York Blood Center imports as much as one-third of its 750,000 units of blood annually from West Germany, Switzerland and Belgium. Although New York Blood Center officials praise this program for its international cooperation, others criticize it severely and contend that New York and other American communities have not done enough to meet their own local blood needs. An international system, they contend, will ultimately fail unless each region carries its share of the burden. New York officials concede that they must do more to persuade donors that there is no risk in donating.

The threat of transfusion- associated AIDS has been accompanied by pressure from patients, doctors and hospitals to abandon the system of voluntary donation of blood and to develop a directed donation system - a variation on the old method. Under this form of directed donation, a patient arranges in advance to provide himself with an adequate blood supply by calling on friends or relatives to donate blood specifically for his use.

Somebody who is scheduled to have hip surgery stands a good chance of receiving two or three units of blood during or just after the operation. In coronary by-pass surgery, it has not been unusual for a patient to receive 10 units of blood. Under directed donations, such patients would ask friends to donate at least that amount of blood in advance.

However, Dr. Johanna Pindyck of the New York Blood Center points out that because many patients require three or more transfusions, the likelihood of individuals' finding enough suitable donors on their own decreases according to the blood type. Statistically, for the individual with O-negative blood, 50 healthy donors would have to be screened to find 3 donors with O-negative blood.

Even more serious, blood- bank officials are gravely concerned that a movement toward directed donations could disrupt and diminish the entire national blood- donor system. The bookkeeping required to keep track of designated blood for, say, 4 coronary by-pass operations a day, with 10 donors for each, might increase the number of mistakes as well as the risk of transfusion- reactions due to someone's getting the wrong blood.

Blood-bank directors say they simply could not process large numbers of designated blood units, which would delay surgery until sufficient supplies of blood were at hand. Availability of blood is not now a major factor in choosing the time of surgery.

In addition, blood-bank officials express concern that if a directed-donor system springs up, it could create a two-tier blood-supply system: the safe blood and the less-safe blood. And the most serious possibility is that a directed-donor system might decrease the overall donor supply, with people waiting until a relative or friend needed blood instead of giving on a regular basis.

Even after a reliable test has been developed for AIDS, some individuals may still decline to donate blood for fear of unexpectedly learning that they have an untreatable fatal illness and thus may possibly be stigmatized by the diagnosis of AIDS.

Researchers are still trying to answer questions relating to a reliable diagnostic test for AIDS. What is the meaning of a positive AIDS blood test? Does it mean immunity caused by a past infection? If so, is such an individual a carrier? Does a positive result mean a currently active infection?

For their part, blood banks and public health officials are concerned about the results of preliminary studies, which indicate that 1 percent of nonhigh-risk groups have evidence of the AIDS virus. One percent may seem small, but 1 percent of 12 million donors means that 120,000 people could receive the AIDS virus.

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ADVANCES IN BLOOD RESEARCH

Current research may eventually change blood banking completely: Use of an enzyme found in coffee beans to convert type B blood into type O. If another enzyme can be found to convert type A to type O blood, and if large-scale testing on humans shows it to be safe and efficacious, blood banks may be able to simplify their collection procedures and transfuse anyone else's blood without matching it specifically. Substances produced by white blood cells called interleukin-2 and interferons are being investigated for use in the treatment of cancer, AIDS and other diseases. Repeated injections of one type of interferon have led to sustained benefits in children who are affected by a condition of the vocal cords called laryngeal papillomatosis. Fibronectin, a plasma protein, is under investigation for help in preventing organ injury in severe trauma, burns and infections. Development of improved immunological tests might even give blood banks a new function - as tissue banks, to store corneas, hearts, lungs, livers, kidneys and other organs. A preservative called Adsol has been designed to keep red cells viable for up to seven weeks, almost two weeks longer than has been the case in the past. If further testing proves its value, Adsol could cut down on wastage due to outdated blood, and a healthy person could safely give up to six units of blood for his own use over a period of weeks in advance of elective surgery. To many it may sound like science fiction, but if genetically engineered pure Factor VIII can be made in vast amounts at low cost, then, some experts speculate, hemophiliacs might be able to swallow the clotting substance instead of injecting it. (Factor VIII must now be injected, because it is destroyed by stomach acid.) Even if the stomach destroys all but 1 percent of the swallowed genetically engineered Factor VIII, that tiny fraction may be just enough to treat the disorder.

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