Diseases & Conditions


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Transplantation


Transplantation is the removal of living, functioning cells, tissues, or organs from the body and then their transfer back into the same body or into a different body.

The most common type of transplantation is a blood transfusion (see Blood Transfusion: Introduction ). Blood transfusions are used to treat millions of people each year. More typically, transplantation refers to the transfer of organs (solid organ transplants) or tissues.

Organ transplantation, unlike blood transfusion, involves major surgery, the use of drugs to suppress the immune system (immunosuppressants), and the possibility of transplant rejection and serious complications, including death. However, for people whose vital organs have failed, organ transplantation may offer the only chance of survival.

Donors

A tissue or organ donor can be a living person or a person who has recently died (deceased donor).

Tissues and organs from living donors are preferable because they are usually healthier. Stem cells (from bone marrow or blood) and kidneys are the tissues most often donated by living donors. Usually, a kidney can be safely donated because the body has two kidneys and can function well with only one. Living donors can also donate a part of the liver or a lung. Organs from living donors are usually transplanted within minutes of being removed. In the United States, being paid to donate an organ is illegal, but reimbursement for cells and tissues is allowed.

Some organs, such as the heart, obviously cannot be taken from living donors. Organs from deceased donors usually come from people who previously agreed to donate organs. In many states, people can indicate their willingness to donate organs on their driver's license, although family members are also consulted even when donor status is indicated on the license. Permission for donation also may be obtained from the deceased's closest family member when the deceased's wishes are unknown. Deceased donors can be otherwise healthy people who have been in a major accident, as well as those who died of a medical disorder. Doctors do not take the potential for organ donation into account when deciding whether to recommend withdrawal of life support from people who are terminally ill or who are brain dead (see Stupor and Coma: Variations in Impaired Consciousness ).

One donor can provide several people with transplants. For example, one donor could provide two corneas, a pancreas, two kidneys, two liver segments, two lungs, and a heart. When people die, organs deteriorate quickly. Some organs last only a few hours outside the body. Other organs, if kept cold, can last a few days.

In the United States, a national organization (United Network for Organ Sharing) matches donors and recipients for transplantation through the use of a computer database. The database includes all people who are on a waiting list for a transplant, along with their tissue type. When organs become available, that information is entered and a match is made, allowing transplantation to occur with minimal delay.

Did You Know...

Some people with medical disorders can still become organ donors. Doctors evaluate the condition of the organs after a person dies and then decide whether they can be used.

Pretransplantation Screening

Because transplantation is somewhat risky and donor organs are scarce, potential recipients are screened for factors that may affect the likelihood of success.

Tissue Matching: The immune system normally attacks foreign tissue (see Biology of the Immune System: Cells ), including transplants. This reaction is called rejection. Rejection is triggered when the immune system recognizes certain molecules on the surface of a cell as foreign. These cell-surface molecules are called antigens.

For blood transfusions, rejection is relatively easily avoided because red blood cells have only three main antigens on their surface. These antigens determine the blood type and are called A, B, and Rh. Doctors test to make sure that antigens in the donor blood and the recipient blood are a complete match.

For organ transplantation, however, many antigens are involved. These antigens are called human leukocyte antigens (HLA) and occur on the surface of every cell in the body. Each person has unique HLA, which determines the tissue type. Ideally, the donor's tissue type exactly matches the recipient's tissue type. However, a perfect HLA match is extremely rare, and some people are too ill to wait for a highly compatible donor. In these cases, doctors sometimes use donor tissue that is not an exact match but that is a close match. A close HLA match between the donor and recipient reduces the frequency and severity of rejection and improves the long-term outcome. With the use of immunosuppressants, the success of transplantation is less affected by the degree of matching.

Before transplantation, the recipient's blood is screened for antibodies against the tissues of the donor. The body may have produced such antibodies in response to a blood transfusion, a previous transplant, or a pregnancy. If these antibodies are present, transplantation is not possible because immediate, severe rejection will occur. Although some procedures and drugs are available to remove the antibodies, there is less experience with these techniques and they are not widely used.

Medical Screening: Some disorders, in particular cancers and infections, can be transmitted during transplantation. Doctors screen donors for cancer by thoroughly reviewing their medical history and carefully inspecting the organ in the operating room at the time of organ recovery. Organs containing cancers are obviously not used for transplant. The decision to use organs from donors who previously had cancer in another organ is made based on the likelihood that tumor cells persist or may have spread to the organ being transplanted.

Most bacterial infections are evident to doctors based on the donor's overall health and have often been diagnosed and treated even before the decision to donate. If treatment has been adequate, organ transplantation is safe, although the recipient may receive additional antibiotic treatment. To prevent transmission of viral infections, which are often not so obvious, doctors usually test the donor's blood. Viral infections for which blood tests are done include cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B and C viruses, human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV). Some viral infections in the donor, such as HIV and HTLV, mean that transplantation cannot be done. Other viral infections, such as CMV and EBV, do not prevent transplantation, but the recipient must take antiviral drugs afterwards.

Because organ transplant recipients are given immunosuppressants in high doses at the time of transplant, recipients who have active infections or cancers cannot undergo transplant until these conditions are controlled or cured. Many immunosuppressants are also unsafe for fetuses, so pregnant women cannot undergo transplant. However, some women who have received a transplant may be able to get pregnant and have healthy babies once the function of their transplanted organ is stable and their immunosuppressants can be specially adjusted.

People with poor overall health, other medical problems in addition to single organ failure, and certain viral infections are less likely to do well with a transplant. The decision to transplant is individualized to the person's specific circumstances.

Psychosocial Screening: The lifelong regimen of drugs, treatments, and follow-up visits required to keep a transplanted organ functioning is quite demanding, and not all people are willing or able to comply. In addition to nurses and doctors, psychiatrists and social workers are involved to help people and their families understand the long-term commitment and difficulties involved in accepting a transplant. Everybody's input is important in determining whether organ transplantation is right for a person.

Suppression of the Immune System

Even if tissue types are closely matched, transplanted organs, unlike transfused blood, are usually rejected unless measures are taken to prevent rejection. Rejection results in destruction of the transplanted organ and can cause fever, chills, nausea, fatigue, and sudden changes in blood pressure. Rejection, if it occurs, usually begins soon after transplantation but can occur after weeks, months, or even years. Rejection can be mild and easily controlled or severe, worsening despite treatment.

Rejection can usually be controlled with drugs that suppress the immune system and the body's ability to recognize and destroy foreign substances. With the use of these immunosuppressants, the transplanted organ is more likely to survive. Immunosuppressants must be taken indefinitely. High doses are usually necessary only during the first few weeks after transplantation or during an episode of rejection. After that, smaller doses can usually prevent rejection (maintenance immunosuppression). A further reduction of immunosuppression may be required if recipients suffer from serious infections or side effects, but reducing the dose of the immunosuppressant increases the risk of rejection. At the first sign of rejection, doctors increase the dose of the immunosuppressant, change the type of immunosuppressant, or add an additional immunosuppressant.

Complications: Although immunosuppressants suppress the immune system's reaction to the transplanted organ, they also reduce the ability of the immune system to fight infections and to destroy cancer cells. Thus, transplant recipients are at increased risk of developing infections and certain cancers.

Recipients may get the same infections that any person recovering from surgery would. Such infections include those of the surgical site or the transplanted organ, pneumonia, or urinary infections. People also are at risk for unusual (opportunistic) infections that affect mainly people with weakened immune systems. Such infections may be caused by bacteria (for example, Listeria or Nocardia ), viruses (for example, CMV or EBV), fungi (for example, Pneumocystis or Aspergillus ), or parasites (for example, Toxoplasma ).

Cancers due to immunosuppression include certain skin cancers, lymphoma, cervical cancer, and Kaposi's sarcoma.

Drugs Used to Prevent Transplant Rejection

Drug Possible Side Effects Comments

Corticosteroids (potent anti-inflammatory drugs that suppress the immune system as a whole)

Dexamethasone

Prednisolone

Prednisone

Excess hair on the face

Facial puffiness

Fragile skin

High blood sugar levels (as occur in diabetes mellitus)

Muscle weakness

Osteoporosis

Stomach ulcers

Water retention

Given by vein in high doses at the time of transplantation

Gradual reduction of the dose to a maintenance dose given by mouth, usually indefinitely

Polyclonal immunoglobulins (antibodies directed toward specialized cells of the immune system)

Antilymphocyte globulin

Antithymocyte globulin

Severe allergic (anaphylactic) reactions with fever and chills, usually occurring only after the first or second dose

Reaction to the foreign proteins in the drug with fever, rash, and joint pain (serum sickness)

Given by vein

Used at the time of transplantation or for rejection episodes

Monoclonal antibodies (antibodies that target lymphocytes)

Basiliximab

Daclizumab

Infliximab

Muromonab (OTK3)

Drug tolerance (the drug becomes less effective for subsequent rejection episodes)

Fever

Irritation of the digestive tract

Joint pain

Muscle pain

Seizures

Severe allergic (anaphylactic) reactions

Shaking (rigors)

Given by vein

Used at the time of transplantation or for rejection episodes

Severe side effects usually only after the first few doses

Calcineurin inhibitors (drugs that prevent activation and expansion of the immune system)

Tacrolimus

Diarrhea

Headache

Heart enlargement

High blood pressure

Increased risk of lymphoma

Insomnia

Kidney damage

Liver damage

Nausea

Tremor

Given by mouth

Used as maintenance immunosuppression in people who have received a solid organ transplant

Cyclosporine

Excessive hairiness (hirsutism)

Gum enlargement

High blood pressure

Increased risk of cancer

Kidney damage

Liver damage

Tremor

Given by mouth

Used as maintenance immunosuppression in people who have received a solid organ transplant

Rapamycins (drugs that prevent proliferation of lymphocytes)

Everolimus

Sirolimus

Anemia

Diarrhea

High blood pressure

Increased cholesterol levels

Increased risk of lymphoma

Joint pain

Low potassium levels

Rash

Given by mouth

Used with corticosteroids or calcineurin inhibitors in people who have received a kidney or liver transplant

Everolimus usually given to people who have received a heart transplant

Mitotic inhibitors (drugs that suppress cell division and thus the production of white blood cells)

Azathioprine

Hepatitis (rare)

Increased risk of infection

Low white blood cell count

Nausea

Tendency to bleed

Tiredness

Vomiting

Given by mouth

Used as maintenance immunosuppression in people who have received a solid organ transplant

Mycophenolate mofetil

Blood infection (sepsis)

Diarrhea

Increased risk of lymphoma

Nausea

Vomiting

Given by mouth

Used as maintenance immunosuppression in people who have received a solid organ transplant

Source: The Merck Manual Home Edition