- Organ Transplants
(Organ Transplant interactive CBS, pop-up window)

Organ Transplants -A transplant is the replacement of a patient's diseased organ with a normal organ(s) from someone--called a donor--who has died. The donor's organ(s) is completely removed and quickly transported to the patient, who may be located across the country. Organs are cooled and kept in a special solution while being taken to the patient (Hearts and lungs only last about 4 hours between donor and recipient).

(CBS News: Prisoner Gets $1M Heart Transplant, new window)

Heart transplants are the third most common (corneas and kidneys are the most common) transplant operations in the U.S. (over 1,500 cases per year). A healthy heart is obtained from a donor who has suffered brain death but remains on life-support. While the patient is deep asleep and pain-free (general anesthesia), an incision is made through the breast bone (sternum). The patient's blood is re-routed through tubes to a heart-lung bypass machine to keep the blood oxygen-rich and circulating. The patient's diseased heart is removed and the donor heart is stitched in place.

Organ Transplant myths (United Network for Organ Sharing, New window)

Transplant Facts The estimated first year charges for a heart transplant are $209,100 with annual followup charges at about $15,000. In the United States, the total transplant waiting list grows by about 5,000 patients each year while the number of donors increases by only 100 to 300 per year.

Type of Transplant	# Patients Waiting
kidney transplant	49,275
liver transplant	17,834
pancreas transplant	1,153
pancreas islet cell transplant	217
kidney-pancreas transplant	2,540
intestine transplant	161
heart transplant	4,234
heart-lung transplant	217
lung transplant	3,742
Total waiting	76,932
Transplants in 2000	22,854

On June 16, 2001 The UNOS national patient waiting list for organ transplant is shown on the left. If you are told by your doctor that you need a new organ ( a transplant) you are put on a list kept by UNOS, The United Network for Organ Sharing. UNOS is a private (non-government), nonprofit organization. composed of transplant hospitals, organ procurement organizations (OPO) and histocompatibility labs . UNOS keeps the list that matches donors and recipients.

Most U.S. organ transplant centers are part of a State University’s medical college. The University of Kentucky has a Transplant Center. Of the 272 U.S. transplant centers, most are affiliated with a University, and the rest are private hospitals and Federal government Veterans’ hospitals.

Organ Tissue sources - Living, Cadaver, Allo-, Xeno-, and Homegrown (Sci. Am.)

Tissue Typing - To prevent rejection, the organs used in transplant operations are "matched" to the recipients body. Each of us has protein markers located on the surface of our cells. One particular group of genetic markers is called HLA or Human Leukocyte Antigens. Tissue typing is the name given to the test which identifies an individual's HLA and matches the donor tissue with the recipient by comparing HLA type.

There are many different HLA antigens, but the ones that seem to be most important for transplantation are HLA-A, HLA-B, and HLA-DR. HLA antigens are very "polymorphic"meaning their form is different in different individuals.That means that in a population they can be found in many different forms. There are more than 25 forms of HLA-A, more than 50 forms of HLA-B, and more than 15 forms of HLA-DR.

It is illegal to buy and sell organs in the United States.

Public Law 98-507 prohibits the sale of human organs.

These different forms are caused by slight differences in the amino-acids that make up the proteins.

This information is critical before a patient receives a donor organ. Since everyone nherits these Human Leukocyte Antigens from their parents, it is possible to distinguish which set of HLA's were inherited from one's father and likewise from one's mother. This is done in some cases to select family members as possible donors.

HLA typing from the University of Pittsburgh Medical Center (new window)

For example, suppose your HLA-A is the following 1, 8, 10/ 2, 7, 11 (each number represents a separate inherited antigen). The antigens are inherited, as a group of three, from each parent. Each set of three antigens is called a haplotype. Keeping in mind that you must inherit one haplotype from each parent, as illustrated below, this is how you might have inherited your HLA:

Remember that the donor organ cells have the Human Leukocyte Antigens on their surface. The patient, on the other hand, can have antibodies in their serum which could injure the donor organ by attacking the HLA. By exposing the patient's serum to the donor's HLA ahead of time, it can be determined if a reaction will take place.

If the patient has antibodies to the donor organ HLA, the organ will be injured and this is referred to as a "positive crossmatch". A positive crossmatch is a contraindication to transplant, since it signifies that the patient has the ability to destroy the donor's cells, and would, most likely destroy the donor's implanted kidney (organ). Therefore, we hope that the crossmatch result will be negative. A negative crossmatch indicates that the patient does not have the HLA antibody against that particular donor, and a transplant can be performed.

The crossmatch test is a sort of "antibody screening", since it utilizes a selection of many different Human Leukocyte Antigens. It is performed by mixing a very small amount of the patient's serum with an equal amount of cells from 60 different individuals, in separate tests (remember the HLA are on the surface of these cells).

It is then determined how many different HLA antibodies a patient has in their blood. This enables us to avoid those antigens when selecting an appropriate donor. If the patient does not have any HLA antibody, the test result will be negative. The antibody screening procedure also identifies how much HLA antibody the patient has. For example, if the patient reacts with 30 out of 60 cells, then the patient is said to have 50% antibody, for that particular serum date. This percent antibody is called the PRA (Percent Reactive Antibody).

Antibody screening provides two very important pieces of information about the patient's serum: The PRA (how much antibody is present) 2) The Specificity (the specific HLA antibody)

Hyperacute rejection occurs within minutes of transplantation due to antibodies in the organ recipients blood stream that react with the new organ and result in organ failure within the first hours after transplantation. The kidney and heart are most susceptible to this problem, the liver is relatively resistant.

Acute rejection generally occurs in the first 6 to 12 months after transplantation. Lymphocytes from the thymus (T-cells) are blamed for causing acute rejection. For most organs, the only way to show unequivocally that rejection is occurring is by biopsy of that organ. For practical reasons, however, biopsies are not always done when acute rejection is suspected. In some circumstances treatment for rejection is begun and a biopsy is performed at a later date if the organ doesn't seem to be improving.

Chronic rejection is less well defined than either hyperacute or acute rejection. It is probably caused by multiple factors: antibodies as well as lymphocytes. The definitive diagnosis of chronic rejection is again generally made by biopsy of the organ in question. The heart is an exception to this generalization: chronic rejection in heart grafts is felt to be manifest by accelerated graft atherosclerosis. In other words, the transplanted heart rapidly develops "hardening of the arteries". Kidneys with chronic rejection have fibrosis (scarring) and damage to the microscopic blood vessels in the substance of the kidney. Livers with chronic rejection have a decreased number of bile ducts on biopsy.

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