Small-bowel length and the dose of cyclosporine in children after liver transplantation

Article Abstract:

Cyclosporine is a compound used to suppress the immune system after organ transplantation, to prevent rejection of the foreign organ. In order to be metabolized by the body, cyclosporine, like all substances, must first be absorbed into the bloodstream, a process occurring in the digestive system. Absorption of this compound, however, is difficult for the human body and calculation of the correct dose can be difficult. Children receiving liver transplants require a much higher dose of cyclosporine than do adults, for reasons that are not fully understood. One possibility is that the intestinal surface across which cyclosporine is absorbed may increase during childhood, changing its absorption rate. Small-bowel length and drug metabolism were investigated in 46 patients aged three months to 20 years who had received liver transplants. The amount of cyclosporine needed to maintain a blood level sufficient to suppress rejection was recorded, as were data that would enable computation of bowel length and body-surface area. Results showed that the required intravenous dose of cyclosporine increased along with body size, while the oral dose necessary decreased as bowel length increased. Larger body surface areas required the same intravenous dose per unit area, but the required oral dose grew smaller as body size increased. Expression of oral dose levels in logarithmic form showed that they were inversely related to bowel length; in other words, children with shorter bowels needed more cyclosporine. It appeared that bowel length is the main factor determining the effective dose of cyclosporine. Individual rates of cyclosporine clearance (metabolism) were also related to oral dose, but were no different in this regard for children than for adults. The amount of bowel available for absorption (functional bowel length) is a function of both body size and the amount that may have been surgically removed as part of the transplantation process. Knowledge of the importance of body size and bowel length for correct calculation of the effective oral dose of cyclosporine should improve treatment after liver transplantation. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research, Measurement, Dosage and administration, Cyclosporine, Cyclosporins, Pediatric gastroenterology, Intestine, Small, Small intestine

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Transmission of idiopathic (autoimmune) thrombocytopenic purpura by liver transplantation

Article Abstract:

Blood platelets, or thrombocytes, are essential for clotting. In the autoimmune disease known as chronic idiopathic thrombocytopenia, antibodies made by one's own body (autoantibodies) attack molecules on the surface of blood platelets and destroy them. The case history is described of a female patient who received a liver transplant from a donor with chronic idiopathic thrombocytopenia. The donor had undergone splenectomy (removal of the spleen), a common treatment for chronic idiopathic thrombocytopenia purpura, and had been treated with several drugs. While the liver transplantation was underway, the recipient's spleen ruptured spontaneously, necessitating its removal. Soon after surgery, the patient's platelet levels fell precipitously, and remained low. Renal deterioration began on day 2 after transplantation, and liver deterioration soon followed. A second liver transplantation procedure was performed, after which the platelet count rose, renal function improved, and recovery was satisfactory. Analysis of the patient's blood after the first procedure revealed the presence of IgG (immunoglobulin G) antibodies that reacted against molecules on the patient's own platelets. A similar antibody was found in blood from the donor. It was concluded that the patient had acquired idiopathic thrombocytopenia from the donor. The most likely way that the autoantibodies were transferred was via donor lymphocytes (white blood cells) trapped in the donated liver, which continued to produce them after transplantation. This case demonstrates a type of graft-versus-host disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Disease transmission, Graft versus host reaction, Graft vs. host disease, Thrombocytopenic purpura

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Brief report: lymphoma of donor origin occurring in the porta hepatis of a transplanted liver

Article Abstract:

Genetic analysis of a lymphoma that developed in a transplanted liver revealed that the tumor was a product of the donated organ not the recipient. The tumor developed 4 1/2 months after the transplant. Cells from the tumor and from the patient's blood were analyzed with a technique based on polymerase chain reaction and gel electrophoresis. Significant differences in genetic material indicated that the tumor developed from the grafted organ. Analysis of a preserved sample of the transplanted liver found genetic patterns similar to those found in the lymphoma. A small correspondence between the recipient's genetic material and that found in the tumor may represent the presence of blood cells from the recipient in the transplant. Treatment of a post-transplant lymphoma is problematic. Discontinuing or reducing the dosage of immunosuppressive drugs may allow the immune system to fight off the disease, but may increase the risk of transplant rejection.

Risk factors, Lymphomas

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