Transplantation

Panel Reactive Antibody

Serum screening for preformed antibodies using a panel of typing cells

Techniques identical to cross match

Expressed as a percentage of cells with which the patient’s serum reacts (0% to 100%)

Sensitization (or increased panel reactive antibody) occurs as a consequence of prior pregnancy, blood transfusion, or transplant

Lymphocytotoxicity cross match. (With permission from Mulholland MW, Lillemoe KD, Doherty GM, et al., eds. Greenfield’s Surgery. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.)

Cross Match

Refers to any test for the detection of recipient sensitization against donor HLA

Presensitization to HLA antibodies occurs only with previous exposure to foreign HLA from blood transfusions, pregnancy, or prior transplantation

Cross matching to exclude the presence of antibodies to donor leukocytes must be carried out immediately prior to transplantation

Hyperacute or accelerated rejection frequently occurs if transplantation is performed with a strongly positive cross match (e.g., a positive HLA I IgG cross match)

Methods

1.Complement-dependent lymphocytotoxicity cross match—Utilizes recipient serum, donor cells (T cells, B cells, or monocytes), and complement. If specific donor antibodies are present, antibody binding leads to fixation of complement and lysis of donor lymphocytes. Most commonly used cross match tests utilize mixed lymphocyte populations (most being T cells), therefore a strong cross match indicates antibodies to HLA I.

2.Flow cytometry (FC)—much more specific and sensitive

Is successful kidney/pancreas transplant associated with stabilization of proliferative retinopathy?

Yes—stabilization or even improvement.

Simultaneous Kidney/Pancreas Transplant

Successful pancreas transplant approximates euglycemia with normalization of glycosylated hemoglobin

Stabilizes or improves diabetic retinopathy

Improves both autonomic and peripheral diabetic neuropathy, but requires months to years to be demonstrable

Prevents recurrence of diabetic nephropathy in transplanted kidneys

Decreases orthostatic hypotension

Not associated with reversal of peripheral vascular disease or coronary artery disease

Overall graft survival rates are up to 90%

Technique of Pancreas Transplant

Pancreas is anastomosed to the common iliac artery and vein

Duodenal drainage is most commonly enteric; however, can be into bladder to monitor urinary amylase

Bladder drainage is associated with hematuria, renal stones, and bicarbonate loss

Simultaneous kidney–pancreas transplant with urinary anastomosis. (With permission from Mulholland MW, Lillemoe KD, Doherty GM, et al., eds. Greenfield’s Surgery. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.)

Simultaneous kidney–pancreas transplant with enteric drainage. (With permission from Mulholland MW, Lillemoe KD, Doherty GM, et al., eds. Greenfield’s Surgery. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.)

The acceptable maximal cold ischemia time is shortest in which organ/s?

Heart and lungs.

Preservation of Donor Organs

Hypothermia (4°C to 7°C) to decrease metabolism

Preservation solutions designed to improve cell wall stability—University of Wisconsin solution (high K and hyperosmolar)

Cold ischemia time

Heart/Lung: 0 to 4 hours (ASAP)

Pancreas: 0 to 12 hours (up to 24)

Liver: 0 to 12 hours (up to 24)

Kidney: 0 to 48 hours (72 with perfusion)

What are the criteria to establish brain death?

No pupillary response to light

No corneal reflex

No eye movement with doll’s eyes or caloric testing

No motor response to supraorbital pain

No cough reflex

Apnea

 

Each year, there are 11,000 to 14,000 cadaveric organ donors

Most donors are victims of trauma, cerebrovascular accidents, cerebral anoxia, or non-metastasizing brain tumors

In 2% of cases, patients are declared dead after cardiovascular death in cases in which brain death criteria have not been met

Prerequisites for Diagnosis of Brain Death

All appropriate diagnostic and therapeutic procedures have been performed and the patient’s condition is irreversible

With hypothermia, the patient must be rewarmed to normothermia

In cases of alcohol ingestion, at least 8 hours must elapse

Clinical Exam for Brain Death

Apnea test documenting no respiratory drive despite a PaCO2 >50

Absence of cephalic reflexes (pupillary, corneal, oculo-auditory, oculovestibular, oculocephalic, cough, pharyngeal, and swallowing)

Confirmatory Test (May Be Required in Some States)

No blood flow to brain on a nuclear medicine perfusion scan

Lack of brain activity on an electroencephalography (EEG)

Donor Exclusion Criteria

HIV infection

Malignancy (except some isolated CNS malignancy)

Bacterial sepsis

Hepatitis B surface antigen positive

Relative Contraindications for Organ Donation

Advanced age

IV drug use/abuse

Extensive trauma

What is the mechanism of action of the commonly used immunosuppressive medications?

Use of Immunosuppression

Induction

Given at the time of transplant to reduce the risk of acute cellular rejection

Monoclonal and polyclonal antibody preparations

IL-2 receptor inhibitors

Maintenance

Provided to decrease incidence of acute rejection over the life of the graft

Steroids

Calcineurin inhibitors

Anti-metabolites

Sirolimus

Treatment of Rejection

Steroids

Monoclonal and polyclonal antibody therapy

Graft irradiation

Complications of Long-term Immunosuppression

Nephrotoxicity in patients treated with cyclosporine or tacrolimus contribute to late renal allograft loss and native renal failure in patients receiving extra-renal organs (heart, liver, lung)

Post-transplant lymphoproliferative disorder: B-cell proliferation with spectrum from benign proliferation that responds to lowering of immunosuppression to malignant B-cell lymphoma requiring chemotherapy. Associated with Epstein Barr virus (EBV).

Cardiovascular disease: Particularly common in renal transplant patients and patients taking rapamycin

A 24-year-old woman presents 3 weeks after kidney transplant with fever of 102 degree. What is the most likely cause?

Bacterial infection.

Timing of post-transplant infections. (With permission from Mulholland MW, Lillemoe KD, Doherty GM, et al., eds. Greenfield’s Surgery. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.)

Fever in Transplant Recipient

Management of Immunosuppressed Patient with Fever

History and physical exam with a focus on wound infection, graft tenderness, dysuria, cough, rash, and diarrhea

Labs/Tests: Urinalysis, chest X-ray, CBC, chemistry, blood cultures

Empiric antibiotics until culture results return

Up to 1 month post-transplant: Most commonly caused by bacterial infection in wound, lung, urinary tract, central line associated bacteremia, Clostridium difficile colitis

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Apr 20, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Transplantation

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