Organ Transplantation

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Organ Transplantation

• Anne Huml, M.D.
• January 21 23, 2009

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Objectives

• Provide a history of transplantation
• Review organs that are transplantable
• Define types of transplants
• Issues related to recipients
• Overview of immunosuppression
• Issues related to donors
• Other considerations

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The History of Organ Transplant

• Prehistoric transplantation exists in
  mythological tales of chimeric beings
• 1903-1905 Modern transplantation began with the
  work of Alexis Carrel who refined vascular
  anastomoses as well as transplanted organs within
  animals
• 1914-1918 Skin grafting in WWI
• 1953 HLA described by Medawar, Billingham and
  Brent
• 1952 Dr. Hume at Peter Bent Bringham Hospital in
  Boston attempted allograft kidney from unrelated
  donor and found that it functioned for a short
  period attributed chronic uremia as suppressant
  of the immune function for the recipient
• 1954 Dr. Joseph E. Murray transplanted kidney
  from Ronald Herrick to his identical twin,
  Richard Herrick, to allow him to survive another
  8 years despite his ESRD
• 1956 First successful BMT by Dr. Donnall Thomas,
  the recipient twin received whole body radiation
  prior to transplant

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The History of Organ Transplant Continued

• 1957 Azathioprine deveoped by Drs. Hitchings and
  Elion
• 1966 First successful pancreas transplant by
  Kelly and Lillehei
• 1967 First successful heart transplant by
  Christiaan Barnard in South Africa, recipient was
  54 yo male who died 18 days after transplant from
  Pseudomonas pneumonia. That same yr., first
  successful liver transplant performed by Thomas
  Starzl
• 1981 First successful heart/lung transplant by
  Dr. Reitz at Standford
• 1983 First successful lung transplant by Dr.
  Joel Cooper cyclosporin approved
• 1984 Congress passed the National Organ
  Transplant Act (NOTA) which stated that it was
  illegal to buy/sell organs, OPTN and UNOS were
  created as well as the scientific registry of
  transplant recipients
• 1990 tacrolimus approved
• 1995 mycophenolate mofetil approved
• 1997 daclizumab approved
• 1999 pancreatic islet cell transplant by Dr.
  Shapiro
• 2008 face transplant

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Transplantable Organs/Tissues

• Liver
• Kidney
• Pancreas
• Heart
• Lung
• Intestine
• Face
• Bone Marrow
• Cornea
• Blood

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Types of Transplant

• Heterotopic or Orthotopic
• different same
• Autograft same being
• Isograft/Syngenetic graft identical twins
• Allograft/homograft same species
• Xenograft/heterograft between species

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Transplantation Regions
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Statistics
On Waitlist as of 1/9/09 (reg 10)
Transplanted in 2007 (reg 10)
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Transplant Regions

• Organs are first offered to patients within the
  area in which they were donated before being
  offered to other parts of the country in order
  to
• reduce organ preservation time
• improve organ quality and survival outcomes
• reduce costs incurred by the transplant patient
• increase access to transplantation
• With the exception of perfectly matched donor
  kidneys.

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Pre-Transplantation Evaluation

• Blood Type (A, B, AB, and O)
• Rh factor does not matter
• Human Leukocyte Antigen (HLA) antigens on WBC
  familial matching can be 100-50-or 0
• Crossmatch if positive, then cannot receive
  organ done multiple times up to 48 hrs prior to
  transplant
• Serology for HIV, CMV, hepatitis
• Cardiopulmonary, cancer screening

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Details of HLA

• HLAHuman Leukocyte Antigens which are found on
  the surface of WBC
• Function of HLA is to help identify and in turn,
  fight foreign stuff
• 2 types of HLA?some for MHC I and MHC II (MHC
  genes are on chromosome 6)
• Most important HLA are types A, B (MHC I) and DR
  (MHC II)
• Remember MHC I present antigens to cytotoxic T
  cells and MHC II use antigen-presenting cells for
  helper T cells
• For this reason, it is important to have closely
  matched HLA between donor and recipient to avoid
  rejectionie. To avoid donor cells being
  presented to recipient immune system by MHC for
  destruction

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Recepient Qualification

• Most cases lt60 yr old
• Disqualified if
• Recent MI
• Active infection
• Malignancy
• Substance abuse
• Limited life expectancy from unrelated disease

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Tools Used to Stratify Transplant Recipients

• MELD/PELD model for end stage liver disease and
  pediatric end stage liver disease
• MELD developed in 2002 to account for objective
  findings rather than subjective findings range
  is 6-40
• Exception is Status 1lt1 of waitlist
• MELDgt12y.o
• Cr, Bili, and INR
• PELDlt12 y.o.
• Alb, BIli, INR, growth failure and age

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Tools Used to Stratify Transplant Recipients

• LAS Lung Allocation Score, range 0-100
• Developed in May, 2005 to reflect medical status
  of recipient as well as likelihood of successful
  transplant
• Agegt12

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Tools Used to Stratify Transplant Recipients

• CPRAcalculated Panel Reactive Antibody
• Used in allocation of kidney, pancreas, and
  kid/pancr
• Developed in 2004
• Measure of antibody sensitization reflects of
  donors not compatible with candidate secondary to
  candidates unacceptable antigens
• Ifgt80, get 4 extra points

POOLED HLA (100 DONORS)
Panel Reactive Antibodies (PRA)
CPRA-calculated from frequency in population
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Tools Used to Stratify Transplant Recipients

• Cardiac transplant uses Candidate Status as
  follows
• 1A admitted to the transplant center with one of
  the following
• Mechanical ventricular assist device x 30 days
  with clinical stability
• Total artificial heart
• IABP
• ECMO

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• Mechanical circulatory support with evidence of
  device related complication
• Continuous mechanical ventilation
• Continuous infusion of high dose single inotrope
  or multiple IV inotropes in addition to
  continuous hemodynamic monitoring of LV filling
  pressures
• 1B L/R VAD with continuous infusion of inotropes
• 2 does not fulfill criteria of 1A/B
• 7 currently unsuitable for transplant

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Immunosuppression
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Immunosuppression (cont)
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The Waiting Game

• As of 1/20/09 there are 100,568 patients waiting
  for organ transplantation
• Average waiting time (as of 2003)
• -heart 230 days
• -lung 1068 days
• -liver 796 days
• -kidney 1121 days
• -pancreas 501 days

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Determination of Brain Death

• Defined formally in 1968 by ad Hoc committee at
  Harvard headed by Beecher
• Defined by government in Office of the President
  with Uniform Determination of Death Act in 1981
• Individual who has sustained either 1.
  irreversible cessation of circulatory or
  respiratory functions or 2. irreversible
  cessation of all functions of the entire brain,
  including brainstem, is dead. A determination of
  death must be made in accordance with accepted
  medical standards.

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Diagnosis of Brain Death

• Pt suffered irreversible loss of brain function
  (either cerebral hemisphere or brainstem)
• Establish cause that accounts for loss of
  function
• Exclude reversible etiology
• Intoxication
• -? perform tox screen
• NM blockade
• Shock
• Hypothermia (lt90 deg F)?warming blanket

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When Etiology Determined and NOT Reversible

• LACK OF CEREBRAL FUNCTION
• ___________________
• Deep coma
• No response to painful stimuli
• Can have spinal cord reflexes

• LACK OF BRAINSTEM FUNCTION
• _______________________
• Pupillary reflexes
• Corneal reflexes
• Occulocephalic reflexes
• Occulovestibular reflexes
• Gag reflex
• Cough reflex

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Apnea Testing
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Brain Death

• Ancillary Testing to Include
• EEG
• Nuclear scan
• Angiography for absence of cerebral blood flow
• -Brain death determined after 6 hr with cessation
  of brain function, 12 hr without confirmatory
  testing
• -Documentation

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Making-up the Difference
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Organ Donation after Cardiac Death

• Death declared on basis of cardiopulmonary
  criteriairreversible cessation of circulatory
  and respiratory function.
• In 2005, IOM declared that donation after cardiac
  death was an ethically acceptable practice in
  end-of-life care and in March, 2007 UNOS/OPTN
  developed rules for it which became effective on
  July 1, 2007.
• Outcomes similar to those for organs transplanted
  after brain death.

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Key Elements in the Process of Donation after
Cardiac Death

• Withdrawal of life sustaining measures
• Pronouncement of death from time of onset of
  asystole (usually btwn 2-5 minutes) 60 sec is
  longest reported time of autoresuscitation
• To avoid conflicts of interest transplantation
  team physicians are not a member of the
  end-of-life care or declaration of death
• Liver within 30 min and kidney within 60 min
• If time to asystole exceeds 5 min, then recovery
  of organs is canceled

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Drawbacks to Transplantation after Cardiac Death

• Healthcare workers may be uncomfortable
  recommending withdrawal of care for one pt to
  obtain organ for a second
• Interval between withdrawal of care and death may
  be shortened and family relationship may be
  altered
• Conflict of interest
• Use of heart in cardiac transplantation

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Other Types of Donation

• Extended Criteria Donation (ECD)
• Defined as brain dead donor who is gt60 yrs of
  age, or donor gt50 yrs of age with 2 of the
  following
• HTN, terminal SCr gt1.5 mg/dl, or death resulting
  from CVA
• Living Donation
• With liver and kidney

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Factors Contributing to Family Consent for
Donation

• JAMA article published in 2001 about a study
  conducted over 5 yrs at 9 trauma centers in PA
  and OH
• Chart audit, then interview of healthcare
  practitioners (HCP) and organ procurement
  organization (OPO) staff as well as family for
  donor-eligible families
• Consent for donation mostly from young, white
  males with death associated with trauma
• Families reported beliefs with organ donation,
  had prior knowledge of patients wishes (through
  donor card or discussion)
• Best process was that HCP approached possibility
  of donation followed by OPO
• HCP were poor judges of who would donate
• Family appreciated open discussions about cost,
  impact on funeral arrangements and organ
  selection for donation

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Other Considerations

• Cost
• 1st year billed charges (250,000-1 mil)
• Religion

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References(in order of appearance)

• National Institute of Allergy and Infectious
  Diseases. Available at http//www3.niaid.nih.gov
  /topics/transplant/history. Accessed January 12,
  2009.
• Sade RM. Transplantation at 100 Years Alexis
  Carrel, Pioneer Surgeon. Ann Thorac Surg.
  2005802415-8.
• United Network for Organ Sharing. Available at
  http//www.unos.org. Accessed January 12, 2009.
• Lindenfeld J, Miller GG, Shakar SF, Zolty R,
  Lowes BD, Wolfel EE, Mestroni L, Page RL,
  Kobashigawa J. Drug Therapy in the Heart
  Transplant Recipient Part II
  Immunosuppressive Drugs. Circulation.
  20041103858-3865.
• Department of Health and Human Services.
  Available at http//www.organdonor.gov.
  Accessed January 10, 2009.
• Ad Hoc Committee of the Harvard Medical School. A
  Definition of Irreversible Coma.
  JAMA.1968205(6)337-40.
• Steinbrook R. Organ Donation after Cardiac Death.
  NEJM. 2007357(3)209-13.
• Pascual J, Zamora J, Pirsch JD. A Systematic
  Review of Kidney Transplantation From Expanded
  Criteria Donors. Am J Kid Dis. 2008
  52(3)553-586.
• Siminoff LA, Gordon N, Hewlett J. Factors
  Influencing Families Consent for Donation of
  Solid Organs for Transplantation. JAMA.
  2001286(1)71-77.