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Cosmos and Damian - 4th century martyrs

Van Meekeren (1668) - dog cranium to human

Macewen (1878) - First clinical allograft

Lexter (1908) - joint transplant

Iclan (1942) - frozen bone

Hyatt (1950) - US navy tissue bank

Elosdorf (1952) - freeze drying of bone

Urist (1953) - BMP

Mankin (1971) - massive osteochondral allograf

Tissue Banking activities in USA:

There are several regional tissue banks in each state. They supply tissue grafts to the whole region. But the processing cost is very high. National programs such as American Red Cross distribute tissues to the region. Some cryobanks produce heart valves and cardiovascular tissues.

Most of the tissue banks have American Association of Tissue Banks(AATB) accreditation. These tissue banks are inspected and accredited by AATB. Four tissue banks in Canada under AATB. There is a network for organ procurement and transplantation. They follow a very strict selection criteria. National Bone Marrow program keeps a registry of living donors who are waiting for bone marrow donation.

Tissue banks also closely work together with organ procurement organizations. Educational programs for public are being held frequently. These include stamps, posters, TV programs etc.

Networking for tissue banking

Hospital staff


Social workers


Surgical services

Pathology services



Medical examiners

Organ transplant programs

Tissue programs

Donor evaluation: medical charts, medical history, culture tests, serology tests


Performs 185 000 blood collections annually between 8 fixed sites, 12 mobile coverings 13 countries in Western Washington.

Perform 10000 random apheresis collections including matched and white cell collections.

Perform 9000 autologous collections and 50+ directed donations.


Inventory production:

Fractionation of 185000 units of blood into components.

RBC (170 000)

FFP/RP (165 000)

Cryo (20 000)

Platelets (105 000)

Leuko-reduction of RBCs (20 000)

Labeling of components


1970-1980: Hepatitis B viral Antigen

1980: HIV-1 antibody, ALT, HTLV-1 antibody, HCV viral protein antibody

1990: HIV 1/2 antibody, HIV 1 antigen, HTLV I and II, HCV-PCR, HIV-PCR


Compatiblity testing:

22 king country hospital

330 000 procedures/year

Order Processing and Distribution:

Distributes 200 000 blood components to king county hospitals and 16 regional hospitals.

Performs 175 000 processing/year.

Red cell reference laboratory

Antibody identification

Prenatal testing

80 000 procedures/year

Hemostasis laboratories:

3000 procedures/year

Satellite Labs (3)



University district

Patient Services:

Bone Marrow Donor Program:

National Marrow Donor Registry

Since 1987- 46000 registered; 326 have donated.

Outpatient Transfusion Services:

Provide transfusion to 350 patient/year in king county

Therapeutic Phlebotomy

Perform 2500 procedures each year.

Therapeutic Apheresis

Plasma exchange, peripheral blood stem cell collection

1000 procedures perform annually.

Transfusion services

Washington, Alaska, Montana and Idaho (WAMI)

Preserved Human Tissues in Clinical use:

Structural Metabolic

Bone red cell

Dura mater platelets

Fascia lata marrow

Tendon semen

Cartilage oocyte

Skin embryo

Heart valve fetal tissue

Amnion parathyroid

Cornea islets



Tissue transplantation from living donors:

Blood, semen, umbilical vein, marrow, ovum, kidney, bone, amnion, pancreas, cord blood, stem cells, liver, (require HIV retest at 6 months)

Preserved human tissue in clinical use:

Living Donor Neurologic death Cardiorespiratory &

(brain death) Neurologic death

Blood kidney cornea

Semen heart bone

Ovum liver skin

Bone marrow pancreas tendon

Bone lung fascia lata

Amnion cartilage

Umbilical vein heart valve

Kidney saphenous vein


Tissue Transplantation Complications:

Disease transmission from graft

Risk reduced by

donor health screen, exam, tests

tissue processing, sterilization

Graft non-function

Due to immune rejection

Poor function due to donor defect or tissue healing

Bone autograft procurement complication

anesthesia, transfusion, pain, infection, scaro-illiac joint instability, hernia of intestine through illium, nerve injury, artery injury, gain disturbance, illium fracture

Infection from Organ transplant:

* hepatitis B * CMV

* HIV * Tuberculosis

* Bacteria * Toxoplasma


Tumor transplanted and spread:

Cryopreserved nipple autograft

Choriocarcinoma with kidney, liver, heart

Renal adenocarcinoma in kidney

Bronchogenic carcinoma in heart.

Melanoma in kidney

Hepatocarcinoma in kidney

Disease transmitted by tissue transplantation:

Bone                     Cornea                     Skin

HBV                      Rabies                  bacteria

TB                          CJD                      CMV

HIV                        yeast                     HIV

Bacteria               bacteria               HCV

HCV                        HBV

Heart valve          Marrow                  Dura

Bacteria              Toxoplasma          CJD

TB                             CMV

Yeast                       EBV

HCV                         HIV


TB from frozen bone

Donor: from thoracoplasty to treat pulmonary TB

Recipient: 4 spine fusions all cases TB wound infection

Hepatitis from frozen grafts:

Donor: 1949 transfused, normal LFT

1952 above knee amputation, age 73(vascular disease)

bone stored

Recipient: Senior medical student, Yale. Depressed fracture tibial plateau grafted, Jaundice 10week later

HCV tissue transmission:

Donor: 34 YO, M, MVA, HCV 1.0 Neg, 2.0 Pos:

Recipient: 9 potential:

2 diceased

4 tendon and bone, AB repeat reactive PCR positive

1 AB non-reactive

2 nontraceable

AIDS from frozen bone (femoral head)

Donor: 52 YO man

Nov 1984 - THR (no HIV test)

July 1986 - PCP, HIV pos, wife HIV pos

(history IV drug abuse)

Neck node biopsy - July 1984

Recipient: Woman

Nov 1984 - spine fusion for scoliosis

Day 21 - fever, diarrhea, node

July 1986 - Axillary node

Feb 1988 - PCP, AIDS, HIV pos

Tissue Transmission of HIV 1

1985 donor

HIV-1 AB negative, PCR positive

1991 recipient

HIV-1 AB positive HIV-1 AB negative

3 organs 2 cornea

2 frozen bone 1 frozen bone

1 frozen tendon 1 freeze dried tendon

28 freeze dried bone

15 FD bone untested

Disease transmission

Risk of bone

                           HIV    Hepatitis     Bacteria

Frozen                +            +                  +

Freeze dried*      -            +                  -

Air dried*             -             +                 -

Ethylene Oxide   -            -                  -

Irradiation             -            -                -

* alcohol soaked

HIV and Cornea:

No cases of transmission

HIV isolated from tears, cornea from infected person

2 HIV infected donors

2 kidney recipients - HIV pos

2 cornea recipients - HIV neg

Rabies from Cornea transplant:

Donor: 39 YO M rancher

Day 1-2 - backpain, numb, weakness arms, legs

Day 3-7 - Weakness, poor swallow and breathing intubated

Day 7 - Flaccid quadriparesis, pneumonia

Day 16 - Died

Recipient: 37 YO Female (keratoconus)

Day 30 - right headache, neck pain, right face numb

Day 32 - Dysarthria, impaired grafts, dysphagia

Day 33 - Comatose, intubated

Day 50 - Died

Rabies found in donor eyes and recipients eye, brain

CJD from cornea transplant:

Donor 55 YO man

2 Month - incoordination, poor memory, myoclonia

died with pneumonia

autopsy - CJD

Recipient: - 55 YO woman

18 month - lethargy, ataxia, nausea, progressive dementia

Impaired swallow, gain, myoclonic jerks

26 months: died, CJD

CJD transmission:

Cornea transplant

Intra cerebral electrodes

Neurosurgery following CJD patient

Recipient of hGH

Dura transplant

Dura Transmitted CJD

25 years old man developed rapidly progressive dementia 31 month after neurosurgery (trauma).

Received Freeze dried irradiated dura (Germany)

Autopsy - CJD

Donor Testing

Antibody ELISA assay:

HIV viral HIV Ab Goat

Lysate or + patient + Antihuman ------> colour

recombinant HRPO development


Infectious disease window periods:

                       NAT         Antigen         Antibody

HIV 1/2          5 days     18 days          22 days

HCV               22 days     N/A              8 2 days

HBV               24 days     37 days       59 days

HTLV I/II        NA               NA              38 days

Donor Files:

Systematic and consistent evaluation of donors (consent, screening, processing, linking, release)

The QA program defines minimum standards for donor screening.

Donor files document that standards have been met.

Inventory Control

Transfer signature

Labeling and packaging integrity.

Tracing mechanism.

Review and Release

Mechanism defined

Donor screening – Medical Director

Graft processing – QA department

Tissue Tracing/Tracking

Transplant Record

Inventory log

Records review

Follow up communications


Tracing vs tracking

Simple to complex

Trace from donor to recipient and back

- Problem identification

Disease transmission

Other adverse outcomes

Most common errors

Corrected In-house

*labeling errors, culturing/micro errors, equipment problems, missing freezing curves, control rate freezer dummy problem, freeze dry tissue problems.

AATB Inspections:

Major deficiencies – Inadequate QA

Lack of comprehension.

Conflict of interest in auditing .

Inadequate donor screening.

Deficiency of SOPs

Equipment maintenance

Improper/incomplete records

Inadequate documentation

Policy and Procedure Manual

The policies and procedures currently in place

Organizational structure

Responsibilities of staff

Quality Assurance program.

Arguing with QA is like wrestling with a pig in the mud. You soon discover that the pig enjoys it.

Definition of Process Validation:

“Process validation is the establishment of documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”

Process development studies:

A document or a set of document that describe the trials done to develop the process step and specifications.

Acceptance criteria not required

Provide the freedom to experiment with the process until consistent parameters are found.

Study conclusions become the specifications for the process in production.

Hazard Analysis:

This analytical tool is used to determine and minimize the potential weakness of the process. The development team defines the process steps and then determines possible hazards for each step. The analysis continues as each hazards can have effects on the process, the product, the product recipient or the staff performing the process. For each hazard, the upstream and down stream precautions are documented. Taking into account the effects and the precautions the team assigns a concern rating (minor, moderate or major) for each hazards.

Calibrated Instruments:

All instruments used to measure critical process parameters are identified. The accuracy of each instrument is investigated and verified to be appropriate for use in the process. Each instrument is also verified to be in current calibration. Ex: of calibrated instruments are timers, thermometers, pipettes.

Equipment Validation:

Each piece of equipment involved in the process must be validated in accordance with a quality practices SOP. Equipment validation is the establishment of documented evidence, through defined tests and challenges that a piece of equipment meets the design criteria that it will perform according to predetermined specifications.

Equipment validation is accomplished by performing an Installation Qualification (IQ) an Operational Qualification (OQ) and a Performance Qualification (PQ) on a given piece of equipment.


All the personnel involved in the process must be trained for their specific responsibilities. Training plans are created and training is documented according to a quality practice SOP.


Each material that is an input to the process should have specifications. The specifications for each material are shown to be met by performing vendor qualifications by performing quality control testing and by writing quality control and quality assurance procedures for the inspection and control of the materials.


If environment condition (temperature, relative humidity, air quality, contamination control or cleanliness) are critical to the process, then engineering controls, quality control programs, monitoring equipment or monitoring programs must be in place.

Standard Operating Procedures:

SOP specific to the process are verified to be written, approved and on file in a suitable location for personnel performing the process. The SOPs must correctly reflect the current process steps.

Product testing:

The process products are verified to meet the specifications for quality and safety and effectiveness. The process products are also shown to be consistent. Product testing is conducted using validated methods, calibrated instruments or certified standards to ensure that the product specifications have been met.

Validation at PSBC:

Validation is conducted for new or modified processes, new or modified equipment and any computer system modifications or enhancement that affect safety, purity, potency of products, accuracy of testing or distribution to patients.


Tissue recovery:

Skin, fascia, tendon, bone, heart valve, surgical bone, stem cells, cord blood, islet cells.

Tissue donors:

Living Donors: 250/year - average age 64 years old

Non-living donors: 250/year - average 40 years old

Tissue Graft distribution/year

* cardiovascular tissue 100

* Tendon/fascia              950

* skin                                 725

* Musculoskeletel          4550

                        Total         6325

PSBC Research and Education:

Hemophilia program

Medical education/ University, Washington

Stem cells

Thrombo protein

Molecular biology

Tissue/organ transplantation

PSBC Research and Development


Cerus, Amgen, Virogen, Flow/Fimbria, Haemonectics, Trans/DX

Hemophilia care program


Medical assessment and treatment

Diagnostic testing

Genetic counseling

Home infusion training

Education and counseling

Clinical trails

Distribution of clotting concentrates

Diagnosis             No of patients

Hemophilia A                    278

Hemophilia B                     55

Von Willebrand disease  98

Other clotting factors       41

Total                                    497

Commercial Clotting Factors:

Factor VIII                  Factor IX

MONARC - M              KONYNE - 80



KOGENATE                 FEIBIA

KOATE - HP             AUTOPLEX - T