1. Surviving Change in the 21st Century
Florida Association of Blood Banks Annual Meeting
Richard R. Gammon, MD
Medical Director

2. Learning Objectives Discuss past model of blood center operations
Cover current challenges
Give an overview of current and future opportunities

3. Past Model of Blood Center Operations

4. Ancient Times Prehistoric man
Left drawings of himself pierced by arrows
Aware of blood
Fearful as life flowed red out of body of animal or enemy
Cave of Lascaux
Rossi’s Principles of Transfusion Medicine. 2009

5. Blood has Mystical Qualities
Romans
Fountain of youth
Medea prepares cauldron of sacrificed black sheep
Gives to Jason’s father Aeson
His hair and beard…assumed the blackness of youth…limbs of vigour and robustness
Bullfinch’s Mythology

6. Middle Ages 1492 Pope Innocent VIII on deathbed
Physician used blood drawn from three boys 10 years of age to save life
All died-no blood received

7. First Animal-to-Human Transfusion
June 15, 1667
Jean Baptiste Denis
Blood of lamb administered to 15 year-old boy – less impurities
Boy had fever and lethargy
Symptoms relieved by transfusion of 9 oz of blood

8. Denis’ Experience Performed transfusions on 3 additional patients
Number 2 survived, but 3 and 4 did not
Patient 4 – 34 year-old Anthony du Mauroy
Experienced bouts of maniacal behavior
Transfused blood of a calf two times

9. The Fate of Mr. du Mauroy
Two months later he began to experience maniacal behavior
Wife sought transfusion therapy
Transfusion could not be accomplished and patient died the next day
Wife tried to extort money from Denis or threatened a malpractice lawsuit
Denis refused and an investigation was launched

10. …and the Answer Is?
Madame du Mauroy had poisoned her husband with arsenic
Judgment April 17, 1668
Denis was exonerated
Madame du Mauroy was held for trial
Transfusion should not be performed unless approved by the Physicians of the Parisian Faculty

11. Death of Washington by Howard Pyle
1700s-Early 1800s
Within 10 years transfusion banned from England and France
Leeches for phlebotomy common
Contributed to death of George Washington
Death of Washington by Howard Pyle

12. The Beginnings Early 1800s James Blundell London obstetrician
Noted frequency of death after delivery

13. The Beginnings Performed 10 transfusions 5 were successful
Developed devices to facilitate transfusion
Against animal transfusions
Blundell’s Gravitator

14. The Victorian Era Media used for transfusion Milk
Cows
Goats
Human milk
Abandoned when saline became available
Adler J. 1892

15. Era of Modern Blood Banking
1900
Karl Landsteiner discovered ABO System
1913
Reuben Ottenberg
Describes compatibility testing
O as “universal”
                                           
Dr. Landsteiner

16. Wars and Technology Anticoagulants Sodium citrate - WW I ACD - WW II
Indirect transfusion -- WWII
Blood collected now
Transfused later
Soldier Receives Transfusion

17. Wars and Technology – WW I
Battlefield Blood Bank

18. Transfusion WW I
Blood Brothers- L'Illustration – 11/21/1914

19. War and Technology-World War II
US begins “Plasma for Britain” project
Dr. Charles Drew heads project
14 million units collected by war’s end

20. The Rise of the Community Blood Center
1937 Dr. Bernard Fantus established first blood storage facility
Cook County Hospital in Chicago
Blood bank
Save in one place
Obtain as needed

21. The Rise of the Community Blood Center
1941
Irwin Memorial Blood Bank opens
First US community blood bank

22. Blood Centers The Early Days
Donor Room Laboratory

23. Blood Centers The Early Days

24. The Creation of Components
Move to component therapy/plastics
Allows extended storage
Multiple products from one donation

25. Derivative Therapy
WW II – Cohn develops cold ethanol method of plasma fractionation
Albumin, fibrinogen, globulin become available
Clotting factor concentrates
1965 Pool discovered Factor VIII could be harvested from cryoprecipitate
Hemophiliacs benefited greatly-reduced disability

26. Volunteerism
1962
Connection made between paid donations and posttransfusion hepatitis
1970
1970 January designated as National Volunteer Donor Month
US moves to all volunteer donor base

27. The 1980s
Discovered that HIV could be transmitted in blood – 20 month infant
Up to 1% of single-donor unit transfusions were infected with HIV
Public confidence in blood supply at all-time low
Concern with slow action by regulatory/professional associations

28. The late 20th/Early 21st Century
Improved testing methods
Nucleic Acid Testing Introduced
HIV (1999)
Hepatitis C (1999)
West Nile Virus (2003)
Hepatitis B (2012)

29. 2010s Error reduction Emerging pathogens Cellular Therapies
Barcodes/RFID
iTrace – FDA clearance 05/29/13
Emerging pathogens
Hemovigilance
Pathogen Inactivation
Cellular Therapies
Blood management
05/13

30. Current Challenges

31. Paradigm Shift
B. Grigsby ABC Meeting 08/11

32. Hospitals Employ More Than 259,000 Physicians, Up 31% From 2000
Physicians hesitate to make decisions contrary to hospital since many are now employees
R Umberstock ABC Meeting 03/13

33. Adapting to Change

34. Adapting to Change

35. More Change…

36. Affordable Care Act

37. Seizing Opportunity

38. Seizing Opportunity

39. Diversification
J Fredericks. ABC Meeting 03/12

40. Diversification - Transplantation

41. Diversification – Transfusion Medicine
Many blood centers have centralized production and outsourced testing

42. Opportunities – Current and Future

43. Role of the Blood Center
ABC Webinar 12/08/10

44. Processing Services

45. Cord Blood Processing and Banking

46. The Possibilities

47. Cumulative Stem Cell Trials Worldwide

48. Cell therapy companies & their products
~300 therapeutic companies with ~250 cell-based therapies in the market or in some stage of clinical development. These therapies can be roughly broken down into the following stages*:
~110 Phase I ~70 Phase II ~30Phase III ~40 Commercial (marketed in at least one country)
Only ~1/3 of the therapies currently marketed (~13) required and received regulatory approval. In contrast, an estimated 90% of the therapies in development are “products” requiring pre-market approval.
__________________________________________________________________________________
* Note that these numbers are limited to industry-sponsored trials and may not capture fully products in early-stage trials where industry “sponsorship” is less than transparent.
ABC Webinar 0212

49. Have the fundamentals changed?
Cell therapy is here – instances of it being routine clinical practice & commercial
There has been incremental success
CT is now very much a part of individual, corporate, academic, policy, and financial consciousness
CT is now part of routine clinical practice and commercial products
Emerging metrics of a maturing industry (e.g., players, orgs, FDA, etc.)
On financial sector’s radar
Now working on second generation (not first generation) products.
Very little of this was true 10 year’s ago.

50. Today’s Market

51. Raw Cellular Material Collection

52. Storage and Logistics

53. Regulatory

54. US blood centers: strengths / opportunities
In 2011 independent blood centers grew cell therapy business from almost nothing to ~2,000 collections in ~35 sites generating >$3M in revenue on track to do ~$6M in 2012.
The growth to-date is exclusively from patient-donor collections.
This market is growing rapidly

55. US blood centers: strengths/opportunities
Other cell-based opportunities exist (more-to-less synergistic):
Custom allogeneic collections (e.g.., cells from diseased patients)
Blood products (e.g.., plasma, etc.)
Post-collection minimal manipulation cell processing (separation/isolation)
Collection from cell sources such as cord blood, bone marrow
Stem cell or tissue banking - cord blood, cord tissue, adult stem cell, tissue
Manufacturing
Collection/processing of other cell sources such as adipose, cadaveric, tissue
Technology (e.g.., device or biologic) development / distribution
Out-patient clinics (clinical infusion)

56. US blood centers: advantages
A cohesive independent blood center network:
Represents one the largest single network of collection centers in the world
Represents the most collection centers with experience collecting for cell therapies
Is comprised of centers staffed by personnel accustomed to working in an environment requiring strict regulatory compliance
ISBT128-compliant
Offers centralized contracting, training, implementation and ongoing central support regarding customer service, data tracking, etc..
Most commercially and technically flexible network of centers

57. US blood centers: weakness / threats
Competitors are hungry for this business.
Academic centers (sourcing and manufacturing)
American Red Cross (dispersed sourcing and future manufacturing)
Fresenius (dispersed sourcing (therapeutic apheresis arm))
HemaCare (dispersed sourcing)
AllCells, Inc. (sourcing – single site)
Synergy BioSolutions (sourcing – single site)
Key Biologics, LLC (sourcing – single site)
Lonza (sourcing – single site and manufacturing)
PCT (manufacturing – sourcing in future)

58. Increasing financial pressures on healthcare
US blood centers: impact of healthcare trends
Increasing financial pressures on healthcare
Cell therapy is big business now
Core business declining volume & diminishing margins while novel areas represent double-digit CAGR = success will go to the nimble
Lines between blood and cells and synthetics are blurring

59. Key drivers to success?
Cohesion. Centralized administration and access for customers.
Identifying leading centers for beta implementations / R&D.
Having and demonstrating expertise with emerging technologies / systems.
Demonstrating commitment to being commercially flexible and service-oriented.
Participating in the field’s leadership & executive network

60. Where Might We Go In 10 years?

61. Summary

62. Provenge - Background Harm et al. ASFA meeting 2012
Study conducted at University of Pittsburg and ITxM
Harm et al. ASFA meeting 2012

63. PROVENGE Processing Process repeated three times
Full course is typically completed in one month

64. Mechanism of Action

65. Mononuclear Cell Collection

67. Patient Demographics

68. Results: Scheduling

69. Scheduling

70. Results: Collections

71. Conclusions
University of Pittsburg and ITxM

72. Sports Medicine- Hope or Hype?
Claims by athletes and doctors that increased popularity of PRP began winter of 2009
Two leading football players
Recovered quickly and went on to play in the Super Bowl
Troy Polamalu
USA Today 06/29/11
NY Times09/07/11
Hines Ward

73. More Questions Than Answers
Testimonials from athletes and their doctors are not credible evidence
Most injuries eventually recover on their own, so if a patient has a treatment and then gets better, would the person have recovered at the same time anyway? Or did the treatment actually slow the healing process?
There is no way to know without a study that compares patients who were randomly assigned to have a treatment with a matched control

74. Costs Hundreds to thousands of dollars per injection
Fails to heal, doctors often inject again and again
Insurers usually do not pay, so patients pay out of their own pocket

75. Transfusion Medicine Reviews 2010; 24: 218-24
Current Studies
Contradicting data are available in the literature with regards to PRP in wound healing
Reported that the PRP injection in patient with Achilles tendinopathy did not result in greater improvement in pain and activity as compared to placebo injected with saline
Transfusion Medicine Reviews 2010; 24:
JAMA 2010; 303:

76. Current Studies – New Zealand
53 adults (mean age 49, 53% men) with symptoms of unilateral mid-portion Achilles tendinopathy for at least three months.
Participants were excluded if they had a history of previous Achilles tendon rupture or surgery or had undergone previous adjuvant treatments such as injectable therapies, glycerol trinitrate patches, or extracorporeal shockwave therapy
BMJ 2013;346:f2310 doi: /bmj.f

77. Results 26 participants were randomly assigned to the treatment group
27 to the control group
50 (94%) completed the six month study, with 25 in each group
Clear and clinically worthwhile improvements in the VISA-A score were evident at six months in both the treatment (change in score 18.7, 95% confidence interval 12.3 to 25.1) and control (19.9, 13.6 to 26.2) groups.

78. Results
Overall effect of treatment was not significant (P=0.689) and the 95% confidence intervals at all points precluded clinically meaningful benefit or harm
There was no significant difference between groups in secondary outcomes or in the levels of compliance with the eccentric calf strengthening program .
No adverse events were reported.

79. Conclusions
The administration of two unguided peritendinous autologous blood injections one month apart, in addition to a standardized eccentric training program , provides no additional benefit in the treatment of mid-portion Achilles tendinopathy.

80. Current Studies
Activity of platelet-derived factors present in PRP could depend upon
Quality of the PRP
Quality of wound
Type of wound
Physiologic conditions of the patients (age)
Other comorbidities
Use of prescription drugs

81. Conclusions
Premature to conclude that the variable results obtained using PRP are due to its inefficacy
A large number of randomized clinical trials are essential to establish the importance and role of PRP under diverse conditions

82. Conclusions
Clinicians and patients often want a magic bullet, and autologous blood products seem to satisfy many requirements of different parties
They are easy to obtain and prepare, they seem to be safe and ethically and socially acceptable
They are not doping, they are hyped by the media, and they allow large profit margins.
Editorial Nicola Maffuli from Italy- Orthopedic surgeon editorial
BMJ 2013;346:f2979 doi: /bmj.f2979 (Published 10 May 2013)

83. Conclusions But do they actually work?
Despite the findings of well conducted studies that suggest that they probably do not, it seems likely that they will continue to be widely used

84. Blood Center Approach Could be opportunity Proceed with caution
Ensure you have protocol
Establish way to recoup costs

85. Other Opportunities Mononuclear cells for in vitro use
HPC collection and processing
NMDP and private facilities
T. Foster – Webinar 04/23/13

86. Phase III Clinical Trials
Refractory angina and chronic myocardial ischemia
Renal cell carcinoma
Multiple sclerosis
Prostate cancer
Similar to Provenge but with some important variations

87. Phase III Clinical Trials
Glioblastoma
Recurrent glioblastoma
Alzheimer’s disease
Utilize plasma exchange for treatment

88. Cell Therapy Opportunities

89. Blood Management Program Evolution
S. Benitez- Santana. Blood Management Summit 11/10

90. Cost of Allogeneic Blood
Englewood Hospital Medical Center, Rhode Island Hospital, Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland), and General Hospital Linz (AKH; Linz, Austria),
All major process steps, staff, and consumables to provide red blood cell (RBC) transfusions to surgical patients, including usage frequencies, and direct and indirect overhead costs contributed to per-RBC-unit costs between $522 and $1183 (mean,$761 $294). These exceed previously reported estimates and were 3.2- to 4.8-fold higher than blood
product acquisition costs. Annual expenditures on blood and transfusion-related activities, limited to surgical
patients, ranged from $1.62 to $6.03 million per hospital and were largely related to the transfusion rate.
Mean per-unit acquisition costs included
units that were wasted and additional services provided (e.g..,
irradiation, washing, cytomegalovirus testing) as described in
the text.
Transfusion 2010; 50:

91. Beneficiaries of Blood Management
Ordering of appropriate blood components
Distribution, handling, and dispensing of blood components
Administration of blood components
Monitoring effects of blood components on patients
Guidelines for Patient Blood Management. AABB Press 2011

92. Sample Collection
Surprisingly high proportion of pretransfusion testing specimens are mislabeled or contain blood from a patient other than the one identified on the specimen label
1 in 165 samples being mislabeled
1 in 1986 samples with wrong blood in tube errors
The samples with labeling errors or omissions are 40-times more likely to be of a different ABO type than the intended recipient

93. Blood Administration Practice
Institutional policies and procedures must list the steps that should be taken before the initiation of a transfusion
Physician’s order for the component and any special instructions regarding its preparation or administration
Informed consent
Patient identification
Unit identification (number, product type, blood type, product modifications, and expiration date)
Confirmation of correct association of unit to patient

94. Blood Administration Practice
The risk of death as a result of mistransfusion from labeling or omission errors exceeds that of hepatitis C or human immunodeficiency virus (HIV)
J. Carson. Ann Int Med 03/26/12

95. Blood Administration Practice
Comprehensive “systems” approach is applied to all aspects of patient, sample, and unit identification to minimize risk of errors
Advocate the use of routine audits to monitor the effectiveness of processes to ensure appropriate and accurate labeling and identification
3% patients have serological findings that require further investigation
One recent study showed that 21 (7%) of the 309 patients scheduled for elective surgery did not have the type-and-screen sample tested before surgery TRANSFUSION 2011;51:
06/13

96. Evaluating and Reporting Adverse Effects of Transfusion
System to track and identify trends in adverse transfusion reactions and to ensure periodic auditing of such reactions
Allows for proper evaluation of trends
2009 NBCUS

97. The Transfusion Committee
AABB Audioconference 05/19/10

98. Peer Review
Assess whether deviations from the transfusion guidelines are clinically justified
Reveal practice patterns of over- and under-use that may benefit from an intervention to improve practice
Concern with repeated patterns, not isolated incidents

99. Peer Review
May lead the transfusion committee to question whether the guidelines are appropriate or should be modified
Effective system of detecting new problems
Any detected problems should be reported to the transfusion committee for further exploration

100. One Center’s Approach Cleveland Clinic
Noted continuing high blood product utilization
Transfusion of 2+ units of PRBCs common for patients with Hgb>10 g/dL
Unreliable blood product usage data
Difficult to assign blood product orders to specific physicians to identify usage
Implemented CPOE inpatient data (Epic)
Revised blood order practice
Parker B. Blood Management Summit 11/10

101. Track By Hospital

102. Track by Department

103. Track By Physician

104. Blood Waste Management

105. Wastage Examined and tracked Involve a minimal number of components
Most often involves products with shelf-lives of 24 hours or less
Temperature-controlled containers outside of the blood bank
Monitored for proper storage conditions
2009 NBCUS

106. Conclusions
Blood management and utilization is a comprehensive program in transfusion therapy
Based on the concept of continuous improvement and centered on the patient

107. Conclusions Consideration of many factors
Patient’s status
Laboratory results
Evidence-based criteria
Defined outcomes
Physician and facility history
Key to the development of a blood management strategy
Improves quality and advances patient safety

108. A Donor Center: Attracting Donors Who Do Not Wish To See Blood
The Cardeza Foundation for Hematologic Research, Thomas Jefferson University in Philadelphia, Pennsylvania, was formally incorporated in 1941 with an endowment from the Cardeza family. Thus a blood bank was established in the Cardeza Foundation.
At that time blood was collected in glass bottles by a technician and a physician as shown in the figure (upper right). Universal precautions did not exist: no gloves were used, blood was collected in a hand-held glass bottle, the technician is set up for mouth suction, and the amount of blood to be collected appears to be determined by sight.
Once the donor center was established, many donors were available but they were set aback by the sight of blood. The solution to the problem was to partition the donor center in such a way that the donor will not see blood and will not see other donors. Privacy might have been another reason for the partition.
This practice continued to the late 1940s or early 1950s. Partitions to separate donors from collectors, rather than from each other, were introduced by Russia in the 1930s and were used in the USSR for many years. Moreover, the practice of donating blood through a window was used by the French in 1939 as was previously described in a transfusion medicine illustrated article.
We are not aware, however, whether this practice was used somewhere else in the United States in addition to Philadelphia.
Transfusion 2013; 53: 13

109. Richard.Gammon@oneblood.org 407-248-5097 direct line
The End…Questions
direct line