1. Clinical Case
• 04/19/02 61 year old male with myeloma received auto PBSCT
• 04/21/02 Fever, LLL pneumonia; Rx with Timentin and Aztreonam
• 04/24/02 Vancomycin added
• 04/24/02 Developed mild chills with 100 mL pooled plts; transfusion
d/c; developed T38.4, BP 60/30, O2 Sat 91%, HR 140 one
hour after transfusion d/c; admitted to ICU for presumptive
septic shock
• 04/26/02 Blood Bank notified of subsequent events
Gram stain of saved segment: 2+ Gram-negative rods
Culture of saved segment: 4+ Klebsiella oxytoca, sensitive to
Timentin and Aztreonam
• 05/30/02 Pt died with multiorgan failure
No post transfusion blood cultures grew Klebsiella
Final source of contaminated platelet component remains
undetermined

2. Bacterial Contamination/ Sepsis
• usually during transfusion but may occur up to 4-6 h post
transfusion
• high fever, severe chill, nausea, vomiting, hypotension,
dyspnea
• can develop shock, DIC, multiorgan system failure

3. Septic Transfusion Reaction
• Bacterial sepsis has been a long-standing, well-known risk of
morbidity and mortality related to platelet transfusion therapy
• Estimates of incidence vary, but universally acknowledged as most
frequent infectious transfusion risk in USA
• Since the early 1980s, more/most attention paid to transmission of
viral infection
• AABB required implementation of methods to limit and detect
bacterial contamination in platelet components in March 2004
• Since 2004, STR have decreased but have not been eliminated

4. Sources for bacterial contamination
of platelet components
• Phlebotomy
– Skin contaminants (inadequate disinfection)
– Skin plug (large bore collection needle)
• Processing
– Contaminated collection bag, tubing, anticoagulant
• Asymptomatic donor bacteremia

5. Bacterial Contamination of Platelets
Components (05/1993-03/2013)
• Coagulase negative Staph – 8
• Bacillus spp. – 4
• S.aureus – 5
• Serratia marcescens – 1
• S. viridans – 2
• Strep Group A – 1
• Klebsiella oxytoca – 1
• E.coli – 1
• Mixed gram negative - 1

6. Bacterial Sepsis
Determinants of Clinical
Severity
• Organism
– Gram-negative organisms elaborating endotoxins
– Virulence factors permitting bacterial growth
• Bacterial load infused
– Time of storage: >3 days for platelets
– Volume of component
• Host characteristics
– Concomitant administration of antibiotic
– Degree of immunosuppression
– Neutropenia

7. Preparation of Blood Components
Red Cells Platelet-Rich Plasma
Red Cells Platelet Concentrate Plasma
Storage
1-6°C 20-24°C -18°C
42 days 5 days 1 year

8. Apheresis Collection
1½ - 3 Hours
Component
Collected
Anticoagulant
Return
Blood Filter
Saline
Blood Cell
Separator
Platelets
Stem Cells
Lymphocytes
Granulocytes
RBC
Plasma

9. Platelet Preparation Process
• Prepared from whole blood or apheresis collection (MSKCC
100%, USA 87%)
• Diversion of first 30-50 mL
• Store at standard condition (20-24oC) for 24-36 h, 8 mL sample
obtained for culture (SCD), culture in FDA approved system 18-
24 h, released to available inventory usually day 3 of 5 day
expiry
• Estimated sensitivity for day 1 culture is only 22-40%
• Residual risk of bacterial contamination on day of transfusion
or outdate is 1:3,000 - 5,000 (clinical significance unknown)

10. Bacterial Infection by
Platelets
From “Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2011”
http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/UCM300764.pdf

11. Comparison Across Institutions
(Blood suppliers)
• ARC Apheresis Collection 12/01/06 – 07/31/08
– 781,936 collections
– Confirmed positive – 130 (1:6015)
– False negative – 9 (1:86,882) reported reactions
– One fatality
• Canadian Blood Services 03/2004 – 02/2006
– 43,732 collections
– Confirmed positive – 3 (1:14,577)
– False negative – 1 reported reaction, not fatal
• Hēma-Quēbec 06/2002 – 02/2006
– 33,272 collections
– Confirmed positive – 3 (1:11,091)
– False negative – 1 reported reaction, possibly fatal

12. Comparison Across Institutions
(Transfusion Services)
• Johns Hopkins Passive Surveillance 03/2004 – 08/2007
– Two STR in 49,625 SDP transfusion(1:24,813); not fatal
• CWRU Active Surveillance 07/1991 – 02/2000 and 03/2004 –
12/2006
– 1:2,060 culture positive at issue (50 units)
– 42 units transfused
– 5 reactions with demonstrated bacteremia (1:20,600)
– 1 death (1:102,998)

13. MSKCC Platelet Transfusion
Total STR
05/1993-02/2004 121,552 18** 1:6753 1.7/year
03/2004-02/2013 124,641 6* 1:20,773 0.7/year
* 01/2009 Staph lugdunensis ** two fatal
11/2011 Staph aureus
12/2011 Strep viridans
03/2012 Strep viridans
03/2013 Staph aureus (2 recipients)
03/2004 – 02/2013
- 23,521 collections
- confirmed positive – 2 (1:11,761)
- False negative - 1

14. AABB Bulletin # 12-04, October 4, 2012:
“Recommendations to Address Residual Risk of Bacterial Contamination of
Platelets”
• Develop a policy to further reduce the residual risk
• Improve the recognition and monitoring of STR
• Optimize the appropriate transfusion practice

15. Bacterial Contamination of Platelet Components
Possible Future Preventive Measures
• Lower storage temperature
• Improve culture methods (↑ volume tested, test split units, sample later)
• Point-of-issue testing (must be simple, rapid):
Culture platelets after the first 24 hours of storage and then retest
day four or day five platelets just once with rapid test on the day of
transfusion
• Pathogen inactivation (loss of cells, ↓ cell function and survival, toxicity, neo-
antigenicity, and expense)
• Limit platelet transfusion

16. MSKCC Platelet Transfusions
*
* Projected
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
1997 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Unitstransfused
*

17. MSKCC Transfusion Guidelines
PLATELETS
1. PLT CT <10,000/uL in non-bleeding patient
WITHOUT other associated hemostatic defects
2. PLT CT <20,000/uL in non-bleeding patient WITH
other associated hemostatic defects
3. PLT CT <50,000/uL and minor bleeding, severe DIC,
invasive procedure or perioperative patient

18. MSKCC Transfusion Guidelines
PLATELETS
4. PLT CT <100,000/uL and clinically
significant bleeding (requiring RBC txn or
into closed space) or bleeding risk
5. Massive transfusion (>8 units RBC/24hr),
continued bleeding and PLT CT
unavailable
6. Other

19. Platelet Transfusion Non-indications
• ITP or TTP unless clinically significant bleeding
• Prophylactic use in massive transfusion

20. Concept of Patient Blood Management
• June 2011, HHS stressed the importance of strengthening
blood management systems to promote the rational use of
blood, cut down on the number of unnecessary transfusions,
reduce transfusion risks, improve patient care and save
hospital resources
• Requires evidence based transfusion guidelines (when
available)

21. Considerations for Risk Reduction in
Transfusion
• transfusion has never undergone prospective randomized
testing in the manner expected of a new drug
• repletion of elements of hemostasis effective in bleeding
patient
• prophylaxis to prevent bleeding in setting of mild-moderate
abnormal test result often lacks evidence-based support
• associated with unfavorable risk-to-benefit ratio

22. MSKCC Transfusion
Guidelines
Platelets Inpatient (%) Outpatient (%)
PLT CT < 10,000/μL 15 5
PLT CT < 20,000/μL 25 12
PLT CT < 50,000/μL 31 6
PLT CT < 100,000/μL 4 1

23. Prophylactic Platelet Transfusion
• most common use of platelet transfusion
• most previous research focused on optimal dose and threshold
• effectiveness is uncertain/unproven compared to therapeutic
strategy
• previous non-randomized comparisons of therapeutic
strategy with historical prophylactic controls have reported no
increase in major bleeding episodes or RBC transfusion, but
significant decrease in platelet transfusion
• current randomized controlled trial to compare prophylactic v
therapeutic in hematologic malignancies for safety and clinical
effectiveness
• if therapeutic is non-inferior, then potential benefit of decreased
transfusion: decreased risks, reactions, cost

24. Prophylactic Platelet Transfusion for Invasive Bedside
Procedures
• bronchoscopy, endoscopy, LP, paracentesis, thoracentesis,
CVC insertion all part of modern medical practice
• no published evidence for increased risks of procedure-
related hemorrhage and no controlled studies that
indicate what platelet count represents contraindication or
that prophylactic transfusion reduces risk of hemorrhage
• no evidence that ASA or NSAIDS increase risk

25. Relationship between hemorrhage and the platelet count in
non-transfused thrombocytopenic patients
Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients.
Transfus Med Rev. 2004 Jul;18(3):153-167 Gaydos, et.al:NEJM, 1962

26. Fecal blood loss in
thrombocytopenic patients
Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients.
Transfus Med Rev. 2004 Jul;18(3):153-167 Slichter:Clin Haem, 1978

27. Gmur: Lancet, 1991

29. Slichter: Blood, 1999

31. Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of Prophylactic Platelet Transfusions and
Prevention of Hemorrhage. N Engl J Med. 2010 Feb 18; 362 (7): 600-613.

32. Friedman: Trans Med Rev, 2002

33. German Therapeutic v Prophylactic Platelet Transfusion Study
Wandt:Lancet,2012
• randomized, multicentre, parallel-group trial
• stable adults, AML and auto SCT (391 patients)
Therapeutic Prophylactic (≤ 10,000/mcL)
Platelets transfused (u) 1.6 2.4 33.5% reduction p < 0.0001
WHO gr ≥ 2 (% per treat) 42 19 p < 0.0001
• 93% of bleeds WHO grade 2
• overall survival, RBC transfusion, hospital days, side effects, durations of TCP and time to
onset of first bleed did not differ
• study not powered to prove significant difference in WHO gr 4 bleeds or lethal events

34. German Therapeutic v Prophylactic Platelet Transfusion
Study
Therapeutic Prophylactic (≤ 10,000/mcL)
AML WHO grade 4 bleed 13 4
1 vaginal bleed 20 myomas (44,000) 4 retinal bleed with visual impairment
4 retinal bleed with visual impairment CT not performed after HA
6 minor cerebral bleed (CT after HA) 2 plt ct > 10,000
2 fatal cerebral bleed
(both HA; protocol violations; 1 plt ct < 10,000)
6 plt ct >10,000

35. TOPPS Trial
• 600 patients
• randomized, non-inferiority trial of therapeutic v prophylactic (<10,000/mcL)
• primary outcome: % patients with WHO grade ≥ 2 bleed
• non-inferiority margin: 15% difference
• adults, hematologic malignancies, chemo or SCT
• no difference in period of TCP, hospital days, SAE
Therapeutic Prohylactic
% transfused 59 89
total transfusion (u) 1.7 3.0
WHO gr ≥ 2 (%) 50 43 non inferiority p = 0.06
auto SCT 47 45 p = 0.04
bleeding days 1.7 1.2
WHO gr 3 – 4* 6/300 1/298 p = 0.13
*Only 2 pts with plt ct < 10,000 (median 16,000; range 3 – 42,000)

36. Platelet Transfusion Guidelines
• 1) PLT CT < 10,000/mcL
• 2) PLT CT < 20,000/mcL for outpatient
• 3) PLT CT < 20,000/mcL for recent hemorrhage (within 5 days)
• 4) PLT CT < 20,000/mcL and patient at risk for fall
• 5) PLT CT < 50,000/mcL for severe DIC
• 6) PLT CT < 50,000/mcL for existing CNS lesion
• 7) PLT CT < 50,000/mcL for invasive procedure (except bone marrow biopsy)
• 8) PLT CT < 50,000/mcL for active bleeding
• 9 PLT CT < 100,000/mcL for CNS invasive procedure (except lumbar puncture)
• 10) PLT CT < 100,000/mcL for life threatening bleeding
• 11) other