Blood Center Experience with Double Red Cell Collections by Apheresis:

Adverse Events and Impact on Capacity

Brian Custer, Hany Kamel, Marj BravoPeter Tomasulo

Blood Systems, Inc.FDA Blood Products Advisory Committee

August 20111

Blood Systems2010: Red Cells Collected – 1.1 Million, Platelets Collected –160,000

Donor Panels Tested – 4.2 Million

2

Allogeneic Donations

PhlebotomyTime (min) Loss of Consciousness

N % Mean (95% CI)

LOC events

LOC Rate/10000

Latest Onset(min)

WB 944,018 75.4 8.7 (8.70-8.72)

2,364 25 252

2RBC 178,803 14.3 31.8 (31.73-31.86)

130 7 33

2RBC and WB Phlebotomy Time and LOC rates in Allogeneic Donations

BSI data, Allogeneic Donations, April 2009 to September 20103

Methods• Study period: January 1 –

December 31, 2007• Reactions studied:

– moderate and severe vasovagal reactions (combined into a single category)

• Statistical analysis:– Logistic regression analyses

that compared 2-RBC to WB donors.

• We report risks of AR using a diverse set of predictors based on an adjusted logistic regression model constructed using manual stepwise deletion.

Kamel et al. Adverse Reactions in Whole Blood and Automated 2-unit Red Cell Donations among 2RBC-eligible allogeneic male donors: a multivariate analysis.

4

Results – Experience, Age, Blood Volume and Collection Method

Kamel et al. Adverse Reactions in Whole Blood and Automated 2-unit Red Cell Donations among 2RBC-eligible allogeneic male donors: a multivariate analysis. 5

Adverse Event Rate / Procedure Type

All Whole Blood 2RBC

Platelet and/or

plasma by apheresis

(PP)

RBC with other

components by apheresis

(RBC+OC) Number of Donations 793,261 555,028 164,424 54,934 18,875 Number of VVRs 3,300 2,872 250 93 85 VVR rates* 41.60 51.74 15.20 16.93 45.03 Moderate reactions rate* 34.92 43.49 12.77 13.65 37.62 Severe reactions rate* 6.23 7.67 2.31 3.09 6.89 Fainting rate*† 21.51 27.38 7.54 3.64 22.25 Fall* 2.40 3.24 0.18 0.91 1.06 Outside Medical Care rate*† 3.49 4.52 0.97 1.09 2.12 Number of NRIs 1,023 474 397 133 19 NRI rates – all incidents* 12.90 8.94 24.14 24.21 10.07 Infiltration* 5.31 0.14 19.34 16.02 3.71 Hematoma* 3.32 3.12 2.92 6.74 2.65 Arterial Puncture* 0.40 0.49 0.24 0.18 0.00 Painful Arm* 4.53 3.26 6.02 13.47 2.65 Outside Medical Care* 0.67 0.81 0.12 0.91 0.53 * Rates per 10,000 donations † Of moderate and severe reactions

Custer et al. Associations between Collection Procedure Type and Donor Adverse Events.

6

Comparison of Vasovagal Reactions Across Time Course of Automated and WB Donations

7

BSI data, Allogeneic Donations, April 2009 to September 2010

8

BSI data, April 2009 to September 2010 9

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Period 1 Period 2 Period 3A Period 3B

By Period:Summary of Adjusted Odds Ratios Across Time Course of Blood

Odd

s Ra

tios

and

Confi

denc

e In

terv

als

Rate of Reactions w/ Onset time

PERIOD 2: Venipuncture to 4 min after needle

removal

PERIOD 3: > 4 min after

needle removal

Period 3A: > 4 min, on-site

Period 3B: > 4 min, off-site

WB 21.96 9.60 12.36 10.98 0.992RBC 6.54 5.71 0.84 0.73 0.06PP 5.80 3.17 2.63 2.30 0.33Multi-component 14.09 6.91 7.18 6.12 0.53

0

5

10

15

20

25

Rate

/100

00 D

onati

ons

Comparison of LOC rate across time course of blood donation by donation type

(44%)

(87%)(55%)

(49%)

(56%)

(13%)(45%)

(51%)

(50%)

(11%)(40%)

(43%)

(5%)

(1%)(6%)

(4%)

Bravo et al. Vasovagal Reaction, Outside Medical Care and Injury Rates During/After Whole Blood and Automated Collections.

11

THE LOC REACTIONS WHICH OCCUR WITH 2 RBC DONATIONS OCCUR EARLIER

THERE ARE FEWER LOC REACTIONS AND FALLS PER DONATION WITH 2 RBC DONATIONS THAN WITH WHOLE BLOOD DONATIONS.

12

RESULTS

Category of Adverse Event Whole Blood (WB)

2RBC Platelet and/or plasma by

apheresis (PP)

RBC with other components by

apheresis (RBC/P)

Number of Donation Visits 944,018 178,803 91,373 37,607 Rates per 10,000 donation visits VVR 40.9 11.4* 16.4* 34.0* LOC 25.4 7.3* 6.4* 16.5* NRI 3.6 15.4* 19.3* 20.7* NRI excluding infiltration 3.6 5.7* 9.8* 11.7* *Indicates automated procedure proportion is significantly different than whole blood proportion (p<0.05)

Custer et al. Donor adverse events: needle related injuries and vasovagal reactions are strongly associated. 13

RESULTSFactors associated with NRI (with VVR as a factor)

Od

ds

Ra

tios

an

d

95

% C

on

fide

nce

In

terv

als

Custer et al. Donor adverse events: needle related injuries and vasovagal reactions are strongly associated. 14

RESULTSFactors associated with VVR (with NRI as a factor)

Od

ds

Ra

tios

an

d

95

% C

on

fide

nce

In

terv

als

Custer et al. Donor adverse events: needle related injuries and vasovagal reactions are strongly associated.

15

• VVR rate is higher for WB than for 2RBC or PP collections

• NRI rate is higher for 2RBC and PP collections• Risk factors for VVR and NRI are not the

same• LOC and NRI are strongly associated• VVR are influenced by NRI, EBV, age, donor

history, donor race and procedure type • NRI are influenced by VVR, donor weight and

procedure type• More likely that NRI VVR than VVR NRI

Custer et al. Associations between Collection Procedure Type and Donor Adverse Events.

16

Collection Capacity

Day Mon Tue Wed Thu Fri Sat Sun Mon Tue Wed Thu Fri Sat Sun Mon

Aph RBC 49 116 139 145 145 110 10 123 282 198 75 137 51 2 114

WB 207 2004 2688 2629 2003 1407 672 2191 9324 9695 6317 4194 1423 633 3655

Donors 256 2120 2827 2774 2148 1517 682 2314 9606 9893 6392 4331 1474 635 3769

Units 285 2195 2923 2873 2246 1604 692 2402 9809 10041 6454 4443 1507 637 3840

17

18

PresentationsEBV & Hgb

Criteria Male % Male Female %

Female Total % Total

EBV <4000ml & Hgb <13.5 g/dL 42,466 9 329,480 65 371,946 37

EBV ≥4000ml & Hgb ≥13.5 g/dL 451,590 91 178,360 35 629,950 62

No EBV or Hgb 3,600 1 2,803 1 6,403 1

Total 497,656 100 510,643 100 1,008,299 100

Estimated blood volume (EBV) and hemoglobin (Hgb) criteria among presenting donors

BSI data, February 2010 to February 201119

20

21

Apheresis in a Disaster:Electric Power

• Electric power needed to pump gasoline and diesel fuel

• Not all BSI collection locations have generators• Not all generators can power apheresis devices

– Most generators dedicated to refrigerators and computers

• Bus mobiles have generators• WB throughput more rapid – capacity loading• Apheresis may be reserved for platelets

22

Summary• Fewer VVR, more NRI from 2 RBC apheresis• Possibly fewer injuries per procedure with 2

RBC• Reserve capacity is significant• Red cell apheresis has little benefit in “routine”

emergencies• May help more in widespread prolonged

disasters affecting donor availability (in which platelet apheresis would also be important)

• Apheresis requires power23

12-month BSI donor loss and possible donor gain with criteria modification

(February 2010 to February 2011)

DONOR LOSS(due to deferrals)

POSSIBLE DONOR GAIN

Current CriteriaIn a yearN (%)

Modified Acceptance criteria

In a year

In a week

In a day

Donor presentations1008299(100%)

 1008299(100%)

19390 3878

Tattoo, 12 months

9625(.95%)

6 months(NAT screening)

4813(0.48%)

93 19

Other risk of exposure to blood and body fluids*:

12 months

3296(0.33%)

6 months (NAT screening)

1648(0.16%)

32 6

Traveled to Malarial Area:12 months

7488(0.74%)

Accept travelers to Mexico: (~60% of malarial travel

deferrals)

4493(0.45%)

86 17

Not eligible due to:Hemoglobin of

11-12.4g/dL

55721(5.5%)

Eligible if Hb =11-12.4 g/dl (Criteria for autologous

donors)

55721(5.5%)

1072 214

Total Deferrals76123(7.5%) Total Gain

66672(6.6%)

1283(6.6)

256(6.6%)

* e.g., jail>72 hrs, blood transfusion, ear/body piercing, needle stick, etc. 24

25