1
Outpatient red blood cell transfusion payments among
2
patients on chronic dialysis
3
4
Matthew Gitlin, PharmD,1 J. Andrew Lee, PhD,1 David M. Spiegel, MD,2 Jeffrey L. Carson,
5
MD,3 Xue Song, PhD,4 Brian S. Custer, PhD,5 Zhun Cao, PhD,4 Katherine A. Cappell, PhD,4
6
Helen V. Varker, BS,4 Shaowei Wan, PhD1 Akhtar Ashfaq, MD1
7
8
1
9
Wood Johnson Medical School, New Brunswick, NJ; 4Truven Health Analytics, Cambridge,
10
Amgen, Inc., Thousand Oaks, CA; 2University of Colorado, Denver, CO; 3UMDNJ-Robert
MA; 5Blood Systems Research Institute, San Francisco, CA
11
12
Email addresses: Matthew Gitlin - mgitlin@amgen.com; J. Andrew Lee - juhol@amgen.com;
13
David M. Spiegel - David.Spiegel@ucdenver.edu; Jeffrey L. Carson - carson@umdnj.edu; Xue
14
Song - Xue.Song@truvenhealth.com; Brian S. Custer - bcuster@bloodsystems.org; Zhun Cao -
15
zhun.cao@truvenhealth.com; Katherine A. Cappell, Katherine.cappell@truvenhealth.com; Helen
16
V. Varker - Helen.varker@truvenhealth.com; Shaowei Wan - shaowei.wan@gmail.com; Akhtar
17
Ashfaq - aashfaq@amgen.com
18
19
Corresponding Author: Matthew Gitlin, PharmD, One Amgen Center Drive, Thousand Oaks,
20
CA 91320-1799; Tel: (805) 447-7481; Fax: (805) 376-1847; Email: matthew.gitlin@amgen.com
21
22
Running Head: Transfusion payments in the dialysis setting
23
1
1
Abstract
2
Background: Payments for red blood cell (RBC) transfusions are separate from US Medicare
3
bundled payments for dialysis-related services and medications. Our objective was to examine
4
the economic burden for payers when chronic dialysis patients receive outpatient RBC
5
transfusions.
6
Methods: Using Truven Health MarketScan® data (1/1/02-10/31/10) in this retrospective micro-
7
costing economic analysis, we analyzed data from chronic dialysis patients who underwent at
8
least 1 outpatient RBC transfusion who had at least 6 months of continuous enrollment prior to
9
initial dialysis claim and at least 30 days post-transfusion follow-up. A conceptual model of
10
transfusion-associated resource use based on current literature was employed to estimate
11
outpatient RBC transfusion payments. Total payments per RBC transfusion episode included
12
screening/monitoring (within 3 days), blood acquisition/administration (within 2 days), and
13
associated complications (within 3 days for acute events; up to 45 days for chronic events).
14
Results: 3283 patient transfusion episodes were included; 56.4% were men and 40.9% had
15
Medicare supplemental insurance. Mean (standard deviation [SD]) age was 60.9 (15.0) years,
16
and mean Charlson comorbidity index was 4.3 (2.5). During a mean (SD) follow-up of 495
17
(474) days, patients had a mean 2.2 (3.8) outpatient RBC transfusion episodes. Mean/median
18
(SD) total payment per RBC transfusion episode was $854/$427 ($2,060) with 72.1%
19
attributable to blood acquisition and administration payments. Complication payments ranged
20
from mean (SD) $213 ($168) for delayed hemolytic transfusion reaction to $19,466 ($15,424)
21
for congestive heart failure.
2
1
Conclusions: Payments for outpatient RBC transfusion episodes were driven by blood
2
acquisition and administration payments. While infrequent, transfusion complications increased
3
payments substantially when they occurred.
4
3
1
2
Keywords
3
dialysis; red blood cell transfusions; payers; cost
4
4
1
2
Background
Anemia is common in end-stage renal disease (ESRD) and results from reduction of
3
erythropoietin production [1]. Prior to the development of pharmacologic treatments for anemia,
4
red blood cell (RBC) transfusions were the mainstay of anemia treatment, and approximately
5
55% to 60% of dialysis patients received RBC transfusions to avoid severe anemia [2-4]. RBC
6
transfusions are associated with a variety of complications, including hemolytic and non-
7
hemolytic transfusion reactions, infections, transfusion-related acute lung injury (TRALI),
8
transfusion-associated circulatory overload (TACO), and hyperkalemia [3, 5-11]. In 2009, the
9
rate of RBC transfusion-associated adverse reactions across all disease states was reported as
10
approximately 0.25% [12]. However, the rates of RBC transfusion-related complications may be
11
higher among chronic dialysis patients because of their significant comorbid disease severity and
12
concerns about patients’ fluid overload. Furthermore, while the overall rates of these
13
complications may be low, their outcomes can be severe (hospitalization or death) and their
14
associated costs are high [13-15].
15
The use of RBC transfusion as a treatment for anemia declined dramatically after the
16
approval of the first erythropoiesis-stimulating agent (ESA) in 1989 [16, 17]. In the 1995 annual
17
report of the United States Renal Data System (USRDS), the reported rate of outpatient RBC
18
transfusion in hemodialysis patients dropped from 16% in 1989 to 2% by 1993 [18]. The overall
19
rate of RBC transfusions (per 1000 patient-years) in the hemodialysis setting decreased by about
20
half from 535.33 in 1992 to 263.65 in 2005 [17]. About 83% to 94% of chronic dialysis patients
21
now use an ESA to treat chronic anemia [19]. With the newly implemented Medicare
22
Prospective Payment System (PPS) for ESRD patients, reimbursement to providers is capitated
23
to include dialysis and separately billable medications and services (ie, ESAs, iron, dialysis
5
1
supplies, lab tests) but does not include blood and blood products. Since RBC transfusion use in
2
ESRD patients on dialysis could potentially increase, it is important to understand transfusion-
3
associated payments and outcomes in this patient population.
4
Incomplete accounting of payments related to RBC transfusion administration may
5
provide misleading information to policy makers determining reimbursement policy in a
6
healthcare system such as Medicare. The purpose of this retrospective claims analysis study was
7
to use a micro-costing approach to examine the economic burden for payers when chronic
8
dialysis patients receive outpatient RBC transfusions. This study will assist in quantifying the
9
economic impact to payers of RBC transfusions as they are tracked within many of the PPS
10
surveillance programs and will inform future studies examining RBC transfusion and associated
11
payments in Medicare claims data.
6
1
Methods
2
Data sources
3
The Truven Health MarketScan® Commercial Claims and Encounter and Medicare
4
Supplemental and Coordination of Benefits Databases were used for this study. These databases
5
are constructed from privately insured paid medical and prescription drug claims. The
6
MarketScan Commercial Database contains the inpatient, outpatient, and outpatient prescription
7
drug experience of approximately 30 million employees and their dependents (in 2010) covered
8
under a variety of fee-for-service plans, managed care health plans, and indemnity plans. In
9
addition, the MarketScan Medicare Database contains the healthcare experience of
10
approximately 3.42 million retirees (in 2010) with Medicare supplemental insurance paid for by
11
employers. Medicare-covered portion of payment, employer-paid portion, and patient-paid
12
portion are included in this database. The MarketScan Commercial and Medicare Databases
13
provide detailed cost, use, and outcomes data for healthcare services performed in both inpatient
14
and outpatient settings. The medical claims are linked to outpatient prescription-drug claims and
15
person-level enrollment data through the use of unique enrollee identifiers. All personal
16
identifiers were removed.
17
18
19
Transfusion episode inclusion criteria
All analyses in this study were performed at the level of the transfusion episode. Eligible
20
patients were first identified using the following criteria: inclusion in the MarketScan
21
Commercial or Medicare Databases with ≥ 2 claims (to ensure that they were treated for chronic
22
disease) for chronic dialysis ≥ 30 days apart and within 365 days between January 1, 2002, and
23
October 31, 2010 (codes used to identify chronic dialysis claims are listed in Table S1 of the
7
1
Supplemental section); had ≥ 6 months of continuous enrollment prior to first chronic dialysis
2
claim to measure baseline clinical characteristics; had ≥ 1 outpatient RBC blood transfusion on
3
or after date of first chronic dialysis claim through January 31, 2011 (codes used to identify RBC
4
blood transfusion claims are listed in Table S2 of the Supplemental section); had no terminating
5
events (defined as end of continuous enrollment, end of MarketScan® data [January 31, 2011],
6
death, or kidney transplant) between first chronic dialysis claim and first outpatient RBC
7
transfusion; and had ≥ 30 days of continuous enrollment after the first RBC transfusion to
8
identify and measure subsequent RBC transfusion-related complications. RBC transfusions were
9
identified using revenue codes (UB-04), Current Procedural Terminology (CPT), and Healthcare
10
Common Procedure Coding System (HCPCS) codes (codes used to identify transfusion-related
11
complications claims are listed in Table S3 of the Supplemental section).
12
RBC transfusion–related complications that could be identified in the coded dataset and
13
could be reasonably attributed to a transfusion episode (based on medical literature and expert
14
clinical opinion) included febrile non-hemolytic transfusion reaction, air embolism, or phlebitis;
15
acute hemolytic transfusion reaction; allergic reaction; TRALI; TACO; delayed hemolytic
16
transfusion reaction; congestive heart failure (CHF); and hyperkalemia. To increase the
17
likelihood that CHF or hyperkalemia complications were directly related to the RBC transfusion
18
episode (rather than a pre-existing condition that coincided with the transfusion), patients with a
19
history of CHF or hyperkalemia during the pre-index period were excluded from the
20
complication cost analyses (but not from overall cost analysis). Because of the short follow-up
21
period post–transfusion episode, we could not collect information on longer-term complications
22
that might require more time to develop or be diagnosed (e.g., transfusion-related infections and
8
1
iron overload). A summary of the patient selection and transfusion episode time frame is
2
presented in Figure 1.
3
4
5
Variable definition and time frame
Demographic information was collected on the date of the first chronic dialysis claim.
6
Clinical characteristics were measured during the 180 days prior to the first chronic dialysis
7
claim. Because some patients had multiple RBC transfusion claims within a short time frame, we
8
combined individual claims within 3 days of each other into a transfusion episode, which was the
9
unit of observation for this study. Because pre- and post-transfusion screening and monitoring
10
payments could not be differentiated for patients with more than 1 transfusion claim within an
11
episode, we combined screening and monitoring payments 3 days prior to and 3 days post–
12
transfusion episode. Blood acquisition and administration payments were examined from
13
transfusion episode date to 2 days post–RBC transfusion episode.
14
With the exception of delayed hemolytic transfusion reactions, all complications were
15
identified up to 0 to 3 days post–RBC transfusion episode. Hemolytic transfusion reactions were
16
identified 4 to 45 days post–RBC transfusion episode (Figure 2). If a claim for RBC
17
transfusion–related complication was linked to ≥ 1 RBC transfusion episode, it was linked to the
18
earliest episode. If a claim for a complication could not be linked to an RBC transfusion episode
19
based on the described time windows, the claim was not included in the analyses.
20
21
22
23
Micro-costing/component analysis approach
We used a micro-costing approach to measure cost based on the components of resource
units and their payment values [20-22]. We included payments for blood acquisition, transfusion
9
1
administration, RBC transfusion–related lab tests, and transfusion complications [22]. For the
2
base-case analysis, we calculated component payments for (1) RBC transfusion screening and
3
monitoring, (2) blood acquisition and administration, and (3) transfusion-related complication,
4
which were summed to calculate (4) total payment for each RBC transfusion episode.
5
We conducted subgroup analyses for (1) patients with an acute bleed or surgery during
6
the 180 days prior to initial dialysis claim, (2) patients with cancer or blood disease during the
7
180 days prior to initial dialysis claim, and (3) patients who experienced an RBC transfusion-
8
related complication, by type of complication. We also performed sensitivity analyses by
9
excluding cost outliers (RBC transfusion episodes with the top 1% of blood acquisition and
10
administration costs or those with costs equal to $0 were excluded), varying the payment time
11
frames (using both a narrow and broad time window [defined in Figure 2] in identifying and
12
defining payment claims to RBC transfusion episodes), and estimating mean payment per unit of
13
blood based on a blood acquisition and administration claim analysis.
10
1
Results
2
Patient sample
3
From an initial sample of 105,260 patients with ≥ 2 chronic dialysis claims, we had a
4
final sample of 3,283 chronic dialysis patients who met all of the selection criteria. Requiring 6
5
months of pre-index data and ≥ 1 outpatient RBC transfusion contributed to the greatest loss of
6
subjects. Among the 3,283 chronic dialysis patients, there were 7,049 outpatient RBC
7
transfusion episodes used in the micro-costing analyses. Mean (standard deviation [SD]) patient
8
follow-up was 494.76 (474.19) days.
9
10
11
Patient demographics and clinical characteristics
Patients’ demographic and clinical characteristics are presented in Table 1. Mean (SD)
12
age was 60.9 (15.0) years, 56.4% of patients were men, and 40.9% of patients had Medicare
13
supplemental insurance. The three most frequent comorbidities were hypertension (93.9%),
14
diabetes (50.6%), and CHF (35.6%). Hemodialysis was performed in 60.8% of patients,
15
peritoneal dialysis in 6.3%, and type of dialysis was unknown in 33.4%. Patients experienced a
16
mean 2.15 transfusion episodes during the follow-up period. Transfusion was administered at
17
outpatient hospital facilities in 82.0%, ESRD facilities in 9.4%, hospital emergency rooms in
18
2.6%, and unknown in 6%.
19
20
21
Red blood cell transfusion episode payments
The component and total payments for RBC blood transfusion episodes are presented in
22
Table 2. Mean (SD) total payment per RBC transfusion episode was $854 ($2,060). The median
23
payment was $427 (25th percentile, $53; 75th percentile, $1071), suggesting that payments were
11
1
not normally distributed. The largest component (72.0%) of the total payment was blood
2
acquisition and administration (mean, $615; SD, $1,237; median, $289). Pre- and post-
3
transfusion screening and monitoring component payments represented 22.6% of the total
4
payment (mean, $193; SD, $616; median, $34). Payments for complications when averaged
5
across all RBC transfusion episodes were relatively low (mean, $75; SD, $1,317; median, $0) but
6
individual episode payments ranged from mean (SD) $213 ($168) for delayed hemolytic
7
transfusion reaction to $19,466 ($15,424) for CHF. When evaluating total payments by primary
8
payer type, the mean payments were similar. Mean payments (median; SD) per RBC blood
9
transfusion episode were $855 ($388; $2,728) and $853 ($457; $1,428) for Medicare primary
10
and commercial primary, respectively.
11
Subgroup analyses
12
We estimated per RBC transfusion episode payments for 3 subgroups (Figure 3).
13
Screening and monitoring costs varied minimally between patients with cancer or blood disease;
14
patients with an acute bleed or surgery; and patients who did not have cancer, blood disease,
15
acute bleed, or surgery. However, there was significant variation in blood acquisition and
16
administration payments. Patients with cancer or blood disease had the highest mean payment
17
(mean, $737; SD, $1,502), followed by patients with neither acute bleed nor cancer (mean, $542;
18
SD, $1,044). Mean total payment per RBC transfusion episode was higher than base-case
19
estimates (Table 2) for patients with cancer or blood disease (mean, $969; SD, $1,948) and lower
20
than base-case estimates for patients with an acute bleed or surgery (mean, $733; SD, $1,195).
21
Figure 4 summarizes payments made for various types of transfusion-related
22
complications. Payments for CHF (mean, $19,466) and allergic reactions (mean, $11,655) were
23
the most expensive complication payments. TACO (63 episodes) and hyperkalemia (51
12
1
episodes), were the most commonly observed types of complications. Among the RBC
2
transfusion episodes associated with hyperkalemia complications, 69.1% of the hyperkalemia
3
events occurred on the same date as the RBC transfusion start date.
4
5
Sensitivity analyses
6
We performed sensitivity analyses by excluding cost outliers, varying time frames
7
(narrow- and broad-window time frames) and reestimating the component and total payments per
8
RBC transfusion episode. As shown in Table 3, relative to base-case estimates, screening and
9
monitoring component payments increased slightly when outliers were excluded (mean, $214;
10
SD, $451) and when we used the broad-window time frame (mean, $225; SD, $712) but
11
decreased slightly when we used the narrow-window time frame (mean, $172; SD, $598). Blood
12
acquisition and administration payments were higher when outliers were excluded (mean, $696;
13
SD, $701) but similar to the base case estimates when narrowing and broadening the time frame.
14
When using the broad-window timeframe, complication payments greatly increased from the
15
base case’s mean (SD) of $75 ($1,317) to a mean of $120 ($1,520). Total payment per RBC
16
transfusion episode was highest when cost outliers were excluded (mean, $971; SD, $1,982) and
17
when we used the broad-window time frame (mean, $931; SD, $2,239) compared to the base-
18
case estimates.
19
Finally, we estimated component payments per blood acquisition and administration unit.
20
Per-unit data were available for 340 outpatient RBC transfusion episodes. When these episodes
21
were analyzed, the transfusion screening/monitoring mean (SD) payment was $245 ($425), the
22
blood acquisition and administration mean payment was $433 ($495), and the mean payment for
23
transfusion complications was $153 ($1,915). Per-unit total transfusion episode mean payment
13
1
was $827 ($2,127).
14
1
Discussion
2
We evaluated 3,283 chronic dialysis patients with at least 1 outpatient setting RBC
3
transfusion episode. Most of the patients had diabetes measured during the pre-index period. In
4
the base case, 72.1% of the total payments were due to blood acquisition and administration,
5
with the remainder of payments attributable to screening and monitoring and, to a lesser extent,
6
transfusion-related complications. Total RBC transfusion payments were higher for patients
7
with cancer or blood disease than those with an acute bleed or in our base-case estimates.
8
Sensitivity analyses suggest that the base-case results were robust. Total payment estimates
9
increased when both the top 1% most expensive episodes and $0 payment episodes were
10
excluded. Payments became slightly lower when a narrow-window time frame was used and
11
increased slightly with a broad-window time frame. The variations in total payments among all
12
sensitivity analyses were less than 15% different from the base-case total payment estimates.
13
Across all sensitivity analyses, the blood acquisition and administration payments consistently
14
were the most expensive component payment.
15
Under the newly implemented Medicare PPS for ESRD patients, reimbursement is
16
capitated to include dialysis and previously separately billable medications and services.
17
Payments for blood and blood products are not, however, included in the new PPS bundle. As
18
patients are treated to a lower hemoglobin level, the resulting lower hemoglobin levels could also
19
create a medical necessity for RBC transfusions. The use of transfusions to supplement ESA
20
therapy in ESRD patients on dialysis may increase because of economic incentives and clinical
21
necessity. It is, therefore, important to comprehensively examine the transfusion-associated
22
payments made within the chronic dialysis patient population in order to understand the
23
economic consequences of the recent changes in reimbursement.
15
1
Our results differ somewhat from a recent cost analysis that used an activity-based
2
costing model of RBC transfusions in a surgical population (based on observation of real-life
3
activities in four hospitals in the United States and Europe) to identify the costs for each
4
transfusion-related task and resource [22]. Overall, total inpatient RBC transfusion costs were
5
$522 to $1183 (mean, $761) per unit across the four hospitals (a considerable portion of the costs
6
was related to pre-surgical testing for blood type/screening in patients who never received a
7
transfusion) [22]. These results were similar but slightly lower than our mean per-unit payment
8
estimate of $827 (SD, $2,127). Blood acquisition costs in the other study were only 21% to 32%
9
($154 to $248 in 2008 dollars) of the total RBC transfusion-related costs. We found blood
10
acquisition and administration payments accounted for 50% to70% of total payments, but could
11
not differentiate acquisition and administration payments with certainty in the claims data.
12
Patient testing and administration and monitoring of RBC transfusions and pretransfusion
13
processes were 24% to 36% of total costs. Managing acute transfusion reactions and
14
hemovigilance contributed to 0% to 2% of costs [22]. The type and level of detail available in
15
the data as well as place of service (inpatient vs outpatient setting) may explain some of the
16
differences in our estimates from those of Shandler et al. Moreover, costs associated with blood
17
acquisition and administration can vary according to the amount (units) and type (eg,
18
leukoreduced or irradiated) of blood.
19
Our study had several limitations. We followed patients for mean 494.76 days, which
20
was not long enough to detect payments for iron overload. The analysis took a conservative
21
approach and excludes a number of potential resources that may increase the potential economic
22
burden. For example, a number of potential long-term complications, including infectious
23
diseases and iron overload, were excluded and may result in an underestimation of the overall
16
1
economic burden of RBC transfusions. In addition, long-term management of acute
2
complications such as medication costs and additional outpatient management were not included
3
in the analysis, all of which may result in underestimation of the overall economic burden of
4
RBC transfusions. Lastly, the economic burden may be underestimated because only
5
hospitalizations related to specific complications listed in Figure 2 were included. The analysis
6
may be potentially underestimating the economic burden by not including hospitalization that
7
may occur the day of or day after a RBC transfusion because this may be a result of the
8
transfusion exacerbating a existing condition or producing a new condition. Another limitation
9
is the potential to include acute renal failure patients in the analysis. Utilizing a large number of
10
dialysis claims over a long period may result in a much healthier population as a result of
11
inclusion criteria. To minimize the potential for including acute renal failure or only including a
12
healthier population of ESRD patients on dialysis, the analysis presented here utilizes specific
13
codes that are only utilized by ESRD patients on dialysis. Another includes hospitalizations
14
related to the specific acute complication events included in the micro-costing design. We did
15
not have information on patient race/ethnicity. We were missing type of dialysis in about one
16
third of cases. We did not evaluate inpatient costs because the inpatient claims data were based
17
on diagnosis-related group codes and could not be separated out into payment components,
18
therefore would have been obtaining what was probably an underestimation of the costs. Finally,
19
patients in our sample had either commercial insurance or Medicare plus Medicare supplemental
20
insurance as their primary coverage, and therefore, the results may not be generalizable to
21
patients who are uninsured, are covered only by Medicare, or have other types of insurance
22
coverage.
23
24
17
1
2
Conclusion
3
This is the first study to examine payments for outpatient RBC transfusions in a
4
population of patients undergoing chronic dialysis. Our study shows that payments for
5
outpatient RBC transfusion episodes are primarily driven by blood acquisition and
6
administration payments. Additionally, there are travel and other costs to dialysis patients for
7
RBC transfusion episodes and increased risk for allosensitization; these could not be estimated
8
here, but are important costs associated with RBC transfusions. While infrequent, transfusion
9
complications increase payments substantially when they occur. Better understanding of RBC
10
transfusion episodes’ payments and costs to patient may help inform policy makers when
11
determining the appropriate reimbursement policy for chronic dialysis patients.
12
18
1
2
Abbreviations
3
CHF, congestive heart failure; CPT, Current Procedural Terminology; DOPPS, Dialysis
4
Outcomes and Practice Patterns Study; ESA, erythropoiesis-stimulating agent; ESRD, end-stage
5
renal disease; HCPCS, Healthcare Common Procedure Coding System; PPS, Prospective
6
Payment System; RBC, red blood cell; SD, standard deviation; TACO, transfusion-associated
7
circulatory overload; TRALI, transfusion-related acute lung injury; USRDS, United States Renal
8
Data System
9
10
19
1
2
Competing Interests
3
Dr. Spiegel has been a consultant, received research funding, and served on the speakers bureau
4
for Amgen, and has served on scientific advisory boards for Amgen and Genzyme. Dr. Carson
5
financial research support from Amgen. Dr. Custer received consulting fees from Amgen for
6
this project. Dr. Song, Dr. Cao, Dr. Cappell, and Ms. Varker are employees of Truven Health,
7
Cambridge, MA, which provides consulting services to clients, including the pharmaceutical
8
industry. Dr. Gitlin, Dr. Lee, Dr. Wan, and Dr. Ashfaq are employees and stockholders of
9
Amgen Inc.
10
11
20
1
2
Author Contributions
3
MG contributed to the conception of the study, study design, analysis and interpretation of the
4
data; contributed to the writing and revision of the manuscript; and approved the final draft for
5
submission. JAL contributed to the conception of the study, study design, analysis and
6
interpretation of the data; contributed to the writing and revision of the manuscript; and approved
7
the final draft for submission. DMS contributed to the conception of the study, study design,
8
analysis and interpretation of the data; contributed to the writing and revision of the manuscript;
9
and approved the final draft for submission. JLC contributed to the conception of the study,
10
study design, analysis and interpretation of the data; contributed to the writing and revision of the
11
manuscript; and approved the final draft for submission. BSC contributed to the conception of
12
the study, study design, analysis and interpretation of the data; contributed to the writing and
13
revision of the manuscript; and approved the final draft for submission. SW contributed to the
14
conception of the study, study design, analysis and interpretation of the data; contributed to the
15
writing and revision of the manuscript; and approved the final draft for submission. AA
16
contributed to the conception of the study, study design, analysis and interpretation of the data;
17
contributed to the writing and revision of the manuscript; and approved the final draft for
18
submission. XS contributed to acquisition of data and analysis and interpretation of the data,
19
contributed to the writing and revision of the manuscript, and approved the final draft for
20
submission. ZC contributed to acquisition of data and analysis and interpretation of the data,
21
contributed to the writing and revision of the manuscript, and approved the final draft for
22
submission. KAC contributed to acquisition of data and analysis and interpretation of the data,
23
contributed to the writing and revision of the manuscript, and approved the final draft for
21
1
submission. HVV contributed to the acquisition of the data, contributed to the writing and
2
revision of the manuscript, and approved the final draft for submission
3
22
1
2
Acknowledgments
3
We wish to thank Linda Rice, PhD, of Amgen Inc. and Julia R. Gage, PhD, of Gage Medical
4
Writing, LLC for their editorial assistance and Tracy Johnson, BA, of Complete Healthcare
5
Communications, Inc. on behalf of Amgen for post-submission editing assistance. This study
6
was funded by Amgen Inc.
7
23
1
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Simon GE, Bove JR: The potassium load from blood transfusion. Postgrad Med 1971,
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11.
Vella JP, O'Neill D, Atkins N, Donohoe JF, Walshe JJ: Sensitization to human
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3
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Health; 2011.
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13.
Allain JP, Stramer SL, Carneiro-Proietti AB, Martins ML, Lopes da Silva SN, Ribeiro M,
8
Proietti FA, Reesink HW: Transfusion-transmitted infectious diseases. Biologicals
9
2009, 37(2):71-77.
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(NIS). Rockville, MD: Agency for Healthcare Research and Quality; 2007-2009.
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Goodnough LT, Strasburg D, Riddell Jt, Verbrugge D, Wish J: Has recombinant human
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erythropoietin therapy minimized red-cell transfusions in hemodialysis patients?
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Clin Nephrol 1994, 41(5):303-307.
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Ibrahim HN, Ishani A, Foley RN, Guo H, Liu J, Collins AJ: Temporal trends in red
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blood transfusion among US dialysis patients, 1992-2005. Am J Kidney Dis 2008,
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Diseases; 1995.
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2
Cruz JM, Kerr PG, Mendelssohn DC et al: Anemia management and outcomes from
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Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR: Activity-
10
based costs of blood transfusions in surgical patients at four hospitals. Transfusion
11
(Paris) 2010, 50(4):753-765.
12
13
14
26
1
Table 1. Demographic and clinical characteristics
Patients
N = 3,283a
Age, mean years (SD)
60.9 (15.0)
Sex, n male (%)
1,850 (56.4)
Geographic region, n (%)
Northeast
253 (7.7)
North Central
975 (29.7)
South
1,459 (44.)
West
585 (17.8)
Unknown
11 (0.3)
Payer, n (%)
Commercial
1,941 (59.1)
Medicare
1,342 (40.9)
Deyo Charlson comorbidity index, mean score (SD)
4.32 (2.45)
Comorbid conditions, n (%)
Hypertension
3,084 (93.9)
Diabetes
1,662 (50.6)
CHF
1,167 (35.6)
Acute bleeding
748 (22.8)
Surgery
719 (21.9)
Cancer
680 (20.7)
COPD
460 (14.0)
Hyperkalemia
423 (12.9)
Dialysis modality, n (%)
27
Patients
N = 3,283a
Hemodialysis
Peritoneal dialysis
Unknown
Transfusion episodes with ≥ 30 days follow-up, mean
1,997 (60.8)
207 (6.3)
1,095 (33.4)
2.15 (3.78)
number (SD)
Length of follow-up, mean days (SD)
1
2
3
4
494.76 (474.19)
Chronic dialysis patients with ≥ 1 outpatient red blood cell transfusion episode.
CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; SD, standard
deviation.
a
28
1
Table 2. Base-case payment per red blood cell transfusion episode
All Patientsa (N= 3,283); All Episodes (N = 7,049)
Payments and Events
Mean
SD
Median
25th
75th
percentile percentile
Min
Max
Transfusion
screening/monitoring
Blood acquisition and
administration
Transfusion complications
$193
$616
$34
$0
$189
$0
$22,673
$615
$1,237
$289
$11
$801
$0
$30,962
$75
$1,317
$0
$0
$0
$0
$61,059
TOTAL screening, transfusion
and complication payments
Number of services per episode
$854
$2,060
$427
$53
$1,065
$0
$74,452
2.87
2.93
2.00
0.09
5.00
0.00
20.00
Blood acquisition and
2.04
1.26
administration
a
2
Patients with ≥ 1 outpatient red blood cell transfusion.
3
SD, standard deviation.
4
2.00
1.00
3.00
1.00
12.83
Average payment per episode
All payers
Transfusion screening/monitoring
29
1
Table 3. Sensitivity analysis of RBC transfusion episode payments by time frame
Drop Top 1%
and Bottom
Narrow
Broad
Base Case
$0 Patients
Window
Window
Mean payments (SD)
(N = 7,049)
(N = 4,844)
(N = 7,049)
(N = 7,049)
Screening/monitoring
$193 (615)
$214 (451)
$172 (598)
$225 (712)
Acquisition/administration
$615 (1,237)
$696 (701)
$615 (1,237)
$615 (1,237)
Complication
$75 (1,317)
$86 (1,541)
$56 (1,149)
$120 (1,521)
$854 (2,060)
$971 (1,982)
$814 (1,940)
$931 (2,239)
Total payment per RBC
transfusion
2
3
RBC, red blood cell; SD, standard deviation.
30
1
Figure Legends
2
Figure 1. Patient selection time frame.
3
Figure 2. Transfusion episode time frame. Abbreviations: CHF, congestive heart failure;
4
TACO, transfusion-associated circulatory overload; TRALI, transfusion-related acute lung
5
injury.
6
Figure 3. Red blood cell transfusion episode payments for patients with history of acute
7
bleed/surgery or cancer/blood diseases.
8
Figure 4. Mean red blood cell transfusion payments for patients with complications, by
9
type of complication. Abbreviations: CHF, congestive heart failure; TACO, transfusion-
10
associated circulatory overload.
11
31
1
2
Figure 1
3
4
5
6
32
1
2
Figure 2
3
4
5
6
33
1
2
Figure 3
3
4
5
34
1
2
Figure 4
3
4
5
35
1
Supplementary Material: Inpatient and Outpatient Transfusion Billing Codes
2
Table S1. Codes for chronic dialysis claims
Code Type
Code
Description
UB-02 (Rev Code)
821
Hemodialysis/composite or other rate
UB-02 (Rev Code)
831
Peritoneal/composite or other rate
UB-02 (Rev Code)
841
CAPD/composite or other rate
UB-02 (Rev Code)
851
CCPD/composite or other rate
CPT
90918
corresponds to HCPCS G0308-G0310, G0320
CPT
90919
corresponds to HCPCS G0311-G0313, G0321
CPT
90920
corresponds to HCPCS G0314-G0316, G0322
CPT
90921
corresponds to HCPCS G0317-G0319, G0323
CPT
90922
corresponds to HCPCS G0324
CPT
90923
corresponds to HCPCS G0325
CPT
90924
corresponds to HCPCS G0326
CPT
90925
corresponds to HCPCS G0327
HCPCS
G0308
End stage renal disease (ESRD) related services during the course of treatment, for patients under
2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and
development, and counseling of parents; with 4 or more face-to-face physician visits per month
HCPCS
G0309
End stage renal disease (ESRD) related services during the course of treatment for patients under 2
years of age to include monitoring for the adequacy of nutrition, assessment of growth and
development, and counseling of parents; with 2 or 3 face-to-face physician visits per month
HCPCS
G0310
End stage renal disease (ESRD) related services during the course of treatment, for patients under
2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and
development, and counseling of parents; with 1 face-to-face physician visit per month
HCPCS
G0311
End stage renal disease (ESRD) related services during the course of treatment, for patients
between 2 and 11 years of age to include monitoring for the adequacy of nutrition, assessment of
growth and development, and counseling of parents; with 4 or more face-to-face physician visits
per month
HCPCS
G0312
End stage renal disease (ESRD) related services during the course of treatment, for patients
between 2 and 11 years of age to include monitoring for the adequacy of nutrition, assessment of
growth and development, and counseling of parents; with 2 or 3 face-to-face physician visits per
month
HCPCS
G0313
End stage renal disease (ESRD) related services during the course of treatment, for patients
between 2 and 11 years of age to include monitoring for the adequacy of nutrition, assessment of
growth and development, and counseling of parents; with 1 face-to-face physician visit per month
HCPCS
G0314
End stage renal disease (ESRD) related services, during the course of treatment, for patients
between 12 and 19 years of age to include monitoring for the adequacy of nutrition, assessment of
growth and development, and counseling of parents; with 4 or more face-to-face physician visits
per month
HCPCS
G0315
End stage renal disease (ESRD) related services during the course of treatment, for patients
between 12 and 19 years of age to include monitoring for the adequacy of nutrition, assessment of
growth and development, and counseling of parents; with 2 or 3 face-to-face physician visits per
month
HCPCS
G0316
End stage renal disease (ESRD) related services during the course of treatment, for patients
between 12 and 19 years of age to include monitoring for the adequacy of nutrition, assessment of
36
Code Type
Code
Description
growth and development, and counseling of parents; with 1 face-to-face physician visit per month
HCPCS
G0317
End stage renal disease (ESRD) related services during the course of treatment, for patients 20
years of age and over; with 4 or more face-to-face physician visits per month
HCPCS
G0318
End stage renal disease (ESRD) related services during the course of treatment, for patients 20
years of age and over; with 2 or 3 face-to-face physician visits per month
HCPCS
G0319
End stage renal disease (ESRD) related services during the course of treatment, for patients 20
years of age and over; with 1 face-to-face physician visit per month
HCPCS
G0320
End stage renal disease (ESRD) related services for home dialysis patients per full month; for
patients under two years of age to include monitoring for adequacy of nutrition, assessment of
growth and development, and counseling of parents
HCPCS
G0321
End stage renal disease (ESRD) related services for home dialysis patients per full month; for
patients two to eleven years of age to include monitoring for adequacy of nutrition, assessment of
growth and development, and counseling of parents
HCPCS
G0322
End stage renal disease (ESRD) related services for home dialysis patients per full month; for
patients twelve to nineteen years of age to include monitoring for adequacy of nutrition,
assessment of growth and development, and counseling of parents
HCPCS
G0323
End stage renal disease (ESRD) related services for home dialysis patients per full month; for
patients twenty years of age and older
HCPCS
G0324
End stage renal disease (ESRD) related services less than full month, per day; for patients under
two years of age
HCPCS
G0325
End stage renal disease (ESRD) related services less than full month, per day; for patients between
two and eleven years of age
HCPCS
G0326
End stage renal disease (ESRD) related services less than full month, per day; for patients between
twelve and nineteen years of age
HCPCS
G0327
End stage renal disease (ESRD) related services less than full month, per day; for patients twenty
years of age and over
CPT
90951
End-stage renal disease (ESRD) related services monthly, for patients younger than 2 years of age
to include monitoring for the adequacy of nutrition, assessment of growth and development, and
counseling of parents; with 4 or more face-to-face physician visits per month
CPT
90952
End-stage renal disease (ESRD) related services monthly, for patients younger than 2 years of age
to include monitoring for the adequacy of nutrition, assessment of growth and development, and
counseling of parents; with 2-3 face-to-face physician visits per month
CPT
90953
End-stage renal disease (ESRD) related services monthly, for patients younger than 2 years of age
to include monitoring for the adequacy of nutrition, assessment of growth and development, and
counseling of parents; with 1 face-to-face physician visit per month
CPT
90954
End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include
monitoring for the adequacy of nutrition, assessment of growth and development, and counseling
of parents; with 4 or more face-to-face physician visits per month
CPT
90955
End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include
monitoring for the adequacy of nutrition, assessment of growth and development, and counseling
of parents; with 2-3 face-to-face physician visits per month
CPT
90956
End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include
monitoring for the adequacy of nutrition, assessment of growth and development, and counseling
of parents; with 1 face-to-face physician visit per month
CPT
90957
End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to
include monitoring for the adequacy of nutrition, assessment of growth and development, and
counseling of parents; with 4 or more face-to-face physician visits per month
37
Code Type
Code
Description
CPT
90958
End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to
include monitoring for the adequacy of nutrition, assessment of growth and development, and
counseling of parents; with 2-3 face-to-face physician visits per month
CPT
90959
End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to
include monitoring for the adequacy of nutrition, assessment of growth and development, and
counseling of parents; with 1 face-to-face physician visit per month
CPT
90960
End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older;
with 4 or more face-to-face physician visits per month
CPT
90961
End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older;
with 2-3 face-to-face physician visits per month
CPT
90962
End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older;
with 1 face-to-face physician visit per month
CPT
90963
End-stage renal disease (ESRD) related services for home dialysis per full month, for patients
younger than 2 years of age to include monitoring for the adequacy of nutrition, assessment of
growth and development, and counseling of parents
CPT
90964
End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 2-11
years of age to include monitoring for the adequacy of nutrition, assessment of growth and
development, and counseling of parents
CPT
90965
End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 1219 years of age to include monitoring for the adequacy of nutrition, assessment of growth and
development, and counseling of parents
CPT
90966
End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 20
years of age and older
CPT
90967
End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per
day; for patients younger than 2 years of age
CPT
90968
End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per
day; for patients 2-11 years of age
CPT
90969
End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per
day; for patients 12-19 years of age
CPT
90970
End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per
day; for patients 20 years of age and older
1
38
1
2
3
4
Table S2. Billing codes for transfusions administered in the outpatient setting
Code Type
Code
Description
UB-04
0390
General Classification: Blood Processing and Services
UB-04
0391
Blood Administration
UB-04
0392
Blood Processing and Storage
UB-04
0399
Other Blood Handling
UB-04
0380
General Classification: Blood Products
UB-04
0381
Packed Red Cells
CPT
36430
Transfusion, blood or blood components
CPT
P9011
Blood (split unit), specify amount
CPT
P9016
Red blood cells, leukocytes reduced, each unit
CPT
P9021
Red blood cells, each unit
CPT
P9022
Red blood cells, washed, each unit
CPT
P9038
Red blood cells , irradiated, each unit
CPT
P9039
Red blood cells, deglycerolized, each unit
CPT
P9040
Red blood cells, leukocytes reduced, irradiated, each unit
CPT
P9051
Whole blood or red blood cells, leukocytes reduced
CPT
P9054
Whole blood or red blood cells, leukocytes reduced, frozen, deglycerol, washed, each unit
CPT
P9057
Red blood cells, frozen/deglycerolized/washed, leukocytes reduced, irradiated, each unit
CPT
P9058
Red blood cells, leukocytes reduced, CMV-negative, irradiated, each unit
Abbreviations: CMV, cytomegalovirus; CPT, current procedural terminology.
39
1
2
3
4
Table S3: Diagnosis codes for transfusion-related complications in the outpatient setting
Code Type
Code
Category
Description
ICD-9-CM Dx
398.91
CHF
Rheumatic (congestive) heart failure
ICD-9-CM Dx
402.x1
CHF
Hypertensive heart disease with heart failure
ICD-9-CM Dx
404.x1
CHF
Hypertensive heart and chronic kidney disease with
heart failure and with chronic kidney disease stage I
through stage IV, or unspecified
ICD-9-CM Dx
404.x3
CHF
Hypertensive heart and chronic kidney disease with
heart failure and chronic kidney disease stage V or end
stage renal disease
ICD-9-CM Dx
428.xx
CHF
Heart failure
ICD-9-CM Dx
708.0
Allergic reaction
Allergic urticaria
ICD-9-CM Dx
995.0
Allergic reaction
Other anaphylactic shock
ICD-9-CM Dx
999.4
Allergic reaction
Anaphylactic shock due to serum
ICD-9-CM Dx
999.83
Hemolytic transfusion reaction
Hemolytic transfusion reaction, incompatibility
unspecified
ICD-9-CM Dx
999.84
Hemolytic transfusion reaction
Acute hemolytic transfusion reaction, incompatibility
unspecified
ICD-9-CM Dx
999.85
Hemolytic transfusion reaction
Delayed hemolytic transfusion reaction,
incompatibility unspecified
ICD-9-CM Dx
999.6x
Hemolytic transfusion reaction
Hemolytic transfusion reactions
ICD-9-CM Dx
999.7x
Hemolytic transfusion reaction
Hemolytic transfusion reactions
ICD-9-CM Dx
276.7
Hyperkalemia
Hyperkalemia
ICD-9-CM Dx
999.1
Febrile nonhemolytic transfusion
reaction, air embolism or phlebitis
Other, including febrile nonhemolytic transfusion
reaction, air embolism or phlebitis following
transfusion
ICD-9-CM Dx
999.2
Febrile nonhemolytic transfusion
reaction, air embolism or phlebitis
Other, including febrile nonhemolytic transfusion
reaction, air embolism or phlebitis following
transfusion
ICD-9-CM Dx
999.80
Febrile nonhemolytic transfusion
reaction, air embolism or phlebitis
Transfusion reaction, unspecified
ICD-9-CM Dx
999.89
Febrile nonhemolytic transfusion
reaction, air embolism or phlebitis
Other, including febrile nonhemolytic transfusion
reaction, air embolism or phlebitis following
transfusion
ICD-9-CM Dx
E934.7
Febrile nonhemolytic transfusion
reaction, air embolism or phlebitis
Other, including febrile nonhemolytic transfusion
reaction, air embolism or phlebitis following
transfusion
ICD-9-CM Dx
276.6x
TACO
Fluid overload disorder
ICD-9-CM Dx
518.7
TRALI
Transfusion-associated acute lung injury (TRALI)
Abbreviations: CHF, congestive heart failure; TACO, transfusion-associated circulatory overload; TRALI, transfusion-related acute lung injury.
5
40