Reducing Costly Complications Associated With Platelet Transfusions

Update 

Leukoreduction by filtration has been shown to significantly reduce the costly complications associated with alloimmune-mediated refractoriness.

Summary of Evidence 

  • Contaminating leukocytes, present in all blood components, cause platelet refractoriness which significantly increases the cost of care for chronically transfused patients.
  • Only leukoreduction by filtration is clinically demonstrated to reduce platelet refractoriness and the associated increased cost of care.7,8
  • The clinical effectiveness of leukoreduction may be method-specific.

For further information on how leukocyte reduction by filtration has been shown to significantly reduce the costly complications associated with alloimmune-mediated refractoriness, select from the following:

Blood Component Therapy Is The High Cost Dilemma

Platelet transfusion therapy is an integral part of the treatment of hematological malignancies. Without it, marrow and stem cell transplantation would be impossible.

Unfortunately, chronic transfusions can also promote complex, clinical complications. One of the most costly of these complications is immunological resistance to platelet transfusion (alloimmune-mediated refractoriness). This complication can significantly increase the number of transfusions required and additionally necessitate the use of more expensive components (i.e., HLA-matched single donor platelets that can cost up to 80% more than other platelet components). In many cases, even HLA-matched platelets still fail to alleviate the problem. Ultimately, alloimmune-mediated refractoriness is costly to manage and can compromise treating a patient’s underlying disease.


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The Cost of Transfusion Therapy…

Data from Sniecinski et al.1, shown in Table 1, indicate that alloimmunized patients require significantly more platelet transfusions (14 vs. 5) and red cell transfusions (24 vs. 6) than those patients who were non-alloimmunized. The additional transfusions increased the cost of transfusion support three-fold, from $3,490 to $10,544 per patient.

Table 1: Impact of Alloimmunization on the Cost of Transfusion Therapy

  Total Cost* Platelet Transfusions Red Cell Transfusions
Cost # of Units Cost # of Units
Alloimmunized $10,544 $7,976 14 $2,568 24
Non-Alloimmunized $3,490 $2,848 5 $642 6

* Represents the total cost of transfusion support per patient per treatment course. Adapted from Sniecinski1


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Leukocytes: The Underlying Clinical Problem


Leukocytes In White Blood
Given the complexities and expense of managing alloimmunized patients who are refractory to platelet transfusion, prevention is an important goal. Since alloimmunization is caused by the creation of alloantibodies directed at HLA antigens, prevention is best achieved by either removing or inactivating the antigenic cells, namely leukocytes.

Most of the clinical studies completed since the early 1980’s have focused on the removal of leukocytes as a means of reducing alloimmunization. Although these single-institution studies had small sample sizes, this aggregate body of research, including the studies shown in Table 2, demonstrates that leukocyte reduction significantly decreases the incidence of alloimmunization (Leukocyte Reduction addresses the underlying problem).



Table 2: Leukocyte Reduction Reduces Alloimmunization

Authors Mean residual leukocytes in: Incidence of alloimmunization:
Platelets Red Cells Controls Leukoreduced
Myllyla et al. (1986)2 1 x 105 1 x 105 1/18 (6%)* 0/21 (0%)
Sniecinski et al. (1988)3 6 x 106 5 x 107 10/20 (50%) 3/20 (15%)
Andreu et al. (1988)4 0.5-1.5 x 108 6 x 107 11/35 (31%) 4/34 (12%)
Saarinen et al. (1990)5 4 x 104 1 x 105 12/17 (71%) 0/18 (0%)
van Marwijk Kooy et al. (1991)6 <5 x 106 <5 x 106 12/26 (46%) 3/27 (11%)

*Percent in parenthesis represents the frequency of occurrence of alloimmunization.


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The Trap Study

BACKGROUND: The beneficial effects of transfusing leukoreduced blood components have been confirmed by the recently published, prospective, randomized, blinded, multi-institutional Trial to Reduce Alloimmunization to Platelets (TRAP study) sponsored by the National Institute of Health. The purpose of this trial was to evaluate the merits of transfusing three different platelet preparations to reduce alloimmune-mediated platelet refractoriness compared with conventional (untreated) pooled platelet concentrates. Red cell transfusions given to all patients were leukoreduced by filtration using either the Pall RC100® or Pall BPF4® filters to prevent contaminating leukocytes in the red cells units from influencing the alloimmunization rate.

TRAP Treatment Arms:

  • Filtration leukoreduction of platelet concentrates using the Pall PL100® filter (six unit pool)
  • Filtration leukoreduction of apheresis platelets using the Pall PL100® filter
  • UV-B irradiation of platelet concentrates (six unit pool)

RESULTS: The primary endpoint of the TRAP study was to determine the rate of platelet refractoriness due to HLA alloimmunization. The results demonstrate that all treatment arms are effective in significantly reducing the incidence of alloimmune-mediated refractoriness as shown in Figure 1.

Figure 1: TRAP Study Results Rate of Alloimmune-Mediated Refractorines (%)



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Pall Leukocyte Reduction Filters Are Cost Effective

Pall leukocyte reduction filters for platelets and red cells have been clinically demonstrated to significantly reduce the cost of care for multiply-transfused patients by reducing the incidence of alloimmunization and refractoriness. Data from Blumberg et al.8, presented in Table 3, clearly show that patients undergoing the same treatment course who received filtered blood components required FEWER, LESS COSTLY platelet transfusions compared to those who received untreated components.

Pall leukoreduction filters have been clinically demonstrated to improve outcomes for multiply-transfused patients and reduce costs.

Table 3: Cost of Transfusion Support for Autologous Marrow Transplant Patients

Patient Group Components Total Units Cost of Blood Components Cost of Filtration Total Cost
Untreated Platelet Conc. 143 $5,720† $0 $6,920
Red Cells 16 $1,200†† $0
Filtered Platelet Conc. Platelet Conc. 71 $2,840‡ $411 $4,147
Red Cells 9 $675‡‡ $221
Total Savings Per Patient $2,773

†$40/platelet concentrate, ††$75/red cell component , ‡$34.70 per Pall Purecell Platelet Filter , ‡‡$24.50 per Pall EZ Prime Red Cell Filter
Adapted from Blumberg et al.8


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Is the Clinical Effectiveness of Leukocyte Reduction Method-Specific?

Leukocyte Reduced Platelet Components, which have been defined as being equivalent based on the quantitative assessment of residual leukocytes 9, Are Not Identical. Platelet components produced by various leukoreduction methodologies (all of which may demonstrate acceptable levels of total residual leukocytes) show strikingly different representation in the various white cell sub-populations (see Figure 2 and Table 4). These Various Residual White Cell Sub-populations are functionally distinct and may therefore contribute differently to clinical outcome10.

Since each leukoreduction methodology has a unique phenotypic makeup, extrapolation of the clinical benefits for one technology to another is not justified and may in fact lead to an inappropriate clinical decision. Therefore, every leukoreduction technology must provide studies that demonstrate its clinical effectiveness.

Pall platelet filters produce leukoreduced blood components which are phenotypically unique from other leukoreduction technologies.

Figure 2: Analysis of WBC Phenotypes Leukoreduction Methods Produce Different Platelet Components


* Spectra and Spectra LRS are trademarks of Cobe BCT, Inc.
** CS-3000® is a registered trademark of Baxter Healthcare Corp.
* Sepacell® PLS-5A is a registered trademark of Asahi Medical Co., Ltd.

Table 4: Residual Leukocyte Sub-populations for Various Leukoreduction Methods per Transfusion Event11

Cell Type Pall Pall RDP Pool Cobe® Spectra Baxter Sepacell®
PL100®
Filtration
PXL
Filtration
(6 units) Spectra
Apheresis
LRS
Apheresis
CS-3000®
Apheresis
PLS-5A
Filtration
Granulocytes ND† ND† 16,470,000 100,800 2,000 120,400 600
Monocytes ND† ND† 46,360,000 637,440 18,480 1,049,200 4,800
Lymphocytes 422,000 23,000 547,170,000 8,861,760 199,320 7,430,400 194,600
Total WBCs 422,000 23,000 610,000,000 9,600,000 220,000 8,600,000 200,000

†Not detected: Detection limit = 2.0WBC/µL. Leukocyte reduced samples are concentrated 1000 times Note: All platelet suspensions were 300mL (n=10, except for the PL100, where n=4)


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Pall Filtration Technology is Cost Effective and Clinically PROVEN

  • Pall filtration technology has been demonstrated to reduce the overall cost of care for chronically transfused patients by decreasing the incidence of alloimmune-mediated refractoriness to platelets.
  • The multi-center TRAP study demonstrates the clinical effectiveness of Pall bedside filters.
  • Pall platelet filters produce leukoreduced blood components which are phenotypically unique from other leukoreduction technologies.

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Pall... Ready, Willing and Able

As a pioneer in leukocyte reduction filtration technology, Pall is fully committed to providing customer solutions with our technology. We support this commitment with a substantial ongoing research and development effort. Pall is ready, willing and able to demonstrate the cost-effectiveness of our leukocyte reduction filtration technology for your specific transfusion needs. Choose Pall Purecell Filters to prevent your patients from incurring costly leukocyte-related transfusion complications.


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References

  1. Sniecinski I. The impact of leukocyte reduced blood components on the cost of transfusion therapy in bone marrow transplantation. Presented at the 1993 Annual Meeting of the American Association of Blood Banks in Miami, FL.
  2. Myllyla G, Ruutu T, Oksanen K, et al. Preparation and properties of leukocyte-free platelet concentrates. 19th Cong Int Soc Blood Transfusion, Sydney, Australia, 1986.
  3. Sniecinski I, O’Donnell B, Nowicki B, and Hill LR. Prevention of refractoriness and HLA-alloimmunization using filtered blood products. Blood 1988:71(No. 5):1402-1407.
  4. Andreu G, Dewailly J, LeBerre C, et al. Prevention of HLA immunization with leukocyte-poor packed red cells and platelet concentrates obtained by filtration. Blood 1988;72:964-969.
  5. Saarinen UM, Kekomaki R, Siimes MA, and Myllyla G. Effective prophylaxis against platelet refractoriness in multitransfused patients by use of leukocyte-free blood components. Blood 1990;75:512-517.
  6. van Marwijk Kooy M, van Prooijen HC, Moes M, et al. Use of leukocyte-depleted platelet concentrates for the prevention of refractoriness and primary HLA alloimmunization: a prospective, randomized trial. Blood 1991;77:201-205.
  7. The Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte-reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med 1997;337:1861-9.
  8. Blumberg N, Heal JM, Kirkley SA, et al. Leukodepleted-ABO-identical blood components in the treatment of hematologic malignancies: A cost analysis. American Journal of Hematology 1995;48:108-115.
  9. Standards for Blood Banks and Transfusion Services, 17th Edition published by the American Association of Blood Banks, 1996:15.
  10. Sowemimo-Coker SO, Kim A, Brandwein H, and Wenz B. Analysis of leukocyte subsets in leukoreduced platelet concentrates: Pall bedside filtered vs. apheresis products. Pall Technical Report 1996:1-6.
  11. Sowemimo-Coker SO, Kim A, Tribble E, Brandwein HB, Wenz B. Leukocyte subsets in apheresis and filtered platelet concentrates. Transfusion (in press).

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