The current state of the platelet supply in the US and proposed options to decrease the risk of critical shortages.

Due to circumstances such as increased demand and an aging donor pool, the likelihood of critical platelet shortages is increasing. The platelet supply could be improved through the expansion of the donor pool, the identification and sustained utilization of high-quality donors, and changes in component processing and storage that result in a longer platelet shelf-life. Refrigerated platelets, stored at 1° to 6°C, have the potential to improve patient safety by decreasing the risk of bacterial contamination while concurrently allowing for a longer storage period (eg, 14 days) and improved hemostatic effectiveness in actively bleeding patients. An approach utilizing remuneration of apheresis platelet donors combined with pathogen reduction of the platelet components could be used as a means to increase the donor pool and identify and sustain safe, reliable, high-quality donors. Remuneration might provide an incentive for underutilized populations (eg, individuals <30 years old) to enter the apheresis platelet donor population resulting in a significant expansion of the platelet donor pool. Over time, approaches such as the use of refrigerated platelets, platelet donor remuneration, and the application of pathogen reduction technology, might serve to attract a large, reliable, and safe donor base that provides platelet collections with high yields, longer shelf-lives and, excellent hemostatic function.

Financial analysis of large-volume delayed sampling to reduce bacterial contamination of platelets.

BACKGROUND: Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). METHODS: Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. RESULTS: Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). CONCLUSIONS: LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

Cost implications of implementation of pathogen-inactivated platelets.

BACKGROUND: Pathogen inactivation (PI) is a new approach to blood safety that may introduce additional costs. This study identifies costs that could be eliminated, thereby mitigating the financial impact. STUDY DESIGN AND METHODS: Cost information was obtained from five institutions on tests and procedures (e.g., irradiation) currently performed, that could be eliminated. The impact of increased platelet (PLT) availability due to fewer testing losses, earlier entry into inventory, and fewer outdates with a 7-day shelf life were also estimated. Additional estimates include costs associated with managing (1) special requests and (2) test results, (3) quality control and proficiency testing, (4) equipment acquisition and maintenance, (5) replacement of units lost to positive tests, (6) seasonal or geographic testing, and (7) health department interactions. RESULTS: All costs are mean values per apheresis PLT unit in USD ($/unit). The estimated test costs that could be eliminated are $71.76/unit and a decrease in transfusion reactions corresponds to $2.70/unit. Avoiding new tests (e.g., Babesia and dengue) amounts to $41.80/unit. Elimination of irradiation saves $8.50/unit, while decreased outdating with 7-day storage can be amortized to $16.89/unit. Total potential costs saved with PI is $141.65/unit. Costs are influenced by a variety of factors specific to institutions such as testing practices and the location in which such costs are incurred and careful analysis should be performed. Additional benefits, not quantified, include retention of some currently deferred donors and scheduling flexibility due to 7-day storage. CONCLUSIONS: While PI implementation will result in additional costs, there are also potential offsetting cost reductions, especially after 7-day storage licensing.

[Platelet concentrates from whole-blood donations (buffy-coat) or apheresis: which one to use?]. / Concentrados de plaquetas procedentes de sangre total (buffy coat) u obtenidos por aféresis; ¿qué producto emplear?

Platelet concentrates (PCs) prepared either from whole-blood donations by the buffy-coat method (BC), or by plateletpheresis are indicated to prevent or treat acute hemorrhage secondary to thrombocytopenia, and there is an ongoing debate about which platelet product should be used. Usage of each of these two products is highly heterogeneous among countries and individual institutions, ranging from 10 to 90%, with a 50:50 ratio in Europe. In comparison of pooled platelets prepared by the BC method and apheresis PCs, data suggest similar efficacy of the products. Regarding recipients' adverse reactions, there is no advantage for apheresis concentrates. From the donor's point of view, evidence favours using the abundance of platelets available from whole-blood donation. As residual viral transmission risk continues to fall, the advantage of apheresis products related to the decrease to donor exposure lessens. While the cost-effectiveness of apheresis products is comparable to that of other accepted blood safety interventions, in case of emerging pathogens, probably pathogen inactivation of pooled BC PCs would be a more desirable strategy.

[The quality of platelet concentrates in dependence on storage time before pathogen inactivation]. / Jakosc koncentratów plytek krwi w zaleznosci od czasu ich przechowywania przed wykonaniem procedury inaktywacji patogenów.

UNLABELLED: Pathogen inactivation procedure performed just before distribution of platelet concentrates (PCs) may decrease costs caused by loss of these components due to relatively short expiry date. THE AIM OF STUDY: To evaluate the quality of PCs pathogen inactivated on the first or the fifth day of storage. MATERIAL AND METHODS: PCs preparated from buffy-coats were suspended in platelet additive solution (Intersol, Baxter Healthcare Corporation, Belgium). The photochemical pathogen inactivation was performed on the 1st or the 5th day of storage using amotosalen and UVA (Cerus, Europe BV). PCs were stored for 7 days. RESULTS: There were observed increased expression of CD62 and CD63, elevated activity of LDH and lower concentration of glucose in PCs pathogen inactivated on day 1 compare to the control group. PCs pathogen inactivated on day 5 showed decreased expression of CD62 and CD63 compare to the control group. There were no significant differences in platelet number, pH, lactate concentration, hypotonic shock response and release of platelet derived microparticles in both groups of pathogen inactivated PCs. CONCLUSIONS: Time of storage of PCs before pathogen inactivation has no significant impact on PCs quality. Pathogen inactivation procedure performed just after having received request for PCs is more cost effective than the routine pathogen inactivation in all PCs before storage.

Treatment of recalcitrant ulcers with allogeneic platelet gel from pooled platelets in aged hypomobile patients.

We evaluated growth factor contents and clinical efficacy of allogeneic platelet gel (PG) prepared with standard blood banking procedures from routine platelet concentrates (PCs) obtained from buffy coats. The PGs were used to treat 11 hypomobile very elderly patients unable to undergo autologous blood processing and previously ineffectively treated with expensive advanced medications for 8-275 weeks. PGs were prepared by platelet activation with human thrombin or commercial batroxobin. Median and range growth factor contents (ng/mL) were: platelet derived growth factor (PDGF-AB/-BB) 112 (31-157) and 20 (3.8-34); transforming growth factor (TGF-ß1/-ß2) 214 (48-289) and 0.087 (0.03-0.28); basic-fibroblast growth factor (b-FGF) 0.03 (0.006-0.214); vascular endothelial growth factor (VEGF) 1.15 (0.18-2.46); epidermal growth factor (EGF) 4.50 (0.87-6.64); insulin-like growth factor (IGF-l) 116 (72-156). In the clinical study, 222 PGs were used within 2 h of activation to treat 14 chronic skin ulcers in the 11 patients. No improvement was seen in 3 patients with 24, 27 and 30 cm(3) ulcers who could be treated for no more than 4, 7 and 8 weeks due to progressively worsening clinical conditions, while 11 ulcers with 3.2 cm(3) median size (range 0.2-3.6) in the remaining 8 patients showed 91 ± 14 % reduction after a median of 12 weeks (range 1-20). Cost of PG treatment (19,976 euro) amounted to about 10% of the ineffective advanced medication hospital reimbursement fees (191,236 euro). This study supports efficacy and feasibility of allogeneic PG to treat recalcitrant ulcers in very elderly hypomobile patients for whom autologous blood processing may be difficult.

Acute plateletpheresis and aprotinin reduces the need for blood transfusion following Ross operation.

The effect of acute intraoperative plateletpheresis (25% platelet yield) in combination with intraoperative low-dose aprotinin (2 million units) on blood conservation was investigated in 18 young adult patients undergoing elective Ross operation. The results were compared with a group of 19 similar patients without plateletpheresis (control group). The hematological and coagulation parameters at admission and discharge were statistically similar in both groups. The total blood product transfusion requirements were significantly reduced in the plateletpheresis group compared with the control group (3.2 units and 5.1 units, respectively, P=0.036). The total blood donor exposure was also reduced significantly in the plateletpheresis group compared with the control group (3.2 and 6.9 donors/patient, respectively, P<0.001). The direct costs for the hospital for the plateletpheresis procedure, including costs for all blood products, were similar to those for blood products alone in the control group. In summary, acute plateletpheresis in combination with low-dose aprotinin significantly reduces the blood product transfusions and blood donor exposures following the Ross operation; the treatment is cost-effective.

Use of random versus apheresis platelet concentrates.

The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the "platelet rich plasma" or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC-PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC-RPC retain much more their in vitro functions than PRP-RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between "modern" RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.

Evaluation of concurrent collection of in-line filtered platelets and packed red blood cells by multicomponent apheresis with three last-generation apparatuses.

BACKGROUND AND OBJECTIVES: Multicomponent apheresis enables the collection and procession of different blood products in a single donation. Different apparatuses vary in terms of principle and efficiency. Knowledge of them is essential to analyse cost effectiveness. MATERIALS AND METHODS: A total of 30 donors, well matched for baseline parameters, were randomly assigned to the concurrent collection of red blood cells (RBCs) and platelets (PLTs) with the Baxter Amicus (AM), the Haemonetics MCS plus (MCS+), and the Gambro Trima Accel (TA). The procedures were prospectively evaluated, focusing on yield, time, efficiency, citrate donor load and in vitro quality. RESULTS: PLT yield (x 10(11)/unit; mean +/- standard deviation) was 3.09 +/- 0.34 (AM), 2.53 +/- 0.35 (MCS+), 2.51 +/- 0.32 (TA). Absolute RBC mass (ml/unit; mean +/- standard deviation) was 177.4 +/- 2.7 (AM), 161.5 +/- 0.7 (MCS+), and 163.7 +/- 5.4 (TA). The programmed RBC collection target of 160-180 ml was reached by all instruments, whereas the programmed PLT yield of 3.0 x 10(11) was met satisfactorily by AM only. All units contained < 1 x 10(6) WBCs. In vitro RBC quality was equivalent among the systems. No significant differences were noted with collection efficiency, processed whole blood or citrate donor load. Owing to high collection and draw rates, the TA was the fastest of all the systems. The MCS+ had the longest donation/needle time and the highest PLT activation, but compensated with significantly lower draw and citrate infusion rates. The overall processing time was longest with the AM, as a result of manual procedures from donor disconnection to the final products. CONCLUSIONS: Multicomponent apheresis was performed safely and efficiently with all three instruments. There was no 'magic apparatus' as each system combined advantages and pitfalls for the diverse parameters evaluated.

Donor selection criteria to maximize double platelet products (DPP) by platelet apheresis.

Variant Creutzfeldt-Jakob disease brought us to perform a study to diminish donor exposure from transfusion of platelet concentrates. The current study aimed to develop donor selection criteria that maximize the likelihood of deriving single donor platelets and producing double platelet products (DPP). Donors were recruited among plasmapheresis donors and among other donors when the selected donors did not show up. Donor precount and body weight and haematocrit were examined as determinants of higher split-rates combined with procedure time. When the criterion was set on 225; 82% of the procedures (n=717) with a precount of >225 yielded DPP compared to 54% of the procedures with a precount <225 (p<.01). Body weight >65 kg gave good results in split-rate. Procedure time showed an inverse correlation with the highest correlating precount (r=-.14; p<.001). Eighty one percent of the donors reported a willingness to donate at least seven times a year and 75% accepted the mean procedure time. This confirmed logistical feasibility of the conversion to AP-PC although profits would be reduce 13% compared to platelets from pooled buffy coats.

Blood collection and transfusion in the United States in 1999.

BACKGROUND: Collection, processing, and transfusion of blood and blood components in the US in 1999 were measured and compared with prior years. STUDY DESIGN AND METHODS: Questionnaires were completed by 2040 blood centers and hospitals. Statistical procedures were used to verify the representativeness of the sample and to estimate national totals. RESULTS: The total US blood supply in 1999 was 13,876,000 units (before testing), 10.1 percent greater than in 1997. It included 13,109,000 allogeneic units, 651,000 autologous units, and 116,000 red cell (RBC) units collected by apheresis. Transfusion of whole blood and RBCs increased by 7.6 percent to 12,389,000 units. Platelet (PLT) transfusions totaled 9,052,000 PLT concentrate equivalent units, of which 66.5 percent were PLTs from apheresis. In comparison with 1997, the total number of PLT units transfused was unchanged, whereas single-donor PLT units transfused increased by 6.7 percent and the transfusion of PLTs from whole blood (PLT concentrates) declined by 10.6 percent (a difference of approximately 400,000 units in each case). CONCLUSIONS: The margin between transfusion demand and the total allogeneic supply in 1999 was 1,203,000 units, 9.1 percent of the supply. By comparison, the margin in 1997 was 7.2 percent, whereas in 1989 it was 13.8 percent. Similarly, the rate of blood collection in 1999 per 1000 population was 11.9 percent higher than the 1997 rate. During the same period, however, the rate of transfusion per 1000 population increased by 5.8 percent. Risk in the future lies primarily in the increasing demand for RBCs and further shrinkage of the supply-and-demand margin.

Economic impact of donor platelet count and platelet yield in apheresis products: relevance for emerging issues in platelet transfusion therapy.

INTRODUCTION: We analyzed donor platelet counts and platelet product yields in 708 consecutive platelet aphereses in our program in order to define the importance of this relationship for emerging issues in platelet transfusion therapy. METHODS: Aphereses performed on the Spectra 3.6 (COBE, Lakewood. Colo.) the CS-3000 Plus (Fenwall-Baxter, Deerfield, Ill.) were analyzed. RESULTS: Mean platelet count was 237+/-49x10(3)/mm3 (mean +/- SD), and mean yield was 4.24+/-1. 09x10(11) platelets. Eigthy-five (12%) procedures generated less that 3x10(11) platelets. Only thirty-eight (5.4%) procedures yielded >/=6x10(11) platelets, so that 'split products' could be obtained. Platelet yields were primarily related to the biologic contribution (baseline platelet count) of the donor. Procedure parameters selected for harvest, and the efficiency of the device also had a significant, but less important role in determining the final platelet yield. An increase in mean donor platelet count achieved with Mpl ligand therapy from 240,000 to 320,000/mm3 would reduce the cost from USD 378 to 267 for each apheresis product, since the fraction of split products would exceed 50% of apheresis procedures. CONCLUSION: Increasing the donor platelet count would have a significant economic impact on platelet apheresis programs, as well as important clinical consequences for the role of platelet apheresis products in future transfusion strategies.

Progress of quality-associated costing: extension to platelet transfusion practice and the manufacturing scope for plasma proteins.

Realistic estimates about the potential misallocation of health service resources, in relation to the cost-beneficial use of blood products, is enabled by tracing manufacturing costs, through product specification elements to corresponding post-transfusion outcomes. This quality-associated costing (QAC) philosophy is completed in this article by understanding the issues that surround the manufacture of platelets, and by its comparison with the generally used but arbitrary methods for blood product costing. Without QAC, cost-beneficial platelet therapy will not be realized, due to an estimated Western underfunding of approximately one quarter of a billion pounds per annum by arbitrary methods. A reciprocal consequence of such platelet QAC is a significant reduction in the currently perceived cost of source plasma. Western estimates, based upon this, demonstrate that the not-for-profit fractionation of source plasma into purified proteins is probably underfunded by approximately one fifth of a billion pounds per annum through the use of arbitrary costing methods.

Cost effectiveness of quality assurance in plateletpheresis.

BACKGROUND AND OBJECTIVES: A quality assurance system (QAS) is part of modern blood banking facilities. Quality control of single donor platelet (SDP) concentrates includes the determination of the platelet (PLT) yield and the white blood cell (WBC) contamination. Improvements in modern apheresis technology allow the collection of high PLT yields and leukoreduced products. Double dose SDPs can be split and WBC-reduced products may be labelled as leukodepleted thereby reducing costs. MATERIAL AND METHODS: 3309 SDPs obtained with the Amicus, AS 104, AS.TEC 204 and MCS + blood cell separators were retrospectively analysed for their PLT yield. SDPs with > or = 4.0 x 10(11) PLTs were considered as double dose SDPs and split. WBCs were determined microscopically in 170 SDPs. SDPs with a leukocyte content < 1.0 x 10(6) were labelled as leukodepleted and no further WBC filtration was recommended. RESULTS: PLT yield was statistically higher in SDPs from the Amicus device, 84.8% of these products could be split. Double dose concentrates were collected in 22.7% with the MCS + machine and in 4.8% with the AS 104/AS.TEC 204 blood cell separators. The savings for disposables was $150,041 and for infectious disease testing $75,766. After the subtraction of the costs for PLT determinations in all SDPs $215,880 could be saved. WBC contamination was statistically lowest in in-line filtered SDPs from the MCS + device (median 0.29 x 10(5), range 0.22-9.96 x 10(5)) and all of these products were considered as fulfilling the criterion of leukodepeletion so that we were able to save $17,135 for bedside filters. Median WBC content was 0.75 x 10(5) (range 0.35-22.5 x 10(5)) in SDPs from the Amicus and 0.9 x 10(5) (range 0.27-99.8 x 10(5)) in SDPs from the AS 104/AS.TEC 204 devices, respectively. CONCLUSION: Blood cell separators of the newest generation allow the collection of leukodepleted double dose SDPs. An intensified QAS in plateletpheresis allows the decision whether a product can be split and/or released as leukodepleted. By this means we were able to save a total of $233,015 per year.

Apheresis platelets: emerging issues related to donor platelet count, apheresis platelet yield, and platelet transfusion dose.

Emerging issues in stimulating apheresis platelet donors with platelet growth factors, the relative costs of apheresis and random donor platelet concentrates, optimal platelet transfusion dose, and leucoreduction of platelet products have caused renewed debate regarding apheresis products vs. random, pooled concentrates. The future role of apheresis products in platelet transfusion therapy will in large part be determined by costs, which are increasingly recognized to be influenced by donor platelet count, apheresis yield, and platelet transfusion dose.

Safety and cost effectiveness of a 10 x 10(9)/L trigger for prophylactic platelet transfusions compared with the traditional 20 x 10(9)/L trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia.

In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 x 10(9)/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 x 10(9)/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 x 10(9)/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.