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Jan 30, 2007 - The aim of this study was to analyze the impact of various donor and machine parameters on PLT yield in 127. PLT apheresis procedures, to ...
Journal of Clinical Apheresis 22:5–9 (2007)

Factors Affecting Platelet Yield and Their Impact on the Platelet Increment of Patients Receiving Single Donor PLT Transfusion A. Aboul Enein,1 E. A. Hussein,1* S. El Shafie,1 and M. Hallouda2 1

2

Department of Hematology, Cairo University, Cairo, Egypt Department of Hematology, Thyodor Bilharz Research Institution, Cairo, Egypt

The aim of this study was to analyze the impact of various donor and machine parameters on PLT yield in 127 PLT apheresis procedures, to optimize PLT yield achieving clinical and economic advantages. One hundred and twenty-seven apheresis procedures were analyzed. Age, gender, volume processed, Hb, and PLT precounts were included as donor predicting variables. AC infusion rate, processing time, and plasma volume collected with PLTs were assessed as machine parameters. We evaluated the post-transfusion effectiveness in 23 patients with thrombocytopenia, studying the effect of PLT dose, ABO group, and PLT storage time. Females gave higher yields, compared to males, P < 0.01. PLT yield correlated positively with PLT precount (r ¼ 0.512), and TBV (r ¼ 0.404), and negatively with donor preapheresis Hb (r ¼ 0.306). Processing time and AC infusion rate had a positive impact on PLT yield. Post-apheresis decrease in PLT count was 53.6  26.3 3 1011. Donors with Hb  12 g/dl, donated safely. Most of the complications were citrate related (13.4% of all procedures). PLT increments in transfused patients correlated positively with the number of units transfused (r ¼ 0.41), and negatively with PLT storage days (r ¼ 0.342). PLT increments in patients receiving ABO-compatible PLTs were 75% higher, compared to the increments in patients receiving incompatible PLTs. PLT count and volume processed were the main predictors of PLT yield. Increasing the processing time, the AC infusion rate, or the volume of plasma obtained with PLTs can increase PLT yields. High PLT dose, short storage time, as well as ABO compatC 2007 Wiley-Liss, Inc. ibility should be considered during PLT transfusion. J. Clin. Apheresis. 22:5–9, 2007 V Key words: PLT apheresis; donor CBC; blood group; PLT dose-storage days

INTRODUCTION

Platelet transfusion is one of the most important forms of support therapy for thrombocytopenic patients. Automated platelet (PLT) apheresis has the advantage of lowering the risk of increased donor exposure per transfusion, preventing alloimmunization, PLT refractoriness, and transmission of infectious diseases.

AIM OF STUDY

The aim of the present study was to assess the effect of various donor factors as well as machine-related parameters on PLT yield and their effect on donors, using COBE Spectra version 7.0. Age, gender, volume processed, hemoglobin (Hb), hematocrit (Hct) and (PLT) precounts were included as donor-predicting variables. Anticoagulant (AC) infusion rate, processing time as well as plasma volume collected during the procedure were assessed as machine-related parameters. We also evaluated the post-transfusion effectiveness in 23 patients with thrombocytopenia, by estimating the posttransfusion PLT increments. They were also evaluated C 2007 Wiley-Liss, Inc. V

for the effect of PLT dose, ABO group, and PLT storage time. MATERIALS AND METHODS Apheresis Donors

Our retrospective study involved data from our hospital apheresis program at Kasr Elainy Cairo University Hospital. All donors met AABB eligibility criteria for donation. Family members and friends of the patients were motivated to donate especially during a period when PLT transfusions were needed. Pre-scheduling apheresis donors was the most effective mode of operaThe work was done in the blood bank of Kasr Elainy Hospitals, Cairo University, Egypt. *Correspondence to: Eiman Abdel wahab Hussein: 5857341, 4 Abdel Nasser St., Elharam Giza, Egypt. E-mail: eimy_20002000@ yahoo.com Received 1 July 2006; Accepted 16 November 2006 Published online 30 January 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jca.20116

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Enein et al.

TABLE I. Machine Variables Variable

Mean

SD

Range

AC infusion rate in ml/min/liter total blood volume (TBV) Procedure time in minutes Plasma collected in ml Volume processed in ml without anticoagulant

0.97

0.06

0.8–1.1

65.5 276 4,946

14 70 886

40–100 00–300 2,992–8,222

tion. The study included 127 normal adult Egyptians (80 males and 47 females). Their mean age was 35.3  9.2 (18–55) years. Donor data included age, gender, volume processed (calculated by the machine using donor gender, height, and weight), and donor CBC including Hb , Hct, and PLT count. Donors were observed for major and minor adverse events (AEs), including: 1. Symptoms related to citrate toxicity (weakness, tingling, numbness, chills, nausea, vomiting, and abdominal pain). They were alleviated by slowing down AC infusion rate and calcium was given orally when symptoms were not relieved. 2. Hypotension. The machine was stopped for a while and donors were placed in trendelenburg position. 3. Venous access–related (pain and hematoma).

TABLE II. Changes in the Donor Peripheral Blood Counts PostApheresis Variable

Pre-pheresis

Post-pheresis

% Reduction

PLTs 3 1,000/ll Hb (g/dl) Hct (%)

254.2  52.4 14.5  1.4 47.7  5.1

200.6  45.8 13.24  1.4 43.8  5.09

20.91  9.5 8.74  4.5 8.13  3.06

Pre and post-apheresis (after 10 ml of blood was discarded from the attached line) blood values were determined using a calibrated cell counter (Cobus Micros, Roche, Montpellier, France) and Sysmyx K-4500 (TOA Electronics, Koebe, Japan). Single-donor platelets (SDP) yield given by the machine at the end of the procedure were compared with lab measurements of the products [1]. SDP samples were diluted 1:5 and PLT concentration was measured, multiplying it by the volume. Leuko-reduction effectiveness was measured once a week for 20% of the products studied. A large volume hemocytometer chamber (Nageotte chamber) was used and an aliquot was removed from the collection bag. The sample was stained with crystal violet, loaded into the chamber ,and allowed to rest for 20 min in a humidified environment. Leukocytes were counted and corrected for the sample dilution. Machine-related variables including AC infusion rate, processing time as well as the volume of plasma obtained were analyzed. (Table I). Assessment of Recipients

Apheresis Protocol

COBE Spectra machine Turbo 7.0 LRS (Gambro BCT Lakewood, CO) is an apheresis machine designed to perform different types of procedures. In our centre, it is used to obtain leuko-reduced PLTs, and plasma from healthy volunteer donors as well as to perform therapeutic plasma exchange (TPE). It is also used for stem cell separation procedures. In our program, double needle procedures were generally performed for all donors; plasma was obtained if the last donation was more than 8 weeks prior. ACD-A was used as anticoagulant and 0.9% saline (250–300 ml) was infused to the donor after the procedure. The blood draw rate was initially based on donors’ total blood volume (TBV) and on AC rate of 0.8 ml/min/ liter TBV. Draw rates were increased to a maximum of 1.1 ml/min/liter TBV if tolerated by the donor. The target end points were set at 3–3.5 3 1011 for single-dose products or 5–6.5 3 1011 for double-dose products in up to 100 min processing time. Several different problems will trigger an alarm to count the product for PLTs and WBCs checking leukoreduction effectiveness and the quality of the apheresis product. Journal of Clinical Apheresis DOI 10.1002/jca

Thirty-three transfusions were evaluated in 23 patients, 9 males (39.1%), 12 females (52.2%), and 2 children (8.7%). Their mean age was 29.3  6.6 (3–45) years. Patients were treated for aplastic anemia (69.7%), acute leukemia (12.1%), lymphoma (6.1%), ITP (idiopathic thrombocytopenic purpura) (6.1%), renal failure (3%), and metastasis (3%). Recipients were assessed for clinical diagnosis, history of previous transfusion, ABO group, and PLT counts. Peripheral blood samples were drawn from thrombocytopenic patients (12–18 hours) after PLT transfusion and their platelet counts were assessed. The PLT increment was estimated (the difference between pre- and post-transfusion counts). Recipients were evaluated for the effect of PLT dose, PLT ABO group, and PLT storage time on their platelet counts. Statistical Analysis

Statistical analysis of this study was performed using SPSS (Statistical product and service solutions) version 11 computer system, which is a software online program for managing and analyzing scientific data (web site: SPSS.com). Analysis included descriptive statistics, frequency distribution, mean, and SD calculation.

Effect of Single Donor PLT on PLT Increments

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TABLE III. Male and Female Data

Gender

Median pre-procedure peripheral PLT count 31,000/ll

Median PLT yield 31011

Median processing time (min)

Median AC infusion rate in ml/min/liter total blood volume

Adverse reactions (%)

Male Female

230 244

5 6.5

75 60

1 0.8

22 1.6

Comparative studies were performed using a paired test. Potential association between parameters was assessed by performing a correction matrix study.

RESULTS Analysis of Donor Population

Changes in the donor CBC profile pre- and postapheresis are summarized in Table II. The PLT yield mean was 5.15  1.88 (1.5–9.9) 31011 in a mean time of 65.5  14 min. PLT yield correlated positively with PLT precount (r ¼ 0.512), processing time (r ¼ 0.522), volume processed (r ¼ 0.404), percent decrease in PLT count (r ¼ 0.480), AC infusion rate (r ¼ 0.345), and the volume of plasma obtained (r ¼ 0.365). Doses as high as 9–9.9 3 1011 were obtained from 6 donors (4.7%) over a processing time of 60–100 min (mean of 83.66  10.3). In donors with preapheresis PLT counts between 150,000 and 180,000 (12 cases: 9.4%), the postapheresis count was below 100,000 in 2 donors: 1.6%. The percent drop in PLT count mean was 20.9  9.5%. It was positively correlating with donation age (r ¼ 0.346), platelet yield (r ¼ 0.480), and donation time (r ¼ 0.409). PLT yield correlated negatively with donor preapheresis Hb (r ¼ 0.306). Donors with preapheresis Hb of 12–12.5 g/dl (16 cases: 12.6%), did not suffer any complications. No major adverse events occurred during or after the procedure. In sum, 23.6% of donations were associated with minor self-limiting side effects. None of these AEs prevented the completion of sessions. Citrate toxicity (minor paresthesia-like hypocalcemic symptoms), 13.4%; venous access problem, 6.3%; machine dysfunctions, 2.4%; and mild hypotension, 1.6%. The run was terminated before the planned time in 3.5% of all procedures, with yields used for premature and small children. Donors who developed citrate toxicity had a significantly higher volume processed, higher recorded mean time of donation, and higher AC infusion rate (median 1 ml/min/liter TBV). It is usually the price paid for higher yields due to higher flow rates. Statistical comparison between yields in males and females showed females giving higher yields (P < 0.01) in a significantly shorter procedure time (P < 0.05).

TABLE IV. Platelet Yield Characteristics Number of donors (%)

PLT yield (31011) 3.5–5 >5–6.5 >6.5

13 20 18 53 23

(10.2) (15.8) (14.2) (41.7) (18.1)

Mean time (minutes) 54.6 57.8 56.8 70.2 74.5

    

5.6 9.6 14.6 10.2 8.9

The median AC infusion rate was 0.8 and 1 ml/min/ liter TBV for females and males, respectively. Two female donors had mild hypotension (1.6% of all donors). No citrate-related AES occurred in females. Male and female data are tabulated in Table III. PLT Yield Characteristics

Ninety-seven percent of products tested for leukoreduction were efficiently leuko-reduced and contained fewer than 5 3 106 WBCs. Leuko-reduction was not affected by AC infusion rate. Higher WBCs contents were observed in sessions that were discontinued several times due to access or machine problems (spillover). PLT yield characteristics are tabulated in Table IV. Evaluation of Patients

The mean count of PLTs transfused was 7.09  2.4 3 1011, with a storage time of 2.2  1.01 days. The PLT transfusions were compatible in 15 transfusions (45.5%) and incompatible in 18 transfusions (54.5%). All PLT were automatically leuko-depleted using COBE version 7.0 turbo LRS. PLTs were irradiated if needed before transfusion. Their mean pre- and posttransfusion PLT count 3 1,000/ll was 16.24  17.22 (000–91) and 36.60  44.27 (5–130), respectively. The Dose Response Effect of PLT Transfusion

Post-transfusion increment increased significantly with the number of units transfused (P < 0.05) and the dose response effect was more evident in the 2 children who were included in our study. Evaluation of the Blood Group Effect:

Studying the effect of blood group on PLT increments, the median PLT increment in patients receiving ABO-compatible PLTs was 75% higher compared to the increments in patients receiving incompatible PLTs. Journal of Clinical Apheresis DOI 10.1002/jca

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Enein et al.

Evaluation of the Effect of Days of Storage of PLTs

PLT increment showed negative correlation with storage days (r ¼ 0.342).

DISCUSSION

In our study, we investigated the effect of various parameters as utilized in the COBE Spectra version 7.0 during PLT apheresis to optimize the collection efficiency. We also evaluated the effect of PLT apheresis on donors, studying their blood profile changes and the adverse effects that occurred during the procedure. Our work focused on separation as well as donorrelated features, for better clinical and economic advantages. With respect to separation features, we found that increasing the processing time, the draw rate, or the volume of plasma obtained with PLTs, can have a positive impact on PLT yield. On evaluation of donorrelated data, we found that PLT precount and volume processed were the main predictors of PLT yield. The higher AC infusion rates and plasma volumes both allowed fast pump rates, hence more blood passed through the machine (volume processed) as was the effect of longer procedure times. The higher PLT counts meant more PLTs were available for collection. Donors with lower Hb had better yields, which could be attributed to the increased volume of their processed plasma. These data were consistent with data obtained in another study, when the authors found that both the donor PLT count and Hb concentration influenced PLT yield: a higher PLT count corresponded to higher yields, while Hb showed an inverse relationship [2]. On evaluating the effect of PLT apheresis on donor complete blood counts, it was found that it varied widely among various donors. The mean decrease in PLT count was 53.6  26.3 3 1,000/ll. PLT apheresis was unlikely to produce clinically significant thrombocytopenia, as PLTs are most probably released from the spleenic stores during donation. Also, the rinse cycle in the COBE machine, which occurs at the end of the run, enables PLTs remaining in the set to be returned to the donor [3]. To consider donors eligible for donation, the standard PLT count was considered 200 3 1,000/ll. However, we were able to obtain PLT yields as high as 5–6 3 1011 from donors with PLT counts between (150–180 3 1,000) by extending the processing time for 15–20 min, or even less in donors with increased TBV. Hb loss during this procedure was minimal (1.3  0.7 g/dl), and donors with Hb of 12 g/dl, donated safely. Similar results were observed in another recent study [3]. Compared to males, females gave higher yields in a significantly shorter time. This could be attributed to the increased volume of their processed plasma due to Journal of Clinical Apheresis DOI 10.1002/jca

their lower Hb. Females also experienced, fewer AEs, probably due to the slower AC infusion rate. The incidence of adverse events in our study was 23.6%, all of them were minor and self-limiting, demonstrating that donating on COBE is relatively safe. Most of the complications were citrate related (13.4% of all procedures). Donors who developed citrate toxicity had a significantly higher volume processed, higher recorded mean time of donation, and higher AC infusion rate. It is usually the price paid for higher yields. However, none of them needed calcium injections, or further emergency room evaluation. Although the incidence of hypocalcaemia symptoms in our study was 13.4%, a lower incidence has been reported previously 0.3% [4], 0.1% [5], and 0.59% [6]. The low incidence of hypotension was probably due to saline infusion at the end of the run. Early recommendations on prophylactic transfusions of thrombocytopenic patients involved a standard PLT dose of about 0.5 3 1011/10 kg body weight. Given the lack of data supporting this dose [7], we prospectively studied the dose response to PLT transfusion. When we evaluated the dose response effect 12–18 h after PLT transfusion, the post-transfusion increment increased significantly with the number of PLTs transfused (P < 0.05). The dose response effect was more evident in the 2 children who were included in our study, probably due to their small surface area. Similar results were observed when 4 doses of PLTs in patients with AML were reviewed by eliminating all factors that could affect transfusion efficacy other than the number of PLTs transfused. Platelets were fresh, ABO compatible, and administered in similar clinical conditions. Beneficial effects of higher PLT doses were observed, not only in terms of higher post-transfusion counts but also in longer intervals between transfusions [7]. Our results were also similar to those obtained in a retrospective study [8]. Having demonstrated the dose effect of PLT transfusion may be helpful to determine an optimal dose of PLTs, Norfolk et al. [7] suggested the optimal dose may be 1.5 U/10 kg body weight. Morrison [9] suggested that 5 U of PLTs were needed for an adult. The NIH consensus suggested 1 U/10 kg body weight per transfusion [10] and the British Committee for Standards in Hematology [11] proposed a formula taking into account the desired PLT increment, the patient’s blood volume, and a recovery factor resulting in a recommended PLT dose of approximately 3 3 1011 plt for adults. When we evaluated the effect of PLT storage days on the increment, we observed that PLT increment was negatively correlating with storage days (r ¼ 0.342). Recently, a criterion based on paired comparison with radiolabelled recovery and survival of fresh PLTs has been proposed that resulted in a recovery of 74.7  12.3% and a survival time of 7.5  1.1 days when

Effect of Single Donor PLT on PLT Increments

PLTs infused were less than 20 hours, but when they were infused on the fifth day, it resulted in a recovery of 58.2  12.0% and a survival time of 6.9  1.4 days [12], suggesting that a high value should be set on a brief storage time. Studying the effect of blood group on PLT increments, the median increment in patients receiving ABO-compatible PLTs was higher compared to the increments in patients receiving incompatible PLTs. Apheresis PLTs provide 250–400 ml of plasma from a single donor. This can magnify the effect of a high titer isoagglutinin in a donor’s plasma that might lead to hemolytic transfusion reaction [13]. There may be a cumulative effect of repeat out-of-group PLT transfusions over a short time even though each product had a low titer. Many authorities recommend tracking the amount of out-of-group plasma received each day [14]. Josephson and his colleagues [15] advocate the use of plasma removal especially if the volume of isoagglutinin is high. However, most doctors would demand the available PLTs even if they were out-of-group in emergency situations. Thus, PLT transfusion efficacy in recipients is influenced by a variety of factors besides alloimmunization and the patient’s clinical condition. These factors include: PLT dose, ABO compatibility, pre-transfusion storage time, and leukocyte contamination [16]. With respect to PLT dose, the SDP product should be transfused entirely and not split. That would not only reduce the need for frequent transfusion support in thrombocytopenic patients but also reduce donor exposure preventing alloimmunization and refractoriness. In our work, we were able to routinely obtain doses as high as 6 3 1011; we were even able to collect doses as high as 9–9.5 3 1011 from donors with high PLT counts and increased TBV. Furthermore, initial studies suggest that a very high PLT count can be obtained after administration of thrombopoietin to PLT donors [17]. Increased donor PLT count would have a significant economic impact on a PLT apheresis program. In the light of our data, it seems possible to increase PLT yield by recruiting donors with increased PLT count and TBV. We could optimize the collection efficiency by altering machine parameters, and increasing the processing time, AC infusion rate, or the volume of plasma obtained with PLTs. This process is completely safe as none of the donors experienced any significant drop in their Hb or PLT count, or suffered any serious adverse events. Females were better donors, suggesting that male donors should not always be our first priority. In order to optimize the efficacy of PLT transfusion, it is important to take into account the brief storage time, high PLT dose, ABO compatibility, as well as

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low leukocyte contamination, which is offered nowadays by new apheresis machine technology. ACKNOWLEDGMENTS

The authors thank the apheresis staff for their technical assistance. REFERENCES 1. Burgstaler EA, Pineda AA. Plateletapheresis: instrumentation validation. Trans Sci 1999;21:153–161. 2. Guerrero-Rivera S, Gutierrez-Espindola G, Talavera JO, MeillonGarcia LA, Pedraza-Echevarria M, Pizzutto-Chavez J. Hemoglobin and platelet count effect on platelet yields in plateletpheresis. Arch Med Res 2003;34:120–123. 3. Bueno JL, Barea L, Garcia F, Castro E. A comparison of platelet collections from two apheresis devices. Transfusion 2004; 44:119–124. 4. Depotis GJ, Goodnough LT, Dynis M, Baorto D, Spitznagel E. Adverse events in Platelet apheresis donors. A multivariate analysis in a hospital based program. Vox Sang 1999;7:24–32. 5. Robinson EA. Donor and therapeutic apheresis. In: Tawes RL, editor. Autotransfusion: therapeutic principles and trends. Detroit: Gregory Appleton. 1997. p 12–23. 6. Silvestro GD, Marson P, Russo GE, Vicarioto M, Donadel C. National survey of apheresis activity in Italy. Transfus Apheresis Sci 2004; February:61–71. 7. Norfolk F, Bierling P, Roudot-Thoraval F, Le Coeur FF, Rieux C, Lavaux A, Kuentz M, Duedari N. Platelet transfusion: a dose response study. Blood 1998;92:1448–1453. 8. Klumpp TR, Herman JH, Caughan JP, Russo RR, Christman RA, Goldberg SL, Ackerman SJ, Bleeker GC, Mangan KF. Transfusion dose: a prospective, randomized, double blind trial. Transfusion 2000;40:383–384. 9. Morrison FS. Platelet transfusion: A brief review of practical aspects. Vox Sang 1966;2:656. 10. The National Institute of Health Consensus Conference: Platelet transfusion therapy. Transfus Med Rev 1987;3:195. 11. Murphy MF, Brozovic B, Murphy W, Ouwehand W, Waters AH, The British Committee For Standards in Haematology: guidelines for platelet transfusions. Transfus Med 1992;2:311. 12. Aubuchon JP, Herschel L, Roger J, Murphy S. Preliminary validation of a new standard of efficacy for stored platelets. Transfusion 2004;44:36–41. 13. Larsson LG, Welsh VJ, Ladd DJ. Acute intravascular hemolysis secondary to out of group platelet transfusion. Transfusion 2000;40:902–906. 14. Herman JH. Apheresis platelet transfusion: does ABO matter. Transfusion 2004;44:802–804. 15. Josephson CD, Mullis NC, Van Demark C, Hillyer CD. Significant numbers of apheresis-derived group O platelet units have high titer antiA/AB: implications for transfusion policy. Transfusion 2004;44:805–808. 16. Heal JM, Blumberg N. Optimizing platelet transfusion therapy. Blood 2004;18:149–165. 17. Goodnough LT, Kuter DJ, McCullough J, Slichter SJ, Dipersio J, Romo J, Peterson R, Smith KJ, Raife T, Tomita D, Armstrong S. Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin. Blood 2001;98:1346.

Journal of Clinical Apheresis DOI 10.1002/jca