Donor Platelet Count Research Articles

The use of PEG‐rHuMGDF in platelet apheresis

Platelet transfusions are increasingly being used to treat thrombocytopenic conditions ranging from aplastic anemia to that caused by cancer chemotherapy. Although historically whole-blood transfusions were the primary source of platelets for transfusion, random donor platelet concentrates and single-donor apheresis platelets are currently the only products used. The use of these products in the United States varies widely for different medical conditions; for example, surgical patients receive random donor platelet concentrates much more commonly than single-donor apheresis products, while the opposite is true for hematology/oncology patients. The past decade has seen a great change in the type of platelet product prescribed. Whereas random donor platelet concentrates were mostly used in the past, over 60% of the platelets transfused are now obtained from donors by apheresis. A crucial variable in the ability to collect platelets by apheresis is the donor platelet count. With the recent availability of thrombopoietin, there has been considerable interest in using this hematopoietic growth factor to stimulate platelet production in donors. Preliminary studies with the administration to platelet donors of one of the thrombopoietic growth factors, PEG-rHuMGDF, have demonstrated a marked increase in the apheresis yield and no side effects. The PEG-rHuMGDF-mobilized platelets were effective upon transfusion. Whether stimulation of platelet production in donors with thrombopoietic growth factors will become a widely accepted method will depend largely on the safety of this approach for the donor as well as on a number of lesser issues which concern the recipient and blood center.

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.

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

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

Changes in blood counts after the administration of granulocyte-colony-stimulating factor and the collection of peripheral blood stem cells from healthy donors.

After the collection of granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells from healthy donors, the donor platelet counts fall. However, the magnitude and duration of this decrease are not known. Sixty healthy people were given G-CSF (5, 7.5, or 10 micrograms/kg/day) for 5 days (Days 1-5), and 1 peripheral blood stem cell component was collected on Day 6. The platelet count, white cell count, absolute neutrophil count, hematocrit, and red cell count were measured before administration of G-CSF (Day 0), before collection of peripheral blood stem cells on Day 6, and on Days 8, 10, 13, 16, and 20. The platelet count fell from 261 +/- 47 x 10(9) cells per L on Day 0 to 159 +/- 30 x 10(9) cells per L on Day 8 (p < 0.0001) and reached its lowest level on Day 10 (146 +/- 30 x 10(9)/L; p < 0.001). Compared to Day 0 levels, the platelet count was lower on Day 13 (185 +/- 49 x 10(9)/L, p < 0.001), was the same on Day 16 (270 +/- 53 x 10(9)/L), and was greater on Day 20 (333 +/- 60 x 10(9)/L, p < 0.0001). The white cell count returned to pretreatment values on Day 13, and the absolute neutrophil count returned to pretreatment values on Day 10 (Day 0 white cell count = 6.05 +/- 1.59 x 10(9)/L and Day 0 absolute neutrophil count = 3.97 +/- 1.52 x 10(9)/L). On Day 20, both were less than pretreatment values (white cell count = 5.14 +/- 1.24 x 10(9)/L, p = 0.0007 and absolute neutrophil count = 3.20 +/- 1.24 x 10(9)/L, p = 0.0036). The red cell counts on Day 16 (4.52 +/- 0.41 x 10(12)/L) and Day 20 (4.42 +/- 0.39 x 10(12)/L) were less than Day 0 values (4.73 +/- 0.43 x 10(12)/L, p = 0.008 and p < 0.0001, respectively). The hematocrit on Day 20 (39.2 +/- 3.2%) was also less than that on Day 0 (41.2 +/- 4.8%; p = 0.01). The changes in these blood counts were not affected by the dose of the G-CSF. After stimulation with granulocyte-colony-stimulating factor and the collection or peripheral blood stem cells, the platelet counts in normal donors were decreased for at least 7 days (Days 6-13). Two weeks after collection of peripheral blood stem cells (Day 20), platelet production was increased, but the production of neutrophils and red cells was decreased. If two or more peripheral blood stem cell components are collected, then the platelet count should be measured after the second and subsequent collections. Further studies on the long-term effect of G-CSF on blood counts are needed.

Prolonged Bleeding Time of Chediak-Higashi Cats Corrected by Platelet Transfusion

Cats with the Chediak-Higashi syndrome (CHS) have a platelet storage pool deficiency (SPD). Ten CHS cats were transfused with a concentrate of 51Cr-labeled platelets prepared from normal donor cats. One hour after transfusion, the donor platelet count in CHS recipient cats was 40,000-60,000/microliters. Bleeding time before transfusion was 9.1 +/- 3.0 min. When donor platelet count in CHS cats was 50,000/microliters, bleeding time was 1.7 +/- 0.2 min. Bleeding time of normal cats was 1.4 +/- 0.3 min. Bleeding time increased to 3.3 +/- 0.2 min and to 5.3 +/- 0.2 min when the platelet count was 30,000/microliters, and 15,000/microliters, respectively. The close inverse relationship between bleeding time and number of donor platelets in CHS cats (r = -0.92), suggests that prolonged bleeding time is due to a platelet abnormality, that platelet transfusion can effectively correct prolonged bleeding time in an animal model of platelet SPD and that CHS cats may be an appropriate animal model to evaluate hemostatic capabilities of transfused platelets.

The effect of plateletpheresis on the Fenwal CS-3000 on donor platelet counts.

To evaluate the risk of significant plateletpheresis-induced thrombocytopenia in normal volunteer donors undergoing plateletpheresis less frequently than every 56 days and to help understand factors influencing platelet yield in these donors, pre- and postapheresis platelet counts (X 10(3)/microliter) and platelet yields were analyzed from 916 plateletpheresis procedures (Fenwal CS-3000) on 607 donors (405 men, 202 women). The mean preapheresis platelet count was 265 +/- 59 (SD) (range 155-650) (men 256 +/- 55 [170-444]; women 284 +/- 65 [155-650]; P less than .001, t-test). After an average platelet yield of 4.08 X 10(11), the mean postplatelet count was 185 +/- 46 (range 72-420) (men 184 +/- 42 [80-345]; women 194 +/- 52 [72-500]; P less than 0.1). The percent decrease in platelet count (mean 29.4 +/- 13, range -28.1-65.5) had positive correlations with platelet yield (P less than .01, r = 0.10), predonation platelet count (P less than .001, r = 0.29), and age (P less than .01, r = .10) and a negative correlation with weight (P less than .001, r = 0.18) Both the percent decrease and platelet yield were significantly higher in women than in men (P less than .001, t-test), and platelet yield was best predicted by preapheresis platelet count in both sexes (r = 0.65). The effects of plateletpheresis on donor platelet count thus vary widely among donors. Although a decrease of greater than 50% was not a rare event (5.9% of all procedures), in only three instances (0.3%) was the actual postapheresis platelet count below 100 (72, 94, 95). Thus, plateletpheresis in normal donors appears unlikely to produce clinically significant thrombocytopenia immediately after apheresis.

Safety of apheresis donation.

Platelet and granulocyte collections have been done for the past 15 years, and studies on the safety of these procedures have been carried out in many institutions in the USA and abroad. In general, no long-term harmful effects have been observed in donors who had undergone frequent cytapheresis. Significant decreases in donor platelet count were noted following repeated platelet apheresis. However, only a few donors became thrombocytopenic (platelet count less than 150,000/microliter). Interestingly enough, if the donor was allowed time to recover a normal platelet count, subsequent repeated platelet collection did not induce thrombocytopenia. Rebound of platelets has also been a common finding. Intensive granulocyte collections have not reduced the number of circulating granulocytes, nor has there been any report of leukopenia in donors who had undergone frequent leukocytapheresis. The limiting factor has been the need for hydroxyethyl starch as a sedimenting agent and corticosteroids to stimulate the granulocyte release from the marrow, which have known adverse effects of their own. No significant changes in plasma proteins and other biochemical and hematological parameters have been reported in cytapheresis donors. There is widely-held concern that because the collections of platelets and granulocytes are not selective to the exclusion of lymphocytes, the repeated cytapheresis may deplete the circulating lymphocytes with theoretical risk associated with long-term alterations of the immune response. In addition, if a significant number of red blood cells are removed, the frequent apheresis donations may render the donor anemic. Because of these theoretical risks, recommendations have been formulated in the USA in an attempt to ensure the safety of apheresis donors.

Comparison of plateletapheresis with two continuous‐flow cell separators using identical donors

Each of 20 donors underwent plateletapheresis on both the CS-3000 (Fenwal) and the 2997 (IBM) blood cell separators. The same operator performed both procedures and conducted all product studies for each donor. Platelet collection efficiency was significantly greater with the 2997 (81%) than the CS-3000 (60%) (p less than .0005). Both techniques provided high platelet yields that were not significantly different (2997: 6.1 X 10(11), CS-3000: 5.7 X 10(11)), permitting comparison of other variables without accounting for different yields. Significantly more leukocytes were present in products collected with the CS-3000 (0.46 X 10(9)) than the 2997 (0.09 X 10(9), p less than 0.0005). More acid-citrate-dextrose was infused during procedures with the 2997 (471 ml) than the CS-3000 (324 ml, p less than 0.0005); the donors' ionized calcium decreased significantly more during procedures with the 2997 (27.3%) than the CS-3000 (17.0%, p less than 0.0005). Hypocalcemic symptoms were more common during procedures with the 2997. Product volume was greater with the 2997 (414 ml) than the CS-3000 (237 ml, p less than 0.0005). All products contained less than 1 ml of red cells. Set-up time was significantly greater with the 2997 (37 minutes) than the CS-3000 (18 minutes, p less than 0.0005), but processing time was significantly less with the 2997 (90 minutes) than the CS-3000 (110 minutes, p less than 0.0005). There was no difference in the decrease in donor platelet count with procedures between the 2997 (27%) and the CS-3000 (26%).(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet collection using the IBM 2997 cell separator.

Platelets were collected using the dual-channel module on the IBM 2997 Blood Fraction Separator. We carried out 320 procedures to harvest platelets for therapeutic purposes and yielded 5.1 +/- 1.5 X 10(11) platelets (mean +/- SD). Infusion into previously unsensitized recipients with hypomegakaryocytic thrombocytopenia achieved increments at 1 hr of 19 +/- 7.3 X 10(9)/liter/m2 (mean +/- SD) and at 24 hr of 15 +/- 6.3 X 10(9)/liter/m2. The only consistent donor reaction was mild hypocalcaemia, easily corrected by calcium gluconate infusion. Changes in donor packed-cell volume and white cell count were not statistically altered (p greater than 0.05) but donor platelet counts fell from 216 +/- 43.1 X 10(9)/liter to 162.5 +2- 41.7 X 10(9)/liter (mean +/- SD) (p less than 0.01). Additional plateletphereses were carried out in seven normal volunteers, using the same technique, in order that the function of the harvested platelets could be studied. Following radiochromium labelling and reinfusion into the same donors, normal in vivo recoveries were obtained at 10 min (59.4 +/- 3.4%; mean +/- SD) and platelet mean life span was also normal (218 +/- 12 hr; mean +/- SD). Furthermore, in vitro platelet factor III availability and aggregation patterns of the harvested platelets did not differ from control values and their ultrastructural appearance was normal.

Description and use of the CS-3000 blood cell separator for single-donor platelet collection.

A new computer‐controlled seal less continuous flow blood cell separator has been developed to harvest platelets, plasma, or leukocytes and perform plasma exchange. One hundred seven platelet collection procedures were performed using an instrument prototype during developmental evaluation of a number of differently configured platelet collection chambers. An average of 3.6 (range 2.6‐5.5) × 1011 platelets was collected during a 90‐minute period (blood withdrawl rate, 32 ml/minute) with the best chamber. Only a small number of other cells, from 0.1 to 0.2 times 109 white blood cells and 0.7 to 1.0 times 109 red cells was collected with the platelets. Total procedure time averaged 115 to 120 minutes and included 5 minutes to install the blood processing pathway, 10 minutes to prime the system under computer control, 5 minutes to return donor erythrocytes at the completion of the procedure, and 5 minutes to remove the processing set and resuspend the platelets. The average donor platelet count declined 48 times103per μ (19%) by the completion of the procedure, and, with the exception of a decline in inorganic phosphorus from 3.4 to 2.5 mg per dl, no unexpected changes in serum chemistry levels were seen.Use of either of two larger separation chambers in a production version of the instrument permitted more rapid blood processing rates (≃45 ml/minute); an average of 4.2 (range 2.1–7.8) × 1011 platelets was collected in 90 minutes using a larger chamber designed for platelet separation (n = 164). Platelets could also be collected using the chamber designed for white blood cell collection by omitting the use of hydroxyethyl starch and by selecting the platelet collection computer program rather than the white cell collection program. Using that chamber, an average of 4.3 ± 1.8 times 1011 platelets was collected in 90 minutes (56% collection efficiency; n = 31). Leukocyte contamination of platelets was greater using the larger chambers. Infusion of autologous platelets labeled with 51Cr demonstrated a 70 percent average recovery and a mean survival of 9.1 days (n = 10). Seven nonalloimmunized thrombocytopenic patients were transfused with platelets collected using the prototype cell separator and an average of 86 percent of the expected number of platelets was present in the circulation 2 hours after transfusion with 63 percent of the cells remaining in the circulation at 24 hours. Template bleeding times were corrected in six of seven recipients following transfusion, and hemostasis was achieved in three bleeding recipients. Therapeutically useful numbers of functionally effective platelets can be collected using this blood processing instrument.

Frequent multiunit plateletpheresis from single donors: effects on donors' blood and the platelet yield.

Two thousand plateletpheresis procedures performed on 335 donors by either semicontinuous flow centrifu‐gation (Haemonetics Model 30) or a multiple bag technique were analyzed for effects on donors and the yield of platelets. The platelet yield was independent of collection method, number of prior donations and donor's hematocrit. It varied directly with the donors' platelet count and was significantly higher for women donating by semi‐continuous flow centrifugation. Even at the lowest platelet harvest, the number of platelets obtained was sufficient to meet federal standards for platelet collection procedures. Donor platelet counts decreased following the first multiunit plateletpheresis procedure. After the equivalent of continued alternate day platelet collections the count reached a mean low of 70 per cent as compared to the precollection count, occurring after six to eight donations. The yield was comparably reduced to a mean of 64 per cent. By the tenth donation platelet counts had returned to baseline values, apparently as a result of increased production by the marrow. Similarly, platelet yields returned to higher (i.e. normal) levels. Further donations did not cause platelet counts or yields to vary from normal values. Repeated daily plateletpheresis resulted in more variability in donor platelet counts. Since none of the donors was subjected to this procedure for more than nine consecutive days, marrow response could not be assessed. Comparing number of donations, donor platelet counts and subsequent yields, there was no difference between daily pheresis and an alternate day schedule. Donor hematocrits were not changed by these frequent collections and other side effects were not observed. This study indicates that repeated multiunit plateletpheresis can continuously provide adequate platelet yields without adversely affecting donors.

Plateletpheresis using the haemonetics model 30 cell separator.

Plateletpheresis using the Haemonetics Model 30 cell separator results in a mean collection of 5.5 X 10(11) platelets. This product contains substantial numbers of erythrocytes and mononuclear cells which can be effectively removed by centrifugation but with a 23% loss of platelets as well. The mean decrement in donor's platelet count during the procedure, which is 78,000/mm3, is not commensurate with the number of platelets collected suggesting donor platelet mobilization. Platelets collected by this technic, when transfused into unselected recipients, give platelet increments comparable to platelets produced in the standard batch manner.

Intensive multiunit plateletpheresis of normal donors.

Intensive plateletpheresis was performed on 39 donors on 104 occasions in order to provide compatible platelets for patients refractory to transfusions from random donors. From three to eight units of platelet concentrate were obtained at each donation and repeated donations could be performed efficiently and safely. As many as 29 units of platelets were removed on four consecutive days. Donor platelet counts decreased an average of 20 per cent during donation. With consecutive donations, there was a 13 per cent day‐to‐day mean decline in count. Platelet yield correlated with the initial count although considerable variation prevented accurate prediction of yield in individual cases. Yields fell between the first and second units removed, but remained stable thereafter and the yield per bag was often greater with five to eight unit plateletphereses than with four unit donations. Donors tolerated the procedure extremely well. It is concluded that repeated multiunit plateletpheresis is a safe and practical means of obtaining large numbers of platelets for transfusion.