Scribd Logo
Upload

Welcome to Scribd!

  • 23 views

    862 Full

    Uploaded by

    Fadel Bilondatu
    transfusion

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd

    862 Full

    Uploaded by

    Fadel Bilondatu
    23 views3 pages
    transfusion

    Original Title

    862.full

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    transfusion

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    23 views3 pages

    862 Full

    Uploaded by

    Fadel Bilondatu
    transfusion

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 3

    TRANSFUSION MEDICINE

    Brief report

    The efficiency of transfusing high doses of platelets in hematologic patients with


    thrombocytopenia: results of a prospective, randomized, open, blinded end point
    (PROBE) study
    Luc Sensebe, Bruno Giraudeau, Laurent Bardiaux, Eric Deconinck, Aline Schmidt, Marie-Laure Bidet, Catherine LeNiger, Elisabeth Hardy,
    Catherine Babault, and Delphine Senecal

    We performed a prospective, randomized, open, blinded end point (PROBE)


    study to assess the efficiency of transfusing high doses of platelets in patients
    with thrombocytopenia, either acute leukemia (AL) or those undergoing autologous hematopoietic stem cell transplantation (AT). Patients were randomly
    assigned to receive transfusions with a
    target dose of 0.5 1011/10 kg (arm A) or

    1 1011/10 kg (arm B). A total of 101


    patients were included, of whom 96 were
    given at least one transfusion. The median time between the first transfusion
    and when the platelet count reached at
    least 20 109/L increased from 63 hours
    to 95 hours in the arm B group (P .001),
    and the median number of transfusions
    was lower in this group (2; P .037). The
    total number of transfused platelets did

    not differ between groups (14.9 1011 for


    arm A versus 18.5 1011 for arm B;
    P .156). In such patients, a prophylactic
    strategy of high doses of platelets could
    improve platelet transfusion efficiency.
    (Blood. 2005;105:862-864)

    2005 by The American Society of Hematology

    Introduction
    In hematologic patients with thrombocytopenia, platelet transfusions remain vital in supportive care. If the dose of 0.5 1011/10
    kg1 remains the standard,2-5 the optimal dose for prophylactic
    treatment is debatable. Results of 2 studies comparing different
    doses of platelets showed an increased platelet count and time
    between 2 transfusions according to the dose.6,7 Both were
    crossover studies; however, transfusion efficiency may be associated with the number of previous transfusions and dose. To assess
    the overall efficiency of transfusing a high dose of platelets, we
    performed a prospective randomized study to compare the effect of
    a single dose (0.5 1011/10 kg) versus a double dose (1 1011/10
    kg) of platelets on repeat transfusion in hematologic patients with
    thrombocytopenia.

    Study design
    Patients
    Patients who had not undergone transfusion who had acute leukemia (AL;
    AML3 excluded) undergoing first-line treatment or autologous hematopoietic stem cell transplantation (AT) without criteria impairing platelet
    efficiency were enrolled.
    Setting and ethical approval
    The study protocol was approved by the institutional review board of Brest,
    France, and written informed consent of patients was obtained. Four
    regional blood banks in France (Etablissement Francais du Sang [EFS]) and

    hematology departments from university hospitals in Angers, Besancon,


    Brest, and Tours, France, participated.
    Trial design
    The design was multicenter, randomized, parallel group. Physicians and
    patients were not blinded to the randomization arm. The main outcome
    parameter was platelet count and the laboratory was blinded to the dose of
    platelets received, thus defining the study as a prospective, randomized,
    open, blinded end point (PROBE) study.8 Randomization was based on the
    center and type of pathology.
    Platelet transfusion protocol
    Blood cells were counted daily between 7:00 and 8:00 AM, and transfusions
    were given when the platelet count was less than 20 109/L. To avoid
    interference with criteria known to impair recovery,9-13 patients were given
    leukocyte-depleted single-donor apheresis platelet concentrates (APCs)
    less than 72 hours old, and ABO identical or donor platelets were
    compatible with patients isoagglutinins. Patients were randomly assigned
    to receive doses in arm A (single dose; target 0.5 1011/10 kg) or arm B
    (double dose; target 1 1011/10 kg) and were followed from the first
    platelet transfusion until they were discharged and had a stable platelet
    count more than 25 109/L or died.
    Outcome measures
    We measured the time between the first transfusion and the daily platelet
    count reaching 20 109/L, which allowed for calculating the risk of retransfusion and the theoretical time between the first and second transfusion. Secondary
    outcome measures were (1) the corrected count increment (CCI), which was
    calculated as (posttransfusion count pretransfusion count) body

    From the EFS Centre-Atlantique, Tours, France; INSERM CIC202, Tours,


    France; Etablissement Francais du Sang (EFS) Bourgogne France-Comte,
    Besancon, France; Hematology Department, CHU Minjoz, Besancon, France;
    Hematology Department CHU, Angers, France; EFS Pays de Loire, Angers,
    France; Hematology Department CHU Morvan, Brest, France; EFS Bretagne,
    Brest, France; and Hematology Department CHU Bretonneau, Tours, France.

    First Edition Paper, September 14, 2004; DOI 10.1182/blood-2004-05-1841.

    Submitted May 14, 2004; accepted August 27, 2004. Prepublished online as Blood

    2005 by The American Society of Hematology

    862

    Supported by a grant from Etablissement Francais du Sang (E.F.S.; FORTS


    no. 99004250837).
    Reprints: Luc Sensebe, EFS Centre-Atlantique, 2 Boulevard Tonnelle, BP
    52009-37020, Tours CEDEX 1, France; e-mail [email protected].

    BLOOD, 15 JANUARY 2005 VOLUME 105, NUMBER 2

    BLOOD, 15 JANUARY 2005 VOLUME 105, NUMBER 2

    HIGH-DOSE TRANSFUSIONS OF PLATELETS

    863

    Table 1. Characteristics of patients with hematologic thrombocytopenia undergoing single or double doses of platelet transfusion
    Single dose (n 50)

    Double dose (n 51)

    AL (n 17)

    AT (n 33)

    Age, y, mean SD

    52 15

    Weight, kg, mean SD

    67 13

    Men, no. (%)

    7 (41.2)

    AL (n 14)

    AT (n 37)

    50 9

    44 16

    49 11

    70 13

    63 13

    16 (48.5)

    6 (42.9)

    71 13
    23 (62.2)

    Hb level, g/L (minimum; maximum)

    88 (72; 157)

    104 (82; 128)

    95 (81; 127)

    98 (77; 138)

    WBC count, 109/L (minimum; maximum)

    1.5 (0.1; 28.4)

    1.3 (0.1; 13.9)

    4.4 (0.1; 57.4)

    1.4 (0.1; 12.6)

    Platelet count, 109/L (minimum; maximum)

    65 (15; 164)

    133 (11; 500)

    64 (21; 178)

    118 (15; 452)

    Hb indicates hemoglobin, WBC, white blood cell.

    surface area (m2)/platelet dose ( 1011) for the first transfusion; (2) number
    of transfusions; and (3) number of transfused platelets. Bleeding complications were assessed daily according to World Health Organization (WHO)
    criteria (0 none; 1 petechial; 2 mild blood loss; 3 gross blood
    loss; 4 debilitating blood loss).
    Sample size
    Hypothesizing an increase of 75% in the median delay between 2
    transfusions, the hazard ratio was thus hypothesized at 0.57, leading to a
    required number of events (retransfusion) of 100 ( 5% and 20%).

    mean number of transfused platelets was 0.57 0.15/10 kg for the


    arm A group and 0.96 0.18/10 kg for the arm B group.
    The median theoretical time between the first and the second
    transfusion was 63 hours (95% confidence interval [CI], 46-65) for
    the arm A group and 95 hours for the arm B group (95% CI, 85-112;
    P .001; Figure 2), the difference remaining significant whatever
    the pathology (AL or AT) or number of subsequent transfusions
    (data not shown). The mean posttransfusion CCI was not statistically different between patients who were given a single or double

    Statistical analysis
    Analyses were conducted according to a prespecified plan based on the
    principle of intention to treat. Patients had to undergo transfusion at least
    once during the study; patients never having a transfusion were excluded.
    Analysis was global and by 2 subgroups (AL or AT groups). The primary
    outcome was analyzed by means of a log-rank test. For the CCI, comparison
    was by means of the Student t test. The number of transfusions and
    transfused platelets were analyzed in the framework of a generalized linear
    model with negative binomial distribution14 and a linear model, respectively. We adjusted for weight at baseline, and patients who died were
    excluded because of lack of transfusion history. Analyses involved use of
    SAS (version 8.1; SAS Institute, Cary, NC).

    Results and discussion


    Between May 1999 and October 2001, 101 patients were randomly
    assigned to receive transfusions in arm A (50 patients, 17 with AL
    and 33 AT) and arm B (51 patients, 14 with AL and 37 AT). The
    groups were balanced according to age, weight, and baseline
    hematology findings (Table 1). Three patients with AL died during
    the study period, with the death not related to bleeding or
    transfusion. We analyzed the results for 96 patients (Figure 1). The

    Figure 1. Procedure for including patients in trial of transfusing platelets in


    patients with hematologic thrombocytopenia. Randomized patients had no
    clinical or biologic features that would impair platelet transfusion efficiency. For the
    final analysis, 5 patients never receiving a transfusion after randomization were
    excluded. (AL indicates acute leukemia undergoing first-line treatment; AT, undergoing autologous hematopoietic stem cell transplantation.

    Figure 2. Probability of retransfusion after the first platelet transfusion . For


    patients with thrombocytopenia undergoing single or double doses of platelet
    transfusion the probability of retransfusion in arm A (single dose) and arm B group
    (double dose): panel A the probability of retransfusion decreased significantly in the
    arm B group (P .001). The probability of retransfusion in patients with AL (panel B;
    17 in arm A group; 12 in arm B) and AT (panel C; 31 in arm A group; 36 in arm B) was
    lower in the arm B than in the arm A group (P .001 for AL, P .003 for AT).
    Comparison involved use of the log-rank test.

    864

    BLOOD, 15 JANUARY 2005 VOLUME 105, NUMBER 2

    SENSEBE et al

    Table 2. Efficiency of the first platelet transfusion in patients with thrombocytopenia receiving single or double doses of platelets
    Total (n 96)

    Platelet count increment,


    CCI

    109/L

    AL patients (n 29)

    Single dose

    Double dose

    Single dose

    20.8 13.5

    44.5 23.5

    .001

    10.6 5.4

    12.5 5.8

    .116

    AT patients (n 67)

    Double dose

    Single dose

    Double dose

    22.6 17.8

    43.0 18.4

    .008

    19.8 10.4

    45.0 25.1

    .001

    12.3 7.7

    12.0 5.2

    .896

    9.6 3.6

    12.6 6.0

    .025

    After the first transfusion, patients receiving a double dose of platelets had increased platelet count increments. CCI was calculated as a median time (time from the first
    transfusion to the next platelet count control) of 23 hours 45 minutes (minimum, 5 hours 56 minutes; maximum, 26 hours 45 minutes) for the arm A group (single dose) and 24
    hours 00 minutes (minimum, 11 hours 30 minutes; maximum, 29 hours 00 minutes) for the arm B group (double dose; P .097). With a double dose, the CCI was increased
    only in patients with AT but remained within a normal range ( 7), which demonstrates good efficiency in every group. Results are expressed as mean SD. Because of
    missing data, analyses were performed in 90 patients for the platelet count increment and 89 for the CCI.

    dose (Table 2). Arm B patients underwent fewer transfusions with a


    median of 2 (range, 1-13) versus a median of 3 (range, 1-12) for the
    arm A group (P .037). This benefit was absent in the AT (median
    2 for the arm B versus 2 for the arm A group; P .064) and AL
    (median 5 versus 5; P .584) subgroups. The adjusted means of
    total number of transfused platelets were not significantly different
    between groups (14.9 1011 arm A versus 18.5 1011 arm B
    group; P .156) and within subgroups: AL, 21.9 1011 (arm A)
    versus 26.7 1011 (arm B; P .356); AT, 11.9 1011 (arm A)
    versus 15.3 1011 (arm B; P .172).
    During the study period, hemorrhaging was seen in 14 patients
    (5 in arm A and 9 arm B; P .247). WHO grade 2 and 3
    hemorrhages were seen equally in the arm A (2 patients) and arm B
    (3 patients) groups. The 3 patients with recurrent bleeding were
    given single-dose transfusions.
    In a retrospective study, Andreu15 found good response to
    platelet transfusion with high doses. In 1998,6 the first prospective
    comparison demonstrated good platelet count increment and increased transfusion time with high doses. In 1999,7 the first
    randomized study to involve 2 different doses (3.1 1011 and
    4.9 1011) found that platelet count and transfusion interval
    increased with increased number of transfused platelets. Finally, in
    a study involving platelets collected from apheresis donors receiving thrombopoietin, increasing the dose of platelets led to an
    increased transfusion interval and platelet count.16 These studies

    did not adjust platelet dosage to body weight, which led to


    underestimated results. Here, for the first time, our randomized
    prospective study of a double dose of platelets and the period of
    platelet transfusion demonstrates increased transfusion interval
    and decreased number of transfusion episodes with a double
    dose of platelets.
    The absence of decreased number of transfusions in patients
    with AL could be due to the small number of patients with AL in
    our study or the known decrease in platelet transfusion efficiency
    over time. Our results on the number of transfusions could be
    underestimated because of a real increase of 68% and not 100% in
    platelet dose between patients given single and double doses.
    Although the number of transfusion events was small, recurrent
    bleeding occurred only in patients given a single dose, which
    suggests a better control of hemorrhage with high doses.
    Thus, for prophylaxis, high doses of platelets can reduce the number
    of transfusions in hematologic patients with thrombocytopenia, without
    a significant increase in amount of transfused platelets.

    Acknowledgments
    We thank C. Monpouet for her excellent data management and G.
    Andreu for helpful comments.

    References
    1. Morrison FS. Platelet transfusion: a brief review
    of practical aspects. Vox Sang. 1966;2:656-678.
    2. The National Institute of Health Consensus Conference. Platelet transfusion therapy. Transfus
    Med Rev. 1987;3:195-200.
    3. Murphy MF. Guidelines for the platelet transfusion. JAMA. 1988;259:2453-2454.
    4. Murphy MF, Brozovic B, Murphy W, et al. The
    British Committee for Standards in HaematologyGuidelines for platelet transfusions. Transfus Med. 1992;2:311-318.
    5. British Society for Haematology. Guidelines for
    the use of platelet transfusions. Br J Haematol.
    2003;122:10-23.
    6. Norol F, Bierling P, Roudot-Thoraval F, et al.
    Platelet transfusion: a dose-response study.
    Blood. 1998;92:1448-1453.

    7. Klumpp TR, Herman JH, Gaughan JP, et al. Clinical consequences of alterations in platelet transfusion dose: a prospective, randomized, doubleblind trial. Transfusion. 1999;39:674-681.
    8. Hansson L, Hedner T, Dahlof B. Prospective randomized open blinded end-point (PROBE) study.
    A novel design for intervention trials. Blood Press.
    1992;1:113-119.
    9. Dumont LJ, AuBuchon JP, Whitley P, et al. Sevenday storage of single-donor platelets: recovery
    and survival in an autologous transfusion study.
    Transfusion. 2002;42:847-854.
    10. Peter-Salonen K, Bucher U, Nydegger UE. Comparison of posttransfusion recoveries achieved
    with either fresh or stored platelet concentrates.
    Blut. 1987;54:207-212.
    11. Carr R, Hutton JL, Jenkins JA, et al. Transfusion
    of ABO-mismatched platelets leads to early plate-

    12.

    13.

    14.

    15.

    16.

    let refractoriness. Br J Haematol. 1990;75:408413.


    Heal JM, Rowe JM, McMican A, et al. The role of
    ABO matching in platelet transfusions. Eur J
    Haematol. 1993;50:110-117.
    Lozano M, Cid J. the clinical implications of platelet
    transfusions associated with ABO or Rh (D) incompatibility. Transfus Med Rev. 2003;17:57-68.
    Wei LJ, Lin DY, Weissfield L. Regression analysis
    of multivariate incomplete failure time data. J Am
    Stat Assoc. 1989;84:1065-1073.
    Andreu G. Transfusions plaquettaires dans les
    insuffisances medullaires. Transfus Clin Biol.
    1995;1:27-36.
    Goodnough LT, Kluter DJ, McCullough J, et al.
    Prophylactic platelet transfusions from healthy
    apheresis platelet donors undergoing treatment
    with thrombopoietin. Blood. 2001;98:1346-1351.

    You might also like