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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 3124-3126
A Restrictive Platelet Transfusion Policy Allowing Long-Term
Support of Outpatients With Severe Aplastic Anemia
By
Markus Sagmeister,
Lic Oec, and
Jürg Gmür
From the Department of Internal Medicine, the Division of Hematology,
University Hospital of Zürich, Zürich, Switzerland.
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ABSTRACT |
The threshold for prophylactic platelet transfusions in patients
with hypoplastic thrombopenia generally recommended in the standard
literature is 20,000 platelets/µL. A more restrictive transfusion
policy may be indicated in patients with chronic severe aplastic anemia
(SAA) in need of long-term platelet support. We evaluated the
feasibility and safety of a policy with low thresholds for prophylactic
transfusions ( 5,000 platelets/µL in stable patients; 6,000 to
10,000 platelets/µL in cases with fever and/or hemorrhagic signs)
combined with progressive lengthening of transfusion intervals (up to
at least 7 days irrespective of the interim course of platelet counts).
The study was based on a retrospective analysis of a total of 18,706 patient days with platelet counts 10,000/µL in patients with
chronic SAA treated (for more than 3 months) on an outpatient basis.
Altogether, 1,135 platelet transfusions were given, 88% at counts
10,000/µL and 57% at counts 5,000/µL. The mean transfusion
interval was 10 days. During the period of observation, three major
nonlethal bleeding complications occurred, which could be well
controlled. We conclude that the restrictive policy with low
transfusion thresholds and prolonged transfusion intervals proved
feasible and safe in chronic SAA patients.
© 1999 by The American Society of Hematology.
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INTRODUCTION |
SEVERE APLASTIC ANEMIA (SAA) is a mostly
chronic bone marrow (BM) failure leading to severe hypoproliferative
pancytopenia. The majority of these patients depend on successful
long-term platelet transfusion support because only a minority can be
treated by allogeneic BM transplantation (BMT). Moreover, if subjected to immunosuppressive treatment attempts, recovery of platelet counts
usually takes several months. Thus, they represent an excellent opportunity for the evaluation of long-term platelet transfusion policies. Such evaluation may be of interest because no consensus exists regarding long-lasting prophylactic platelet support.
Prophylactic transfusions to prevent hemorrhagic complications are
commonly given when platelet counts fall below
20,000/µL.1,2 This approach usually calls for transfusion
intervals of 2 to 3 days. However, the risk of complications such as
infectious disease transmission, early alloimmunization, and impairment
of quality of life because of frequent hospital visits are increased by
a series of transfusions at short intervals. In addition, economical considerations and shortage of platelet resources also demand a more
stringent policy.
Reduced utilization of platelets may be attained by various
restrictions. Thresholds for prophylactic platelet transfusions may be
lowered below 20,000 platelets/µL as was done successfully by
Gmür et al3 in patients with acute leukemia
undergoing induction chemotherapy. On the other hand, platelets could
be given for bleeding complications rather than prophylactively. In
this study, we analyzed the results of a policy using low thresholds for prophylactic platelet transfusion combined with a progressive lengthening of transfusion intervals irrespective of the interim course
of platelet counts in all cases with good tolerance. In particular, the
feasibility and safety of this more restrictive transfusion policy were
evaluated in patients with SAA in need of extended series of platelet transfusions.
| |
MATERIALS AND METHODS |
Study design.
The analysis includes all patients with SAA treated for time periods of
at least 3 months on an outpatient basis at the University Hospital of
Zurich, in the years of November 1973 to December 1996. The
retrospective evaluation took into account both outpatients and
inpatient periods. Patients were followed until partial (transfusion independence, but abnormal blood counts) or complete remission of SAA,
BMT, or death. After ensuring the diagnosis of SAA, long-term platelet
support was started according to the following criteria for a same-day
platelet transfusion: (1) Platelet count <5,000/µL in stable
patients (body temperature 38°C, no coagulation disorder, no
extensive minor or major bleeding); (2) platelet count between 5,000 and 10,000/µL in case of recent hemorrhage and/or fever >38°C
only; (3) platelet count >10,000/µL in case of major bleeding events (World Health Organization grade >2 [gross blood loss and/or life threatening bleeding]) or before minor surgery only.
Besides this stringent threshold for prophylactic platelet
transfusions, our goal was to lengthen the transfusion intervals irrespective of the interim course of the platelet count to at least 7 days when good tolerance was observed (ie, no major or no intolerable
minor bleeding complication). Shorter intervals were allowed in cases
of insufficient increase of posttransfusion platelet count (absolute
increase <10,000/µL), in the presence of major bleeding
complications, in preparation for surgical interventions, or for
bridging over long weekends or vacations.
Platelet counts and transfusions.
Platelet counts were obtained from edetic acid (EDTA) anticoagulated
venous blood as previously published.3 Platelets were counted before and 30 to 60 minutes after the transfusion to evaluate the posttransfusion increment. If two consecutive platelet counts were
documented 10,000/µL, the assumption was made that for the days in
between, the platelet counts were also 10,000/µL. An extrapolation
was made by summation of these days. Platelets for transfusion were
obtained from single random donors unless alloimmunization required
HLA-matched platelet transfusions. Criteria to use HLA-compatible platelets included refractoriness (corrected count increment <4,000 platelets/µL in two consecutive transfusions) and anti-HLA-antibody positivity.
Statistics.
Data were collected from the patient records. Mean values, median
values, ranges, and standard deviations were calculated using a Systat
software package (Systat Inc, Evanston, IL). The Student's t-test (independent samples) and Pearson chi-squared test were used for comparisons of the samples. Two-sided P
levels of 5% were taken to indicate statistical significance.
| |
RESULTS |
The data of 25 patients fulfilling the requirements were analyzed
(Table 1). One (additional) case could not
be included for lack of complete data. In 19 cases, the SAA was
idiopathic, in the other cases it was assumed to be due to drug
toxicity (5) or to viral hepatitis (1). All cases were treated by at
least one course of immunosuppressive therapy (ALG, cyclosporine, ± steroids). Three patients received androgens and 3 others received BMT
after a prolonged course of chronic SAA. The period of observation amounted to a total of 55,239 patient-days. On the average, the patients were followed for over 1,775 days (median) with a range from
293 to 8,414 days. The total number of patient-days with platelet
counts below 10,000/µL was 18,706. The median number of days per
patient with platelet counts 10,000 was 310 (range, 17 to 3,696 days). The total number of days without transfusion despite a
documented platelet count <10,000/µL was 773. In 23 patients
platelet transfusions were withheld despite a documented platelet count
5,000/µL at 230 events. The total of platelet transfusions given to
the patients was 1,135 (range, 2 to 253 per patient). A total of 1,318 inpatient-days, mainly for primary diagnosis or for intercurrent
infections, was recorded. Bleeding complications led to 28 inpatient-days.
Pretransfusion platelet counts.
The mean pretransfusion platelet count was 6,000 ± 5,000/µL.
Eighty-eight percent of all transfusion were given at platelet counts
10,000 platelets/µL and 57% with platelet counts 5,000/µL (Fig
1). The pretransfusion platelet counts in
outpatients and inpatients showed only small differences, which were
statistically barely significant (outpatient average 5,800 platelets/µL v inpatient average 6,500 platelets/µL;
P = .046). This shows that in most cases both outpatients and
(severely ill) inpatients received transfusions according to the same
restrictive policy.
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| Fig 1.
Comparison of the relative distribution of pretransfusion
platelet counts (%) between a hospital ( ) versus an outpatient
setting ( ) (platelet counts in 103/µL).
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Platelet transfusion intervals.
The mean interval between two consecutive platelet transfusions (Fig
2) was 10 ± 18 days (median, 7 days;
range, 0 to 363 days). In outpatients the goal of keeping transfusion
intervals at 7 days or longer was attained in the majority (77.8%) of
cases with a mean of 11.9 days (median, 7 days). In nearly half of the outpatient transfusions (47.4%) the interval was 7 to 10 days, and in
an additional quartile (24.7%) the interval could be lengthened to 11 to 21 days. Inpatients were given transfusions at shorter intervals
(mean and median, 4 days). Only 14.8% of transfusions given to
hospitalized patients showed intervals of 7 days or longer. This
difference between the two groups (outpatient v inpatient) was
statistically highly significant (P < .01). This indicates to what extent the inpatients (ie, the severely ill) are monitored and
transfused more frequently than outpatients (generally in a stable
phase).
View larger version (23K):
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[in a new window]
| Fig 2.
Comparison of the relative distribution of platelet
transfusion intervals (%) between a hospital ( ) versus an
outpatient setting ().
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Major bleeding complications.
A total of three major, nonlethal bleeding episodes were observed
(gastrointestinal hemorrhage with angiodysplasis, retinal hemorrhage
with blurred vision, hemascos). These three cases were hospitalized
(with a total of 19 inpatient days). Bleeding complications leading to
or contributing to death were recorded in 5 cases. However, all of them
were no longer transfused according to our transfusion policy.
Alloimmunization had developed in 4 of them preventing effective
platelet support because of lack of HLA-compatible donors. All 5 were
in a terminal condition after a prolonged period of chronic SAA and
refused any medical treatment including transfusions before lethal
hemorrhage ensued (1 cerebral and 1 gastrointestinal bleeding, totaling
9 inpatient days; 3 suspected hemorrhages of unknown location death at
home, no autopsy).
Final outcome.
The 19 survivors showed the following outcomes: complete remissions or
transfusion independent partial remissions, 14 patients; BMTs, 3;
deaths not related to SAA (cardiac failure), 1; lost to follow-up, 1;
still under outpatient follow-up with persistent SAA, 1.
| |
DISCUSSION |
There is no uniform consensus about the optimal platelet count
threshold below which prophylactic platelet transfusion should be given
for prevention of bleeding. Standard literature still recommends a
threshold of 20,000 platelets/µL.1,2 In fact, a survey of
630 hospitals in the United States showed that the 20,000/µL
threshold still is common practice in about 60% of the institutions.4 However, Gmür et al3
reported their results of a 10-year study on prophylactic platelet
transfusion in acute leukemia applying much more restrictive decision
policiesthe same policy that was adopted in the evaluation reported
here. Later on, Heckman et al5 did not find any significant
differences in morbidity and in mortality when comparing groups with
thresholds of 10,000 and 20,000 platelets/µL, respectively, during
induction therapy for acute leukemia. Rebulla et al6
confirmed the safety of the 10,000/µL threshold. Recently Wandt et
al7 also proved the safety and cost effectiveness of a
10,000/µL threshold. However, these studies3,5-7 showed
effectiveness and safety of a stringent policy only for short periods
of platelet transfusion dependence.
This is the first study showing that a restrictive policy for
prophylactic platelet transfusions (5,000 platelets/µL in stable patients; 10,000 platelets/µL in cases with fever and/or fresh bleeding) can be safely applied in chronic SAA patients in need of
prolonged platelet support. According to our policy, 57% of all
transfusions were at platelet counts 5,000/µL. Even more importantly, the majority tolerated a progressive lengthening of
transfusion intervals. It is worth noting that intervals of 7 days or
longer were achieved in 78% of all outpatient transfusions, in
contrast to the 2 to 3 days generally observed.
The reported deaths from hemorrhage were associated either with
alloimmunization and/or patient refusal of further medical treatment
including transfusions. The few other major bleeding complications were
manageable. The improvement in quality of life with fewer hospital
visits, the decreased risks of infection transmission, and
alloimmunization are important advantages of a more restrictive transfusion practice. Cost savings and reduced utilization of platelet
resources due to fewer transfusions should also be taken into account.
We conclude that our restrictive policy with low thresholds for
platelet transfusions (outpatients and hospitalized patients), combined
with a gradual lengthening of transfusion intervals to at least 7 days
in outpatients with chronic SAA, has proven feasible, safe, and economical.
| |
FOOTNOTES |
Submitted August 11, 1998; accepted December 15, 1998.
The publication costs of this
article were defrayed in part by
page charge payment. This article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
Address reprint requests to Jürg Gmür, MD, Department of
Internal Medicine, Division of Hematology, University Hospital
Zürich, Rämistrasse 100, CH 8091 Zürich, Switzerland.
| |
REFERENCES |
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Shadduk R:
Aplastic anemia, in
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Williams Hematology (ed 5). New York, NY, McGraw-Hill, 1995, p 238.
3.
Gmür J, Burger J, Schanz U, Fehr J, Schaffner A:
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Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/µL versus 20,000/µL.
J Clin Oncol
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ABSTRACT
INTRODUCTION