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Transfusion
Table 1: Baseline Patient Characteristics
imputed for mortality in studies reporting safety outcomes without any
mention of patient deaths. All calculations were performed using SAS
®
Characteristics IV RhIG IVIG
software version 8.1 and SPSS
®
software version 13.0. The three
tn%tn%
randomised trials directly comparing IV RhIG versus IVIG are described
or mean or mean
separately in the results section.
Total patients evaluated 36 1,027 100 85 2,063 100
Gender Males 22 362/648 56 60 642/1,345 48
Females 22 283/648 44 60 703/1,345 52
Results
Age of Children 32 583/869 67 81 1,257/1,845 68
population (<16 years) Studies
Adults 32 283/869 33 81 588/1,845 32
The initial search yielded 1,014 citations, of which the vast majority were
Mean age range (years) 22 387 3–69 58 1,347 3–65
excluded at abstract level for obvious rejection reasons (e.g. reviews, not
ITP duration (range, months) 10 161 29 (1–124) 23 428 21 (0–101)
ITP population, no IV RhIG or IVIG treatments). Full publications were
ITP type Acute 30 315/839 38 73 1,040/1,621 64
retrieved for 280 abstracts for further review. Of these, 181 publications
Chronic 30 517/839 62 73 552/1,621 34
ITP cause Primary 29 645/811 80 79 1,728/1,854 93
were rejected for reasons such as review article, fewer than 10 patients
HIV-related 30 157/909 17 79 77/1,854 4
per treatment group and non-English language. Ninety-nine publications
Other secondary 29 6/811 1 79 19/1,854 1 met all eligibility criteria for inclusion in the database. During screening
Patients Rh+ 29 723/737 98 4 100/114 88 and extraction, linkages were identified among the accepted studies.
Prior ITP Naïve 19 224/367 61 45 832/1,150 72
Linked studies were those in which the same patient population was
treatments Steroids 20 151/393 38 51 297/1,194 25
reported, in part or in total, in more than one publication. The study with
IVIG 18 60/358 17 37 4/969 0.4
the most complete data was designated the ‘parent’ study, and the other
IV RhIG 14 7/297 2 31 2/873 0.2
Splenectomy 28 18/737 2 52 79/1,195 7
related papers were designated ‘kins’. Data elements were extracted from
Baseline Mean (range 10 184 15 (9–31) 38 794 16 (4–45)
the parent studies and supplemented by information presented in kin
platelet of means)
studies when appropriate. After determining these kin relationships, the
count Median (range 16 328 13 (5–34) 34 656 13 (2–40) final database of accepted studies consisted of 92 parent studies with
(x10
9
/l) of medians)
seven linked (kin) studies. Of the 92 primary accepted studies, three
t = number of treatment groups; n = number of patients with characteristic/all
single-arm studies were excluded from all analyses as they evaluated
patients evaluated; IV = intravenous; RhIG = rhesus immune globulin; IVIG = intravenous
immunoglobulin, ITP = immune thrombocytopenic purpura.
combination treatments of IVIG
12,13
and IV RhIG
14
with steroids. The first
study treatment consisted of IV high-dose methylprednisolone (20mg/kg
•‘Response within 24 hours’ includes any response reported within that in 30 minutes) followed by IV gamma globulin (Gamimune-N, 1g/kg over
time interval. five hours).
12
In the second study the patients previously received
•‘Response within ~7 days’ includes studies reporting response in the prednisone 20–40mg/day, and the steroid therapy continued during the
interval between five and 10 days of IG treatment. We used the IVIG treatment.
13
In the third study, patients received prednisone at
definitions of authors of acute and chronic ITP, which were commonly 1mg/kg/day as a single dose for 14 days and then diminished every three
defined as acute-onset, short-term (<6 months) for acute ITP and days by half the previous dose until reaching a dose of 5mg/day for
thrombocytopenia persisting for >6 months for chronic ITP. three days, and then discontinued.
14
This review focused primarily on
monotherapy with IV RhIG and IVIG, although patients might have been
Data Synthesis and Analysis allowed to receive steroids or other treatments during the study.
Basic descriptive statistics were applied to summarise study, patient and
treatment characteristics. The response outcomes (overall response, The final analysable data set consisted of 89 primary studies, of which 77
24-hour response, seven-day response, time to response, duration of were full publications and 12 were abstracts. Not surprisingly, there were
response, time to peak PC and maximum platelet increase) and selected more than twice as many studies evaluating IVIG as there were evaluating
safety outcomes (headache, fever, chills, vomiting, aseptic meningitis, IV RhIG. Of the total 3,127 patients evaluated, 67% (n=2,096) were treated
bleeding, dyspnoea, asthaenia and haemoglobin change) for patients with IVIG, and 33% (n=1,031) with IV RhIG. WinRho was specifically
treated with IV RhIG and IVIG were first estimated using pooled analyses identified as the IV RhIG used in 60% of all IV RhIG studies evaluating at
(as weighted means for continuous variables and as proportions for least 72% of all IV RhIG-treated patients. Other IV RhIG brands used were
binary outcomes). In addition, response rates were analysed using Partogamma, Rhesuman, Rhogam and HypRho-D. Of the 50 studies
random-effects model (REM) meta-analyses.
11
The REM meta-analyses published between 1995 and 2005, 38 were full publications and 12 were
weighted response rates by a combination of study sample size and meeting abstracts. The IVIG product used was not specified in 20 studies,
between-study variation. The higher the between-study variation (i.e. and in nine studies patients were treated with various IVIG products. In
the more heterogeneous the study results), the less impact that study studies reporting this information, Sandoglobulin was most commonly used
sample had in weighting the studies in the analysis. Studies not defining (k=15). Other IVIG products included Venoglobulin, Venogamma, Polygam,
response or not specifying time interval of response were included only Gamimune, Gammagard and Gamunex. Of the 89 studies, the vast majority
in the ‘overall response’ analysis. Subgroup analyses for efficacy (83%) were prospective trials, and the most common study design was
outcomes were performed for patients with acute versus chronic ITP. single-arm trial. Of the 43 comparative studies, 26 were randomised trials.
Heterogeneity in all meta-analyses was examined using Cochran’s Q Only three of these randomised trials (n=243) directly compared IV RhIG and
statistic. No formal meta-analytical comparison between IV RhIG and IVIG,
15–17
and the latter two were available only in abstract form at the time
IVIG treatments was performed due to lack of head-to-head studies of this review. Although these two studies have subsequently been
and variability of outcome reporting. For safety analyses, zeros were published, the most important data were included in the abstracts, so data
38 EUROPEAN HAEMATOLOGY 2007
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