CRD summary

This review evaluated interventions (mostly drug treatments) for patients with idiopathic thrombocytopenic purpura (low platelet count) persisting after standard treatment with glucocorticoids and splenectomy. The authors concluded that there is minimal evidence for the effectiveness of any available treatment. Despite the methodological limitations of the review, the low quantity and quality of the available evidence support the authors' conclusion.

Authors' objectives

To determine the effectiveness of treatments for idiopathic thrombocytopenic purpura (ITP) in adult patients who have not responded to splenectomy.

Searching

MEDLINE was searched from January 1966 to 30 September 2003; the search terms were reported. The search was limited to articles reported in English. The bibliographies of all retrieved articles were checked for further relevant references.

Study selection

Assessment of study quality

The authors assessed validity based on a hierarchy of study designs, which ranged from randomised controlled clinical trials (RCTs) to retrospective analyses of data from selected patients. Two authors independently assessed the studies for validity based on study design. Any disagreements were resolved by consensus among all the authors.

Data extraction

Two authors independently extracted data on the outcomes. Any disagreements were resolved by consensus. Platelet count responses to treatment were tabulated as the number and percentage of patients showing a complete, partial or no response to each treatment. Where possible, the data were subdivided according to baseline platelet count (less than 50E9, 30E9 and 10E9 cells/litre). Data on deaths and bleeding events were extracted, but the numbers of these events associated with different treatments were not presented.

Methods of synthesis

Results of the review

Ninety studies with 656 participants were included in the review. Eighty-nine of these studies were cohort studies or uncontrolled case series. One study was an RCT but the randomisation was not relevant to the review question. Of the included participants, 182 (28%) were reported from prospective cohort studies of consecutive patients and 279 (43%) were apparently from retrospective analyses of selected patients.

Across all treatments, 14% of patients achieved a complete response, 40% a partial response and 46% no response. The largest numbers of complete responses were reported with azathioprine (18 out of 109; 17%), cyclophosphamide (22 out of 83; 27%) and rituximab (10 out of 41; 24%). However, 36 to 42% of the patients had no response to these three treatments. Among patients with the lowest pre-treatment platelet counts, no treatment was studied in more than 20 patients. The results for bleeding events and mortality were only reported for small numbers of patients.

Authors' conclusions

There was minimal evidence for the effectiveness of any treatment for patients with ITP and persistent thrombocytopenia after splenectomy.

CRD commentary

The review question was clearly defined and inclusion criteria for the patients, interventions and outcomes were clear. The inclusion criteria for study designs were not specified. The search relied mainly on MEDLINE and was restricted to English language material, making it possible that relevant studies could have been missed. The authors did not attempt to search for unpublished studies, which again risked making the review less comprehensive, and publication bias was not assessed. Validity was assessed in terms of a hierarchy of study designs, which is not by itself an adequate method. Two independent reviewers selected the studies and extracted the data, thus minimising the risk of bias and errors during the review process.

Relevant details of the included studies were tabulated. The authors pooled data from different studies without assessing heterogeneity among them, so the results of the synthesis should be treated with caution. Overall, however, the small numbers of treated patients and the lack of controlled trials support the authors' conclusion that none of the currently available treatments has been shown to be effective for ITP after splenectomy.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that, based on the frequency of complete responses and numbers of treated patients, cyclophosphamide, azathioprine and rituximab appear the most promising treatments for further study. Potentially effective treatments should be evaluated in RCTs.

Funding

DAISY Foundation.

Bibliographic details

Vesely S K, Perdue J J, Rizvi M A, Terrell D R, George J N. Management of adult patients with persistent idiopathic thrombocytopenic purpura following splenectomy: a systematic review. Annals of Internal Medicine 2004; 140(2): 112-120. [PubMed: 14734334]

Original Paper URL

http://www.annals.org/cgi/content/full/140/2/112

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Hemorrhage /etiology; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic /blood /complications /therapy; Splenectomy; Treatment Outcome

AccessionNumber

12004008086

Database entry date

31/12/2005

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.