Medical treatments for idiopathic thrombocytopenic purpura during pregnancy

 

Abstract

Background

Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of the maternal-fetal risk of ITP during pregnancy is controversial. Labour management of pregnant women with ITP remains controversial. Management of ITP during pregnancy is complex because of the disparity between maternal and fetal platelet counts.

Objectives

To assess the effectiveness and safety of corticosteroids, intravenous immunoglobulin, vinca alkaloids, danazol, dapsone, and any other types of pharmacological treatments for the treatment of idiopathic thrombocytopenic purpura during pregnancy.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (February 2009), LILACS (1982 to 8 February 2009), ClinicalTrials.gov (8 February 2009), Current Controlled Trials (16 February 2009), Google Scholar (16 February 2009) and ongoing and unpublished trials cited in the reference lists of relevant articles.

Selection criteria

Randomised controlled trials (RCTs) on any medical treatments for idiopathic thrombocytopenia purpura during pregnancy.

Data collection and analysis

Two review authors independently evaluated methodological quality and extracted trial data. Any disagreement was resolved by discussion or by consulting a third review author.

Main results

This review included one RCT in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed.

This RCT comparing the effect of betamethasone (1.5 mg/day) with no medication found no statistically significant difference in neonatal thrombocytopenia (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.62 to 2.05) and neonatal bleeding (RR 1.00, 95% CI 0.24 to 4.13). Review authors conducted an intention-to-treat analysis which showed similar findings: RR 1.18, 95% CI 0.57 to 2.45 and RR 1.05, 95% CI 0.24 to 4.61, respectively. Maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage were not studied by this RCT.

Authors' conclusions

Current evidence indicates that compared to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support the use of betamethasone for treating ITP. This Cohrane review does not provide evidence about other medical treatments for ITP during pregnancy. This systematic review also identifies the need for well-designed, adequately powered randomised clinical trials for this medical condition during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use betamethasone for ITP in pregnant women. Any future trials on medical treatments for treating ITP during pregnancy should test a variety of important maternal, neonatal or both outcome measures, including maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage.

 

Plain language summary

Drug therapy for treating idiopathic thrombocytopenic purpura during pregnancy

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated hematologic disorder caused by a low blood platelet count (thrombocytopenia). Antiplatelet antibodies act against the platelets resulting in platelet destruction by the spleen. In adults, the clinical features of ITP often have an insidious onset and are highly variable, ranging from no symptoms, mild bruising, to mucosal bleeding, and skin discolorations. Management of ITP during pregnancy is complex because of large differences between maternal and fetal platelet counts. The circulating antibodies can cross the placenta and cause a neonatal passive immune thrombocytopenia that may increase the risk of cerebral haemorrhage in the newborn infant. For this reason, it seems reasonable that cesarean section delivery is safer for the infant than vaginal delivery yet the mode of delivery may not affect the rate of haemorrhage. Many different pharmacological interventions are used for treating this medical disorder and treatment for ITP in pregnant women is not standardised. Some of these drugs have potential side effects for pregnant women and some can cause fetal malformation.

Current evidence from one randomised controlled trial indicates that betamethasone does not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy when compared to no medication. We could not identify evidence on other medical treatments for ITP during pregnancy.

This review included one controlled trial in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed. There was also a severe imbalance between comparison groups. Giving the mother betamethasone (1.5 mg/day) did not result in a difference in the neonatal platelet count at birth and at the first week of life. The study reported that the maternal platelet count of peripheral blood did not change significantly during the study period for both the betamethasone and no treatment groups. Maternal postpartum haemorrhage and neonatal intracranial haemorrhage were not studied. Nor were maternal clinical and pregnancy outcomes reported. The researchers used no treatment in the control group, which may have increased the risk of performance bias in the trial.

 

摘要

背景

懷孕時自發性血小板缺乏紫斑症之藥物治療

自發性血小板缺乏紫斑症是一種免疫反應引起的血小板過低症引起的血液異常。懷孕時自發性血小板缺乏紫斑症對母嬰風險的重要性有所爭議，自發性血小板缺乏紫斑症孕婦的生產處置也有爭議。懷孕時自發性血小板缺乏紫斑症之處置相當複雜，因為母親和胎兒之血小板數量不同。

目標

評估皮質類固醇、靜脈注射免疫球蛋白、長春花生物鹼類(Vinca alkaloids)、danazol、dapsone、和其他藥物用於治療懷孕時自發性血小板缺乏紫斑症之效果與安全性。

搜尋策略

我們搜尋Cochrane Pregnancy和Childbirth Group's Trials Register (2009年2月)、LILACS (1982年–2009年2月8日)、ClinicalTrials.gov (2009年2月8日)、Current Controlled Trials (2009年2月16日)、Google Scholar (2009年2月16日)，以及相關文獻之參考資料中引述之進行中的與未發表的試驗。

選擇標準

任何用於治療懷孕時自發性血小板缺乏紫斑症之隨機控制試驗(Randomised controlled trials (RCTs))。

資料收集與分析

2位回顧作者獨立評估方法學品質以及摘錄資料，若有意見不一致時，則討論或與第3位回顧作者諮商。

主要結論

本回顧納入1篇隨機控制研究，有38名婦女(41次懷孕經驗)被隨機分組，只有26名婦女(28次懷孕經驗)被分析。這篇隨機控制研究比較使用betamethasone (1.5 mg/day)和未用藥的效果，發現新生兒血小板過低症(RR為1.12, 95%CI為0.62–2.05)以及新生兒出血(RR為1.00, 95% CI為0.24–4.13)並無統計上的顯著差異。回顧作者進行治療意向分析(intentiontotreat analysis)，得到相似的結果：分別是RR為1.18, 95% CI為0.57–2.45、RR為1.05, 95% CI為0.24–4.61。這篇隨機控制研究並未探討母親之死亡、出生前後死亡、產後出血以及新生兒顱內出血。

作者結論

目前的證據指出，與未使用藥物比較，betamethasone不會減少懷孕時自發性血小板缺乏紫斑症孕婦之新生兒血小板過低症和新生兒出血風險，沒有足夠證據支持使用betamethasone治療懷孕時自發性血小板缺乏紫斑症。此次的Cochrane review並未提供其它用於懷孕時自發性血小板缺乏紫斑症的藥物治療證據。此次系統性回顧發現需要設計良好、適當強度的隨機臨床試驗，探討自發性血小板缺乏紫斑症孕婦的醫療處置。如果用Betamesasone作為自發性血小板缺乏紫斑症孕婦的治療方式，需要有經隨機臨床試驗證實的治療有效證據，也需權衡利弊。任何將來有關此疾病孕婦藥物治療的臨床試驗，應探討母親死亡、週產期死亡、產後出血和新生兒顱內出血等有關母嬰健康的重要議題 。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

懷孕時自發性血小板缺乏紫斑症之藥物治療：自發性血小板缺乏紫斑症是一種因免疫反應使血小板數量減少的(血小板過低症)血液異常。抗血小板抗體的血小板作用導致脾臟破壞血小板。就成人而言，自發性血小板缺乏紫斑症之臨床特徵通常是不知不覺發生，且變化相當大：沒有症狀、輕微挫傷、黏膜出血、皮膚變色。懷孕時自發性血小板缺乏紫斑症之處置很複雜，因為母親和胎兒的血小板數量不一樣。血液循環中的抗體會通過胎盤，引起新生兒被動免疫血小板過低，而增加新生兒腦出血風險，因此，對嬰兒來說，剖腹產似乎比自然產更安全，但是生產方式對出血率似乎沒有影響。有多種藥物被用來治療這個疾病，孕婦之自發性血小板缺乏紫斑症治療並無標準，有部份藥物可能對孕婦有副作用，有些則會引起胎兒畸形。現有的一篇隨機控制試驗的證據指出，對於懷孕時自發性血小板缺乏紫斑症，相較於未治療，betamethasone不會減少新生兒血小板過低和新生兒出血的風險。我們並未找到其他懷孕時自發性血小板缺乏紫斑症藥物治療方式的研究證據。此次回顧納入1篇試驗、有38名婦女(41次懷孕經驗)被隨機分組，只有26名婦女的資料(28次懷孕經驗)用於分析。比較之組別之間有相當大的差異。給予母親betamethasone (1.5 mg/day)，對於新生兒出生後一週內的血小板數量並不會有影響。研究報告指出，在研究期間，betamethasone組和無治療組，母親週邊血液的血小板數量並未顯著改變。並未探討母親產後出血與新生兒顱內出血，也沒有關於母親之臨床和懷孕結果的報告。研究者在對照組並未使用治療方式，這可能會增加試驗的執行偏差。