Key messages
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Antifibrinolytics help prevent bleeding by stopping blood clots from breaking down too quickly. Tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are two antifibrinolytic medications.
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Compared to placebo (an inactive 'dummy' medicine), TXA probably makes little or no difference to the number of people with thrombocytopenia and blood disorders who experience moderate or worse than moderate bleeding. It may make little or no difference to the number who experience severe, life-threatening bleeding, or dangerous blood clots in the blood vessels (thromboembolism).
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We do not know if EACA helps because there was a lack of data.
What are haematological disorders?
Haematological (i.e. blood) disorders are conditions that affect the blood and blood-forming organs (such as bone marrow). They disrupt the blood's normal functions of oxygen transport, clotting, and immunity. Some of these blood disorders are not cancer and may cause problems like anaemia or sickle cell anaemia. Others are cancers of the blood, such as leukaemia, lymphoma, and myeloma.
How are haematological disorders treated?
People with haematological (blood) cancers and other blood disorders are frequently at risk of severe or life-threatening bleeding from having low platelet counts (thrombocytopenia). When the number of platelets in the blood is low, the blood does not clot as it should, so people may bruise or bleed more easily. This may be from bone marrow failure due to an underlying blood disorder, but also from the toxic effect of treatment (chemotherapy) on the bone marrow.
People with low platelets may be given platelet transfusions: that is, receive platelets from donated blood to help prevent bleeding. These transfusions carry risks, ranging from mild reactions such as fevers, to more serious or even life-threatening consequences. These include infections transmitted to the patient from the transfused platelets, despite stringent attempts to prevent this.
What did we want to find out?
Clearly, ways to safely prevent bleeding in people with thrombocytopenia whilst also minimising exposure to transfused platelets would be welcome. One possible way of achieving these goals is the use of antifibrinolytics (also known as lysine analogues): tranexamic acid (TXA) and epsilon aminocaproic acid (EACA).
These medications help to stabilise the clots that form after bleeding, therefore reducing the chances of further bleeding as well as the need for transfusing platelets. There may be risks associated with the use of TXA and EACA: the most important is the increased risk of forming unwanted blood clots (such as deep vein thrombosis (DVT)), which could be potentially life-threatening.
We wanted to find out if TXA and EACA are better than placebo (an inactive 'dummy' medicine) or no medication at reducing the number of people who:
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experienced moderate bleeding or worse;
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experienced severe or life-threatening bleeding;
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experienced any type of thromboembolism (dangerous blood clots);
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died.
We also wanted to find out if TXA or EACA caused any serious unwanted, harmful effects.
What did we do?
We searched for studies that compared TXA or EACA with placebo or no treatment in people with haematological (blood) disorders who have a low platelet count and would usually be treated with platelet transfusions. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and the number of participants involved.
What did we find?
We found eight studies with a total of 1041 participants. Six studies compared TXA to placebo, one compared EACA to no EACA, and one compared EACA to standard platelet transfusion. Seven studies were in adults and one was in children. Five studies were funded by governments, universities, or other non-pharmaceutical organisations; one study received funding from a pharmaceutical company; and the remaining two studies did not provide information about funding.
Main results
In people with haematological disorders who have a low platelet count, tranexamic acid (TXA) compared to placebo:
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probably makes little or no difference to the number who experience moderate or worse than moderate bleeding;
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may make little or no difference to the number who experience severe, life-threatening bleeding, or dangerous blood clots in the blood vessels (thromboembolism).
There was not enough evidence to reach conclusions about the effect of TXA on the risk of death or the risk of serious side effects.
The two studies that looked at epsilon aminocaproic acid (EACA) did not report enough information to allow us to analyse their results.
What are the limitations of the evidence?
In general, we have little to no confidence in the evidence because there were too few studies to be certain about the results of our outcomes. In addition, some of the events we were looking for (e.g. death, dangerous blood clots) happened in very few people, which makes the results uncertain. These limitations mean it is difficult to draw firm conclusions about the effectiveness and safety of antifibrinolytic medications.
How current is this evidence?
The evidence is current to January 2025. This is an update of a review last published in 2016.
閱讀完整摘要
People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013.
目的
To determine the benefits and harms of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders.
搜尋策略
We searched CENTRAL, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Transfusion Evidence Library, and ongoing trial databases on 21 January 2025. We handsearched the reference lists of all identified randomised controlled trials (RCTs). We contacted the authors of relevant studies, study groups, and experts worldwide known to be active in the field to request information about unpublished material or further information on ongoing studies.
選擇標準
We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA.
資料收集與分析
Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data.
主要結果
We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA.
Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.
Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity.
We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies.
Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence).
All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD -5.60 platelet units, 95% CI -9.02 to -2.18: induction; 38 participants, MD -1.00 platelet units, 95% CI -9.11 to 7.11; very low-quality evidence).
Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence).
None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL).
作者結論
For people with thrombocytopenia and haematological malignancies, TXA probably makes little to no difference to clinically significant bleeding (i.e. grade 2 or higher), and may make little to no difference to severe or life-threatening bleeding (i.e. grade 3 or higher) or any thromboembolism. The evidence is of very low certainty for all-cause mortality and serious adverse events attributable to antifibrinolytic drugs.
For EACA compared to no EACA, there are insufficient data to assess clinically significant bleeding, life-threatening bleeding, any thromboembolism, all-cause mortality, and serious adverse events.
Those making decisions about administration of prophylactic TXA to people with thrombocytopenia and haematological malignancies should consider that current evidence does not show a benefit or harm for TXA for preventing clinically significant or life-threatening bleeding.
Funding
This Cochrane review had no dedicated funding.
Registration
Protocol (2012): DOI: 10.1002/14651858.CD009733.
Original review (2013): DOI: 10.1002/14651858.CD009733.pub2.
Review update (2016): DOI: 10.1002/14651858.CD009733.pub3.kljkj
