Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders

Abstract

Background 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. Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. Selection criteria 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. Data collection and analysis 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. Main results 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 child...

Successful treatment of bleeding with tranexamic acid in a series of 12 patients with immune thrombocytopenia

“…Although there is concern regarding thrombotic complications due to TA , the drug has not been associated with an increased thromboembolic risk when used prophylactically in major paediatric surgery or during total knee arthroplasty . A similar finding was reported in the above mentioned Cochrane study .…”

“…Most importantly, epsilon aminocaproic acid, the predecessor antifibrinolytic agent of TA, has been shown to prevent bleeding in severely thrombocytopenic patients with haematological malignancies . However, the result of a Cochrane review indicated that the evidence available for the use of antifibrinolytics in haematology is very limited .…”

Alternatives to allogeneic platelet transfusion

“…A key question before considering alternatives to transfusion is whether prophylactic platelet transfusion is necessary at all. RCTs in ITP, haematological malignancy undergoing chemotherapy, MDS and liver disease Antifibrinolytics (Estcourt et al, 2016) In clinical use largely outside the setting of thrombocytopenia. (Afdhal et al (2014), Geissler et al (2003), Prica et al (2014), Zeng et al (2011) In clinical use in some types of thrombocytopenia.…”

“…This approach is appealing, as these agents are cheap and have been shown to be effective in a number of other patient settings (not necessarily characterised by thrombocytopenia, such as trauma) with minimal adverse events (Ker et al, 2012;Shakur et al, 2010). A recent systematic review focussing on the use of tranexamic acid in patients with haematological malignancies (Estcourt et al, 2016) identified three trials examining tranexamic acid and one trial examining epsilonaminocaproic acid, all of which were of low quality, and small sample size. A recent systematic review focussing on the use of tranexamic acid in patients with haematological malignancies (Estcourt et al, 2016) identified three trials examining tranexamic acid and one trial examining epsilonaminocaproic acid, all of which were of low quality, and small sample size.…”

“…(Afdhal et al (2014), Geissler et al (2003), Prica et al (2014), Zeng et al (2011) In clinical use in some types of thrombocytopenia. RCTs in ITP, haematological malignancy undergoing chemotherapy, MDS and liver disease Antifibrinolytics (Estcourt et al, 2016) In clinical use largely outside the setting of thrombocytopenia. Limited RCT evidence in setting of haematological malignancy.…”