Antifibrinolytic therapy to reduce haemoptysis

Haemoptysis is the coughing up of blood or of blood-stained sputum from the lower respiratory tract. It is a common pathology around the world and can be caused by a number of different diseases, including bronchitis, pneumonia, lung cancer, and tuberculosis.

Antifibrinolytic agents (tranexamic acid, aminocaproic acid, nafamostat and aprotinin) are drugs that act by inhibiting the process that dissolves clots, thereby reducing bleeding.

We identified two trials up to the 19th September 2016. Both of them evaluated the use of tranexamic acid, one for haemoptysis caused by tuberculosis and the other for haemoptysis from a variety of causes.

Tranexamic acid significantly reduced the bleeding time, but it did not make any difference to the number of patients who were still suffering from haemoptysis when it was evaluated at seven days after the start of treatment. Severe adverse effects were not reported and mild side effects were not different between patients receiving tranexamic acid and those not receiving tranexamic acid.

There is too little evidence to judge whether any antifibrinolytics should be used to treat haemoptysis.

Authors' conclusions: 

There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding.

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Background: 

Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious characteristics. Antifibrinolytic agents are commonly used to manage bleeding from different sources, but their usefulness in pulmonology is unclear.

Objectives: 

To evaluate the effectiveness and safety of antifibrinolytic agents in reducing the volume and duration of haemoptysis in adult and paediatric patients.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, EMBASE and LILACS for publications that describe randomized controlled trials (RCTs) of antifibrinolytic therapy in patients presenting with haemoptysis. We also performed an independent search in MEDLINE for relevant trials not yet included in CENTRAL or DARE. Searches are up to date to the 19th September 2016. We conducted electronic and manual searches of relevant national and international journals. We reviewed the reference lists of included studies to locate relevant randomized controlled trials (RCTs). An additional search was carried out to find unpublished RCTs.

Selection criteria: 

We included RCTs designed to evaluate the effectiveness and safety of antifibrinolytic agents in reducing haemoptysis in adult and paediatric patients of both genders presenting with haemoptysis of any etiology and severity. The intervention of interest was the administration of antifibrinolytic agents compared with placebo or no treatment.

Data collection and analysis: 

All reviewers independently assessed methodological quality and extracted data tables pre-designed for this review.

Main results: 

The electronic literature search identified 1 original study that met the eligibility criteria. One unpublished study was also identified through manual searches. Therefore two randomized controlled trials met the inclusion criteria: Tscheikuna 2002 (via electronic searches) and Ruiz 1994 (via manual searches).

Tscheikuna 2002, a double-blind RCT performed in Thailand, evaluated the effectiveness of tranexamic acid (TXA, an antifibrinolytic agent) administered orally in 46 hospital in- and outpatients with haemoptysis of various etiologies. Ruiz 1994, a double-blind RCT performed in Peru, evaluated the effectiveness of intravenous TXA in 24 hospitalised patients presenting with haemoptysis secondary to tuberculosis.

Pooled together, results demonstrated a significant reduction in bleeding time between patients receiving TXA and patients receiving placebo with a weighted mean difference (WMD) of -19.47 (95% CI -26.90 to -12.03 hours), but with high heterogeneity (I² = 52%). TXA did not affect remission of haemoptysis evaluated at seven days after the start of treatment. Adverse effects caused by the drug's mechanism of action were not reported. There was no significant difference in the incidence of mild side effects between active and placebo groups (OR 3.13, 95% CI 0.80 to 12.24).

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