Tranexamic Acid Per Inhalation for Treatment of Pulmonary Hemorrhage in Pediatric Patients

Pulmonary hemorrhage can be severe and life-threatening. In children, etiologies of pulmonary
hemorrhage include respiratory infection, foreign bodies, bronchiectasis, pulmonary vascular
disorders, parenchymal lung disease, and post-surgical complications. Initial management of
pulmonary hemorrhage includes stabilization of the patient, securing the airway, initiative
high positive end-expiratory pressure to attempt to tamponade the source of hemorrhage and
repletion with blood products. Following stabilization of the patient, investigation and
further management of hemorrhage includes bronchoscopy, surgery, or catheterization. Sources
of bleeding such as endobronchial lesions are often identified and managed with bronchoscopy
and the instillation of vasoactive medications or cold water to induce vasospasm and/or
balloon tamponade. Vascular bleeding can be surgically ligated or embolized via
catheterization. Unidentifiable bleeding occurs with distal vascular injury and is limited to
attempted catheter guided embolization of bleeding vessels if found, supportive treatment,
and correction of a coagulopathy if present. As etiologies of pulmonary hemorrhage vary,
outcomes and prognosis in pediatric pulmonary hemorrhage are difficult to determine, however,
mortality still remains a risk.

Tranexamic acid (TXA) is a lysine analog that blocks the conversion of plasminogen to plasmin
and the interaction with fibrin, preventing blood clot breakdown, thereby reducing bleeding.
The United States (US) Food and Drug Administration approved the intravenous formulation of
TXA for the treatment of bleeding patients with hemophilia in 1986 and the oral formulation
for the use of severe menorrhagia in 2009. In 2011, The World Health Organization listed TXA
as an essential medication based on its successful use in adult trauma-related hemorrhage.
Studies show the successful off-label use of TXA in children for congenital heart surgery,
orthopedic procedures, neurosurgical procedures, trauma, immune thrombocytopenic purpura,
epistaxis, hemorrhage complicating a procedure, bilateral lung transplantation, chemotherapy
injections, and bone marrow biopsies among other diagnoses and procedures. Very little data
on the use of TXA for pediatric pulmonary hemorrhage exists. Only two case reports show TXA
controlling hemoptysis in children with cystic fibrosis-related hemoptysis. A systematic
review concluded that the use of TXA for hemoptysis was associated with a significant
reduction in length of bleeding. A recent randomized control trial showed the TXA decreased
the severity of the hemoptysis and may be used as a bridge to other interventions.

The powerful anti-fibrinolytic properties and relatively low side-effect profile lend TXA to
the off-label use in children to reduce bleeding in other diagnoses. There are not enough
studies and data, however, to recommend the routine use of TXA in hemoptysis.