Background: We observed diffuse alveolar hemorrhage (DAH) relatively frequently at our Bone Marrow Transplant and Nephrology Units (ANCA positive vasculitis + DAH). We tried to refine DAH medical treatments, cooperating with intensive care specialists. During the last 3 years we treated 14 DAH cases (4 posttransplant, 1 cirrhosis, and 9 pulmonary vasculitis).

Patients, treatments

The patient cohorts according to the underlying disease, DAH severity (micro or macro DAH according to Uptodate recommendations), hemostatic drug dose, way of application, responses are summarised in Table I.

Table 1.
Patient cohortsDAH severityrFVIIa dose way of applicationintratraecheal tranexamic acid doserepeatedreponse comment
Bone marrow transplant related DAH (amyloidosis, AML, CNS lymphoma) macro 3
micro 1 		50 ug/kg in 10 ml bronchoscopy 500 mg in 5 ml bronchoscopy 1 day later 1x, few days later 2x inhalation bleeding stopped
combined with iv rFVIIa + tranexamic acid in 2 cases with systhemic bleeding 
Primary biliary cirrhosis, liver failure macro 50 ug/kg 10 ml bronchoscopy 500 mg in 5 ml bronchoscopy inhalation 1 day later 1x bleeding stopped 
ANCA positive vasculitis induced DAH macro 3
micro 4 		50 ug/kg 10 ml bronchoscopy
40 ug/kg rFVIIa, 		500 mg in 5 ml bronchoscopy inhalation 1 day later 1x
2 hours 		bleeding stopped
bleeding stopped 
Patient cohortsDAH severityrFVIIa dose way of applicationintratraecheal tranexamic acid doserepeatedreponse comment
Bone marrow transplant related DAH (amyloidosis, AML, CNS lymphoma) macro 3
micro 1 		50 ug/kg in 10 ml bronchoscopy 500 mg in 5 ml bronchoscopy 1 day later 1x, few days later 2x inhalation bleeding stopped
combined with iv rFVIIa + tranexamic acid in 2 cases with systhemic bleeding 
Primary biliary cirrhosis, liver failure macro 50 ug/kg 10 ml bronchoscopy 500 mg in 5 ml bronchoscopy inhalation 1 day later 1x bleeding stopped 
ANCA positive vasculitis induced DAH macro 3
micro 4 		50 ug/kg 10 ml bronchoscopy
40 ug/kg rFVIIa, 		500 mg in 5 ml bronchoscopy inhalation 1 day later 1x
2 hours 		bleeding stopped
bleeding stopped 
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The diagnostic evaluation of DAH was run according to international standard requirements, based upon repeated bronchoalveolar lavage. Platelet transfusions and factor supplementation were applied according to the recommendations. Standard non-specific DAH related intensive care was provided for all cases

The basis of our DAH drug treatment approach was intrapulmonary (bronchoscopical/intratracheal or inhalatory) or systhemic (iv) recombinant FactorVIIa (Novoseven) application, combining with systhemic or local tranexamic acid. Novoseven (rFVIIa) has received Orphan Drug Status from FDA and EMA recently. Novoseven is usually combined in severe systhemic bleedings with tranexamic acid, however, there is very limited information available on the combined approach in DAH.

Results, discussion

All of our DAH bleeding was stopped or impressively reduced after rFVIIa+tranexamic acid interventions. However, overall survival was determined mostly by the underlying condition (i.e. amyloid heart disease, refractory AML, etc.)

The pattern of bleeding was somewhat different according to etiology: posttransplant and hematological background predisposed to more macro DAH, bleeding cessation could be well achieved, usually repeated interventions were necessary. Patients with non malignant disease (vasculitis, liver failure) had both micro and macro DAH, bleed slightly less, interventions seemed to produce more durable responses.

DAH seemed to be less modifyed by systhemic hemostatic parameters, than some other bleeds. Platelet transfusion alone rarely achieved significant improvement. We did not observe thrombotic events in our cases following intratracheal or iv treatments..

In conclusion: if DAH develops, the combined application of systhemic (iv) and/or intrapulmonary rFVIIa/tranexamic acid combination achieves a relatively quick bleeding cessation and improvement of respiration, allowing time for other interventions to improve underlying conditions and outcome. For micro DAH iv rFVIIa (40 ug/kg, repeated 2 hourly if needed) +tranexamic acid seems to be safe and effective. For fulminant macro DAH we do suggest to apply rFVIIa 50 ug/kg+tranexamic acid 50 mg in 10-15 ml volume, which stops bleeding quickly, improves respiration and can be life saving. This intervention might be repeated after 24 hours, usually by inhalation. In less severe makro DAH the inhalatory approach might be useful.

We do support to register DAH treatment approaches to further optimalise results.

Disclosures

No relevant conflicts of interest to declare.

Topics:
diffuse alveolar hemorrhage, hemostatics, hemorrhage, recombinant coagulation factor viia, bronchoscopy, microbiology procedures, tranexamic acid, vasculitis, antineutrophil cytoplasmic autoantibody, bone marrow transplantation

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2015 by The American Society of Hematology
2015
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