Successful pulmonary administration of activated recombinant factor VII in diffuse alveolar hemorrhage

Heslet, Lars; Nielsen, Jørn Dalsgaard; Levi, Marcel; Sengeløv, Henrik; Johansson, Pär I.

doi:10.1186/cc5132

Cited by 91 publications

(48 citation statements)

References 24 publications

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“…DAH is a syndrome characterized by injury to the alveolocapillary basement membrane, resulting in red blood cell extravasation into the alveolar spaces. Treatment largely relies on supportive care; however, a small Denmark series demonstrated that local (endobronchial) administration of recombinant activated factor VII (FVIIa) at 50 mcg/kg in 50 cc of normal saline may be beneficial [ 8 ]. The therapeutic effect of endobronchial FVIIa draws on its ability to directly bind receptors on the alveolar surface where tissue factor resides in large concentrations.…”

Section: Discussionmentioning

confidence: 99%

A curious case of acute respiratory distress syndrome

Crawford

Grimm

Magruder

et al. 2015

Journal of Surgical Case Reports

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Gestational acute respiratory distress syndrome (ARDS) is a complicated problem with the potential to gravely harm both mother and fetus. This case report describes a young woman in her second trimester of pregnancy who developed progressive respiratory failure in the setting of newly diagnosed influenza, diffuse alveolar hemorrhage and lymphangioleiomyomatosis. The patient's condition was refractory to conventional interventions and required extracorporeal membrane oxygenation (ECMO) support. Her course was further complicated by preeclampsia requiring preterm delivery with cesarean section while on ECMO. Through novel therapies and a multidisciplinary approach to care, both the patient and her child would overcome these unique and challenging conditions and survive.

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Section: Discussionmentioning

confidence: 99%

A curious case of acute respiratory distress syndrome

Crawford

Grimm

Magruder

et al. 2015

Journal of Surgical Case Reports

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“…As late as in 2011 it is still suggested that treatment of DAH should be based “on the underlying cause of hemorrhage, with corticosteroids as a mainstay of therapy in most cases”,22 despite of the first series of a systematic treatment of DAH with local intrapulmonary FVIIa in 2006 31. This study documented an effect of administering a small intrabronchial dose of FVIIa.…”

Section: Introductionmentioning

confidence: 85%

“…Using a micropump nebulizer ensures that there will not be any interference with the active site of the FVIIa molecule. The only documented case of inhalation of FVIIa by a micropump where the DAH has been treated with success was a patient with Wegener’s granulomatosis 31. The patient had been extubated a few hours earlier after a bout of hemoptysis and had presented with recurrence of the DAH through bloody tinged expectorate.…”

Section: Introductionmentioning

confidence: 99%

Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) – a review of a new treatment paradigm

Heslet¹,

Nielsen²,

Nepper-Christensen³

2012

BTT

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BackgroundDiffuse alveolar hemorrhage (DAH) is a clinical syndrome with typical symptoms dyspnea and hemoptysis. DAH is a complication of specific diseases, in some cases with acute catastrophic hemoptysis, while other patients present low grade alveolar bleeding with a need of chronic transfusion as in pulmonary hemosiderosis.MethodsCurrent literature in the PubMed database and other sources was reviewed in order to evaluate the current treatment recommendations, efficacy of this treatment, and finally the risk of complications after off-label use of rFVIIa in respect to DAH.Objectives(i) To elucidate the clinical aspects of alveolar hemorrhage, (ii) to develop a simple diagnostic algorithm in order to separate DAH from other important pulmonary diseases with similar clinical picture and comparably high mortality. Such an algorithm has important therapeutic consequences because these diseases: acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and bronchiolitis obliterans organizing pneumonia (BOOP) have different therapies, (iii) to evaluate and discuss whether local pulmonary administration may improve outcome and reduce mortality in DAH, and (iv) to suggest a treatment schedule.ResultsHitherto the diagnosis and treatment of DAH has been based on anecdotal reports. The treatment has relied on different unspecific treatment modalities based on a mixture of treatment of the underlying disease and treatment without evidence targeted to stop the alveolar bleeding. However, recently a number of publications have advocated the use of intrapulmonary rFVIIa. Even in severe bleeding DAH has been shown to respond promptly without thromboembolic complication when FVIIa was administered locally via the air side, because the FVIIa does not penetrate the alveolo-capillary membrane to the blood-side. The incidence of DAH (in the US and Europe is 100,000–150,000, and 50,000 patients annually are at risk of developing DAH following hematopoietic stem cell transplant (HSCT) and autoimmune diseases. Finally 50,000–100,000 patients may be falsely categorized as having acute respiratory distress syndrome/acute lung injury (ARDS/ALI) because DAH and ARDS cannot be separated clinically. A new treatment paradigm of DAH is proposed as no other intervention has been able to ensure pulmonary hemostasis in DAH. The diagnosis of DAH is simple, a series of broncho-alveolar washes which become increasingly bloody. This test should be performed in all patients with pulmonary opacities in order to separate ARDS/ALI from DAH. FVIIa administrated via pulmonary route is “drug of choice”, because it stops bleeding in the life-threatening syndrome DAH. Hemostasis is obtained after only one to two small doses of FVIIa (50 μg/kg body weight per dose) and after hemostasis the oxygen transport quickly improves.ConclusionIntrapulmonary administration of rFVIIa is recommended as the treatment of choice for DAH and blast lung injury (BLI) because the treatment has been shown to be successful and uncomplicated in spite of the fact that on...

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“…[66] Recombinant activated factor VII can be administered locally[67] or systemically as used by Tatopoulos et al . [66] Several thrombotic complications, including myocardial ischemia and deep venous thrombosis, have been reported with use of recombinant activated factor VII.…”

Section: Treatmentmentioning

confidence: 99%

Pulmonary manifestations of leptospirosis

Gulati

2012

Lung India

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Leptospirosis has a spectrum of presentation which ranges from mild disease to a severe form comprising of jaundice and renal failure. Involvement of the lung can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome. Of late, it has been identified that leptospirosis can present atypically with predominant pulmonary manifestations. This can delay diagnosis making and hence optimum treatment. The purpose of this review is to bring together all the reported pulmonary manifestations of leptospirosis and the recent trends in the management.

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Successful pulmonary administration of activated recombinant factor VII in diffuse alveolar hemorrhage

Cited by 91 publications

References 24 publications

A curious case of acute respiratory distress syndrome

A curious case of acute respiratory distress syndrome

Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) – a review of a new treatment paradigm

Pulmonary manifestations of leptospirosis

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Successful pulmonary administration of activated recombinant factor VII in diffuse alveolar hemorrhage

Cited by 91 publications

References 24 publications

A curious case of acute respiratory distress syndrome

A curious case of acute respiratory distress syndrome

Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) &ndash; a review of a new treatment paradigm

Pulmonary manifestations of leptospirosis

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Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) – a review of a new treatment paradigm