A 55 year old man presented to hospital with acute onset shortness of breath, cough and a multiple episodes of small volume haemoptysis. The patient reported several months of rhinitis, sinusitis, arthralgia, myalgia, fever and weight loss. Past medical history includes hypertension for which ramipril is taken.
On examination the patient is coughing up fresh red clots, respiratory rate is 30 breaths/min, SpO2 90% on 15L/min O2 through a non -rebreathe mask and there are bilateral crackles to the mid zones. He is peripherally cold to touch, capillary refill time is 3 seconds, heart rate is 100 beats/min and blood pressure is 96/50. A palpable purpuric rash on his legs and conjunctivitis are also noted.
Investigation findings include:
- Arterial blood gas: pH 7.31, P02 7.5kPa, PC02 4.6kPa, HCO3 20 mmol/L, BE -4
- CXR: diffuse perihilar airspace shadowing with sparing of the apices
- Venous bloods: Hb 85g/L, WCC 25 x109/L, Platelets 304 x109/L, CRP 150mg/l, ESR > 100 mm/h, Urea 15.5 mmol/L, Creatinine 322 µmol/L, Na+ 134 mmol/L, K+ 5.8 mmol/L. Liver function tests and coagulation are normal.
What differential diagnosis are important to consider?
Malignancy with vascular erosion
The most likely diagnosis is vasculitis with pulmonary haemorrhage.
What are the causes of pulmonary haemorrhage?
Pulmonary haemorrhage is a relatively uncommon condition that can present as an isolated finding or as a feature of a multi-systemic disorder. It can be divided into Diffuse Alveolar Haemorrhage or Focal Haemorrhage. The initial distinction between the two may be unclear however alveolar haemorrhage is less likely to cause massive haemopytysis1,2.
Diffuse Alveolar Haemorrhage (originating from pulmonary microvasculature)
- Immune disorders (vasculitis, pulmonary renal syndromes, connective tissue diseases)
- Infection bacterial/ viral/ fungal
- Congestive cardiac failure
- Bleeding disorders including thrombocytopenia, DIC
- Various drugs including cocaine
Focal Haemorrhage (originating from the bronchial circulation or lung parenchyma)
- Vascular erosion
- AV malformation
- Malignancy primary bronchial or metastatic disease
- Local trauma iatrogenic injuries from PA catheter, aortic graft or stent insertion, post bronchoscopic procedures, penetrating chest injuries
- Suppurative lung disease bronchiectasis including cystic fibrosis
- Pulmonary embolism/ septic embolus/ abscess
What rate of blood loss constitutes life threatening pulmonary heamorrhage?
There is no universally agreed volume of blood loss that constitutes massive haemorrhage, however a rate of >100ml/hr or >500ml/day is considered life threatening3.
What is the initial management of suspected pulmonary haemorrhage?
Management of haemopytysis and hypoxic respiratory failure should follow an A-E approach with airway protection, ventilation and circulatory support with ongoing resuscitation and reversal of coagulation abnormalities.
- Secure airway if there is ongoing moderate to large volumes of haemoptysis with evidence of hypoxic respiratory failure to minimise aspiration.
- A large Endotracheal Tube (size 8.0mm or above) should be used with regular suctioning to keep clear and prevent blockage from clots.
- Double lumen tubes can be used to provide single lung ventilation and isolation of bleeding side however can be difficult to place and prone to blockage with large clots.
- For mild to moderate pulmonary haemorrhage: nebulised or intravenous tranexamic acid has been reported to decrease haemoptysis and can be used as a temporising treatment prior to definitive management4.
- In life threatening massive haemorrhage ongoing volume resuscitation with blood products and vasopressor therapy will be required. Thoracic surgery opinion should be sought for rapid intervention with rigid bronchoscopy to tamponade bleeding sites or for definitive surgical management1.
What is the initial diagnostic investigation for pulmonary haemorrhage?
- The investigation of choice is an urgent CT Thorax angiogram to diagnose and differentiate diffuse alveolar haemorrhage from focal haemorrhage via identification of a focal bleeding point. This can then be used to guide endovascular embolization by interventional radiology if appropriate5,6.
- Flexible bronchoscopy can be used to locate an endobronchial lesion but can also differentiate a diagnosis of diffuse alveolar hemorrhage vs focal bleeding using serial bronchoalveolar lavage (BAL). Three 30ml syringes are flushed into a bronchus then aspirated. If blood clears with repeated flushing this suggests bleeding from a bronchial source. If on flushing BAL becomes progressively more hemorrhagic this is suggestive alveolar haemorrhage. This technique is time consuming, operator dependent and does not always give a definitive diagnosis. BAL can also be sent for culture to identify infective cause.
The case continued….
The patient is stabilised and intubated for severe respiratory failure. He has a CT angiogram which does not demonstrate a focal bleeding point amenable to intervention, but does demonstrate patchy bilateral infiltrates with a diffuse ground glass appearance consistent with diffuse alveolar haemorrhage.
What additional investigations may be helpful?
- Diagnostic work up should include full septic screen with blood cultures and viral throat swab to assess for infectious cause.
- Given the history a vasculitis screen should be carried out and includes ANA, dsDNA, RF, C3, C4, Immunoglobulins, Cryoglobulins, ANCA (anti-myeloperoxidase & anti-Protease-3) and also urinalysis to assess for haematuria and proteinuria with a suspected nephritis in pulmonary- renal syndrome.
What management should be initiated in ICU?
- Standard supportive ICU care, lung protective ventilation with tidal volumes of 6-8ml/kg
- Antibiotics with early initiation of steroids if vasculitis suspected cause and to cover for possible infectious cause; antibiotics can be discontinued within 24-48 hours, based on cultures and procalcitonin
- Steroid treatment should be guided by MDT for suspected vasculitis. Treatment regimes often consist of pulsed methylprednisolone (e.g 125-250 mg IV QDS for three days followed by 1mg/kg for maintenance)
- Other treatment options for antibody-mediated diseases include plasma exchange therapy and other immunosuppressive agents such as cyclophosphamide
The case continued….
The patient was transferred to the intensive care unit for ongoing management. He was initiated on broad spectrum antibiotic therapy with pulsed steroids due to the suspicion of vasculitis. Urgent vasculitis screen revealed positive C-ANCA and anti-PR3 confirming the diagnosis of Granulomatosis with Polyangiitis. He went on to receive plasma exchange and cyclophosphamide on specialist advice of rheumatology. Alveolar haemorrhage can be the presenting manifestation in approximately 10% of patients with Granulomatosis with Polyangiitis.
Take home messages
- Pulmonary haemorrhage can be life threatening and can be associated with high mortality
- Clinical presentation may mimic multiple pathologies.
- Initial aetiology may not be clear and treatment for potential underlying causes with resuscitation should be initiated early
- CT thorax angiogram is the initial investigation of choice and can guide diagnosis, differentiate between diffuse alevolar and focal haemorrhage and also guide embolisation if appropriate.
- Suspect pulmonary haemorrhage as a differential diagnosis in a patient with new anaemia, haemoptysis and hypoxic respiratory failure
1) Kathuria, H., Hollingsworth, H.M., Vilvendhan, R. et al. Management of life-threatening hemoptysis. j intensive care 8, 23 (2020). https://doi.org/10.1186/s40560-020-00441-8
2) Ficker JH, Brückl WM, Suc J, Geise A. Hämoptoe : Intensivmedizinisches Management von Lungenblutungen [Haemoptysis : Intensive care management of pulmonary hemorrhage]. Internist (Berl). 2017 Mar;58(3):218-225. German. doi: 10.1007/s00108-017-0190-7. PMID: 28138763.
3) Hirshberg B, Biran I, Glazer M, Kramer MR. Hemoptysis: etiology, evaluation, and outcome in a tertiary referral hospital. Chest. 1997;112(2):440–
4) Bellam BL, Dhibar DP, Suri V, Sharma N, Varma SC, Malhotra S, et al. Efficacy of tranexamic acid in haemoptysis: a randomized, controlled pilot study. Pulm Pharmacol Ther. 2016;40:80–3.
5) Revel MP, Fournier LS, Hennebicque AS, Cuenod CA, Meyer G, Reynaud P, et al. Can CT replace bronchoscopy in the detection of the site and cause of bleeding in patients with large or massive hemoptysis? AJR Am J Roentgenol. 2002;179(5):1217–24
6) Ittrich H, Klose H, Adam G. Radiologic management of haemoptysis: diagnostic and interventional bronchial arterial embolisation. Rofo. 2015;187(4):248–59.