Pulmonary Haemorrhagic Syndromes:Approach and Management

1. Pulmonary Haemorrhagic
Syndromes: Approach and
Management
Presented by: Dr Harshita Das (Junior Resident Department of Respiratory Medicine)
Moderated by:
Dr R.G. Nautiyal ( HOD; Professor Department of Respiratory Medicine)
Dr Ravi Kumar Sharma (Assistant Professor Department of Respiratory Medicine)

2. Contents
1. Introduction
2. Etiology
3. Diagnosis and Evaluation
4. Treatment
5. Specific Diseases

3. Introduction
Pulmonary Haemorrhagic Syndromes are life- threatening
medical conditions characterized by widespread hemorrhage
from the pulmonary microcirculation (arterioles, capillaries,
and venules)involving majority of the alveolar capillary
surface.

4. Etiology
Vasculitis
● Wagner's Granulomatosis
● Microscopic Polyangitis
● Isolated pulmonary
capiliritis
● Mixed cryoglobulinemia
● Bachet’s Syndrome
● Henoch Scholein Purpura
● Pauci immune
glomerulonephritis
Immunological
● Good Pasture’s
Syndrome
● Connective tissue
disorder
● Immune complex
associated
glomerulonephritis
● Acute Pulmonary
allograft rejection

5. Other Causes
● Coagulation disorders
● Idiopathic Pulmonary Hemosiderosis
● Drug/ Toxins
● Diffuse alveolar damage
● Diffuse Infiltrative Lung Disease
● Mitral Stenosis
● Lymphangioleomyomatosis
● Tuberous sclerosis

6. DIAGNOSIS AND
EVALUATION

7. HISTORY
Cardinal symptom: Hemoptysis (absent in 1/3
cases).
Non specific: Shortness of breath , cough ,
fever, chest pain.
Short duration of days to weeks
Recurrent symptoms

8. Careful drug history
Smoking history
History of underlying illnesses such as valvular
heart disease,
Social history, in particular crack cocaine usage

9. History of any renal, skin, nose ,sinuses, or eye
diseases,
History of any immunocompromised status,
bone marrow transplant , radiation
therapy,coagulation disorders, auto immune
disorders

10. Physical examination:
Pallor, fever, pulse oxymetry
Abnormalities suggesting systemic
involvement, includes sinusitis, iridocyclitis,
palpable purpura , dermatological
leukocytoclastic vasculitis, rash, synovitis and
glomerulonephritis.
Inspiratory crackles comman but not
universal.

11. Chest radiography: CXR & HRCT
SCAN
Nonspecific, focal or generalized infiltrates
Rapidly progressive bilateral infiltrates,
Ground glass opacities,
Reticulation as interstitial fibrosis in presence of recurrent
disease
Kerley’s B line suggestive of valvular etiology, also in conditions
associated with myocarditis, pulmonary venoocclusive disease

14. Hematological investigations
Low or falling hematocrit or hemoglobin
In the setting of chronic or recurrent episodes, low serum iron
Nonspecific elevations of white cell count Thrombocytopenia
Elevation of ESR BT, CT ,APTT
ABG –hypoxemia.
RFT –raised serum creatinine.

15. Urine analysis
Proteinuria,
Microscopic hematuria,
Red cell casts suggest glomerulonephrits

16. Serology
● anti neutrophilic cytoplasmic antibodies(ANCA),
● anti-GBM antibodies,
● antinuclear antibodies(ANA),
● anti-dsDNA antibodies,
● antiphospholipid antibodies,
● rheumatoid factor (RF),
● complement levels should be ordered to find out the
underlying disorder.

17. Pulmonary function test
Raised DLCO in acute cases,
Restrictive pattern associated with fibrosis or obstructive
patterns with marked emphysematous changes in chronic
cases.

18. FOB
Bronchoscopy with BAL is essential to the accurate
identification of DAH.
Serial BAL specimens for cell count and differential count.
Increasing red blood cell count among sequential samples
with hemosiderin laden macrophages considered consistent
with the diagnosis.

20. Quantitative scoring of the hemosiderin concentration
(>25%) in alveolar macrophages obtained by BAL cytology
has a good sensitivity for the diagnosis of DAH.
Importantly, BAL serves to rule out other conditions in the
differential diagnosis such as infection, acute lung injury, and
rare interstitial diseases such as acute eosinophilic
pneumonia and pulmonary alveolar proteinosis.

21. Histopathological diagnosis
Diagnostic biopsy remains the gold standard.
Biopsy specimen (renal, lung, other site-skin, upper airway).
Video-Assisted Thoracoscopic Surgery(VATS) is preferred
from open lung biopsy as it is associated with less morbidity
and mortality.

24. Tissue should be frozen (for IF studies),
Fixed in formalin (for H&E and special stains)
Placed in a normal saline solution for culture.
Renal biopsy is preferred as more convenient.
Percutaneous renal biopsy is commonly performed.

25. Pigment-laden alveolar macrophages to be full of iron (blue
cytoplasm) indicative of prior hemorrhage (Prussian blue
stain)

27. Treatment

28. Corticosteroids
Irrespective of etiology, the most immediate concern in
patients with severe immune DAH is to control
intrapulmonary bleeding, which may be fatal.
Adequate oxygenation & supportive measures.
Corticosteroids are considered part of standard therapy for
all immune-mediated DAH syndromes

29. For severe cases (e.g., severe hypoxemia, respiratory failure),
high-dose “pulse” methylprednisolone (1000 mg daily for 3
days) should be given.
Rapid resolution of bleeding can occur, often within 24 to 72
hours of initiation of therapy.
Following the 3-day pulse, corticosteroids (dose of
methylprednisolone 60 to 120 mg per day or equivalent)
should be continued for a few days, until control of the
bleeeding.

32. The subsequent dose and rate of corticosteroid taper need to
be individualized , based upon clinical, radiographic, and
serological response.
The presence of renal involvement, vasculitis, or progression
of DAH on corticosteroids is an indication for adding
cyclophosphamide (or occasionally other immunosuppressive
agents).
Rituximab may be as effective, and possibly more effective
than CYP for ANCA-associated vasculitis, but data are limited
for DAH.

33. Plasmapheresis
Plasmapheresis is a central component of therapy for anti-
GBM disease
Plasmapheresis may have an adjunctive role in patients with
autoimmune DAH and severe renal insufficiency (i.e., serum
creatinine >4 mg%) and in patients with severe or progressive
DAH refractory to corticosteroids or immunosuppressive
agents.

34. Mechanical Ventilation
Mechanical ventilatory support, often with positive end-
expiratory pressure, may be necessary in fulminant cases of
DAH, to prevent death due to refractory hypoxemia.

35. Blood transfusion
Transfusion of red blood cells may be required to maintain an
acceptable hematocrit (more than 25%) and adequate blood
pressure.

36. Specific Diseases

37. Wegener’s granulomatosis
Vasculitis in middle aged adults with necrotizing granulomas
in upper and lower respiratory tract.
c ANCA + Focal segmental necrotizing GN
DAH with capillaritis(subacute and recurrent)
Treated with Corticosteroids and cyclophosphamide.
Newer agent are IVIG, Cotrimox, Antilymphocyte monoclonal
antibodies,tumor necrosis factor inhibitor.

39. Microscopic polyangitis
Small vessel variant of polyangitis.
p ANCA + Focal segmental necrotizing GN.
DAH with capillaritis is common.
Treated with corticosteroid+cyclophosphamide
/azathioprine.
Short term mortality is 25%. 5 yr survival rate is >60%

41. Good pasture’s syndrome
Young smoker
HLA B7 and HLA DR w2 – severe renal disease and poor
prognosis.
DAH + GN + ABMA in serum / tissue
Treated with corticosteroids/cyclophosphamide/az
/plasmapheresis/ MMF/ anti CD20
Predictors of response - %of glomerular involvement + renal
insufficiency.

43. Collagen vascular disease
SLE
<2% of SLE patients have DAH.
Low complement level ANA +, dsDNA
Treatment: corticosteroids/cyclophosphamide/az /plasmapheresis.
Mortality of SLE with DAH is 50%
Rheumatoid arthritis
Scleroderma
MCTD

45. Idiopathic pulmonary hemosideros
Young children and adults
Caused: linked to Stachybotrys atra, immune mediated
20% pediatric patients have LNEand hepatosplenomegaly.
Diagnosis of exclusion (needs lung biopsy to prove as bland
DAH)
Treatment: Corticosteroid / azathioprine Lung transplant.

46. Drugs
Penicillamine: DAH+ immune complex mediated GN
Drugs with capillaritis: prophythiouracil, phenytoin ,
mitomycin.
Trimellitic anhydride: DAH

47. Mitral stenosis
All DAH without renal/ systemic manifestations needs ECHO
to rule out MS

48. Mixed cryoglobulinemia
Purpura+arthritis+hepatitis+Glomerulonephritis
Associated with Hepatitis B / C infections

49. Behcets syndrome
Auto-inflammatory systemic vasculitis of unknown etiology.
Mucocutaneous manifestations, including recurrent oral and
genital ulcerations, ocular manifestations, especially chronic
relapsing uveitis, and systemic vasculitis involving arteries
and veins of all sizes.
5-10% have lung manifestations small vessel vasculitis

50. Lymphangioleomyomatosis
● Premenopausal women
● Proliferation of smooth muscle walls of the pulmonary
lymphatics.
● Chylothorax.
● Pneumothorax- 40%
● Hemoptysis: 40% focal (DAH is rare)

51. Tuberous Sclerosis
● Mutations in TSC1 and TSC 2 gene
● Triad of mental retardation, epilepsy, dermal
angiofibroma.
● Lung involvement : 1%
● Death due to neurological complications

52. Summary
● DAH is a clinico pathologic
syndrome that results from a variety
of conditions and should be
considered a life-threatening event.
● A systematic approach to early
recognition, establishment of
diagnosis, and aggressive treatment
likely decreases the morbidity and
mortality associated with untreated
or unrecognized DAH.

53. References 1) Pulmonary Diseases and Disorders
Book by Alfred Fishman

54. Thank You