Diffuse alveolar hemorrhage (DAH) is a life-threatening condition characterized by widespread bleeding from the pulmonary microcirculation. It can be caused by capillaritis due to conditions like Wegener's granulomatosis or idiopathic. Diagnosis involves clinical evaluation, chest imaging, hematological and urine tests, and bronchoscopy with BAL. Treatment focuses on controlling bleeding with corticosteroids, immunosuppressants, and supportive care. DAH requires prompt diagnosis and treatment to reduce high morbidity and mortality risks.

1. ALVEOLAR HEMORRHAGE
PRABHAKAR K

2. Learning objectives
 INTRODUCTION
 DIFFUSE ALVEOLAR HEMORRAHGE (DAH)
 ETIOLOGY OF DAH
 PATHOLOGY OF DAH
 DIAGNOSIS AND EVALUATION
 TREATMENT
 SOME SPECIFIC CONDITIONS
 SUMMARY

3. INTRODUCTION
 Bleeding from the lung originates from the
bronchial vessels, the pulmonary vessels, or the
microcirculation of the lung.
• Bleeding of bronchial origin is usually a result of
bronchiectasis or endobronchial malignancy.

4. • Pulmonary hemorrhage originating from the
small, medium, and large pulmonary vessels
is most commonly due to systemic vasculitis,
which can also involve the microcirculation.
• Vasculitides involving the microvasculature is
known as pulmonary capillaritis.

5.  Unlike the more common forms of pulmonary
hemorrhage that result from focal lesions (e.g.,
necrotizing pneumonia, bronchitis,
bronchiectasis, malignancy, pulmonary
infarction, arteriovenous malformation), DAH
affects the majority of the alveolar capillary
surface.

6. DIFFUSE ALVEOLAR
HEMORRAHGE
 Diffuse alveolar hemorrhage is a life-
threatening medical condition characterized
by widespread hemorrhage from the
pulmonary microcirculation (arterioles,
capillaries, and venules)involving majority of
the alveolar capillary surface.
 Intrapulmonary hemorrhage / Pulmonary
alveolar hemorrhage / Pulmonary capillary
hemorrhage / Microvascular lung
hemorrhage.

7. Etiology of DAH

8. Capillaritis
 Wegener’s granulomatosis
 Microscopic polyangitis
 Isolated pulmonary capillaritis
 Connective tissue disorder
 Primary antiphospholipid syndrome
 Mixed cryoglobulinemia
 Behcets syndrome
 Henoch scholein purpura
 Goodpasture’s syndrome
 Pauci-immune glomerulonephritis
 Immune complex associated glomerulonephritis
 Drug induced
 Acute lung allograft rejection

9. Without Capillaritis
 Idiopathic pulmonary hemosiderosis
 Systemic lupus nephritis
 Good pasture’s syndrome
 Diffuse alveolar damage
 Penicillamine
 Timellitic anhydride
 Mitral stenosis
 Coagulation disorder
 Pulmonary veno-occlusive disease
 Pulmonary capillary hemangiomatosis
 Lymphangioleiomyomatosis
 Tuberous sclerosis

10. Pathology
• PULMONARY CAPILLARITIS : has a unique
histopathologic appearance consisting of
 interstitial neutrophilic predominant
infiltration,
 fibrinoid necrosis of the alveolar and capillary
walls, and
 leukocytoclasis.

11.  The infiltrating neutrophils undergo cytoclasis,
nuclear debris accumulates within the
interstitium, and there is a subsequent loss of
the integrity of the alveolarcapillary
basement membrane.
 The disruption of the alveolar-capillary
basement membranes that results in the
accumulation of RBCs in alveolar spaces.

12. (A) Polymorphoneutrophils invading the
capillary walls (arrow head)
(B) RBC accumulation in the alveolar spaces
and

13.  BLAND HEMORRAGE (without
capillaritis) RBC’s in the alveolar spaces,
but alveolar walls appear normal except
for type II epithelial cell hyperplasia.
 Diffuse alveolar damage:
Hyaline membrane formation, alveolar
and interstitial edema, microthrombi, and
capillary congestion are present

14. Acute hemorrhage with blood filling
alveolar spaces.

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

16. DIAGNOSIS AND EVALUATION
 CLINCAL EVALUATION
 CHEST RADIOGRAPHY
 HEMATOLOGICAL INVESTIGATIONS
 URINE ANALYSIS
 SEROLOGY
 PULMONARY FUNCTION TEST
 FOB
 HISTOPATHOLOGICAL DIAGNOSIS

17. Clinical evaluation
 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..

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

19.  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.

20.  Physical examination:
Pallor , fever, pulse ox..
 Clinical evaluation should include search for
abnormalities suggesting systemic
involvement, includes
sinusitis, iridocyclitis, palpable purpura
dermatological leukocytoclastic vasculitis,
rash
synovitis and glomerulonephritis.
• Inspiratory crackles comman but not
universal.

21. 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

22. Chest radiographs show bilateral diffuse alveolar
opacities secondary to diffuse alveolar
hemorrhage in patient with microscopic
polyangiitis

23. High-resolution computed tomography scan of diffuse alveolar
hemorrhage: confluent and patchy greyish areas.

24. 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.

25. Urine analysis
 Proteinuria,
 microscopic hematuria,
 red cell casts suggest glomerulonephrits.

26. 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.

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

28. 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.

30.  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.

31. 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.

32.  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.

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

34. syndrom
e
ane
mia
ren
al
arthr
itis
ski
n
ANA Ds
DN
A
RF Com
plem
ent
ABM
A
ANCA Histopatholog
y /immuno
fluroscence
Wegener
G
+ + + + ± – ± N – C + Capillaritis
/ Granular
Micro PA + + + + ± – ± N – P + Capillaritis /
No
deposits
IP
Capillariti
s
+ – – – – – – N – – Capillaritis /
No deposits
Good
Pastures
+ + – – – – – N + – Bland/capill
aritis
/Linear IgG
SLE + + + ± + + ± Low – – Bland/Capill
ariitis/Gran
ular IgG
IP
Hemosi
+ – – – – – – N – – Bland /
No deposits
Clinical Differentiation of Common Diffuse Alveolar Hemorrhage
Syndromes

35. Treatment
 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

36.  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.

37.  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.

38.  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.

39.  Mechanical ventilatory support, often with
positive end-expiratory pressure, may be
necessary in fulminant cases of DAH, to
prevent death due to refractory hypoxemia.
 Transfusion of red blood cells may be
required to maintain an acceptable hematocrit
(more than 25%) and adequate blood
pressure.

40. Wegener’s granulomatosis
 Sytemic 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.

41. 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%.

42. 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

44. 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.

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

46. Mitral stenosis: all DAH without renal/ systemic
manifestations needs ECHO to r/o MS.
Mixed cryoglobulinemia:
Purpura+arthritis+hepatitis+GN A/w Hepatitis
B / C infections
Leucocyclastic vasculitis.
Behcets syndrome:
5-10% have lung manifestations
small vessel vasculitis

47. Lymphangioleomyomatosis:
 premenopausal women
 proliferation of smooth muscle wallsof the
pulmonary lymphatics.
 chylothorax.
 pneumothorax- 40%
 hemoptysis: 40% focal (DAH is rare)

48. Tuberous sclerosis
 mutations in TSC1 and TSC 2 gene
 triad of mental retardation,
 epilepsy, derma angiofibroma.
 lung involvement : 1%
 death due to neurological
 complication

49. Summary
 DAH is a clinico pathologic syndrome that
results from a variety of conditions and
should be considered a life-threatening
event.
 Once believed to be a rare syndrome,
DAH is being recognized with increasing
frequency.

50.  A systematic approach to early
recognition, establishment of diagnosis,
and aggressive treatment likely
decreases the morbidity and mortality
associated with untreated or
unrecognized DAH.

51. THANK YOU
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