DIFFUSE ALVEOLAR DIFFUSE ALVEOLAR HEMORRHAGE HEMORRHAGE

Dr.Shahid PervaizDr.Shahid Pervaiz

Resident PulmonologyResident Pulmonology

Nishtar Hospital MultanNishtar Hospital Multan

DIFFUSE ALVEOLAR DIFFUSE ALVEOLAR HEMORRHAGEHEMORRHAGE

• acute, life-threatening eventacute, life-threatening event

• repeated episodes can lead to: repeated episodes can lead to:

• organizing pneumoniaorganizing pneumonia

• collagen deposition in small airwayscollagen deposition in small airways

• fibrosisfibrosis

DIFFUSE ALVEOLAR DIFFUSE ALVEOLAR HEMORRHAGEHEMORRHAGE

• Wegener granulomatosisWegener granulomatosis

• microscopic polyangiitismicroscopic polyangiitis

• Goodpasture syndromeGoodpasture syndrome

• connective tissue disordersconnective tissue disorders

• antiphospholipid antibody syantiphospholipid antibody sy

• infectious or toxic exposuresinfectious or toxic exposures

• neoplastic conditionsneoplastic conditions

CAUSES OF DIFFUSE CAUSES OF DIFFUSE ALVEOLAR HEMORRHAGEALVEOLAR HEMORRHAGE

• vasculitis or capillaritis vasculitis or capillaritis

• pulmonary haemorrhage without pulmonary haemorrhage without capillaritis or vasculitis (»bland« capillaritis or vasculitis (»bland« pulmonary haemorrhage) pulmonary haemorrhage)

• alveolar bleeding associated with alveolar bleeding associated with another process or condition another process or condition

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONS

week) week)

• dyspnea, dyspnea,

• cough, cough,

• fever,fever,

• haemoptysis are the most common haemoptysis are the most common clinical manifestations of Acute or clinical manifestations of Acute or subacute (present for less than a DAH. subacute (present for less than a DAH.

**Haemoptysis may be absent at time of presentation in up to a third of patients.Haemoptysis may be absent at time of presentation in up to a third of patients.

DIAGNOSTIC DIAGNOSTIC EVALUATIONEVALUATIONChest X-rayChest X-ray

• diffuse, bilateral diffuse, bilateral consolidation or consolidation or ground-glass opacities ground-glass opacities due to alveolar filling due to alveolar filling

• distributed in the distributed in the perihilar regions, perihilar regions, sparing the apices and sparing the apices and costophrenic angels costophrenic angels

DIAGNOSTIC DIAGNOSTIC EVALUATIONEVALUATIONHRCTHRCT

• better evaluate the better evaluate the extent of disease extent of disease

• more sensitive in more sensitive in identifying ground-identifying ground-glass opacities, but glass opacities, but not more specificnot more specific

DIAGNOSTIC DIAGNOSTIC EVALUATIONEVALUATIONLaboratory testsLaboratory tests

• anemia, leukocytosisanemia, leukocytosis

• ESR, CRPESR, CRP

• blood urea and serum blood urea and serum creatinine, abnormal creatinine, abnormal findings of urin analysis findings of urin analysis in pulmonary-renal sy in pulmonary-renal sy

• anti-GBM, ANCA, C3 anti-GBM, ANCA, C3 and C4, anti-ds-DNA, and C4, anti-ds-DNA, antiphospholipid Ab antiphospholipid Ab

Pulmonary Pulmonary functionfunction testtest

• increased diffusing increased diffusing capacity capacity

• restrictive changes restrictive changes

• obstructive obstructive changeschanges

DIAGNOSTIC DIAGNOSTIC EVALUATIONEVALUATIONBronchoscopyBronchoscopy

• to document alveolar hemorrhage by BAL to document alveolar hemorrhage by BAL

• to exclude airway sources of bleedingto exclude airway sources of bleeding

• to exclude an associated infectionto exclude an associated infection

Within the first 48 hours of symptoms the diagnostic yield is Within the first 48 hours of symptoms the diagnostic yield is higher!higher!

BALBAL

• is the method of is the method of choice choice

• by showing free by showing free red blood cells and red blood cells and hemosiderin-laden, hemosiderin-laden, iron-positive iron-positive macrophages macrophages

TREATMENT OF DAHTREATMENT OF DAH

• combination of treatment autoimmune combination of treatment autoimmune destruction of the alveolare capillary membrane destruction of the alveolare capillary membrane and the underlaying conditionand the underlaying condition

• immunosupresive agents are the mainstay of immunosupresive agents are the mainstay of therapy, especially if DAH is associated with therapy, especially if DAH is associated with systemic or pulmonary vasculitis, Goodpasture systemic or pulmonary vasculitis, Goodpasture syndrome or conective tissue disorderssyndrome or conective tissue disorders

• treatment of small vessel vasculitis of the lung is treatment of small vessel vasculitis of the lung is largely the same, regardless of aetiology or largely the same, regardless of aetiology or whether it is isolated to the lung or a component whether it is isolated to the lung or a component of a systemic diseaseof a systemic disease

TREATMENT OF DAHTREATMENT OF DAH

Immunosupresive agentsImmunosupresive agents• MethylprednisoloneMethylprednisolone and and• Cyclophosphamide Cyclophosphamide are the mainstay of therapy.are the mainstay of therapy. • Plasmapheresis - Plasmapheresis - clinical benefit in Goodpasture clinical benefit in Goodpasture

syndrome syndrome • Recombinant activated human factor VII-Recombinant activated human factor VII-

successful in several case reports of treating successful in several case reports of treating alveolar hemorrhage due to allogenic alveolar hemorrhage due to allogenic hematopoietic stem cell transplantation, ANCA hematopoietic stem cell transplantation, ANCA associated vascullitis, SLE or antiphospholipid associated vascullitis, SLE or antiphospholipid syndrome.syndrome.

TREATMENT OF DAH-other TREATMENT OF DAH-other possible management possible management measures:measures:• supplemental oxygen, supplemental oxygen,

• bronchodilators, bronchodilators,

• reversal of any coagulopathy, reversal of any coagulopathy,

• intubation with bronchial tamponade,intubation with bronchial tamponade,

• protective strategies for the less involved protective strategies for the less involved lung,lung,

• mechanical ventilation mechanical ventilation

should be done in the course of the disease if should be done in the course of the disease if they are needed.they are needed.

CONCLUSIONCONCLUSION

• DAH can be a catastrophic illness if DAH can be a catastrophic illness if recognition and treatment are delayed.recognition and treatment are delayed.

• Diagnosis is often aided by other systemic Diagnosis is often aided by other systemic findings, associated illnes and serological findings, associated illnes and serological results. results.

• Patients with unexplained isolated DAH Patients with unexplained isolated DAH should undergo a lung biopsy with should undergo a lung biopsy with immunofluorescent studies and routine immunofluorescent studies and routine histological tests. histological tests.

• During therapy close monitoring, due to During therapy close monitoring, due to potential complications of treatment and the potential complications of treatment and the possibility to relapses, is needed.possibility to relapses, is needed.

Alveolar haemorrhage Alveolar haemorrhage syndromes syndromes

• Is a rare in potentially life Is a rare in potentially life threatening condition characterized threatening condition characterized by diffuse blood leakage from the by diffuse blood leakage from the pulmonary micro circulation in to the pulmonary micro circulation in to the alveolar spaces due to the alveolar spaces due to the microvascular damage. microvascular damage.

• It is not a single disease but a clinical It is not a single disease but a clinical syndrome that may have numerous syndrome that may have numerous cause including autoimmune diseases, cause including autoimmune diseases, infection, drug toxicities, coagulopathies, infection, drug toxicities, coagulopathies, malignancies and CV disorders.malignancies and CV disorders.

• Clinical worsening may occur within days Clinical worsening may occur within days and lead to acute respiratory failure or and lead to acute respiratory failure or damage to extra thoracic organs such as damage to extra thoracic organs such as kidnies kidnies

• Admission to the intensive care unit Admission to the intensive care unit is required up to 50% of cases.is required up to 50% of cases.

• Average mortality is 30%.Average mortality is 30%.

• Prompt therapy may be life saving Prompt therapy may be life saving and preserve organ function.and preserve organ function.

•Rapidly and accurately Rapidly and accurately identifying the cause of identifying the cause of AH is therefore a key AH is therefore a key issue.issue.

• AH must be distinguished from localized AH must be distinguished from localized bleeding originating from the bronchial bleeding originating from the bronchial circulation caused by air way disorders such circulation caused by air way disorders such as as

1)1)BronchiectasisBronchiectasis

2)2)InfectionInfection

3)3)TumoursTumoursHaemorrhage of bronchial origin always manifest with Haemorrhage of bronchial origin always manifest with

haemoptysis.haemoptysis.

In contrast Ah occurs distally in the alveolar spaces In contrast Ah occurs distally in the alveolar spaces and haemoptysis is not always present despite and haemoptysis is not always present despite significant blood loss which may cause severe significant blood loss which may cause severe anemia anemia

Sub divisions of AHSub divisions of AH

1.1.Acute Acute

2.2.Sub acute Sub acute

3.3. chronicchronic

1. Acute1. Acute

• Presence of macroscopically Presence of macroscopically haemorrhagic either pink or red BAL haemorrhagic either pink or red BAL fluid which classically becomes fluid which classically becomes increasingly red on successive increasingly red on successive aliquot aliquot

2. Sub Acute2. Sub Acute

• BAL cytology shows numerous blood BAL cytology shows numerous blood cells and haemosiderin laden cells and haemosiderin laden macrophages when AH last for > 3 macrophages when AH last for > 3 days.days.

3 . Chronic3 . Chronic

• Presence of haemosiderin laden Presence of haemosiderin laden macrophages representing a greater macrophages representing a greater then 30% of the macrophages BAL then 30% of the macrophages BAL population with or without RBC.population with or without RBC.

CAUSESCAUSES

1)1)Immune (42%)Immune (42%)

2)2)Non Immune (58%)Non Immune (58%)

1. Immune1. Immune

• Microscopic polyangitis Microscopic polyangitis

• Wegener’s granulomatosisWegener’s granulomatosis

• Goodpasture syndromeGoodpasture syndrome

2.2. Non ImmuneNon Immune

• Heart disease Heart disease

• Coagulation disorders Coagulation disorders

• InfectionsInfections

• MalignanciesMalignancies

Clinical manifestations Clinical manifestations

HaemoptysisHaemoptysis

Diffuse alveolar opacitiesDiffuse alveolar opacities AnaemiaAnaemia

At CXRAt CXR

AH should be suspected when atleast two signs AH should be suspected when atleast two signs are presentare present

• Haemoptysis Haemoptysis

is present in 40-80% of is present in 40-80% of cases but is rarely abundant even in cases but is rarely abundant even in severe AH because of the distal location severe AH because of the distal location of the bleeding source of the bleeding source

DyspnoeaDyspnoea

is of variable severity and result is of variable severity and result from both V/Q mismatch and anaemia.from both V/Q mismatch and anaemia.

Systemic symptoms ( fever, myalgias, Systemic symptoms ( fever, myalgias, arthralgias) ocular manifestation, ENT arthralgias) ocular manifestation, ENT symptoms or skin changes may be symptoms or skin changes may be present.present.

THANK YOUTHANK YOU