Thrombosis in small and medium-sized pulmonary arteries in Wegener’s granulomatosis: A confocal laser scanning microscopy study J Bras Pneumol.2010;36(6):724-730 - PowerPoint PPT Presentation

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Thrombosis in small and medium-sized pulmonary arteries in Wegener’s granulomatosis: A confocal laser scanning microscopy study J Bras Pneumol.2010;36(6):724-730

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Thrombosis in small and medium-sized pulmonary arteries in Wegener s granulomatosis: A confocal laser scanning microscopy study J Bras Pneumol.2010;36(6):724-730 – PowerPoint PPT presentation

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Title: Thrombosis in small and medium-sized pulmonary arteries in Wegener’s granulomatosis: A confocal laser scanning microscopy study J Bras Pneumol.2010;36(6):724-730


1
Thrombosis in small and medium-sized pulmonary
arteries in Wegeners granulomatosis A
confocal laser scanning microscopy studyJ Bras
Pneumol.201036(6)724-730
  • Lisa Lewis

2
Wegeners Granulomatosis (WG)
  • Multi-system disease
  • Inflammation of the blood vessels which affects
    blood flow to organs/tissues causing damage
  • Respiratory tract kidneys mainly affected
  • Cause unknown auto-immune
  • ANCA (Anti-neutrophil cytoplasmic antibodies)
  • Over 90 of patients with WG exhibit ANCA
  • Response to immunosuppressive therapy supports
    auto-immune link

3
Wegeners Granulomatosis (WG)
  • Diagnosis based on clinical features, raised ANCA
    titre, histopathology
  • FBC, ESR, ANCA, renal function tests, chest
    X-ray, CT scan, lung biopsy, kidney biopsy
  • Early diagnosis important so early treatment can
    prevent pulmonary renal damage
  • Aggressive immunosuppressive therapy required
  • If untreated 80 of patients die within 1 year,
    mean survival 6 months

4
Diagnostic Techniques for WG
Immunofluorescence assay Cytoplasmic
anti-neutrophil cytoplasmic antibody
(c-ANCA) surgical-pathology.com
Chest X-ray pulmonary haemorrhage emedicine.meds
cape.com
Chest CT scan lung lesions vcuthoracicimaging.co
m
Lung biopsy vasculitis inflammation emedicine
.medscape.com
Immunofluorescence assay Cytoplasmic
anti-neutrophil cytoplasmic antibodies
(c-ANCA) emedicine.medscape.com
Lung biopsy vasculitis inflammation emedicine
.medscape.com
5
INTRODUCTION
  • WG ANCA-associated vasculitis causing
    inflammation and necrosis of small and
    medium-sized arteries
  • Severe clinical presentation commonly seen
  • kidney failure lung haemorrhage
  • Thromboembolic events have only recently been
    seen in WG patients
  • Few histopathological findings of thrombi in
    patients with ANCA-associated vasculitis
  • Study conducted to determine presence of fibrin
    thrombi in pulmonary arteries using confocal
    laser scanning microscopy

6
AIMS OF STUDY
  • To study pulmonary microcirculation
  • small medium-sized pulmonary arteries in
    patients with WG
  • To quantify fibrin thrombi in pulmonary arteries
    of patients with WG
  • To provide evidence for benefit of anticoagulant
    therapy in treatment of patients with WG

7
METHODS
  • All patients tested to diagnose pulmonary
    diseases
  • All patients had abnormal chest X-ray abnormal
    lung biopsy positive ANCA
  • 6 patients diagnosed with WG
  • 4 patients without WG (control group)
  • 4 arteries were analyzed in each patient
  • (24 WG 16 control samples)
  • Calculated size of three main areas of vessel
  • total vessel area / free lumen area /
    thrombotic area
  • Calculated the thrombotic index
  • (thrombus area divided by the total vessel
    area as a percentage)

8
METHODS
  • Endothelial cell marker CD34 and confocal laser
    scanning microscopy used to detect intravascular
    fibrin thrombi
  • Tissue sections incubated with monoclonal
    antibody Anti-CD34
  • Sections were revealed with a secondary antibody
    linked to fluorescein isothiocynate
  • Sections mounted with an aqueous mounting medium
  • A confocal laser scanning microscope with three
    lasers, magnification of x40 fluorescence
    microscope
  • Argon (488 nm), HeNe1 (543 nm), HeNe2 (633
    nm)
  • used to obtain 1 mm thick serial images of
    each vessel

9
RESULTS
  • Mean total vessel area was similar in WG and
    non-WG groups
  • Thrombi present in 92 of 24 WG patient samples
    and in 0 of the 16 non-WG patient samples
  • Mean thrombotic area significantly greater in WG
    group than non-WG group
  • Mean free lumen area significantly smaller in WG
    group than non-WG group
  • Mean vessel wall area significantly larger in WG
    group than non-WG group

10
RESULTS
Pulmonary artery control patient
Pulmonary artery control patient
Pulmonary artery WG patient
11
RESULTS
Table to show comparison between area sizes of
pulmonary arteries in Wegeners granulomatosis
patient group control group
WG Wegeners granulomatosis
12
CONCLUSIONS
  • Confocal laser scanning microscopy revealed a
    significant association between pulmonary
    microvascular thrombosis and WG
  • Microvascular thrombosis may play a role in
    pathophysiology of pulmonary WG
  • Thrombosis may cause strokes, deep vein
    thrombosis (DVT), pulmonary embolisms (PE) in WG
    patients
  • Anti-coagulant therapy could be used
  • - to treat thrombosis in patients with pulmonary
    WG
  • - as prophylaxis of thromboembolism in WG
    patients
  • - as an anti-inflammatory therapy

13
CONCLUSIONS
  • Study has limitations
  • Sample size small
  • Only small medium-sized pulmonary arteries
    studied
  • No coagulation studies performed
  • Further studies needed to confirm findings
  • Randomised clinical trials needed to test role of
    anticoagulant therapy in these patients
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