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Wegener's Granulomatosis (WG). Multi-system diseaseInflammation of the blood vessels which affects blood flow to organs/tissues causing damageRespiratory tract
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1. Thrombosis in small and medium-sized pulmonary arteries in Wegener’s granulomatosis: A confocal laser scanning microscopy studyJ Bras Pneumol.2010;36(6):724-730 Lisa Lewis
2. Wegener’s 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. Wegener’s 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
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
11. RESULTS
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