Effect of Prostacyclin Treatment on Lesions of Pulmonary Arterial Hypertension
JE Pogoriler, S Rich, M Gomberg-Maitland, S Archer, AN Husain. University of Chicago, Chicago
Background: Pulmonary arterial hypertension (PAH) is a rare disease characterized by abnormal remodeling of peripheral vessels. Therapy involves both warfarin and continuous infusion of prostacyclin analogs. In addition to its immediate vasodilatory effects, prostacyclin is speculated to slow the disease process by decreasing inflammation, thrombosis, and smooth muscle proliferation; however, there has been no examination of the long term effects of prostacyclin on the lesions of adult PAH.
Design: We evaluated the morphology of vascular lesions in 22 autopsy cases with clinical diagnoses of PAH, including prostacyclin-treated and untreated patients. We used CD61 staining to determine the presence of platelet thrombi and CD3 and CD68 staining to quantify vascular inflammation.
Results: Patients dying within one year of starting prostacyclin therapy frequently had an underlying diagnosis of scleroderma, and they displayed primarily concentric vascular lesions and pulmonary capillary hemangiomatosis-like (PCH) foci. Four of the six patients who survived for a year or more (1-18 years) following initiation of prostacyclin therapy had idiopathic or anorectic-drug related disease, and in addition to concentric arterial disease they had large plexiform lesions with dilations. The average size of plexiform lesions in treated cases was significantly larger (0.39 mm2, n=5) than in untreated cases (0.15 mm2, n=6). Fewer plexiform lesions from treated cases had platelet thrombi (25%) than those from untreated cases (76%). Both groups had a similar number of thrombi in other vessel types, with the exception of cases with angioma-like lesions, which had extensive capillary platelet aggregates despite prostacyclin and warfarin therapy. Quantification of macrophages and T cells revealed no differences in inflammatory infiltrates between treated and untreated cases either in plexiform lesions alone or in abnormal vessels as a whole.
Conclusions: The increased plexiform lesion size in patients treated with prostacyclin may reflect prostacyclin's effect on vascular remodeling or the natural progression of the disease under conditions of prolonged survival. The decrease in platelet thrombi might be due to prostacyclin or warfarin treatment. Unexpectedly, treatment with prostacyclin did not decrease vascular inflammation. Together these results provide the first description of possible treatment effect on the morphology of end-stage PAH.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 7, Monday Morning