Megakaryocytes and platelet homeostasis in diffuse alveolar damage

Platelet homeostasis reflects a balance between the production of platelets via cytoplasmic fragmentation of megakaryocytes in the pulmonary microvasculature and their catabolism. Increased numbers of megakaryocytes are entrapped in the injured lung, potentially affecting circulating platelet counts. We enumerated pulmonary megakaryocytes and blood platelets in patients with diffuse alveolar damage (DAD) in order to determine their association with clinical outcome. Lung biopsies were examined from 21 patients with histologically documented DAD in its proliferative phase and secondary to a variety of causes. Blood platelet counts were determined within 24 h prior to lung biopsy, and CD61+ pulmonary megakaryocytes were localized in in situ immunohistochemical stains. The overall mortality in this series was 67%. Patients with DAD attributable to drug toxicity (DAD-D) had higher mortality (80%) and greater number of intrapulmonary CD61+ megakaryocytes than those with DAD due to other causes (23+/-7, 10+/-2, p<0.05). Patients with blood platelet counts =350 th/cm(3) showed increased survival (p<0.05). The findings support the hypothesis that abnormal platelet homeostasis is associated with increased mortality in acute lung injury and indicate that thrombocytosis in ARDS is associated with improved survival. The mechanisms of altered platelet homeostasis in DAD merit further investigation.