Familial Occurrence of Pulmonary Embolism after Intravenous, Adipose Tissue-Derived Stem Cell Therapy
A forty-one year old man visited our hospital because of chest pain starting one month earlier. During the diagnostic work-up, chest CT revealed wedge-shaped consolidation at the subpleural area of the right upper lobe (). In addition, multiple emboli were found in small pulmonary artery branches of both lungs with right pleural effusion (). There was mild elevation of D-dimer (0.8 µg/mL, normal; 0-0.5 µg/mL) which suggested the diagnosis of pulmonary embolism and infarct. Full diagnostic work-up for hypercoagulability was done. Antinuclear antibody, anti-dsDNA and lupus anticoagulant were all negative. Levels of anti-cardiolipin antibody, homocysteine and anti-thrombin III and activity of protein C and S were within normal range. Factor V Leiden gene mutation was not detected. There was no evidence of deep vein thrombosis in his lower extremities by Doppler ultrasound. He was a non-smoker and did not have chronic illnesses. He did not take a medicine and had not recently taken airplane for a long period. We were puzzled about the cause of the multiple embolism and infarct. We checked his medical history more closely and he confessed to having taken autologous adipose tissue-derived stem cell therapy for cervical herniated intervertebral disc three times intravenously. The each stem cell therapy was at intervals of one month and the last treatment was finished one month before his visit. We considered the possibility of pulmonary embolism by intravenous infusion of hASC. The suspicion of IV stem cell therapy as the cause of pulmonary embolism became more solidified when we came to know that his parents had taken the same therapy for treatment of knee osteoarthritis five times. We invited them for diagnostic work up. They had no specific respiratory symptoms. His father was a current smoker (40 pack years) and his mother was a non smoker. Except for old age, they did not have risk factors for thromboembolism. His father's chest CT showed similar findings: there were multiple emboli at both pulmonary artery branches with right pleural effusion (). In addition, pulmonary infarct was noted at the periphery of right lower lobe. Serum D-dimer was also elevated (1.0 µg/mL). As for his mother, we also confirmed multiple emboli in the pulmonary artery branches in both lungs () with mild elevation of serum D-dimer (1.1 µg/mL). They had no abnormal findings in the tests for hypercoagulability either. The index patient was first treated with enoxafarin, and then overlapped and switched to warfarin. Anti-coagulant therapy was stopped after a month because of the development of hematuria. His parents were observed without anti-coagulation therapy. Follow-up chest CT taken three month later showed disappearance of pleural effusion in index patient () and in his father. Pulmonary emboli were not detected in any of them.