Congenital Abnormal Antithrombin III

We found a family which had congenitally abnormal antithrombin III (AT-III ) showing remarkable difference between biological and immunological activity. We studied genetic trait and effects of heparin and thrombin on AT-III.Case: A 23 years old female developed thrombophrebitis on her left leg in July, 1979. After a while she seemed to have developed thrombi on bilateral iliac vein. She had also abdominal tumor, and a cystic kidney was found to be by an exploratory laparatomy. Five days after the operation, she was hemiparalyzed on her left. Cranial angiography disclosed obstruction of right middle cerebral artery by thrombi. Laboratory findings were as follows: Fibrinogen 145 mg/dl, FDP 40 ug/ml, platelets 8.6xl04/cmm, a-PTT 30.6 sec and PT 100%. The biological activity of AT-III was 26%, which dissociated from immunological activity of 54 mg/dl. Two dimension immunoelectrophoretical analysis showed two or three peaks at the albumin area after the addition of heparin to normal AT-III. However her AT-III did not move from α2-macroglobulin area. Her parents were cousins each other, and her parents and her sister also had abnormal AT-III. This indicates congenitally abnormal AT-III is transmitted autosomally dominantly. The administration of concentrated AT-III preparation raised its concentrate to 70%, and coagulation disorders disappeared. Immunoelectrophoresis revealed that administered AT-III disappeared in five or seven days after infusion. Oral anticoagulant therapy could prevent thrombi formation.Conclusion: We found a patient who had abnormal AT-III which brought on intravascular coagulation. Biologically active AT-III was much less than immunologically active one. Immunoelectrophoresis disclosed this AT-III did not bind with heparin. We treated the patient with oral anticoagulant therapy. Abnormal AT-III is transmitted autosomally dominantly.