Occult antithrombin III deficiency: a potentially lethal complication of the postphlebitic limb

Chronic venous insufficiency is a frequent sequel to lower extremity venous thrombosis. A relatively uncommon, but potentially lethal, cause of the thrombosis is congenital antithrombin III deficiency. Recognition and treatment of this occult deficiency is critical. The following report describes a family treated by the authors for this problem. In one generation of nine siblings, three males had documentation of the disease with functional antithrombin III levels in the range of 50% to 60%. Before evaluation for the deficiency one female sibling died at the age of 20 years as a consequence of a proven pulmonary embolus. Antithrombin III levels in another female sibling, who was free of symptoms, were normal (80% to 120%). Four other siblings who were free of symptoms (one female, three males) refused evaluation. All three men with the deficiency had severe, chronic, bilateral, lower extremity, venous insufficiency manifested by pain, varicosities, edema, pigmentation, and ulceration. Despite chronic warfarin therapy, one experienced recurrent pulmonary embolization with eventual loss of perfusion of the entire right lung. Ascending venography in the symptomatic males with the deficiency revealed evidence of recurrent and diffuse venous thrombosis with partial recanalization. Recurrent lower extremity venous thrombosis consequent to antithrombin III deficiency causes a particularly fulminant postphlebitic syndrome with characteristic venographic findings. Although potentially lethal if unrecognized and treated simply as venous insufficiency, chronic therapy with warfarin offers palliation and prolongs life.