Recurring thromboembolic disease and pulmonary hypertension associated with severe hypoplasminogenemia

Abstract

In a patient with pulmonary hypertension and a history of recurrent venous thrombosis, plasma concentrations of all known coagulant and inhibitor proteins were normal except for severe deficiency of plasminogen. Repeated analyses showed the circulating plasma plasminogen level to be 30% of normal by either functional or immunologic methods. We sought evidence for either increased activation of plasminogen or for dysplasminogen. There was no evidence for the former. Purified plasminogen studies disclosed a normal number of active sites and normal activation. Generated plasmin had normal catalytic activity. Isoelectric focusing disclosed normal distribution of isoforms. Affinity chromatography with lysine-sepharose showed the presence of the two variant forms; however, an increased proportion of the protein eluted in the first peak. Danazol administration induced an increase in circulating plasminogen, but the differences in affinity chromatography elution profile remained. We conclude that this patient has a deficiency of normally functioning plasminogen, probably due to decreased synthesis.