This study concerns a case of congenital homozygous deficiency in alpha 2-antiplasmin associated with a severe
hemorrhagic diathesis. Heterozygous family members also show a mild
bleeding tendency. The propositus is a 17-yr-old male born of white parents and showing a severe
hemorrhagic diathesis characterized by spontaneous
bleeding in the joints since his early childhood. He was originally suspected of having
factor XIII deficiency but was found to have normal functions of the coagulation system and the platelets. Except for alpha 2-antiplasmin, all
protease inhibitors showed normal plasma values. With the immediate
plasmin inhibition test (synthetic substrate), only 2% of normal functional inhibition was detected, while no reaction with monospecific
antisera for alpha 2-antiplasmin was observed. Inhibition of activator-induced fibrinolysis in vitro was reduced. No enhanced spontaneous in vitro fibrinolysis was detected nor were there signs of increased in vivo fibrinolysis during an asymptomatic period. During recovery from a hemorrhagic episode, signs of previous consumption of
antithrombin III, alpha 2-macroglobulin,
factor XIII, and
inter-alpha-trypsin inhibitor were noted. After the diagnosis was made, treatment with
tranexamic acid (4 daily doses of 1 g) was effective for about 2 yr. Among the 37 family members studied, a separate group of 16 individuals (including the father and mother of the propositus) with approximately one-half normal plasma levels of alpha 2-antiplasmin both functionally (59% +/- 6%) and immunologically 48% +/- 8%) was discovered. The defect appeared to be inherited as an autosomal recessive gene; no ancestral consanguinity could be shown. The group of apparent heterozygotes as a whole showed increased levels of
alpha 1-antitrypsin (142% +/- 39%; p less than 0.01), indicating systemic consequences of the deficiency and reduced binding (+/- 50%) of
alpha 2-antiplasmin to
fibrin. Six exhibited a mild
hemorrhagic diathesis for which no explanation was provided by routine screening of coagulation and platelet functions; also, within the group of heterozygotes, the occurrence of the
bleeding tendency did not correlate with differences in residual
alpha 2-antiplasmin levels and functions. It is concluded that not only the absence of
alpha 2-antiplasmin but also a reduction in its plasma level to +/- 60% of normal may predispose to a
hemorrhagic diathesis.