Fibrinolytic studies in 13 unrelated families with factor XII deficiency.
METHODS
We report the results of extensive "in vitro" fibrinolytic studies in 18 homozygous and 14 obligatory heterozygous subjects belonging to 13 unrelated families with factor XII deficiency. All homozygotes had unmeasurable factor XII activity (XII:C) and antigen (XII:Ag). None had bleeding symptoms, whereas a myocardial infarction occurred in one of them at age 51. In heterozygotes XII:C and XII:Ag were 55.9 +/- 14.1% and 52.1 +/- 16.4% (corresponding figures in 40 normals 100.6 +/- 18.3% and 101.5 +/- 29.7%). Total intrinsic fibrinolytic activity was assayed on fibrin plates in the dextran sulfate euglobulin fraction of plasma from resting subjects, to which flufenamate was added to inhibit blood plasminogen activator inhibitors.


RESULTS
Fibrinolytic activity was reduced in all homozygotes (40 +/- 12 BAU/ml) in comparison to heterozygotes (103 +/- 12 BAU/ml) and normals (98 +/- 20 BAU/ml). The addition of purified activated beta-XII led to a complete restoration of fibrinolysis in homozygotes. The addition of anti-urokinase antibodies completely suppressed the reduced intrinsic fibrinolytic activity in homozygotes (4 +/- 7 BAU/ml), whereas a reduction to about 50% was evident in heterozygotes and normals.


CONCLUSIONS
Our data confirm that reduced "in vitro" intrinsic fibrinolytic activity is a common finding in homozygous factor XII deficiency and that two independent mechanisms, one factor XII-dependent and urokinase-independent and the other factor XII-independent and urokinase-dependent, are responsible for the generation of intrinsic fibrinolysis in human plasma.
Rodeghiero
F
F
Dipartimento di Ematologia, Ospedale San Bortolo, Vicenza, Italy.
Castaman
G
G
Ruggeri
M
M
Cazzavillan
M
M
Ferracin
G
G
Dini
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D005174:Factor XII / Q000378:metabolism; D005175:Factor XII Deficiency / Q000235:genetics*; D005260:Female; D005342:Fibrinolysis / Q000235:genetics*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000097:blood / Q000378:metabolism*; D011288:Prekallikrein / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000378:metabolism
D005174:Factor XII; D011288:Prekallikrein; D007610:Kallikreins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator