Fibrinogen Milano. VI: A heterozygous dysfibrinogenemia (A alpha 16 Arg----His) with bleeding tendency.
Congenital heterozygous dysfibrinogenemia was diagnosed in a young woman with bleeding tendency. 3 other asymptomatic members of her family (mother and the 2 sisters) had abnormal fibrinogen. The proposita's plasma exhibited prolonged thrombin and reptilase times. Plasma fibrinogen concentration determined by functional assay was 0.3 g/l, whereas immunologic assay revealed normal fibrinogen levels. Turbidity curves, representing the rate of thrombin-induced fibrin formation, were markedly delayed both in the presence and absence of Ca2+. Isoelectric focusing and SDS electrophoresis of reduced fibrinogen showed normal charge and size of the subunit chains. Release of fibrinopeptide B by thrombin was normal, whereas HPLC elution diagrams of fibrinopeptide A showed an abnormal peak A* with a slightly shorter retention time than the normal fibrinopeptide A. The amino acid analysis showed that the arginine in peak A* is replaced by histidine (A alpha 16 Arg----His).
Bögli
C
C
Istituto di Medicina Interna, Università di Milano, Italia.
Cofrancesco
E
E
Cortellaro
M
M
Della Volpe
A
A
Hofer
A
A
Furlan
M
M
Zanussi
C
C
D000293:Adolescent; D000596:Amino Acids / Q000032:analysis; D001778:Blood Coagulation Disorders / Q000097:blood / Q000235:genetics*; D002118:Calcium / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D015241:Fibrinogens, Abnormal / Q000235:genetics* / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D005345:Fibrinopeptide B / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007525:Isoelectric Focusing; D007700:Kinetics; D008297:Male; D010375:Pedigree; D010974:Platelet Aggregation; D013917:Thrombin / Q000378:metabolism
D000596:Amino Acids; D015241:Fibrinogens, Abnormal; C065183:fibrinogen Milano VI; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D013917:Thrombin; D002118:Calcium