Rare inherited disorders of fibrinogen.
Fibrinogen, a hexameric glycoprotein encoded by three genes - FGA, FGB, FGG - clustered on chromosome 4q is involved in the final steps of coagulation as a precursor of fibrin monomers required for the formation of the haemostatic plug. Inherited disorders of fibrinogen abnormalities are rare and not as well clinically characterized as some other inherited bleeding disorders. To characterize the clinical manifestations, molecular defects and treatment modalities of these rare disorders, a Medline search from January 1966 to September 2007 for these disorders reported in large studies and registries was undertaken. Inherited fibrinogen disorders can manifest as quantitative defects (afibrinogenemia and hypofibrinogenemia) or qualitative defects (dysfibrinogenemia). Quantitative fibrinogen deficiencies may result from mutations affecting fibrinogen synthesis, or processing while qualitative defects are caused by mutations causing abnormal polymerization, defective cross-linking or defective assembly of the fibrinolytic system. Clinical manifestations vary from being asymptomatic to developing catastrophic life-threatening bleeds or thromboembolic events. Management of bleeds includes use of purified plasma-derived concentrates, cryoprecipitate or fresh frozen plasma. Use of some of these products carries risks of viral transmission, antibody development and thromboembolic events. Establishment of registries in Iran, Italy and North America has fostered a better understanding of these disorders with an attempt to explore molecular defects. Rare Bleeding Disorder Registries developed through the United States and international efforts hopefully will encourage development and licensure of safer, effective products.
Acharya
S S
SS
Department of Pediatrics, Weill Medical College of Cornell University, New York, NY 10021, USA. ssa2001@med.cornell.edu
Dimichele
D M
DM
D000328:Adult; D000347:Afibrinogenemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D001777:Blood Coagulation / Q000235:genetics; D003029:Coagulants / Q000008:administration & dosage; D005169:Factor VIII / Q000008:administration & dosage; D005260:Female; D005340:Fibrinogen / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006470:Hemorrhage / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007492:Iran / Q000453:epidemiology; D007558:Italy / Q000453:epidemiology; D016239:MEDLINE; D008297:Male; D009154:Mutation; D009656:North America / Q000453:epidemiology; D010641:Phenotype; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000235:genetics* / Q000628:therapy; D011296:Prenatal Diagnosis; D035583:Rare Diseases / Q000235:genetics
D003029:Coagulants; C026912:cryoprecipitate coagulum; D005169:Factor VIII; D005340:Fibrinogen