Inherited dysfibrinogenemia: clinical phenotypes associated with five different fibrinogen structure defects.
Hereditary dysfibrinogenemia is a rare clotting disorder, which results from mutations in at least one of the three fibrinogen genes. We examined the frequency of hemostatic clinical and laboratory anomalies at presentation of 37 probands from 12 unrelated families with five different defects (Aalpha R16C, gamma A357T, gamma318-319 del, gamma M310T, and Aalpha R16S), among. The median age was 51 years (11-86 years). Among 62% who were women three (13%) had experienced one or more spontaneous abortion. More than half of the probands had experienced one or more undue bleeding episode, easy bruising being by far the most common. In 19% of probands (9/37, all above age of 50 years), had experienced at least one episode of arterial or venous thrombosis. Among these, were two (7%) with deep venous thrombosis, seven with arterial thrombosis, and five (14%) had experienced both. We propose that the higher frequency of prolonged PT than aPTT, in ours and in other reported studies, reflects the polymerization delay, which in aPTT is attenuated owing to contact activation prior to calcium addition.
Miesbach
Wolfgang
W
Medical Clinic III, Institute of Transfusion Medicine, Goethe University, Frankfurt, Germany. Wolfgang.Miesbach@kgu.de
Scharrer
Inge
I
Henschen
Agnes
A
Neerman-Arbez
Marguerite
M
Spitzer
Silvia
S
Galanakis
Dennis
D
D000022:Abortion, Spontaneous / Q000097:blood / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000347:Afibrinogenemia / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000209:etiology; D001780:Blood Coagulation Tests; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D006470:Hemorrhage / Q000097:blood / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D006473:Postpartum Hemorrhage / Q000209:etiology; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000209:etiology; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D011693:Purpura / Q000097:blood / Q000209:etiology*; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000097:blood / Q000209:etiology*; D055815:Young Adult
D021122:Protein Subunits; D005340:Fibrinogen