Procarboxypeptidase U (TAFI) and the Thr325Ile proCPU polymorphism in patients with hereditary mucocutaneous hemorrhages.
BACKGROUND
Patients with hereditary mucocutaneous bleeding are difficult to diagnose and many of them fulfill the category of bleeders of unknown cause (BUC). The pathogenic role of hyperfibrinolysis has received little attention, despite the successful use of antifibrinolytic drugs in treating many of these patients. Theoretically, decreased plasma procarboxypeptidase U (proCPU) levels or lower carboxypeptidase U (CPU) stability would result in higher fibrinolytic activity and bleeding tendency.


METHODS
We analyzed plasma proCPU and the distribution of the Thr325Ile proCPU polymorphism in 193 patients with mucocutaneous bleeding of whom 116 were bleeders of unknown cause (BUC), and in 143 healthy, age and sex-matched controls.


RESULTS
ProCPU concentration was higher in women than in men, increased with age, and was significantly correlated with clot lysis time, platelet count, APTT, and PT. However, proCPU levels were unexpectedly higher in patients than in controls (968+/-134 vs. 923+/-147 U/L, p=0.004). The allele distribution of the Thr325Ile proCPU polymorphism was similar in both groups, with a low percentage of homozygous Ile/Ile.


CONCLUSIONS
Our results indicate that the proCPU system is not of major importance in the bleeding pathogenesis of these patients. The higher proCPU levels in the patients may even modestly counteract the bleeding tendency.
Matus
Valeria
V
Department of Haematology-Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Willemse
Johan
J
Quiroga
Teresa
T
Goycoolea
Manuela
M
Aranda
Eduardo
E
Panes
Olga
O
Pereira
Jaime
J
Hendriks
Dirk
D
Mezzano
Diego
D
D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D025901:Carboxypeptidase B2 / Q000097:blood* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006470:Hemorrhage / Q000097:blood* / Q000235:genetics / Q000503:physiopathology*; D006474:Hemorrhagic Disorders / Q000097:blood* / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007532:Isoleucine / Q000737:chemistry / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013912:Threonine / Q000737:chemistry / Q000235:genetics; D055815:Young Adult
D007532:Isoleucine; D013912:Threonine; D025901:Carboxypeptidase B2