C1 inhibitor infusion modifies platelet activity in hereditary angioedema patients.
BACKGROUND
C1 inhibitor (C1-INH) is an alpha2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The alpha-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE).


OBJECTIVE
To evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE.


METHODS
Assessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate.


METHODS
In 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria.


METHODS
Platelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5 microM; collagen, 5 microg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay).


RESULTS
After C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate- and collagen-induced platelet aggregation versus preinfusion values (maximum after 1-2 days; P <.001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively.


CONCLUSIONS
These data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.
Coppola
Ludovico
L
Department of Gerontology, Geriatric and Metabolic Diseases, Second University of Naples, Naples, Italy.
Guastafierro
Salvatore
S
Verrazzo
Giovanni
G
Coppola
Antonino
A
De Lucia
Domenico
D
Tirelli
Angelo
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000799:Angioedema / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D050718:Complement C1 Inhibitor Protein; D004305:Dose-Response Relationship, Drug; D015956:Factor XIIa / Q000032:analysis; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D011516:Prothrombin
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D000244:Adenosine Diphosphate; D011516:Prothrombin; D003094:Collagen; D015956:Factor XIIa