Plasma fibrinogen gamma' chain content in the thrombotic microangiopathy syndrome.
BACKGROUND
Human fibrinogen gamma chain variants, termed gamma' chains, contain a unique 20-residue sequence after gamma chain residue 407 that ends at gamma'427, and is designated gamma'(427L). Full-length (FL) gamma'(427L) chains are constituents of a fibrin-dependent thrombin inhibitory system known as antithrombin I, whereas a gamma' chain processed in vivo, termed gamma'(423P), lacks the C-terminal tetrapeptide EDDL, and does not bind thrombin. Together, the gamma'(423P) and gamma'(427L) chains comprise the total plasma fibrinogen gamma' chain content.


OBJECTIVE
Lowered plasma gamma' chain content (i.e. gamma' chain-containing fibrinogen/total fibrinogen ratio) has been shown to correlate with susceptibility to venous thrombosis, thus prompting this study on the total and FL gamma' chain content in 45 subjects with thrombotic microangiopathy (TMA), a disorder characterized by microvascular thrombosis.


METHODS
We measured by enzyme-linked immunosorbent assay the total gamma' chain-containing fibrinogen/total fibrinogen (Total gamma'-fgn/Total fgn) ratio and the FL gamma' chain-containing fibrinogen/total fibrinogen (FL gamma'-fgn/Total fgn) ratio in these plasmas and in healthy subjects (n = 87).


RESULTS
In healthy subjects, the mean Total gamma'-fgn/Total fgn ratio was 0.127, whereas the FL gamma'-fgn/Total fgn ratio was somewhat lower at 0.099 (P < 0.0001), a difference reflecting the presence of gamma'(423P) chains. In TMA plasmas, both the Total gamma'-fgn and FL gamma'-fgn/Total fgn ratios (0.099 and 0.084, respectively) were lower than those of their healthy subject counterparts (P < 0.0001).


CONCLUSIONS
These findings in TMA suggest that reductions in the gamma' chain content indicate reduced antithrombin I activity that may contribute to microvascular thrombosis in TMA.
Mosesson
M W
MW
The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201-2178, USA. mosesson@bcw.edu
Hernandez
I
I
Raife
T J
TJ
Medved
L
L
Yakovlev
S
S
Simpson-Haidaris
P J
PJ
Uitte DE Willige
S
S
Bertina
R M
RM
D051722:ADAM Proteins / Q000097:blood; D000071120:ADAMTS13 Protein; D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000743:Anemia, Hemolytic / Q000097:blood; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000208:ethnology / Q000503:physiopathology; D012016:Reference Values; D013577:Syndrome; D013927:Thrombosis / Q000097:blood* / Q000208:ethnology / Q000503:physiopathology; D044465:White People
C027539:fibrinopeptides gamma; D005337:Fibrin; D005340:Fibrinogen; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human