Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver.
This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.
Meijer
C
C
Department of Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Wiezer
M J
MJ
Hack
C E
CE
Boelens
P G
PG
Wedel
N I
NI
Meijer
S
S
Nijveldt
R J
RJ
Statius Muller
M G
MG
Wiggers
T
T
Zoetmulder
F A
FA
Borel Rinkes
I H
IH
Cuesta
M A
MA
Gouma
D J
DJ
van de Velde
C J
CJ
Tilanus
H W
HW
Scotté
M
M
Thijs
L G
LG
van Leeuwen
P A
PA
D000005:Abdomen / Q000601:surgery; D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000032:analysis; D018988:Bacterial Translocation; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D015897:Comorbidity; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D004211:Disseminated Intravascular Coagulation / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D004311:Double-Blind Method; D019446:Endotoxemia / Q000209:etiology* / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000601:surgery; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000097:blood / Q000601:surgery; D017093:Liver Failure / Q000097:blood / Q000209:etiology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D010958:Plasminogen / Q000032:analysis; D011184:Postoperative Period; D011446:Prospective Studies; D018805:Sepsis / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000032:analysis; D000979:alpha-2-Antiplasmin / Q000032:analysis; D000511:alpha-Macroglobulins / Q000032:analysis
D015415:Biomarkers; D001779:Blood Coagulation Factors; D003174:Complement C1 Inactivator Proteins; D004731:Endotoxins; D007074:Immunoglobulin G; D015850:Interleukin-6; D008565:Membrane Proteins; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; C046193:antithrombin III-protease complex; C025357:endotoxin binding proteins; D000990:Antithrombin III; D005340:Fibrinogen; D010958:Plasminogen; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D001663:Bilirubin