A possible role of thrombin-activatable fibrinolysis inhibitor in disturbances of fibrinolytic system in renal transplant recipients.
BACKGROUND
Cardiovascular disease (CVD) is a major cause of death in renal transplant recipients (RTR). Suppression of fibrinolysis plays a role in the progression of atherosclerosis. Accelerated progression of atherosclerosis and fibrinolytic system suppression has been observed in RTR. Despite many years of intensive research, the reason for impaired fibrinolysis in this patient population is not fully understood. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently discovered glycoprotein combining coagulation and fibrinolysis. This study was conducted to evaluate concentrations of TAFI, markers of thrombin generation, endothelial injury, and some standard laboratory parameters in RTR receiving triple immunosuppressive drug regimen.


METHODS
The study was performed in 29 stable, non-diabetic kidney transplant recipients treated with cyclosporin A, azathioprine, and prednisone and in 18 age- and sex-matched healthy volunteers. Soluble thrombomodulin (sTM), prothrombin fragments F1+2 (F1+2), thrombin--antithrombin complexes (TAT), plasmin--antiplasmin complexes (PAP), and TAFI were measured with commercially available kits.


RESULTS
The RTR group had significantly higher plasma levels of TAT, F1+2, sTM and TAFI than the healthy volunteers. There were no differences in PAP concentrations between the two groups. Plasma sTM correlated inversely with creatinine clearance, body mass index, haemoglobin, and albumin. Plasma TAT level was positively associated with total cholesterol. TAFI antigen influenced negatively PAP antigen concentration.


CONCLUSIONS
On the basis of our research, we concluded that elevated circulating TAFI antigen might be a new link in the pathogenesis of impaired fibrinolysis in RTR, and thus atherosclerosis progression. In the patient group there is also evidence of endothelial injury, followed by secondary activation of the coagulation cascade. Hypercholesterolaemia in RTR is associated with enhanced thrombin activity.
Hryszko
T
T
Department of Nephrology and Internal Medicine, Medical Academy of Bialystok, Bialystok, Zurawia, Poland.
Malyszko
J
J
Malyszko
J S
JS
Brzosko
S
S
Pawlak
K
K
Mysliwiec
M
M
D000328:Adult; D000368:Aged; D000933:Antifibrinolytic Agents / Q000097:blood; D000990:Antithrombin III; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000097:blood*; D005260:Female; D005341:Fibrinolysin; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D011516:Prothrombin / Q000032:analysis; D012995:Solubility; D018180:Thrombomodulin / Q000097:blood; D000979:alpha-2-Antiplasmin
D000933:Antifibrinolytic Agents; D010446:Peptide Fragments; D018180:Thrombomodulin; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C037742:plasmin-plasmin inhibitor complex; D000990:Antithrombin III; D011516:Prothrombin; D002268:Carboxypeptidases; D010447:Peptide Hydrolases; D025901:Carboxypeptidase B2; D005341:Fibrinolysin