Summary
Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the TF-dependent coagulation
system. In meningococcal disease, up-regulation of tissue factor expression on blood
monocytes and possibly on endothelial cells has the potential to trigger the activation
of the TF-dependent pathway of coagulation. Intravascular coagulation is considered
to be a major pathogenic factor in meningococcal disease. We postulated that imbalance
between TF expression and TFPI concentration might lead to uncontrolled coagulation
in meningococcal disease. The aim of this study was to assess the levels of total
TFPI in the plasma of patients with meningococcal disease and assess whether increased
leaking of the TFPI was occurring. TFPI antigen levels and activity were measured
in the plasma of 54 patients with meningococcal disease, and 13 healthy control children.
TFPI antigen level were also determined in the urines of 14 of the 54 and 9 healthy
control children. Plasma TFPI activity was reduced in the meningococcal diseased patients
(mean of 0.503 ± 0.341 U/ml; control, 1.010 ± 0.199 U/ml; p <0.0001), as was the TFPI
antigen levels (mean of 54.85 ± 35.05 ng/ ml; Control, 94.51 ± 11.44 ng/ml; p <0.0001).
In contrast, TFPI antigen levels were increased in the urine of these patients when
compared to the levels found in the urine of the healthy control children (mean of
12.96 ± 5.392 ng/mmol creatinine; Control, 0.239 ± 0.191 ng/mmol creatinine; p <0.035).
A lack of correlation between TFPI-activity and TFPI-antigen plasma levels was observed
(r = 0.002, p = 0.85). This data is consistent with the hypothesis that in meningococcal
disease there is increased inactivation of plasma TFPI by the up regulation of tissue
factor expression but in addition increased clearance of TFPI in urine is occurring.
Keywords
Tissue factor pathway inhibitor - meningococcal disease - glycosaminoglycans - capillary
leak