High levels of tissue factor pathway inhibitor in patients with nephrotic proteinuria.
Acquired deficiency of naturally occurring anticoagulant proteins, due to loss in the urine, has been proposed as one of the major thrombogenic alterations in nephrotic proteinuria. The aim of this study was to investigate if proteinuria may induce deficiency of tissue factor pathway inhibitor (TFPI). TFPI, protein C (PC) and antithrombin (AT) were measured in 31 patients with nephrotic proteinuria, compared with 62 age- and sex-matched controls. Plasma levels of TFPI activity, total TFPI antigen and free TFPI antigen were significantly higher in patients with nephrotic proteinuria than in controls, and none of the patients had TFPI deficiency. Intravenous injection of 7500 IU unfractionated heparin induced a significant further increase of TFPI in two patients with high pre-heparin levels. Also plasma levels of PC were significantly higher in patients than in controls. Mean AT antigen levels were not significantly different between patients and controls, and AT activity was only marginally increased with borderline significance. Three out of 31 patients had substantial acquired AT deficiency. In conclusion, proteinuria is not associated with TFPI deficiency, but with a marked increase of this anticoagulant protein. The acquired thrombophilic diathesis of patients with nephrotic proteinuria can therefore not be attributed to TFPI deficiency.
Ariëns
R A
RA
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Italy. r.a.s.ariens@leeds.ac.uk
Moia
M
M
Rivolta
E
E
Ponticelli
C
C
Mannucci
P M
PM
D000328:Adult; D000368:Aged; D000991:Antithrombins / Q000172:deficiency / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000172:deficiency; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood* / Q000150:complications; D011486:Protein C / Q000378:metabolism; D011507:Proteinuria / Q000097:blood* / Q000150:complications; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology
D000991:Antithrombins; D008074:Lipoproteins; D011486:Protein C; C051928:lipoprotein-associated coagulation inhibitor