Summary
An association between deficiency of tissue factor pathway inhibitor (TFPI) and thrombosis
has not been clearly demonstrated in humans, but previous studies have focused on
the measurement of plasma TFPI, which is only a small part of the total body TFPI.
The major fraction of this natural anticoagulant can be measured in plasma after release
by heparin injection. To investigate if deficiency of heparin-releasable TFPI is associated
with thrombosis, we measured TFPI activity in plasma before and 10 min after intravenous
injection of 7500 IU unfractionated heparin in 64 young patients with venous thrombosis,
49 young patients with arterial thrombosis and 38 healthy individuals. Post-heparin
TFPI activity levels were significantly lower in the group of patients with venous
thrombosis than in controls (mean ± SD: 230% ± 39 vs 260% ± 34, p = 0.0002), whereas
there was no difference for patients with arterial thrombosis. Defining the normal
range as the mean ± 2 SD of TFPI activity in controls, twelve patients had low post-heparin
TFPI activity levels, seven with venous and five with arterial thrombosis. Low levels
of TFPI activity were confirmed by immunoassay in six of the seven patients with venous
thrombosis and two of the five patients with arterial thrombosis, and were present
also in at least one first degree relative of six patients, suggesting that the defect
might be inheritable. However, the causative role of low heparin-releasable TFPI remains
uncertain, because co-segregation of the defect with thrombotic symptoms could not
be demonstrated in the small number of families studied.
