Measurement of tissue factor pathway inhibitor in normal and post-heparin plasma

Hubbard, A. R.; Weller, Lynne J.; Gray, Elaine

doi:10.1097/00001721-199410000-00020

Cited by 24 publications

(12 citation statements)

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“…A major pool (approximately 50-80% of total) is bound to the vessel wall and is released into plasma fol lowing injection of heparin [5,[30][31]. A smaller pool (approximately 10-50% of total) is cir culating in plasma at a concentration of 50-150 ng/ml (~2.5 nM) [32] and is to a great extent in complex form with lipoproteins [32][33][34].…”

Section: Degradation Of Tfpimentioning

confidence: 99%

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Tissue Factor Pathway Inhibitor (Tfpi) – An Update

Sandset

1996

Pathophysiol Haemos Thromb

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There is compelling experimental evidence that tissue factor pathway inhibitor (TFPI) exerts important role(s) as a natural anticoagulant. Iinmunodepletion of TFPI lowers the treshold by which tissue factor (TF) can induce disseminated intravascular coagulation. Conversely, infusion of recombinant TFPI protects against thrombosis and disseminated intravascular coagulation in numerous experimental models. Since TFPI mutants associated with thrombosis have not yet been identified, a definite role of TFPI in coagulation is yet to be assigned. Current research on TFPI is mainly focused on the cell biology of TFPI, on the contribution of TFPI to the anticoagulant action of heparins, and on the role of lipoprotein-associated TFPI. TFPI is produced constitutively in endothelial cells, and is to a great extent bound to its surface. The binding molecule(s) have not yet been characterized, but TFPI is rapidly released by heparin and other negatively charged ions. In other cell lines degradation of TFPI is mediated by the low density lipoprotein receptor-related protein, which may be important for its clearance. In plasma, TFPI contributes strongly to the postheparin anticoagulant effect seen in dilute prothrombin time assays. The effect is probably mediated by redistribution of TFPI. Moreover, in the presence of heparin, antithrombin and TFPI cooperate to inhibit activation of coagulation. Antithrombin abrogates activation of factor VII bound to TF, whereas TFPI inhibits factor VIIa/TF complexes formed. The role of lipoprotein associated TFPI is still essentially unknown, but may play an important role in atherosclerosis.

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Section: Degradation Of Tfpimentioning

confidence: 99%

“…The release of TFPI results in a 2-4 fold increase in TFPI activity [19,31], 3-10 fold increase in TFPI total antigen levels 130-31], and 8-15 fold increase in TFPI free antigen levels [34, 41J. The discordant effects are probably related to assay methodology and stan dards.…”

Section: Degradation Of Tfpimentioning

confidence: 99%

Tissue Factor Pathway Inhibitor (Tfpi) – An Update

Sandset

1996

Pathophysiol Haemos Thromb

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“…After intravenous heparin injection, the release of TFPI is maximal 3-10 min postinjection, and then rapidly decays at a rate related to the elimination of heparin. The release of TFPI results in a two-fold to fivefold increase in total TFPI activity [44,45], a three-fold to ten-fold increase in TFPI total antigen levels [33], and an eight-fold to fifteen-fold increase in TFPI free antigen levels [46,47]. After subcutaneous injection of either UFH or LMWH, the release is maximal after only 30-60 min as compared with the maximal anti-factor Xa and anti-factor IIa activities after 3-5 h [35, [47][48][49].…”

Section: Introductionmentioning

confidence: 99%

Physiological Function of Tissue Factor Pathway Inhibitor and Interaction with Heparins

Sandset

Bendz²,

Hansen³

2000

Pathophysiol Haemos Thromb

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Tissue factor pathway inhibitor (TFPI) is now recognized as a major physiological anticoagulant. Its main role is to modulate factor VIIa/tissue factor catalytic activity. Another important role is to potentiate the effect of heparins. TFPI is released from the vascular endothelium after injection of either unfractionated heparin (UFH) or low-molecular-weight heparins (LMWHs), which may then provide high concentrations of TFPI at sites of tissue damage and ongoing thrombosis. In dilute prothrombin-time-based assays, released TFPI contributes approximately one-third to the anticoagulant effect of heparin, the remaining being accounted for by antithrombin. Released TFPI, but not plasma TFPI, contains the basic carboxy-terminal tail which is important for the anticoagulant effect. UFH and LMWH exert differential effects on intravascular TFPI. UFH, but not LMWH, given in therapeutic doses, is associated with a progressive depletion of TFPI, which is associated with a strong rebound activation of coagulation after cessation of treatment. Such depletion may explain the apparent superior efficacy of LMWH observed in clinical trials.

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“…5,6 The intravenous injection of heparin releases TFPI from the endothelium, resulting in a 2-to 10-fold increase in the plasma TFPI concentration. 7,8 Increased TFPI concentrations have been observed in a number of diseases, such as acute myocardial infarction, disseminated intravascular coagulation, septicemia, and malignant neoplasia. [9][10][11][12] Therefore, studying the alterations in plasma TFPI concentrations may help us to better understand the mechanism of coagulation during CPB.…”

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confidence: 99%

“…Although Cardigan et al 13 measured plasma TFPI activity during CPB, many investigations suggest that the TFPI antigen assay is more sensitive than the functional assay. 8,14 In the present study, plasma TFPI antigen levels during open-heart surgery were measured and the hypothesis that plasma TFPI levels may increase during cardiopulmonary bypass was tested.…”

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confidence: 99%

Altered Plasma Antigen Levels of Tissue Factor Pathway Inhibitor During Open-Heart Surgery

et al. 2000

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Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the extrinsic pathway of the coagulation cascade that is activated by cardiopulmonary bypass (CPB) during open-heart surgery. In the present study, we investigated whether the plasma TFPI antigen increases during CPB in 12 patients who underwent bypass procedures. The plasma levels of free and total TFPI antigens were measured using an enzyme-linked immunosorbent assay, and heparin concentrations were measured using a chromogenic substrate assay. We found that changes in the total plasma TFPI antigen level were significantly dependent on the level of free TFPI antigen (r = 0.96, P < 0.0001) which increased significantly after heparin injection (P < 0.0001), and increased further during the bypass period (P < 0.005). The increased free TFPI antigen level during CPB correlated with the duration of bypass (r = 0.65, P = 0.02). When heparin was neutralized by protamine, the free TFPI antigen level decreased immediately, but remained higher than the preoperative level (P < 0.005). These results suggest that plasma TFPI antigen levels increase during CPB.

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Measurement of tissue factor pathway inhibitor in normal and post-heparin plasma

Cited by 24 publications

References 0 publications

Tissue Factor Pathway Inhibitor (Tfpi) – An Update

Tissue Factor Pathway Inhibitor (Tfpi) – An Update

Physiological Function of Tissue Factor Pathway Inhibitor and Interaction with Heparins

Altered Plasma Antigen Levels of Tissue Factor Pathway Inhibitor During Open-Heart Surgery

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