The present status of tissue factor pathway inhibitor

Lindahl, Anne Karin; Pm, Sandset; Abildgaard, Ulrik

doi:10.1097/00001721-199203040-00011

Cited by 116 publications

(67 citation statements)

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“…TFPI activity was most markedly elevated in the microalbuminuric patients and PAI-1 activity was correlated with UAE in the diabetic patients, thus confirming earlier studies (17,18). After synthesis by the vascular endothelium, TFPI is bound to the endothelial surface and to a lesser degree released into plasma (38). In plasma TFPI is mainly transported by lipoproteins (39), which probably explains the association between TFPI and LDL cholesterol in the present study.…”

Section: Discussionsupporting

confidence: 91%

Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions.

et al. 1999

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It is unknown whether and to what extent changes in various endothelial functions and adrenergic responsiveness are related to the development of microvascular complications in type 1 diabetes. Therefore, endothelium-dependent and endothelium-independent vasodilatation, endothelium-dependent hemostatic factors, and one and two adrenergic vasoconstrictor responses were determined in type 1 patients with and without microvascular complications. A total of 34 patients with type 1 diabetes were studied under euglycemic conditions on two occasions (11 without microangiopathy, 10 with proliferative and preproliferative retinopathy previously treated by laser coagulation, 13 with microalbuminuria, and 12 healthy volunteers also were studied). Forearm vascular responses to brachial artery infusions of N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside, acetylcholine (ACh), clonidine, and phenylephrine were determined. The ACh infusions were repeated during coinfusion of L-arginine. Furthermore, plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator antigen levels, von Willebrand factor antigen levels, tissue factor pathway inhibitor (TFPI) activity, and endothelin-1 levels were measured. No differences in endothelium-dependent or endothelium-independent vasodilatation or adrenergic constriction were observed between the diabetic patients and the healthy volunteers. In comparison to the first ACh infusion, the maximal response to repeated ACh during L-arginine administration was reduced in the diabetic patients, except in the patients with proliferative and preproliferative retinopathy previously treated by laser coagulation. In these patients, the combined infusion of L-arginine and ACh resulted in an enhanced response. TFPI activity was elevated, and PAI-1 activity was reduced in the type 1 diabetic patients. Furthermore, PAI-1 activity was positively correlated with urinary albumin excretion (r = 0.48, P < 0.01) and inversely correlated with the vasodilatory response to the highest ACh dose (r = -0.37, P < 0.05). The response to the highest ACh and L-NMMA dose were positively correlated with mean arterial blood pressure (r = 0.32, P < 0.01; r = 0.41, P < 0.01, respectively). Forearm endothelium-dependent and endothelium-independent vasodilatation and adrenergic responsiveness were unaltered in type 1 diabetic patients with and without microvascular complications. Relative to healthy control subjects, endothelium-dependent vasodilatation was depressed during a repeated ACh challenge (with L-arginine coinfusion) in the diabetic patients without complications or with microalbuminuria. In contrast, this vasodilatation was enhanced in the patients with retinopathy. Elevation of TFPI was the most consistent marker of endothelial damage of all the endothelial markers measured.

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Section: Discussionsupporting

confidence: 91%

Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions.

et al. 1999

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“…Relatively high levels of TFPI were found in the supernatant of the melanoma cell-line LOX and in the colon cell-line WIDR (unpublished observations). In contrast, no evidence of TFPI synthesis was found in a small-celled pulmonary cell-line H-146, monocytes, lymphocytes nor in a promyeloid leukaemia cell line (HL-60) (Lindahl et al, 1992b;unpublished observations). However, an immunohistological study failed to demonstrate TFPI associated with tumour tissues such as malignant melanoma and colon cancer (Werling et al, 1993).…”

Section: Discussionmentioning

confidence: 92%

“…A variety of malignant cells actually produce TFPI in culture (Broze & Miletich, 1987;Wun et al, 1990;Lindahl et al, 1992b). Relatively high levels of TFPI were found in the supernatant of the melanoma cell-line LOX and in the colon cell-line WIDR (unpublished observations).…”

Section: Discussionmentioning

confidence: 96%

Elevated TFPI in malignant disease: relation to cancer type and hypercoagulation

Iversen¹,

Lindahl²,

Abildgaard³

1998

Br J Haematol

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Summary.We have previously reported high levels of the coagulation inhibitor TFPI in the blood of patients with gastrointestinal cancer. TFPI is not an acute-phase reactant, but high levels have also been reported in patients with septicaemia and disseminated intravascular coagulation (DIC). To study its relationship with other types of malignancy, TFPI activity was first determined in plasma samples from 214 patients with various malignancies. In a second cohort of 83 patients, total and free TFPI antigen, protein C, antithrombin, fibrin monomer and D-dimer were also measured. Elevated TFPI activity and antigens were found in about half of the patients with solid tumours. In contrast, elevated TFPI was rare in haematological malignancies (12%). In the 18 patients with acute nonlymphocytic leukaemia (ANLL), elevated free TFPI was found only in patients who also had DIC. No correlation was found between TFPI levels and fibrin monomer or D-dimer levels. Only four out of 20 patients with solid tumours had normal levels of fibrin monomer and D-dimer, yet three out of these four had elevated TFPI. In conclusion, elevated TFPI in ANLL is related to the coexistence of DIC. In solid tumour disease increased TFPI may reduce protective fibrin formation, but the pathogenic mechanism is as yet unknown.

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“…About 50-90% of total TFPI is bound to the endothelium via heparan sulphate and other glycosaminoglycans on the endothelial cell surface [6]. It is released into the circulation following displacement by heparin.…”

Section: Introductionmentioning

confidence: 99%

The tissue factor pathway in ischemic stroke

Adams

Thom²,

Hankey³

et al. 2006

Blood Coagulation &Amp; Fibrinolysis

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To explore the role of the the tissue factor (TF) pathway in ischemic stroke. We measured blood concentrations of markers of the TF pathway [TF antigen, free tissue factor pathway inhibitor antigen (TFPIf) and activity (TFPIac), and activated factor VII (FVIIa)] within 7 days (acute phase) and after 3-6 months (convalescence) in 150 patients with first-ever ischemic stroke and 150 community controls. During the acute phase, TF antigen and TFPIf were not significantly altered but TFPIac was increased (mean 1.27 versus 1.13 U/ml, P = 0.04) and FVIIa was decreased in cases compared with controls (mean 43.3 versus 57.9 mU/ml, P = 0.0004). After adjusting for baseline differences between cases and controls, increasing quartiles of TFPIf were independently associated with reduced odds of stroke, and reducing quartiles of FVIIa and increasing quartiles of TFPIac with increased odds of stroke. During the convalescent phase, FVIIa and TFPIac returned to normal but TF antigen and TFPIf were significantly decreased compared with controls [median TF antigen, 110 (follow-up) versus 155 pg/ml (controls), P = 0.0008; median TFPIf, 15.5 (follow-up) versus 23.3 ng/ml (controls), P = 0.002]. Alterations of blood concentrations of TF pathway markers are common in patients with acute ischemic stroke. The mechanisms are unclear but may relate to enhanced formation of TF-FVIIa complexes and upregulation and release of TFPI during the acute phase, and ongoing consumption of TF antigen and TFPIf during the chronic phase as the atherosclerotic plaque heals.

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The present status of tissue factor pathway inhibitor

Cited by 116 publications

References 0 publications

Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions.

Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions.

Elevated TFPI in malignant disease: relation to cancer type and hypercoagulation

The tissue factor pathway in ischemic stroke

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