Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action

Hansen, John‐Bjarne; Sandset, Per Morten; Huseby, Kirsten Raanaas; Huseby, Nils‐Erik; Bendz, Bjørn; Østergaard, Per; Nordøy, Arne

doi:10.1046/j.1365-2141.1998.00770.x

Cited by 56 publications

(39 citation statements)

References 48 publications

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“…As expected, 12 TFPI values increased almost 3-fold after administration of UFH or LMWH (PϽ0.01 versus placebo; Figure 1). Anti-Xa values rose sharply in the UFH group to peak values of 1.6 U/mL (95% CI 1.4 to 1.9 U/mL) at 60 minutes after LPS infusion.…”

Section: Tf Expression On Monocytesmentioning

confidence: 56%

“…2 Heparin enhances inactivation of thrombin and factor Xa via antithrombin III but also increases plasma levels of endogenous TF pathway inhibitor (TFPI). 11,12 Animal data suggest that enhancement in TFPI activity represents an upstream and even more specific anticoagulatory action in LPS-induced coagulation. 13 Injection of LPS into human volunteers provides a standardized model to study the pathogenesis of the initial phase of systemic coagulation activation.…”

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confidence: 99%

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Heparin Blunts Endotoxin-Induced Coagulation Activation

et al. 1999

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Background-Lipopolysaccharide (LPS) is a major trigger of sepsis-induced disseminated intravascular coagulation (DIC) via the tissue factor (TF)/factor VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used repeatedly to explore this complex pathophysiology, but little is known about the effects of clinically used anticoagulants in this setting. Therefore, we compared with placebo the effects of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) on LPS-induced coagulation. Methods and Results-In a randomized, double-blind, placebo-controlled trial, 30 healthy male volunteers received LPS 2 ng/kg IV followed by a bolus-primed continuous infusion of UFH, LMWH, or placebo. In the placebo group, activation of coagulation caused marked increases in plasma levels of prothrombin fragment F 1ϩ2 (PϽ0.01) and polymerized soluble fibrin, termed thrombus precursor protein (TpP; PϽ0.01); TF-positive monocytes doubled in response to LPS, whereas levels of activated factor VII slightly decreased and levels of TF pathway inhibitor remained unchanged. UFH and LMWH markedly decreased activation of coagulation caused by LPS, as F 1ϩ2 and TpP levels only slightly increased; TF expression on monocytes was also markedly reduced by UFH. TF pathway inhibitor values increased after either heparin infusion (PϽ0.01). Concomitantly, factor VIIa levels dropped by Ͼ50% at 50 minutes after initiation of either heparin infusion (PϽ0.01). Conclusions-This

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Section: Tf Expression On Monocytesmentioning

confidence: 56%

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confidence: 99%

Heparin Blunts Endotoxin-Induced Coagulation Activation

et al. 1999

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“…Meanwhile, tissue factor pathway inhibitor (TFPI) is released from the vascular endothelium by heparin, perhaps delivering higher concentrations of this potent anticoagulant to the sites of ongoing thrombosis. [79][80][81][82][83] The effects of heparin on fibrinolysis are more complex, because both activators and inhibitors can be affected. 84,85 Heparin can also bind and potentially neutralize a wide variety of cytokines and chemokines.…”

Section: Heparin-mediated Interactions That Are Potentially Beneficiamentioning

confidence: 99%

Trousseau's syndrome: multiple definitions and multiple mechanisms

Varki

2007

Blood

703

548

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In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet-and endotheliumum-based selectin-dependent microangiopathy associated with mucinproducing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms.(Blood.

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“…Subcutaneous administration of a LMWH (enoxaparin) resulted in larger increases in circulating TFPI levels than heparin [7]. In addition, plasma free TFPI antigen and heparin releasable TFPI were depleted during repeated or continuous treatment with heparin, but not during subcutaneous treatment with LMWHs [8,9,11]. In a recent study [10] with two different LMWHs, a clear dose-response relationship has been noted for dalteparin and enoxaparin on the release of endogenous TFPI.…”

Section: Introductionmentioning

confidence: 96%

Molecular weight dependent tissue factor pathway inhibitor release by heparin and heparin oligosaccharides

Töbü

Schultz

et al. 2007

Thrombosis Research

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Heparin and low molecular weight heparins exert their vascular effects by mobilizing tissue factor pathway inhibitor (TFPI) from the vascular endothelium into the blood circulation. We compared the influence of molecular weight on the TFPI release by heparin and its fractions in a non-human primate model. Primates were treated with unfractionated heparin, a low molecular weight heparin (gammaparin), or a heparin-derived oligosaccharide mixture (C3). Endothelial TFPI release was determined using both immunologic and functional assays. After intravenous administration, all agents significantly increased TFPI levels ( p < 0.05) in a dose dependent manner. The increase produced by unfractionated heparin and gammaparin was greater than that by C3 at an equal dosage (p < 0.05). With subcutaneous injection, all agents produced less TFPI release. Repeated administration of heparin-derived oligosaccharides gradually increased TFPI release. A 1.89 fold increase in TFPI levels was observed 4 days after C3 treatment (2.5 mg/ kg). Our findings indicated that TFPI release is dependent on the molecular weight of heparin and its derivatives. Heparin oligosaccharides exert their vascular effects through increased TFPI release after longterm repeated administration.

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Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action

Cited by 56 publications

References 48 publications

Heparin Blunts Endotoxin-Induced Coagulation Activation

Heparin Blunts Endotoxin-Induced Coagulation Activation

Trousseau's syndrome: multiple definitions and multiple mechanisms

Molecular weight dependent tissue factor pathway inhibitor release by heparin and heparin oligosaccharides

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