Tissue factor pathway inhibitor antigen and activity in 96 patients receiving heparin for cardiopulmonary bypass

Adams, Murray J.; Cardigan, Rebecca; Marchant, Warwick; Grocott, Michael P.W.; Mythen, Monty; Mutch, M; Purdy, G.; Mackie, Ian; Machin, Samuel J.

doi:10.1053/jcan.2002.29677

Cited by 23 publications

(17 citation statements)

References 21 publications

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“…Although additional experiments are necessary to characterize the association of TFPI with the endothelium of other vascular beds, these data using placenta suggest that a GPI anchor is the predominant mechanism for the association of TFPI with endothelium and that heparin infusion does not induce a significant redistribution of the total TFPI within the vasculature. This conclusion is consistent with the recent findings of Adams et al, 24 who measured the circulating TFPI concentration in 96 patients receiving heparin for cardiopulmonary bypass. Two patients with low amounts of heparin-releasable TFPI were identified, but neither experienced an adverse clinical outcome.…”

Section: Discussionsupporting

confidence: 92%

Characterization of the Association of Tissue Factor Pathway Inhibitor With Human Placenta

Mast¹,

Acharya²,

Malecha³

et al. 2002

ATVB

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Objective-Tissue factor pathway inhibitor (TFPI) is an endothelial-associated inhibitor of blood coagulation. Because the mechanism for attachment of TFPI to endothelium is not clear, we investigated its association with human placenta. Methods and Results-Western blots demonstrate that treatment with phosphatidylinositol-specific phospholipase C (PIPLC) removes more placental TFPI than either PBS or heparin, a finding confirmed by immunohistochemistry. The amounts of heparin-releasable and PIPLC-releasable TFPI activity on placental endothelium were measured in placentas from 5 individuals. PIPLC removes Ͼ10-fold more TFPI activity from the placental fragments than 10 U/mL heparin and Ͼ100-fold more than 1 U/mL heparin. Pretreatment of the placental fragments with PIPLC increases the amount of heparin-releasable TFPI by Ϸ3-fold. An antibody specific for the C-terminal region of TFPI recognizes PIPLC-releasable TFPI in Western blots. Conclusions-GPI-anchored TFPI is the predominant form on placental endothelium. Heparin-releasable TFPI likely represents only a small portion of the total TFPI on endothelium that remains attached to cell-surface glycosaminoglycans after cleavage of the GPI anchor by endogenous enzymes. The predominance of GPI-anchored TFPI suggests that heparin infusion does not significantly redistribute TFPI within the vasculature. The intact C-terminus in GPI-anchored TFPI indicates it is not directly attached to a GPI anchor. Rather, it most likely associates with endothelium by binding to a GPI-anchored protein.

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Section: Discussionsupporting

confidence: 92%

Characterization of the Association of Tissue Factor Pathway Inhibitor With Human Placenta

Mast¹,

Acharya²,

Malecha³

et al. 2002

ATVB

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“…It is generally accepted that thrombin is generated by the contact between blood and the surface of the extracorporeal circuit by initiation of factor X or XII as well as by tissue factor released from the wound and activated monocytes [7,8,19]. We observed an inverse correlation of F1+2 and AT III levels.…”

Section: Discussionmentioning

confidence: 52%

“…TFPI inhibits factor VIIa/TF complex and factor Xa. Consumption of TFPI offers insight in extrinsic coagulation disorders such as disseminated intravascular coagulation [7,8]. …”

Section: Introductionmentioning

confidence: 99%

Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity

et al. 2006

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“…In the revised hypothesis, factor VIIa/ tissue factor is responsible for the initiation of coagulation, but because of TFPI-mediated inhibition, sustained hemostasis requires the persistent procoagulant action of intrinsic factors VIII, IX, and XI. Very large amounts of TFPI are released after heparin administration and during CPB presumably to counteract the potent tissue factor-induced procoagulant stimulus [3,68,140]. Most of TFPI in plasma is bound to lipoprotein.…”

Section: Thrombin and The Coagulation Cascadementioning

confidence: 99%

“…The importance of extrinsic pathway inhibitors such as TFPI in limiting thrombosis at sites of vascular injury has been shown by several animal studies and in vitro studies with human tissues [1,56,94,153]. Additionally, TFPI increases 3 to 4 fold after the administration of heparin prior to CPB [3,106]. It is reasonable to hypothesize that augmentation of the effect of TFPI during CPB would limit thrombin generation during CPB, perhaps synergistically with the anticoagulant effects of heparin.…”

Section: Thrombin and The Coagulation Cascadementioning

confidence: 99%

Thrombin and cardiopulmonary bypass – A paradigm for evaluation of the regulation of hemostasis

Ferraris

2011

Int J Angiol

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Extracorporeal circulation for the purpose of cardiopulmonary bypass (CPB) is used extensively for repair of cardiac defects. Complex mechanisms, many of which involve the generation of thrombin, are initiated by the institution of CPB. Thrombin is generated during CPB in spite of high doses of heparin. The tissue factor/ factor VII pathway is also activated and is probably responsible for generation of most of the thrombin seen during CPB. Plasma proteins (humoral phase) along with platelets, endothelium and white cells (cellular phase) are also activated by contact of blood with synthetic surfaces. Small amounts of thrombin activate endothelial cells which then generate tissue plasminogen activator (t-PA). Plasmin is generated by the action of t-PA and fibrinolysis ensues. The blood becomes a mix of vasoactive substances that alter vascular smooth muscle tone and endothelial cell contraction. The sum of these reactions is called the Ôwhole body inflammatory responseÕ and is responsible for postoperative morbidity including bleeding and organ system dysfunction.Attempts to control the morbidity of CPB have focused on reversible inhibitors of some of the reactions described above. Potentially helpful new strategies may include: 1) enhanced production of thrombin-activatable fibrinolysis inhibitor (TAFI) to limit fibrinolysis, 2) synthesis of thrombin receptor blockers to limit platelet and endothelial activation, 3) protection of endothelial cell receptors during CPB, 4) control of CPB-induced platelet-PMN and endothelial-PMN adhesion in order to limit postoperative organ system dysfunction, and 5) limitation of tissue factor pathway activation in order to minimize thrombin production during CPB. This review highlights recent developments in the understanding of the molecular mechanisms of the action of thrombin induced by CPB.

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Tissue factor pathway inhibitor antigen and activity in 96 patients receiving heparin for cardiopulmonary bypass

Cited by 23 publications

References 21 publications

Characterization of the Association of Tissue Factor Pathway Inhibitor With Human Placenta

Characterization of the Association of Tissue Factor Pathway Inhibitor With Human Placenta

Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity

Thrombin and cardiopulmonary bypass – A paradigm for evaluation of the regulation of hemostasis

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