Inhibition of Tissue Factor Pathway During Intermittent Pneumatic Compression

Abstract

Abstract-Intermittent pneumatic compression (IPC) devices are an effective prophylaxis against lower extremity deep vein thrombosis. Their antithrombotic effect has been attributed to a reduction in venous stasis and enhanced fibrinolysis. The initiating mechanism for blood coagulation is the tissue factor (TF) dependent pathway, which is inhibited by tissue factor pathway inhibitor (TFPI). We have investigated the effect of IPC on the TF pathway in 6 normal subjects and 6 patients with postthrombotic venous disease undergoing IPC for 120 minutes; all subjects were studied with each of 5 IPC devices. In normal subjects and patients, plasma factor VIIa (FVIIa) activity (the activated form of factor VII [FVII]) declined from mean values ranging 51 to 65 and 50 to 53 mU/mL before IPC with different devices to 10 to 13 and 20 to 22 mU/mL at 180 minutes, respectively (PϽ0.001 for all groups). FVII antigen levels were unchanged. Plasma TFPI (PϽ0.001) rose from mean baseline values ranging 69 to 79 and 57 to 61 ng/mL to 76 to 123 and 71 to 79 ng/mL at 180 minutes in normal subjects and patients, respectively (PϽ0.001 for all groups). Plasma prothrombin fragment F1.2 levels showed minimal changes. There was an inverse relationship between TFPI and FVIIa in normal subjects (rϭϪ0.31, Pϭ0.001) and patients (rϭϪ0.37, PϽ0.001). IPC results in an increase in plasma TFPI and decline in FVIIa. Inhibition of TF pathway, the initiating mechanism of blood coagulation, is a possible mechanism for the antithrombotic effect of IPC. Key Words: intermittent pneumatic compression Ⅲ tissue factor pathway Ⅲ factor VIIa Ⅲ tissue factor pathway inhibitor Ⅲ factor VII I ntermittent pneumatic compression (IPC) is an established nonpharmacological method of prophylaxis against deep vein thrombosis. 1 The mechanisms for the antithrombotic effects of IPC are unclear and generally considered to be due to reduction of venous stasis in the lower extremities and stimulation of endogenous fibrinolytic mechanisms. 1-4 However, the effects of IPC on the early events of blood coagulation are unknown. The initiating mechanism of blood coagulation is the tissue factor (TF)-dependent pathway, which is regulated primarily by the tissue factor pathway inhibitor (TFPI), a Kunitz type inhibitor circulating in plasma. [5][6][7] This pathway is initiated when factor VIIa (FVIIa, the activated form of FVII) is exposed to its cofactor, tissue factor (TF), leading to formation of TFFVIIa complex, which proteolytically activates factor X (FX) and factor IX (FIX). 5-7 TFPI inhibits FXa directly and the TF-FVIIa complex in the presence of FXa. 5-8 Thus TFPI is a key natural anticoagulant that functions at the initial steps of blood coagulation. 5-7 Although a thromboembolic disease secondary to an inherited TFPI deficiency is yet to be recognized, there is evidence in rabbits suggesting that TFPI protects against thrombosis after exposure of blood to TF 9,10 and decreases mortality in Escherichia coli-induced shock in baboons. 11 Plasma TFPI levels are elevated after ...

Endothelial nitric oxide production during in vitro simulation of external limb compression

“…Total nitrite production values were normalized to the number of cells in each group. To assess the NO 3 Ϫ component, in separate tests, nitrate in HUVEC-conditioned medium was converted to nitrite with 50 mU of nitrate reductase from Aspergillus niger (Sigma) and 10 M ␤-NADPH for 1 h at room temperature. This protocol converted Ͼ95% of nitrate to nitrite.…”

“…It has been hypothesized that hemodynamic action stimulates fibrinolytic activity via production of tissue-type plasminogen activator (tPA) by the vascular endothelium (16). 2) Chouhan et al (3) showed that EPC results in an increase in plasma tissue factor pathway inhibitor (TFPI) and a decline in factor VIIa. This result suggests that inhibition of the tissue factor pathway, the major physiological initiating mechanism of blood coagulation, might be an important mechanism for the antithrombotic effect of EPC.…”

The Means of Progress in Improving the Results of in vitro Fertilization Based on the Identification and Correction of the Pathology of Hemostasis

“…In the meantime, the correlation of the activities presented by these participants of the fibrinolysis system determines its overall efficacy. Some publications relate the mechanism of the IPC antithrombotic effect to the inhibition of coagulation cascade due to the expression of the tissue factor pathway inhibitor (TFPI) into blood flow and the decrease in the level of factor VIIa (Chouhan et al, 1999;Christen et al, 1997). Currently IPC is used worldwide for thromboprophylaxis in patients with strokes, after arthroplasty and a number of other operative invasions, in medical emergency,and applicable, firstly, in cases when administration of anticoagulants is dangerous due to the development of haemorrhage (Geerts & Selby, 2003;Gordon et al, 2012).…”

Toward the individual approach to the evaluation of risks and prevention of postoperative venous thromboembolism

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