Elevated levels of free tissue factor pathway inhibitor antigen in cases of disseminated intravascular coagulation caused by various underlying diseases

Abstract

Tissue factor pathway inhibitor (TFPI) is primarily synthesized by vascular endothelial cells and is found in vivo in association with endothelial cells, lipoproteins, or in free form. Free TFPI is the most potent and important type, because it is released from endothelial cells following an injection of heparin, or as a result of pathological stimuli. In order to study the role of TFPI in disease, the concentration of free form TFPI was measured in the plasma of 114 patients suffering from disseminated intravascular coagulation (DIC), as the result of several underlying diseases. Plasma antigen levels of free TFPI were significantly higher even in those patients not exhibiting DIC than in normal healthy subjects. These levels were even higher among patients exhibiting DIC, especially those with acute promyelocytic leukemia or cancer, receiving continuous heparin drip infusions. A significant correlation was observed between the plasma antigen levels of free form TFPI and those of fibrin/fibrinogen degradation products, and free form TFPI and plasmin inhibitor complex (r = 0.428, P < 0.0001 and r = 0.329, P < 0.0001, respectively) among 114 DIC patients. There were no significant differences between the plasma levels of free TFPI in DIC patients with or without multiple organ failure. It has been suggested that the plasma levels of free TFPI are closely related to the levels of fibrinolysis occurring in DIC patients, although further study is required to clarify the degree to which TFPI is expressed by endothelial cells during DIC.

Tissue Factor and Tissue Factor Pathway Inhibitor in Chronically Inflamed Gallbladder Mucosa

“…This inhibitor is synthesised by the endothelial cells and in majority is associated with the vessel wall [9]. Both lack of upregulation and downregulation of TFPI as compared with the healthy subjects found in the current study may be most likely due to cleavage of TFPI by proteases of inflammatory cells [10]. It is worth emphasising that, as it was previously reported, the lack of TFPI upregulation may be important contributing factor responsible for procoagulation state in acute and chronic inflammatory conditions [11, 12].…”

Successful Administration of Recombinant Human Soluble Thrombomodulinα(Recomodulin) for Disseminated Intravascular Coagulation during Induction Chemotherapy in an Elderly Patient with Acute Monoblastic Leukemia Involving the t(9;11)(p22;q23)MLL/AF9Translocation

“…In DIC patients with leukemia, leukemia cells and tumor cells damaged by cytotoxic chemotherapy excrete tissue factor (TF) [3]. The increased TF release initiates the coagulation cascade in the blood [25, 26], and TF serves as a receptor and essential cofactor of factors VII and VIIa, which activate the extrinsic coagulation pathway and require anticoagulation rescue by activated protein C (APC). Thus, cytoplasm-derived TF and insufficient rescue by APC result in DIC in leukemia patients at the time of diagnosis as well as during cytotoxic chemotherapy.…”

“…They classified 83% of t(9;11) AML patients into the M5 subtype (FAB) and found that the median CR duration and median survival of t(9;11) AML patients who had been treated with a standard cytarabine and daunorubicin induction regimen were significantly better than those of AML patients with 11q23 translocations ( P = 0.02 or P = 0.009, resp.). They also found that the percentage organ involvement in adult de novo AML patients with the t(9;11) translocation was as follows: involvement of the skin, 4%; gum hypertrophy, 21%; splenomegaly, 8%; hepatomegaly, 21%; lymphadenopathy, 17%, but no significant difference was seen compared with 11q23 translocation associated AML [30], suggesting that adult patients with MLL leukemia tend to suffer from extramedullary or extranodal lesions; that is, display gingival or skin infiltration, in which cancer infiltration has the potential to activate TF, resulting in DIC [25]. Therefore, strict control of initial DIC or chemotherapy-induced DIC during induction therapy would bring about a better prognosis in patients with 11q23/ MLL AML.…”

Back to the future: testing in disseminated intravascular coagulation

“…Its exposure rapidly induces the expression and activity of tissue factor pathway inhibitor, which increase with increasing severity in DIC [12]. Although new sources of tissue factor expression may continue to sustain thrombin generation, such as via monocyte-derived microparticles, recruitment of other …”