Biomedical subjects

Marek Z Wojtukiewicz

Publications and source records attributed to Marek Z Wojtukiewicz.

At least 19 recordsLinked to original sources

PubMed2006

Enhanced prolidase activity and decreased collagen content in breast cancer tissue.

Adherent interactions between integrins and extracellular matrix (ECM) proteins play an important role in tumorigenicity and invasiveness. The major component of ECM is collagen that plays a central role in the interaction with integrins. The expression of certain collagenases (gelatinases) by tumour cells is one of the characteristic features of the so-called metastatic phenotype, presumably by breaking down ECM barriers as well by altering the ECM-cell interaction. Although extracellular collagenases initiate the breakdown of collagen, the final step of collagen degradation is catalysed by intracellular prolidase. Collagen deposition, gelatinolytic and prolidase activities, expression of beta(1)-integrin receptor and their possible relationships were studied in seven operable breast cancer cases. In breast cancer tissue, we have found significant decrease in the amount of collagen. The decrease in collagen deposition in breast cancer tissue was accompanied by increase in the tissue gelatinolytic and prolidase activities. Simultaneously, a slight decrease in the expression of beta(1)-integrin receptor in breast cancer tissue was observed. These results suggest that alteration in collagen metabolism in breast cancer tissue may reflect tissue remodelling, characteristic for invasive phenotype of cancer cells. Increased gelatinolytic and prolidase activities in breast cancer tissue may enhance stromal matrix degradation and thus may promote metastatic dissemination. On the basis of the data, it seems that compounds endowed with gelatinolytic and prolidase inhibitory activities may be considered as a potential drug candidates for breast cancer therapy.

Blotting, Western↗

PubMed2006

[Expression of blood coagulation inhibitors in colon cancer].

UNLABELLED: Colon cancer morbidity in Poland is still increasing. During the course of the disease thromboembolic complications are often observed. It was documented that components of the hemostatic system influence cancer progression. The presence of coagulation factors was revealed in colon cancer tissue. So far the information on the presence of inhibitors of coagulation in this tumor type was lacking. The aim of the study was to evaluate the expression of coagulation inhibitors in loco in colon cancer. MATERIAL AND METHODS: Immunohistochemical method employing polyclonal antibodies directed against tissue factor pathway inhibitor (TFPI), antithrombin III (AT Ill), protein C (PC) and protein S (PS) was introduced. RESULTS: The presence of TFPI was observed in cancer cells in a part of examined specimens, but the intensity of the staining was different. In most cases of colon cancer AT III expression of low intensity was revealed in a few cancer foci. In approximately 15% of cases there was no AT Ill expression, while in other 15% of examined fragments of colon cancer AT Ill was readily detected. Weak expression of TM was observed in most colon cancer tissues, but only in some cancer foci. In 1/3 of examined cases the strong expression of TM was revealed. Weak and heterogeneous intensity of expression of PC was demonstrated in about 75% of colon cancer cases, whereas in about 25% of the specimens--the expression of this protein was strong. Furthermore in most cases there was no or weak expression of PS. Only in about 25% of the cases the staining for PS was strong. Expression of TFPI, AT III and PC was revealed in macrophages, whereas TFPI and AT Ill were detected in mucus in the lumen of neoplastic glands, and TM--in endothelial cells. CONCLUSIONS: Weak representation or the lack of coagulation inhibitors in colon cancer in most cases may facilitate coagulation activation in the tumor burden, and consequently promote colon cancer progression. Heterogeneous and inconstant presence of blood coagulation inhibitors in colon cancer in loco may suggest, that nonocoagulant biological activities of these inhibitors may influence the cancer growth or its inhibition in an individual patient. Obtained results suggest that introducing various forms of blood coagulation inhibitors in the treatment of colon cancer patients may be beneficial in selected group of patients.

Animals↗

PubMed2005

First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study.

PURPOSE: We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients. PATIENTS AND METHODS: Patients were randomly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2) docetaxel. The primary end point was the percentage of patients developing febrile neutropenia (defined as body temperature >/= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after). Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia, intravenous (IV) anti-infectives required for febrile neutropenia, and the ability to maintain planned chemotherapy dose on time. Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles. RESULTS: Nine hundred twenty-eight patients received placebo (n = 465) or pegfilgrastim (n = 463). Patients receiving pegfilgrastim, compared with patients receiving placebo, had a lower incidence of febrile neutropenia (1% v 17%, respectively; P < .001), febrile neutropenia-related hospitalization (1% v 14%, respectively; P < .001), and use of IV anti-infectives (2% v 10%, respectively; P < .001). The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo (80% and 78%, respectively), as would be expected of the study design. Pegfilgrastim was generally well tolerated and safe, and the adverse events reported were typical of this patient population. CONCLUSION: First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia, febrile neutropenia-related hospitalizations, and IV anti-infective use.

Adult↗

PubMed2005

Cancer procoagulant in patients with adenocarcinomas.

Cancer procoagulant (CP) is a cysteine proteinase that may be produced by malignant and foetal tissue. The possible role of CP in the pathogenesis of cancer-related thrombosis has been suggested recently. The purpose of the study was to evaluate coagulation prothrombotic markers and their relation to CP concentration in the blood of patients with gastrointestinal adenocarcinomas (GIAC). The study group consisted of 45 patients with confirmed diagnosis of adenocarcinoma (stomach, 18 patients; colon, 27 patients) and without evident metastatic disease. In 24 patients further observation showed metastases. The control group for CP was composed of 10 healthy subjects. Blood samples were drawn on the admission day, before any treatment. Among 45 patients with GIAC, deep venous thrombosis was observed in two (4.4%). In all patients the CP activity in the serum was found, and the mean CP activity shortened the coagulation time almost three times compared with the healthy control group. Also, the mean thrombin-antithrombin complex concentration was above the normal range. A significant elevation of the mean prothrombin fragment 1+2 plasma content in this group of patients was noticed. Despite these observations, CP remained within the normal range and did not correlate with thrombin-antithrombin complex or prothrombin fragment 1+2 plasma concentrations. A positive correlation was observed between serum CP and fibrinogen concentration, and a negative correlation between CP and free protein S plasma content (P = 0.04 and P = 0.025, respectively). A negative correlation between activated protein C resistance ratio and protein C activity in the plasma was confirmed. Protein C activity in the plasma showed a correlation with free protein S plasma content. Analysis of factors influencing the activated partial thromboplastin time revealed the presence of antiphospholipid antibodies in seven persons from the study group (in three cases of IgG and in four cases of IgM class). Our data suggest that CP is a minor risk factor for deep venous thrombosis in GIAC patients. To confirm this, however, the number of patients and controls should be larger. After 3 years of observation, the follow-up in 10 living GIAC patients showed nobody with thromboembolic disease.

Adenocarcinoma↗

PubMed2005

Evaluation of urokinase-type plasminogen activator and its receptor in neointima of polyester vascular grafts.

The aim of the study was to assess the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in neointima of polyester vascular grafts. Anastomotic areas were examined at 1, 4 and 12 months after prosthesis implantation in dogs, as well as in human vascular grafts. Immunohistochemistry was performed for uPA and uPAR. Graft neointima in dogs was positively stained for uPA with increased intensity at 4 and 12 months, whereas uPAR expression appeared at 4 and its intensity was increased at 12 months. Intensive uPA and positive uPAR labeling was shown in human grafts. The results demonstrated that in the early period of the healing process of polyester vascular grafts only uPA is present in the neointima in the region of the graft to adjacent artery anastomosis, whereas in healed grafts in dogs and humans uPAR is found as well.

Animals↗

PubMed2004

Expression of fibrinolysis activators and their inhibitor in neointima of polyester vascular grafts.

The aim of the study was to evaluate dynamic changes in the expression of fibrinolytic system components in neointima forming in polyester vascular grafts. The study was carried out on 18 mongrel dogs divided into three groups, that underwent replacement of abdominal aorta with a polyester double velour prosthesis. Grafts were removed at 1, 4 and 12 months. The specimens were fixed according to AMeX method. Immunohistochemical labeling for von Willebrand factor (vWf), tissue plasminogen activator (t-PA), urokinase (u-PA), its receptor (u-PAR), plasminogen activator inhibitor type 1 (PAI-1) and D-dimer (DD) was performed. Increasing intensity of vWf expression on the graft luminal surface was found in successive periods of the study. A light positive t-PA and u-PA staining was shown in neointima at 1 month and its intensity was significantly increased at 4 and 12 months. Expression of u-PAR appeared at 4 months. A light positive PAI-1 and DD staining was demonstrated in neointima in all periods of the study. The results demonstrated increasing expression of fibrinolysis activators in neointima of polyester vascular grafts. Intensive expression of plasminogen activators, when compared to their inhibitor may reduce thrombotic properties of graft neointima particularly in the late period after prosthesis implantation.

Blood Vessel Prosthesis↗

PubMed2004

Contribution of the hemostatic system to angiogenesis in cancer.

It is now recognized that the hemostatic system plays an important role in cancer growth and dissemination, processes known to be vitally dependent on new tumor blood vessel formation (angiogenesis). There is also an increasing body of evidence supporting the link between the various components of the coagulation/fibrinolysis systems and angiogenic activity in cancer patients. Tissue factor (TF), thrombin, fibrinogen, fibrin, and plasminogen activation system, as well as platelets, all are able to promote angiogenesis. On the other hand, coagulation inhibitors, as well as cryptic (proteolytically released) domains of hemostatic proteins, are also known to act as angiogenesis inhibitors. Indeed, modulation (stimulation or inhibition) of angiogenesis may result from either classical functions of various molecular components of the hemostatic cascade, their less studied "alternative" activities, or both. Although much remains to be understood about this complex circuitry these considerations support the judicious use of anticoagulants in patients with malignancy as well as encourage the search for novel antiangiogenic activities that may reside within molecular and cellular components of the hemostatic system.

Blood Coagulation Factors↗

PubMed2004

Platelets and angiogenesis in malignancy.

There is increasing evidence that platelets play an important role in the process of tumor angiogenesis. Thrombocytosis is a frequent finding in cancer patients (10-57%). Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity and growth factors, platelet-derived microparticles, and factors secreted from bone marrow endothelial cells, as well as growth factors released by megakaryocytes (acting via an autocrine loop), are postulated to influence this process. The progression of cancer is associated with hypercoagulability, which results from direct influences of tumor cells and diverse indirect mechanisms. Activated platelets serve as procoagulant surfaces amplifying the coagulation reactions. It is well known that hemostatic proteins are involved in different steps of the angiogenic process. Furthermore, platelets adhering to endothelium facilitate adhesion of mononuclear cells (which exert various proangiogenic activities) to endothelial cells and their transmigration to the extravascular space. It was also documented that platelets induce angiogenesis in vivo. Platelets are a rich source of proangiogenic factors. They also store and release angiogenesis inhibitors. In addition, platelets express surface growth factor receptors, which may regulate the process of angiogenesis. Platelets also contribute directly to the process of basement membrane and extracellular matrix proteolysis by releasing proteinases, or indirectly via inducing endothelial cells and tumor cells to release proteolytic enzymes, as well as through the proteolytic activities of platelet-derived growth factors. The multidirectional activities of platelets in the process of new blood vessel formation during tumor development and metastasis formation may create the possibility of introducing antiplatelet agents for antiangiogenic therapy in cancer patients. Thus far experimental studies employing inhibitors of glycoprotein IIb-IIIa have yielded promising results.

Blood Platelets↗

PubMed2004

Interfering with hemostatic system components: possible new approaches to antiangiogenic therapy.

Inhibition of angiogenesis has progressed from a theoretical and esoteric discipline scrutinized in but a few laboratories far removed from the clinic, to mainstream experimental clinical cancer therapeutics. Dramatic progress in this field represents a triumph of the concept of translational biomedical research. Growth of knowledge in this discipline has brought to light a bewildering yet tantalizing array of interacting enzymatic algorithms that participate in the highly orchestrated process of new blood vessel formation critical for tumor growth and dissemination. It is clear that pathways of blood coagulation (in broad context) and angiogenesis are inextricably linked. The facts that much is already known about many components of these pathways and that stalling of tumor growth has already been demonstrated for several interventions aimed at participants in these reactions send a clear signal that more effective and less toxic cancer therapy may be at hand in the near future. There is no lack of candidate targets for intervention brought to light by preclinical scientists. Numerous well-characterized investigational agents are on hand for testing. The challenge is clearly in the hands of the clinical investigators to proceed with human intervention studies while armed with knowledge of opportunities and pitfalls that should guide insightful clinical trial design. A particularly compelling feature of this treatment paradigm is that it is not aimed directly at destruction of tumor through inhibition of the DNA replication machinery of the cell. Rather it is aimed at restoring the normal state by modulating the dysregulated interaction of tumor cells with their environment that is characteristic of cancer.

Angiogenesis Inhibitors↗

PubMed2004

Proteasome inhibitor prevents experimental arterial thrombosis in renovascular hypertensive rats.

Recent studies indicate that highly selective proteasome inhibitors can be useful in prevention of some cardiovascular events. Here we demonstrate that proteasome inhibitor, Z-Ile-Glu (Ot-Bu) Ala-Leucinal (PSI), is active in the prevention of platelet-dependent arterial thrombosis induced in renovascular hypertensive rats (two-kidney, one clip Goldblatt model, and 2K1C, n=5). The administration of PSI intravenously at a single dose of 0.3 mg/kg before induction of arterial thrombosis markedly increased carotid final flow rate, as compared to control (vehicle) group (10.36 +/- 1.8 ml/min and 1.2 +/- 1.2 ml/min, respectively), significantly decreased the wet (1.23 +/- 0.23 mg and 4.1 +/- 0.94 mg, respectively), and dry (0.46 +/- 0.145 mg and 1.46 +/- 0.39, respectively) thrombus weight, and completely prevented arterial occlusion. Moreover, platelets from PSI - treated thrombotic 2K1C rats, showed in response to collagen a significant inhibition of aggregation in the whole blood (10.26 +/- 0.6 ohms vs. 15.51 +/- 0.91 ohms in the control group). In contrast, collagen-induced platelet aggregation was not inhibited in vitro, after pre-treatment of the blood with PSI at the concentration of 10 microM that effectively inhibited the 20S proteasome activity in platelets, indicating that ex vivo anti-aggregatory effect of PSI proceeds through an indirect mechanism not associated with suppression of 20S proteasome activity in platelets. In conclusion, our in vivo findings demonstrate that proteasome inhibitor, Z-Ile-Glu(Ot-Bu)Ala-Leucinal, prevents the development of arterial thrombosis in renovascular hypertensive rats and effectively suppresses platelet aggregation by an indirect mechanism. Thus the data provide a new insight into the potential role for the proteasome-dependent pathway in cardiovascular events.

Animals↗

PubMed2003

Tissue factor-dependent coagulation activation and impaired fibrinolysis in situ in gastric cancer.

Thromboembolism frequently complicates gastric cancer. This study examined the solid phase interaction between gastric cancer and coagulation proteins in situ that may explain coagulation activation and that may contribute to tumor progression and angiogenesis in this tumor type. Immunohistochemical techniques were applied to tissues from 37 cases of adenocarcinoma of the stomach obtained at surgical resection. Fibrinogen was present throughout the tumor stroma. Fibrin and its D-dimer cross-link sites occurred at the host-tumor interface. Subunit "a" of factor (F) XIII and F VII, IX, X, and XII were observed on cancer cells. Prothrombin and prothrombin fragment F1+2 (F1+2) were demonstrated in the tumor stroma on cancer cells and on small blood vessels. Tissue factor (TF) was present on cancer cells and tumor-associated macrophages. Protein C was observed on cancer cells and small blood vessels, whereas protein S was present only in the vascular bed. There was no staining for tissue factor pathway inhibitor (TFPI). High-molecular-weight (HMW) urokinase plasminogen activator (u-PA) antigen was not detected, but weak and inconsistent staining for low-molecular-weight (LMW) u-PA was demonstrated on cancer cells. Weak staining for tissue plasminogen activator (t-PA) occurred on cancer cells and in the tumor stroma. In contrast, plasminogen activator inhibitor-1 (PAI-1) expression was strong in the tumor stroma, along with PAI-2 and PAI-3. The endothelium of small stromal blood vessels, particularly near the host-tumor interface, demonstrated von Willebrand factor antigen (vWF Ag). Vascular endothelial growth factor (VEGF) was present on cancer cells and stromal macrophages. These results demonstrate tumor cell-associated TF-dependent extravascular coagulation activation in situ in gastric cancer that does not appear to be counterbalanced by TFPI or sufficient fibrinolytic activity. Colocalization of VEGF with hemostatic proteins suggests that they may cooperate in the pathogenesis of gastric cancer.

Blood Coagulation↗

PubMed2003

Occurrence of components of fibrinolytic pathways in situ in laryngeal cancer.

Malignancy is characterized by the occurrence of components of coagulation reaction pathways in situ within tumor tissues detectable immunohistochemically. However, tumors vary in the details of this coagulation-cancer interaction. We have previously described tumor cell-associated tissue factor (TF), factor (F) VII, and F X in laryngeal carcinoma tissues. Fibrinogen and F XIIIa were found in the tumor connective tissue. Tissue factor pathway inhibitor (TFPI) occurred in the tumor connective tissue and on microvascular endothelial cells and normal squamous epithelial cells but not in the tumor cells. Fibrin (thrombin-cleaved fibrinogen) existed at the host-tumor interface and the margins of tumor nodules consistent with an active tumor cell-associated clotting pathway in this tumor type. Studies were extended here to detect components of fibrinolytic pathways. Plasminogen and tissue plasminogen activator (t-PA) were detected on laryngeal tumor cells, particularly in more well-differentiated cases. Low-molecular-weight urokinase plasminogen activator (LMW u-PA) was primarily a feature of more undifferentiated laryngeal carcinoma cells. Staining to a lesser extent was found for high-molecular-weight u-PA (HMW u-PA) on tumor cells and various normal cell types in the tumor tissue. Relatively weak and variable tumor cell staining was found for plasminogen activator inhibitors (PAI) 1, 2, and 3. Trace staining was found for u-PA receptor (u-PAR) in differentiated tumor cells. The significance of coagulation and fibrinolytic pathways present in situ to the economy of laryngeal carcinoma remains to be determined.

Fibrinolysis↗

PubMed2003

Coagulation activators and inhibitors in the neointima of polyester vascular grafts.

The surface of synthetic vascular grafts is thrombogenic, which implies a risk for their occlusion. The aim of the study was to evaluate expression of coagulation components in the polyester vascular grafts neointima. The study was carried out on 18 dogs, which underwent replacement of the abdominal aorta with a polyester prosthesis. Grafts were removed after 1, 4 and 12 months. Immunohistochemical labeling for von Willebrand factor, tissue factor, factor XII, tissue factor pathway inhibitor, thrombomodulin, protein C, protein S and prothrombin activation fragment F1 + 2 was performed. Increasing intensity of von Willebrand factor expression was found in successive periods of the study. Factor XII was shown in the whole neointima after 1 month, whereas in the following periods its presence was limited to the luminal surface. Tissue factor expression was demonstrated after 1 month and its intensity increased in later periods. Tissue factor pathway inhibitor and thrombomodulin expression was demonstrated after 4 and 12 months. Protein C and protein S were present in all observation periods, as well as prothrombin activation fragment F1 + 2. Results indicate a high thrombotic potential of the graft neointima early after prosthesis implantation, whereas in the late postoperative follow-up increasing expression of coagulation inhibitors reduces thrombotic properties of the graft neointima.

Animals↗

PubMed2003

Immunohistochemical localization of tissue factor pathway inhibitor-2 in human tumor tissue.

The progression of neoplasms is frequently associated with thromboembolic complications. Coagulation proteins, particularly tissue factor (TF), have been shown to play a role in tumor growth and metastatic dissemination. TFPI is the principal inhibitor of TF-dependent pathway of blood coagulation, but previous studies failed to detect antigenic TFPI in cancer tissue. Recently, a second inhibitor of tissue factor dependent pathway, TFPI-2 (also known as placental protein 5 [PP5] or matrix-associated serine protease inhibitor [MSPI]), has been described. Information on the presence of TFPI-2 within the malignant tumor tissue still remains obscure, and thus the aim of this study was to evaluate the expression of TFPI-2 in loco in several different neoplasms. TFPI-2 expression was demonstrated by immunohistochemical procedures in neoplastic cells of laryngeal, breast, gastric, colon, pancreatic, renal and endometrial cancer, as well as glial neoplasms. The intensity of staining was not uniform, with higher intensity in more differentiated tumors. G3 breast, gastric, endometrial and colon cancer cells revealed populations of cells that were either TFPI-2 positive or negative. Gastric and renal cancer tissue exhibited the presence of TFPI-2 in tumor infiltrating macrophages. TFPI-2 was also observed in normal tissue of the breast, stomach, colon and pancreas. These data demonstrate that the expression of TFPI-2 diminishes with an increasing degree of malignancy, which may suggest a role for TFPI-2 in the maintenance of tumor stability and inhibition of the growth of neoplasms.

Carcinoma↗

PubMed2003

[Primary location on non-Hodgkin's lymphoma in the jaw: a case study].

A rare case of primary non-Hodgkin's lymphoma (NHL) of the jaw is reported. Precise diagnosis of such primary manifestation of NHL may pose a diagnostic problem due to unspecific clinical and radiological findings as well as difficult interpretation of biopsy specimens. The prognosis is related to the clinical stage, tumour aggressiveness and response to treatment.

Biopsy↗

PubMed2003

[The location of components of fibrinolytic system in laryngeal cancer].

Laryngeal cancer is the most common neoplasm of the head and neck region. Laryngeal cancer patients experience thromboembolic complications more often than the general population. Our previous studies revealed in loco activation of blood coagulation in laryngeal cancer. The purpose of the present study was to examine the interactions among the laryngeal cancer cells and fibrinolytic system components in loco. Twenty-two cases of squamous carcinoma of the larynx were examined. AMeX method-preserved cancer tissues were examined using immunohistochemical ABC method. Fibrin and D-D fibrin dimers were demonstrated in the matrix, predominantly on the tumor-host front. Plasminogen, tissue-type plasminogen activator (t-PA) and plasmin were detected in cancer cells, but the intensity of their expression revealed a negative correlation with the degree of malignancy. A weak expression of high molecular weight urokinase (HMW-UK) was observed in cancer cells in the centers of the cancer foci, and a product of its degradation--low molecular weight urokinase (LMW-UK) was observed in cancer cells on the invasion front. The presence of plasminogen activator inhibitors (PAI-1, PAI-2, PAI-3) was also documented in the cancer cells. The expression of urokinase receptor (u-PAR) was very weak. Based on the results of the study, we suggest that in laryngeal cancer a suboptimal activation of fibrinolysis occurs that contributes to fibrin deposition in the tumour.

Antibodies↗

PubMed2003

[Protein Z].

Protein Z (PZ) is a 6.2 kDa vitamin K-dependent protein, synthesized in the liver. The gene for human PZ is localized to chromosome 13 at band 34 q. The structure of PZ is very similar to that of factors VII, IX, X and protein C. Very low plasma levels of protein Z were observed under oral anticoagulant treatment. The cause of this phenomenon might be increased protein Z binding on the surface of endothelial cells. Protein Z is consumed during coagulopathy. About 60% of humans suffering from a bleeding tendency of unknown origin presented with decreased plasma levels of protein Z. PZ forms a Ca(2+)-dependent complex with activated factor X (Xa) on phospholipid surfaces, that leads to the inhibition of factor Xa and decrease in thrombin generation. Inhibition of factor Xa may be caused directly by protein Z or indirectly by the activity of protein Z-dependent protease inhibitor (ZPI). ZPI is a 72 kDa member of the serpin family of proteinase inhibitors, synthesized in the liver. ZPI circulates in plasma in complex with protein Z. ZPI in the presence of Ca2+ and phospholipids inhibits factor Xa. The presence of protein Z enhances this process by more than 1000 times. ZPI also inhibits activated factor XI in the absence of protein Z, Ca2+ or phospholipids. Protein Z deficiency may induce bleeding as well as prothrombotic tendencies and might occur as an inherited disorder. Protein Z deficiency may aggravate mild bleeding tendency in subjects with diagnosed borderline decrease in von Willebrand factor and factor VII activity. Patients presenting with factor V Leiden mutation and low protein Z levels show earlier onset and higher frequency of thromboembolic events comparing to patients with normal protein Z levels.

Blood Proteins↗

PubMed2002

[Tissue factor pathway inhibitors].

Activation of the extrinsic pathway of blood coagulation plays the key role in the process of blood coagulation. The hemostasis is influenced by the activity of procoagulant factors and its inhibitors. In this work we summarize existing data on tissue factor pathway inhibitors: TFPI and TFPI-2. Despite structural similarity between them, they exhibit many differences in synthesis, distribution and mechanism of action. TFPI inhibits the activity of factor Xa and the complex of tissue factor and factor VIIa (TF/VIIa). Conversely, TFPI-2 does not inhibits factor Xa, but it is a strong inhibitor of factor XIa, plasma kallikrein, plasmin and trypsin.

Anticoagulants↗