Examination of biomarker expressions in sepsis-related DIC patients.

BACKGROUND: Disseminated avascular coagulation (DIC) is the main cause of death among patients with sepsis. In particular, low platelet count is predictive of poor outcome. However, the significance of platelet activation in patients with sepsis-related DIC is poorly understood. To determine the characteristics of platelet-related abnormality in patients with sepsis-related DIC, we assessed the expression levels of several biomarkers. METHODS: Plasma levels of biomarkers, including cytokines, chemokines, soluble selectins, platelet-derived microparticles (PDMPs), soluble vascular adhesion molecule 1, and high mobility group box protein 1 were measured by enzyme-linked immunosorbent assay at baseline and after 4, 7, 14, and 21 days of DIC treatment. RESULTS: Differences in platelet activation and in the elevation of activated platelet-related PDMPs and of soluble P-selectin were seen between patients suffering from sepsis and hematologic malignancy with DIC. In addition, the elevation of interleukin (IL)-6 and thrombopoietin (TPO) was significant in sepsis patients with DIC. Furthermore, IL-6 and TPO promoted platelet activation in vitro. CONCLUSION: Assessment of PDMPs, sP-selectin, IL-6, and TPO may be beneficial in the primary prevention of multi-organ failure in sepsis patients with DIC.

Immunohistochemical analysis of NANOG expression and epithelial-mesenchymal transition in pulmonary sarcomatoid carcinoma.

Pulmonary sarcomatoid carcinomas (PSCs) are defined as a group of poorly differentiated non-small cell lung cancers that demonstrate sarcoma-like differentiation. The mechanism of mesenchymal differentiation in PSC is epithelial-mesenchymal transition (EMT). The expression of homeobox protein NANOG (NANOG), which regulates the pluripotency of embryonic stem cells, is associated with the EMT process. Therefore, the present study aimed to assess the expression level of NANOG and the status of the EMT process in PSC. The data of patients with PSC were retrospectively reviewed and immunohistochemical analyses were performed on patient samples to examine the expression of NANOG and EMT-associated proteins. The comparator group included randomly selected patients with matched clinicopathological characteristics who had pulmonary adenocarcinoma (PA). In the present study, 12 patients with PSC (4 females and 8 males) were enrolled; their median age was 65 years (range, 36-79 years), and the number of patients with stage IB, IIB, IIIA, IIIB and IV disease were 1, 1, 1, 1 and 8, respectively. The immunoreactive score (IRS) for E-cadherin was significantly lower in the PSC group compared with the PA group (P<0.0001), whereas the IRS for vimentin was significantly higher in the PSC group compared with the PA group (P<0.0001). However, the IRS for NANOG was significantly decreased in the PSC group compared with the PA group (P<0.0001), which suggests that NANOG does not serve an essential role in EMT in PSC. In addition, the overall survival of patients with PSC was significantly lower compared with that of patients with PA (median survival time, 7.0 vs. 35.6 months, respectively; P=0.0256). However, no significant difference was observed in the OS of patients who expressed low compared with high levels of NANOG (P=0.4416). In conclusion, it was clearly demonstrated that cytoplasmic NANOG expression was significantly lower in PSC compared with PA, and that the EMT process in PSC was accelerated, compared with that in PA.

Microparticles as Biomarkers of Blood Coagulation in Cancer.

Cancer is associated with hypercoagulopathy and increased risk of thrombosis. This negatively influences patient morbidity and mortality. Cancer is also frequently complicated by the development of venous thromboembolism (VTE). Tumor-derived tissue factor (TF)-bearing microparticles (MPs) are associated with VTE events in malignancy. MPs are small membrane vesicles released from many different cell types by exocytic budding of the plasma membrane in response to cellular activation or apoptosis. MPs may also be involved in clinical diseases through expression of procoagulative phospholipids. The detection of TF-expressing MPs in cancer patients may be clinically useful. In lung and breast cancer patients, MPs induce metastasis and angiogenesis and may be indicators of vascular complications. Additionally, MPs in patients with various types of cancer possess adhesion proteins and bind target cells to promoting cancer progression or metastasis. Overexpression of TF by cancer cells is closely associated with tumor progression, and shedding of TF-expressing MPs by cancer cells correlates with the genetic status of cancer. Consequently, TF-expressing MPs represent important markers to consider in the prevention of and therapy for VTE complications in cancer patients.

Clinical significance of procoagulant microparticles.

Microparticles (MPs) are small membrane vesicles that are released from many different cell types by exocytic budding of the plasma membrane in response to cellular activation or apoptosis. MPs may also be involved in clinical diseases because they express phospholipids, which function as procoagulants. Although flow cytometry is the most widely used method for studying MPs, some novel assays, such as tissue factor-dependent procoagulant assay or the ELISA method, have been reported. However, the use of quantification of MP as a clinical tool is still controversial. Elevated platelet-derived MP, endothelial cell-derived MP, and monocyte-derived MP concentrations are documented in almost all thrombotic diseases occurring in venous and arterial beds. However, the significance of MPs in various clinical conditions remains controversial. An example of this controversy is that it is unknown if MPs found in peripheral blood vessels cause thrombosis or whether they are the result of thrombosis. Numerous studies have shown that not only the quantity, but also the cellular origin and composition of circulating MPs, are dependent on the type of disease, the disease state, and medical treatment. Additionally, many different functions have been attributed to MPs. Therefore, the number and type of clinical disorders associated with elevated MPs are currently increasing. However, MPs were initially thought to be small particles with procoagulant activity. Taken together, our review suggests that MPs may be a useful biomarker to identify thrombosis.

Fatal TRALI associated with neutrophil antibodies in a recipient of pre-storage leukocyte-reduced blood components.

A 53-year-old man developed possible transfusion-related acute lung injury (TRALI) after red cell component transfusion. The patient developed autoimmune neutropenia with the expression of neutrophil antibodies. Neutrophil aggregation, endothelial damage, and development of a large thrombus containing platelets were observed post mortem in his pulmonary vessels. The patient also had subacute organizing pneumonia. He received blood components treated with universal pre-storage leuko-reduction. Even though leukocytes in the blood components are reduced to a few million by this process, TRALI can be fatal, as was the case for this recipient, who had subacute organizing pneumonia in conjunction with immune-mediated neutropenia.

The significance of EMAP-II after allogeneic stem cell transplantation.

Endothelial monocyte-activating polypeptide-II (EMAP-II) appears to play an important role in neovascularization and endothelial abnormalities. However, the role of EMAP-II in development of graft-versus-host disease (GVHD) after allogeneic SCT is poorly understood. We measured and compared the levels of EMAP-II, cytokines, and soluble factors in patients undergoing allogeneic SCT. The subjects were 23 patients who underwent allogeneic SCT. Most of the cytokines/soluble factors exhibited a significant elevation after allogeneic SCT, although Angiopoietin-1 did not change. On the other hand, the levels of these factors did not change significantly in the recipients of autologous SCT. When the relationship between EMAP-II and cytokines/soluble factors was analyzed, EMAP-II levels correlated positively with sIL-2R, sVCAM-1, sE-selectin, sFasL and EDMP. However, IL-6, Angiopoietin-1, Angiopoietin-2 and VEGF were not correlated with EMAP-II. Our results suggest that EMAP-II plays an important role in endothelial cell dysfunction related to GVHD after allogeneic SCT.