thromboplastin and Tuberculosis

Venous thromboembolic disease often arises as a complication of another pathological condition and/or triggering event. Infectious diseases result from both the direct action of the pathogens themselves and their effect on the immune system. The resulting inflammatory process and the coagulation and fibrinolysis processes share common pathways, explaining why infection is associated with thrombosis. In this brief overview, besides certain chronic infectious diseases, we also consider some acute infections, as the mechanisms are likely to be similar, particularly in the initial infective stage or the more acute episodes of a chronic infection. The infectious agent can be viral, bacterial, fungal, or parasitic. However, the literature on the link between infections and venous thromboembolism (VTE) is uneven, favoring infections that are found in more developed countries where physicians have access to VTE diagnostic tools. Thus, large epidemiological studies in this field are restricted to a limited number of the common chronic infectious diseases such as tuberculosis, while for other infections, particularly parasitic and fungal infections, the link with VTE is only evoked in a few scattered case reports.

Topics: Cell-Derived Microparticles; Chronic Disease; Developed Countries; Developing Countries; Disease Susceptibility; Endothelium, Vascular; HIV Infections; Humans; Infections; Inflammation; Macrophages; Models, Biological; Risk; Thrombophilia; Thromboplastin; Tuberculosis; Venous Thromboembolism

<b>Background and Objective:</b> Immune complexes and pro-inflammatory cytokines deduced from communicable diseases have been manifested to induce pro coagulopathy and tissue factor (TF) assertion in macrophages and the endothelial cells that remain at critical risk in tuberculosis (TB) patients. The current study was carried out among Sudanese patients with Pulmonary tuberculosis aimed to determine the long-term impacts of Tb infection on the coagulation cascade. <b>Materials and Methods:</b> A cross-sectional study was conducted among 30 patients who are already diagnosed with tuberculosis compared with the control group. Pulmonary Tuberculosis diagnosis of cases was emphasized in accordance with clinical examination, chest X-ray and positive Ziehl-Neelsen (ZN) smear. The questionnaire was used for the collection of demographic and baseline data. About 2.5 mL of venous blood was collected in trisodium citrate containers and 2.5 mL of blood was collected in EDTA container. SPSS version 21 statistical software was used for statistical analysis. <b>Results:</b> PLT count showed a significant difference (p = 0.03) with a mean (329.20×10³ and 287.60×10³ μL¹) among patients and control, respectively. APPT shows a significant difference (p = 0.00), Mean of PLT decreased as the disease progressed (336.20±36.02, 345.43±16.02, 511.04±42.02) showed a significant correlation between PLT count of test and duration of disease (p = 0.00). Additionally, a significant correlation between PLT count, MPV and APTT and the status of the patient's drug resistance was revealed (p<u><</u>0.02, 0.01 and 0.02). <b>Conclusion:</b> There is a significant alteration in coagulation parameters (PT, APTT and platelets count) among Sudanese pulmonary tuberculosis patients, which may indicate a feature of a hypercoagulable state.

Topics: Cross-Sectional Studies; Endothelial Cells; Humans; Inflammation Mediators; Sputum; Thromboplastin; Tuberculosis; Tuberculosis, Pulmonary

Tuberculosis (TB) is a chronic lung infectious disease characterized by severe inflammation and lung granulomatous lesion formation. Clinical manifestations of TB include hypercoagulable states and thrombotic complications. We previously showed that Mycobacterium tuberculosis (M.tb) infection induces tissue factor (TF) expression in macrophages in vitro. TF plays a key role in coagulation and inflammation. In the present study, we investigated the role of TF in M.tb-induced inflammatory responses, mycobacterial growth in the lung and dissemination to other organs. Wild-type C57BL/6 and transgenic mice expressing human TF, either very low levels (low TF) or near to the level of wild-type (HTF), in place of murine TF were infected with M.tb via aerosol exposure. Levels of TF expression, proinflammatory cytokines and thrombin-antithrombin complexes were measured post M.tb infection and mycobacterial burden in the tissue homogenates were evaluated. Our results showed that M.tb infection did not increase the overall TF expression in lungs. However, macrophages in the granulomatous lung lesions in all M.tb-infected mice, including low TF mice, showed increased levels of TF expression. Conspicuous fibrin deposition in the granuloma was detected in wild-type and HTF mice but not in low TF mice. M.tb infection significantly increased expression levels of cytokines IFN-γ, TNF-α, IL-6 and IL-1ß in lung tissues. However, no significant differences were found in proinflammatory cytokines among the three experimental groups. Mycobacterial burden in lungs and dissemination into spleen and liver were essentially similar in all three genotypes. Our data indicate, in contrast to that observed in acute bacterial infections, that TF-mediated coagulation and/or signaling does not appear to contribute to the host-defense in experimental tuberculosis.

Topics: Animals; Bronchoalveolar Lavage Fluid; Inflammation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mycobacterium tuberculosis; Thromboplastin; Tuberculosis

A number of earlier studies reported the occurrence of thrombotic complications, particularly disseminated intravascular coagulation and deep vein thrombosis, in tuberculosis (TB) patients. The aberrant expression of tissue factor (TF), the primary activator of coagulation cascade, is known to be responsible for thrombotic disorders in many diseases including bacterial infections. Further, expression of TF by cells of the monocyte/macrophage lineage is also shown to contribute to the development and progression of local and systemic inflammatory reactions. In the present study, we have investigated whether Mycobacterium tuberculosis (Mtb) infection induces TF expression in macrophages, and various host and pathogenic factors responsible for TF expression. We have tested the effect of live virulent Mtb H37Rv, gamma-irradiated Mtb H37Rv (γ-Mtb) and various components derived from Mtb H37Rv on TF expression in macrophages. The data presented in the manuscript show that both live virulent Mtb and γ-Mtb treatments markedly increased TF activity in macrophages, predominantly in the CD14(+) macrophages. Detailed studies using γ-Mtb showed that the increased TF activity in macrophages following Mtb treatment is the result of TF transcriptional activation. The signaling pathways of TF induction by Mtb appears to be distinct from that of LPS-induced TF expression. Mtb-mediated TF expression is dependent on cooperation of CD14/TLR2/TLR4 and probably yet another unknown receptor/cofactor. Mtb cell wall core components, mycolyl arabinogalactan peptidoglycan (mAGP), phosphatidylinositol mannoside-6 (PIM6) and lipomannan (LM) were identified as factors responsible for induction of TF in the order of mAGP>PIM6>LM. A direct contact between bacteria and macrophage and not Mtb-released soluble factors is critical for TF induction by Mtb. In summary, our data show that Mtb induces TF expression in macrophages and Mtb signaling pathways that elicit TF induction require cooperation of multiple receptors, co-receptors/co-factors including Toll-like receptors. The importance of TF in granuloma formation and containment of Mtb is discussed.

Topics: Extracellular Signal-Regulated MAP Kinases; Humans; Lipopolysaccharide Receptors; Macrophages; Mycobacterium tuberculosis; Protein Kinase C; RNA, Messenger; Thromboplastin; Transcriptional Activation; Tuberculosis; Tumor Necrosis Factor-alpha

Activation of endothelial cells occurs in response to numerous physiological stimuli and results in the concerted expression of endothelial cell proteins that change the nonthrombogenic intimal surface of a vessel into a thrombogenic surface, with the subsequent development of local thrombosis. For example, both type 1 plasminogen activator inhibitor and tissue factor expression are mediated by endothelial cell stimulation in vitro; however, in contrast to type 1 plasminogen activator inhibitor, it has been difficult to detect tissue factor associated with endothelial cells in vivo. This case study describes the presence of both type 1 plasminogen activator inhibitor and tissue factor antigen associated with pulmonary arterial endothelial cells of a patient exhibiting a mycobacterial infection. The disease was associated with chronic hemoptysis and characterized by extensive tissue destruction and local thrombosis within the pulmonary artery. The data show that conditions occur in vivo in which local thrombosis is associated with increased levels of type 1 plasminogen activator inhibitor and tissue factor.

Topics: Arteries; Endothelium, Vascular; Humans; Immunoenzyme Techniques; Immunohistochemistry; Lung; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Thromboplastin; Thrombosis; Tuberculosis

Experiments were carried out to examine relationships between alveolar macrophage maturity and amounts of tissue factor (Clotting Factor III) in these cells under physiologic conditions and during immunologically induced pneumonitis. Using discontinuous density gradient centrifugation, alveolar macrophages from healthy rabbits were rapidly isolated into five subpopulations at different stages of maturation, as demonstrated by morphologic and morphometric evaluation. Very large amounts of tissue factor activity were found in fully mature cells that were purified in the lowest density subpopulation and assayed without preliminary in vitro stimulation or culture. In the remaining four subpopulations of increasing density, amounts of tissue factor were found to progressively diminish in direct correlation with declines of cell maturity. These differences at mean levels were as great as 35-fold. In addition, blood monocytes had less than 1/219 and less than 1/6 of the activity of the fully mature and the least mature subpopulations, respectively. After 16 h culture of the five isolated subpopulations in the absence of lymphokines or of significant numbers of lymphocytes, tissue factor activity increased in inverse correlation with the preincubation stage of cell maturity (2,387 and 109% in the least mature and most mature subpopulations, respectively). These increases required protein synthesis and were accompanied by morphologic and morphometric changes which indicated cellular maturation during the period of tissue factor activity generation in vitro, thus further demonstrating relationships between macrophage maturity and tissue factor content. In additional experiments, direct correlations between cell maturity and tissue factor activity content were also found in activated alveolar macrophage populations from rabbits with Bacillus Calmette Guering (BCG)-induced granulomatous pneumonitis. However, as compared with controls, the BCG populations had increased total amounts of tissue factor activity due to the presence of large numbers of mature alveolar macrophage forms that had high levels of the procoagulant. Thus, tissue factor activity in alveolar macrophages is a marker of cellular maturation in vivo and in vitro. Increased amounts of this initiator of the extrinsic clotting pathway, as found in alveolar macrophage populations from animals with granulomatous pneumonitis induced by BCG hypersensitivity, suggest that alveolar macrophage tissue factor may

Topics: Animals; Cell Separation; Cells, Cultured; Female; Macrophages; Monocytes; Mycobacterium bovis; Pneumonia; Rabbits; Thromboplastin; Tuberculosis

The alterations in succinic dehydrogenase activity during the course of infection with Mycobacterium tuberculosis strains H37Rv and BCG, as well as with dead bacilli, has been described. A tissue factor has been described which is prepared from normal bovine kidney and will restore enzyme activity in vitro. This factor is prepared by chromatographic analysis and contains a nucleotide with an ultraviolet absorption maxima at 250 mmicro (pH 3) and a free sulfhydryl group. The role of this factor in the response to tuberculosis is discussed.

Topics: Animals; Cattle; Guinea Pigs; Kidney; Mycobacterium tuberculosis; Oxidoreductases; Succinate Dehydrogenase; Thromboplastin; Tuberculosis; Tuberculosis, Renal

Topics: Humans; Pleurisy; Thromboplastin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Anti-Bacterial Agents; Blood; Hemostatics; Prothrombin; Thromboplastin; Tuberculosis; Tuberculosis, Pulmonary