Diffuse Fibrin Deposition Research Articles

Clinical manifestations of pseudomembranous colitis

Pseudomembranous colitis is a pathological condition in which there is damage to the mucous membrane of the large intestine with focal or diffuse fibrin depositions resulting from exposure to factors of the pathogenicity of Clostridium difficile. This disease has become quite widespread in recent years. The widespread and not always properly controlled prescription of antibiotics can lead to the development of a serious complication caused by this pathogen. The pathological condition develops against the background or after the end of the ongoing antibiotic therapy; its initial manifestation is antibiotic-associated diarrhea (AAD). Most often, this condition is diagnosed in postoperative patients against the background of a general decrease in immunity, as well as as a result of prolonged and uncontrolled intake of antibiotics. It has been proven that the frequency of Clostridium difficile colonization increases sharply during hospitalization, thus, this infection was referred to hospital ones. The main clinical manifestation of pseudomembranous colitis is diarrhea; stool can become more frequent, up to 5-7 times a day, while feces are scanty and not abundant. In addition to diarrhea, abdominal pain and flatulence may occur. The diagnosis is established on the basis of the fact of increased stool within two or more days for 8 weeks after taking antibiotics confirmed by the patient.

Typhlocolitis by Edwardsiella tarda in a Cow

Typhlocolitis by Edwardsiella tarda in a Cow

Maternal floor infarction: Management of an underrecognized pathology

Maternal floor infarction is a relatively rare condition characterized clinically by severe early onset fetal growth restriction with features of uteroplacental insufficiency. It has a very high recurrence rate and carries a significant risk or fetal demise. Pathological characteristics include massive and diffuse fibrin deposition along the decidua basalis and the perivillous space of the basal plate. We present a case of recurrent maternal floor infarction and propose diagnostic clues as well as potential therapeutic options.

Increased Thrombin Generation Capacity in Septic Patients with DIC.

Variety clinical conditions may cause systemic activation of coagulation, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of widespread systemic activation of coagulation, resulting in diffuse fibrin deposition in small and midsize vessels. However, little is known about thrombin generation capacity in patients with DIC. To investigate the thrombin generation capacity, we measured thrombin generation in septic patients with DIC (n=20) and acute promyelocytic leukemia (APL)-induced DIC (n=5). Thrombin generation was determined by the Throbogram-Thrombinoscope assay (Thermo Electron Corporation, Netherlands). The analyzed TG parameters ware the peak of thrombin activity (Peak) and endogenous thrombin potential (ETP).The thrombin antithrombin complexes (TAT) levels were higher in both DIC patients as reported by others. In the septic patients with DIC, we found significant elevations in peak of thrombin activity and ETP as compared with normal controls (determined in 17 healthy males and 14 healthy female). However, the peak of thrombin activity and ETP levels were severely decreased by 60% n the APL patients with DIC. There was slightly correlation between the ETP and TAT levels in septic patients with DIC. Also, there was correlation between the ETP and bleeding tendency in APL patients with DIC.These results suggest that assess of thrombin generation capacity may be helpful in the making the diagnosis in septic patients with DIC. It appears that assess of ETP may contribute to evaluate bleeding tendency in APL patients with DIC.Sepsis with DICAPL with DICControls (n=31)Peak (nM)325.3 ± 55.5*88.2 ± 47.2*281.2 ± 40.9ETP (nM.min)1 ± 326.1*652.1 ± 274.5*1469.2 ± 227.3TAT (μg/ml)28.4 ± 17.5*22.5 ± 15.3*<3*(P<0.05) significantly different controls

Phosphatidylserine/Phosphatidylcholine Microvesicles Can Induce Preeclampsia-Like Changes in Pregnant Mice

We established a phosphatidylserine (PS)/phosphatidylcholine (PC) microvesicles-induced preeclampsia-like model in mice. PS/PC were prepared by mixing 80% PC and 20% PS, and suspended in 0.05 M Tris-HCl at a concentration of 10 mg/mL. One hundred microliters of PS/PC (n = 6) and saline as a control (n = 10) were injected in tail veins of Institute of Cancer Research (ICR) mice every day from days 5.5 to 16.5 of pregnancy. Systolic blood pressure (SBP) was measured by means of the tail-cuff method. On day 17.5, the mice were anesthetized by diethyl ether and euthanized with the collapse of the circulation by drawing blood from the heart. The animals were dissected and the fetuses and placentas removed. Fetal weight and placental weight were evaluated. Plasma antithrombin activity (AT), thrombin-antithrombin complex (TAT), platelet counts, and proteinuria were measured on day 17.5. Placentas were fixed in 4% paraformaldehyde for histologic studies. Statistical analysis was evaluated by analysis of variance and Welch's t-test. Mice injected with PS/PC showed a significant elevation in SBP (124 versus 101 mm Hg; p < 0.001), a significant increase in TAT levels (23 versus 6.6 mug/L; p < 0.05), a significant decrease in platelet counts (88 versus 102 x 10 (10)/L; p < 0.05), a decrease in AT, an increase in proteinuria, and a significant reduction in fetal weight (1.2 versus 1.3 g; p < 0.0001) and placental weight (0.13 versus 0.15 g; p < 0.001), compared with controls. Placentas of mice injected with PS/PC showed diffuse fibrin depositions in the labyrinth layer. We have demonstrated that the artificial PS/PC vesicles induce intrauterine growth restriction with elevations of SBP. The elevation of plasma TAT and the diffuse fibrin depositions in the placentas indicate enhanced thrombin formation, and the significant elevations of SBP indicate preeclampsia-like changes that can be induced by hypercoagulation in the placenta.

New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology

A variety of clinical conditions may cause systemic activation of coagulation, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of a widespread systemic activation of coagulation, resulting in diffuse fibrin deposition in small and midsize vessels. There is compelling evidence from clinical and experimental studies that DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. In addition, the massive and ongoing activation of coagulation, may result in depletion of platelets and coagulation factors, which may cause bleeding. Recent understanding of important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with sepsis and a derangement of coagulation. Thrombin gener‐ation proceeds via the (extrinsic) tissue factor/factor VIIa route and simultaneously occurring depression of inhibitory mechanisms, such as antithrombin III and the protein C system. Also, impaired fibrin degradation, due to high circulating levels of the fibrinolytic inhibitor plasminogen activator inhibitor, type 1 (PAI‐1), contributes to enhanced intravascular fibrin deposition. Interestingly, an extensive cross‐talk between activation of inflammation and coagulation exists, where inflammatory mediators (such as cytokines) not only activate the coagulation system, but vice versa activated coagulation proteases and protease inhibitors may modulate inflammation through specific cell receptors. Supportive strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor‐mediated activation of coagulation or restoration of physiological anticoagulant pathways, for example by means of the administration of recombinant human activated protein C.

Decreased Fibrinolytic Activity in Porcine-to-Primate Cardiac Xenotransplantation

One major barrier to successful xenotransplantation is acute vascular rejection, a process pathologically characterized by microvascular thrombosis and diffuse fibrin deposition in transplant blood vessels. This pathologic picture may result from a disturbance in the coagulant or fibrinolytic pathways that regulate normal vascular patency. This study evaluated the regulation of fibrinolytic activity defined by tissue plasminogen activator and plasminogen activator inhibitor-1 as it may exist in the setting of acute vascular rejection. Serial biopsies from cardiac xenotransplants evaluated by immunofluorescence microscopy demonstrated progressive decreases in tissue plasminogen activator and increases in plasminogen activator inhibitor-1. In vitro studies measuring fibrinolytic activity of cell culture medium from porcine aortic endothelial cells stimulated with human serum or autologous porcine serum revealed that human serum triggered as much as 93% increase in antifibrinolytic activity. These findings demonstrate that porcine vascular endothelial cells change toward an antifibrinolytic state following stimulation with human xenoreactive antibodies and complement. The shift is at least partly explained by an increased ratio of plasminogen activator inhibitor-1 to tissue plasminogen activator, and is at least in part mediated by the activation of complement. This increased antifibrinolytic activity may contribute to the thrombotic diathesis seen in acute vascular rejection in pig-to-primate xenografts.