PNI is useful for predicting the prognosis of patients with soft tissue sarcoma: A retrospective study.

BACKGROUND: It is known that preoperative Prognostic Nutritional Index (PNI) is useful in predicting prognosis in gastrointestinal diseases and that preoperative improvement of nutritional status improves prognosis. However, there have been few large-scale reports examining the prognostic value of PNI in soft tissue sarcomas. Therefore, the aim of this study is to investigate whether the PNI can be useful for predicting overall survival in soft tissue sarcoma. METHODS: Between January 2006 and March 2022 at our hospital, 111 patients with pathologically diagnosed soft tissue sarcoma were included, retrospectively. Several nutritional or inflammatory biomarkers such as PNI were calculated from the pretreatment blood sample results. The patients were classified into two groups (low and high groups) based on the median value of each parameter. Overall survival was analyzed by the Kaplan‒Meier method and log-rank test. Univariate and multivariate analyses using the Cox proportional hazards model were used to investigate prognostic factors for overall survival. RESULTS: The median overall survival was 24.3 months (mean 37.3 months), and the high PNI group had a significantly longer overall survival than the low PNI group (p < 0.0001). PNI was the most significant univariate factor for overall survival among other nutritional and inflammatory parameters (HR: 5.64, 95% CI: 2.26-14.12, p = 0.0002). The multivariate proportional hazards model was built using variables with prognostic potential as suggested by previous analysis with respect to patient characteristics and PNI. As potential confounding factors, we included PNI, stage, age, and tumor location. PNI was also an independent prognostic factor in multivariate analysis (HR: 7.02, CI: 2.52-19.40, p = 0.0002). CONCLUSION: PNI is a useful prognostic factor among various parameters for overall survival in patients with soft tissue sarcoma.

A rare case of intra-articular synovial sarcoma of the hip joint: a case report with intra-articular findings via hip arthroscopy.

Although synovial sarcoma is a relatively common soft tissue sarcoma, primary intra-articular cases are extremely rare. Herein, we report a case of primary intra-articular synovial sarcoma arising from the hip joint, that was initially treated with hip arthroscopy. A 42-year-old male presented with a history of pain in the left hip for 7 years. Radiography and magnetic resonance imaging revealed the primary intra-articular lesion and simple excision with an arthroscopy was performed. Histological findings revealed spindle cell proliferation with abundant psammoma bodies. SS18 gene rearrangement was confirmed by fluorescence in situ hybridization, and the tumor was diagnosed as synovial sarcoma. Adjuvant chemotherapy and radiotherapy were performed. Local control without metastasis was achieved 6 months after excision. This is the first case of intra-articular synovial sarcoma of the hip joint excised via hip arthroscopy. When an intra-articular lesion is identified, malignancies such as synovial sarcoma should be included in the differential diagnosis.

Characteristics of Patients with Giant Cell Tumor of Bone and High Serum Tartrate-Resistant Acid Phosphatase 5b Levels: Comparison of Tumor Volume and Clinical Factors.

BACKGROUND: Serum tartrate-resistant acid phosphatase 5b is well known to be increased in giant cell tumors of bone. However, there are only a few studies that analyzed the association with tartrate-resistant acid phosphatase 5b expression in those patients. Therefore, we analyzed the characteristics of patients with giant cell tumors of bone and high tartrate-resistant acid phosphatase 5b expression. METHODS: This retrospective study included 26 patients with giant cell tumors of bone. The correlation between tartrate-resistant acid phosphatase 5b before initial treatment and tumor volume was evaluated. Patients were divided into two groups according to tartrate-resistant acid phosphatase 5b level. Statistical analysis was performed between the two groups. RESULTS: Tartrate-resistant acid phosphatase 5b was elevated in 17/26 patients, and the mean value was 852 mU/dL. There was no correlation with tumor volume (r = 0.034, P = 0.86). The mean age of 34.5 years in the HT group was significantly younger than the mean age of 47.4 years in the LT group (P = 0.040). Pathologically, 19/26 cases showed at least one focal area with features of typical giant cell tumor of bone. Although 11/18 patients in the LT group exhibited relatively noticeable secondary changes, all patients in the HT group exhibited typical features (P = 0.0074). CONCLUSIONS: Tartrate-resistant acid phosphatase 5b levels were not elevated in some giant cell tumors of bone. This study suggested that tartrate-resistant acid phosphatase 5b may be elevated in younger patients and in cases with fewer pathological secondary changes, regardless of tumor volume.

Correction: A multicenter, randomized controlled trial of individualized occupational therapy for patients with schizophrenia in Japan.

[This corrects the article DOI: 10.1371/journal.pone.0193869.].

A multicenter, randomized controlled trial of individualized occupational therapy for patients with schizophrenia in Japan.

The individualized occupational therapy (IOT) program is a psychosocial program that we developed to facilitate proactive participation in treatment and improve cognitive functioning and other outcomes for inpatients with acute schizophrenia. The program consists of motivational interviewing, self-monitoring, individualized visits, handicraft activities, individualized psychoeducation, and discharge planning. This multicenter, open-labeled, blinded-endpoint, randomized controlled trial evaluated the impact of adding IOT to a group OT (GOT) program as usual for outcomes in recently hospitalized patients with schizophrenia in Japanese psychiatric hospitals setting compared with GOT alone. Patients with schizophrenia were randomly assigned to the GOT+IOT group or the GOT alone group. Among 136 randomized patients, 129 were included in the intent-to-treat population: 66 in the GOT+IOT and 63 in the GOT alone groups. Outcomes were administered at baseline and discharge or 3 months following hospitalization including the Brief Assessment of Cognition in Schizophrenia Japanese version (BACS-J), the Schizophrenia Cognition Rating Scale Japanese version, the Social Functioning Scale Japanese version, the Global Assessment of Functioning scale, the Intrinsic Motivation Inventory Japanese version (IMI-J), the Morisky Medication Adherence Scale-8 (MMAS-8), the Positive and Negative Syndrome Scale (PANSS), and the Japanese version of Client Satisfaction Questionnaire-8 (CSQ-8J). Results of linear mixed effects models indicated that the IOT+GOT showed significant improvements in verbal memory (p <0.01), working memory (p = 0.02), verbal fluency (p < 0.01), attention (p < 0.01), and composite score (p < 0.01) on the BACS-J; interest/enjoyment (p < 0.01), value/usefulness (p < 0.01), perceived choice (p < 0.01), and IMI-J total (p < 0.01) on the IMI-J; MMAS-8 score (p < 0.01) compared with the GOT alone. Patients in the GOT+IOT demonstrated significant improvements on the CSQ-8J compared with the GOT alone (p < 0.01). The present findings provide support for the feasibility in implementing an IOT program and its effectiveness for improving cognitive impairment and other outcomes in patients with schizophrenia.

Development of an Individualized Occupational Therapy Programme and its Effects on the Neurocognition, Symptoms and Social Functioning of Patients with Schizophrenia.

We described an individualized occupational therapy (IOT) programme and examined the effects of adding IOT to group OT (GOT) on improving neurocognition, symptoms and social functioning among recently hospitalized patients with schizophrenia. The Brief Assessment of Cognition in Schizophrenia-Japanese version (BACS-J), the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning scale were used for outcome evaluations. Fifty-one patients were voluntarily assigned to either the GOT + IOT (n = 30) or GOT alone (n = 21) groups based on their preferences. Retention in the GOT + IOT group was 100%. Three-month baseline to discharge assessments in the GOT + IOT group showed significant improvements in BACS-J verbal memory, working memory, verbal fluency, attention, executive function and composite score, and in PANSS positive subscale, general psychopathology subscale, and total score compared to the GOT alone group. Study limitations notwithstanding, the present findings provide preliminary support for the feasibility of implementing IOT and its effectiveness for improving cognitive impairment and symptoms in patients with schizophrenia. The results of this study indicate that IOT in psychiatric facilities may improve psychosocial treatment of schizophrenia. Additional study is warranted to replicate the effects of IOT as demonstrated in this Japanese study. Copyright © 2016 John Wiley & Sons, Ltd.

Factors Influencing Rehospitalisation of Patients with Schizophrenia in Japan: A 1-year Longitudinal Study.

OBJECTIVE/BACKGROUND: This longitudinal study explored factors influencing the rehospitalisation of patients with schizophrenia in Japan. METHODS: Participants comprised patients with schizophrenia who were discharged from a psychiatric hospital in Japan. The investigations were conducted at the time of discharge and one year later. Demographics and clinical characteristics included the following: the type of occupational therapy (OT) interventions (group and individualized or group only); the assessment scales' scores on hospitalisation; the community living conditions after discharge; and the contents of outpatient treatment (outpatient OT, day-care treatment, home-visit nursing, and adherence to outpatient treatment and medication). All variables were examined in a binomial logistic regression analysis to identify the factors for rehospitalisation. RESULTS: The rehospitalisation rate was 31.8%, as 14 of 44 participants were rehospitalised within one year after discharge. The type of OT interventions (OR = 7.05, 95% CI = 1.36 -36.69, p = .020) and the adherence to outpatient treatment and medication (OR = 9.48, 95% CI = 1.82-49.33, p = .008) were significant contributing factors to rehospitalisation. CONCLUSION: This study provided preliminary support for the finding that individualized occupational therapy and proper adherence to outpatient treatment and medication are associated with reducing the rehospitalisation of patients with schizophrenia in Japan.

[Deep vein thrombosis in Noto Peninsula earthquake victims].

The earthquake occurred in the Noto Peninsula in the northern part of Ishikawa prefecture, Japan, at 9:25 a.m. on March 25th 2007. Medical activities for prevention of deep vein thrombosis (DVT), early detection of DVT, and early treatment of DVT were performed immediately after the earthquake on the basis of a previous report regarding earthquake disasters. This report described the conditions involved in the development of DVT. General inhabitants in shelters were examined by questionnaires, venous ultrasonography of lower limb, and blood tests. The DVT-positive rate was 10.6% (21 cases/198 cases), and the soleal vein was the most common location of DVT accounting for 71.4% of cases(20 lower limbs/28 lower limbs). Plasma levels of fibrin/fibrinogen degradation products and D-dimer in the DVT-positive group (20 cases) were significantly higher than those in the DVT-negative group(162 cases) (P<0.03). No deaths or cases of serious illness caused by DVT were reported in the earthquake. The medical activities described here were effective due to the past experience and the cooperation of many people.

Changes in molecular markers of hemostatic and fibrinolytic activation under various sampling conditions using vacuum tube samples from healthy volunteers.

Molecular makers such as thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), and D-dimer, are useful markers in the diagnosis and assessment of various thrombotic conditions. These markers are measured in plasma after blood sampling. Difficult blood sampling is known to falsely elevate plasma TAT levels. However, it is not known exactly why this occurs. In the present study, we examined how levels of molecular markers of haemostatic and fibrinolytic activation change under various sampling conditions using vacuum tube samples from healthy volunteers. When blood was sampled continuously by taking 10 consecutive vacuum tube samples following application of a tourniquet, blood sampling resulted in an accurate assessment of these molecular makers. When blood was sampled continuously by taking vacuum tube samples every one minute over a total of 9 minutes to investigate possible changes in the levels of the molecular markers over time, plasma levels of TAT, SF, and F1+2 gradually increased with time. Plasma levels of TAT, F1+2, and SF increased beyond the normal range over the course of nine minutes. When blood was sampled using three alternative methods, which varied in terms of the duration of needle puncture (sampling B), duration of tourniquet use (sampling C), or both (sampling A), plasma TAT and SF levels were significantly increased with all three methods, compared to control samples. Plasma F1+2 levels were significantly increased with sampling methods A and B, compared to control samples, but not with sampling method C. On the other hand, plasma D-dimer levels were not significantly altered by any of the sampling methods. In conclusion, the results suggest that molecular markers of haemostatic and fibrinolytic activation, except for D-dimer, may be affected by sampling method, particularly the duration of needle puncturing. Therefore, care needs to be taken when using TAT, F1+2, and SF levels to diagnose and estimate activation of the coagulation system.

[The positive rate of lupus anticoagulant according to the each understanding disease in our hospital].

We investigated positive rate of lupus anticoagulant (LA) according to the each understanding disease in our hospital. 596 cases (F/M 477/149, 7-87 y.o.) were examined from 2003 to 2004 years. LA tests were performed using 2 methods such as kaolin clotting time (KCT) mixing test and dilute Russell's viper venom time (dRVVT). The LA tests were most frequently ordered in dermatology, and the most common purpose of LA test was the check of existence of antiphospholipid (aPL) in patients with collagen diseases. The LA positive rate was the highest in patients with SLE among the collagen diseases, and in patients with cerebral infarction among the thrombotic diseases. The LA positive rate exceeded 40% in ITP and livedo reticularis. Moreover, LA positive rate was 16% in preoperative tests of the orthopedic patients without any physical diseases. Thus, it was suggested that there were considerable numbers of the asymptomatic LA positive persons. The LA positive cases based on KCT only accounted for about 60% of all the LA positive cases. Among the thrombotic patients, there were not the DVT/PE patients with only KCT positive. On the other hands, the KCT positive rate was higher than the dRVVT positive rate in patients with cerebral infarction. There were not dRVVT single positive cases in patients with recurrent abortion and ITP, but KCT single positive case accounted for about 90%. From these results, it is suggested that there is a difference in KCT and dRVVT about detecting aPL, and that care should be taken to interpret the LA test.

No interplay between the pathways mediating coagulation and inflammation in tissue factor-induced disseminated intravascular coagulation in rats.

OBJECTIVE: Previous reports have suggested an interplay between the pathways mediating coagulation and inflammation in endotoxemia and sepsis. The present study was designed to examine whether cross-signaling between the pathways mediating coagulation and inflammation occurs, as suggested by the pattern of cytokine production observed following tissue-factor (TF)-induced disseminated intravascular coagulation (DIC). DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6-7 wks, and weighing 160-170 g. INTERVENTIONS: Male Wistar rats were administered TF (3.75 units/kg every 4 hrs), TF, and tranexamic acid (TA; 50 mg/kg every 4.5 hrs) or lipopolysaccharide (30 mg/kg every 4 hrs) via the tail vein, and blood was sampled at 0, 4, 8 and 12 hrs. MEASUREMENTS AND MAIN RESULTS: Subsequent alterations in thrombin-antithrombin complex and fibrinogen levels, as well as platelet counts, indicated that the severity of both types of experimental DIC (TF-induced and lipopolysaccharide-induced) was similar with respect to hemostatic activation and development of consumption coagulopathy. In lipopolysaccharide-induced DIC, a sharp increase in plasma tumor necrosis factor levels was observed at 4 hrs, after which a sharp decline was noted. Plasma levels of interleukin-6 were markedly increased at 4 hrs, after which a sustained elevation was observed for the duration of the experimental period (tumor necrosis factor, 1270 +/- 280, 180 +/- 40, and 120 +/- 30 pg/mL at 4, 8 and 12 hrs, respectively; interleukin-6, 5810 +/- 1320, 4850 +/- 730, and 5230 +/- 1280 pg/mL at 4, 8 and 12 hrs, respectively). On the other hand, tumor necrosis factor and interleukin-6 were not detected following TF-induced DIC (0 +/- 0 at 4, 8, and 12 hrs for both tumor necrosis factor and interleukin-6). In the TF+TA group, significant increases in tumor necrosis factor and interleukin-6 were observed, compared with the TF group. CONCLUSIONS: There is no overt interplay between the pathways mediating coagulation and inflammation in TF-induced DIC, as observed in lipopolysaccharide-induced DIC.

Successful treatment of minimal residual disease-positive Philadelphia chromosome-positive acute lymphoblastic leukemia with imatinib followed by reduced-intensity unrelated cord blood transplantation after allogeneic peripheral blood stem cell transplantation.

We describe a 35-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic sibling donor peripheral blood stem cell transplantation (PBSCT) and entered a second complete remission. Upon detection of BCR-ABL transcripts after PBSCT, the patient received imatinib, leading to molecular remission. Following the failure of donor leukocyte infusions, she underwent reduced-intensity unrelated cord blood transplantation (RI-UCBT), and has continued durable molecular remission for more than 30 months without substantial graft-versus-host disease. Because of a lack of adverse effects of imatinib on transplantation outcome, a treatment strategy consisting of molecular monitoring-guided initiation of imatinib followed by RI-UCBT may be promising in the management of Ph+ ALL after allogeneic SCT.

Immunoglobulin preparations attenuate organ dysfunction and hemostatic abnormality by suppressing the production of cytokines in lipopolysaccharide-induced disseminated intravascular coagulation in rats.

OBJECTIVE: We attempted to clarify the effect of immunoglobulin concentrates on the rat lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) model. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6 to 7 wks and weighing 160 to 170 g. INTERVENTIONS: Two kinds of experiments were performed. In the first, experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 hrs via the tail vein, and two doses of immunoglobulin (25 or 100 mg/kg/4.5 hrs) were administered to rats 30 mins before infusion of LPS, after which immunoglobulin infusion was continued for a further 4 hrs. In the second, experimental DIC was induced by sustained infusion (5 mg/kg/1 hr) of LPS for 1 hr, and one dose of immunoglobulin (100 mg/kg/4 hrs) was administered to rats after LPS induction. The parameters were estimated at 4 hrs and 8 hrs in the first experiment and at 1, 5, and 10 hrs in the second one. MEASUREMENT AND MAIN RESULTS: Similar results were observed in the two experiments. Consumption coagulopathy and hemostatic activation were attenuated, especially when immunoglobulin was administered before LPS infusion. Plasma levels of creatinine and alanine aminotransferase were significantly depressed by coadministration of immunoglobulin. Marked glomerular fibrin deposition was observed in the LPS-induced DIC model, but this deposition was reduced by immunoglobulin. In the first stage of the experiment, plasma levels of tumor necrosis factor (TNF) and interleukin (IL)-6 were suppressed by coadministration of immunoglobulin. In the second, plasma levels of IL-6 were significantly suppressed by immunoglobulin. CONCLUSION: It was concluded that plasma levels of TNF and IL-6 could be significantly suppressed by immunoglobulin in the LPS-induced DIC model. Moreover, hemostatic abnormality, organ dysfunction, and glomerular fibrin deposition in this model were all ameliorated by immunoglobulin.

Kasabach-Merritt syndrome associated with giant liver hemangioma: the effect of combined therapy with danaparoid sodium and tranexamic acid.

n patients with Kasabach-Merritt syndrome (KMS), local activation of coagulation commonly results in disseminated intravascular coagulation (DIC). Progress of DIC is associated with 30-40% mortality as a result of uncontrollable hemorrhage. A 39-year-old woman with an enlarging giant liver hemangioma was diagnosed as having KMS with DIC. To control the hemorrhagic diathesis, we commenced combination therapy for DIC with danaparoid (1,250 Ux2/day, intravenously (IV)) and tranexamic acid (0.5 g x 3/day, peros (PO). Rapid improvement of the bleeding tendency and coagulopathy occurred in response to this treatment - that is, DIC was controlled without removing the giant hemangioma. The therapy did not restrict the behavior of the patient by continuous drip and angiography could be performed without bleeding. Such therapy may be beneficial in chronic DIC with activation of fibrinolysis.

[Reliability of low platelet counts--comparison of microscopic counts with automated hematology analyzer XE-2100].

Sysmex XE-2100 is an automated hematological analyzer with excellent features that can count platelets by both impedance and optical fluorescent method. Particularly, it is notable that platelet counts by optical fluorescent method (PLT-O) are automatically adopted when platelet counts by impedance method (PLT-I) are less than 50 x 10(3)/microl or platelets have abnormal distribution. We compared PLT-I with PLT-O, and also with microscopic counts, using the samples with thrombocytopenia. Regarding reproducibility, mean coefficient of variation values were 5.3% in both PLT-I and PLT-O, when no flags of "PLT Abn Distribution" appeared in the samples with thrombocytopenia. Coefficient of variation values was 10.4% in PLT-I and 5.9% in PLT-O, when flags of "PLT Abn Distribution" appeared in the sample with thrombocytopenia. Correlation among the data obtained by PLT-I, PLT-O and microscopic counts were excellent. When a large difference was observed between PLT-I and PLT-O, PLT-O was more closely consistent with microscopic counts. PLT-O was useful compared with PLT-I, and this system was considered to measure platelet counts more correctly in the samples with thrombocytopenia. Thus, it was suggested that reliable platelet counts could be reported even in the samples with thrombocytopenia by switching system in XE-2100.

Beneficial effects of urokinase on lipopolysaccharide-induced disseminated intravascular coagulation in rats: focus on organ function and endothelin levels.

In a rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC), we used urokinase (UK) in an attempt to clarify the role of fibrinolysis and to investigate changes in plasma endothelin levels. Two kinds of experiment were performed. The first one: experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 h via the tail vein, and two doses of UK (2.0 or 10.0 IU/g/4.5 h) were administered to rats 30 min before infusion of LPS, after which UK infusion was continued for a further 4 h. The second one: experimental DIC was induced by sustained infusion of 1 mg/kg/10 min LPS for 10 min, and two doses of UK (2.0 or 10.0 IU/g/4 h) were administered to rats at 30 min after LPS infusion. The parameters described below were determined at 4 h in the first experiment, at 4 h and 8 h in the second one. The similar results were observed in both kinds of experiment. There were no significant differences in plasma thrombin-antithrombin complex, fibrinogen or platelet number among the three DIC groups, in both kinds of experiment. Plasma levels of D-dimer were significantly increased in the LPS + higher dose of UK group when compared with the LPS group. The increased plasma plasminogen activator inhibitor (PAI) activity seen in the LPS group was significantly suppressed in the groups receiving UK (especially higher dose of UK). In addition, the increased plasma levels of creatinine and alanine aminotransferase seen in the LPS group were significantly suppressed in the groups receiving UK (especially higher dose of UK). Plasma levels of endothelin, known to be a potent vasoconstrictive agent, were markedly elevated by LPS infusion, and were significantly suppressed in the groups receiving UK of both kinds of experiment, in a dose-dependent fashion compared with LPS group. Glomerular fibrin deposition was significantly suppressed in the groups receiving UK when compared with the LPS group. No manifestations of bleeding were observed in any of the groups. Enhanced fibrinolysis and depressed endothelin induced by UK thus appear to play an important role in preventing the development of organ failure in the LPS-induced DIC model.

Isolated hyperkalemia associated with cyclosporine administration in allogeneic stem cell transplantation for renal cell carcinoma.

Two patients with advanced renal cell carcinoma underwent allogeneic hematopoietic stem cell transplantation and received cyclosporine (CSP) as part of their immunosuppressive therapy. Despite adequate renal function, both patients developed hyperkalemia. CSP was the only pharmaceutical agent to which this electrolyte abnormality could be attributed. Evaluation of renal tubule function suggested that CSP-associated isolated hyperkalemia resulted from tubular resistance to aldosterone. We propose that the presence of a single functional kidney may be a risk factor for isolated hyperkalemia due to CSP.

Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid.

OBJECTIVE: We examined the role of coagulation and fibrinolysis in lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats, studying their contribution to fibrin deposition and organ failure in rats with LPS-induced DIC by concurrent administration of low molecular weight heparin (LMWH) with or without tranexamic acid (TA). METHODS: DIC was induced in male Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In the LPS+LMWH group LMWH (200 u/kg) was administered to rats from 30 min before the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 microg/kg) and TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS for 4.5 h. RESULTS: In the LPS+LMWH group lower plasma levels of TAT, D dimer, creatinine, and alanine aminotransferase were observed, along with less glomerular fibrin deposition and improved survival over rats administered LPS alone. However, these effects of LMWH were completely eliminated and damage beyond that observed in rats administered LPS alone resulted from combined administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels remained lower than in the group administered LPS alone. CONCLUSIONS: Suppression of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased organ damage in this study, suggesting that depressed fibrinolysis plays a large role in organ failure resulting from LPS-induced DIC, even though hemostatic activation is moderately suppressed by LMWH.

Relationship between endothelin and the pathophysiology of tissue factor-induced and lipopolysaccharide-induced disseminated intravascular coagulation in rats: a study examining the effect of an endothelin receptor antagonist.

We investigated the relationship between endothelin, a potent vasoconstrictor peptide, and the pathophysiology of disseminated intravascular coagulation (DIC), using two models of DIC. Experimental DIC was induced by sustained infusion of 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg thromboplastin, for 4 h via the rat tail vein. The effect of administration of a non-selective endothelin receptor antagonist (TAK-044) (2, 10, or 50 mg/kg, from -0.5 to 4 h) on thromboplastin-induced DIC was not significant. However, LPS-induced elevation of alanine aminotransferase, creatinine and glomerular fibrin deposition was significantly suppressed by co-administration of TAK-044 in a dose-dependent manner, although no effect of TAK-044 was observed on the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of D-dimer, which reflect the grade of fibrinolysis of cross-linked fibrin, were significantly increased by co-administration of each dose of TAK-044 in the LPS-induced DIC model in rats. Our results suggest that vasoconstriction, as well as depressed fibrinolysis, contribute to severe organ dysfunction in LPS-induced, but not thromboplastin-induced, DIC, and that endothelin plays a role in the development of organ injury in LPS-induced DIC in rats.

Significance of decreased plasma D-dimer levels following lipopolysaccharide-induced disseminated intravascular coagulation in rats.

Plasma D-dimer (DD) is considered to be one of the most useful markers in the diagnosis and assessment of disseminated intravascular coagulation (DIC). The present study was performed to clarify the role of DD in a rat model of lipopolysaccharide (LPS)-induced DIC in which low-molecular-weight heparin (LMWH) and tranexamic acid (TA) were used. We investigated whether a relationship exists between plasma DD levels and severity of DIC. Experimental DIC was induced in rats by a sustained 4-hour infusion of 30 mg/kg LPS administered via the tail vein (LPS group). Rats received either LPS alone (LPS group) or LPS combined with 200 U/kg LMWH (LPS+LMWH group) or 50 mg/kg TA (LPS+TA group) from -30 minutes to 4 hours. Blood was drawn from each rat at 4, 8, and 12 hours. Plasma levels of thrombin-antithrombin complex (TAT) and creatinine were suppressed in the LPS+LMWH group, and less glomerular fibrin deposition was observed compared with the LPS group. On the other hand, an increased level of creatinine and increased glomerular fibrin deposition were observed in the LPS+TA group compared with the LPS group. LMWH demonstrated a protective effect against LPS-induced DIC, resulting in increased survival at 12 hours, whereas TA had the opposite effect. From these results, it appears that LMWH protects against LPS-induced DIC, but TA exacerbates LPS-induced DIC. It was interesting that plasma levels of DD were almost completely suppressed by concurrent administration of either TA or LMWH in this LPS-induced DIC model. This finding suggested that plasma levels of DD were suppressed by inhibition of coagulation (reduced deposition of fibrin) in the LPS+LMWH group and that DD levels were also suppressed by inhibition of fibrinolysis (reduced degradation of fibrin by plasmin) in the LPS+TA group. Thus care should be taken when evaluating the significance of plasma DD levels, because suppressed levels can occur with progressive fibrin deposition and worsening organ dysfunction or improvement in the course of DIC.