Identification and Prognostication of End-of-Life State Using a Japanese Guideline-Based Diagnostic Method: A Diagnostic Accuracy Study.

Purpose: Prognostic uncertainty can be a barrier to providing palliative care. Accurate prognostic estimation for patients at the end of life is challenging. This study aimed to evaluate the accuracy of end-of-life diagnosis using our unique diagnostic method. Patients and Methods: A retrospective longitudinal observational study was conducted through collaboration among three medical facilities in a rural super-aged community in Japan. In 2007, we established a unique end-of-life diagnostic process comprising (1) physicians' judgement, (2) disclosure to patients, and (3) discussion at an end-of-life case conference (EOL-CC), based on Japanese end-of-life-related guidelines. Research subjects were consecutive patients discussed in EOL-CC between January 1, 2010, and September 30, 2017. The primary outcome was mortality within 6 months after the initial EOL-CC decision. Sensitivity, specificity, and diagnostic odds ratio were calculated using EOL-CC diagnosis (end-of-life or non-end-of-life) as an index test and overall survival (<6 months or ≥6 months) as a reference standard. Results: In total, 315 patients were eligible for survival analysis (median age 89, range 54-107). The study population was limited to patients with severe conditions such as advanced cancer, organ failures, advanced dementia with severe deterioration in functioning. EOL-diagnosis by our methods was associated with much lower survival rate at 6 months after EOL-CC than non-EOL-diagnosis (6.9% vs 43.5%; P < 0.001). Of the patients, 297 were eligible for diagnostic accuracy analysis (median age 89, range 54-107). The EOL-diagnosis showed high sensitivity (0.95; 95% confidence interval [CI] 0.92-0.97) but low specificity (0.35; 95% CI 0.20-0.53) against the outcomes. It also showed a high diagnostic odds ratio (10.32; 95% CI 4.08-26.13). Conclusion: The diagnostic process using the Japanese end-of-life guidelines had tolerable accuracy in identification and prognostication of end of life.

Blue Rubber Bleb Nevus Syndrome Complicated by Enhanced-Fibrinolytic-Type DIC: A Case Report.

A 54-year-old Japanese man was diagnosed with blue rubber bleb nevus syndrome (BRBNS) due to venodilation in the lower extremities at birth and gastrointestinal vascular malformations. He also had small bowel bleeding and enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). Endoscopic sclerotherapy for intestinal hemangioma could not be performed because of bleeding concerns; instead, a combined anticoagulant and antifibrinolytic treatment was performed. Although combination treatment with unfractionated heparin and tranexamic acid proved ineffective for small bowel bleeding, combination treatment with apixaban and tranexamic acid dramatically improved enhanced-fibrinolytic-type DIC. In BRBNS, treatment strategies should be considered after performing detailed coagulation tests.

Congestive heart failure associated with POEMS syndrome that was adequately distinguished from cardiac amyloidosis: a case report and literature review.

Congestive heart failure (CHF) is a common complication in patients with AL amyloidosis but is rare in another plasma cell dyscrasia, POEMS syndrome. A 52-year-old man developed POEMS syndrome with a solitary plasmacytoma complicated by CHF mimicking cardiac amyloidosis (CA). His neurological symptoms and CHF did not improve after radiotherapy (50 Gy) targeting the plasmacytoma. Based on typical findings of noninvasive examinations such as elevated serum NT-proBNP (12,631 pg/mL), a pseudo-infarct pattern on electrocardiography, interventricular septal thickening with a granular sparkling appearance and an apical sparing pattern of longitudinal strain on echocardiography, and late gadolinium enhancement of the left ventricular wall on cardiac magnetic resonance imaging (MRI), severe CA ineligible for autologous peripheral blood stem cell transplantation (auto-PBSCT) was strongly suspected. However, myocardial biopsy failed to reveal amyloid deposits, and CHF markedly improved after only one cycle of chemotherapy with melphalan and dexamethasone. Accordingly, CA was denied as the etiology of his heart failure, and the patient was finally diagnosed with POEMS syndrome. As a result, high-dose melphalan followed by auto-PBSCT improved his neurological symptoms. Careful evaluation is therefore needed to appropriately treat patients with POEMS syndrome complicated by CHF, even when the results of non-invasive examinations are typical for AL amyloidosis.

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin.

IVIG is occasionally used for preventing and treating severe infections of patients who are to undergo transplantation. Administration of IVIG, which includes high-titer antibodies (Abs) against HLA class I and II, might have a substantial influence on the HLA Ab test results of these patients. However, this issue has remained unreported. METHODS: Anti-HLA Ab titers were determined in 4 types of IVIG preparations, fresh frozen plasma, and the sera of 11 patients with hematological diseases before and after IVIG administration. RESULTS: Although anti-HLA Abs were not detected in any of the fresh frozen plasma products, various anti-HLA class I and II Abs were detected in all 4 IVIG preparations. Six out of 11 patients who had received IVIG showed a low titer of anti-HLA class II Abs, which were not detected before IVIG administration. Conversely, no anti-HLA class I Abs were detected in any of the 11 patients. Furthermore, all 4 (100%) patients who were positive for anti-HLA class II Abs initially and were assessable became negative for anti-HLA Abs after the discontinuation of IVIG treatment (median, d 79; range, d 22-192). CONCLUSIONS: IVIG preparations consist of high-titer anti-HLA class I and II Abs, but the latter can be transiently detected in the sera of patients who had received IVIG. When these patients are screened for the presence of donor-specific Abs, some may be incorrectly deemed positive for HLA class II Abs. Thus, caution is necessary when only donor-specific Abs specific to class II HLAs are detected in patients.

Pulmonary Pleomorphic Carcinoma Mimicking Primary Sarcoma of the Neck: A Case Report and Literature Review.

We describe our challenge in diagnosing an unusual and rapidly progressing case of pulmonary pleomorphic carcinoma (PPC)-a rare, poorly differentiated, or undifferentiated non-small-cell carcinoma that can metastasize locally or distantly and has a poor prognosis. Our patient was an elderly man with a one-month history of abdominal pain, anorexia, and weight loss, diagnosed with atrophic gastritis via endoscopy, and treated medically without improvement. A week later, this patient developed pain in the head, neck, and shoulder area, and further examination revealed a thickening of his left neck and shoulder, with no palpable lymph nodes. Computed tomography (CT) of the neck, chest, and abdomen led us to believe that we might be dealing with primary sarcoma of the neck since no lung mass was evident. Further investigation could not be performed because the patient's status deteriorated rapidly. An autopsy revealed that soft tissue in the left neck and the mesentery was invaded by poorly differentiated polymorphic malignant cells, which were also seen in the lung lesion. Immunohistochemically, these malignant cells were all positive for AE1/AE3, CAM5.2, TTF-1, Napsin-A, and Vimentin. The cells were also positive for programmed death-ligand 1 staining with a low level of tumor proportion score (over 1%). The final diagnosis was PPC with metastases to soft tissues in the left neck and the mesentery. A review of previous case reports of PPC revealed that soft tissue is an uncommon site for metastasis, and that our CT findings were rather unusual. We hereby present our case and review of published case reports, with the hope that an awareness of the heterogeneous features of PPC could prompt timely biopsy and histological diagnosis.

Coagulation and fibrinolytic features in AL amyloidosis with abnormal bleeding and usefulness of tranexamic acid.

Abnormal bleeding is sometimes observed in patients with immunoglobulin light chain (AL) amyloidosis. Although several theories have been proposed regarding the pathological causes of the bleeding tendency in AL amyloidosis, many lacked sufficient evidence and full consensus. We conducted a retrospective survey at a single institution to assess bleeding manifestations, methods for evaluating hematological abnormalities, and treatments for bleeding in patients with systemic AL amyloidosis over the past 13 years. The participants were 10 men and 14 women, aged 39-84 years (mean 65 years). The prevalence of bleeding was 29%. Prolonged prothrombin time (PT), elevated plasmin-α2-antiplasmin complex, and factor X deficiency were distinctive to the bleeding group. Two case studies showed that tranexamic acid was effective for treating this hematological condition. However, two patients with normal PT and activated partial thromboplastin time (APTT) also had a bleeding manifestation. The rates of administration of coagulation and fibrinolytic tests were relatively low in the non-bleeding group. Therefore, a close investigation concerning coagulation and fibrinolysis should be performed in every patient with AL amyloidosis regardless of the PT/APTT values. A more careful, comprehensive, and large-scale study is required to reinforce these findings.

Antithrombotic therapies for elderly patients: handling problems originating from their comorbidities.

Compared with younger people, elderly people have higher risks for both thrombosis and bleeding. Furthermore, comorbidities frequently found in elderly patients complicate the management of antithrombotic therapy. Thus, when treating these patients, physicians often find it difficult to incorporate the principles of evidence-based medicine and must determine the best treatment option for each patient. Recently, in the fields of cerebrovascular and cardiovascular diseases, researchers have been rapidly accumulating new data regarding antithrombotic therapy, particularly in the areas of direct oral anticoagulants (DOACs) and dual antiplatelet therapy (DAPT). However, information related to elderly patients receiving antithrombotic therapy is still relatively limited. There are also more and more publications describing how antithrombotic therapy affects the pathogenesis of non-thrombotic diseases. Similarly, the number of reports concerning adherence to this therapy has been increasing lately. However, no review articles detailing these findings have yet been published. In actual clinical practice, antithrombotic therapy in the elderly is not a treatment strategy targeted to only one organ or disease. Rather, it requires an interdisciplinary approach aimed at maintaining the overall health of the patient. Thus, to assist physicians' decision-making processes for elderly patients, an overview of recent findings related to the evidence regarding concomitant medications, the secondary benefits of antithrombotic therapy for patients with comorbidities, and evidence regarding medication adherence is provided.

A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma.

A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

A comprehensive intervention following the clinical pathway of eating and swallowing disorder in the elderly with dementia: historically controlled study.

BACKGROUND: Eating problems in patients with advanced dementia are strongly associated with their deteriorating survival. Food and drink intake in people with dementia may be supported by specific interventions, but the effectiveness of such interventions is backed by almost no evidence. However, comprehensive geriatric assessment (CGA) might potentially clarify the etiology of decreased oral intake in people with dementia; thus improving their clinical outcomes. METHODS: This study was a single-arm, non-randomized trial that included historically controlled patients for comparison. We defined elderly patients with both severely decreased oral intake depending on artificial hydration and/or nutrition (AHN) and dementia as "Eating and Swallowing Disorder of the Elderly with Dementia (ESDED)". In the intervention group, participants received CGA through the original clinical pathway with multidisciplinary interventions. This was followed by individualized therapeutic interventions according to assessment of the etiology of their eating problems. RESULTS: During the intervention period (between 1st April 2013 and 31st March 2015), 102 cases of ESDED were enrolled in the study and 90 patients had completed receiving CGA. Conversely, 124 ESDED patient controls were selected from the same hospital enrolled during the historical period (between 1st April 2011 and 31st March 2012). Most participants in both groups were bedridden with severe cognitive impairment. For the intervention group, an average of 4.3 interventional strategies was recommended per participant after CGA. Serological tests, diagnostic imaging and other diagnostic examinations were much more frequently performed in the intervention group. Recovery rate from ESDED in the intervention group was significantly higher than that in the historical group (51% v.s. 34%, respectively, P = 0.02). The 1-year AHN-free survival in the intervention group was significantly higher than that in the historical group (28% v.s. 15%, respectively, P = 0.01). No significant difference between the two groups was found for 1-year overall survival (37% v.s. 28%, respectively, P = 0.08). CONCLUSIONS: Use of CGA with multidisciplinary interventions could improve the functional status of eating and allow elderly patients with severe eating problems and dementia to survive independently without the need for AHN. TRIAL REGISTRATION: ISRCTN57646445 , this trial was retrospectively registered on 8th December 2015.

Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip.

Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition.

Autopsy-Proven Intravascular Lymphoma Presenting as Rapidly Recurrent Strokes.

We present a 79-year-old Japanese woman diagnosed with cerebral infarction. In spite of enough antiplatelet and anticoagulant therapy, she presented rapidly recurrent strokes three times for 3 months. Magnetic resonance imaging showed progression of bilateral cerebral infarcts, and chest-abdominal computed tomography showed multiple bilateral nodular lesions in the lung and multiple tumor lesions in the liver. Autopsy revealed diagnosis of intravascular lymphoma (IVL). This case indicates that IVL is rare and usually goes undiagnosed until time of autopsy because of its protean neurological manifestations; hence, it should be considered as a possible etiology if multiple strokes occur in a short period of time.

Persistent molecular remission of refractory acute myeloid leukemia with inv(16)(p13.1q22) in an elderly patient induced by cytarabine ocfosfate hydrate.

The prognosis of relapsed acute myeloid leukemia (AML) in elderly patients is dismal, even if the AML exhibits a good prognostic karyotype, such as inv(16)(p13.1q22). We present a 72-year-old female with AML with inv(16)(p13.1q22) who suffered five episodes of relapse with temporary complete remission. Maintenance chemotherapy with oral cytarabine ocfosfate hydrate eventually produced persistent molecular complete remission of her AML that had not been induced by conventional regimens including intensive chemotherapy and low dose cytarabine therapy. The high level of tolerability to oral cytarabine ocfosfate hydrate may offer elderly patients with this type of AML a good chance for a cure.

A novel type of selective immunoglobulin m deficiency in a patient with autoimmune liver cirrhosis with recurrent hepatocellular carcinoma: a case report and review of the literature.

A 64-year-old female with advanced liver cirrhosis who had never experienced severe infections presented in 2004 with general malaise. At the time, her serum showed low levels of immunoglobulin (Ig) M (11 mg/dl) with high levels of both IgG (2,942 mg/dl) and IgA (808 mg/dl). Because serum levels of IgG and IgA in previous cases of selective IgM deficiency were normal, this case could have a novel immunological mechanism. By 2006, serum IgM was undetectable (<5 mg/dl). Liver biopsy showed liver cirrhosis from autoimmune hepatitis. She had no other autoimmune diseases or hematological malignancies. She developed hepatocellular carcinoma (HCC) several times and died of liver failure. Immunological analyses performed before the first diagnosis of HCC showed polyclonal γ-globulin elevation, normal chromosome and normal gene rearrangement of immunoglobulin heavy chain Cµ. Peripheral blood showed low count B cells with few surface IgM-positive B lymphocytes, but the percentages of T cell subsets were normal. Expression of activation-induced cytidine deaminase (AID), which plays a critical role in immunoglobin class switching, was found to be overexpressed in the HCC tissue and B cells in bone marrow. This phenomenon could account for the clinical and immunological features of this case. In conclusion, we propose a novel type of selective IgM deficiency in association with the overexpression of AID.

[Comprehensive intervention for the management of elderly patients with aspiration pneumonia].

AIM: Comprehensive management, including medical treatment, care and nursing, rehabilitation, and nutrition management is essential for elderly patients with aspiration pneumonia. We designed and attempted a unique comprehensive intervention method for aspiration pneumonia, and analyzed whether it could improve their prognosis. METHODS: The subjects were patients aged 75 years or more, in whom aspiration pneumonia had been diagnosed between January 15(th) and April 15(th), 2008. Immediately after diagnosis, our project team analyzed the pathophysiology of each case based on the checklists and conference records, and planned an individualized strategy of comprehensive intervention. We analyzed their mortality due to pneumonia, duration of their hospitalization and recurrence-free survival 1 year after antibiotic therapy (1-year RFS), and compared them with those of patients who were managed without antibiotic intervention during the same period in the previous year. RESULTS: There were 41 events in 34 patients (15 men, 19 women, age 87.5±5.7) which were eligible for analysis as an intervention group and 51 events in 46 patients (24 men, 22 women, age 87.5±6.4) were eligible as a control group (age 87.5±6.4). Our comprehensive intervention tended to reduce aspiration pneumonia mortality (4.9% vs. 17.6%, P=0.061). There was no significant difference in the duration of hospitalization between the 2 groups (47.2±35.0 days vs. 55.6±52.1 days, P=0.454). The 1-year RFS of the intervention group was significantly higher than that of the control group (48.5% vs. 24.3%, P=0.040). CONCLUSIONS: Our comprehensive intervention for the management of elderly patients with aspiration pneumonia achieved a significant improvement in 1-year RFS.

Haploidentical hematopoietic stem cell transplantation to adults with hematologic malignancies: analysis of 66 cases at a single Japanese center.

Sixty-six adult patients with hematologic malignancies underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) without T cell depletion. The patients were preconditioned with a reduced intensity regimen, and tacrolimus was used for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment occurred in 60 patients (90.1%) and graft rejection in only 4 patients (6.1%). Among the 60 engrafted patients, only 5 developed severe (grade III or IV) acute GVHD. Twenty patients, including 19 relapse-free patients were alive at a median follow-up of 48 months (range 6-77 months). The overall survival (OS) at 6 years was 29.3%. The OS of 45 patients < 60 years of age was 43.6%, which was superior to that of 21 patients who were 60 years of age and older (9.5%) (P < 0.01). The OS of 11 patients from human leukocyte antigen (HLA) 1 locus-mismatched donors (63.6%) was higher than that of 28 patients from HLA 3 loci-mismatched donors (12.5%) (P < 0.01). Organ injury and infection were the main causes of mortality. Notably, immunosuppressive therapy could be successfully stopped in 9 patients transplanted from HLA 2 or 3 loci-mismatched donors with a median duration of 45 months (range 5-71 months). These data suggest that haplo-HSCT is a promising treatment for patients who need urgent allogeneic transplantation but lack HLA-identical family donors.

Evaluation of the risk of intercostal artery laceration during thoracentesis in elderly patients by using 3D-CT angiography.

OBJECTIVE: Our study was undertaken to determine the location of the tortuous intercostal artery in elderly patients by using 3D-CT angiography in order to prevent laceration during thoracentesis. METHODS: We evaluated the data of 3D-CT angiography of the intercostal artery in consecutive patients who had undergone contrast chest CT scan in our hospital from December 2007 to April 2008. We considered the "percent safe space" (the shortest lower rib-to-intercostal artery distance/the upper rib-to-lower rib distance) to be an index of safety that can be used to prevent laceration of the intercostal artery during thoracentesis. We measured this index at 3 points: the total site (5-10 cm lateral to the spine), the lateral site (9-10 cm lateral to the spine), and the medial site (5-6 cm lateral to the spine). RESULTS: We evaluated 33 cases (25 males and 8 females; mean age, 74.2 years). The mean percent safe space at the total site was 58.6%. The percent safe space at the total site tended to decrease with advancing age, but the correlation was low (p=0.0378, r=-0.3631). The percent safe space at the lateral site (mean, 79.8%) was significantly higher than that at the medial site (61.2%, p<0.0001). CONCLUSION: We showed that the intercostal artery is tortuous and does not always lie along the inferior edge of the rib and that the percent safe space at the lateral site is significantly higher than that at the medial site in elderly patients.

Expression of annexin II in human atherosclerotic abdominal aortic aneurysms.

BACKGROUND: Annexin II is a receptor for tissue-type plasminogen activator (t-PA) that converts plasminogen to plasmin. Although the fibrinolytic system is known to play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs), the relationship between annexin II and AAA development is unknown. Therefore, we examined annexin II localization in the wall of human atherosclerotic AAAs. METHODS AND RESULTS: Specimens from 13 patients undergoing elective repair of an AAA were taken. Annexin II expression was evaluated by immunohistochemical analysis. Immunostaining results were semiquantitatively analyzed using histology scores and WinROOF software based on staining intensity. The expression of annexin II was increased and the histology score was higher in the shoulder region of the atheromatous plaque than in the atheroma and fibrous plaque regions. Annexin II appeared to have greater expression and the histology score was higher in regions where the media was preserved. Furthermore, there was a significant inverse correlation between AAA size and histology score in the fibrous plaque region. CONCLUSIONS: The present work demonstrates various levels of annexin II expression within the aneurysm wall. Therefore, we suggest that alteration of annexin II expression within the aortic wall may be associated with the development of an aneurysm.

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.

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.