Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The innate immune response to intraportally infused adenoviral vector was evaluated in rhesus monkeys. A first-generation adenovirus-expressing lacZ (Ad-lacZ) was administered at a dose just below that which causes severe morbidity. The response to vector was evaluated for the initial 24 h following infusion. Clinical findings during this time were primarily limited to petechiae, consistent with the development of thrombocytopenia and biochemical evidence of disseminated intravascular coagulation. Serum transaminases were elevated and a lymphopenia developed. Tracking of fluorescent-labeled vector demonstrated distribution to macrophages and dendritic cells of the spleen and Kupffer cells of the liver. A systemic release of the cytokine IL-6 occurred soon after vector infusion. Analysis of splenic cells revealed acute activation of macrophages and dendritic cells followed by massive apoptosis. Bone marrow cultures demonstrated normal erythroid and primitive progenitors with a significant decrease in myeloid progenitors. Similar findings, except the abnormality in bone marrow cultures, were observed in monkeys who received an identical dose of Ad-lacZ in which vector genes were inactivated with psoralen and UV irradiation. These data suggest that inadvertent targeting of antigen-presenting cells following intraportal infusion of vector leads to a systemic cytokine syndrome which may be triggered by the viral capsid proteins.
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PMID:Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors. 1135 76

The recent advances in the psychoneuroimmunology have suggested that the hematopoiesis may be under a neuroendocrine regulation, mainly exerted by the pineal gland. In particular, melatonin (MLT), which is the main pineal hormone, has appeared to stimulate platelet generation, probably by promoting the megakaryocyte fragmentation and modulating the cytokine network involved in platelet production. On this basis, we have evaluated the effect of pharmacological doses of MLT on platelet number in patients with persistent thrombocytopenia due to different causes. The study included 200 patients, who were randomized to receive supportive care alone or MLT at 20 mg/day orally in the evening, for al least 1 month. No MLT-related toxicity occured. Platelet mean number rapidly and significantly increased in response to MLT, and a normalization of platelet number was achieved on MLT therapy in 71/98 (72%) patients. The least responsive form of thrombocytopenia was DIC. This study shows that the pineal hormone MLT may represent a well tolerable and effective therapy of thrombocytopenia due to different pathogenetic mechanisms.
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PMID:Growth Factors: Thrombopoietic Property of the Pineal Hormone Melatonin. 1139 74

It is increasingly apparent that there is a bidirectional interaction between the maternal immune system and the reproductive system during pregnancy. Pregnancy is associated with a suppression of maternal specific immune responses, which process underlies the protection of fetal tissues expressing paternally inherited alloantigens. However, recent evidence indicates that the suppression of specific, lymphocyte-mediated immune responses during pregnancy is accompanied by activation of the non-specific arm of the maternal immune response. In the present study, we have investigated the effect of pregnancy on the non-specific immune response induced by bacterial lipopolysaccharide (LPS, endotoxin) in mice. Pregnancy enhanced the LPS-induced production of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and interferon-gamma. On the other hand, LPS-induced levels of the anti-inflammatory cytokine IL-10 were suppressed in pregnant mice. These alterations in cytokine production correlated with an increased susceptibility for endotoxemic mortality in the pregnant mice. Although adrenergic receptors are important regulators of cytokine production in non-pregnant mice, the alpha(2)- and the beta-adrenoceptor-mediated modulation of cytokine production ceases to operate during pregnancy associated with severe endotoxemia. These data may explain how excessive activation of the non-specific immune responses during pregnancy can contribute to the increased severity of some maternal diseases, including septic shock, and can be an important pathophysiological factor in disseminated intravascular coagulation or preeclampsia.
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PMID:Enhanced tumor necrosis factor-alpha-specific and decreased interleukin-10-specific immune responses to LPS during the third trimester of pregnancy in mice. 1169 56

The incidence of sepsis and complications stemming from septicemia has remained constant in recent years despite improved levels of monitoring and care. Disseminated intravascular coagulation (DIC), a syndrome that occurs frequently in septic patients, is associated with increased mortality. Organ dysfunction is also a common sequela that is strongly correlated with DIC. Cytokines released early in the course of sepsis stimulate a procoagulant state that causes development of intravascular fibrin deposition. In a later stage of DIC, bleeding may occur in parallel because of consumption of clotting factors and inhibitors. Therapeutic strategies to attenuate or reverse these conditions have focused on multiple stages of the molecular cascade of events, including preventing cytokine induction, inhibiting coagulation processes, and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC associated with severe sepsis. Studies of other novel therapeutic avenues are still ongoing. Future efforts may be directed at combining 2 or more agents to achieve prompt and successful reversal of DIC.
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PMID:Pathogenesis and treatment of disseminated intravascular coagulation in the septic patient. 1181 2

A 42-year-old woman was diagnosed as systemic lupus erythematosus (SLE), because of the findings of polyarthritis, leukopenia, positive antinuclear antibody, and positive anti DNA antibody. She was treated with predonisolone (PSL) at 10 mg per day. She was admitted to our hospital on October 2000 because of spiking high fever, skin eruption, and lymph node swelling. Since her illness of SLE was considered to be worsening, high dose of corticosteroids were given. However, high fever persisted and liver dysfunction was developed with increased serum ferritin. Her bone marrow smear showed hemophagocytosis. We made a diagnosis of hemophagocytic syndrome (HPS) complicated by disseminated intravascular coagulation (DIC). HPS was thought to be induced by viral infection, even though causative viral infection was not detected. Her general condition worsened with persistent high fever and liver dysfunction. Plasma exchange was carried for two consecutive days, followed by cyclosporine A and lipo-dexamethasone, which improved her fever rapidly. Her general condition gradually improved. Serum levels of ferritin, soluble interleukin 2 receptor (sIL 2-R), interferon-gamma and interleukin 6 decreased associated with improvements of her clinical condition. We thought plasma exchange could be effective to decrease serum levels of cytokine, which was suggested to be the pathogenic to HPS. However serum levels of IFN-gamma and IL 6 after plasma exchange did not change in this case. Further studies are required to confirm the effects of plasma exchange for HPS.
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PMID:[Case report of systemic lupus erythematosus patient with hemophagocytic syndrome, treated with plasma exchange, with specific reference to clinical profile and serum cytokine levels]. 1183 Oct 15

The pathophysiologic mechanisms, clinical, and laboratory manifestations of DIC are complex in part due to interrelationships within the hemostasis system. Only by clearly understanding these extraordinarily complex pathophysiologic interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Many therapeutic decisions to be made are controversial and lack validation. Nevertheless, newer antithrombotic agents, and agents that can block, blunt, or modify cytokine activity and the activity of vasoactive substances appear to be of value. The complexity and variable degree of clinical expression suggests that therapy should be individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis and hemodynamics and other appropriate clinical parameters. At present, treatment of the triggering event, low-dose heparin or antithrombin concentrate and wise choice of components when indicated appear to be the most effective modes of therapy.
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PMID:Disseminated intravascular coagulation: a review of etiology, pathophysiology, diagnosis, and management: guidelines for care. 1199 Dec 36

The conditioning regimen preceding hematopoietic stem cell transplantation (HSCT) causes a rapid decrease in the platelet count and signs of disseminated intravascular coagulation, possibly indicating platelet activation. As impacts during the conditioning regimen may predict later transplantation-associated complications, we investigated changes in platelet membrane glycoproteins (GP) and the liberation of microparticles. Platelet receptors and granules of 49 patients undergoing HSCT were evaluated by flow cytometric analysis before and after the different phases of the conditioning regimen [chemotherapy, total body irradiation (TBI), therapy with antithymocyte globulin (ATG)] and final transplantation. Following chemotherapy a high surface expression of CD62P, a low mepacrine staining, and a reduced surface expression of CD42b (part of the GP Ib/V/IX complex) were found, indicating an irreversible activation of platelets. In addition, elevated levels of circulating microparticles were observed, which may reinforce the thrombosis risk in these patients. Treatment with ATG leads to an elevated surface expression of PAC-1 epitopes, which are neoepitopes appearing after activation of GP IIb/IIIa. However, a significant degranulation was not detectable, which may be the consequence of inhibitory influences on platelets during ATG-induced cytokine release syndrome. TBI and transplantation itself had no influence on platelets. This study was able to demonstrate activating effects on platelets by certain phases of the conditioning regimen in patients receiving HSCT. Chemotherapy, in particular, leads to a strong and irreversible platelet activation and a generation of microparticles, which may cause an increased thrombosis risk. Our findings underline the impact of platelets on the pathogenesis of hemostatic complications during HSCT.
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PMID:Platelet flow cytometric findings in patients undergoing conditioning therapy for allogeneic hematopoietic stem cell transplantation. 1222 3

Antithymocyte globulin (ATG) is commonly used in allogeneic haematopoietic stem cell transplantation (HSCT). Little information is available, however, as to the optimal protocol for use and the side-effects occurring if ATG is administered in high daily doses (10-30 mg/kg). We report our experience with ATG Fresenius (ATG-F) in conditioning for allogeneic HSCT. During a period of 3 days, 47 patients received doses between 10 and 30 mg/kg either over 4 h preceded by 1-1.5 mg/kg prednisolone 30 min before the start of ATG-F (protocol A) or alternatively, over 12 h with 3-4 mg/kg prednisolone being administered before and 6 h after start of ATG (protocol B). During treatment with ATG-F, the side-effects observed included inflammation, disseminated intravascular coagulation, hyperdynamic circulation and renal dysfunction. Although these complications caused substantial morbidity, they were reversible within a few days. Side-effects were significantly more severe in patients treated according to protocol A than in those treated according to protocol B. As prolonged infusion of ATG-F does not reduce T cell clearance due to the long half-life of ATG-F, and since less cytokine release during conditioning might have beneficial long-term effects, we recommend administering ATG-F over 12 h preceded by high-dose steroid treatment.
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PMID:The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation. 1223 18

We report here three cases of peripheral T-cell lymphoma unspecified (PTCL-US), which presented with bone marrow infiltration and hepatosplenomegaly and were successfully treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were all characterized by cytokine-induced symptoms such as fever, anasarca, cytopenia, poor general condition, and disseminated intravascular coagulation syndrome. Laboratory data showed extremely high levels of soluble interleukin-2 receptor, beta(2)-microglobulin, and ferritin. All three patients were negative for anti-adult T-cell leukemia antibody. In one patient, hemophagocytosis was revealed by a histological examination of the bone marrow. The International Prognostic Index was high for all three patients, and they all achieved complete remission after the intensive chemotherapy for remission induction. During complete remission, they were treated with HDCT [modified interleukin-converting enzyme regimen] followed by auto-PBSCT. The recovery of hematopoiesis after auto-PBSCT was prompt and sustained engraftment was obtained. No serious adverse effects other than myelosuppression were noted. One patient died due to cerebrovascular disease without relapse 18 months after auto-PBSCT. The other two patients are still alive and have not suffered from relapse. Our observations suggest that auto-PBSCT following HDCT may be an effective and safe therapeutic modality for high-risk PTCL-US patients characterized by hepatosplenomegaly and cytokine-induced syndrome.
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PMID:High-dose chemotherapy and autologous peripheral blood stem cell transplantation for treatment of unspecified peripheral T-cell lymphoma presented with hepatosplenomegaly and hypercytokinemia syndrome: report of three cases. 1242 41

A central position in the development of systemic inflammation is played by activation of the vascular endothelium and monocyte- macrophage system. Both are associated with the formation of inflammatory cytokines, the primary mission of which is mobilization of the organism to cope with the infection. The so-called acute stage response develops with typical clinical manifestations and laboratory values. When it is impossible to stop the inflammation the syndrome of systemic inflammatory response develops with excessive activity of inflammatory cytokines and immune mechanisms. This apparently favourable system can be highly toxic for the organism and can lead to the syndrome of multiorgan failure, to disseminated intravascular coagulation, to depression of the myocardium, refractory vasodilatation, hypertension and septic shock. The compensatory antagonistic mechanism which develops due to the formation of anti-inflammatory cytokines leads sometimes to the development of a balanced state of immunity which is most favourable from the prognostic aspect. In case of their excess however immunodepression develops which is equally dangerous for the patient as excessive cytokine activity. From what has been said ensues the need of regular monitoring of patients with sepsis and thus also detailed investigation of their immune system.
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PMID:[Role of cytokines in the development of local and systemic inflammation and septic shock]. 1242 7


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