Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombotic microangiopathy (TMA) can be a late complication of bone marrow transplantation (BMT). A patient is described in whom the haemolytic uraemic syndrome developed 10 months after BMT and who died of E. coli sepsis while on maintenance haemodialysis. The literature is reviewed, regarding clinical presentation, incidence, pathogenesis and therapy. TMA can be observed, after an interval of 3-12 months, in about 6-26% of patients following BMT. Reported cases vary considerably in clinical severity, from mild presentations to severe TMA with high mortality rates despite intensive therapy. Important pathogenetic roles are ascribed to the conditioning total body irradiation and the use of cyclosporin A, but other factors may be involved as well. Next to supportive therapy, plasma exchange and the use of ACE inhibitors may be of value in treating BMT-associated TMA.
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PMID:Haemolytic uraemic syndrome following bone marrow transplantation. Case report and review of the literature. 867 33

Thrombotic microangiopathy (TMA) is more common in HIV-infected individuals than in the normal population. In idiopathic TMA, plasmapheresis with or without prednisone decreases the mortality rate from almost 100 to 10%. Patients with HIV-associated TMA, who do not have AIDS, have a similar favorable outcome when treated with plasmapheresis. However, all 12 patients previously reported with AIDS-associated TMA have died. We report another patient with AIDS-associated TMA, who had a fulminant hospital course and died despite plasmapheresis. None of the reported AIDS-associated TMA patients had evidence of opportunistic infections, sepsis or disseminated malignancies at the time of their death. Since many infections and malignancies can be associated with TMA, it is possible that TMA can be an association of the terminal illness rather than an independent cause of death in AIDS patients. To examine this possibility, we reviewed the charts of all the patients who were hospitalized and died of AIDS at our medical centers from 1987 to 1994. Of the 214 patients reviewed, 15 patients (7%) had evidence of TMA at the time of their death. Seven of the 15 patients (47%) had no direct cause of death other than TMA. The remaining 8 patients had evidence of sepsis and other overwhelming infections. In conclusion, TMA is common in AIDS patients. While HIV-associated TMA has a good prognosis similar to that of idiopathic TMA, AIDS-associated TMA has a grave prognosis. The etiology of the higher mortality in AIDS-associated TMA as compared to HIV-associated TMA remains unclear.
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PMID:Disparate prognosis of thrombotic microangiopathy in HIV-infected patients with and without AIDS. 962 48

P-selectin is a 140 kD protein found in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells. On cell activation it is expressed on the cell surface and also secreted into plasma. Whether the circulating soluble P-selectin (sP-selectin) originates from platelets, endothelial cells, or both, is not known. We studied the level of sP-selectin in diseases with different platelet counts, with or without evidence of endothelial cell activation. Endothelial cell activation was confirmed by the detection of sE-selectin and ED1-fibronectin. A significant positive correlation between platelet count and sP-selectin concentration was observed in healthy controls, and in patients with thrombocytopenia due to bone marrow aplasia, or with thrombocytosis (r = 0.85; n = 47; p < 0.001). In patients with idiopathic thrombocytopenic purpura (ITP) the sP-selectin concentration was 110 +/- 39 ng/ml (n = 10), compared to 122 +/- 38 ng/ml in healthy controls (n = 26). However, their mean platelet count was lower (58 x 10(9)/l versus 241 x 10(9)/l in the control group). Accordingly, the levels of sP-selectin expressed per platelet increased to significantly higher levels (2.0 +/- 1.2 versus 0.6 +/- 0.2 fg/platelet in the control group; p < 0.0001). This suggests increased platelet turnover in patients with ITP. High levels of sP-selectin were found in patients with sepsis (398 +/- 203 ng/ml; n = 15) and with thrombotic thrombocytopenic purpura (TTP; 436 +/- 162 ng/ml; n = 12). Compared with patients with ITP, the concentration of sP-selectin per platelet was higher in patients with sepsis (4.8 +/- 4.3 fg/platelet; p < 0.005) or TTP (17.1 +/- 9.5 fg/platelet; p < 0.001). Endothelial cells are very likely to be the source in these patients and the presence of endothelial cell activation was confirmed by increased levels of circulating E-selectin and ED1-fibronectin. This study suggests that platelets are the major source of circulating sP-selectin in healthy individuals. Endothelial cell activation is associated with an increased sP-selectin concentration per platelet.
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PMID:The origin of P-selectin as a circulating plasma protein. 924 36

The combination of CPT-11 with 5-fluorouracil (5-FU) in advanced colorectal cancer (ACC) represents an attractive approach. A phase II study was conducted to assess the tolerance and efficacy of CPT-11 in combination with leucovorin-modulated bolus plus infusional 5-FU given according to the de Gramont regimen in chemonaive patients with ACC. Fifty-four patients with histologically confirmed ACC were enrolled. The patients' median age was 65 years; 30 (55.5%) patients were men; performance status (World Health Organization) was 0 in 27 (50%) patients, 1 in 22 (41%), and 2 in 5 (9%). Patients received leucovorin (200 mg/m2/d) as a 2-hour intravenous infusion, followed by 5-FU as an intravenous bolus at 400 mg/m2/d, and then as a 22-hour continuous infusion at 600 mg/m2/d, repeated on 2 consecutive days. CPT-11 (180 mg/m2; 30-minute intravenous infusion) was administered on day 1, simultaneously with leucovorin administration. This cycle was repeated every 2 weeks. Complete response was achieved in 4 patients (8%) and partial response in 19 (37%) (overall response rate: 45%; 95% CI: 24-50.5%). Stable disease was achieved in 16 (31%) patients and progressive disease in 13 (25%). The median duration of response and the median TTP were 5 and 8 months, respectively. After a median follow-up period of 11 months, 33 (61%) patients are still alive; the median overall survival has not yet been reached. Thrombocytopenia and anemia were very rare. Grade III/IV neutropenia developed in 19 patients (36%); febrile neutropenia developed in 4 patients, and 1 of them died of sepsis. Grade IV diarrhea was seen in 7 (13%) patients, and 4 of them required hospitalization. Grade III and IV mucositis was observed in two (4%) and one (2%) patients, respectively. Other toxicities were mild. The combination of CPT-11 and bolus plus infusional 5-FU is a relatively well-tolerated and effective first-line treatment in ACC. Final results from large phase III trials are awaited to clarify whether the CPT-11/5-FU combinations should be considered as "standard" first-line treatment in ACC.
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PMID:Irinotecan (CPT-11) in combination with infusional 5-fluorouracil and leucovorin (de Gramont regimen) as first-line treatment in patients with advanced colorectal cancer: a multicenter phase II study. 1182

In summary, use of plasmapheresis has changed in recent years given advances in medical technology that have allowed a wider clinical application in the critical care setting. Membrane filtration technology has provided an alternative to centrifugation that can be easily applied in intensive care units. Use of plasmapheresis has also changed in recent years reflecting the availability of evidence largely obtained from controlled prospective studies. However, the clinical efficacy of plasmapheresis for many acute renal conditions is still controversial. Plasmapheresis appears to be a useful adjunct to conventional therapy in the treatment of anti-GBM nephritis, severe dialysis-dependent forms of pauciimmune RPGN, cryoglobulinemia, and HUS-TTP. Reported data also suggest a possible benefit of plasmapheresis in patients with myeloma cast nephropathy, sepsis, and poisoning/overdose, but the case for plasmapheresis in these disorders is largely unproven and the reported evidence insufficient to recommend its use outside research settings. In contrast, data from controlled trials do not support a role for plasmapheresis in immune complex-mediated RPGN, such as lupus nephritis, and acute allograft rejection. The more widespread application of prospective, randomized, controlled clinical trials should help to better define the value of plasmapheresis for treatment of acute renal diseases.
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PMID:Plasmapheresis. Technical aspects and indications. 1205 39

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93

Thrombotic thrombocytopenic purpura (TTP) has been associated with scleroderma renal crises (SRC) in the past. However such reports markedly diminished after the onset of ACE inhibitor use. Recently, reports again have surfaced that describe scleroderma patients presenting with clinical evidence of TTP. We describe a 50-year-old female with longstanding limited cutaneous scleroderma who presented with hematochezia and thrombocytopenia along with other findings suggesting TTP. A colon biopsy revealed thrombi within the lumen. Her course was complicated by renal failure and hypertension that did not respond to ACE inhibitor therapy alone. She improved after a course of plasma exchange. She was discharged home only to return 2 months later with grand mal seizures and hypertension. During her course she developed adult respiratory distress syndrome. She again responded to plasma exchange and she was discharged home. She has remained stable for 2 years. This report emphasizes the importance of fully evaluating patients with longstanding limited cutaneous scleroderma who present with renal failure, hypertension, and thrombocytopenia in association with multiorgan complications. All possible etiologies, including SRC, TTP, vasculitis, and sepsis should be considered. Tissue biopsies (in this case, a colon biopsy revealed thrombi within the vessel lumen) may prove beneficial in assisting with the diagnosis. For such patients who fail treatment with ACE inhibitors, plasma exchange may be considered.
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PMID:Thrombotic thrombocytopenia purpura in a patient with systemic sclerosis. 1703 6

Thrombotic microangiopathy (TMA) is a grave complication after haematopoietic stem cell transplantation (HSCT) and effective treatment is undefined. Five patients with postHSCT TMA, which was refractory to at least 1 week of plasma exchange and prednisolone, were treated with rituximab (375 mg/m(2)/week x 4). Remission was achieved in four patients, of whom three remained in remission and one had died of sepsis at a median follow-up of 10 months. ADAMTS13 levels were low in all evaluable patients, and only one patient showed significant anti-ADAMTS13 antibody. The levels of ADAMTS13 and anti-ADAMTS13 antibody did not change significantly with rituximab-induced remission.
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PMID:Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab. 1785 24

Thrombotic thrombocytopenic purpura (TTP) describes syndromes with multiple etiologies, some of which are rapidly fatal without plasma exchange treatment. Although there have been advances in understanding the pathogenesis of TTP, evaluation and management remain difficult because there are no specific diagnostic criteria, as TTP can be clinically similar to other acute disorders, such as sepsis, disseminated malignancy, malignant hypertension, and preeclampsia, and because urgent treatment is required. An unexpected observation of anemia and thrombocytopenia should trigger consideration of TTP; evidence that the anemia is due to microangiopathic hemolysis, suggested by the presence of red cell fragmentation on the blood smear, supports the diagnosis. When the diagnostic criteria of microangiopathic hemolytic anemia and thrombocytopenia without an apparent alternative etiology are fulfilled, plasma exchange treatment is appropriate. However, plasma exchange has risks for severe complications and death; therefore, this management decision must be balanced against the confidence in the diagnosis. With plasma exchange treatment, approximately 80% of patients survive, in contrast to only 10% in the era prior to the availability of plasma exchange. The continuing mortality from TTP, the risks of plasma exchange treatment, and the potential for recurrent episodes of TTP are clinical challenges that remain to be solved.
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PMID:Evaluation and management of patients with thrombotic thrombocytopenic purpura. 1745 28

The time from the start of incubation to a positive reading of blood cultures (time-to-positivity; TTP) is related to the concentration of bacteria in blood. Information concerning the correlation of TTP with clinical parameters, and its usefulness as a prognostic factor in patients with Escherichia coli bacteraemia, is limited. To investigate the relationship of TTP to clinical parameters, 459 cases of monomicrobial E. coli bloodstream infections from a single institution between 1997 and 2005 were reviewed. All cases involved patients who were not undergoing antibiotic treatment at the time of blood sampling. The in-hospital mortality rate was 6.3%. Median TTP was significantly shorter for patients who died than for those who survived (9.7 h, inter-quartile range 7.85-11.05 h vs. 11.2 h, inter-quartile range 10.1-11.4 h; p <0.001). Patients with TTP in the lowest quartile were more likely to be female, to have a non-urinary tract or an unknown origin of bacteraemia, to have severe sepsis or shock, and to subsequently die. In a multivariable Cox regression model, the hazard ratio for death from any cause for patients with a short TTP was 3.13 (95% CI 1.28-7.64; p 0.01). TTP in patients with E. coli bacteraemia provides prognostic information beyond that provided by the presence of haematological illness, a Charlson score > or =3, a non-urinary tract origin of bacteraemia, and the presence of severe sepsis or shock.
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PMID:Time-to-positivity in patients with Escherichia coli bacteraemia. 1772 85


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