Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 5-day-old newborn presented with neonatal enteroviral infection. The patient's hospital course was complicated by acute liver dysfunction, renal insufficiency, fluid overload, respiratory failure, hypertension, catheter related thrombosis, Klebsiella pneumoniae sepsis, intracerebral and intraventricular hemorrhage, and disseminated intravascular coagulation (DIC). Administration of fresh frozen plasma (FFP) and cryoprecipitate failed to control the patient's hemostasis and led to significant fluid overload. Recombinant activated factor VII (rFVIIa, Novoseven NovoNordisk, Bagsvaerd, Denmark) was given to the neonate as a bolus (rFVIIa at 60-80 microg/kg body weight), followed by a continuous infusion (2.5-16 microg/kg/hr). Recombinant activated factor VII controlled hemostasis, until the patient's liver function recovered. The patient's blood product requirement significantly decreased and his fluid overload resolved. Administration of rFVIIa appears to have stabilized the coagulation process. The patient appears to have fully recovered from the infection's complications.
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PMID:Management of coagulopathy with recombinant factor VIIa in a neonate with echovirus type 7. 1523 86

The transmembrane glycoprotein tissue factor (TF) is the initiator of the coagulation cascade in vivo. When TF is exposed to blood, it forms a high-affinity complex with the coagulation factors factor VII/activated factor VIIa (FVII/VIIa), activating factor IX and factor X, and ultimately leading to the formation of an insoluble fibrin clot. TF plays an essential role in hemostasis by restraining hemorrhage after vessel wall injury. An overview of biological and physiological aspects of TF, covering aspects consequential for thrombosis and hemostasis such as TF cell biology and biochemistry, blood-borne (circulating) TF, TF associated with microparticles, TF encryption-decryption, and regulation of TF activity and expression is presented. However, the emerging role of TF in the pathogenesis of diseases such as sepsis, atherosclerosis, certain cancers and diseases characterized by pathological fibrin deposition such as disseminated intravascular coagulation and thrombosis, has directed attention to the development of novel inhibitors of tissue factor for use as antithrombotic drugs. The main advantage of inhibitors of the TF*FVIIa pathway is that such inhibitors have the potential of inhibiting the coagulation cascade at its earliest stage. Thus, such therapeutics exert minimal disturbance of systemic hemostasis since they act locally at the site of vascular injury.
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PMID:Tissue factor: (patho)physiology and cellular biology. 1538 18

Hepatocyte transplantation has been investigated in patients with liver-based metabolic disorders and acute liver failure. We report the first use of hepatocyte transplantation in two brothers with severe inherited coagulation factor VII deficiency. Patient 1 received a total of 1.09x10(9) cryopreserved hepatocytes, and patient received 2.18x10(9) fresh and cryopreserved hepatocytes through a Hickman line inserted in the inferior mesenteric vein. Infusion of isolated human hepatocytes improved the coagulation defect and markedly decreased the requirement for exogenous recombinant factor VII (rFVIIa) to approximately 20% of that before cell transplantation. In both patients, episodes of line sepsis were associated with an increase in rFVIIa requirement. Six months posthepatocyte transplantation, higher rFVIIa doses were required, suggesting loss of transplanted hepatocyte function. Because of increasing problems with venous access and long-term uncertainty of the efficacy of hepatocyte transplantation, orthotopic liver transplantation was performed successfully in both cases.
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PMID:Hepatocyte transplantation for inherited factor VII deficiency. 1561 56

Effective treatment of severe or uncontrolled bleeding is a challenge for physicians in the operating room and intensive care unit. However, even aggressive conventional therapy may ultimately fail in some patients. Administration of recombinant activated factor VII (rFVIIa) may be the only remaining therapeutic option to stop life-threatening coagulopathic bleeding. We here describe the clinical course of 5 patients exhibiting severe continuous bleeding that could not be stopped by surgical intervention and appropriate hemostatic management but resolved after a mean dose of 90 microg/kg of rFVIIa (range, 90-120 microg/kg). Four of the five patients recovered completely, and one patient died after developing sepsis in multiorgan failure. In all patients, bleeding from wound surfaces stopped within minutes of the administration of rFVIIa. Coagulation measurements improved, and transfusion requirements declined considerably. No adverse effects associated with rFVIIa were observed.
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PMID:Successful reversal of deleterious coagulopathy by recombinant factor VIIa. 1561 51

Acute hemorrhage is a sometimes serious complication that may arise in patients admitted to the intensive care unit with coagulopathy. The usual therapy is transfusion of blood components: fresh frozen plasma, platelets, fibrinogen, red cell concentrate and vitamin K. Tolerance or response can sometimes be poor. We present three patients aged 18 months, 4.5 and 10 years who suffered an acute episode of severe, life-threatening hemorrhage in the course of meningococcal sepsis (gastric hemorrhage), myelomonocytic leukemia (during splenectomy) and in the postoperative period after cardiovascular surgery. Traditional therapy was ineffective and activated factor VII was administered at doses of 50-70 microg/kg, with rapid control of bleeding.
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PMID:[Use of activated factor VII in severe acute hemorrhage]. 1587 29

Endothelium plays a critical role in the pathobiology of sepsis by integrating systemic host responses and local rheological stimuli. We studied the differential expression and activation of tissue factor (TF)-dependent coagulation on linear versus branched arterial segments in a baboon sepsis model. Animals were injected intravenously with lethal doses of Escherichia coli or saline and sacrificed after 2 to 8 hours. Whole-mount arterial segments were stained for TF, TF-pathway inhibitor (TFPI), factor VII (FVII), and markers for endothelial cells (ECs), leukocytes, and platelets, followed by confocal microscopy and image analysis. In septic animals, TF localized preferentially at branches, EC surface, leukocytes, and platelet aggregates and accumulated in large amounts in the subendothelial space. FVII strongly co-localized with TF on ECs and leukocytes but less so with subendothelial TF. TFPI co-localized with TF and FVII on endothelium and leukocytes but not in the subendothelial space. Focal TF increases correlated with fibrin deposition and increased endothelial permeability to plasma proteins. Biochemical analysis confirmed that aortas of septic baboons expressed more TF mRNA and protein than controls. Branched segments contained higher TF protein levels and coagulant activity than equivalent linear areas. These data suggest that site-dependent endothelial heterogeneity and rheological factors contribute to focal procoagulant responses to E. coli.
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PMID:Tissue factor-dependent coagulation is preferentially up-regulated within arterial branching areas in a baboon model of Escherichia coli sepsis. 1619 50

Pulmonary hemorrhage is a rare but well-known complication in preterm infants. We present a case of massive pulmonary hemorrhage in a 9-day-old male infant, successfully treated with intravenous recombinant activated factor VII (rFVIIa) (NovoSeven; Novo Nordisk). The infant was diagnosed with sepsis-related disseminated intravascular coagulation and required ventilator support for respiratory distress syndrome and blood transfusions due to active bleeding from endotracheal tube. After administration of the second dose of rFVIIa (120 microg/kg per dose, every 2 h), the active bleeding subsided dramatically and a significant improvement in the oxygenation index was seen 8 h after the third dose of rFVIIa treatment. There were also significant improvements in the prothrombin time, International Normalized Ratio, activated partial thromboplastin time and plasma fibrinogen levels after the third dose of rFVIIa treatment. The infant was discharged on day 82 of life and there was no finding of thrombosis during the hospitalization period. At month 18 of follow-up, there was no morbidity related to the pulmonary and central nervous systems. This case suggests that rFVIIa is effective as an alternative therapy in controlling massive pulmonary hemorrhage of preterm infants.
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PMID:The use of recombinant activated factor VII in the treatment of massive pulmonary hemorrhage in a preterm infant. 1657 60

We evaluated the score for disseminated intravascular coagulation (DIC) recently published by the International Society for Thrombosis and Haemostasis (ISTH) in a well-defined series of sepsis patients. Thirty-two patients suffering from severe sepsis and eight patients with septic shock were evaluated following the ISTH DIC score. Fibrin monomer and D-dimer were chosen as fibrin-related markers (FRM), respectively. DIC scores for nonsurvivors (n = 13) as well as for septic shock patients were higher (P < 0.04) compared with survivors and patients with severe sepsis, respectively. Using fibrin monomer and D-dimer, 30 and 25% of patients suffered from overt DIC. Overt DIC was associated with significantly elevated thrombin-antithrombin complexes and plasminogen activator inhibitor type-1 levels as well as with significantly lower factor VII clotting activity. Patients with overt DIC had a significantly higher risk of death and of developing septic shock. Since more than 95% of the sepsis patients had elevated FRM, the DIC score was strongly dependent on prolongation of the prothrombin time and platelet counts. The ISTH DIC score is useful to identify patients with coagulation activation, predicting fatality and disease severity. It mainly depends on the prolongation of the prothrombin time and platelet counts.
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PMID:International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients. 1690 47

Bleeding diatheses are frequent alterations during sepsis and surgical-anesthetic aggression. Generally, the bleeding is related with platelet dysfunction, inadequate surgical hemostasis, vitamin K deficit, etc. We present the case of a patient with no background of coagulopathy who, after two surgical interventions, developed abdominal sepsis and peritoneal hematoma after puncture for drainage of abdominal collection, due to an autoimmune origin factor VIII acquired deficit. The hematoma caused a picture of hypovolemic shock that required transfusion of several units of red blood cells, expansion and drug support. Finally, the bleeding was controlled by treatment with immunosuppressants, recombinant activated factor VII (RFVIIa) and polyvalent gammaglobulin. The peritoneal hematoma was drained surgically and the patient evolved towards improvement until being discharged from the intensive therapy unit.
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PMID:[Peritoneal bleeding due to acquired hemophilia during an abdominal sepsis clinical picture]. 1706 8

Postpartum haemorrhage remains a dangerous obstetrical complication, which is the main cause of maternal mortality in developing countries. The diagnosis must be immediate and its management is both medically and surgically in life-threatening haemorrhage. We present a case of a thirty-three-year-old woman who asked a pregnancy interruption for premature rupture of membranes at 21(th) gestational week for her second pregnancy; she underwent a caesarean section at term for her first pregnancy. She delivered vaginally and developed a postpartum haemorrhage with hemorrhagic shock which was resistant to medical, surgical and radiological management. We decided to use recombinant activated factor VII (rFVIIa, NovoSeven) as a final attempt to rescue the patient. During surgery, two intravenous bolus injections (60, 120 mug/kg) were successfully given with a control of bleeding and haemoglobin. The patient developed later a splenic thrombosis that can be related to either rFVIIa or to the hypovolemic shock or to the sepsis. Recombinant activated factor VII is an interesting and promising haemostatic agent in the management of life-threatening postpartum haemorrhage unresponsive to conventional treatment.
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PMID:[Life-threatening postpartum hemorrhage and recombinant activated factor rFVIIa NovoSeven use]. 1729 58


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