Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to measure the coagulation inhibitors in two groups of uremic patients treated with hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) to evaluate the differences in anticoagulant activity. In 20 patients on HD and 20 on CAPD, mean age 66 +/- 8 and 58 +/- 14 years, respectively, the following parameters were determined between dialysis exchanges: protein C (PC), protein S (PS), antithrombin III (AT III), electrophoresis, prothrombin activation fragment (F1+2), alpha 1 antitripsin (alpha 1 AT), prothrombin time (PT), and activated partial thromboplastin time (PTT). The mean values of PC, PS, and AT III were respectively, 95.7 +/- 16 on HD and 92 +/- 23 on CAPD; 82.2 +/- 13.6 on HD and 90.5 +/- 13.6 on CAPD; the mean value F1+2 was 1.2 +/- 0.5 on HD and 1.04 +/- 0.5 on CAPD (p < 0.05). A good correlation between PS and AT III% functional activity (p < 0.03, r = 0.5) in both groups was found. More-over, PS functional activity was inversely correlated with duration of dialysis (p < 0.05, r = -0.3). HD patients showed a reduction of coagulation inhibitors compared with CAPD patients. Such a phenomenon could justify the increased thrombotic risk in HD patients. Since 80% of those on HD and only 20% of those on CAPD received erythropoietin (EPO), the prothrombotic state in HD could be due to reduced PS activity secondary to EPO treatment.
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PMID:Reduced blood levels of coagulation inhibitors in chronic hemodialysis compared with CAPD. 853 85

We studied 37 hemodialysis patients during hemodialysis in order to assess the effects of dialysis on endogenous plasma coagulation inhibitors (antithrombin III, protein C, free and total protein S). The patients were examined prior to erythropoietin (EPO) treatment, upon reaching target hemoglobin (Hb) and after 3 months at steady state Hb levels. The levels of protein C increased significantly during dialysis. However, EPO treatment did not affect the levels of any of the endogenous coagulation inhibitors, either upon reaching target Hb or after 3 months of steady state Hb. The sequence of change during dialysis of protein C, free and total protein S was constant when comparing respective patterns prior to EPO treatment to those at target Hb and steady state Hb respectively. In conclusion, hemodialysis seems to activate synthesis of endogenous coagulation while partial correction of anaemia with EPO does not affect the levels of these inhibitors.
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PMID:Effects of hemodialysis and long-term erythropoietin treatment on protein C, and on free and total protein S. 858 93

Recombinant human erythropoietin (rHu-EPO) in the treatment of renal anemia might predispose to an increased risk of thrombotic complications. In an attempt to comprehend the involvement of the physiologic inhibitors of coagulation in this process, we studied 2 groups of hemodialysis patients. Group I included 21 patients receiving a starting dose of 90 IU/kg/week s.c., and group II included 17 patients without rHu-EPO. The following coagulation tests were performed before rHu-EPO treatment, and after 1, 6 and 12 months: prothrombin time; activated partial fistula thromboplastin time; fibrinogen; plasminogen activity; antithrombin III activity; protein C activity; total and free protein S antigens, and C4b binding protein. Only the latter three parameters were changed in group 1, while high baseline levels of protein S antigens were found in both groups. A decrease in total and free protein S was observed within 1 month of treatment. At the 6th month total protein S returned to near pretreatment values, whereas a significant fall in free protein S (p = 0.007) was observed. All three parameters returned to near baseline values by 12 months. These results suggest that protein S activity can be altered at the beginning of EPO therapy, a change that under favoring circumstances might contribute to the thrombotic events reported during the early phase of rHu-EPO treatment.
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PMID:Effects of long-term treatment with recombinant human erythropoietin on physiologic inhibitors of coagulation. 938 55

The effects of recombinant human erythropoietin (rHuEPO) on plasma and peritoneal effluent levels of antithrombin III (AT-III), protein C (PC) activity, and protein S (PS) activity were evaluated in 10 uremic children on continuous ambulatory peritoneal dialysis (CAPD). The findings were compared with values obtained from ten healthy children. Levels of AT-III and of PC and PS activity in plasma and peritoneal effluent were measured before, and at 8 and 12 weeks after, rHuEPO treatment. Baseline levels of AT-III and PC activity in plasma were lower than the control values. Levels of PC activity increased during the trial, while levels of AT-III remained unchanged, and levels of PS activity decreased. Baseline levels of PC activity in peritoneal effluent were lower than those obtained during rHuEPO treatment, while no change in peritoneal levels of PS activity and AT-III was observed after rHuEPO treatment. A significant positive correlation was seen between plasma and peritoneal levels of PC activity at baseline. A significant positive correlation was also seen between plasma levels of PS activity and hemoglobin at week 12, and a significant negative correlation between plasma levels of AT-III and albumin at week 8. No correlation was found between the plasma natural coagulation inhibitors and CAPD duration. These results suggest that plasma PS activity can be decreased, and plasma PC activity increased, by rHuEPO treatment in children.
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PMID:Effects of recombinant human erythropoietin on physiological inhibitors of coagulation in children on continuous ambulatory peritoneal dialysis. 1068 17

We performed a crossover study to compare the effects of different dialysis membranes on 20 patients with frequent dialyser clotting and requiring > or = 5,000 units of heparin per dialysis session. Low-flux dialysers are C15NL (cellulose - Terumo) and E15NL (vitamin-E-coated - Terumo) while high-flux dialysers were F60 (polysulphone) and EE15NL (vitamin-E-coated - Terumo). Ten patients underwent dialysis for 2 months with C15NL then switched to E15NL for 2 months. Similarly, the other 10 patients were started on the high-flux dialyser F60 and then switched over to EE15NL for 2 months. The following parameters were measured at the beginning of the study, 2 weeks, 1 month and then at 2 months: hemoglobin, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, protein C, protein S, antithrombin III (ATIII) and factor 12 activity. Dialyser clotting, heparin and erythropoietin requirements were assessed during each dialysis session. There was a significant reduction in clotting with E15NL in comparison to C15NL (22.8 +/- 17 and 44.1 +/- 22.8 (p = 0.0233), respectively). Similarly, heparin requirements were less in the vitamin-E-coated (E15NL) dialysers, 4, 754 +/- 1,427 vs. 6,011 +/- 856 units (p = 0.0281) and erythropoietin usage was also significantly reduced, 4,630 +/- 2,620 vs. 7,850 +/- 4,069 units (p = 0.049). There was a significant increase in hemoglobin with E15NL compared to C15NL, 115 +/- 10.4 vs. 108 +/- 13.1 (p = 0.0343). When the high-flux dialysers were compared there was a tendency towards less dialyser clotting with the EE15NL compared to F60, though this did not achieve statistical significance (p = 0.0561). We could not demonstrate any significant changes between the different dialysers with regards to PT, PTT, fibrinogen factor 12 activity, protein C, protein S and ATIII. In conclusion, we have shown that the use of vitamin-E-modified dialysers is associated with less clotting in patients with persistent clotting problems. In addition, this was associated with less heparin and erythropoietin requirements.
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PMID:Effect of vitamin-E-modified dialysers on dialyser clotting, erythropoietin and heparin dosage: a comparative crossover study. 1109 92

Hyperleptinemia is also common in chronic renal failure, particularly in CAPD. On the other hand, cardiovascular events related to thrombosis are a predominant cause of death and account also for an important morbidity in uremic patients. Treatment with recombinant human erythropoietin (rHuEPO) may shift the precarious hemostatic balance towards thrombosis. Therefore, the aim of the study was to assess the relationships between leptin and platelet aggregation and some hemostatic parameters in CAPD patients treated with rHuEPO. The study was performed on 15 patients maintained on CAPD given rHuEPO and 13 subjects without rHuEPO therapy served as a control group. Platelet aggregation was studied in both platelet-rich plasma (PRP) and in the whole blood. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) (antigens and activities), von Willebrand factor, trombomodulin, protein C, thrombin activatable fibrinolysis inhibitor (TAFI) and leptin (serum and dialysate) were assayed by using commercially available kits. Patients in both groups studied did not differ significantly with respect to age, BMI, duration of renal replacement therapy, and other hematological and hemostatic parameters studied as well as leptin serum and dialysate leptin. In CAPD patients treated with rHuEPO serum and dialysate leptin significantly correlated with tissue factor pathway inhibitor, protein C, thrombomodulin, ristocetin-induced platelet aggregation in the whole blood and PRP. In CAPD patients not treated with rHuEPO the significant correlations were observed between serum and dialysate leptin and protein C. Positive correlations between platelet aggregation and leptinemia in CAPD patients might indicate that hyperleptinemia could be associated with the cardiovascular disease in dialyzed patients. Leptin might contribute at least in part to the thrombotic complications observed in CAPD patients.
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PMID:Leptin correlates with some hemostatic parameters in CAPD patients. 1237 66

We present the results on Anaemia Management in Fresenius Medical Care Spain dialysis centres as reported by EuCliD (European Clinical Database), evaluating a population of 4,426 patients treated in Spain during the year 2001. To analyse the erythropoietin dose and the haemoglobin levels we divided the population in two groups according to the time with dialysis treatment: patients treated less than six months and patients between six months, and four years on therapy. We compared our results with the evidence based recommendations Guidelines: the European Best Practice Guidelines (EBPG) and the US National Kidney Foundation (NKF-K/DOQI). We also compared our results with those presented by the ESAM2 on 2,618 patients on dialysis in Spain carried out in the second half of the year 2000. We observed that 70% of the population reaches an haemoglobin value higher that 11 g/dl, with a mean erythropoietin (rHu-EPO) dose of 111.9 Ul/kg weight/week (n = 3,700; SD 74.9). However, for those patients on treatment for less than six months, the mean Haemoglobin only reaches 10.65 g/dl (n = 222; SD 1.4). The rHu-EPO was administrated subcutaneously in 70.2% of the patients. About the iron therapy, 86% of the patients received iron treatment and the administration route was intravenous in 93% of the population. The ferritin levels were below 100 micrograms/dl in 10% of the patients and 26.4% showed a transferrin saturation index (TSAT) below 20%. The erythropoieting resistance index (ERI), as rHu-EPO/haemoglobin, has been used to evaluate the response to rHu-Epo, according to different variables. It was observed that the following factors lead to a higher rHu-EPO resistance: intravenous rHu-EPO as administration route, the presence of hypoalbuminemia, increase of protein C reactive, Transferrin saturation below 20% and starting dialysis during the last six months.
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PMID:[Anemia management in haemodialysis. EuCliD database in Spain]. 1251 89

Patients receiving maintenance hemodialysis (HD) present with hemostatic abnormalities, which may be aggravated by comorbid conditions, especially liver disease. The factors that influence plasma levels of thrombomodulin (TM), an initiator of the anticoagulant protein C pathway, and those of tissue factor (TF), which triggers the extrinsic coagulation pathway, were assessed. In 63 HD patients, TM and TF levels were higher than those in healthy controls. In bivariate analysis, TF positively correlated with TM, and both were directly associated with the presence of viral hepatitis B or C marker, serum liver enzymes, use of erythropoietin therapy, hemoglobin levels, and duration of HD therapy, and inversely correlated with body mass index. TF was also positively associated with plasma von Willebrand factor (vWF) antigen, and inversely associated with activated partial thromboplastin time. In multivariate analysis, increased vWF, alanine aminotransferase, and use of erythropoietin independently predicted both TF and TM levels. HD patients with vWF and ALT levels lower than middle, and not treated with erythropoietin had normal TF but increased TM concentrations compared with levels in healthy controls. Increased plasma levels of TM and TF in patients on maintenance HD are surrogates of vascular endothelial injury. Liver disease and use of erythropoietin treatment are also important determinants of these markers, and should be considered in further studies.
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PMID:Tissue factor and thrombomodulin in hemodialysis patients: associations with endothelial injury, liver disease, and erythropoietin therapy. 1465 47

Sepsis with acute organ dysfunction (severe sepsis) results from a systemic proinflammatory and procoagulant response to infection. Organ dysfunction in the patient with sepsis is associated with increased mortality. Although most organs have discrete anatomical boundaries and carry out unified functions, the hematologic system is poorly circumscribed and serves several unrelated functions. This review addresses the hematologic changes associated with sepsis and provides a framework for prompt diagnosis and rational drug therapy. Data sources used include published research and review articles in the English language related to hematologic alterations in animal models of sepsis and in critically ill patients. Hematologic changes are present in virtually every patient with severe sepsis. Leukocytosis, anemia, thrombocytopenia, and activation of the coagulation cascade are the most common abnormalities. Despite theoretical advantages of using granulocyte colony-stimulating factor to enhance leukocyte function and/or circulating numbers, large clinical trials with these growth factors are lacking. Recent studies support a reduction in the red blood cell transfusion threshold and the use of erythropoietin treatment to reduce transfusion requirements. Treatment of thrombocytopenia depends on the cause and clinical context but may include platelet transfusions and discontinuation of heparin or other inciting drugs. The use of activated protein C may provide a survival benefit in subsets of patients with severe sepsis. The hematologic system should not be overlooked when assessing a patient with severe sepsis. A thorough clinical evaluation and panel of laboratory tests that relate to this organ system should be as much a part of the work-up as taking the patient's blood pressure, monitoring renal function, or measuring liver enzymes.
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PMID:The hematologic system as a marker of organ dysfunction in sepsis. 1283 83

Many advances have improved the care of critically ill patients, but only a few have been through the use of pharmaceutical agents. Recently, the US Food and Drug Administration (FDA) approved drotrecogin alfa (activated), or recombinant human activated protein C, for the treatment of patients with a high risk of death from severe sepsis. Drotrecogin alfa (activated) has antiinflammatory, antithrombotic and fibrinolytic properties. When given as a continuous intravenous infusion, recombinant human activated protein C decreases absolute mortality of severely septic patients by 6.1%, resulting in a 19.4% relative reduction in mortality. The absolute reduction in mortality increases to 13% if the population treated is restricted to patients with an APACHE II score greater than 24, as suggested by the FDA. The most frequent and serious side effect is bleeding. Severe bleeds increased from 2% in patients given placebo to 3.5% in patients receiving drotrecogin alfa (activated). The risk of bleeding was only increased during the actual infusion time of the drug, and the bleeding risk returned to placebo levels 24 hours after the infusion was discontinued. Patients treated in the intensive care unit frequently develop anemia, usually severe enough to require at least one transfusion of red blood cells. With the recent discovery of the harmful effects of allogeneic red blood cell transfusions and the increasing shortage of available red blood cell products, emphasis has been placed on minimizing transfusions. Patients who receive exogenous recombinant human erythropoietin maintain higher hemoglobin levels, in spite of requiring fewer transfusions during their stay in the intensive care unit. Recombinant human erythropoietin appears to be effective whether it is given as 300 units/kg of body weight subcutaneously every other day or as 40,000 units subcutaneously every week. Differences in hemoglobin values were not apparent until at least one week of therapy, but they continued to diverge after that initial week. Furthermore, the incidence of adverse events was similar to that of patients receiving placebo and there was no difference in mortality, suggesting that avoidance of blood transfusions did not translate into increased survival. Thus, recombinant human erythropoietin appears to be both safe and effective in treating the anemia found in critically ill patients, but it is less clear that such treatment is cost effective, especially in the higher dose regimens. Hypotension in patients with septic shock is often difficult to correct. Despite enormous dosages of catecholamines, many of these patients continue to have inadequate blood pressures. Inadequate levels of vasopressin have been identified in patients with septic shock, as well as in other patients with hypotension secondary to refractory vasodilatation. Vasopressin is a peptide hormone secreted from the posterior pituitary in response to hyperosmolality, hypovolemia or hypotension. Levels of vasopressin initially rise in patients with septic shock, but as hypotension persists, vasopressin levels fall below normal. Administration of exogenous vasopressin in physiologic dosages significantly increases blood pressure in patients with shock associated with sepsis and other vasodilatory states. This rise in blood pressure is often significant enough that endogenous catecholamines can be decreased and frequently discontinued entirely. Early withdrawal of the vasopressin replacement infusion results in recurrent hypotension. Unfortunately, randomized, blinded, placebo-controlled trials showing improvement in long-term outcomes such as mortality and length of stay are still lacking.
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PMID:New additions to the intensive care armamentarium. 1504 37


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