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)

A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.
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PMID:Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin. 143 39

The effect of subcutaneous administration of recombinant human erythropoietin (rHuEPO) on plasma natural coagulation inhibitors (protein C, protein S, and antithrombin III) was evaluated in 10 uremic patients on continuous ambulatory peritoneal dialysis (CAPD). These patients were commenced on a 16 week-course of twice weekly rHuEPO by the subcutaneous route. The hemoglobin increased significantly from 6.9 +/- 1.3 g/dl to 9.6 +/- 1.9 g/dl after subcutaneous rHuEPO treatment (p less than 0.01) at an average dose of 84 +/- 9 U/kg body wt/week. With rHuEPO therapy, a significant increase in platelet counts was observed, albeit within the normal range. A significant increase in the prothrombin time was demonstrated at 6 weeks after treatment and increased activated partial thromboplastin time was observed at 6 weeks and 16 weeks after rHuEPO administration although these measurements still remained in normal range. CAPD patients have comparable or even higher plasma levels of natural coagulation inhibitors compared with healthy controls supporting our previous findings that patients on CAPD have normal plasma levels due to an effective compensatory production despite peritoneal losses of these proteins with CAPD. No change in either the immunological or the functional activity of these natural coagulation inhibitors was demonstrated with rHuEPO therapy and clinical thrombosis was not observed during and after rHuEPO therapy. We conclude that there is no laboratory evidence of increased risk of thrombogenesis due to reduction of natural coagulation inhibitors with rHuEPO therapy.
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PMID:Effect of subcutaneous administration of recombinant human erythropoietin on plasma protein C, protein S, and antithrombin III levels in patients on continuous ambulatory peritoneal dialysis. 160 9

Thrombotic events occur frequently in myeloproliferative disorders, namely polycythaemia vera and essential thrombocythaemia. Standard diagnostic criteria are designed quite stringent, so that a number of patients could be underdiagnosed. Spontaneous erythroid colonies formation from bone marrow or peripheral blood in the absence of exogenous erythropoietin is considered a reliable index of myeloproliferative disorder even at early stages. Endogenous erythroid colonies (EECs) formation was assessed in 43 patients having recently suffered from venous thrombosis prior to 45 years and without a previous diagnosis of hematological disease favouring thrombosis. A screening for coagulative abnormalities associated with thrombophilia was also carried out: in 5 patients (11.6%) a plasmatic thrombogenic defect was found (quantitative deficiency of antithrombin III, 1 case, protein C, 2 cases, protein S, 1 case, and plasminogen, 1 case). In 10 patients (2 males and 8 females) (23.2%) EECs assay was positive, allowing diagnosis of myeloproliferative disease even though 7 of them did not fulfill standard diagnostic criteria. In the other 3 patients who met the criteria for diagnosis of overt myeloproliferative disease the thrombotic event was the inaugural manifestation. In all these EECs-positive patients thrombosis involved mesenteric and portal veins (n = 4), hepatic veins (n = 3), portal vein (n = 2), mesenteric vein (n = 1). One of them was simultaneously affected from congenital protein C deficiency. Thus latent or atypical forms of myeloproliferative disease as well as the overt stages were the most frequent recognized cause of splanchnic venous thrombosis, accounting for 55% of the cases of our series. On the contrary no EECs-positive subject was found among the 25 patients with other sites of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematological causes of venous thrombosis in young people: high incidence of myeloproliferative disorder as underlying disease in patients with splanchnic venous thrombosis. 164 18

An increased incidence of fistula thrombosis has been reported in haemodialysis patients treated with recombinant human erythropoietin (rHuEpo). The present study sought to investigate this problem by measuring fistula blood flow, blood viscosity, and a variety of tests of coagulation and haemostasis in a group of ten haemodialysis patients treated with rHuEpo. Fistula blood flow did not alter during the first 12 months of rHuEpo despite a significant increase in whole-blood viscosity. Bleeding time improved in all ten patients after 4 months of therapy, and this improvement was maintained at 12 months. There were no significant changes in one-stage prothrombin time, kaolin cephalin clotting time, whole-blood clotting time, prothrombin consumption index, plasma fibrinogen factor VII, factor VIII, antithrombin III, or platelet aggregability to ADP over the first 4 months of rHuEpo. In contrast, protein C decreased from 84.3 to 66.4% (P less than 0.01) and protein S from 124.1 to 68.3% (P less than 0.001) over the first 4 months. By 8 and 12 months, the concentrations of these substances had returned to pretreatment values. The levels of protein C and S attained at 4 months are known to predispose to thrombosis, and it is possible that this effect may contribute to the increased incidence of fistula thrombosis observed in haemodialysis patients treated with rHuEpo.
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PMID:Coagulation studies and fistula blood flow during erythropoietin therapy in haemodialysis patients. 132 49

A natural antibody with binding specificity for recombinant tissue-type plasminogen activator (t-PA) expressed in mouse C127 cells was present in almost all disease-free humans and patients with thrombotic disease examined. This antibody was specific for a carbohydrate, alpha 1-3-linked galactose residue, and was isolated by affinity chromatography using Synsorb 90 coupled with the glycosidic epitope Gal alpha 1-3Gal beta 1-4Glc-R as an immunoadsorbent. The evaluation of various glycoproteins for ability to bind the purified antibody in ELISA demonstrated that not only recombinant t-PA from C127 cells but also recombinant erythropoietin (EPO) and recombinant protein C produced in C127 cells have alpha 1-3-linked galactose residues on their sugar side chains. This anti-alpha-galactosyl antibody also interacted with natural t-PA from human vascular trees (vascular t-PA) and placenta (placenta t-PA), but not to melanoma t-PA, recombinant t-PA, EPO or protein C expressed in Chinese hamster ovary (CHO) cells.
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PMID:Specificity of human natural antibody to recombinant tissue-type plasminogen activator (t-PA) expressed in mouse C127 cells. 211 46

We studied 37 hemodialysis patients, treated with erythropoietin (EPO), prior to and upon reaching target Hb and after 3 months at steady state Hb levels. Our aim was to analyze the effects of EPO on markers of all stages of coagulation and anticoagulation during a standardized hemodialysis procedure upon reaching target Hb as well as long term effects of a stable Hb. The Hb rose from 82 +/- 9 to 111 +/- 12 g/L at target Hb (p < 0.0001) and was 108 +/- 15 g/L after 3 months of steady state. The heparin dose was individually titrated, using a whole blood activated coagulation time method (WBACT) and kept constant during the first phase of the study. The titrated heparin dose increased significantly at target Hb and this increase persisted after 3 months at steady state. Accordingly the increase in WBACT decreased significantly. There was a significant increase in platelets at target Hb and this increase persisted at steady state. beta-thromboglobulin increased significantly at target Hb and this increase persisted after 3 months at steady state. Platelet factor 4 was unchanged throughout the study period. Inhibitors of plasma coagulation: AT III, protein C and total and free protein S were unchanged throughout the study period. There was no changes in indicators of intravascular coagulation: TAT, fibrin monomers or FPA throughout the study period. There was no FPA generation during dialysis. The residual blood volume in the dialyzer was unaffected throughout the study period. There was a significant decrease in D-dimers at target Hb and after 3 months at steady state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of erythropoietin treatment on the coagulation system during standardized hemodialysis. 760 81

Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. Therefore in the present study an attempt has been made to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment. 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week. Bleeding time was shortened significantly as early as after 1 week of the therapy, whereas hematocrit and hemoglobin increased after 2 weeks. These changes lasted throughout the study. Only a transient rise in platelet count, collagen-induced platelet aggregation, beta-thromboglobulin and VIII:C activity were observed during therapy relative to baseline values. ADP- and arachidonic acid-induced platelet aggregation seemed to be unaffected by rHuEPO treatment, whereas a gradual and progressive enhancement in platelet aggregation in response to ristocetin was found, starting from the 2nd week of the therapy. It lasted throughout the study and correlated inversely with the bleeding time and positively with a rise in both blood and platelet serotonin. rHuEPO did not alter plasminogen, fibrinogen, platelet factor 4, alpha 2 macroglobulin levels, protein C activity and euglobulin clot lysis time. A decline in protein C and S concentrations and antithrombin III activity observed during the therapy were counterbalanced by a fall in the activity of alpha 2 antiplasmin, C1 esterase inhibitor and plasminogen activator inhibitor. It is concluded that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy.
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PMID:A study of platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin in hemodialyzed patients under erythropoietin therapy. 774 May 5

Twenty chronic hemodialysis patients with renal anemia (hematocrit < 25%) received recombinant human erythropoietin (40 IU/kg body weight 3 x weekly) intravenously after each dialysis. Prior to and at 4, 8 and 12 weeks after commencement of erythropoietin therapy, hematocrit together with hemostasis and microhemolysis parameters were determined. There were significant increases in hematocrit, platelet count and platelet retention, but a significant fall in the initial clearly prolonged bleeding time. Free plasma hemoglobin likewise increased. Conversely, lactate dehydrogenase, prothrombin time, fibrinogen, antithrombin III activity, protein C activity and protein S concentration were all unaltered. The positive effect on bleeding time and platelet retention is most probably caused by an increase in adenosine diphosphate due to the hematocrit-dependent rise in the blood shear stress via physiologic microhemolysis (raised free plasma hemoglobin).
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PMID:Influence of recombinant human erythropoietin on hematological and hemostatic parameters with special reference to microhemolysis. 777 78

Treatment with recombinant human erythropoietin (rhEPO) for the anemia of end-stage renal disease has been associated with thrombotic complications. To detect prothrombotic changes in autologous blood donors given 500 U/kg rhEPO subcutaneously (twice weekly during a 3-week period), changes in variables of hemostasis and fibrinolysis and in blood rheology before and at the end of treatment were investigated. In 21 patients, platelet count increased from 272 +/- 55 x 10(9)/L to 313 +/- 55 x 10(9)/L (p < 0.05). Although activated partial thromboplastin time and protein C antigen decreased significantly during rhEPO treatment, these changes remained within normal ranges. No changes in the hemostatic variables prothrombin time, fibrinogen, factor V, von Willebrand factor antigen, antithrombin III activity, protein S antigen, and prothrombin fragments F 1 + 2 were found. Measurements of plasminogen activity, alpha 2-antiplasmin activity, tissue plasminogen activator, and plasminogen activator inhibitor-1, representing variables of fibrinolysis, were normal and constant during the study. In 5 patients no changes in red cell deformability and whole blood viscosity, corrected for differences in hematocrit, were observed. Plasma viscosity showed a slight but clinically not relevant increase in 4 out of 5 patients. The absence of evident (pro)thrombotc changes in this study confirms the safety of high-dose rhEPO therapy in autologous blood donors, who donate 2 units (i.e., 2 x 450 ml) of blood.
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PMID:The effect of recombinant human erythropoietin on hemostasis, fibrinolysis, and blood rheology in autologous blood donors. 803 97

To clarify the effects of correction of anemia with recombinant human erythropoietin (rHuEPO) on blood coagulation, fibrinolysis and endothelium, these markers were examined in 19 regular hemodialysis patients before and 4, 8, 12 weeks on rHuEPO treatment, and 5 weeks after the end of treatment. Hematocrit significantly increased from 22.8 +/- 2.0 to 31.1 +/- 2.7% at 12 week (p < 0.001). Coagulation and fibrinolysis markers did not show significant changes except for minor and transient alteration of protein C, thrombin-antithrombin III complex and alpha 2-plasmin inhibitor plasmin complex (PIC) throughout the treatment. Endothelin and 6-keto-prostaglandin F1 alpha (PGF1 alpha) significantly increased from 6.1 +/- 4.5 to 14.2 +/- 2.9 pg/ml (p < 0.001) and from 51.9 +/- 14.7 to 66.5 +/- 18.5 pg/ml (p < 0.05) at 12 week, respectively. Human atrial natriuretic peptide (ANP) significantly decreased from 277.9 +/- 88.6 to 179.4 +/- 73.3 pg/ml at 12 week (p < 0.001). Endothelin and PGF1 alpha after 6 month treatment with rHuEPO showed high values as same as those of 12 weeks. These data suggests that rHuEPO therapy did not affect blood coagulation and fibrinolysis, however exerts effects on the endothelium. Changes in endothelial function after rHuEPO may be one of the pathogenetic mechanisms of hypertension and may contribute to a decrease in thrombotic complications.
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PMID:[Changes in endothelial vasoactive substances and blood coagulation and fibrinolysis functions under recombinant human erythropoietin therapy in hemodialysis patients]. 831 81


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