Fibrinolysis in chronic renal failure, dialysis and renal transplantation.

The best known function of the fibrinolytic system is its ability to dissolve blood clots. The key enzyme of fibrinolysis, plasmin, is formed by conversion from plasminogen through the action of activators, the most important of which is tissue type plasminogen activator (tPA). Low levels of tPA or excessive levels of plasminogen activator inhibitor-I (PAI-I) cause hypofibrinolysis, causally related to the development of atherosclerosis and associated thrombotic complications, as well as with the development of venous and arterial thrombosis. A chronic decrease in renal function leads to hypofibrinolysis due primarily to low levels of tPA. Hypofibrinolysis is present both in patients treated by long-term hemodialysis and by peritoneal dialysis. The hemodialysis procedure acutely raises the plasma levels of tPA, primarily as a result of the bioincompatibility of materials in the extracorporeal circuit. In peritoneal dialysis, dialysis solution dwell time is associated with an increase in PAI-I levels in the abdominal cavity. Fibrinolysis defects occur also in renal transplant recipients. In transplant patients, the main abnormality is also hypofibrinolysis which, however, unlike the situation with the other methods of renal replacement therapy, is secondary to a rise in PAI-I. A role in the increase of the plasma levels of PAI-I in transplant patients is played by steroid- and cyclosporine-based immunosuppression, most likely by metabolic disorders such as insulin resistance or dyslipoproteinemia, and by genetic factors. Animal experiments with chronic rejection have shown abnormalities in local fibrinolysis in the graft, particularly increased PAI-I expression. Fibrinolysis defects may contribute to an early and frequent development of atherosclerosis in patients with chronic renal failure, to chronic dysfunction of the renal transplant, or to peritoneal fibrosis and peritoneal catheter obstruction in patients on peritoneal dialysis. The exact role of hypofibrinolysis in the development of these complications, and the potential for modulating it, warrant further research.

The effect of heparin rinse on the biocompatibility of continuous veno-venous hemodiafiltration.

UNLABELLED: The aims of our cross-over randomized study were (1) to assess hemostasis in patients with acute renal failure (ARF) and (2) to determine whether or not the generally recommended heparin rinse of the extracorporeal circuit (ECC) prior to the procedure affects thrombogenicity, complement activation, and leukocyte count in blood during continuous venovenous hemodiafiltration (CVVHDF). Eleven critically ill ARF patients were treated, in random order, using CVVHDF in postdilution setup following ECC rinse with saline (A) with heparin at a concentration of 2,000 IU/L (10 procedures), (B) with heparin at a concentration of 10,000 IU/L (7 procedures), and (C) without heparin (9 procedures). Except for the rinse, anticoagulation therapy did not differ in individual patients during the procedures. Blood was withdrawn before, and at minutes 15, 60, and 360 invariably at diafilter inlet and outlet. Compared with healthy individuals, patients showed lower blood thrombocyte counts (153 vs 233*10(9)/L, p<0.01, arithmetic means, Student's t test), longer aPTT (44 vs 36 s, p<0.05), higher plasma levels of heparin (0.1 vs 0.0 U/mL, p<0.05), D-dimer (1129 vs 36 ng/mL, p<0.001) and beta-thromboglobulin (BTG) (159 vs 37 U/mL, p<0.001) prior to CVVHDF. The comparison of procedures with different rinsing technique did not reveal any significant difference in their effects on blood thrombocyte and leukocyte counts, aPTT, plasma levels of heparin, BTG, thrombin-antithrombin III complexes, D-dimer, or the C5a complement component. CONCLUSIONS: (1) Patients indicated for CVVHDF show impaired hemostasis involving thrombocytes, coagulation, and fibrinolysis, (2) no beneficial effect of heparin rinse on CVVHDF ECC thrombogenicity, complement activation or blood leukocyte counts was demonstrated.

The effects of a polyacrylonitrile membrane and a membrane made of regenerated cellulose on the plasma concentrations of erythropoietin during hemodialysis.

In vitro studies have shown that some dialysis membranes significantly adsorb erythropoietin (EPO), a fact that might have an effect on anemia in long-term hemodialysis (HD) patients and on anemia treatment with recombinant human EPO. The purpose of the study was to determine whether the ability of adsorption demonstrated in vitro also has an effect on EPO concentrations in vivo. In a crossover study, the plasma concentrations of EPO were examined in 11 patients on chronic HD during HD using a polyacrylonitrile (AN69) membrane (high in vitro adsorption) plus EPO administered subcutaneously after the HD session, HD using a Cuprophan membrane (low in vitro adsorption) plus EPO administered subcutaneously after the HD session, HD using an AN69 membrane plus EPO administered subcutaneously after the HD session plus EPO administered intravenously immediately before HD, or HD using a Cuprophan membrane plus EPO administered subcutaneously after the HD session plus EPO intravenously immediately before HD. The intradialysis plasma concentrations of EPO (not detectable in the dialysate) determined at the dialyzer inlet and outlet at Minutes 5 and 240 of the procedure did not differ significantly after its subcutaneous administration from its predialysis concentrations with either the Cuprophan or AN69 membrane. A comparison of EPO concentrations between AN69 and Cuprophan did not reveal marked differences either. The course of concentrations after additional EPO intravenous administration was similar with no statistically demonstrable difference between the 2 membranes. In conclusion, under clinical conditions, AN69 and Cuprophan membranes do not differ in their effects on plasma EPO concentrations. The differences in EPO adsorption between AN69 and Cuprophan, demonstrated in vitro, do not seem to be of clinical importance.

Tissue-type plasminogen activator (tPA) and its inhibitor (PAI-1) in patients treated with continuous ambulatory peritoneal dialysis.

AIM: To establish whether the values of two key enzymes of fibrinolysis, tissue-type plasminogen activator (tPA) and its inhibitor (PAI-1), differ between patients treated with continuous ambulatory peritoneal dialysis (CAPD) and healthy volunteers and whether plasma and dialysate tPA and PAI-1 values vary during one exchange of dialysis solution. METHODS: A total of 11 patients with chronic renal failure, treated with CAPD during the peritoneal equilibration test (in addition with blood sampling at time 0), and a control group of 11 healthy volunteers were examined. To identify the factors involved in the changes in tPA and PAI-1, 9 CAPD patients were subsequently monitored, in a crossover manner, during dialysis with solutions of 1.36 and 3.86% dextrose and off dialysis. RESULTS: Compared with healthy individuals, CAPD-treated patients showed a significantly lower tPA activity (0.39 vs. 0.81 IU/ml, p < 0.05). Changes in plasma fibrinolysis during one exchange of dialysis solution were characterized mainly by a decrease in PAI-1 concentrations and activities caused by the circadian rhythm of fibrinolysis. To explain, in the crossover part of the study, the values of plasma PAI-1 antigen at time 0 (07.00 h) and at time 2 (09.00 h) were 9.4 versus 6.5 ng/ml with the 1.36% solution (p < 0.05), 8.2 versus 4.9 with the 3.86% solution (p < 0.05), and 14.1 versus 9.1 ng/ml off dialysis (p < 0.01). Compared to baseline (0 ng/ml with 1.36 as well as 3.86% solutions), the levels of PAI-1 antigen in dialysis solution rose, apparently due to local production in the peritoneal cavity, to 0.5 ng/ml (p < 0.05) with the 1.36% solution, to 0.7 (p < 0.05) with the 3.86% solution after a 2-hour dwell time, and to 1.6 (p < 0.05) and 1.3 ng/ml (p < 0.05) after a 4-hour dwell time, respectively. Hence, the different dextrose levels in the dialysis solutions had no effect on the monitored parameters of fibrinolysis. CONCLUSION: The lower activity of plasma tPA, and the increase in PAI-1 levels in dialysis solutions may contribute to the development of thromboses in CAPD patients and to fibrin formation on the peritoneal surface with consequences such as peritoneal fibrosis.

[The effect of dialysis solutions containing amino acids on the nutritional status of patients treated with continuous ambulatory peritoneal dialysis]. / Vliv dialyzacního roztoku s obsahem aminokyselin na nutricní stav nemocných lécených kontinuální ambulantní peritoneální dialýzou (CAPD).

BACKGROUND: In the patient population which is subjected to haemodialysis or peritoneal dialysis is a high prevalence of protein-energy malnutrition which independently on the causal factor causes a deterioration of their prognosis. To influence protein nutrition in patients on peritoneal dialysis Nutrineal was developed, i.e., a dialysis solution using as an osmotic agent a 1.1% amino acid mixture instead of glucose used as a rule. The objective of the present study was to evaluate the effect of its administration on some nutritional indicators in patients treated by continuous ambulatory peritoneal dialysis (CAPD) and to assess its tolerance. METHODS AND RESULTS: The authors investigated eight patients aged 45.5 years (29-78 years, median, minimal and maximal value), treated for 19.9 (5-42) months by CAPD. For a period of four weeks Nutrineal was administered once a day instead of glucose based solution to patients without diseases complicating nutrition, with a serum albumin concentration (ALB) below 35 (20-34) g/l. Before treatment and after its termination an anthropometric examination was made, the rate of protein catabolism was examined (PCR), plasma concentrations of total proteins were assessed, as well as ALB, transferrin (TRF) and 14 free amino acids substituted by the dialysis solution. For statistical comparison the paired Wilcoxon test was used. As compared with the baseline value of 0.83 g/kg/24 h after treatment a significant increase of PCR was recorded--to 0.96 g/kg/24 h (p < 0.05) as well as a significant increase of the urea concentration from 18.4 (10.9-34.8) mmol/l to 26.7 (19.6-33) mmol/l (p < 0.05). The value of phosphorus declined significantly from 2.25 (1.6-2.6) to 1.9 (0.9-2.5) mmol/l (p < 0.05). No significant difference was recorded in the anthropometric findings and in concentrations of total proteins, ALB, TRF and amino acids. CONCLUSIONS: Four weeks administration of a solution with amino acids raised significantly the PCR which may be indirect evidence of an anabolic effect and it reduced plasma phosphates which participate in uraemic toxicity. The solution was well tolerated by the patients. Final evaluation of the values of the solution containing amino acids calls for long-term and controlled studies.

A clinical study to assess the effect of heparin in dialyzer rinsing solutions.

The solution usually recommended for rinsing the blood side, which is an indispensable step in preparing a dialyzer for hemodialysis (HD), contains saline and heparin. The heparin used for rinsing is said to reduce the thrombogenic properties of the dialysis membrane and, hence, also the need for systemic heparinization during the whole procedure. The aim of our study was to establish whether this postulate also applies to polysulphone steam-sterilized dialyzers. To do so, 16 patients on long-term dialysis were randomized into two groups of eight. One group was subsequently treated with polysulphone low-flux dialyzers (F6HPS), the other with polysulphone high-flux dialyzers (F6OS). Both groups were examined, in a crossover manner during HD using a dialyzer previously rinsed with 1000 ml of saline plus 2,000 IU of heparin, and during HD using a dialyzer previously rinsed with 500 ml of saline without heparin. Except for the rinsing, HD conditions were completely identical. Blood obtained before HD, and at 15, 60 and 240 min of HD at the dialyzer inlet, was used to determine the activated partial thromboplastin time (to test heparinization control), the thrombin-antithrombin III complex (ELISA, to evaluate coagulation system activation), platelet factor 4 (ELISA, a substance with antiheparin activity), and platelet count. None of the above parameters showed, at any of the collecting intervals, a statistically significant difference between HD with and without heparin with a reduced volume of rinsing solution, or between HD using low- and high-flux dialyzers. It is concluded that heparin used to rinse polysulphone dialyzers before HD has no effect on blood coagulation or on the need for heparin during the procedure.

Hemocompatibility in hemodialysis and erythropoietin therapy.

Two studies designed to investigate the effect of recombinant human erythropoietin (rHuEPO) treatment of anemia in chronic dialysis patients on hemocompatibility were conducted. Study 1, whose main aim was to establish whether treatment with rHuEPO enhances coagulation activation during dialysis, included 15 patients before rHuEPO therapy at a mean hematocrit (HCT) of 22.3% and then during therapy at a HCT of 29.3%. The plasma concentrations of the thrombin-antithrombin III complex were not higher during rHuEPO therapy than before it when performing hemodialysis with a Cuprophan membrane. No significant difference was demonstrated either in the values of activated clotting times (Hemochron), thrombocyte or white blood cell counts (Coulter S+II), or in plasma C5a concentrations (ELISA) established during dialysis sessions before and during rHuEPO therapy. In Study 2, which focused primarily on the question of whether or not rHuEPO therapy increases thrombocyte activation during hemodialysis, 8 patients on chronic dialysis were examined both before therapy at a mean HCT value of 22.1% and during rHuEPO therapy at a HCT of 31.5%, invariably during dialysis with either a Cuprophan or polyacrylonitrile (AN69HF) membrane. The plasma concentrations of beta-thromboglobulin (ELISA) did not differ between the examinations made during rHuEPO and before rHuEPO therapy; however, statistically significant differences were found between dialysis sessions involving Cuprophan and AN69HF membranes. No significant difference between examination before and during rHuEPO was demonstrated in activated clotting time nor thrombocyte and white blood cell counts in this study either. The authors conclude that rHuEPO therapy does not enhance coagulation activation during hemodialysis, does not have an effect on thrombocyte activation, and does not influence complement activation and changes in white blood cell counts.

[The effect of erythropoietin on fibrinolysis in hemodialyzed patients]. / Vliv erytropoetinu na fibrinolýzu u hemodialyzovaných nemocných.

BACKGROUND: According to some data treatment with human recombinant erythropoietin (EPO) in dialyzed patients leads to a more frequent occurrence of thromboses. One of the possible causes could be reduced fibrinolysis. The objective of the present study was to assess the effect of EPO in dialyzed patients on two key enzymes of fibrinolysis, i.e. the tissue activator of plasminogen (t-PA) and the inhibitor of the plasminogen activator (PAI-1). METHODS AND RESULTS: In eight patients dialyzed for prolonged periods examined under otherwise equal conditions before EPO treatment (haematocrit 22.9%--median value) and after 9.5 weeks of EPO treatment (Recormon, s.c.) when a haematocrit of 30% was achieved, activities (chromogenic substrates) and antigens (ELISA of t-PA and PAI) were assessed. All examinations were made before and after venous occlusion. Between examinations made before treatment and during EPO treatment no significant difference was found in the t-Pa activities assessed before venous occlusion (before EPO 0.9 IU/ml--during EPO 0.6, not significant Wilcoxon's paired test) nor after venous occlusion (3.2-3.8, n.s.). PAI activities before venous occlusion (10.9 U/ml-18.3, n.s.) and after venous occlusion (9.7-11.5, n.s.) did not differ significantly either, when comparing values before and in the course of EPO treatment. Similarly as in the case of activities in antigens t-PA and PAI no difference was found before and during EPO. CONCLUSIONS: No effect of EPO on the investigated indicators of fibrinolysis was found. The results of the presented investigation are at variance with the idea that EPO reduces fibrinolysis in dialyzed patients and thus contributes to the development of thrombotic complications.

[Hemostasis in patients with acute leukemia treated with high doses of cytosine-arabinoside: the effect of chemotherapy and infectious complications on hemostasis]. / Hemostáza u nemocných s akutní leukémií lécených vysokými dávkami cytosin-arabinosidu: vliv chemoterapie a infekcních komplikací na hemostázu.

Haemostatic parameters were studied in 12 adult patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in complete remission using high-dose cytosine arabinoside regiments together with with other drugs. Increased tissue plasminogen activator (t-PA:Ag) antigen 4 hours after AraC application (p < 0.05) as well as increased levels of plasminogen activator inhibitor activity (PAI) (p < 0.05) and fibrinopeptide A (FPA) antigen (p < 0.05) were observed on day 2. All patients during bone marrow aplasia suffered from infectious complications (7 from sepsis and 5 from fever of undetermined origin). During that period of infection the increased levels of FPA on day 21 (p < 0.05), PAI on days 15 and 21 (p < 0.05) and fibrinogen on day 21 (p < 0.05) as well as decreased values of antithrombin III (p < 0.05) on day 21 and protein C on day 15 (p < 0.05) were measured. t-PA:Ag, plasminogen, alpha 2 antiplasmin and fibrin(ogen) degradation products were within normal throughout infectious complications. None of the patients experienced clinically manifest thrombotic complication. Though the results demonstrate that changes found were not clinically important (even if they were statistically significant), and that haemostasis was compensated as well as that thrombosis was not serious problem, authors recommend routine haemostasis monitoring in acute leukaemia patients, especially at diagnosis, in association with chemotherapy and during infectious complications.

The influence of induction chemotherapy and remission status on haemostasis in patients treated for acute myeloid leukaemia.

Haemostatic parameters were studied in 31 adult patients treated for acute myeloid leukaemia (AML) using the 3 + 7 regimen. Lower values of antithrombin III (AT-III), alpha 2-antiplasmin (alpha 2AP) and plasminogen were observed on days 8 and 14 (P < 0.05). Fibrinopeptide A (FpA) levels were higher at diagnosis (P < 0.05), increased again during chemotherapy on days 4 and 8 and eventually returned to the normal range. Tissue plasminogen activator, plasminogen activator inhibitor, protein C and fibrin(ogen) degradation products were normal throughout the period of observation. Complete remission (CR) was achieved in 19 of 31 patients (61%). In order to compare haemostatic changes in CR patients with those in refractory cases, patients were divided into two groups. In patients with refractory AML (n = 12) AT-III, plasminogen and alpha 2 AP were significantly lower than in those in CR. FpA levels were increased in all patients at diagnosis. This elevation progressed in both groups during chemotherapy (on days 4 and 8) and then normalized only in patients in CR. However, in resistant patients, higher FpA values persisted or even increased further on day 14. The fact that none of our patients suffered from clinically manifest thrombotic complications suggested that haemostasis was well compensated and the observed changes were of no clinical importance, even if they were significant statistically.

[Hypofibrinolysis after venous occlusion in patients treated with long-term hemodialysis]. / Hypofibrinolýza po zilní okluzi u nemocných lécených dlouhodobou hemodialýzou.

BACKGROUND: Haemodialysis patients with chronic renal failure suffer not only from thromboses of the vascular access but frequently also from atherosclerosis with thrombotic complications. Knowledge of the etiopathogenesis of thrombotic complications in haemodialysis patients are incomplete. The aim of the present study was to evaluate fibrinolysis at the level of plasminogen activation under conditions of a dynamic test, using methods which reflect sensitively and specifically the activity of the tissue-type plasminogen activator (t-PA) and the activity of the inhibitor of the tissue-type plasminogen activator (PAI-1). METHODS AND RESULTS: The group of examined subjects was formed by 16 patients (9 men and 7 women, mean age 42 years, range 26-63) who suffered from chronic renal failure (causes: 9x chronic glomerulonephritis, 6x interstitial nephritis, 1x polycystic kidneys) treated by long-term haemodialysis on average for 52 (20-110) months; the control group of 11 healthy volunteers was very close as regards age distribution. t-PA and PAI-1 were examined after stimulation by venous occlusion (VO). In healthy subjects VO significantly raises the t-PA activity (first value before, second after VO: t-PA 0.81-2.19 IU/ml, p < 0.01), specific t-PA activity (0.19-0.31 IU/ng, p < 0.05) and t-PA/PAI (0.06-0.24 IU/U, p < 0.01, decreases PAI activity (11.80-10.98 U/ml, p < 0.05) and specific PAI activity (0.52-0.40 U/ng, p < 0.01). In the group of haemodialysis patients VO did not change significantly the t-PA activity (p = NS), the specific t-PA activity (p = NS), nor the ratio of t-PA/PAI (p = NS); the PAI declined significantly (13.78-10.65 U/ml, p < 0.05), similarly as the specific PAI activity (0.97-0.65 U/ng, p < 0.01). From comparison of the results of fibrinolysis from healthy and dialysis subjects ensues that the response to VO in dialysis patients differs from that in healthy subjects. CONCLUSIONS: Dialysis patients have impaired fibrinolysis manifested by a lacking rise of activity of the plasminogen tissue activator after stimulation by venous occlusion. The small rise of t-PA activity after venous occlusion can contribute to the development of thrombotic complications in haemodialyzed patients.

Clinical study of high-flux cuprammonium rayon hemodialysis membranes.

The aim of this crossover clinical study was to gain basic information on the hemocompatibility and effectiveness of recently developed high-flux membranes made of cuprammonium rayon with ultrafiltration coefficients of 10, 17, and 19 ml/mm Hg/h (S12W, SU12W, and SS12W dialyzers, respectively), and to identify any possible differences from a conventional membrane made of the same material with an ultrafiltration coefficient of 6 ml/mm Hg/h (C12W dialyzer). All the tested membranes led to an abrupt drop in leukocyte count in the initial phase of hemodialysis. In high-flux membranes, C5a anaphylatoxin would pass into the dialysate, but mean C5a anaphylatoxin concentrations in the dialysate were lower by orders of magnitude than its plasma concentrations, which behaved, in high- and low-flux membranes alike, typically of those made of nonsubstituted cellulose with no intermembrane differences. As judged by the concentrations of the thrombin-antithrombin III complex, the coagulation system was activated--again, without differences between membranes. The reduction rates for urea, creatinine, and phosphates were comparable for all the tested membranes. Compared with baseline, the post-dialysis serum concentrations of beta 2-microglobulin in high-flux membranes, unlike the low-flux membrane, were significantly lower. We conclude that there are no significant differences between the tested high- and low-flux membranes made of cuprammonium rayon in the monitored hemocompatibility parameters, and that high-flux membranes are capable of reducing serum beta 2-microglobulin concentrations.

[The significance of plasminogen activator inhibitor 2 in patients with hematologic malignancies]. / Význam inhibitoru aktivátoru plazminogenu 2. typu u nemocných s hematologickými nádory.

The authors investigated the incidence of the plasminogen activator inhibitor-2 (PAI-2) in 88 patients with haematological tumours. In four patients (4.5%) an elevated PAI-2 level was found: in patient (no. 1) with non-differentiated leukaemia which developed as a result of transformation of myelodysplastic syndrome, in a female patient (no. 2) with non-differentiated blastic crisis of chronic myeloid leukaemia, in a female patient (no. 3) with acute monocytic leukaemia (M5) and in a pregnant female (patient no. 4) with a malignant lymphogranuloma. In none of the other patients with another type of acute myeloid leukaemia or other haematological tumours PAI-2 was detected. High PAI-2 levels after successful cytostatic treatment and attainment of complete remission reached normal levels, during a relapse high PAI-2 levels were recorded again. The authors assume that the presence of PAI-2 may suggest a monocytic origin of the cells which produce it. They conclude also that its value may reflect the activity of the disease with high levels during presentation or relapse of the disease and a drop or disappearance of PAI-2 after successful treatment and achieved remission.

[The effect of erythropoietin therapy on biocompatibility in hemodialysis]. / Vliv lécby erytropoetinem na biokompatibilitu pri hemodialýze.

In order to evaluate the treatment with erythropoietin (EPO) on selected indicators of biocompatibility the authors examined 8 patients dialyzed for prolonged periods before treatment (HTK = 0.23, median), during EPO treatment (Recormon, administered by the s.c. route, HTK = 0.28) in the course of 4-hour haemodialysis on dialyzers with a Cuprophan membrane. The examination before and during treatment was made under equal conditions. Heparinization was also equal despite the fact that during EPO in four patients the residual blood volume in the dialyzer was increased. Comparison of the results before treatment and during EPO treatment did not reveal at any of the collection times (before dialysis, during the 15th, 10th, 60th and 235th minute of the procedure significant differences in the number of leucocytes, plasma concentrations of the C5a complement component, number of thrombocytes and activated coagulation times. Plasma concentrations of the thrombin-antithrombin III complex were in EPO during the 60th minute of haemodialysis significantly lower (p < 0.05) than before EPO. The authors conclude that EPO treatment does not have a significant effect on changes in the number of leucocytes in blood during haemodialysis nor on the activation of complement by an alternative way. EPO does not lead to a greater activation of the coagulation system during haemodialysis; the lower concentration of the thrombin-antithrombin III complex suggests the opposite. Explanation of this finding, similarly as detection of the cause of the increased residual blood volume in some patients, calls for further investigation.

[Clinical study of biocompatibility of dialysis membranes made from non-modified and modified cellulose]. / Klinická studie biokompatibility dialyzacních membrán z nesubstituované a substituované celulózy.

Basic biocompatibility parameters of dialysis membranes made of non-substituted regenerated cellulose (NRC) and cellulose membranes with hydroxyl groups substituted, to a higher (H) or lower (L) degree, by dl-ethyl-amino-ethyl groups (DEAE), or by acetate (CA) were investigated in a 16-week clinical study, involving 10 long-term haemodialysis patients. In the 15th minute of dialysis, the decrease in blood leukocyte count, while using NRC (0.24 +/- 0.03 of baseline value, arithmetic mean +/- SEM) was deeper compared with that seen in DEAE-L (0.88 +/- 0.10, p < 0.001), in DEAE-H (0.79 +/- 0.10, p < 0.01), and in CA (0.73 +/- 0.05. p < 0.05). In the 15th minute of the procedure, C5a concentrations, reflecting complement activation, were higher in NRC (4.4 +/- 0.51 micrograms/L) than in DEAE-L (1.41 +/- 0.22, p < 0.001), in DEAE-H (1.68 +/- 0.47, p < 0.01), and in CA (1.68 +/- 0.22, p < 0.01). Activated clotting times were, in the 10th minute of the procedure, significantly longer in NRC (2.94 +/- 0.37 of baseline value) than in DEAE-H (1.74 +/- 0.10, p < 0.05) and, by the end of dialysis, the difference between these membranes (NRC: 1.47 +/- 0.21, DEAE-H: 0.85 +/- 0.08, p = 0.07) was close to the level of statistical significance. The authors conclude: 1. Substitution of the hydroxyl groups of regenerated cellulose reduces the decrease in leukocyte count and complement activation in the initial phase of haemodialysis. 2. At the same time, substitution by DEAE groups may raise thrombogenicity, as indicated by the shorter activated clotting times.(ABSTRACT TRUNCATED AT 250 WORDS)

[Results of studies of indicators of hemostasis in hemodialyzed patients during administration of 1-deamino-8-D-arginine vasopressin]. / Výsledky vysetrení nekterých ukazatelu hemostázy u hemodialyzovaných nemocných pri podání 1-deamino-8-d-arginin vasopresinu.

The fibrinolytic activity (FA) evaluated according to the euglobulin clot lysis time was in haemodialyzed patients (3.0 +/- 0.2 arb. u.) lower than in patients with chronic renal failure treated by conservative methods (4.7 +/- 0.6, p less than 0.05) and than in healthy subjects (4.2 +/- 0.4, p less than 0.05). After stimulation by intravenous administration of 1-deamino-8-D-arginine vasopressin the FA in haemodialyzed patients rose to (4.5 +/- 1.6), less than in conservatively treated (14.1 +/- 2.1, p = 0.06) and than in healthy subjects (18.2 +/- 3.9, p less than 0.001). By using specific methods it was proved that the inadequate rise of FA in haemodialyzed patients after stimulation is conditioned by a defect of the release of the plasminogen tissue activator from the vascular wall. Contrary to healthy subjects (7.0 +/- 1.3 vs. 16.7 +/- 2.3 ng/ml, p less than 0.01) is plasma concentration in haemodialyzed subjects (5.3 +/- 0.5 vs. 7.9 +/- 0.8, NS) did not increase significantly. Repeated examinations of some of the haemodialyzed patients revealed that almost 20 months of regular haemodialysis do not lead to further changes of basal (2.9 +/- 0.3 vs. 2.8 +/- 0.2) nor stimulated (4.2 +/- 0.5 vs. 4.8 +/- 0.9) FA. Basal plasma concentrations of the von Willebrand factor were in the dialyzed patients (89.1 +/- 8.8%) higher than in healthy subjects (67.2 +/- 4.4, p less than 0.05). After stimulation the concentration of the von Willebrand factor increased significantly in healthy subjects (99.1 +/- 4.3, p less than 0.01), but not in dialyzed patients (82.9 +/- 3.1, NS), obviously due to the pathological reactivity of their vascular wall. The above findings may be associated with thromboses and atherosclerosis in patients on long-term dialysis.

What are the factors contributing to the changes in tissue-type plasminogen activator during haemodialysis?

Haemodialysis (HD) is associated with stimulation of the fibrinolytic system. The increase of fibrinolytic activity seems to be primarily due to tissue-type plasminogen activator (t-PA) released from the vessel wall. The aim of our study was to determine whether the t-PA release is the consequence of uraemic intoxication adjustment, extracorporeal circulation effect, heparin administration, or whether a mere reflection of the circadian rhythm of fibrinolysis is involved. To identify the factor, fibrinolytic system parameters were determined during HD, sham HD (SD), after the administration of heparin alone outside HD, and during a control period (CP). The plasma concentrations of t-PA antigen indicate that HD is associated with the release of t-PA from the vessel wall; 3.70 ng/ml before HD, 4.35 (NS) at the 15th min, 4.88 (P less than 0.05) at the 20th min, and 5.09 (P less than 0.05) after HD (medians). The respective values for a CP are 4.05, 4.37 (NS), 4.40 (NS), and 4.22 (NS). The effect of heparin alone and SD was evaluated for 120 min only, with the following t-PA concentrations determined after heparin: 5.10, 6.22 (NS), 4.72 (NS), 4.72 (NS); during SD and 4.50, 5.14 (NS), 5.20 (P less than 0.05). We conclude that t-PA is released from the vessel wall during HD. A factor contributing to its release is the extracorporeal circulation system.

[Disorders of fibrinolysis and thrombophilic states, risk factors and possibilities of dietary effects]. / Poruchy fibrinolýzy u trombofilních stavu, jejich rizikové faktory a moznost ovlivnení dietou.

An inadequate efficiency of the fibrinolytic system was revealed in 50-60% of subjects suffering young age from venous thrombosis or myocardial infarction. In a group of 27 patients with the history of deep venous thrombosis of the idiopathic type the authors revealed a significant relationship between the elevated body weight and inadequate fibrinolysis manifested by a reduced fibrinolytic capacity and excess inhibitor of plasminogen activator and its inadequate decline after desmopressin infusion (DDAVP). In a group of 29 patients, who had suffered a myocardial infarction when young, the authors revealed a significant association between reduced fibrinolytic capacity and elevated body weight, hypertriglyceridaemia and increased immunoreactive insulin secretion after a glucose load. In half the investigated subjects it proved possible to improve the reduced fibrinolytic capacity by a low energy diet.

[Changes in hemostasis in blood donors on the Fenwal CS 3000 separator]. / Sledování zmen hemostázy u dárcu na separátoru FENWAL CS 3000.

During thrombocytophereses on a blood cell FENWAL CS 3000 separator in one group of donors the anticoagulant solution ACD-A recommended by the manufacturer was used, in the other group of donors ACD-A with heparin was used. The authors give an account of the changes in some parameters of haemostasis in these donors on the separator incl. examination of fibrinopeptide A which is the most sensitive indicator of clotting activity during separation. Heparin administration prevented a rise of fibrinopeptide A and did not lead to a reduced platelet yield.