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Biomedical subjects

K Pawlak

Publications and source records attributed to K Pawlak.

At least 37 records · Page 2Linked to original sources
PubMed1998

Long-term effects of erythropoietin on platelet serotonin storage and platelet aggregation in hemodialysis patients with reference to ketanserin treatment.

Correction of uremic platelet serotonin (5-HT) storage pool deficiency is one of the very early hemostatic effects of erythropoietin (Epo) therapy. In this work, platelet 5-HT with relation to primary hemostasis was studied in 15 hemodialysis patients treated with Epo for 8 months. Moreover, effects of ketanserin, a blocker of platelet and vascular smooth muscle cell 5-HT2A receptors, in these patients were followed. The parameters studied were compared with relevant values in healthy controls and in hemodialysis patients not treated with Epo, and remeasured in the long-term Epo patients after a 14-day oral ketanserin trial. Platelet 5-HT content in the eighth month of Epo therapy was not different from the one in untreated patients. Ristocetin- and collagen-induced platelet aggregation were enhanced in comparison with both control groups, as opposed to unaltered response to ADP and arachidonic acid. Fibrinogen concentration was lower than in the untreated group. An inverse correlation between ADP-induced platelet aggregation and the skin bleeding time (r=-0.536, p<0.05) and a positive one between the former and platelet 5-HT (r=0.644, p<0.01) were found. Platelet count correlated positively with both platelet 5-HT (r=0.823, p<0.0002) and ADP-induced platelet aggregation (r=0.596, p<0.02). Ketanserin produced a decrease in ristocetin-induced platelet aggregation, fibrinogen, and prolongation of the bleeding time. The first two of the changes correlated positively with their pre-ketanserin values (r=0.923, p<0.00001 and r=0.839, p< 0.0001, respectively). Post-ketanserin, positive correlations between depressed ristocetin- and arachidonic acid-induced platelet aggregation (r=0.760, p<0.005), and between collagen- and corresponding values of arachidonic acid- (r=0.622, p<0.02), ADP-induced platelet aggregation (r=0.396, p<0.01), and platelet 5-HT (r=0.654, p<0.05) were found. Efficient hemostasis in hemodialysis patients on protracted Epo therapy is, in part, dependent on enhanced platelet aggregability. Correction of platelet 5-HT storage pool deficiency is not evident in this stage but 5-HT still influences complex mechanisms of primary hemostasis. Ketanserin is of anticoagulant value in these patients but its effects must be weighted against possible exacerbation of the anemia.

Adolescent↗
PubMed1997

[Use of low-molecular weight heparin during hemodialysis].

Coagulation parameters--platelet aggregation, beta-thromboglobulin, fibrinopeptide A were analyzes in patients with final chronic renal insufficiency during haemodialysis after a low molecular weight heparin application. In the study was documented that standard heparin is able to induce platelet aggregation. A low molecular weight heparin is suggested as sefex, because no influence on platelet aggregation was determined.

Adult↗
PubMed1997

[The influence of multiple dialyzer reuse on selected coagulation parameters].

The aim of the study was to follow effects of multiple dialyzer reuse on some coagulation parameters. In a random group of 10 patients undergoing intermittent hemodialysis treatment, platelet coagulant, fibrinogen, BTG and PF4 concentrations were determined after 1st dialyzer usage and after 2 consecutive dialysis sessions after which the dialyzer was reused by manual method with 1% Dialyne solution. An increase in fibrinogen concentration after 240 min of HD procedure was shown when dialyzer was used for 1st and 3rd time. BTG activity increased after 240 min of HI procedure when the dialyzer was used for 3rd time. There was a fall in platelet count after 30 min of HD during the 1st and the 3rd dialyzer use. The fall in platelet count lasted all dialysis session when dialyser was used for 3rd time. The PF4 activity was decreased after 30 min of HD session after the 1st and the 2nd dialyzer use.

Adult↗
PubMed1996

The coagulo-lytic system and endothelial function in cyclosporine-treated kidney allograft recipients.

Since thromboembolic complications in transplanted patients are generally attributed to combined abnormalities in platelets and coagulo-lytic system, some hemostatic parameters tPA (tissue plasmogin activator):Ag and activity, its inhibitor-PAIAg and activity, tPA/PAI, thrombin-antithrombin (TAT) and plasmin-antiplasmin complexes (PAP), urokinase-uPA, euglobulin clot lysis time-ECLT, fibrinogen, plasminogen, protein C activity, D-dimer, prothrombin fragments1+2 (F1+2), fibrin monomers, fibronectin, lipoprotein-a, and von Willebrand factor(vWF), were evaluated using commercially available kits. The studies were performed on kidney transplant recipients treated with CsA, azathioprine and prednisone (n=21), and healthy volunteers (n=21). ECLT was significantly prolonged in kidney transplant recipients together with a rise in F1+2,lipoprotein-a, fibrinogen, fibronectin, and vWF when compared with controls. The TPA level was lower, whereas the PAI level was higher in kidney transplant recipients when compared with controls. In conclusion, CsA-treated kidney transplant recipients show evidence of pronounced impairment in fibrinolysis and endothelial damage in comparison with healthy volunteers.

Adult↗
PubMed1996

Hemostasis, platelet function and serotonin in acute and chronic renal failure.

A pathogenetic role for fibrin deposition and platelet activation in the kidney is thought to play a role in the pathogenesis of acute renal failure (ARF). Thus, some fibrinolytic parameters and platelet function have been studied in 17 patients with ARF and compared to healthy volunteers and subjects with chronic renal failure (CRF). Since serotonin may participate in pathological processes resulting from platelet/vessel wall interactions, its level in the whole blood and plasma was also assayed. In ARF and CRF platelet aggregatory responses in both whole blood and in platelet rich plasma upon stimulation with various agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those obtained in healthy volunteers. Increased levels of lipoprotein (a), von Willebrand factor (vWF) and fibronectin were found in ARF relative to controls. Protein C activity was significantly lower in patients with ARF. Euglobulin clot lysis time was prolonged in ARF and CRF, reflecting a decreased overall fibrinolytic activity. Activity of tissue plasminogen activator (tPA) inhibitor (PAI) and PAI:Ag were higher in ARF, whereas tPA:Ag, urokinase, tPA/PAI complexes, thrombin-antithrombin complexes (TAT), plasmin-antiplasmin (PAP) complexes, fibrinogen, and F1+2 did not differ between ARF and controls. In CRF elevated levels of TAT, PAP, fibrinogen and prothrombin fragments F1+2 were found, whereas concentration of fibronectin was lowered when compared to controls. In both groups of renal failure patients increased levels of fibrin monomers and d-dimer were found relative to healthy volunteers. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in patients with ARF and CRF relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with ARF and CRF. Chronic renal failure exhibit a slightly different pattern of coagulopathies that acute renal failure.

Acute Kidney Injury↗
PubMed1996

Peripheral serotonergic system in uremia.

Several data suggest that platelet-derived serotonin (5-HT), previously classified as a trivial modulator of blood-borne cardiovascular disease (1), may play a decisive role in various pathological processes, resulting from abnormal platelet-vessel wall interactions (2). Following platelet activation upon a contact with a damaged vessel wall, 5-HT, released from platelets upon the activation of 5-HT2 receptors, may amplify the action of other agents on vascular smooth muscle cells and platelets (3,4). Platelets play a unique role in 5-HT metabolism: they take it up, store in their dense granules and release upon stimulation. Platelet dysfunction, alteration in platelet count, their consumption and turnover are common in renal diseases (5). Storage pool deficiency regarding 5-HT and ADP was reported in renal failure (6). Previously we reported that 5HT2 receptor blockers may serve as potent antiplatelet drugs in uremic patients, which are prone to thrombotic complications (7,8). Up to date there have been a few reports dealing predominantly with 5-HT levels in renal patients. Thus, we focused on peripheral serotonergic mechanisms including 5-HT uptake and release and kinetics of its uptake in uremic patients.

Adult↗
PubMed1996

Erythropoietin and uremic platelet aggregation in vivo and in vitro.

Erythropoietin treatment is known to correct anemia and to improve hemostasis. Since platelets may contribute to thromboembolic complications, we assessed platelet aggregation in whole blood and platelet-rich plasma from chronically hemodialyzed patients treated with erythropoietin and evaluated in vitro effects of this drug on aggregatory responses of uremic and normal platelets. Recombinant human erythropoietin was given to uremic patients at a dose of 2,000 IU subcutaneously three times a week. Platelet aggregation in whole blood and platelet-rich plasma was induced by collagen, ADP, arachidonic acid, and ristocetin. In uremic patients, erythropoietin therapy resulted in an enhancement of platelet sensitivity to various agonists, particularly in platelet-rich plasma, reaching values comparable to those of healthy volunteers. In vitro studies we were unable to show any direct effect of erythropoietin, used at concentrations that occurred post intravenous administration, on platelet aggregation both in whole blood and in platelet-rich plasma.

Adenosine Diphosphate↗
PubMed1996

Inverse relationships between haemoglobin and ristocetin-induced platelet aggregation in haemodialysis patients under erythropoietin therapy.

BACKGROUND: Amelioration of the anaemia of chronic renal failure and subsequent improved haemorheology result in correction of bleeding diathesis as evidenced by shortening of the skin bleeding time (BT). However, the relationship between the haematocrit and platelet-vessel wall interactions in haemodialysis (HD) patients under recombinant human erythropoietin (rHuEpo) therapy, assessed by platelet aggregation in response to ristocetin is more complex and somewhat inconsistent. METHODS: We investigated the relationship between haemoglobin (Hb) levels and whole blood ristocetin-induced platelet aggregation (electric impedance method) in 28 HD patients treated with rHuEpo, and with normal BT. The measurements were repeated in 16 subjects after having reduced platelet aggregability with orally administered ketanserin. RESULTS: Ristocetin-induced platelet aggregation in the whole group was comparable to those found in 21 age-matched healthy subjects (normals) and in 25 HD patients not treated with rHuEpo (uraemics). Interestingly, a significant inverse correlation between this aggregation and Hb concentration was found (r = -0.392, P < 0.05). In the group of 16 patients, the pre-ketanserin aggregation was more intensive than in the normals and uraemics (P < 0.05). Ketanserin produced a fall in ristocetin-induced platelet aggregation (P < 0.02), prolongation of the BT (P < 0.02) and, unexpectedly, a decrease in serum Epo concentration (P < 0.0002) and the Hb level (P < 0.001). Again, an inverse correlation between depressed ristocetin-induced platelet aggregation and lowered Hb concentration was found (r = -0.590, P < 0.02). Moreover, a strong positive correlation between the extent of preketanserin platelet aggregation and the decrease in the intensity of this process that followed the trial was observed (r = 0.919, P < 0.000005). There were no changes in other haematological parameters or arterial blood pressure. CONCLUSIONS: Considering the role of von Willebrand factor and fibrinogen in mediating ristocetin-induced platelet aggregation, and enhanced synthesis and/or release of these macromolecules in response to uraemia or inflammation, we suggest that exaggerated whole-blood platelet aggregability to ristocetin points to blunted erythropoiesis in HD patients on rHuEpo therapy.

Adult↗
PubMed1996

Ketanserin: a new perspective in posttransplant erythrocytosis?

We have recently shown that ketanserin, an antagonist of peripheral serotonin 5-HT2 receptors lowers blood erythropoietin (Epo) levels in some chronic hemodialysis patients. Based on this finding, a preliminary study was undertaken to investigate the effect of a 3-week oral ketanserin administration on serum Epo concentration and relevant hematological parameters in 4 renal allograft recipients with posttransplant erythrocytosis (PTE). We found a marked decrease in Epo concentrations following ketanserin administration, from 48% to 76% of the abnormally elevated pretreatment values with subsequent increases at 3 weeks after discontinuation of the drug in all patients studied. In 3 of them a corresponding decrease or no rise in the erythrocyte count were noted. During the 6-week study period, the need for monthly phlebotomies was eliminated in these patients. It is hypothesized that ketanserin diminishes erythropoietin synthesis and may become a new drug in the treatment of posttransplant erythrocytosis.

Adult↗
PubMed1996

Antithrombotic activity of dermatan sulphates, heparins and their combination in an animal model of arterial thrombosis.

Dermatan sulphates have been shown to inhibit thrombus formation and thrombus growth in different experimental model of venous thrombosis. At variance with heparins, they show a remarkably low haemorrhagic potential. On the other hand, very few data are available on the effect of dermatan sulphates on arterial thrombus formation. We evaluated the effects of a low molecular weight (LMW)-dermatan sulphate, a high molecular weight (HMW)-dermatan sulphate and sulodexide (a mixture of fast-moving heparin fraction and dermatan sulphate) in comparison with LMW- and HMW-heparin, in a model of arterial thrombosis in rats. The insertion of an artificial prosthesis into the abdominal aorta of the animals induced the formation of an occluding thrombus within 2-5 days. The time in which 50% of the loops became occluded (OT50) was also calculated and used to compare the efficacy of the different drug treatments. This was 2.84 days for control animals and 4.25 and 5.80 days for HMW- and LMW-dermatan sulphate, respectively. Neither drug changed the "template" bleeding time, even at higher doses. In contrast, HMW-heparin at doses (8 mg/kg, sc, twice a day) inducing an antithrombotic activity comparable to that of dermatan sulphates, dramatically prolonged the bleeding time. LMW-heparin at the same doses was ineffective. Sulodexide (10 mg/Kg, sc, twice a day) prolonged the occlusion time to the same extent as HMW-heparin (OT50 5.10 vs. 4.14 days), with less an effect on the bleeding time (144 +/- 6 s vs. > 300 s, respectively). Histological examination confirms that the prolongation of occlusion time induced by the drugs is really related to thrombus formation inhibition at the site of arterial wall injury. Acetyl salicylic acid (ASA) (100 mg/kg/day in drinking water as lysine acetylsalicylate) did not modify the effect of Desmin 370 and Sulodexide on both occlusion and bleeding time. However, while it did not increase the antithrombotic activity of HMW-heparin, it significantly prolonged its haemorrhagic effect. In conclusion, dermatan sulphates are effective inhibitors of arterial thrombosis in rats, without inducing bleeding complications.

Animals↗
PubMed1996

[Effect of treating glomerulonephritis with omega 3 fatty acids for selected parameters of hemostasis, blood platelet function and lipid metabolism].

Disturbances in serum lipids, hemostasis and platelet functions are frequent features in some kidney diseases and may contribute to the progression of atherosclerosis with its complications. Recently, an attention has been paid on beneficial effects of fish oil on serum lipids and hemostasis, and proteinuria. The purpose of this work was to assess platelet functions, some hemostatic parameters and serum lipids in patients with chronic glomerulonephritis treated with Trienyl. The study was performed on 7 patients with glomerulonephritis, before, 3 and 6 months following fish oil treatment. A small and nonsignificant rise in cholesterol, HDL and LDL was found, whereas triglycerides level fell significantly following 3 and 6 months of therapy Fibrinogen concentration was lowered significantly 6 months following fish oil administration. Platelet aggregation in platelet-rich plasma remained unaltered during therapy, whereas platelet responses to ADP and arachidonic acid in the whole blood were inhibited after 6 months of the therapy. Unsaturated omega 3 fatty acids in Trienyl alter lipid metabolism, platelet/vessel wall interactions and proteinuria and therefore might be beneficial in therapy of glomerulonephritis, particularly in combination treatment.

Adult↗
PubMed1995

Ketanserin lowers erythropoietin concentration in hemodialyzed patients treated with the hormone.

Ketanserin, an antagonist of peripheral serotonin receptors when given to hemodialyzed patients treated with recombinant human erythropoietin (rHuEpo) corrects some changes in hemostasis but also apparently delays an increase in hematocrit. We wished to elucidate the effects of oral administration of ketanserin on serum Epo, some hematological and biochemical blood parameters, arterial blood pressure (BP), and bleeding time in hemodialyzed patients receiving rHuEpo therapy. We noted a 33% decrease in Epo concentration (p < 0.05) after a 4-week ketanserin trial in patients in the initial stage of rHuEpo therapy. Although a concomitant decrease in erythrocyte count and hemoglobin did not reach statistical significance, these changes correlated positively with decreasing Epo level (r = 0.749 and 0.787, respectively). Ketanserin administered for 14 days to patients between 32 and 34 weeks of rHuEpo therapy also produced a decrease of 26% in Epo concentration (p < 0.005). This decrease correlated (r = 0.629) with a decrement in the red blood cell (RBC) count (p < 0.005). Hemoglobin concentration followed the same pattern (p < 0.005). However, the decreases in the reticulocyte count did not reach statistical significance. The decrease in hormone concentration resulted in a concomitant thrombocyte decrease (p < 0.05) only in patients who received ketanserin in the interval between 8 and 12 weeks of rHuEpo therapy. The previously normal bleeding time was significantly prolonged (p < 0.05) in both groups of patients. There were no changes in leukocyte count, iron status parameters, or calcium, phosphorus, or bilirubin concentration. Administration of ketanserin even for 4 weeks did not influence BP in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Levels of dimethyl-L-arginine in ultrafiltrate and blood pressure in patients during hemodialysis].

The contant of dimethyl-L-arginine in the ultrafiltrate obtained during dialysis session from 30 patients with end-stage renal failure maintaned on chronic hemodialyses was studies. 14 patients were normotensive and 16 were hypertensive. In patients with hypertension dimethyl-L-arginine level was significantly elevated (mean value 7.67 mumol/l), when compared to patients with normal blood pressure (mean value 2.37 mumol/l). Prolongation of the dialysis session is postulated in hypertensive patients.

Adult↗
PubMed1994

[Ketanserin decreases erythropoietin concentration in hemodialyzed patients on rHuEPO therapy].

Serotonergic mechanisms are partially responsible for changes in haemostasis and blood pressure rise in haemodialyzed patients treated with recombinant human erythropoietin (rHuEPO). Ketanserin--an antagonist of platelet and blood vessel serotonin receptors, given concomitantly to patients on rHuEPO therapy, prevents certain changes in haemostasis. Preliminary observations suggest that ketanserin also inhibits an increase in haemoglobin and haematocrit. So far there have been no reports on ketanserin affecting erythropoiesis. We studied an influence of the 2-week oral ketanserin administration on some haematologic parameters, serum erythropoietin concentration, blood pressure and relevant biochemical blood indexes in 15 haemodialyzed patients treated with rHuEPO for 32 weeks. We found a significant fall in serum EPO concentration (p < 0.005) measured with the ELISA technique that correlated positively (r = 0.629) with a decrease in erythrocyte count (p < 0.005). Haemoglobin concentration followed the same pattern (p < 0.005). The previously normal bleeding time prolonged significantly (p < 0.02) after ketanserin therapy. There were no changes in plasma iron and ferritin concentration, total iron binding capacity, transferrin saturation index, calcium, phosphorus and bilirubin concentration nor reticulocytosis. The decrement in EPO concentration did not affect peripheral blood platelet or leukocyte counts. The 14-day treatment with ketanserin did not influence arterial blood pressure in the patients. The study shows that ketanserin administered to haemodialyzed patients on long-term rHuEPO therapy induces a decrease in erythropoietin concentration and inhibits erythropoiesis. This phenomenon seems to result from diminished endogenous hormone synthesis caused by ketanserin.

Adolescent↗