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R Knöfler

Publications and source records attributed to R Knöfler.

15 recordsLinked to original sources
PubMed2001

Thrombolytic therapy in children--clinical experiences with recombinant tissue-plasminogen activator.

For the improvement of thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA) in children, more clinical data are needed. We retrospectively analyzed the clinical course of 20 patients (age ranging from 1 day to 16 years) with venous thrombosis (n = 16), arterial thrombosis (n = 2), and purpura fulminans by meningococcosis (n = 2). The venous thromboses were localized in the iliac-femoral veins (n = 9), brachiocephalic-jugular-subclavian veins (n = 6), and the superior caval vein (n = 1). The arterial occlusions were localized in the abdominal aorta and in the left pulmonary artery. Central venous catheters were of pathogenetic importance in seven cases. The patients were treated with rt-PA for 3 hours to 13 days. The dose ranged between 0.2 and 0.5 mg/kg for the initial bolus and 1.0 to 2.0 mg/kg/d for the continuous infusion. Nineteen patients received simultaneously low-dose unfractionated heparin. Complete clot lysis was detected in 11 cases, a partial lysis in 1, and in 8 patients thrombolytic therapy was not successful. An episode of hematemesis in one patient represented the only serious side effect observed in our study. A systemic decrease in fibrinogen concentration was also rare. In conclusion, thrombolysis with rt-PA represents an effective and safe therapy for children at the dosage used.

Child↗
PubMed1999

Clinical importance of prothrombotic risk factors in pediatric patients with malignancy--impact of central venous lines.

UNLABELLED: To evaluate the role of inherited thrombophilia in the development of central venous line (CVL)-related thrombosis, the following parameters were determined in 77 pediatric-oncologic patients with CVL: activated protein C (APC)-ratio, factor V (FV) G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin, coagulation factor XII, lipoprotein (a) and homocysteine. An inherited prothrombotic risk factor was found in 17 patients (23%). Four out of 14 patients with a single detect (hyperlipoproteinemia, heterozygous FV G1691A and prothrombin G20210A mutation, protein C deficiency type I) and all three patients with combined defects (heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A variant, protein S deficiency or hyperlipoproteinemia) suffered from CVL-related thrombosis. In 11 out of 77 patients (14%) a CVL-related thrombosis was detected. In 2 children thrombosis occurred a few days after asparaginase therapy and in another three thrombosis was associated with CVL-related septicemia caused by Staphylococcus epidermidis. After removal of CVL, thrombosis was detected in 5 children, in 2 without clinical symptoms but in the presence of inherited prothrombotic risk factors. CONCLUSION: The present study demonstrates the clinical importance of CVL in combination with inherited thrombophilia in the development of thrombosis in pediatric-oncologic patients. Before or shortly after insertion of CVL, patients should be tested for the presence of factor V G1691A mutation, prothrombin G20210A variant and increased lipoprotein (a) values.

Adolescent↗
PubMed1998

Molecular markers of the endothelium, the coagulation and the fibrinolytic systems in healthy newborns.

Endothelium derived substances may play a role in the physiological adaptation processes at the time of birth. The aim of this study was to investigate plasma concentrations of activation markers of the endothelium (endothelin-1, thrombomodulin, von Willebrand factor), of the coagulation and the fibrinolytic systems (thrombin-antithrombin III complex, D-dimer, plasmin-alpha2-antiplasmin complex) during the first days of life. Venous blood from peripheral veins was collected from 79 healthy newborns and for comparison from 38 healthy infants and schoolchildren, as well as from 17 healthy adults. Except for endothelin and von Willebrand factor, the concentrations of activation markers were significantly higher in the newborn group. During the first 12 days of life thrombomodulin, thrombin-antithrombin III complex, and plasmin-alpha2-antiplasmin complexes showed a continuous decline whereas the concentrations of endothelin, von Willebrand factor and D-dimer did not change. The highest D-dimer concentrations were found at low umbilical arterial pH and after birth by vaginal operation suggesting an influence of birth stress. Thrombomodulin was correlated with endothelin (r=+0.471) and with von Willebrand factor (r=-0.415). In conclusion, endothelial, coagulation, and fibrinolytic systems are activated in newborns which might occur during birth by the mechanical stress, the adaptation of circulation, and the short-term hypoxic state. An additional intrauterine activation should also be considered.

Adult↗
PubMed1998

Platelet function tests in childhood. Measuring aggregation and release reaction in whole blood.

Blood samples from 42 newborns, 78 infants and schoolchildren, and 81 healthy adults were tested for the parameters of primary hemostasis. Only whole blood techniques were used. Agonist-induced aggregation and release-reaction studies were performed in a whole blood lumi-aggregometer simultaneously. The release of adenosine triphosphate (ATP) was detected by the luciferin-luciferase method. The in vitro bleeding time was measured by the PFA 100 system. The results of these studies were ostensibly influenced by blood cells. Many aggregation phenomena were correlated with the platelet count. Aggregation and release reaction by collagen were inversely correlated with the hematocrit. In the PFA 100, hematocrit and leukocyte count were also inversely correlated with the closure time and the maximal blood flow velocity. Both parameters were diminished in newborns. The aggregation response to adenosine diphosphate (ADP) was similar in the three groups. The same was true for the aggregation and release reaction by arachidonic acid and for the agglutination by ristocetin. The aggregation and release reaction by collagen were diminished in the specimens from newborns. For the explanation of this transient hypofunction, only theoretical considerations exist. Beyond the postnatal period and during childhood, no remarkable differences from the adult norm were found.

Adenosine Triphosphate↗
PubMed1997

Release of adenosine triphosphate by adenosine diphosphate in whole blood and in erythrocyte suspensions.

In whole blood samples from thrombocytopenic patients, large amounts of ATP were released by ADP, exceeding the level obtained with samples from normal persons by far. Because we suspected that the high potential of ATP in erythrocytes would be the main source for this phenomenon, the release of ATP by ADP was measured in whole blood samples from normal, thrombocytopenic, and leukocytopenic persons and in suspensions of washed erythrocytes. The release was recorded by a Whole Blood Lumi-Aggregometer type 500 VS (Chrono-Log Corporation, Havertown, PA) using the luciferin-luciferase system. Not only in samples from thrombocytopenic persons but also with normal platelet count, increasing amounts of ATP were released with increasing ADP concentrations, finally exceeding the ATP releasable from thrombocytes by thrombin. The amounts of ADP required to match the ATP release of thrombin were closely correlated with the platelet counts in the samples. With lower platelet counts, the release mechanism from erythrocytes could be stimulated more easily by low concentrations of ADP. The binding of ADP to platelets occurred with ostensibly higher affinity. The phenomenon of overshooting ATP release was also observed in samples from extremely leukocytopenic patients. A very large release of ATP was also achieved in suspensions of washed erythrocytes. In this way our hypothesis of ATP release from erythrocytes by ADP was confirmed again. The mechanism of the release from erythrocytes remains unclear. We speculate that its purpose is to regulate extracellular nucleotides in the circulating blood.

Adenosine Diphosphate↗
PubMed1996

Critical evaluation of the quantification of ATP release reaction in whole blood.

The influence of erythrocyte and thrombocyte content on the release of adenosine triphosphate (ATP) in whole blood was tested. Citrated blood from 39 healthy persons was diluted gradually. The release reaction was induced by arachidonic acid (1.25 mM), adenosine diphosphate (ADP; 30 microM) and collagen (1.0 and 5.0 micrograms/ml). The peak of the obtained curves was transformed into percent values of the maximal deflection by the undiluted sample (PEAK IN RELATION) and into ATP concentrations (ABSOLUTE PEAK). By rising dilution an increase of the peak in relation with all inducers was observed which was mainly due to the luminescence-optical effect. As expected the absolute peak decreased but only under arachidonic acid and collagen. Under ADP despite of the rising dilution constant amounts of ATP were released suggesting an additional release from other blood cells. High ATP release curves in response to ADP were observed in patients with pancytopenia and with thrombocytopenia when compared to health persons. ADP seems not to be suited for the measurement of ATP release reaction in whole blood. Collagen at a final concentration of 1.0 micrograms/ml was found as the optimal inducer. The ATP standard is essential for the quantification of release reaction.

Adenosine Diphosphate↗
PubMed1995

Daily variation of serum lipids in relation to the circadian rhythm of platelet aggregation in healthy male persons.

The circadian rhythm of platelet aggregation was compared with that of serum lipids in seven healthy male persons. Daily variations of remnant lipoprotein-cholesterol and of remnant lipoprotein-triglycerides were related to those of arachidonic acid-, ADP (adenosine diphosphate)-, and collagen-induced aggregation in platelet-rich plasma and to ADP-induced aggregation in whole blood, respectively. Statistical analyses indicate that the time course of remnant-cholesterol was correlated to that of ADP-induced aggregation in platelet-rich plasma and the time courses of blood cholesterol and triglyceride were correlated to arachidonic acid- and serotonin-induced platelet aggregation in platelet-rich plasma, respectively. In whole blood, the time course of remnant lipoprotein-triglyceride was correlated only to ADP-induced platelet aggregation. In contrast, the daily variation of HDL (high density lipoprotein)-cholesterol did not influence either that of platelet aggregation in platelet-rich plasma or that in whole blood. Our findings are of clinical interest regarding the development of atherosclerosis and thrombotic events in persons with an elevated level of serum lipids.

Adolescent↗
PubMed1995

Remnant-like lipoproteins stimulate whole blood platelet aggregation in vitro.

We have developed a simple, rapid assay method to measure remnant-like lipoproteins by using an immunoaffinity gel mixture of anti apo B-100 and apoA-1 antibodies to Sepharose 4B. Characterization of the unbound lipoproteins has shown that they represent chylomicron and VLDL remnant particles (RLP). Preincubation of whole blood with RLP resulted in the enhanced activation of aggregation with ADP and collagen. Such enhancement was not observed in the presence of lipoprotein deficient serum or albumin preparation. The extent of enhancement was 2.78 times by 7.5 microM of ADP and 44 times by 0.5 microgram/ml of collagen in the presence of RLP-preparation 1 (RLP-1), respectively. In the presence of RLP-2, the enhancement was 5.37 times by 7.5 microM of ADP and 102 times by 0.5 microgram/ml of collagen, respectively. On the other hand RLP slightly inhibited PRP aggregation by these agonists. Inhibitions were 19% by 7.5 microM of ADP and 18% by 1.0 microgram/of collagen in the presence of RLP-1, respectively. Incubation of whole blood with RLP did not result in the release of factors to stimulate platelets or ADP- or collagen-induced platelet aggregation in vitro. The extents of enhanced aggregation in whole blood or inhibition in PRP were not correlated with RLP-cholesterol nor RLP-protein concentrations of RLP preparations used. These results may indicate that RLP not only interact with platelets but with erythrocytes or leukocytes. Our findings support the hypothesis that the postprandial increase in remnant lipoproteins is an atherosclerotic risk factor and may be a part of the reasons of thrombotic complications by stimulating platelets in patients with remnant hyperlipoproteinemia.

Adenosine Diphosphate↗
PubMed1995

In vitro effect of endothelin-1 on collagen, and ADP-induced aggregation in human whole blood and platelet rich plasma.

The effect of ET-1 on ADP- and collagen-induced platelet aggregation in whole blood and platelet rich plasma (PRP) was studied in 39 healthy volunteers. Although ET-1 itself did not cause platelet aggregation, a marked enhancement of ADP-induced aggregation after the preincubation with ET-1 for 5 min was observed in whole blood, but not in PRP. This ET-1 concentration and preincubation time-dependent phenomenon could be demonstrated only at threshold concentrations (5 and 7.5 microM) of ADP and is probably due to an interaction of ET-1 with cells which are involved in the whole blood aggregation, such as polymorphonuclear neutrophils. In whole blood and PRP an inhibition of collagen-induced aggregation after the preincubation with ET-1 was detected. In contrast to ADP, a direct influence of ET-1 on platelet activation after the addition of collagen is therefore more likely. These results suggest that human platelets may possess ET-1 receptor(s) and that ET-1 may also interact with other blood cells.

Adenosine Diphosphate↗
PubMed1995

Effects of nicotine and electric footshock on peripheral serotonergic measures and on platelet aggregation in whole blood of rats.

The effects of nicotine and electric foot shock as well as of their combination on blood serotonergic measures and on whole blood aggregation have been analyzed. In rats subjected to electric footshock a rise (p < 0.05) in plasma but not in whole blood serotonin was observed, whereas this parameter was not influenced in nicotine-treated rats when compared to the control group. The combination of nicotine with electric footshock only slightly increased plasma serotonin and showed no effect on whole blood serotonin, but 5-hydroxyindole acetic acid (5-HIAA), the major metabolite of serotonin (5-HT), as well as the 5-HIAA/5-HT ratio were markedly increased (p < 0.01) suggesting an enhanced turnover of 5-HT under these conditions. The collagen-induced aggregation in whole blood was not influenced in nicotine-, in footshock- nor in combined-treated rats when compared to the controls. Our data indicate that stress as well as the combination of stress with nicotine may affect the serotonergic system which is in contrast to the exposure to nicotine alone.

Animals↗
PubMed1994

N,N,N-trimethylsphingosine modifies aggregatory response and ATP release from platelets in whole blood.

We investigated the influence of N,N,N-trimethylsphingosine (TMS), a potent inhibitor of protein kinase C (PKC), on whole blood aggregation and ATP release from platelets. The preincubation with TMS at 1 microM for 2 min enhanced ATP release during arachidonic acid-induced aggregation. The ristocetin-induced agglutination was inhibited in a TMS concentration-dependent manner, which suggests that TMS may interact with the vWF receptor on platelets. TMS suppressed aggregatory response and ATP release from platelets after the addition of collagen. In contrast, the platelet aggregation induced by ADP and 12-O-tetradecanoylphorbol-13-acetate (TPA) was only slightly inhibited and the ATP release was not influenced after preincubation with TMS. Our results are in contrast to previous reported data, which were obtained using PRP and washed platelets.

Adenosine Diphosphate↗