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Biomedical subjects

W Speiser

Publications and source records attributed to W Speiser.

At least 19 recordsLinked to original sources
PubMed1992

[Decreased fibrinolytic capacity in coronary patients by increased plasminogen activator inhibitor activity].

The fibrinolytic capacity of the blood mainly depends on the amount of tissue-plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI). In this study the fibrinolytic response to a venous occlusion test (VOT) was measured in 109 patients with angiographically documented coronary artery disease (CAD) and in 20 healthy volunteers at comparable age (controls). CAD-patients had higher plasma plasminogen activator inhibitor capacity before (24.4 +/- 11.0 vs. 15.4 +/- 5.2 arbitrary units [AU/ml]; p less than 0.0002) and after VOT (19.6 +/- 13.2 vs. 10.9 +/- 5.3 AU/ml; p less than 0.0001) compared with controls. Furthermore they showed significant lower plasma t-PA activity after VOT (3.0 +/- 6.8 vs. 6.6 +/- 10.6 AU/ml; p less than 0.0001). However there were no difference between both groups in plasma t-PA antigen levels after VOT (17.3 +/- 12.1 vs. 18.7 +/- 14.4 ng/ml). In 10% of patients the decrease in fibrinolytic activity resulted from a lower t-PA release ("lower" was defined as mean minus one standard deviation of the control group). 40% showed elevated plasma PAI capacity before VOT ("elevated" was defined as mean plus two standard deviations of the control group). Both caused significantly reduced post occlusion plasma t-PA activity and prolonged Euglobulin clot lysis time (p less than 0.003). A positive correlation was found between PAI capacity and serum triglyceride levels. Reduced fibrinolytic activity in 109 patients with coronary heart disease based either on a decrease in t-PA antigen release or a increased in PAI capacity in comparison with healthy controls. The mechanism of these findings is not yet well-known.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Interleukin-4 counteracts pyrogen-induced downregulation of thrombomodulin in cultured human vascular endothelial cells.

Inflammatory mediators such as tumor necrosis factor (TNF) or interleukin-1 (IL-1) and bacterial lipopolysaccharides (LPS) were shown to shift the hemostatic balance of the endothelial cell (EC) surface in favor of procoagulant activities by inducing tissue factor (TF) expression and downregulation of thrombomodulin (TM). In the present study, the effects of IL-4 on these regulatory mechanisms were investigated using cultured human umbilical vein EC. TM downregulation induced by the pyrogens IL-1 (100 U/mL), TNF (500 U/mL), and LPS (20 micrograms/mL) to less than 50% of TM activity of untreated cells during a 12-hour incubation period was completely neutralized when these mediators were coincubated with IL-4 (100 U/mL). In accordance with TM surface activity, TM messenger RNA was decreased by IL-1, TNF, and LPS to less than 40% of untreated cells; this effect was in part antagonized by IL-4. No influence of IL-4 on EC tissue factor induction by IL-1, TNF, and LPS was found. Binding studies using 125I-radiolabeled IL-4 suggest that EC express a single class of high-affinity binding sites (kd = 3.2 pmol/L; 2,000 to 2,500 receptors per cell). These results show that IL-4, in part, protects the EC surface against pyrogen-induced procoagulant changes. Transcriptional regulatory mechanisms seem to be involved in EC surface TM regulation.

Cell Membrane↗
PubMed1991

Interleukin 4 promotes expression of mast cell ICAM-1 antigen.

Cell recognition molecules play a crucial role in the regulation of immune cells. We recently found that mast cells (MCs) express leukocyte recognition molecules, including ICAM-1 antigen, a natural ligand of LFA-1. We here report that interleukin 4 (IL-4), a pleiotropic cytokine and mast cell differentiation factor, selectively promotes expression of surface ICAM-1 antigen and ICAM-1 mRNA in human MCs. IL-4 also up-regulates ICAM-1 antigen in cells of monocyte/macrophage lineage but has no effect on ICAM-1 antigen expressed on basophils, fibroblasts, or lymphocytes. The increase in expression of mast cell/macrophage ICAM-1 antigen induced by IL-4 may contribute to the accumulation of leukocytes and facilitate cell-contact-dependent regulation of immune cells in inflamed tissues.

Antigens, CD↗
PubMed1991

Pacing-induced myocardial ischemia does not affect the endothelial release of coagulant and fibrinolytic factors into the coronary circulation.

The present study addresses the potential effects of pacing-induced myocardial ischemia on the secretion of coagulant and fibrinolytic factors within the coronary circulation. In 6 patients undergoing programmed ventricular stimulation with repeated induction of clinical ventricular tachycardia, the coronary release of tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) capacity, von Willebrand factor antigen (WF:Ag), and prostacyclin (6-keto-PGF 1a) was measured. Blood samples were collected simultaneously from the ascending aorta and the coronary sinus at baseline and immediately after the induction of ventricular tachycardia. The occurrence of pacing-induced myocardial ischemia was established by myocardial net lactate production. Myocardial ischemia was induced in every patient by repeated pacing trials. Pacing-induced ischemia did not affect the coronary release of any of the above factors. Consequently, there was no alteration of transcardiac gradients of thrombin-antithrombin complexes and D-dimer. The present results indicate that pacing-induced myocardial ischemia does not affect the release of coagulant and fibrinolytic endothelial factors or prostacyclin into the coronary circulation.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Disseminated intravascular coagulation and decrease in fibrinogen levels induced by vincristine/prednisolone therapy of lymphoid blast crisis of chronic myeloid leukemia.

Therapy with vincristine (2 mg i.v. weekly) and prednisolone (100 mg p.o. daily) caused a decrease in fibrinogen levels in nine patients treated for lymphoid blast crisis LBC) of chronic myeloid leukemia (CML). During the first days of treatment disseminated intravascular coagulation (DIC), evidence by a positive ethanol gelation test, markedly increased thrombin-antithrombin III complex and fibrin-split product D-dimer levels, and a rapid fall in fibrinogen levels was observed in two patients. The induction of DIC in these two patients caused profuse bleeding in one and necessitated substitution therapy with fibrinogen and platelet concentrates. The remaining seven patients revealed no signs of DIC; nevertheless, four of them showed a moderate increase in D-dimer levels after initiation of therapy. In these patients a well-known side effect of long-term steroid therapy, namely a decrease of fibrinogen levels, was observed within the first week of treatment. Fibrinogen levels did not fall below 150 mg/dl and increased after dose reduction from 100 mg/day to 50 mg/day. We conclude from our results that two types of disturbances in fibrinogen metabolism can be observed during vincristine/prednisolone therapy of LBC of CML: (a) a decrease of fibrinogen levels due to a steroid-mediated impairment of liver synthesis, and (b) a rapid fall in fibrinogen levels in the course of DIC, most likely induced by the release of procoagulants from deteriorating blast cells, leading to severe bleeding in selected cases.

Adult↗
PubMed1991

Coincidence of acquired factor-X deficiency and disseminated intravascular coagulation in patients with acute nonlymphoblastic leukemia.

Systematic clotting studies were performed in 157 patients with de novo acute nonlymphoblastic leukemia (ANLL) prior to treatment. Sixteen patients had disseminated intravascular coagulation (DIC). Three of the patients with DIC (two with M3, one with M5 leukemia) had a marked isolated factor-X deficiency (factor X:C 21%, 33%, and 41%, respectively). Another four patients had a mild isolated factor-X deficiency (factor X:C 55%-68%). In these seven patients the remaining liver-synthesized clotting factors (factors II, VII, IX, V) as well as serum albumin and cholinesterase were within the normal range. Liver disease or vitamin-K deficiency could therefore be excluded. In none of the 141 patients without DIC was a marked isolated factor X deficiency observed; two patients had moderately reduced factor X:C levels but normal liver-synthesized proteins. Induction treatment led to the control of DIC with an almost parallel increase of fibrinogen and factor X up to normal in all patients with factor-X deficiency who achieved complete remission. In one patient, recurrence of leukemia was associated with reoccurrence of DIC and marked factor-X deficiency. We conclude that there is a coincidence of isolated factor-X deficiency and DIC in some patients with ANLL. In some patients, this factor-X deficiency may be severe enough to contribute to the bleeding tendency.

Adult↗
PubMed1991

Anticardiolipin antibodies in patients with venous thrombosis.

The levels of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) were measured in 266 consecutive unselected patients with a history of venous thrombosis. 19 (7.1%) had elevated levels of IgG- or IgM-ACA. The prevalence of LAC was 1 of 266 (0.4%) in the whole patient group and 1 of 19 (5.3%) in the ACA-positive group. Patients with elevated ACA levels did not differ from those with normal ACA with regard to age at the first thrombosis, risk of recurrence, presence of arterial thrombosis, and other clinical features. 8 out of 19 (42.1%) patients with elevated ACA levels also had elevated levels of antinuclear antibodies, but only 1 fulfilled the criteria of systemic lupus erythematosus. These data indicate that in some patients with elevated ACA, autoimmune processes may be present. The clinical significance of elevated ACA levels is uncertain.

Adolescent↗
PubMed1991

Pulmonary embolism. Efficacy of D-dimer and thrombin-antithrombin III complex determinations as screening tests before lung scanning.

The aim of the study was to evaluate if D-dimer and thrombin-antithrombin III complex determinations in patients with clinically suspected pulmonary embolism create a discrimination between patients to be further investigated with lung scanning and those who should be investigated for other diseases mimicking pulmonary embolism. The Data-Fi Dimertest Latex Assay, MAbCO Dimertest EIA, and TAT EIA were performed in 100 consecutive patients (26 percent outpatients) who were sent to our institution for lung scanning by their attending physicians because of clinically suspected pulmonary embolism. The D-dimer Latex Assay was positive (greater than 500 ng/ml) in 12 (48.0 percent) of 25 patients with high probability of pulmonary embolism and in one (11.1 percent) of nine with intermediate probability, respectively. Only one patient (1.5 percent) with a normal scan had a positive latex assay, presumably due to inapparent bleeding after a computed tomographic (CT)-guided liver biopsy. Referring to 120 ng/ml as upper limit of normal (mean +/- 2 SD of healthy controls), the D-dimer enzyme immunoassay (EIA) was positive in 21 (84.0 percent) of 25 patients with high probability, in six (66.7 percent) of nine patients with intermediate probability, and in 40 (60.6 percent) of 66 patients with normal/low probability of pulmonary embolism, respectively. The TAT EIA was positive (greater than mean +/- 2 SD of healthy controls = 3.53 ng/ml) in 18 (72.0 percent) of 25 patients with high probability, in five (55.6 percent) of nine patients with intermediate probability and in 16 (24.2 percent) of 66 patients with normal/low probability of pulmonary embolism. A normal result in one of these hemostaseologic tests did not predict a low probability of pulmonary embolism after lung scanning. Thus, it is not justified to exclude patients with clinically suspected pulmonary embolism from further investigation by lung scanning because of a normal result in one of these tests.

Adult↗
PubMed1990

D-dimer in local thrombolytic therapy with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease.

The generation of D-dimer was studied in the course of local thrombolytic therapy of peripheral arterial occlusions with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in 7 patients. Intermittent local application of rt-PA resulted in a marked increase in D-dimer exceeding values usually seen after intravenous application of manifold higher doses used in myocardial infarction. The increase in D-dimer was related to the estimated thrombus size (length of the occlusion) and the total dose of rt-PA applied. During local rt-PA infusion of 6 of 7 patients maintained plasminogen activator inhibitor capacity (PAI-cap) between 34% and 79% of their corresponding pre-treatment levels; detectable levels of PAI-cap in circulating blood during the procedure did not interfere with the success of therapy.

Adult↗
PubMed1990

D-dimer and TAT measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness.

The plasma levels of thrombin-antithrombin III-complexes (TAT) and the fibrin split product D-Dimer were measured in 39 patients with phlebographically proven acute DVT: 34 patients had proximal DVT, 5 had calf DVT. The sensitivity of D-Dimer and TAT measurements in the diagnosis of proximal DVT was found to be dependent on the duration of symptoms: 0 to 7 days (n = 27): elevated D-Dimer levels (greater than 120 ng/ml) = 1, D-Dimer Latex test positive (greater than 500 ng/ml) = 1, elevated TAT levels (greater than 6 ng/ml) = 0.88. Eight to 14 days (n = 7): elevated D-Dimer levels = 1, D-Dimer Latex test positive = 0.33, elevated TAT levels = 0.66; specificity: elevated D-Dimer: 0.48, D-Dimer Latex test: 1, elevated TAT: 0.76. Calf DVT patients (n = 5) had elevated D-Dimer levels, negative Latex tests and 3 of them had normal TAT values. Hemostatic and fibrinolytic parameters were also determined in 13 patients during heparin treatment of proximal DVT. Elevated D-Dimer and TAT levels rapidly decreased after initiation of anticoagulant therapy. In 2 of 13 patients a marked increase in D-Dimer and TAT levels was observed in periods of ineffective heparinization, documented by normal or only slightly prolonged thrombin clotting times. We conclude from our results that 1) D-Dimer EIA measurement, in contrast to TAT measurement, shows a very high sensitivity in the diagnosis of DVT, 2) due to low specificity this test can only be used to exclude thrombosis in patients with suspected DVT, and 3) the determination of the plasma levels of D-Dimer and TAT may be useful for judging the effect of anticoagulant treatment on thrombotic processes.

Adult↗
PubMed1990

Activation of coagulation and fibrinolysis in patients with arteriosclerosis: relation to localization of vessel disease and risk factors.

Activation markers of blood coagulation and fibrinolysis and several fibrinolytic parameters were determined in arteriosclerotic patients to investigate the relation between extension and main localization of vessel disease, risk factors and disturbances within the blood coagulation and the fibrinolytic system. Indications of an increased intravascular fibrin formation and subsequent fibrinolysis were found in peripheral artery disease (PAD) patients but not in coronary artery disease (CAD) patients. Compared with healthy controls PAD patients had elevated TAT (median: 3.2 ng/ml, 1.5-70 vs. 2.1, 1.2-4.7, p less than 0.005) and D-Dimer (median: 365 ng/ml, range 85-2000 vs. 185, 79-360; p less than 0.0001) plasma levels, whereas TAT (2.4, 1.2-13) and D-Dimer (190, 58-1000) levels of CAD patients were in the normal range. No associations were detected between risk factors of arteriosclerosis (hyperlipidemia, diabetes mellitus, cigarette smoking, hypertension) and the plasma levels of the activation markers TAT and D-Dimer. Independent from risk factors PAD and CAD patients had elevated plasma plasminogen activator inhibitor capacity (PAI cap). Our results provide evidence that 1) increased plasma levels of blood coagulation and fibrinolysis activation markers are not related to risk factors of arteriosclerosis but seem to be unspecifically caused by activation processes on arteriosclerotic vessel wall defects, 2) increased plasma PAI cap found in arteriosclerotic patients is a relatively unspecific phenomenon associated with arterial vessel disease.

Antithrombin III↗
PubMed1990

Diagnosis of protein C deficiency in patients on oral anticoagulant treatment: comparison of three different functional protein C assays.

The efficacy of three different protein C activity assays and of protein C antigen determination for the diagnosis of protein C deficiency was studied in 13 protein C deficient patients (11 with type I, 2 with type II deficiency) and in 51 presumably non-deficient patients (control group), both groups being on oral anticoagulant (OAC) treatment. For protein C activity measurement (1) the assay according to Francis (slightly modified) with thrombin activation and measurement of activated protein C in the aPTT system, (2) an assay using Protac activation and chromogenic substrate (Protac-CS) and (3) an assay using Protac activation and the aPTT system (Protac-PTT) were used. Protein C antigen was determined by Laurell immunoelectrophoresis. The three activity assays gave different results, with the highest values obtained by the Protac-CS assay and the lowest values by the Protac-PTT assay. The Francis assay gave intermediate results. Protein C activity and antigen values were significantly lower in protein C deficient patients compared to the control group. Protein C activity tests had a higher discriminative power than the antigen determination. After taking into account the intensity of treatment, by the Francis assay all deficient and non-deficient patients were correctly classified, by the Protac-CS and the Protac-PTT assay 2 and 4 patients, respectively, were misclassified and by the antigen assay 8 patients were misclassified. Calculation of the ratios of protein C activity to factor II activity was of high discriminative power. We conclude that for diagnosis of protein C deficiency protein C activity tests are superior to antigen determination not only in type II but also in type I deficient patients.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Hydroxycoumarins↗
PubMed1990

Hemostatic and fibrinolytic parameters in patients with acute myeloid leukemia: activation of blood coagulation, fibrinolysis and unspecific proteolysis.

Blood coagulation, fibrinolytic and unspecific proteolytic parameters were investigated in 34 patients with acute myeloid leukemia. An increased activity of the coagulation system, documented by elevated thrombin-antithrombin III-complex (TAT) plasma levels, was found in 91% of the patients; 50% had increased elastase plasma levels. Hyperfibrinolysis, as shown by elevated fibrin split-product D-Dimer plasma levels, was detected in 91% of AML patients. Activation of these enzyme systems was not associated with relevant defects in blood coagulation or fibrinolysis in the majority of the patients investigated. In selected cases of promyelocytic M3 and monoblastic M5 leukemia, however, hypofibrinogenemia and alpha 2-plasmininhibitor deficiency was found, most likely due to depletion of these proteins in the course of disseminated intravascular coagulation and secondary hyperfibrinolysis. Significant correlations were calculated between TAT and fibrinogen (r = -0.57, P less than 0.005), TAT and D-Dimer (r = 0.89, P less than 0.0005), and D-Dimer and alpha 2-plasmininhibitor (r = -0.77, P less than 0.0005) levels. Indications of a pathogenetic importance of primary hyperfibrinolysis or unspecific proteolysis for hypofibrinogenemia and alpha 2-PI deficiency were not found.

Acute Disease↗
PubMed1990

Effect of ritanserin, a 5-hydroxytryptamine2-receptor antagonist, on platelet function and thrombin generation at the site of plug formation in vivo.

To investigate the role of serotonin in platelet plug formation we studied, in eight healthy volunteers, the effect of ritanserin (a 5-hydroxytryptamine2-receptor antagonist) on the platelet release reaction (represented by beta-thromboglobulin release) platelet prostaglandin metabolism (represented by thromboxane B2 formation), and thrombin generation (represented by fibrinopeptide A formation) in the microvasculature. After administration of ritanserin lower amounts of thromboxane B1 were generated in the initial stages of plug formation, suggesting an inhibitory effect on the platelet prostaglandin metabolism. Similar amounts of beta-thromboglobulin were released after the administration of ritanserin compared with placebo, indicating a minor effect of ritanserin on the release reaction. Reduction of thrombin formation by ritanserin in the later stages of hemostasis suggested an inhibitory effect of this substance on the procoagulatory activity of platelets or endothelial cells. This could be attributable to interference with the formation or function of coagulation factor complexes on cell surfaces, or it could be the consequence of a reduction of the platelet activity.

Adult↗
PubMed1990

[A posttraumatic pseudoaneurysm of the hepatic artery. Duplex sonographic diagnosis and follow-up in spontaneous thrombosis].

Guided percutaneous biopsy represents a standard procedure in establishing specific diagnosis of focal liver lesions. We report a case of left hepatic artery pseudoaneurysm diagnosed by means of Duplex Doppler sonography (DS) immediately before percutaneous biopsy should be performed. Selective hepatic artery embolization was planned, but spontaneous thrombosis of the pseudoaneurysm was documented by DS and angiography, respectively. DS is able to identify the vascular nature of a lesion and is helpful to avoid puncture of an aneurysm.

Abdominal Injuries↗
PubMed1989

Increased tissue-plasminogen activator (t-PA) levels in patients under oral anticoagulant therapy.

The fibrinolytic system was investigated in 30 patients under oral anticoagulant therapy, and in 23 control patients not receiving oral anticoagulants. Patients under oral anticoagulant therapy had significantly higher tissue-plasminogen activator (t-PA) antigen levels than patients in the control group. Mean t-PA levels before venous occlusion were 18.4 ng/ml in the anticoagulated patients vs. 7.9 ng/ml in the control patients (p less than 0.001). After venous occlusion for 10 minutes, t-PA levels were 45.0 ng/ml in the anticoagulated patients and 24.2 ng/ml in the control patients (p less than 0.01). Plasminogen activator inhibitor (PAI) capacity was not significantly different in the two groups before venous occlusion (VO) but differed slightly (p less than 0.05) after VO. The net decrease in euglobulin lysis time (ELT) after venous occlusion (= ELT before VO - ELT after VO), indicating the relative potency of the fibrinolytic activity in blood, was also significantly higher in the anticoagulated patients (median 240 min vs. 125 min, p less than 0.001). These data indicate that oral anticoagulant therapy increases the fibrinolytic activity in blood, and thus may have an additional therapeutic effect in addition to anticoagulation.

4-Hydroxycoumarins↗
PubMed1988

Clot lysis mediated by cultured human microvascular endothelial cells.

The lysis of fibrin clots on the surface of cultured human omental tissue microvascular endothelial cells (HOTMEC) and cultured human umbilical vein endothelial cells (HUVEC) was studied. Fibrin clots were made by mixing fibrinogen, plasminogen and thrombin on the surface of both cell types. Clot lysis was seen only on the surface of HOTMEC, which were found to synthesize about 100-fold more tissue plasminogen activator (tPA) antigen than HUVEC. Clot lysis of HOTMEC could be blocked by anti-tPA IgG but was not affected by the incorporation of exogenous plasminogen activator (PAI) into the clot in concentrations (75 arbitrary units) exceeding the tPA activity (21 +/- 2.5 IU) of the cells. Thus, it is likely that tPA secreted by HOTMEC is protected from inhibition by PAI in the presence of fibrin and endothelial cells. The stimulation of EC to release an excess of tPA over PAI, in contrast to the secretion of an excess of PAI over tPA found in unstimulated cells in the absence of fibrin, is obviously no prerequisite for the initiation of fibrinolysis on the surface of HOTMEC. As thrombin was used for clot formation, its influence on tPA and PAI synthesis of both cell types was investigated. In contrast to HOTMEC, which were not affected by alpha-thrombin, HUVEC revealed a dose-dependent increase in tPA and PAI synthesis upon incubation with the enzyme. This increase in tPA production by HUVEC was not sufficient to lyse the clots within 48 hours. Furthermore, HUVEC behaved differently towards thrombin as these cells in contrast to HOTMEC revealed the typical shape change reaction upon incubation with the enzyme.

Capillaries↗