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Biomedical subjects

H Vinazzer

Publications and source records attributed to H Vinazzer.

At least 19 recordsLinked to original sources

Heparin cofactor II: experimental approach to a new assay and clinical results.

By a series of experiments it could be shown that an activity test of heparin cofactor II (HC II) is only specific after a complete depletion of antithrombin III. Also when dermatan sulfate which does not enhance the action of AT III is used for the activation of HC II there is a considerable influence on the remaining thrombin activity which alters the test results. Furthermore, in a system which contains plasma as well as thrombin the formation of a clot is likely to occur which by its opacity influences photometric results. A chromogenic substrate assay is described which excludes the influence of these variables. This assay was used to examine the activity of HC II in healthy persons as well as in patients. Three members of a family were found who had a heterozygous deficiency of HC II without any history of thrombosis. On the other hand, a total of 16 patients with heterozygous deficiency of HC II suffered from recurrent thromboembolic episodes. For this reason it is assumed that a deficiency of HC II has a certain importance in the occurrence of thrombophilia though it is apparently less thrombogenic than a deficiency of other inhibitors.

Antibodies

Low haemoglobin in haemophilia children is associated with chronic immune activation.

Anaemia is a frequent complication in patients with human immunodeficiency virus type 1 (HIV-1) infection. We tested 14 children with severe haemophilia (9 HIV-1 antibody seropositive CDC stage IIA, 5 seronegative) for haemoglobin and urinary neopterin concentrations and found a negative correlation between neopterin and haemoglobin (rs = -0.745, p = 0.007; Spearman's rank correlation). This finding suggests that chronic immune activation, possibly along with the release of specific cytokines such as interferon gamma and tumor necrosis factor alpha may be involved in the pathogenesis of anaemia.

Adolescent

Autologous platelet-labeling in thrombocytopenia.

Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after 111In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous 111In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

Adolescent

Prophylaxis of thromboembolism in general surgery: comparison between standard heparin and Fragmin.

In a double blind randomized trial on 250 patients undergoing elective abdominal surgery the effect of Fragmin was compared with heparin. Patients over 40 years of age except appendectomy and herniotomy were included. The dose of heparin was 5,000 IU b.i.d. whilst Fragmin was given in a dose of 2,500 U once per day and the second injection was a placebo. Prophylaxis started 2 h preoperatively and was maintained for 7 days. The fibrinogen uptake test was used as a screening method for thrombosis which was confirmed by phlebography. 124 patients were in the heparin group and 126 in the Fragmin group. Comparability between groups was found in: age, sex, Broca index, amount and type of risk factors, type of surgery. Thromboembolism was found in 10 cases in each group. Blood transfusions on the postoperative days 1 to 6 were required in 2 Fragmin and in 12 heparin patients. The total amount of blood given during that time was 6 units in the Fragmin and 37 units in the heparin group. These differences were significant.

Adult

[Risk factors for venous thromboembolism].

In addition to the well known general risk factors for thromboembolic events certain alterations of the clotting system are of considerable importance and are, therefore, described in detail. Such preexisting alterations should be suspected when spontaneous thrombosis is found in patients under 40 years of age and when there is also a history of thrombosis in the patient's family.

Blood Coagulation Factors

[Use of antithrombin III concentrates].

Concentrates of antithrombin III (AT III) have been applied in congenital as well as in acquired AT III deficiency. Congenital defects only require substitution during surgery and in the case of pregnancy. Otherwise prophylaxis of thrombosis can be successfully carried out with oral anticoagulants. In acquired AT III deficiency substitution was found to be useful in cases of advanced DIC. When AT III activity was constantly kept around 100% the duration of DIC could be considerably shortened. No beneficial effect of additional administration of heparin was found. In cases of DIC due to septic shock the survival rate could be increased from an average of 20% without substitution to over 70% with AT III substitution as could be shown by different authors.

Antithrombin III

Antithrombotic therapy in patients with known risk factors for thromboembolism.

In about 50% of the cases of spontaneous deep vein thrombosis a congenital deficiency of an inhibitor of coagulation or an insufficient fibrinolytic mechanism can be detected. In arterial thromboembolism a connection with hyperactive platelets or with a diminished availability of tissue plasminogen activator can be found in about 70%. However, in these cases the defect which provokes thrombosis is mostly acquired and is connected with hyperlipidemia and/or with atherosclerotic alterations of the vessel wall. A study on patients with thromboembolic tendency and detectable risk factors was carried out. A total of 470 patients could be observed for 2 years under an adequate antithrombotic prophylaxis. The occurrence of thromboembolic episodes 2 years prior to prophylaxis and 2 years under prophylaxis was compared. In venous cases thrombosis could be controlled almost completely by coumarins when the underlying cause was a deficient plasmatic inhibitor. In patients with diminished fibrinolysis there was only a partial effect of oral anticoagulants. A better result could be obtained when pentosan polysulfate was administered. In arterial thromboembolism the results of prophylaxis were less convincing. The efficacy of ASA in patients with an increased platelet function was only moderate. In addition, ASA hat to be discontinued in about 20% of the patients because of gastrointestinal problems. Pentosan polysulfate in patients with a diminished fibrinolytic capacity had a fairly good effect and resulted in a 60% reduction of thromboembolic manifestations. It is shown that an exact diagnosis of the underlying deficiency which is likely to cause thrombosis can also improve the efficacy and the specificity of prophylaxis.

Age Factors

Immunological status and HIV antibodies in patients with haemophilia--a longitudinal study.

Various immunological parameters were investigated in 12 children suffering from severe haemophilia A or B receiving substitution therapy over a follow-up period of 3 1/2 years. At the beginning of the study, the therapy was changed to heat-treated concentrates of factors VIII or IX. Antibodies to HIV were found in 9 out of these patients. There were no AIDS-related clinical symptoms, but HIV antigen was detectable in one case. Abnormalities of immunological parameters were found independently of HIV infection, but were more pronounced in anti-HIV seropositive patients. Elevated levels of immunoglobulins gave evidence of polyclonal B-cell activation whilst increased levels of neopterin indicated activated T-cells and macrophages. There was no close association between these two types of activation. However, peak activation of both immune compartments was found approximately 1 year after changing the therapy. Thereafter a continuous tendency towards normalization of neopterin levels was observed. At the final visit immunoglobulin levels also tended to decrease. The HIV antigen seropositive child showed the highest neopterin levels during the whole study period. Our data indicate that the primarily high risk of developing AIDS in anti-HIV-seropositive haemophiliacs is declining.

Acquired Immunodeficiency Syndrome

Basics and practice in evaluating plasminogen.

There exist different ways of assays of plasminogen which give information about different properties of this proenzyme. The concentration of plasminogen can be determined by its antigenicity. Since the normal concentration of plasminogen in plasma is between 15 and 25 mg/dl the test can be carried out by simple methods such as radial immunodiffusion on Partigen plates. The possibility of errors is small and there is no need of special apparatus. The disadvantages are the lapse of 24 h until the result is available and the fact that the knowledge of the concentration does not give any information about the activity. The activity can be measured by different coagulation tests. A typical assay would involve activation of plasminogen to plasmin, addition of plasminogen-free thrombin and measuring of the lysis time. The result is however, dependent on more than one variable. Plasmin is rapidly inhibited by alpha-2-antiplasmin (APL) and there is also a dependence of the lysis time on the amount of clottable fibrinogen in the test system. Better results can be obtained by the use of diluted test plasma and addition of a constant amount of plasminogen-free fibrinogen. A different way would be the use of the euglobulin fraction instead of plasma. This has however, the possible disadvantage of incomplete precipitation of plasminogen. Instead of coagulation tests the activity can also be determined when diluted activated plasma is placed on plasminogen-free fibrin plates and the amount of lysis in the plate is recorded. All assays of this group also depend on the method of activation of plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests

New diagnostic possibilities for the detection of thrombophilic states.

A series of coagulation tests is described by which an increased thrombotic tendency is likely to be detected. These tests were carried out in 268 patients with venous thromboembolic disease and in 583 patients with arterial thrombotic manifestations. In venous thromboembolism alterations which point to hypercoagulability were found in 50% of all cases. Most frequent findings were a diminished availability of t-PA followed by low levels of Protein C, AT III and of Heparin cofactor II. In arterial thrombotic disease alterations of the clotting system were found in 77% of the patients. There was a high frequency of increased spontaneous platelet aggregation, of a diminished t-PA availability and of a combination of both alterations. Other abnormal results were rare with the exception of a diminished Heparin cofactor II which was found in 3% of the patients. The consequences which arise for prophylaxis and therapy when the defect is known are discussed.

Adult

Heparin cofactor II: a simple assay method and results of its clinical application.

A simple assay method of heparin cofactor II (HC II) activity is described. The procedure is based on the following principle: Antithrombin III (AT III) in plasma is inactivated by addition of an IgG fraction of goat serum after immunization of the animals against human AT III. Complete inactivation of AT III could be shown by absence of an anti Xa-effect of heparinized plasma treated with this antibody. Thrombin was only partially inhibited after inactivation of AT III. The characteristics of this inhibition were typical for the action of HC II. This method was applied for an assay of HC II activity. After optimizing of the method practical application in clinical routine screening was carried out. A diminution of HC II was observed in liver cirrhosis and in DIC but not in AT III deficiency. In 15 out of 269 cases of recurrent DVT there were HC II activities below 70% of normal. In 4 out of these patients activities of HC II were repeatedly between 44% and 52%. In arterial obstructive disease there was an HC II activity of less than 60% in 18 out of 583 patients and in 11 of them the HC II levels were repeatedly between 45% and 54%.

Antithrombin III

[Modification of eicosanoid synthesis by calcium dobesilate].

Calcium dobesilate is a vasoactive drug with well-known effects on endothelial integrity, vascular wall permeability and blood viscosity. A clinical study demonstrated that serum thromboxane formation is significantly decreased by calcium dobesilate in patients suffering from peripheral vascular disease. Hence an in vitro study has been undertaken to determine the influence of calcium dobesilate on eicosanoid formation both by platelets and the arterial wall. Radio-thin-layer chromatography (RTLC) of human platelets does not show any influence of the drug on eicosanoid conversion in a dose range from 10 to 1000 micrograms/ml. By contrast, the vascular conversion of eicosanoids shows a dose-dependent trend towards a decrease in cyclooxygenase products. However, using the same doses, no effect is observed on vascular PGI2 formation in vitro, as assessed by means of the platelet aggregation bioassay and thus no inhibitory effect on cyclooxygenase of the arterial wall can be deduced. These laboratory findings provide no explanation for the clinical efficacy of calcium dobesilate and the diminution in serum thromboxane. A different mode of metabolic conversion of endogenous and exogenous arachidonic acid is suggested as explanation for these contradictory results.

Arachidonic Acid

[New methods of thrombolysis].

Different possibilities of clinical thrombolysis are described. The classical therapy with streptokinase has the disadvantages of antigenicity and of a considerable influence on the clotting system. For this reason new methods of thrombolysis were examined. Urokinase, plasmin and t-PA are physiological substances and have, therefore, no antigenicity. However, plasmin also has a considerable influence on the clotting system whilst coagulation is only moderately influenced by urokinase. This necessitates additional administration of heparin when the dose of urokinase is low. t-PA is adsorbed onto the fibrin clot in the same manner as plasminogen. Thereby both substances acquire a considerably higher affinity for each other. In addition, inactivation by physiological inhibitors is considerably diminished after adsorption. This causes an almost exclusive lysis of the clot without alterations of systemic coagulation. Clinical results after application of the newer thrombolytic drugs are presented.

Coronary Disease

Protein C: comparison of different assays in normal and abnormal plasma samples.

Two assay methods for Protein C (PC) are described. Both tests are based on the activation of PC by a fraction of the venom of the Copperhead snake. Activated PC can be measured either by cleaving of a chromogenic substrate or by an APTT test. Both tests were compared with ELISA tests for PC. In 27 healthy persons the results were around 100% by all test systems when compared with normal pooled plasma. In 13 patients under stable anticoagulant therapy the average results were 54% for the ELISA and 52% for the chromogenic substrate test whilst the corresponding figures were 22% for the APTT test and 25% for the Quick test. In 4 cases of liver cirrhosis PC was diminished and there was no difference between the three tests. In two patients with congenital PC deficiency all results were close to 50% and in three patients the ELISA and the substrate tests were normal but the APTT test showed results of 44, 28 and 54% respectively. These results give rise to the conclusion that the snake venom activator is also capable of activation of decarboxylated PC molecules which can thereby split a chromogenic substrate but remain inactive in an APTT test.

Biological Assay