PubMed Health⌕ Search

Biomedical subjects

U Hedner

Publications and source records attributed to U Hedner.

At least 127 records · Page 7Linked to original sources
PubMed1984

Actions and interactions of acetylsalicylic acid, salicylic acid and diflunisal on platelet aggregation.

Acetylsalicylic acid (ASA) is increasingly employed in the secondary prophylaxis of thromboembolic diseases, due to its capacity to inhibit platelet aggregation. The anti-aggregatory effect of ASA on platelets can be inhibited in vitro by a high concentration of salicylic acid (SA). SA is generated in vivo upon ASA administration, and the SA thus formed might impair the antiplatelet effect of ASA. To assess this possibility, the platelet response to ASA was tested in healthy volunteers before and after medication for 1 week with ASA 1 g t.i.d., with SA 1 g t.i.d., and with the SA derivative diflunisal 0.5 g b.i.d. Pre-medication test doses of 1 g ASA always inhibited platelet aggregation in vivo. Neither treatment with SA nor diflunisal, producing plasma steady-state concentrations of about 1.0 and 0.35 mmol/l, respectively, inhibited platelet aggregation. Nor did administration of SA, diflunisal or ASA itself impair the anti-aggregatory effect of a fresh test dose of ASA. ASA inhibited platelet aggregation in vitro at 0.03 mmol/l, whereas SA and diflunisal failed to impair platelet aggregation until concentrations exceeding 2.0 and 0.5 mmol/l, respectively, were reached. These findings make it unlikely that SA formed upon administration of ASA would impair the anti-aggregating capacity of ASA.

Adult↗
PubMed1984

The effect of sodium hyaluronate and sodium chondroitin sulfate on the coagulation system in vitro.

Healon (sodium hyaluronate) and sodium chondroitin sulfate (CDS) are injected in the ocular cavities in a variety of operations, mainly intraocular lens (IOL) implantation. Both Healon and CDS are structurally similar to heparin. We found that like heparin CDS has an inhibiting action on blood coagulation in vitro. The inhibiting activity is of the antithrombin type. Healon does not possess anticoagulant activity. Since the anticoagulant effect of sodium chondroitin sulfate is observable at concentrations likely to occur in vivo the substance may impair ocular hemostasis.

Blood Coagulation↗
PubMed1984

Tolerance and biochemical effects from intravenous injection of ioxaglate in healthy volunteers.

The influence of intravenous injection of ioxaglate (Hexabrix, 320 mg I/ml) on various biochemical, coagulation and fibrinolytic parameters, fractionated plasma proteins, precordial ECG and blood pressure was prospectively and sequentially studied in 9 healthy volunteers. One ml/kg body weight of the contrast medium was injected within one minute into an antecubital vein. Small, but statistically significant, changes in some of the biochemical parameters were found during the observation period, 2 to 4 days. All values of the biochemical parameters were, however, within the normal reference range for each parameter. No significant alterations were seen in the coagulation parameters. Increased fibrinolysis was recorded in some subjects both before and after the injection. No fibrinolytic degradation products were found indicating that the fibrinolysis was nominal. No significant changes were observed in the fractionated plasma proteins. The heart rate decreased significantly 15 seconds after commencing the injection. No significant changes in blood pressure were recorded. Two participants became nauseated and one of them vomited during the injection. Apart from this, no adverse effects were noted. No clinically significant changes following the injections were found.

Adult↗
PubMed1984

Postoperative haemostatic changes in patients given thromboembolic prophylaxis with dextran 70--alone, or in combination with dihydroergotamine.

Haemostatic changes were studied in 107 patients undergoing elective general and urologic surgery or hip replacement. All patients received dextran 70 and half of them, randomly chosen, were also given dihydroergotamine. Blood samples were taken before operation and on the fourth postoperative day. In all patients increases in factor VIII:C, VIII:R Ag and fibrinogen were noted, and decreases in thrombin time, antithrombin III and alpha 2-macroglobulin. In patients undergoing hip replacement, alpha 2-antiplasmin (measured amidolytically) also increased. No major intergroup differences were noted. Comparison between elective hip patients given general anaesthesia and those given epidural analgesia revealed no major differences in haemostatic response. From our findings it would appear that the coagulation and fibrinolytic systems remain unaffected by dihydroergotamine.

Aged↗
PubMed1983

Anticoagulant effects of two types of low molecular weight heparin administered subcutaneously.

Two types of LMW heparin were prepared by gel filtration of standard heparin (LMW fraction) and by degradation of heparin by nitrous acid (LMW fragment), respectively. The effects on factor Xa inhibition (XaI), APTT, platelet aggregation and AT III level of these preparations were studied after subcutaneous administration to humans and compared with those of standard heparin. At a dose of 5000 IU (XaI) the LMW fraction and LMW fragment induced peak plasma XaI activity of 0.32 IU/ml and 0.41 IU/ml respectively, compared to 0.07 IU/ml for heparin. Still 11.5 h after administration both LMW preparations gave higher activities than heparin ever induced. Following administration of 10,000 IU (XaI) of the LMW fragment the plasma peak XaI activity was 0.81 IU/ml. This prolonged the APTT from 36 sec to 46 sec only. The half-lives of the XaI activity in plasma were between 3 and 4 hours. No effect on platelet aggregation or AT-III level was demonstrated.

Adult↗
PubMed1983

The effect of dihydroergotamine on platelets, coagulation and fibrinolysis, studied in healthy humans and in dogs.

The effect of dihydroergotamine (DHE) on platelets, coagulation and fibrinolysis was studied in healthy volunteers ex vivo before and after intravenous administration (0.5 mg). In addition, the effect of DHE in different concentrations on platelet aggregation was evaluated in vitro. Haematocrit was found to increase, as did factor VIII:C and antithrombin III - though the latter increases were not significant when correction was made for the altered haematocrit. Though platelet function ex vivo was unchanged, inhibition of adrenaline induced platelet aggregation was noted in vitro when the plasma concentrations of added DHE were higher than those obtained with clinically relevant doses. No effect on fibrinolysis was noted.

Adult↗
PubMed1983

Induced tolerance in hemophilia patients with antibodies against IX:C.

Two patients with severe hemophilia B complicated with antibodies against factor IX have been treated 13 and 10 times, respectively, with high doses of factor IX concentrate in combination with cyclophosphamide over a period of 10 years. During this treatment a lowering of the anamnestic response was observed over the years. Both patients have now been treated with factor IX and hydrocortisone but no cyclophosphamide in order to find out if real tolerance was induced. One patient received such treatment three times and the other once. Their inhibitor titer following these treatment episodes never exceeded 0.3 U/ml (approximately 0.9 BU/ml) and 0.9 U/ml (approximately 2.7 BU/ml) which is of the same order of magnitude as following the combined treatment (factor IX, hydrocortisone and cyclophosphamide). It is therefore suggested that these patients have been converted from high responders (10-100-fold increase in the inhibitor titer on the original treatment with factor IX and hydrocortisone) into low responders showing a very reasonable inhibitor increase after treatment with factor IX and hydrocortisone but no cyclophosphamide.

Adult↗
PubMed1983

Influence of operative trauma on factor XII and inhibitor of plasminogen activator.

A parallel decrease of factor (F) XII and a fibrinolytic inhibitor of plasminogen activation (PA inhibitor) was found in a series of 52 patients subjected to vascular surgery. It was at a maximum on days 2-4 postoperatively. The most extensive decrease was found in patients undergoing aortoiliac bypass operation. These patients had the highest blood loss and the longest operation times indicating that the changes were correlated to the magnitude of surgical procedure. The parallel decrease of F XII and the fibrinolytic inhibitor suggests an association between these two proteins in vivo.

Adult↗
PubMed1983

Use of human factor VIIa in the treatment of two hemophilia A patients with high-titer inhibitors.

Two patients with hemophilia A complicated with high-titer alloantibodies have been treated by repeated infusions of microgram quantities of pure human Factor VIIa. Patient 1 was presented with a gastrocnemius muscle bleeding that involved the knee joint. Upon treatment with Factor VIIa the circumference of the muscle decreased and joint mobility increased substantially. Patient 2 was given Factor VIIa concurrent with tranexamic acid in association with the extraction of two primary molars. No significant gingival bleeding occurred after Factor VIIa and tranexamic acid treatment. Furthermore, no deleterious side effects or increase of the alloantibody level were observed in either patient throughout the Factor VIIa infusion. These results, although limited and preliminary in nature, suggest that trace quantities of Factor VIIa can act as a Factor VIII bypassing activity and restore hemostasis in these patients.

Adolescent↗
PubMed1983

Pregnancy and venous thrombo-embolism.

In 30 patients with objectively diagnosed and 13 with clinically diagnosed venous thrombosis during pregnancy the extension and localization of the thrombotic process was analysed in relation to the coagulation and fibrinolytic status at least 6 months after thrombosis. Left-sided thrombi pre-dominated, being more extensive and proximal on the left side. Most thrombi started during the last two trimesters. Few changes were found in the coagulation system. Nineteen per cent of the patients showed a defective fibrinolytic system, as diagnosed by a reduced release capacity and/or a reduced fibrinolytic activity in the vessel wall. No great differences were found between patients with clinical vs. objective diagnosis.

Adult↗
PubMed1983

A technique for specific removal of factor IX alloantibodies from human plasma: partial characterization of the alloantibodies.

A method for specific removal of large amounts of factor IX:C alloantibodies by a resin to which highly purified factor IX was linked (factor IX CH-Sepharose) is described. Factor IX was isolated from human plasma by a three-step procedure, including barium citrate adsorption and elution, DEAE-Sepharose CL-6B chromatography, and dextran sulfate agarose chromatography. Approximately 100 mg factor IX was obtained from 60 liters of plasma. The preparation was about 95% pure as judged by SDS-PAA gel electrophoresis. Its specific coagulant activity was 160 U/mg (IX) and its factor IX clotting antigen (IX:Ag) 500-600 U/mg. Essentially quantitative coupling of the factor IX preparation to activated CH-Sepharose 4B was obtained (4 mg factor IX/ml gel; 2300-3000 U/IX:Ag/ml). This resin bound 1500-2000 U factor IX inhibitor/ml gel and could be re-used at least 5 times without any loss in binding capacity. The binding capacity was dependent on the flow rate. No signs of activation of the coagulation, fibrinolytic, or complement system were observed in vitro. Using this factor IX resin, factor IX alloantibodies were isolated and found to consist of two portions, one minor bound to the resin only in the presence of Ca2+ and another major portion Ca2+ independent. The specific inhibitory activity/milligram IgG of the Ca2+-dependent alloantibodies was about 5 times higher in the presence of Ca2+. It is concluded that 25 ml of the factor IX resin described can remove about 40,000 factor IX inhibitor units (comparable to 120,000 Bethesda U) in one run, provided the flow rate does not exceed 20 ml/hr. By using such a technique for removal of antibodies it seems feasible to convert hemophilia-B patients complicated with inhibitors against factor IX into ordinary hemophilia-B patients for treatment at an emergency or in association with major surgery.

Calcium↗
PubMed1982

Demonstration of 99mTc-labelled plasmin on the surface of ex vivo thrombi.

In an vitro system using the Chandler model for the preparation of in vitro thrombi trace amounts of porcine or human 99mTc-labelled plasmin was found to adsorb to the surface of a preformed thrombus. A radioactive lining of the thrombus could be demonstrated using autoradiography after addition of 99mTc-labelled plasmin in concentrations of 0.04 - 0.07 or 0.4 - 0.7 CTA u/thrombus made from 2 ml whole blood (0.035 - 0.35 microM). The same pattern was found for porcine as for human plasmin. The presence of tranexamic acid in concentrations of 3 to 12 mM did not affect the binding of plasmin indicating that the plasmin binding to fibrin was independent of the lysine binding sites. Furthermore alpha 2-antiplasmin was demonstrated on/in the thrombus also when no plasmin was present indicating a binding of alpha 2-antiplasmin to the thrombus. The plasmin bound to the thrombus was proteolytically inactive. In order to obtain thrombolysis most of the alpha 2-antiplasmin in the surrounding medium had to be neutralized.

Animals↗
PubMed1982

Oral contraceptives and venous thromboembolism.

In 58 patients with phlebographically diagnosed deep vein thrombosis during oral contraception the extension and localization of the thrombotic process was analysed in relation to the coagulation and fibrinolytic system 6 months after thrombosis. Left-sided thrombi dominated and the thrombi were more extensive and proximal on the left side. This left-sided dominance was more apparent with higher oestrogen content in the pills. The right-sided thrombi more often were the source of pulmonary embolism. In 31% of the patients a defective fibrinolytic system was found; this defect was seen more often in patients with right-sided thrombi. Only very few defects were found in the coagulation system. No patients had an antithrombin III deficiency.

Adolescent↗
PubMed1982

Prospective study of a phenformin-like substance (moroxydine chloride) in patients with deficient vessel wall fibrinolysis.

It is known that ethylestrenol and/or phenformin can normalize deficient fibrinolysis in the vessel walls and prevent recurrent thromboembolism (Hedner et al., 1976; Nilsson et al., 1975, 1981). Because of the side-effects of phenformin, we studied the effect of a phenformin-like substance: moroxydine chloride (Kabi 1886), which unlike phenformin, does not cause lactic acidosis. A prospective randomized clinical trial was carried out on 49 patients with a decreased release capacity of fibrinolytic activity (venous occlusion test for 20 min as described by Robertson et al. (1972) on at least two occasions. They received either moroxydine chloride in a dose of 0.04 g/kg a day or no specific treatment. Most of the patients had earlier at least one episode of deep venous thrombosis. At review 6 months after entering the trial, it was found that out of 26 patients receiving moroxydine chloride, the release capacity was normal in 16 (62%), compared with 5 (22%) of the 23 controls. Dicoumarol alone did not seem to have any effect on the fibrinolysis. The only side-effects were occasional diarrhea in two, which was controlled by reduction of the dose, and itching requiring withdrawal of the drug in one. Moroxydine chloride, thus, seems to normalize a defective release capacity of vessel wall in a fair percentage of cases.

Adolescent↗