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Biomedical subjects

D Lockner

Publications and source records attributed to D Lockner.

At least 37 records · Page 2Linked to original sources
PubMed1990

Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT).

In a prospective, randomized, open study 119 consecutive patients with phlebographically verified deep venous thrombosis (DVT) of the leg (36% distal and 64% proximal) were treated either with a low molecular weight heparin (Fragmin, Kabi-Vitrum) subcutaneously (120 anti-FXa U/kg) twice daily or standard heparin (SH) as continuous intravenous infusion (480 IU kg-1 day-1). The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2-0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection. The SH dose was modified to prolong the APTT 2-3 times. Repeat phlebography after 5-7 days showed improvement in 34/45 patients (76%) in the Fragmin group and in 30/49 patients (61%) in the SH group and progress in 2/45 (4%) and 3/49 (6%), respectively. The mean Marder scores decreased from 18.7 +/- 12.1 to 15.7 +/- 12.7 in the Fragmin group and from 16.9 +/- 12.0 to 14.4 +/- 11.8 in the SH group (ns). Two patients in the SH group and none in the Fragmin group had major bleedings. After 22 +/- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group. Postthrombotic signs and symptoms were similar in both groups. We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg.

Adult↗
PubMed1990

Fatal pulmonary embolism caused by streptokinase treatment of deep venous thrombosis of the leg?

During the last 10 years, four of 150 (2.7%) patients with deep venous thrombosis (DVT) treated with streptokinase (SK) at our department have died of pulmonary embolism (PE). A retrospective study of 1393 DVT patients treated with heparin during the period 1973-1986 showed that five (0.36%) of these patients died of PE while still on heparin. In this paper we describe the four patients treated with SK who developed fatal PE. In our opinion this increase in mortality does not warrant the use of SK in routine treatment of DVT of the leg before a proper trial has been conducted to compare the frequencies of pulmonary embolism after both treatments.

Adult↗
PubMed1988

Clinical experiences in the administration of a low molecular weight heparin (Fragmin, Kabi-Vitrum) to healthy volunteers and in the treatment of established deep venous thrombosis.

A low molecular weight heparin (Fragmin, Kabi-Vitrum) with a mean molecular weight of 4,000-5,000 D has been investigated in healthy volunteers and in patients with DVT. We found a T 1/2 of 4 hours and a high bioavailability after subcutaneous injection in volunteers. In a randomised study, patients with phlebographically verified DVT, 120 U(anti-FXa)/kg Fragmin injected twice daily was found to be as effective as 240 U/kg, 12 h standard heparin as continuous infusion in preventing DVT progress. No major bleedings were seen in the Fragmin group. We conclude that Fragmin administered subcutaneously twice daily results in adequate anticoagulation and is safe and practical in the treatment of DVT.

Biological Availability↗
PubMed1987

A pilot study; desmopressin (DDAVP) in the treatment of deep venous thrombosis.

In a pilot study on 9 patients with acute deep venous thrombosis of the leg the fibrinolytic response and the possible thrombolytic effect of desmopressin (DDAVP), when given supplementary to standard heparin treatment, was examined. Six injections of 0.3-0.4 microgram DDAVP/kg b.w. at 12 hours intervals were given. No serious side effects were observed. The fibrinolytic variables that followed showed that plasma levels of t-PA increased significantly and most pronounced after the first injection. Rephlebography 4-7 days after hospitalization showed partial thrombolysis in 7 out of 9 patients. The phlebographic score according to Marder was reduced from 22.7 +/- 12.1 to 18.4 +/- 10.1 (p = 0.018), corresponding to a thrombus size reduction of 19%. No correlation between the level of the fibrinolytic variables measured and the degree of thrombolysis in the individual patients, could be demonstrated in this small number of patients.

Antigens↗
PubMed1987

Acute unidentified hepatitis in a hypogammaglobulinaemic patient on intravenous gammaglobulin successfully treated with interferon.

A 59-year-old male with acquired hypogammaglobulinaemia since 1978 developed a fulminant hepatitis. The hepatitis appeared after two years intravenous treatment with Sandoglobulin (Sandoz, Switzerland). No virus markers could be detected in the body fluids or liver tissue. Blood transfusions had not been given within one year before development of the liver disease. There was strong suspicion that the patient had acquired non-A non-B hepatitis from the gammaglobulin infusions. Treatment with alpha-interferon ran parallel to a normalization of the pathological liver enzymes and the histology of the liver. This observation suggests a direct antiviral effect of alpha-interferon, despite the anecdotical and noncontrolled character of these data.

Agammaglobulinemia↗
PubMed1986

Low molecular weight heparin (KABI 2165, Fragmin): pharmacokinetics after intravenous and subcutaneous administration in human volunteers.

The pharmacokinetics of a low molecular weight heparin (LMWH) with a mean mw of 4000-6000 D (KABI 2165, Fragmin) was studied in 6 healthy volunteers after intravenous (iv) and subcutaneous (sc) administration of 120 U (anti FXa)/kg. The half-life in plasma of the anti FXa activity after iv injection was 119 +/- 17 min, the volume of distribution (Vd) 3.4 +/- 0.5 1 and the total clearence 20.5 +/- 2.5 ml/min. The maximal anti FXa activity determined 3 min after iv bolus injection amounted to 2.2 +/- 0.3 U (anti FXa)/ml with a corresponding increase of the APTT from 31 +/- 7 sec to 113 +/- 35 sec. The elimination of the anti FXa activity was a monoexponential first order process. After sc administration the plasma half-life of the anti FXa activity was longer than after iv injection, 228 +/- 40 min, corresponding to the absorption rate thus found to be the rate limiting step. After sc administration the peak was reached after 4 hours (0.6 +/- 0.1 U (anti FXa)/ml; APTT increase 5 sec). The bioavailability after sc injection was calculated to be 87 +/- 6%. As a consequence of the high bioavailability and long T1/2 of the anti FXa activity, Fragmin administered sc seems to induce adequate levels of heparin-like activity making this regimen worth further investigation as an alternative for the treatment of deep venous thrombosis.

Adult↗
PubMed1986

Long-term sequelae of calf vein thrombosis treated with heparin or low-dose streptokinase.

A prospective randomized study was performed to investigate the long-term sequelae of calf vein thrombosis (CVT) and correlate them to the success of the initial treatment. Thirty-six patients with symptomatic CVT, verified by venography, were treated with heparin or low-dose streptokinase (SK) combined with low-dose heparin. Venography was repeated after 1 week, and long-term follow-up was performed clinically and with foot volumetry after an average of 5 years. Since the low-dose SK regimen led to serious hemorrhagic side-effects in a parallel study, the present investigation was discontinued prematurely. The thrombolysis achieved was greater with SK but, since the initial thrombi were somewhat larger in this group, no significant difference in the average size of the thrombi after therapy could be displayed between the groups. The long-term sequelae and results of foot volumetry were also equal. Signs or symptoms of venous insufficiency were found in 37%, and foot volumetry showed deep venous insufficiency in 26% of the cases. There was a correlation between the hemodynamic change, as assessed by foot volumetry, and the venographic severity. This relation was stronger for the size of the thrombus after treatment than for the initial size. Thus, it seems important to limit the extent of a CVT in order to minimize the long-term sequelae, but administration of SK is not justified due to side-effects.

Acute Disease↗
PubMed1986

Pharmacokinetics of intravenously and subcutaneously administered Fragmin in healthy volunteers.

Studies in 8 healthy volunteers showed that the low molecular weight heparin Fragmin KabiVitrum is eliminated according to first order kinetics without dose dependency after intravenous injection of doses between 40 and 120 anti-Xa U/kg. Fragmin remains in the circulation more than twice as long as unfractionated heparin (UFH). Fragmin administered subcutaneously has a bioavailability which is much greater than that of UFH. Fragmin administered subcutaneously twice a day results in a significant anti-Xa activity and provides an alternative to intravenous infusions.

Adult↗
PubMed1986

Intravenous and subcutaneous administration of Fragmin in deep venous thrombosis.

54 patients with venographically verified deep venous thrombosis (DVT) were randomized to treatment with either intravenous infusions of 240 anti-Xa U/kg/12 h unfractionated heparin (UFH) or 240 or 120 anti-Xa U/kg/12 h of the low molecular weight heparin Fragmin. Repeated venographies showed improvement in 48% of the UFH-treated patients and 50 and 77%, respectively, in the Fragmin-treated patients. Progression was seen only in the UFH-treated patients and was observed in 11%. Two bleeding complications were seen in the Fragmin group in 2 patients receiving the very high dose of 240 anti-Xa U/kg/12 h. Anti-Xa activity in plasma and activated partial thromboplastin time (APTT) does not correlate in the Fragmin-treated patients. Fragmin was as effective as UFH in preventing the progress of thrombosis in DVT. In another study 120 anti-Xa U/kg Fragmin given subcutaneously 2 times daily to 13 patients with DVT resulted in adequate anti-Xa activity but with a tendency for accumulation of the Fragmin-induced activity. Subcutaneous injections of Fragmin 2 times daily also appears to prevent the progression of thrombosis effectively.

Adult↗
PubMed1985

A comparison between low molecular weight heparin (KABI 2165) and standard heparin in the intravenous treatment of deep venous thrombosis.

In order to study whether a low molecular weight heparin (LMWH) of mw 4000 D is effective in the treatment of deep venous thrombosis (DVT), patients with DVT verified by phlebography were randomized to treatment by continuous intravenous infusion of either unfractionated heparin (UFH) or LMWH. The initial dose was 240 U (anti F Xa)/kg/12 h. This study (study I) was stopped because of major bleeding in 2 newly operated patients in the LMWH group after 27 patients had been treated. The heparin activity measured as F Xa inhibition assayed in retrospect, was found to be much higher in the LMWH group (mean 1.6-2.0 anti F Xa U/ml) than in the UFH group (mean 0.5-0.8 anti F Xa U/ml). A second study was therefore initiated in which the DVT patients were randomly given UFH (240 U/kg/12 h) or LMWH only 120 U (anti F Xa)/kg/12 h, as initial doses (study II). In this study 27 patients could be evaluated, the mean heparin activity still being higher in the LMWH group (0.9-1.2 anti F Xa U/ml) than in the UFH group (0.5-0.7 anti F Xa U/ml). A second phlebographic investigation showed progression of thrombus size in 3 (11%) of the UFH patients of studies I and II (n = 29) and improvement in 14 (48%). There was no progression in any LMWH patient, 6 (50%) had improved in study I and 10 (77%) in study II. The mean decrease of thrombus size score (according to Marder) during treatment did not differ between the 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Thrombolysis and fibrinolytic parameters during heparin treatment of deep vein thrombosis.

Thirty-nine patients with symptomatic, venographically verified deep vein thrombosis (DVT) were studied during treatment with heparin in order to investigate the correlation between the venographic changes and parameters of heparin therapy or fibrinolytic components. Venograms were scored with a 40-grade scale, and after one week a significant improvement with an average reduction of the thrombi of 17% was observed. No statistically significant correlation was found between reduction of thrombus size and duration of heparin treatment, total amount of heparin administered, mean levels of APTT, plasmin-alpha 2-antiplasmin complex (PAP), tissue plasminogen activator (t-PA) antigen or t-PA-inhibitor. Only a short history of the thrombus was significantly correlated to thrombolysis. The concentrations of PAP and t-PA-inhibitor were not influenced, while that of t-PA antigen showed a significant increase during heparin infusion. Even if statistically significant correlations were not obtained, the patients with pronounced thrombolytic effect had high PAP-levels. Furthermore, patients with high t-PA-inhibitor levels had no lysis. The results suggest, that also other factors than plasminogen dependent fibrinolysis are of importance for the thrombolytic effect.

Blood Coagulation Tests↗
PubMed1985

A human pharmacological study comparing conventional heparin and a low molecular weight heparin fragment.

The pharmacokinetics of a heparin fragment of low molecular weight (LMWH) of 4000-5000 D and unfractioned standard heparin (UFH) have been studied after i.v. injections of different doses and infusions in 8 humans. The heparin activity was significantly higher and the effect on APTT lower after LMWH fragment as compared to UFH in the same doses. The half-life of heparin activity was about 1 hr for UFH and about 2 hr for LMWH. LMWH was found to be eliminated according to first order kinetics and there were no signs of dose dependency.

Adult↗
PubMed1985

Relationship between thromboembolic complications and intensity of treatment during long-term prophylaxis with oral anticoagulants following DVT.

The frequency of thromboembolic recurrencies during secondary prophylaxis after DVT was retrospectively studied and related to the intensity of the oral anticoagulation. All patients receiving oral anticoagulation after DVT at our hospital during April 1972-May 1980 were studied. Treatment was given to 596 patients for 724 thrombotic events for a total of 4450 months. Thirty-six thromboembolic complications, all objectively verified, occurred. Patients with cancer had complications throughout the entire range of anticoagulation. Patients without neoplastic disease (15 events) never had complications below a prothrombin complex level of 27% as assessed with Simplastin A, corresponding to a BCT-ratio of 1.9. This study confirms, that the lower limit of the therapeutic range, determined by the risk of thromboembolic complications, should be set at a Simplastin A-level of approx. 25% corresponding to BCT 2.0.

Administration, Oral↗
PubMed1985

Kinetics of the spontaneously occurring common variable hypogammaglobulinemia: an analysis of two individuals with previously normal immunoglobulin levels.

Two males with previously normal serum immunoglobulin levels who spontaneously developed common variable hypogammaglobulinemia were investigated. In one patient serum samples obtained before and after the development of hypogammaglobulinemia were analyzed. A parallel decrease in serum IgM, IgG (all 4 subclasses), IgA (both subclasses) as well as kappa and lambda light chains was found. Serum IgD and IgE also decreased but reached a minimum level before the other immunoglobulin classes. A bone marrow aspirate obtained before the development of hypogammaglobulinemia in this patient showed 1.2% plasma cells, whereas the frequency was only 0.1% when low serum immunoglobulins were recorded. These observations demonstrate the existence of adult onset hypogammaglobulinemia.

Adult↗
PubMed1985

The duration of oral anticoagulation after deep vein thrombosis. A randomized study.

Eighty patients with deep vein thrombosis (DVT) were randomized between our routine duration of oral anticoagulation and 50% reduction thereof, in order to evaluate whether shorter therapy could be given without increased risks. The study was stratified, so that 20 patients with the 1st episode of DVT caused by a temporary risk factor were treated for 1.5 or 3 months, 40 patients with the 1st episode of DVT caused by a permanent risk factor for 3 or 6 months, and 20 patients with the 2nd episode of DVT for 6 or 12 months. When warfarin therapy was discontinued, the patients were followed by means of venous occlusion plethysmography every 3 months for 1 year, and clinically for 15-27 months in the different subgroups. Thromboembolic complications were registered and verified by venography and perfusion lung scan. We could not detect any difference between the groups. The rate of rethrombosis and embolism during 12 and 24 months after cessation of anticoagulant therapy was 8 and 10%, respectively, among the patients with reduced duration of treatment and 8 and 14%, respectively, among those with regular duration. One fatal, warfarin-induced hemorrhage occurred. It is important to reduce unnecessary extension of oral anticoagulation after DVT in order to minimize the negative side-effects without increasing the recurrence rate. More extensive trials should be performed to confirm our results and define the optimal duration of treatment.

Adult↗
PubMed1985

Factors and inhibitors of blood coagulation and fibrinolysis in acute nonlymphoblastic leukaemia.

Factors of coagulation and fibrinolysis have been evaluated in 15 patients with untreated acute nonlymphoblastic leukaemia (ANLL). 10 patients had major bleeding (MB) and 6 had laboratory signs of DIC. 5 patients went into complete remission (CR). Antithrombin III (AT III) was decreased in 7 patients, antiplasmin (AP) in 9, fibronectin (FN) in 6 and factor XIII in 4/12. The ratio between factor VIIIR:Ag and factor VIII:C was over 2.0 in 11 patients, and high values were especially seen in patients with MB and patients with DIC. Spontaneous proteolytic activity, measured with S-2288 was increased in 3 patients who all had MB, and none of whom achieved CR. 2 patients with promyelocytic leukaemia (M3) had low fibrinogen and AP, high FDP and normal AT III, speaking for primary fibrinolysis, which in addition to proteolytic enzymes in the blast cells are important contributing factors regarding MB in ANLL.

Adult↗
PubMed1984

Intensive initial oral anticoagulation and shorter heparin treatment in deep vein thrombosis.

In order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation ("low-dose") and heparin or a more intense oral anticoagulation ("high-dose") with a shorter period of heparin treatment. In the first part of the study 129 patients were randomized. The "low-dose" group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the "high-dose" group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis. In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 ("low-dose") and 3.7 ("high-dose") days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred. Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

Administration, Oral↗