High-Dose Systemic Streptokinase and Acylated Streptokinase-Plasminogen Complex (BRL 26921) in Acute Myocardial Infarction: Alterations of the Fibrinolytic System and Clearance of Fibrinolytic Activity

Kohler, Malcom; Hellstern, Peter; Doenecke, P; Schwerdt, Holger; Özbek, Cem; Miyashita, C.; Winter, Rachel; Blohn, G. von; Bette, L; Wenzel, E.

doi:10.1159/000215556

Cited by 14 publications

(8 citation statements)

References 23 publications

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“…Anisoylated plasminogen-streptokinase activator complex (APSAC, BRL 26921) is modified SK-plasminogen similar to the guanidinobenzoylated plasminogen-strepto kinase activator complex described by us [10], IC administration of 5-20 mg of APSAC was shown to result in 74% reperfu sion [57] while IV infusion of 30 mg of the drug gave 60% reperfusion [58], APSAC ad ministration gave rise to bleeding complica tions [56,59,60] and was found to cause hypotension in patients [61]. APSAC is inac tivated by streptokinase antibodies and to achieve reperfusion a 30-mg dose is re quired.…”

Section: Biological Activity Of Streptokinasementioning

confidence: 99%

Streptokinase - Biochemistry and Clinical Application

Reddy

1988

Enzyme

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Section: Biological Activity Of Streptokinasementioning

confidence: 99%

Streptokinase - Biochemistry and Clinical Application

Reddy

1988

Enzyme

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“…Platelet function tests, i.e. thromboxane B2 formation, collagen-and ristocetin-induced platelet aggregation, were per formed in platelet-rich plasma as recently described [7], The preparation of euglobulin precipitate and the fibrin plate assay are described in detail elsewhere [9], the fibrin plate assay was calibrated against the WHO tissue-type plasminogen activator (t-PA) standard provided by the NIBSC, London. Plasminogen acti vator inhibitor (PAI) was determined as described by Chiemelewska et al [2] using reagents from KabiVitrum, Munich.…”

Section: Laboratory Methodsmentioning

confidence: 99%

Subcutaneous Injection of Desmopressin (DDAVP): Evaluation of a New, More Concentrated Preparation

Köhler

Hellstern²,

Tarrach³

et al. 1989

Pathophysiol Haemos Thromb

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A more concentrated desmopressin (DDAVP) preparation (40 µg/ml), which required small injection volumes (< 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 µg/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII·C (factor VIII·Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII·C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p < 0.05). No serious local or systemic untoward side effects were observed.

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“…Estimates based on fibrin plate lysis assay in patients with acute myocardial infarction have demonstrated a half-life of approximately 37 minutes (Gemmill et al 1991;Kohler et al 1987) which is slightly longer than the 18 to 29 minutes based on other functional assays such as 125I-fibrin tubes or amidolytic assay of plasminogen activator activity in euglobulin fractions (Fears et al 1989;Martin 1982;Mentzer et al 1986). Estimates based on fibrin plate lysis assay in patients with acute myocardial infarction have demonstrated a half-life of approximately 37 minutes (Gemmill et al 1991;Kohler et al 1987) which is slightly longer than the 18 to 29 minutes based on other functional assays such as 125I-fibrin tubes or amidolytic assay of plasminogen activator activity in euglobulin fractions (Fears et al 1989;Martin 1982;Mentzer et al 1986).…”

Section: Pharmacokinetic Propertiesmentioning

confidence: 98%

Streptokinase

Battershill¹,

Benfield²,

Goa³

1994

Drugs & Aging

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Streptokinase has been administered to many thousands of elderly patients with acute myocardial infarction. Results of large, randomised trials provide convincing evidence that intravenous streptokinase confers a distinct survival benefit in this population subgroup following myocardial infarction. The placebo-controlled ISIS-2 study demonstrated a 5-week absolute mortality reduction of 38 per 1000 patients aged 60 to 69 years administered streptokinase, compared with only 16 per 1000 for patients aged less than 60 years. Combining streptokinase with aspirin further reduces mortality, as shown by a 5-week absolute mortality reduction of 70 per 1000 patients aged 60 to 69 years administered this regimen in the ISIS-2 trial. While ideally patients should receive streptokinase as soon as possible after symptom onset, late benefit has been observed in patients presenting up to 12 hours after pain onset, as is often the case with the elderly. Indeed, in patients treated > 6 hours after infarct in the GUSTO trial, streptokinase produced lower mortality results than accelerated recombinant tissue plasminogen activator (rt-PA). However, in contrast to the similar effects of streptokinase and conventionally administered rt-PA on overall survival demonstrated in previous large trials, the GUSTO study showed a lower mortality rate for accelerated rt-PA than for streptokinase in the elderly and in the total patient population. The most frequent adverse effects associated with streptokinase therapy are haemorrhagic complications, with an incidence of 0.4% for major bleeding (requiring transfusion) and 3.6% for minor bleeding among the total population in the GISSI-1 and ISIS-2 trials. An excess of stroke, particularly haemorrhagic stroke, occurring with rt-PA in GUSTO and other major mortality trials affirms the use of streptokinase as a suitable option in the elderly who are at increased risk of this complication. Significantly reduced values of end-systolic volume and regional wall motion index have been observed in elderly patients following streptokinase therapy. Overall, streptokinase and rt-PA seem to cause similar improvements in left ventricular function in this age group. Patency of occluded coronary arteries appears to be achieved in a high percentage of elderly patients following streptokinase therapy, based on a small sample. Thus, in view of the extensive clinical experience that now exists, intravenous streptokinase represents an appropriate alternative in elderly patients with acute myocardial infarction, and may be considered a first-line therapy in selected individuals, such as those with multiple risk factors for stroke or who present later than 6 hours after infarct.(ABSTRACT TRUNCATED AT 400 WORDS)

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High-Dose Systemic Streptokinase and Acylated Streptokinase-Plasminogen Complex (BRL 26921) in Acute Myocardial Infarction: Alterations of the Fibrinolytic System and Clearance of Fibrinolytic Activity

Cited by 14 publications

References 23 publications

Streptokinase - Biochemistry and Clinical Application

Streptokinase - Biochemistry and Clinical Application

Subcutaneous Injection of Desmopressin (DDAVP): Evaluation of a New, More Concentrated Preparation

Streptokinase

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