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Intrapleural streptokinase in management of parapneumonic effusions. Report of series and review of literature.

Noncommunicating locules of fluid may develop in the setting of a thoracic empyema or a complicated parapneumonic effusion. When this occurs a single chest tube may not provide adequate drainage. In an effort to promote drainage and thereby obviate the need for further procedures, instillation of streptokinase into the involved pleural space has been advocated. This communication reviews the literature and reports our experience with intrapleural streptokinase. In our retrospective review of nine patients, instillation of streptokinase resulted in an obvious increase in chest tube drainage in six. Of the nine patients, four with improved drainage required no further procedures. Two patients with improved drainage and the three with no change in drainage required an additional chest tube, a decortication procedure, or were lost to follow-up. None of the four patients with an empyema were benefitted. Intrapleural instillation of streptokinase may be a useful adjunct in the treatment of a complicated parapneumonic effusion but appears less likely to be of benefit in the management of an empyema.

Adult↗

[Modification of the streptokinase functional groups during iodination].

Modification of tyrosine residues was detected in streptokinase molecule during iodination. A nonlinear type of the modification reaction allowed to suppose that tyrosine residues were heterogenous. As shown by gel chromatography the modified streptokinase did not develop stable complexes with human plasminogen even at low ratios of iodine/streptokinase, however the activating effects of the streptokinase were maintained. During iodination the secondary structure of streptokinase appears to be altered, the level of which depended on the molar ratio iodine/streptokinase.

Humans↗

Lymphocytic angiitis following streptokinase therapy.

A palpable, purpuric, nonpruritic eruption occurred in a 64-year-old man nine days after he received intravenous streptokinase therapy, which was successful in treating acute myocardial infarction. Perivascular mononuclear and eosinophilic infiltration was noted on routine staining of skin biopsy specimens: immune complexes, fibrin, and complement deposition in the skin microvasculature were demonstrated on immunofluorescent studies. These findings confirm the diagnosis of lymphocytic angiitis induced by streptokinase. Intermediate-type hypersensitivity reactions to streptokinase apparently have variable levels of severity. Clinicians who use streptokinase as a therapeutic agent should be aware of this potentially serious complication.

Fluorescent Antibody Technique↗

[Blood coagulation shifts in patients with myocardial infarction treated with streptokinase].

Variation in major coagulation parameters was assessed in 87 patients with acute myocardial infarction, treated with streptokinase and/or heparin under angiographic control. Streptokinase treatment was associated with a drop in plasma fibrinogen, plasminogen and alpha 2-antiplasmin, and an increase in serum fibrin/fibrinogen degradation products. The magnitude of coagulation shifts was greater in case of intravenous streptokinase infusion (1,000,000 units over 60 min), as compared to intracoronary streptokinase administration in lower doses (120,000-180,000 units over 60-90 min). In all patients with regained coronary flow, fibrinogen, plasminogen and alpha 2-antiplasmin levels began to decline significantly earlier and/or became normal significantly later, as compared to patients with persisting coronary occlusion. The rates and severity of hemorrhagic complications were basically similar in intravenous and intracoronary routes of administration, in spite of different doses and magnitude of coagulation shifts.

Adult↗

[The treatment of myocardial infarct with streptokinase].

The current situation concerning the use of Streptokinase in the treatment of recent myocardial infarction does not make it possible to draw any definite conclusions with regard to its therapeutic value:--mortality would not appear to be significantly modified in the majority of series;--the occurrence rate of major complications during the acute phase is not notably altered but it seems possible that the electrocardiographic course of the necrosis is more favourable under the influence of Streptokinase when treatment is begun early. The long term course cannot be assessed. Finally, it is certain that the tolerance of Streptokinase therapy has been good in all the published series. In particular, Streptokinase does not appear to have been associated with severe haemorrhagic complications nor a higher prevalence of cardiac rupture.

Blood Viscosity↗

Immunology of a serum sickness/vasculitis reaction secondary to streptokinase used for acute myocardial infarction.

We have studied six patients who received streptokinase for acute myocardial infarction (MI). One of these patients experienced a serum sickness/vasculitis reaction nine days after receiving the drug. Immunologic investigation of serum obtained from these individuals demonstrated that IgE and IgG anti-streptokinase antibody concentrations (measured by radioimmunoassay) were significantly elevated, both pre and post (IgE antibody, 36-fold increase) drug exposure, in the individual having the serum sickness/vasculitis reaction. Two of five of the remaining MI patients receiving the drug had post-exposure elevation of IgE anti-streptokinase antibody, but no patient had the immunologic profile seen in the individual with vasculitis. One should be aware that the serum sickness/vasculitis reaction can occur late after administration of streptokinase when the acute MI patient is recuperating.

Adult↗

[Study of the bleeding mechanism during fibrinolysis induced by streptokinase in the rabbit (author's transl)].

Our aim in this work has been to obtain precisions on the bleeding mechanism during fibrinolysis induced by streptokinase in the rabbit. Haemostasis was studied in vivo by the method oh Honour and Russell. The injection of 40 000 u/kg of streptokinase in 10 minutes induces rapidly fibrinolysis, which lasts for approximately one hour which is not accompanied by changes either in coagulation factors, or in platelet function. In vivo : . the adhesion of platelets to the vascular lesion is normal; . platelet aggregation is normal as is the formation of intravascular thrombi; . on the other hand the intra mural platelet thrombus is unstable. The embolization of the intravascular thrombi is responsible for new hemorrhages which can be correlated with the intensity of fibrinolysis. Thus, even in the absence of fibrinogenolysis, of fibrinogen degradation products FPD, of abnormal thrombin generation and of altered platelet function, the fibrinolytic activity induced by streptokinase could alone be responsible for bleeding episodes, occuring during thrombolytic treatment by streptokinase in man.

Animals↗

[Formation of streptokinase-heparin complexes and their properties].

Streptokinase and heparin developed complex at the ratio 3.2:1, w/w, respectively, and neutral values of pH, which was registered by means of thin-layer chromatography and differential UV-spectroscopy. IR-, differential UV- and CD-spectroscopic methods showed that secondary and tertiary structures of streptokinase were altered in the complex. Streptokinase containing in the complex exhibited the higher thermostability at 50 degrees as compared with native protein. After intravenous administration of the complex into rabbits more distinct alterations were observed in thrombin time, blood clot lysis and in blood plasma fibrinolytic activity as compared with native streptokinase effect.

Animals↗

[Effect of adenine nucleotides on the activator function of streptokinase].

The addition of ATP or 3,5-AMP (but not UTP, GTP, CTP, AMP, 2,3-AMP, ADP, inorganic pyrophosphate) at a final concentration of 10(-1) M into streptokinase solution, pH 7.0 or 9.5, causes a dramatic inhibition of streptokinase-induced fibrinolysis. The specificity of ATP effect is fully lost at pH 3.0, when all nucleotides completely inhibit the activating function of streptokinase. Ribose-5-phosphate causes a similar effect at pH 3.0. The character of nucleotide action on the activating function of streptokinase considerably differs from their influence on proteolytic reactions.

Adenine Nucleotides↗

Low-dose intra-arterial streptokinase infusion therapy of peripheral arterial occlusions and occluded vein grafts.

To study the effectiveness of low-dose thrombolytic therapy the authors report their experience with local, low-dose, intra-arterial streptokinase infused at a rate of 5000 units/h in four patients with occluded vein grafts and eight with peripheral arterial occlusions presenting with limb-threatening ischemia. The patients had had symptoms for 4 hours to 6 weeks. The streptokinase infusion successfully declotted two occluded vein grafts and restored distal blood flow in five patients with peripheral arterial occlusion. Complications resulting in early withdrawal of thrombolytic therapy included surgical wound hematomas in two patients. Two patients had severe bleeding at the arterial puncture site leading to the death of one of them. Treatment after cessation of thrombolytic therapy included femoropopliteal bypass in three patients, percutaneous transluminal balloon dilatation of a stenotic popliteal artery in one patient and thromboembolectomy in three patients. Two patients required below-knee amputation because of irreversible ischemia. The authors conclude that in carefully selected patients, intra-arterial infusion of streptokinase locally in low dosage is an important adjunct in the treatment of limb-threatening ischemia caused by occluded vein grafts and acute arterial thrombosis. They warn that selective thrombolytic therapy with streptokinase must be used with caution since it may be associated with serious complications.

Aged↗

[Effect of intracoronary streptokinase infusion and verapamil treatment on the size of the affected area in myocardial infarct patients].

The effect of intracoronary streptokinase administration (31 patients), verapamil treatment (23 patients) and conventional therapy (27 patients) on the size of the affected area was examined in patients with acute myocardial infarction (MI). Streptokinase was administered in a dose of 250,000-500,000 IU within the first 3 to 20 hours of myocardial infarction, and verapamil, 360 to 400 mg, daily within the first 5 to 12 hours of the attack. The occluded coronary artery was recanalized in response to streptokinase administration in 21 patients. Serial measurements of CPK activity and serum myoglobin levels, and electrocardiographic precordial cartograms demonstrated a reduction in MI size following streptokinase administration. Verapamil had no basic effect on the final size of myocardial lesion, although it improved somewhat the clinical course of the disease.

Coronary Angiography↗

Streptokinase clot lysis in acute occlusions of the cranial circulation: study in rabbits.

An animal model of acute cerebrovascular thromboembolism was developed to evaluate the feasibility of selective fibrinolysis. In 20 Flemish Giant rabbits, autologous clot was deposited via selected catheterization of the distal end of the common carotid artery. The rates of clot lysis with streptokinase were compared in eight control rabbits and after three different dosage regimens in four rabbits each. Group A received selective infusion of 5000 U/hr; group B received 4000 U/min for 1 hr, 3000 U/min for 2 hr, and 5000 U/hr for 2 hr; and group C was treated similar to group B plus receiving an initial 20,000 U bolus of streptokinase. Lysis was evaluated by serial angiograms obtained hourly for up to 6 hr after the clot was deposited. Five proximal vessels arising from the common carotid artery were chosen for the angiographic grading system. The control group showed beginning lysis after 5-6 hr. Group A appeared to show a slight improvement about 4 hr after clotting. Group B demonstrated an early and greater improvement at 2 hr that appeared to be sustained throughout the experiment. Group C showed no difference compared with the control group. The Dunnet t procedure and the Kruskel-Wallis nonparametric analysis of variance were used for comparing the angiograms of the treatment groups with those of the control group at corresponding study times. The results of these animal experiments do not indicate a definite benefit of streptokinase treatment alone over no treatment. Further controlled studies are needed before the value of streptokinase in routine clinical practice can be determined.

Animals↗

Effect of streptokinase on fibrinogen and related proteins in plasma.

We investigated the effect of streptokinase on determination of fibrinogen and related clottable proteins in an effort to assess the relative reliability of these determinations in monitoring patients being treated with streptokinase. Citrated plasma was incubated with and without streptokinase, then assayed for fibrinogen (I), fibrin(ogen) degradation products (II), total clottable protein (III), and plasminogen (IV). Values for I decreased rapidly. Values for III and IV generally paralleled those for I, values for III lacked adequate sensitivity. II, low initially, increased to 80 mg/L in 1-2 h. Soybean trypsin inhibitor effectively stabilized all these constituents (except IV) in streptokinase-treated plasma, and we recommend that this (or some other such) inhibitor of fibrinolysis be used routinely when specimens are collected for these determinations. Data are presented that suggest that transient polymers are formed, the clinical significance of which is not known.

Blood Coagulation Tests↗

Late thrombosis of the Björk-Shiley tilting disc valve in the tricuspid position. Thrombolytic treatment with streptokinase.

The main complication after implantation of a Björk-Shiley tilting disc valve in the tricuspid position is late thrombotic obstruction. Of 28 patients with tricuspid valve replacement (16 with mitral, aortic, and tricuspid valve replacement; 12 with mitral and tricuspid valve replacement), with a mean follow-up of 5.2 years, seven (25%) had thrombosis of the tricuspid prosthesis. Three patients had a recurrent thrombotic malfunction, for a total of ten thrombotic malfunctions in 146 patient-years, a rate of 6.8 per 100 patient-years. Thrombosis occurred late in all patients. Clinical deterioration presented with signs of congestive heart failure. In all patients the click of the tricuspid prosthesis was not audible and new diastolic or systolic murmurs were. The diagnosis was confirmed with cineradiography and bidimensional echocardiography (immobile disc, diminished opening angle of the disc). Thrombolytic treatment with streptokinase was used in all seven patients. Two patients required 12 hours of therapy and five patients, 24 hours. Thrombolytic treatment was monitored by the thrombin time. Complete regression of clinical, cineradiographic, and echocardiographic signs fo thrombosis was seen in all seven patients during the first 24 hours of therapy. There were no bleeding complications. In one patient clinical signs of mild pulmonary embolism occurred and were confirmed with chest radiographs. Follow-up, after successful treatment, extends from 4 to 30 months (mean 16.5 months). In four patients long-term results are excellent: There have been no clinical, cineradiographic, or echocardiographic signs of rethrombosis of the tricuspid prosthesis during the follow-up. Rethrombosis of the tricuspid prosthesis was observed in three patients 4, 7, and 14 months after initial treatment with streptokinase. Repeat thrombolytic treatment with streptokinase was successful in all three of these patients. Our experience with streptokinase treatment of thrombosis of tricuspid Björk-Shiley prostheses indicates that this form of treatment should always be applied before surgical intervention.

Adult↗

[Absorption and hematologic effect of streptokinase-streptodornase (varidase) after intracavital or oral administration].

A series of patients who received intracavitary streptokinase/streptodornase after thoracotomy or laparotomy were compared with a control group. They showed a highly significant increase in plasma streptokinase tolerance, indicating absorption of the streptokinase from the cavity. Changes in blood coagulation, plasma cell count and immunoglobulins were not observed. In a series of patients with leg ulcers treated with streptokinase/streptodornase by mouth, no increase in plasma streptokinase tolerance was observed, indicating that orally administered streptokinase is not absorbed from the gastro-intestinal tract.

Abdomen↗

[Studies of the heterogeneity of streptokinases of different origin (author's transl)].

Streptokinases of six different strains of group A streptococci (Strep. pyogenes), and of one strain each of streptococcal groups C and G were isolated from supernatants of the cultures. The purified or partial purified streptokinases were characterized by electrophoresis in agar-acrylamidgels, isoelectric focussing in acrylamide gel and by determinations of the molecular weights by means of sodium dodecylsulphate acrylamide electrophoresis and gel filtration on sephadex G-100. Furtheron these streptokinases were compared serologically using human antistreptokinase-antiserum. It was found that all of the streptokinases examined in this study were different in their isoelectric points (5.05-6.5) and that they showed serological cross-reactions. The molecular weights are not significantly different and were determined to about 45 000 daltons.

Cross Reactions↗

Treatment of acute peripheral arterial and graft thromboses with low-dose streptokinase.

Seventeen patients with acute peripheral arterial or graft occlusion were treated with local low-dose intra-arterial streptokinase. The series includes eight patients with native vessel occlusion, six patients with vein graft occlusion, two patients with prosthetic graft occlusion, and one patient with renal allograft artery occlusion. The duration of occlusion prior to streptokinase therapy varied from 2 hours to 5 weeks. The treatment was successful in 14 of the 17 instances. In conjunction with the successful thrombolytic therapy, percutaneous transluminal angioplasty was performed subsequently in 10 of the patients and reconstructive surgery in three. One major and five minor hemorrhagic complications occurred and were considered to be secondary to the streptokinase therapy. In follow-up of up to 9 months, 11 of the 14 successfully treated patients continued to have a good result, without any indication of recurrent arterial occlusion. Two patients have died of causes unrelated to thrombolytic therapy and one patient required bypass grafting for recurrent thrombosis. None of the successfully treated patients lost a limb. Of the three patients in whom thrombolysis was unsuccessful, two required amputation. Local intra-arterial low-dose streptokinase appears to be a promising alternative to immediate operative treatment in carefully selected cases of arterial occlusion. Definitive treatment of the underlying cause of the thrombus usually is required and changes of success may be enhanced by the thrombolytic therapy.

Adult↗

Coronary reocclusion after selective administration of streptokinase.

Intracoronary streptokinase was given to 40 patients with acute transmural myocardial infarction. In 34 of the patients (85%), it resulted in reflow or improved flow. Six patients showed no reflow and six reocclusion within 2 hours. No consistent explanation was found for this resistance to therapy. Five other patients developed reocclusion after 6 days to 11 months, when heparin or warfarin anticoagulation had been stopped. Percutaneous angioplasty at the time of streptokinase infusion was performed in seven, with six successes. Bypass surgery was performed after successful streptokinase administration in eight. Follow-up revealed recurrent ischemia in patients successfully treated with streptokinase alone, but not in patients with successful angioplasty or bypass surgery. Long-term coronary patency after thrombolysis may require careful anticoagulation or a procedure that modifies or bypasses the residual stenosis.

Angioplasty, Balloon↗