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Biomedical subjects

M Verstraete

Publications and source records attributed to M Verstraete.

At least 109 records · Page 6Linked to original sources
PubMed1987

[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism].

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g. protein C, protein S, antithrombin III and cofactor II of heparin. Also a hindered activation of the fibrinolytic system may predispose to thrombosis; the impaired activation may be due to deficient synthesis and/or release of tissue-plasminogen activator, an increased level of its inhibitor or a functional defect of the plasminogen molecule. A few cases of congenital dysfibrinogenemia have been described in which the functional defects of the molecule are held responsible for recurrent thrombosis. An acquired thrombotic disorder is due to the presence of immunoglobulins which prolongs phospholipid-dependent coagulation by binding to epitopes of some phospholipids. This so-called lupus anticoagulant was originally described in patients with systemic lupus erythematosus but is a misnomer as it is more frequently encountered in patients without lupus.

Blood Coagulation Disorders↗
PubMed1987

Comparison of quantification methods of 111In-labelled platelet deposition in peripheral bypass grafts.

The action of antithrombotic drugs can be evaluated by measuring the deposition of 111In-labelled platelets on peripheral bypass grafts several days after injection. This evaluation can be performed qualitatively (visual interpretation on the daily images) or quantitatively. Four different methods which calculate the ratio of platelet uptake with a reference region are compared: two methods use a gamma camera and two a detector. A blood sample or the region under the sternal angle are used as reference. The daily ratio of the counts, recorded by a gamma camera in a region of interest covering the graft, and the blood radioactivity interpolated from a platelet survival curve appears to be the most reliable method. The information of all the ratios can be combined in a single thrombogenicity index which reflects the daily rise of a linear or exponential regression versus time.

Aged↗
PubMed1986

Pharmacokinetics and effects on fibrinolytic and coagulation parameters of two doses of recombinant tissue-type plasminogen activator in healthy volunteers.

Pharmacokinetics and pharmacological effects of two intravenous doses of recombinant tissue-type plasminogen activator (rt-PA) (40 and 60 mg over 90 min) were determined in healthy volunteers. Mean maximum plasma concentrations were 1080 and 1560 ng/ml respectively. The steady state level during subsequent maintenance infusion of 30 mg over 6 h was 250 ng/ml. The pharmacokinetics of rt-PA showed a bi-exponential disappearance from plasma consistent with a 2-compartment model of t1/2 alpha = 5.7 min, a t1/2 beta = 1.3 h and a total clearance of 380 ml/min. Mean fibrinogen levels at the end of the infusions of 40 mg or 60 mg rt-PA over 90 min, measured in thawed plasma samples collected on citrate/aprotinin, decreased to 74% and 57% of the preinfusion values respectively. Plasminogen fell to 55% and 48%, and alpha 2-antiplasmin to 28% and 18% of initial values. No further decrease of these parameters was observed during the infusion of 30 mg rt-PA over 6 h. Only 2% of the preinfusion fibrinogen levels could be recovered as fibrinogen-fibrin degradation products. This moderate extent of systemic fibrinogenolysis is much less than that reported for therapeutic i.v. infusions of streptokinase.

Adult↗
PubMed1986

[Intracoronary thrombolysis or brief intravenous infusion of high-dose streptokinase in the treatment of acute myocardial infarction].

Intracoronary infusions of streptokinase result in recanalization in about 80% of patients treated during the 4 hours following the first symptoms of myocardial infarction. With short, high dose intravenous infusions (streptokinase 1,500,000 units in 30 min) the recanalization rate is of the order of 60-75%. The high dose of streptokinase is well tolerated, and the intravenous infusion presents the advantage of shortening by about 2 hours the delay required to start intracoronary administration.

Animals↗
PubMed1986

Heparin-induced thrombocytopenia platelet aggregation studies in the presence of heparin fractions or semi-synthetic analogues of various molecular weights and anticoagulant activities.

One case of heparin-induced thrombocytopenia is reported. Aggregation was observed in the platelet-rich plasma of this patient in the presence of two commercial standard heparin preparations (from a final concentration of 0.025 IU/ml upwards), of two semi-synthetic heparin analogues (0.1 APTT U/ml) and of three low-molecular weight heparin (LMWH) fractions (0.1 anti-Xa U/ml) but not in the presence of five other LMWH fractions. The patient's isolated platelets no longer aggregated in the The patient's isolated platelets no longer aggregated in the presence of heparin but the phenomenon recurred after addition of the patient's platelet poor plasma (PPP). Furthermore, addition of patient's PPP to control platelets led to heparin-induced aggregation. The phenomenon was associated with thromboxane generation and could be blocked by in vitro addition of aspirin, PGI2, and PGD2 whereas the lag phase was dose-dependently prolonged by adenosine. It is concluded that platelet aggregation may be induced in some patients by standard heparin and by certain LMWH fractions or semi-synthetic analogues, independently of their molecular weight and anticoagulant activity.

Adenosine↗
PubMed1986

Role of platelet activation and fibrin formation in thrombogenesis.

Further progress in the search for more effective but safe antithrombotic agents is coupled to an improved understanding of the factors involved in arterial and venous thrombogenesis. Although arterial thrombosis is initiated by formation of a layer of platelets on modified endothelium or subendothelial constituents and subsequent recruitment of passing-by platelets, this phenomenon is not sufficient to lead to a full thrombus. Further growth of such a platelet mass depends, to a large extent, on the presence of free thrombin. Thrombin is mainly generated by activation of factor XI on the platelet contact with collagen. In addition, thrombin leads to formation of fibrin, which maintains the stability of the arterial platelet thrombus and is the main component of the venous thrombus. The search for agents that inhibit platelet activation and thrombin formation is, therefore, a logical endeavor.

Blood Coagulation↗
PubMed1986

Pharmacology of thrombolytic drugs.

Streptokinase and urokinase have proved to be useful in a limited number of clinical conditions. Mainly because of the risk and unpredictability of bleeding with this first generation of thrombolytic agents, thrombolysis has not been ingrained in medical practice. In the interim, more fibrin-specific thrombolytic agents have been developed such as acylated streptokinase-human plasminogen complex, tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator (scu-PA or pro-urokinase). Only the latter two drugs do not induce major systemic fibrinogenolysis at thrombolytic effective doses. These two agents, obtained by recombinant techniques, as well as acylated streptokinase-plasminogen complex are available for clinical investigations. The first results of systemic administration of recombinant tissue-type plasminogen activation (t-PA) in patients with acute myocardial infarction were published and are promising. Continued experimentation with t-PA and pro-urokinase in evolving myocardial infarction and other thrombotic disorders is essential to better delineate their therapeutic index.

Drug Combinations↗
PubMed1986

Thromboembolism and antithrombotic therapy in peripheral arterial disease.

Atherosclerosis complicated by thromboembolism is the main cause of obstructive arterial disease in the legs. Two studies from West Germany suggest that antiplatelet drugs may slow the progress of atherosclerosis in leg arteries and prevent occlusive thrombosis under some circumstances. The same agents may also reduce the risk of rethrombosis after successful vascular repair in the femoropopliteal region; in one trial, aspirin decreased the incidence of reocclusion after thromboendarterectomy and, in another, the combination of aspirin and dipyridamole was effective after bypass with synthetic material. Antithrombotic drugs are used in most centers after percutaneous transluminal angioplasty, but there is no definite evidence for their need. Thus, it appears that in contrast to cardiac and cerebrovascular disease, few efforts have been made to determine the true value of antithrombotic therapy in peripheral arterial disease. The management of acute thromboembolism in the legs requires a multidisciplinary approach. Depending on the type (embolic or thrombotic), length and localization of the arterial occlusion, surgical (embolectomy, thromboendarterectomy, peripheral bypass surgery) or nonsurgical (systemic fibrinolysis or local thrombolytic therapy with or without balloon angioplasty) treatment is preferred. The importance of nonsurgical therapeutic approaches may become even greater in elderly patients with a poor operative risk. This review discusses the available therapeutic modalities in acute and chronic peripheral thromboembolic arterial disease.

Angioplasty, Balloon↗
PubMed1986

Venous thromboses in particular organs.

Although venous thrombosis most often occurs in the return circulation of the legs and pelvis, it may also occur in the veins of several organs and compromise venous return. Thus, the clinician, in any field will regularly be confronted with manifestations of venous thrombosis in particular organs. This review summarizes the pathogenesis and the main clinical features of venous thrombosis in the central retinal vein, the cerebral veins and sinuses of the skull, the renal and the portal veins and the hepatic and mesenteric veins as well as priapism. The principles of treatment are outlined.

Budd-Chiari Syndrome↗
PubMed1986

Coronary thrombolysis with recombinant tissue-type plasminogen activator: patency rate and regional wall motion after 3 months.

In a double-blind, placebo-controlled, randomized trial the long-term (+/- 3 months) effects of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) versus placebo were compared in relation to left ventricular function, coronary patency rate and antigenicity in 28 patients with a first myocardial infarction. Patency rate of the infarct-related coronary artery at the end of the rt-PA/placebo infusion and after 3 months of medical treatment (including oral anticoagulant agents) was 86 and 71%, respectively, in the rt-PA group, and 21 and 58%, respectively, in the placebo group. Regional wall motion of the infarct-related area was quantitated with digital subtraction angiography. Intrapatient comparisons revealed significant improvement in regional wall motion after 3 months in both the rt-PA and placebo groups. The improvement in the rt-PA group was not significantly greater than that in the placebo group. Thirteen patients (10 with rt-PA and 3 with placebo) with persistent patency (both early and late) of the infarct-related coronary artery showed a significant improvement of both global and regional left ventricular function, while 8 patients (2 with rt-PA and 6 with placebo) with persistent occlusion showed no changes. Antibodies against rt-PA were not detected in serum 2 weeks after the infusion, which is indicative of the lack of antigenicity of rt-PA and allows for its repeated administration.

Angiography↗
PubMed1986

Evaluation of antiplatelet agents in the prevention of aorto-coronary bypass occlusion.

The cumulative occlusion rates of aorto-coronary artery venous bypass grafts average from 16 to 26% per distal anastomosis within 12 months and about 2% per following year. The potential benefit of oral anticoagulants and platelet inhibitor drugs has been tested to prevent graft occlusion and to retard the atherosclerotic process. Oral anticoagulants started on the third postoperative day do not significantly reduce graft occlusion after 6 months. Among the platelet inhibitor drugs, dipyridamole started before surgery, followed by dipyridamole and aspirin soon after surgery, was the drug regimen with the best results. More randomised double-blind clinical trials are highly desirable to confirm these findings and to resolve the question of relative efficacy and safety for the various drugs reported to have shown benefit when used in combination.

Administration, Oral↗
PubMed1986

Analysis of coagulation and fibrinolysis during intravenous infusion of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction.

Coagulation and fibrinolysis were studied in patients with acute myocardial infarction during intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 90 min, n = 101), streptokinase (1,500,000 IU over 60 min, n = 61), or placebo (n = 40). In the rt-PA group, the plasma level of rt-PA antigen was 1.2 +/- 0.6 micrograms/ml (mean +/- SD) and the euglobulin fibrinolytic activity (EFA) was 910 +/- 735 IU t-PA/ml. In the streptokinase group, the EFA was equivalent to 430 +/- 435 IU t-PA/ml. At the end of the infusion, the plasma fibrinogen level measured with a coagulation rate assay was decreased to 57 +/- 33% of the preinfusion value in the rt-PA group, to 7 +/- 10% in the streptokinase group, and remained unchanged in the placebo group. Fibrinogen-fibrin degradation products increased to 0.75 +/- 0.54 mg/ml in the streptokinase group but to only 0.10 +/- 0.13 mg/ml in the rt-PA group. The plasma levels of alpha 2-antiplasmin, plasminogen, and factor V decreased to between 30% and 45% in the rt-PA group but significantly more in the streptokinase group (to between 15% and 25%). Thus rt-PA induced much less systemic fibrinolytic activation than streptokinase. In the patients who received rt-PA, a weak correlation (r = .21, n = 89, .1 greater than p greater than .05) was found between the extent of fibrinogen breakdown at 90 min and the plasma rt-PA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1986

Synergism of thrombolytic agents in vivo.

The existence of significant synergism between tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA), and between t-PA and urokinase in thrombolysis in vivo is described. In a quantitative preparation of thrombolysis, consisting of rabbits in which a blood clot was induced in the jugular vein with 125I-labeled fibrin, intravenous infusion over 4 hr of t-PA, scu-PA, or urokinase in amounts of 0.5, 1.0, or 2.0 mg/kg body weight resulted in significant thrombolysis (30% to 60%). The simultaneous infusion of t-PA and scu-PA or of t-PA and urokinase had a significantly greater (p less than .001) thrombolytic effect than could be anticipated on the basis of the added effects of each agents alone. However, no synergism was observed between scu-PA and urokinase. The observed alpha 2-antiplasmin consumption and fibrinogen breakdown after urokinase at higher doses did not occur with the equivalent thrombolytic combinations of t-PA and urokinase. The combined use of synergic thrombolytic agents in patients may permit a significant reduction in total administered doses, probably with elimination of the systemic activation of the fibrinolytic system and the concomitant fibrinogen breakdown that is unavoidable with the currently used thrombolytic doses of each agent.

Animals↗
PubMed1986

Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction.

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗