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Biomedical subjects

M M Samama

Publications and source records attributed to M M Samama.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Staphylokinase].

Myocardial infarction is due to thrombotic occlusion of a coronary artery. Current thrombolytic agents have demonstrated their major value by inducing a significant reduction of mortality, but they nevertheless present certain limits: 1) excellent arterial patency is obtained in only about 50% of cases; 2) reocclusions persist in 5 to 10% of cases; 3) very severe complications, such as cerebral haemorrhages, have not disappeared (about 0.5% of cases). There is therefore a large field of action for development of the optimal thrombolytic agent. Research concerning staphylokinase, classified among third generation thrombolytic agents, is therefore situated in this context. Staphylokinase is a protein known to possess profibrinolytic properties for more than four decades, but has been the subject of renewed interest over recent years. This article reviews the characteristics, mechanism of action and fibrinolytic properties of staphylokinase. It recalls the main results obtained in animal models and summarizes the main clinical trials in man.

Animals↗
PubMed1998

[Heparin-induced thrombopenia: significance and difficulties of precise identification of the immunologic mechanism].

Heparin-induced thrombocytopenia (HIT) is a drug induced immunohematologic adverse reaction which is a rare but potentially very severe accident. Its diagnosis is important for epidemiologic and drug surveillance studies and in order to decide the most appropriate treatment. Its importance is enhanced since there is no gold standard diagnostic criteria. In clinical practice the diagnosis is based on a group of criteria related to clinical events and laboratory tests. We have established a score based on anamnestic criteria which allowed us to evaluate and compare two different laboratory tests: a platelet aggregation test (PAT) and a test for the detection of heparin dependent antibodies (Heparin Platelet Induced Antibodies or HPIA). The functional test PAT which is commonly used in expert laboratories detects antibodies inducing platelet aggregation in the presence of heparin. The HPIA test more recently developed is an ELISA test which detects antibodies directed at heparin-platelet factor 4 complexes. The relative value of theses two methods for the diagnosis of HIT is not well documented. We have analysed the results of these two tests in 273 consecutive patients with a suspicion of HIT. The results were concordant in 70% of patients. In selecting the patients with the lowest and the highest probability of HIT according to the score, PAT was found a more sensitive and HPIA a more specific test than the other. At low probability PAT is more often positive than HPIA 18% and 9% respectively. No test is 100% reliable, the specificity being limited for both tests since in about 20% of cases one or both tests are negative contrasting with a highly probable HIT. In this last group of patients, PAT was more frequently positive (86%) than HPIA (72%). Both tests are negative in 6% of patients suggesting the existence of presently unknown antigenic targets. Considering a group of 19 patients with a high probability of HIT, we have found antibodies against IL-8 or NAP-2 in only 7 patients. The discrepancy between a HPIA positive and a PAT negative encountered in 8% of patients may be explained by the existence of IgA or IgM immunoglobulins since in contrast to IgG they are unable to promote platelet aggregation via the CD32 platelet membrane receptor. This work suggests than neither test is 100% reliable and that they play a complementary role in the diagnosis of HIT. The potential advantage of using both tests should be confirmed in complementary studies

Aged↗
PubMed1997

[Multigenic thrombophilia: genetic anomaly of factor II and mutation of factor V Leiden. Study in a French family].

BACKGROUND: A genetic variation of the prothrombin (factor II) gene, a G to A transition at nucleotide position 20210, was recently found in patients with familial thrombophilia (predisposition to venous thrombosis). It seems to be frequent in patients with the factor V Leiden mutation. We report a family with the factor V Leiden and/or the genetic variation of prothrombin in 3 members. CASE REPORT: The patient had repeated episodes of deep vein thromboses starting at the age of 30 during the 4th pregnancy. She is a heterozygous carrier of both the factor V Leiden nutation and the prothrombin mutation 20210 A. She has 4 asymptomatic children, aged 28 to 32 and 3 of them have been explored: one son has the prothrombin mutation, one daughter the factor V Leiden and one has none of them. DISCUSSION: This case report illustrates the polygenic nature of thrombophilia which may explain the heterogeneity of clinical expression observed in isolated congenital abnormalities, especially in factor V Leiden mutation.

Chromosome Aberrations↗
PubMed1997

[Severe hemorrhagic complications during treatment with low molecular weight heparin. Apropos of 2 cases].

Two cases of fatal bleeding in patients treated with low molecular weight heparin for deep vein thrombosis are reported. Risk factors for bleeding were: severe underlying disease (cancer in one case, morbid obesity and cardiac failure in the other), age over 80 years and worsening of renal insufficiency in both cases, recent surgical procedure in one case. Anti-Xa activity was beyond the therapeutic range at the time of bleeding in both cases. The usefulness of biologically monitoring the treatment of deep vein thrombosis with low molecular weight heparin is discussed.

Aged↗
PubMed1997

[Value of carbon in the thrombogenicity of cardiovascular prostheses].

Forty five Carbon-lined (CL) and 45 Standard (ST) 4 mm internal diameter polytetrafluoroethylene (PTFE) grafts were implanted as aortic interpositions in 90 New Zealand rabbits. In a pilot study of 20 animals, 10 CL and 10 ST grafts were used to develop microsurgical techniques, then 60 grafts were placed in 60 rabbits with lower morbidity. The 2-hour graft patency (Doppler study, Transonic flow probe and 8 mHZ) showed a better patency rate in the CL group (93% versus 80%). In 10 animals, platelet accumulation was investigated in vivo using scintigraphy after injection of autologous platelets labeled with Indium111. In vitro, radioactivity counting of the explanted midgrafts sections at 2 hours revealed a 6-fold higher activity in ST grafts (6.60 +/- 1.98 x 103 platelets/mm2 versus 0.82 +/- 0.25 x 103 platelets/mm2; p < 0.05). Light microscopy found platelet and fibrin deposition (PFD) in nearly all ST grafts, whereas PFD were found in only 13% of the CL grafts corresponding to those thrombosed grafts (chi2:61.117; p < 0.001). Carbon-lining decreases platelet accumulation on PTFE grafts and the rabbit aortic interposition appears to constitute a quantitative and reproducible model for investigation of antithrombotic drugs.

Animals↗
PubMed1997

Comparative effects of recombinant staphylokinase and streptokinase on platelet aggregation.

Recombinant staphylokinase (RSTA) has been shown to offer promise as a thrombolytic agent. In contrast to streptokinase (SK), few studies have been devoted to possible effects of RSTA on platelets. We have compared the capacity of RSTA and SK to trigger platelet aggregation and to modify ADP (2.5 microM) response in platelet-rich plasma (PRP) of 125 healthy subjects. Thus, exposure of PRP to SK (40 to 50 micrograms/ml) induced platelet aggregation in 6 out of 25 subjects. However, under the same conditions, RSTA failed to induce platelet aggregation in all cases (25 out of 25 subjects). In contrast to RSTA, SK (0.4 to 50 micrograms/ml) greatly reduced ADP-induced platelet aggregation in 12 out of 25 subjects. Preincubation of plasma with SK is associated with a decrease in the fibrinogen concentration. Furthermore, there was a good correlation between SK-induced fibrinogenolysis and SK-induced platelet aggregation defect (r2 = 0.9; p = 0.001). No fibrinogenolysis was observed when different amounts of RSTA (0.4 to 50 micrograms/ml) were incubated in plasma for one min. However, there was a marked decrease in fibrinogen level (about 50%) when the plasma was incubated for five min with a very high concentration of RSTA. SK markedly enhanced the platelet response to ADP in 13 out of 25 subjects. In PRP of 6 out of 25 subjects, SK induces platelet aggregation and potentiates platelet response to ADP, however in PRP of 7 out of 25 subjects, SK caused only the increase of platelet response to ADP. The monoclonal antibody anti-Fc gamma RIIa1, I-3 (2 micrograms/ml), abolished SK-induced platelet aggregation and SK-enhanced ADP-induced platelet aggregation. In all cases (25 out of 25 subjects), RSTA failed to potentiate platelet response to ADP. These findings confirm that RSTA has a lesser fibrinogenolytic ability than SK and suggest its negligible effect on platelet function.

Adenosine Diphosphate↗
PubMed1997

Acute ischemic stroke and heparin treatments.

Several case-control studies have reported enhanced platelet activity, hypercoagulation and/or reduced fibrinolytic activity in patients with acute ischemic stroke. However, results of these studies are conflicting and do not allow to make recommendations regarding heparin treatment. The aim of heparin treatment in stroke patients is to prevent venous thromboembolic complications, to improve patient neurologic outcome, to reduce mortality and to prevent early recurrence. Unfortunately, only the first objective has been confirmed. As far as neurologic outcome and mortality are concerned, only trials performed since the CT era should be taken into account because the former ones did not rule out cerebral haemorrhages. The most recent clinical trials using LMWHs gave better results than the previous trials with UFH, but data are still conflicting and firm recommendations cannot be made until the results of ongoing megatriasl (such as IST) become available. As regards prevention of early recurrence, most authors agree that heparin is indicated in cardioembolic stroke.

Anticoagulants↗
PubMed1997

[Comparison of two groups of 22 women homozygous or heterozygous for factor V Leiden mutation].

Clinical characteristics of thrombophilia associated with heterozygous mutation of factor V are well characterized. In contrast, they are not well documented in homozygous subjects who are rare. Moreover, estroprogestative intake and pregnancy are important precipitating factors of venous thromboembolism in women with factor V mutation. In order to determine difference in clinical expression between homo and heterozygous subjects, two groups of 22 age matched women were compared. A modified technique for the diagnosis of activated protein C resistance has been used, and its great specificity and sensitivity has been confirmed. In these two small series of patients, a greater severity of clinical profile was not clearly evident. However, recurrences and thrombosis during pregnancy were more frequent in homozygous than in heterozygous women. However, the differences did not reach significance. Molecular markers of hypercoagulable states were not regularly increased even in homozygous untreated patients, but they were more often increased in untreated than in treated patients. In contrast, to other varieties of thrombophilia, homozygous mutation of factor V may be associated with a minor clinical severity suggesting the role of environmental factors and/or still unknown molecular alterations.

Factor V↗
PubMed1997

[Anti-streptokinase antibodies].

The use of thrombolytics has significantly improved the management of patients with acute myocardial infarction but available molecules remains imperfect: restoration of normal coronary patency in about half the cases, risks of reocclusion, risk of bleeding. Streptokinase (SK), which is the least expensive agent, has disadvantages as do the other thrombolytics. SK, an immunogenic bacterial protein, has another feature: administration of SK leads to an immunitory response with the production of specific anti-streptokinase antibodies. These anti-streptokinase antibodies may interfere with the future administration of a compound containing SK either by inducing an allergic response or by neutralising the SK and making it ineffective. Moreover, anti-streptokinase antibodies, the result of previous streptococcal infections, are present in the circulation. Although the prevalence of anti-streptokinase antibodies in the general population, especially coronary patients at risk of myocardial infarction, is not well known and their potentially harmful effects are even less well known. In particular, the platelet aggregant effect in vitro of these antibodies in the presence of SK was not taken into account in the trials studying the influence of anti-streptokinase antibodies in the results of thrombolysis by SK. The anti-lytic effect of anti-streptokinase antibodies is well documented. For this reason, it is not recommended to readminister SK in patients who have previously been thrombolysed with a product containing SK.

Antibodies, Bacterial↗
PubMed1996

AREVA: multicenter randomized comparison of low-dose versus standard-dose anticoagulation in patients with mechanical prosthetic heart valves.

BACKGROUND: Moderate anticoagulation may be proposed to reduce the risk of hemorrhage for certain patients with a mechanical prosthesis, but the consequences for risk of thromboembolism are debated. METHODS AND RESULTS: The purpose of the AREVA trial was to compare moderate oral anticoagulation (international normalized ratio [INR] of 2.0 to 3.0) with the usual regimen (INR of 3.0 to 4.5) after a single-valve replacement with a mechanical prosthesis, either Omnicarbon or St Jude. Patients included were between 18 and 75 years old, in sinus rhythm, and with a left atrial diameter < or = 50 mm on the time-motion echocardiogram. Patients were randomized for INR after surgery. From 1991 to 1994, 433 patients underwent valve replacement (aortic, 414; mitral, 19) with 353 St Jude and 80 Omnicarbon prostheses; 380 patients were randomized for INR: 188 for INR 2.0 to 3.0 and 192 for INR 3.0 to 4.5. Mean follow-up was 2.2 years (1 to 4 years). Analysis of 18001 INR samples showed that the mean of the median of INR was 2.74 +/- 0.35 in the 2.0 to 3.0 group and 3.21 +/- 0.33 in the 3.0 to 4.5 group (P < .0001). Thromboembolic events, as assessed from clinical data and CT brain scans, occurred in 10 patients in the 2.0 to 3.0 INR group and 9 patients in the 3.0 to 4.5 INR group (P = .78). Hemorrhagic events occurred in 34 patients in the 2.0 to 3.0 INR group and 56 patients in the 3.0 to 4.5 INR group (P < .01), with 13 and 19 major hemorrhagic events, respectively (P = .29). CONCLUSIONS: In selected patients with mechanical prostheses, moderate anticoagulation prevents thromboembolic events as effectively as conventional anticoagulation and reduces the incidence of hemorrhagic events.

Administration, Oral↗
PubMed1996

Effects of long travels in sitting position in elderly volunteers on biological markers of coagulation activation and fibrinolysis.

OBJECTIVE: To evaluate whether long travel in sitting position is associated with an increase of coagulation activation and/or a decrease of fibrinolytic activity. DESIGN: Comparison of blood coagulation and fibrinolysis parameters before and after two pleasure trips by bus organized in winter period (600 km in 8 hours) and in summer period (1200 km in 16 hours). SUBJECTS: 31 and 23 healthy elder volunteers for the winter and the summer trip respectively. Nine other elder volunteers were selected as a control group for the winter study. MAIN OUTCOME MEASURES: prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III (TAT), D-dimers (D-D), factor VII activated, plasminogen activator inhibitor (PAI), tissue-type plasminogen activator (t-PA), plasma albumin. RESULTS: A significant difference before and after the travel was only observed for TAT in the summer period. However all values of TAT were in the normal range. No volunteer presented with thromboembolic disease during the month following the travel. CONCLUSION: In the condition of our study, long travel in sitting position does not lead to an enhanced procoagulant state for elderly with varicose veins. These results suggest that there is no biological support to propose heparin prophylactic therapy for the elderly with varicose veins wishing to travel by bus.

Aged↗