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Biomedical subjects

M M Samama

Publications and source records attributed to M M Samama.

At least 19 recordsLinked to original sources
PubMed2005

[Type 2B and pseudo type 2B Von Willebrand disease; a report of three cases].

Increased affinity of Von Willebrand factor (VWF) for its platelet receptor GPIb-GPIX complex is responsible of an hemorrhagic disease, which is the Von Willebrand disease (VWD) type 2B when the molecular abnormality is located on the VWF, and the platelet-type 2B VWD when the mutation concern the platelet receptor. Haemostatic abnormalities in these bleeding disorders are similar; prolonged bleeding time, fluctuating thrombocytopenia, decreased factor VIII-VWF complex, and an increased response to low dose of ristocetin in platelets rich plasma. High molecular weight VWF multimers are decreased. We report here 2 cases of type 2B VWD and 1 case of platelet type 2B VWD. The distinction between these 2 diseases was established by studying platelet aggregation with weak doses of ristocetin in mixtures of washed platelets (of normal control or patient)+poor platelets plasma (normal or patient). In one case, VWD 2B was discovered late in a 49 years old man, and the factor VIIIC-VWF complex was not diminished. The distinction between these two congenital diseases is important for the treatment of bleeding manifestations which need VWF concentrates infusions in type 2B VWD and administration of platelets concentrates in pseudo type 2B VWD.

Adult↗
PubMed2005

D-dimer levels, constitutional thrombophilia, and venous thrombosis prediction: clinical aspects and implications.

The negative predictive value of D-dimers in the diagnosis of a recent venous thromboembolism (VTE) episode is well established. The plasma level of D-dimer is usually increased in hypercoagulable states. The measurement of D-dimer could be of clinical interest in patients with constitutional thrombophilia as there is no close relationship between the clinical expression and the genotype indicating the existence of a hypercoagulable state. Moreover, the predictive value of D-dimer testing in patients with thrombophilia has been questioned. The review of the literature and results of a recent study of our group are presented. Decreased levels of D-dimer are observed in patients receiving an oral anticoagulant treatment versus untreated patients. In contrast, no significant difference was observed between those with and those without thrombophilia among treated or untreated patients. Patients with constitutional thrombophilia are supposed to have an increased risk of postoperative VTE. The review of the existing literature could not confirm this opinion but this could be due to the fact that most patients receive a prophylactic treatment. Thus, there is an indirect evidence of its efficacy in these patients.

Administration, Oral↗
PubMed2005

Primary and secondary prophylaxis of venous thromboembolism with low-molecular-weight heparins: prolonged thromboprophylaxis, an alternative to vitamin K antagonists.

Low-molecular-weight heparins (LMWHs) are used widely in the treatment and prevention of venous thromboembolism (VTE). The LMWHs dalteparin and enoxaparin reduce the rate of VTE by at least 50% if administered for 4-5 weeks following major orthopedic surgery, compared with in-hospital prophylaxis for 7-15 days. Meta-analyses have confirmed that the size of the reduction is similar for both clinical and asymptomatic VTE. Vitamin K antagonists (VKAs) have been shown to be associated with significantly higher bleeding rates compared with LMWH when used as prolonged prophylaxis against VTE following major orthopedic surgery. Patients with cancer are a recognized group at high risk of VTE, and those undergoing major surgery for their malignancy are at particular risk. Evidence from clinical trials is amassing to show that prolonged prophylaxis with LMWH (dalteparin, enoxaparin) in these patients can significantly reduce the rate of postoperative VTE. In cancer patients with acute VTE, the traditional approach is to initiate acute treatment with unfractionated heparin or LMWH followed by long-term treatment with VKA to prevent recurrence. However, clinical trial data have confirmed that the LMWH dalteparin, when administered for 6 months, is significantly more effective than VKA in preventing recurrence, cutting the rate of VTE by 52% without increasing the risk of bleeding. A new and intriguing area of interest is whether LMWH can enhance survival in patients with cancer. Preliminary data suggest that a biological effect of LMWH may act to prolong survival in patients with cancer.

Anticoagulants↗
PubMed2005

Thrombophilia and venous thromboembolism. International consensus statement. Guidelines according to scientific evidence.

Thrombophilia is the term now used to describe predisposition to increased risk of venous and occasionally arterial thromboembolism due to hematological abnormalities. It can be a multifactorial disorder where congenital defects of anticoagulant or procoagulant factors may be combined with acquired hematological abnormalities. It should be considered in patients with a documented unexplained thrombotic episode or a positive family history. The aim of this document is to provide guidelines for investigation and management of patients with thrombophilia in the presence or absence of venous thromboembolism (VTE).

Activated Protein C Resistance↗
PubMed2003

Comparative study of the pharmacokinetic profiles of two LMWHs--bemiparin (3500 IU, anti-Xa) and tinzaparin (4500 IU, anti-Xa)--administered subcutaneously to healthy male volunteers.

Pharmacokinetic profiles of bemiparin (3500 IU, anti-Xa) and tinzaparin (4500 IU, anti-Xa) administered subcutaneously to 12 healthy male volunteers were compared in a monocentric study. Each of the 12 subjects underwent successively the two low-molecular-weight heparin (LMWH) preparations in a randomised order and was considered as its own control. Anti-Xa activity, free and total tissue factor pathway inhibitor (TFPI), and thromboplastin-thrombomodulin-mediated time were determined as main variables. Activated partial thromboplastin time (APTT), thrombin clotting time, and anti-IIa activity were also determined. Bemiparin (3500 IU, anti-Xa) exerts a significantly more rapid, more potent, and more prolonged anti-Xa activity than tinzaparin (4500 IU, anti-Xa). The plasma level increase for free and total TFPI is significantly lower with bemiparin than with tinzaparin. Free and total TFPI peak levels occur earlier than anti-Xa activity peak levels for both LMWH preparations, but no statistical difference appeared between the two preparations for TFPI T(max). No significant effect was observed for both preparations for thromboplastin-thrombomodulin-mediated time. Subcutaneous injection of bemiparin exerts only minimal anti-IIa activity and does not prolong thrombin time, whereas tinzaparin elicits significant anti-IIa activity and prolongs thrombin clotting time. Bemiparin exerts a significantly lower prolongation of APTT than tinzaparin. No difference was observed for APTT prolongation T(max) between the two preparations. Globally, the overall tolerability of both formulations revealed no relevant adverse effects. In conclusion, bemiparin and tinzaparin are not bioequivalent. Bemiparin exerts an important and more prolonged anti-Xa activity in comparison with tinzaparin. An original finding of this study is the difference observed between the two formulations for free TFPI release.

Adolescent↗
PubMed2003

Potential use of D-dimer measurement in patients treated with oral anticoagulant for a venous thromboembolic episode.

AIM: We compared the level of plasma D-dimer in patients with previous venous thromboembolism (VTE), receiving or not oral anticoagulant treatment (OAT) and investigated its predictive value for the risk of VTE recurrence after OAT withdrawal. METHODS: We have studied 149 patients, 81 receiving oral anticoagulants and 68 after treatment interruption. Patients with known causes of D-dimer increase were excluded. D-dimer measurements were performed by Vidas analyzer (bioMérieux, France). RESULTS: A significantly lower D-dimer plasma level was found in patients under OAT than in untreated patients, 197+/-134 ng/ml versus 399+/-239 ng/ml, respectively (p<0.001). This decrease was similar in the different age populations and whether the patient had thrombophilia (n=84) or not. There was no correlation between INR and D-dimer levels. During a mean follow-up of 30 months, no recurrence occurred in patients under OAT versus 7 untreated patients. Among them, 3 had a D-dimer below 500 ng/ml, and 3 others had a level above 500 ng/ml. The last patient was not tested. CONCLUSION: The physician should be informed of the decrease of D-dimer under OAT, since the usual cut-off of 500 ng/ml used for deep vein thrombosis (DVT) exclusion is probably lower in such treated patients. It has been recently proposed that normal D-dimer level had a high negative predictive value for VTE recurrence when this dosage was performed 3 months after OAT interruption. The small number of recurrences observed in our study with an available result of D-dimer measured more than 3 months after OAT discontinuation does not allow a definite

Administration, Oral↗
PubMed2002

Markers of activated coagulation in patients with factor V Leiden and/or G20210A prothrombin gene mutation.

The activated protein C (APC) resistance phenotype associated with an abnormal factor V Leiden (FVL), and the G20210A prothrombin gene mutation are the most common findings in patients with venous thromboembolism (VTE). In a group of 210 patients, we compared the levels of markers of coagulation activation in carriers of FVL (71 heterozygous, 30 homozygous), G20210A prothrombin mutation (88 heterozygous) or both mutations combined (21 heterozygous), in order to assess whether these markers allow identification of a group of patients with a higher risk of thrombosis; they were also compared to normal values. A total of 143 patients had a personal history of VTE and 67 were asymptomatic. None of them had other hereditary causes of thrombophilia or an antiphospholipid syndrome. None were currently treated with either anticoagulant or hormonal treatment. Pregnant women were excluded. No significant difference between the four groups of patients could be found in the levels of F1+2, TAT and DDI. Levels were all significantly higher than the control values (p<0.05). The levels of F1+2 and TAT were similar in patients with or without a history of VTE, regardless of the type of mutation. DDI levels were significantly higher in patients with a history of VTE than in asymptomatic subjects (443+/-248 vs. 333+/-222 ng/ml, p=0.02) but with only 57% sensitivity and specificity. In conclusion, our study confirms the hypercoagulable state found in mutation carriers and points out the inability of F1+2 and TAT assays to identify a group of subjects at higher risk of thrombosis, within carriers of genetic risk factors. Although the sensitivity and specificity of DDI assay are low, high DDI concentrations tend to be associated with the risk of VTE.

Adult↗
PubMed2002

[Treatment of deep venous thrombosis by low molecular weight heparins. Comments on the recommendations of the North American Consensus].

LMW heparins have recently come into use in North America for treatment of venous thrombosis. Their first line recommendation is a major innovation of the last north american consensus conference on antithrombotics published in Chest at the beginning of 2001. This recommendation is grade 1A regarding its advantageous benefit-risk ratio. An earlier oral vitamine K antagonist treatment and a more regular nomogram use allow to reduce the relay duration and to obtain more often the targeted INR. The more predictable anticoagulant response with weight-based doses induces a simplified anti-Xa activity survey limited to renal dysfunction and obese or less than 50 Kg body weight persons but a regular platelet count remains mandatory. Several questions need to be discussed: once or twice daily subcutaneous injection use and treatment duration which seem related to the persistence of triggering factors, the variety of thrombophilia and comorbidity conditions. Due to a greater evidence-based medicine, the antithrombotic strategy becomes more related to a closer evaluation of the individual thrombotic risk level.

Adult↗
PubMed2002

Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery.

BACKGROUND: Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death. Two regulatory reviews in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs. The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery. METHODS: This prospective, randomized multicentre trial evaluated the risks of death, increased surgical site bleeding, gastrointestinal bleeding, acute renal failure, and allergic reactions, with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment. Patients were followed for 30 days after surgery. RESULTS: A total of 11,245 patients completed the trial at 49 European hospitals. Of these, 5634 patients received ketorolac and 5611 patients received one of the comparators. 155 patients (1.38%) had a serious adverse outcome, with 19 deaths (0. 17%), 117 patients with surgical site bleeding (1.04%), 12 patients with allergic reactions (0.12%), 10 patients with acute renal failure (0.09%), and four patients with gastrointestinal bleeding (0.04%). There were no differences between ketorolac and ketoprofen or diclofenac. Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac (odds ratio=2.65, 95% CI=1.51-4.67) and the comparators (odds ratio=3.58, 95% CI=1.93-6.70). Other risk factors for serious adverse outcomes were age, ASA score, and some types of surgery (plastic/ear, nose and throat, gynaecology, and urology). CONCLUSION: We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery.

Acute Kidney Injury↗