Clot waveform analysis: Where do we stand in 2017?

Analysis of the optical waveform generated during global coagulation assays, such as activated partial thromboplastin time and prothrombin time, can provide much precious information on the global coagulation state of the plasma sample tested, in addition to a single clotting time. Many studies have been published concerning patient diagnosis and management in haemophilia A, and in the early diagnosis and prognosis of disseminated intravascular coagulation and sepsis. However, many other works have also been published on further potential clinical applications such as lupus anticoagulant diagnosis and anticoagulant monitoring. Altogether, these publications have demonstrated the ability for clot waveform analysis (CWA) to improve patient management, especially as this tool is inexpensive, rapid and readily available on coagulation analysers with optical detection systems. By an extensive review of the literature related to studies performed on CWA, this publication aims at providing a review of current knowledge in this specific field, ranging from research data to potential clinical applications and future trends.

[Two new anticoagulants available in 2010--Dabigatran Etexilate and Rivaroxaban: expected progresses--raised problems]. / Deux nouveaux anticoagulants disponibles en 2010--Dabigatran Etexilate et Rivaroxaban: progrès attendus--problèmes posés.

After having been used for decades, heparins (unfractionated heparin [UFH] or low molecular weight heparins [LMWH]) and vitamin K antagonists (VKA), which are only parenterally active or which are responsible for frequent iatrogenicity respectively, have to face the competition of new anticoagulant drugs targeting either factor Xa or factor IIa (thrombin). Rivaroxaban (Xarelto(®)) and Dabigatran Etexilate (Pradaxa(®)) are the two leading components. They are more convenient to use and do not require routine coagulation monitoring. They are already marketed for venous thromboembolism prevention in major orthopaedic surgery. Although manufacturers claim that no biological monitoring is required, these two compounds may interfere in routine coagulation tests such as PT or aPTT, and in esoteric assays such as anti-Xa activity (the results of which are usually expressed in international anti-Xa units either UFH or LMWH unit) for Rivaroxaban or anti-IIa activity for Dabigatran Etexilate. Noteworthy is the fact that, in the case of these new anticoagulant drugs, results should be expressed in active product units (nanogram per millilitre of Rivaroxaban or Dabigatran). The new anticoagulants are associated with a bleeding risk comparable to that of VKA and heparins.

[From old to new anticoagulants: the role of the biologist]. / Des anciens aux nouveaux anticoagulants : le rôle du biologiste.

Anticoagulant drugs are of great interest to patients and clinical physicians, as well as research scientists. The latter two groups combine their efforts to unravel the related mechanisms of action, as well as means of monitoring and proper dosing. Unfractionated heparin and low molecular weight heparins and vitamin K antagonists have been on board for several decades by now. They act on several clotting factors in certain sequences. Newer drugs, produced by chemical synthesis, act on a more specific target, often factor Xa or factor IIa. These newer anticoagulants have a great convenience in being orally administered and not needing routing laboratory monitoring - which is their main advantage. Hirudine and fondaparinux have been registered for a few years. This year, that is 2008 + 2009, two of these new anticoagulants have been registered and approved for use in Europe and Canada - these are dabigatran etexilate (Pradaxa) and rivaroxaban (Xarelto). Both do not require routine laboratory monitoring. However, coagulation assays for measuring their activity have been studied. A small number of standardized tests should be perfected.

[Epilepsy and Sabril]. / L'epilepsie et le Sabril.

This article presents a litterature overview of the ophthalmologic secondary effects due to Sabril. First, a review of the visual field loss that can be related to Sabril treatment is presented; the epidemiological and physiopathological aspects of this visual field loss are considered based on experimental and clinical data. The link that can be established between electrophysiology and physiopathology following these data is further examined. Finally, two ophthalmologic follow-up algorithms are proposed for patients treated by Sabril, one for adults and the other for children.

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.

[Heparin-induced thrombocytopenia]. / Thrombopénies induites par l'héparine.

Heparin-induced thrombocytopenia is a threatening complication of heparin treatment. The physio-pathological mechanism is the production of antibodies, the most frequent target of which is the complex heparin-platelet factor 4. These antibodies may activate the coagulation and lead to venous or arterial thromboembolic manifestations. Clinical features as well as functional and immunological tests are used for the diagnosis. The treatment consists in discontinuing heparin administration and in setting up an alternative treatment for which two drugs are indicated in France: Orgaran and Refludan.

Determination of iodide in serum and urine by ion-pair reversed-phase high-performance liquid chromatography with coulometric detection.

An HPLC method is described for the determination of iodide in serum and urine using ion-pair chromatography with coulometric detection. After adding hexadecyltrimethylammonium chloride, the ions pairs formed with the iodide in the sample are extracted using an organic solvent. The solvent is then evaporated and the dry residue obtained is mixed with an appropriate volume of mobile phase so as to concentrate the sample prior to injection into the chromatograph. For a sample of 0.5 ml of serum, the method features a limit of detection (signal-to-noise ratio of 3) of 0.2 microgram l-1, sufficient to be applied in paediatric assays for the diagnosis of both iodide deficiency and excess.

Huygens-Fresnel principle in the near field.

The Huygens-Fresnel principle provides a conceptual understanding for wave propagation and diffraction. Recently the principle has been reexamined to suggest that it is also valid in the near field. We reformulate the problem in terms of nonradiative optics, focusing particularly on the obliquity factor inherent in the forward-directed propagation of light. In the near field of matter no explicit obliquity factor exists.

Detection of micronuclei after exposure to mitomycin C, cyclophosphamide and diethylnitrosamine by the in vivo micronucleus test in mouse splenocytes.

A micronucleus detection test using mouse splenocytes has been adapted from a method previously carried out using human lymphocytes. An ex vivo protocol was chosen: male C57B16 mice were treated with various compounds. Splenocytes were then isolated and placed in culture for 48 h and stimulated with concanavalin A and conditioned medium. The cytokinesis-block method reported by Fenech and Morley was used to detect and score micronuclei in the proliferating lymphocytes (3 micrograms/ml of cytochalasin B for 16 h). Three mutagenic clastogens, mitomycin C (MMC), a direct alkylating agent (0.4, 0.8 and 1.6 mg/kg), cyclophosphamide (CP), an indirect alkylating agent (25, 50 and 100 mg/kg) and diethylnitrosamine (DEN), an indirect alkylating agent with labile metabolites (25, 50 and 100 mg/kg), were tested at four sampling times (2, 4, 8 and 15 days). All three compounds were detected from 48 h after treatment. This method was indeed able to detect clastogenic compounds normally detected by the mouse bone marrow micronucleus test (MMC, CP) as well as a compound with labile metabolites which is not usually detected by this test (DEN). Maximum micronucleus induction was observed after 4 days for MMC, 2 days for CP and 15 days for DEN. This method thus appears to offer a potentially useful toxicological test for assessing in vivo clastogenicity.

Superresolution of near-field optical microscopy defined from properties of confined electromagnetic waves.

The experimental resolution that is obtained with a near-field microscope by optical tunneling detection is far beyond the Rayleigh criterion. We discuss the principal physical characteristics of this superresolution. Three different examples are presented. They show that the resolution increases as the collector width and collector-to-object distance decrease. It is interesting to note that, in the near-field microscope, as in all local probe microscopes, the resolution cannot be defined from the characteristics of the microscope only. In all tunnel devices the detector cannot be separated from the object. The superresolution that can be obtained results from this fact. This paper also points out the importance ofevanescent waves in near-field optics and makes the connection between resolving power and evanescent fields.

Modeling of the field transfer through thick dielectric lines: use in linewidth measurement.

A numerical method for calculating the optical image of a thick line object is presented. It consists of slicing (fictitiously) the object and of analyzing the propagation through each elementary slice. The method is first developed for coherent light and then generalized for partially coherent illumination. Some results are compared with other simulations and with experiments.

Salivary lactoferrin in primary Sjögren's syndrome.

Parotid salivary lactoferrin (LF) levels were measured in 26 patients with Sjögren's syndrome (SS), 19 patients with keratoconjunctivitis sicca (KCS) and 32 normal controls, by using a radial-immunodiffusion technique. The levels of LF were higher in SS than in KCS patients (23 +/- 21, 10 +/- 10, p less than 0.03) and in SS patients than in normals (7 +/- 6 micrograms/ml, p less than 0.001). There was some relationship of the LF level to the labial salivary gland histopathology grade.