- A systematic review of clinical practice guidelines on the use of low molecular weight heparin and fondaparinux for the treatment and prevention of venous thromboembolism: Implications for research and policy decision-making. [Journal Article]
- PlosPLoS One 2018; 13(11):e0207410
- CONCLUSIONS: Our findings contributed to the recommendation that the formulary listing for LMWH and FDP be streamlined to include coverage for specific outpatient indications. The paucity of available evidence on the comparative efficacy of specific LMWH agents against each other and FDP limited agent-specific listing recommendations, highlighting the need for high-quality comparative studies on this topic.
- An update on evidence based diagnostic and confirmatory testing strategies for heparin induced thrombocytopenia using combined immunological and functional assays. [Review]
- TATransfus Apher Sci 2018 Oct 30
- This manuscript aims to provide a concise review on current diagnostic/ confirmatory strategies of Heparin Induced Thrombocytopenia (HIT) with the combined use of immunological / functional assays in...
This manuscript aims to provide a concise review on current diagnostic/ confirmatory strategies of Heparin Induced Thrombocytopenia (HIT) with the combined use of immunological / functional assays in addition to the clinical probability. Laboratory diagnosis of HIT is of primordial importance as the related complications could become rapidly severe and life-threatening and can provoke limb amputation in some cases. The first action in the presence of HIT suspicion is to withdraw heparin and to initiate an alternative anticoagulant. Whilst vitamin K antagonists are not appropriate, anticoagulant options include Fondaparinux, Sodium Danaparoid, DOACs, Argatroban, and Bivalirudin. However, if HIT is excluded, patients can benefit again from the high therapeutic and antithrombotic efficacy of this drug, which remains superior to all the substitutive anticoagulant treatments. HIT is suspected in the presence of a platelet count drop > 50% on 2 successive counts, or a platelet count < 100 G/L, and of a significant clinical probability (4 Ts score). Testing patients' plasma is required for establishing the diagnosis. Laboratory investigation involves first the immunological measurement of heparin dependent IgG antibodies (mainly targeted to Heparin-Platelet Factor 4 complexes). When positive, a functional assay for platelet activation, performed at a low and high heparin concentration, allows confirming this disease. In any case, if the immuno-assay is negative, HIT can be excluded with a high probability, and heparin can be continued (if clinical examination favors this decision). Conversely, the higher the IgG antibody concentration is (and affinity), the higher is the probability of developing HIT. The functional assay has now become for confirming the platelet activation capacity of antibodies, and therefore confirming the presence of HIT. Up to now, the gold reference method for testing antibody-dependent platelet activation is the C14-Serotonin Release Assay, available only in very few laboratories working with radio-isotopes. A simple, sensitive, and accurate flow cytometry assay becomes now available to all clinical sites, and it can be easily used for testing the capacity of heparin dependent-antibodies to activate platelets, at low heparin concentration. This technique can be performed in any laboratory equipped with a flow cytometer and can make the HIT confirmation diagnosis rapidly available, which introduces a great improvement for management of patients with HIT. We believe that an evidence-based update on this topic is timely and well warranted.
- Treatment of Lower Extremity Superficial Thrombophlebitis. [Journal Article]
- JAMAJAMA 2018 Nov 01
- Which treatments for lower extremity superficial thrombophlebitis (ST) are associated with lower rates of venous thromboembolic events (VTEs) vs placebo?
Which treatments for lower extremity superficial thrombophlebitis (ST) are associated with lower rates of venous thromboembolic events (VTEs) vs placebo?
- Regulation of myelin structure and conduction velocity by perinodal astrocytes. [Journal Article]
- PNProc Natl Acad Sci U S A 2018 Oct 29
- The speed of impulse transmission is critical for optimal neural circuit function, but it is unclear how the appropriate conduction velocity is established in individual axons. The velocity of impuls...
The speed of impulse transmission is critical for optimal neural circuit function, but it is unclear how the appropriate conduction velocity is established in individual axons. The velocity of impulse transmission is influenced by the thickness of the myelin sheath and the morphology of electrogenic nodes of Ranvier along axons. Here we show that myelin thickness and nodal gap length are reversibly altered by astrocytes, glial cells that contact nodes of Ranvier. Thrombin-dependent proteolysis of a cell adhesion molecule that attaches myelin to the axon (neurofascin 155) is inhibited by vesicular release of thrombin protease inhibitors from perinodal astrocytes. Transgenic mice expressing a dominant-negative fragment of VAMP2 in astrocytes, to reduce exocytosis by 50%, exhibited detachment of adjacent paranodal loops of myelin from the axon, increased nodal gap length, and thinning of the myelin sheath in the optic nerve. These morphological changes alter the passive cable properties of axons to reduce conduction velocity and spike-time arrival in the CNS in parallel with a decrease in visual acuity. All effects were reversed by the thrombin inhibitor Fondaparinux. Similar results were obtained by viral transfection of tetanus toxin into astrocytes of rat corpus callosum. Previously, it was unknown how the myelin sheath could be thinned and the functions of perinodal astrocytes were not well understood. These findings describe a form of nervous system plasticity in which myelin structure and conduction velocity are adjusted by astrocytes. The thrombin-dependent cleavage of neurofascin 155 may also have relevance to myelin disruption and repair.
- Cost-effectiveness of alternative anticoagulation strategies for postoperative management of total knee arthroplasty patients. [Journal Article]
- ACArthritis Care Res (Hoboken) 2018 Oct 28
- CONCLUSIONS: Extending post-operative anticoagulation to 35 days increases QALYs compared to standard 14-day prophylaxis. Prolonged rivaroxaban and prolonged warfarin are most likely to be cost-effective post-TKA; the costs of fondaparinux and LMWH precluded their being preferred strategies. This article is protected by copyright. All rights reserved.
- Current and emerging pharmacotherapy for ischemic stroke prevention in patients with atrial fibrillation. [Journal Article]
- EOExpert Opin Pharmacother 2018 Oct 25; :1-11
- Atrial fibrillation (AF) is associated with high morbidity and mortality rates due to thromboembolic complications, and anticoagulation is central to the management of this common arrhythmia to preve...
Atrial fibrillation (AF) is associated with high morbidity and mortality rates due to thromboembolic complications, and anticoagulation is central to the management of this common arrhythmia to prevent acute thromboembolic events. The traditional anticoagulants: heparin, fondaparinux, and vitamin K antagonists (VKA, e.g. warfarin, acenocoumarol or phenprocoumin) have long served as pharmacotherapy for ischemic stroke prophylaxis. Areas covered: In this review article, the authors provide an overview on current and emerging pharmacotherapy for ischemic stroke prevention. Furthermore, they review the data from novel therapeutic targets in the coagulation cascade, and investigational anticoagulant drugs currently assessed in preclinical and clinical studies. Expert opinion: The introduction of nonvitamin K antagonist oral anticoagulants (NOACs) was an important milestone, as these drugs show relative efficacy, safety, and convenience compared to the VKAs. Nevertheless, their clinical use still has some limitations with, for example, patients with severe renal impairment and those with mechanical heart valves, high bleeding risks, lack of standard laboratory monitoring and (some) reversal agents. To overcome some of these limitations, various attempts are now underway to discover new strategies and targets via the hemostatic pathway in order to develop new coagulation inhibiting drugs.
- The Low Molecular Weight Heparin Tinzaparin Attenuates Platelet Activation in Terms of Metastatic Niche Formation by Coagulation-Dependent and Independent Pathways. [Journal Article]
- MMolecules 2018 Oct 24; 23(11)
- An intimate interplay with platelets is an initial key issue for tumor cells in terms of hematogenous metastasis. Tumor cells activate platelets by different pathways and receive, upon forming a plat...
An intimate interplay with platelets is an initial key issue for tumor cells in terms of hematogenous metastasis. Tumor cells activate platelets by different pathways and receive, upon forming a platelet cloak, protection from immune surveillance and support in metastatic niche creation. Therapeutic intervention with this early interaction is promising to antagonize the whole metastatic cascade. Here we aimed to investigate the capability of low molecular weight heparin (LMWH), unfractionated heparin (UFH), and a non-anticoagulant heparin derivative or FXa inhibitor fondaparinux to interfere with platelet activation by tumor cells. Coagulation-dependent and independent pathways of platelet activation by three tumor cell lines, and interference therewith were analyzed by fluorigenic thrombin formation assay, platelet aggregometry, ATP and VEGF release and endothelial tube formation assay. LMWH and UFH were found to repress various routes of platelet activation, reflected by attenuated endothelial tube formation. This confirms the duality of anti-coagulative and anti-adhesive properties of heparin. While non-anticoagulative heparin (RO-heparin) depressed platelets' ATP and VEGF release by contact inhibition sufficiently, fondaparinux just attenuated tissue factor mediated thrombin generation. Concluding, these data suggest that LMWH as a guideline-based drug for anticoagulative strategies in oncology is promising to provide additional benefit for interference with metastatic activities.
- Comparison of antithrombin-dependent and direct inhibitors of factor Xa or thrombin on the kinetics and qualitative characteristics of blood clots. [Journal Article]
- RPRes Pract Thromb Haemost 2018; 2(4):696-707
- CONCLUSIONS: All agents delayed thrombus formation. However, the compounds differed substantially with respect to fibrin polymerization rate and clot firmness. Comparison of the data obtained by thrombin generation assessment with those obtained by the thromboelastometric study shows that the delay in clot formation is principally associated with prolongation of the initiation phase of thrombin formation as well as a reduction of the propagation phase. Tinzaparin was much more potent than the other agents both with regard to suppression of thrombin generation and by delay in clot formation.
- Systematic review of fondaparinux for heparin-induced thrombocytopenia: When there are no randomized controlled trials. [Journal Article]
- RPRes Pract Thromb Haemost 2018; 2(4):678-683
- CONCLUSIONS: Fondaparinux appears to be an effective and safe anticoagulant for treatment of acute HIT despite the absence of randomized trials. Caution should exercised when using fondaparinux in patients with renal insufficiency.
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- Evaluation of unfractionated heparin versus low-molecular-weight heparin and fondaparinux for pharmacologic venous thromboembolic prophylaxis in critically ill patients with cancer. [Journal Article]
- JTJ Thromb Haemost 2018 Oct 22
- CONCLUSIONS: The use of a LMWH VTE prophylaxis was not associated with a reduction in the incidence of in-hospital VTE as compared to UFH, but was associated with significant reduction in clinically important bleeding events and incidence of HIT in critically ill patients with cancer. This article is protected by copyright. All rights reserved.