Venous Thromboembolism Treatment and Prophylaxis after Surgery for IBD.

Fixed-dose low-molecular-weight heparin, bemiparin, in the long-term treatment of venous thromboembolism in patients with transient risk factors in standard clinical practice: the FLEBUS study.

Low-molecular-weight heparins (LMWHs) have largely replaced unfractionated heparins for both prophylaxis and treatment of venous thromboembolism in nonpregnant patients. However, until recently, evidence in pregnant women was lacking, despite the increasing use of LMWHs during pregnancy in clinical practice. This review covers recent literature on the use of LMWHs in relation to pregnancy. The main areas covered in this review are the use of LMWHs in both prophylaxis and treatment of venous thromboembolism in pregnancy. The review also considers issues relating to monitoring of LMWHs in pregnancy, and safety from both a maternal and a fetal perspective. The available evidence demonstrates that LMWHs are of at least equivalent efficacy but have a better safety profile compared with unfractionated heparins in both prophylaxis and treatment of maternal venous thromboembolism, and are more convenient to administer. There is no consensus with respect to whether these agents require monitoring during pregnancy other than periodic checking of the platelet count. The clinical implication from the available evidence is that LMWHs should now be regarded as the anticoagulant agents of choice for both prophylaxis and treatment of maternal venous thromboembolism.

Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline

BackgroundDirect oral anticoagulants (DOACs) have recently been tested in multiple randomised controlled trials (RCTs) for the prophylaxis and treatment of cancer-associated venous thromboembolism (VTE) leading to changes in guidelines. To quantify the risks and benefits of DOACs in the prophylaxis and treatment of cancer-associated VTE, we performed a systematic review and meta-analysis of published RCTs.MethodsA systematic search of PubMed, Cochrane Library and Google Scholar databases for all phase-3 RCTs of DOACs in patients with cancer was conducted. Pooled estimates for the cumulative incidence of VTE, recurrent VTE, major bleeding and clinically relevant non-major bleeding (CRNMB) for each arm and pooled hazard ratio (HR) with 95% confidence intervals (CI) for VTE, recurrent VTE, major bleeding, CRNMB and overall survival were calculated by using random-effect model.ResultsSix phase-3 RCTs (N = 4341) which studied DOACs in prophylaxis or treatment of cancer-associated VTE were included. DOACs significantly reduced the risk of VTE versus placebo in prophylaxis (5% versus 9%, HR 0.51 and 95% CI:0.32–0.82) and the risk of recurrent VTE versus low-molecular-weight heparin in the treatment setting (4% versus 9%, HR 0.58 and 95% CI: 0.40–0.87) although, at a cost of increased risk of major bleeding (HR 1.46 and 95% CI: 1.0–2.12) or CRNMB (HR 1.42 and 95% CI: 1.10–1.81), there was no effect on survival (HR 1.01 and 95% CI: 0.85–1.20).ConclusionIn this meta-analysis, we found that DOACs not only significantly decreased the risk of VTE or recurrent VTE in patients with cancer but also significantly increased the risk of bleeding and CRNMB, with neither beneficial nor detrimental effects on survival. The quantification of these benefits and risks will assist in individualised shared decision-making.

Venous thromboembolism is a major health problem with substantial morbidity, mortality and related health care costs. Low-molecular-weight heparins (LMWHs) are drugs of first choice in the prophylaxis and treatment of venous thromboembolism. Bemiparin is a new LMWH with a higher antithrombotic activity than other LMWHs at equivalent dosing and a low bleeding tendency. Bemiparin was a dominant strategy over enoxaparin in major orthopedic surgery providing better outcomes and cost savings. Postoperative start of prophylaxis allowed a third of patients scheduled to undergo total knee or hip replacement to be admitted the same day of surgery, thus potentially reducing hospital stay costs. In the acute treatment of deep vein thrombosis, bemiparin was a dominant strategy over unfractionated heparin providing net cost savings and increased quality-adjusted life expectancy compared with unfractionated heparin plus oral anticoagulants. Outpatient management of venous thromboembolism with bemiparin in selected patients resulted in significant cost savings compared with in-patient treatment, while maintaining effectiveness and safety. Bemiparin may be a safer and cost-neutral alternative to oral anticoagulants for long-term treatment (secondary prophylaxis) of venous thromboembolism.

Review question/objective The objective of this review is to identify, appraise and synthesise the best available evidence on the facilitators and barriers to compliance with Venous Thromboembolism (VTE) risk assessment and prophylaxis clinical practice guidelines in the acute care setting. More specifically, the review question is: To what extent are clinical practice guidelines for risk assessment and prophylaxis of VTE adhered to in the acute care setting, and what are the facilitators and barriers? Inclusion criteria Types of participants This review will consider any studies that include all health care professionals regardless of their designated involvement with venous thromboembolism risk assessment and prophylaxis in the acute care setting. Phenomena of interest This review will consider studies that evaluated the facilitators and barriers to venous thromboembolism compliance with clinical practice guidelines in the acute care setting. The qualitative component of the review will consider as phenomena of interest any studies that identify facilitators and/or barriers to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The quantitative component of the review will consider any studies that report on the barriers and facilitators to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The textual component of the review will consider any paper that discusses the facilitators and/or barriers to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. Types of outcomes This review will consider studies that include measures of compliance as their outcome measures. The qualitative component of the review will consider any studies that identify facilitators and/or barriers to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The quantitative component of the review will consider any studies that report on the barriers and facilitators to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The textual component of the review will consider any paper TRUNCATED AT 350 WORDS

Venous Thromboembolism Risk Assessment and Prophylaxis: A Comprehensive Systematic Review of the Facilitators and Barriers to Healthcare Worker Compliance with Clinical Practice Guidelines in the acute care setting.

SummaryObjectives: To determine the attitude of physicians towards the ASCO evidence-based clinical practice guidelines for venous thromboembolism (VTE) prophylaxis and treatment in patients with cancer.Methods: The ASCO guideline was published in Jan. 2015. Two specialists in in the field assembled a list of arguments for and against each of the ASCO recommendations. ASCO recommendations and pro & con arguments were presented to physicians attending 3 educational seminars on hemostasis in cancer patients. After the presentation each attendee was asked to fill out a questionnaire on how much he agreed with the recommendations and the pro & con arguments.Results: A total of 89 physicians attended the three meetings. 56 questionnaires were returned. The ASCO recommendation with the highest degree of support was that patients undergoing major cancer surgery should receive prophylaxis for 7–10 days and for four weeks after major abdominal or pelvic surgery with high-risk features (84 % Pro). The recommendation with the lowest degree of support was that anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications (56 % Pro = indifference). Arguments based on A) the scientific evidence underlying each recommendation, B) on clinical practicability and patients’ preferences/adherence, C) on the desire to avoid toxicity, malpractice litigation, and cost concerns, ranked equally.Conclusion: The degree of support for ASCO guideline recommendations on prophylaxis and treatment of VTE in cancer is variable. For some key recommendations it is close to indifference. Scientific evidence for a recommendation is just one decision factor among others. Our study underscores the need to further promote educational activities on VTE prophylaxis and treatment in cancer patients particularly among all physicians caring for cancer patients.

In this chapter, we discuss the key-role of heparin in the prophylaxis and treatment of venous thromboembolism (VTE) and other thrombotic disorders. Heparin exerts its antithrombotic effects by facilitating the ability of antithrombin (AT), a plasma serum protease inhibitor, to inhibit thrombin (factor IIa) and factor Xa. Different heparin formulations can be used for the prophylaxis of thrombosis and treatment, going from unfractionated heparin (UFH), different low-molecular-weight heparin (LMWH) preparations, to the recently introduced synthetic pentasaccharide fondaparinux. All heparin formulations can be administrated only by the parenteral route, including the intravenous (iv) and the subcutaneous (sc) route. We will overview the clinical evidence for the use of different heparin formulations in the prophylaxis and treatment of venous thromboembolism, of superficial vein thrombosis and of acute coronary syndromes (ACS). Special issues, like the use of heparins in pregnancy or in children, will also be discussed. Although heparin is an almost one century-old drug it remains a cornerstone of antithrombotic treatment.

Targeted inhibition of coagulation: oral agents show promise in phase III trials.

Articles in this Series: Heit J. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol. 2008;28:370-372. Moll S. A clinical perspective of venous thromboemobolism. Arterioscler Thromb Vasc Biol. 2008;28:373-379. Gross P and Weitz J. New anticoagulants for treatment of venous thromboemobolism. Arterioscler Thromb Vasc Biol. 2008;28:380-386. Wakefield TW, Myers DD, Henke PK. Mechanisms of venous thrombosis and resolution. Arterioscler Thromb Vasc Biol. 2008;28:387-391. Link RP. National heart, lung, and blood institute programs for deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2008;28:392-393. Beckman MG, Critchley SE, Hooper WC, Grant AM, Kulkarni R. CDC division of blood disorders: public health research activities in venous thromboembolism. Arterioscler Thromb Vasc Biol. 2008;28:394-395. Fenninger R. Patient advocacy to promote public awareness about thrombosis and thrombophilia. Arterioscler Thromb Vasc Biol. 2008;28:396-397. Hunt BJ. The awareness and politics of venous thromboembolism in the United Kingdom. Arterioscler Thromb Vasc Biol. 2008;28:398-399. In 2005, the US Senate declared March as deep vein thrombosis (DVT) awareness month in the United States to increase the American public’s understanding of deep vein thrombosis.1 This was triggered by the death of 39-yr-old David Bloom, a National Broadcasting Company (NBC) reporter who died on April 6, 2003 from a massive pulmonary embolism (PE), and the activities of his widow, Melanie Bloom.2 Two days before his death David Bloom had developed cramping leg pain that was not recognized as a DVT2—leg DVT was only found postmortem. He had several risk factors for DVT and PE (collectively called venous thromboembolism [VTE)]): (1) prolonged immobility (working and sleeping in a cramped position in a tank in the war in Iraq); (2) long distance flights between the US and Kuwait, (3) dehydration, and (4) postmortem the discovery that he was heterozygous for the prothrombotic variant of factor V called factor V …

Rationale:The efficacy of direct oral anticoagulants (DOACs) in the treatment and prophylaxis of cancer-related venous thromboembolism (VTE) is reportedly similar to that of heparin. However, the effect of DOACs on the prophylaxis of cancer-related arterial thromboembolism (ATE) remains unclear. To our knowledge, we present the 1st case where cerebral ATE was encountered during edoxaban administration for VTE in a patient with lung adenocarcinoma.Patient concerns:In March 2017, a 63-year-old female was diagnosed with lung adenocarcinoma (cT2aN3M1b stage IVa) along with having asymptomatic VTE; thus, 60 mg/day edoxaban administration was initiated. In addition, 1st-line chemotherapy generated a partial antitumoral response. However, owing to lung cancer progression, a secondary treatment with pembrolizumab administration was initiated. The patient suddenly experienced aphasia 11 days after pembrolizumab administration.Diagnosis:The patient was diagnosed as multiple cerebral ATE using brain magnetic resonance imaging. However, VTE recurrence was not observed. Based on the findings of lung cancer progression and increased coagulation, cerebral ATE was diagnosed as Trousseau syndrome.Interventions:DOAC administration was switched to heparin administration.Outcomes:Coagulation profile normalized and aphasia improved without any further disease symptoms.Lessons:We considered that DOACs are effective for the treatment and prophylaxis of VTE but may be insufficient for ATE prevention. Therefore, DOACs should be replaced with heparin to prevent ATE when cancer and coagulation become uncontrollable with DOAC.

Low-molecular-weight heparins (LMWHs) form a heterogeneous group of compounds that exhibit an extended range of pharmacodynamic profiles and, potentially, different anti-thrombotic properties. Bemiparin has the lowest MW (3600 Da), the longest half-life (5.3 h) and the highest anti-FXa/anti-FIIa activity ratio (8:1) of any second-generation LMWH. The safety and efficacy of bemiparin has been demonstrated in several studies and it is currently licensed for treatment and prophylaxis of venous thromboembolism (VTE), as well as for the prevention of clotting in the extracorporeal circuit during hemodialysis. In particular, bemiparin is the only LMWH licensed in Europe for starting thromboprophylaxis after either general or orthopedic surgery. Results from multicenter pharmacoeconomic studies in the Spanish Health Care System indicate that bemiparin is more cost effective than enoxaparin for the prevention of VTE in total knee replacement and may be a safe, cost-saving alternative to unfractionated heparin in the short-term treatment of VTE, and a safe cost-neutral alternative to oral anticoagulant therapy in long-term treatment. In the near future, information from ongoing clinical trials could be key to establishing the potential of bemiparin in different clinical settings.

Thrombo-embolism of the venous system consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE) is common and associated with high morbidity and mortality. Symptomatic venous thromboembolism (VTE) manifests in about 1/3 of cases as PE and 2/3 as DVT. There is a strongly compound between early mortality after venous VTE and PE, age, malignancies and cardiovascular diseases. Anticoagulation therapy is the main therapeutic approach for the treatment of acute VTE and to prevent recurrent VTE events. For decade's classic anticoagulants like heparin, low-molecular-weight heparins (LMWHs), fondaparinux, and vitamin K antagonists have been the gold standards in therapy and are widely used. Novel oral anticoagulants (NOAC) like the direct thrombin inhibitor (dabigatran etexilate) and the direct factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) have been introduced to overcome the drawbacks of vitamin K antagonists. The efficacy and safety of these NOAC have been investigated in several randomized trials. Here we want to give an overview about the NOACS in the treatment of acute and chronic VTE and their use for primary prevention of acute VTE.

ObjectivesTo evaluate the incidence of paediatric venous thromboembolic events (VTEs) across university hospitals of Leicester trust.To analyse the risk factors preceding new thrombotic events to see if the implementation of...