How Do We Treat Pregnancy-Related Venous Thromboembolism?

2019 ◽  
Vol 40 (01) ◽  
pp. 054-063 ◽  
Author(s):  
Birgit Linnemann ◽  
Birgit Seelbach-Goebel ◽  
Susanne Heimerl ◽  
Christina Hart
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Treatment Strategies ◽  
Factor Xa ◽  
Study Data ◽  
Time Interval ◽  
Uncomplicated Pregnancy ◽  
Delivery Date ◽  
Maternal Morbidity And Mortality ◽  
Dosing Regimens

AbstractVenous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy and the postpartum period. Due to a lack of adequate study data, therapeutic strategies for pregnancy-related VTE are deduced from observational studies and extrapolated from recommendations for nonpregnant patients. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low-molecular-weight heparins (LMWHs) are the anticoagulant treatment of choice in cases of VTE during pregnancy. Once- and twice-daily dosing regimens are suitable. There is no evidence that measurement of factor Xa activities and consecutive LMWH dose adjustments improve clinical outcomes. There is no support for the routine use of vitamin K antagonists, direct oral thrombin or factor Xa inhibitors, fondaparinux, or danaparoid in uncomplicated pregnancy-related VTE. Management of delivery deserves special attention, and treatment strategies depend on the time interval between the diagnosis of acute VTE and the expected delivery date. In lactating women, an overlapping switch from LMWH to warfarin is possible. Anticoagulation should be continued for at least 6 weeks postpartum or for a minimum period of 3 months.

Treatment of pregnancy-associated venous thromboembolism - position paper from the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

VASA ◽  
2016 ◽  
Vol 45 (2) ◽  
pp. 103-118 ◽  
Author(s):  
Birgit Linnemann ◽  
Ute Scholz ◽  
Hannelore Rott ◽  
Susan Halimeh ◽  
Rainer Zotz ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Women’S Health ◽  
Women's Health ◽  
Working Group ◽  
Management Strategies ◽  
Factor Xa ◽  
Study Data ◽  
Time Interval ◽  
Anticoagulant Treatment ◽  
Dosing Regimens

Abstract. Venous thromboembolism (VTE) is a major cause of maternal morbidity during pregnancy and the postpartum period. However, because there is a lack of adequate study data, management strategies for pregnancy-associated VTE must be deduced from observational stu-dies and extrapolated from recommendations for non-pregnant patients. In this review, the members of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) have summarised the evidence that is currently available in the literature to provide a practical approach for treating pregnancy-associated VTE. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low molecular weight heparin (LMWH) is the anticoagulant treatment of choice in cases of acute VTE during pregnancy. No differences between once and twice daily LMWH dosing regimens have been reported, but twice daily dosing seems to be advisable, at least peripartally. It remains unclear whether determining dose adjustments according to factor Xa activities during pregnancy provides any benefit. Management of delivery deserves attention and mainly depends on the time interval between the diagnosis of VTE and the expected delivery date. In particular, if VTE manifests at term, delivery should be attended by an experienced multidisciplinary team. In lactating women, an overlapping switch from LMWH to warfarin is possible. Anticoagulation should be continued for at least 6 weeks postpartum or for a minimum period of 3 months. Although recommendations are provided for the treatment of pregnancy-associated VTE, there is an urgent need for well-designed prospective studies that compare different management strategies and define the optimal duration and intensity of anticoagulant treatment.

scholarly journals New anticoagulants for the treatment of venous thromboembolism

2016 ◽  
Vol 42 (2) ◽  
pp. 146-154 ◽  
Author(s):  
Caio Julio Cesar dos Santos Fernandes ◽  
José Leonidas Alves Júnior ◽  
Francisca Gavilanes ◽  
Luis Felipe Prada ◽  
Luciana Kato Morinaga ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
New Anticoagulants ◽  
Acute Pulmonary Thromboembolism ◽  
Deep Vein

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

Management of cancer-associated venous thromboembolism – a case-based practical approach

VASA ◽  
2018 ◽  
Vol 47 (2) ◽  
pp. 77-89 ◽  
Author(s):  
Minna Voigtlaender ◽  
Florian Langer
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Clinical Trial Data ◽  
Thrombin Inhibitors ◽  
Current Standard ◽  
Randomized Controlled Studies ◽  
Symptomatic Pulmonary Embolism ◽  
Direct Head

Abstract. In patients with solid tumours or haematological malignancies, venous thromboembolism (VTE) is a leading cause of death and significantly contributes to morbidity and healthcare resource utilization. Current practice guidelines recommend long-term anticoagulation with low-molecular-weight heparin (LMWH) as the treatment of choice for cancer-associated VTE, based on clinical trial data showing an overall improved safety and efficacy profile of LMWH compared to vitamin K antagonists. However, several open questions remain, e. g. with regard to the intensity and duration of LMWH therapy; moreover, recent real-world evidence indicates that adherence to parenteral anticoagulation with LMWH over the course of treatment is poor in clinical practice. In this regard, the direct oral factor Xa or thrombin inhibitors (DOACs) have emerged as potential alternatives in the management of patients with cancer-associated VTE, albeit findings from randomized controlled studies with a direct head-to-head comparison of DOACs with LMWH, the current standard of care, are still lacking. Based on the case of a lymphoma patient experiencing symptomatic pulmonary embolism during immunochemotherapy, this article aims at both highlighting the current state-of-the-art approach to cancer-associated VTE and pointing out some of the unresolved, controversial issues clinicians have to face when taking care of haematology and oncology patients with already established or with high risk of developing VTE. These issues include the management of patients with incidental pulmonary embolism or thrombocytopenia, the use of DOACs, and the initiation of pharmacological thromboprophylaxis in non-surgical cancer patients.

The long path to NOAC

Phlebologie ◽  
2016 ◽  
Vol 45 (04) ◽  
pp. 245-251
Author(s):  
S. Haas
Keyword(s):  
Mode Of Action ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Thrombin Inhibitor ◽  
Renal Elimination ◽  
Early 21St Century ◽  
Recombinant Production ◽  
Anticoagulant Drugs ◽  
Venous Thromboembolic ◽  
Dosing Regimens

SummaryThe discovery of anticoagulant drugs occurred at a time when the process of blood coagulation only had been roughly described and their mode of action was unknown. Nevertheless, heparin – which was discovered 100 years ago – and warfarin – which was developed in the 1920s – had taken off on a triumphal course which is unique in medical history. The synthesis of anticoagulants with targeted mode of action was only achieved at the end of the last century, e. g. the inhibitor of factor Xa fondaparinux or the recombinant production of the direct thrombin inhibitor hirudin, closely followed by the synthesis of the direct oral inhibitors of factor Xa and thrombin. These compounds had been clinically developed in the early 21st century and meanwhile, they have become available for several indications. Dabigatran is the only thrombin inhibitor and rivaroxaban, apixaban and edoxaban are the three factor Xa inhibitors which entered the market and have started replacing the conventional anticoagulants for treatment of venous thromboembolic complications and for prevention of stroke in patients with atrial fibrillation. They have several characteristics in common such as a reproducible bioavailability, much shorter halflives than vitamin K antagonists, low interaction with other drugs, fixed dosing regimens without the necessity for routine coagulation controls and a better risk-/benefit profile than conventional anticoagulants. However, there are differences between the various compounds with regard to metabolism, renal elimination and the various dosing regimens which definitely need to be considered when prescribed to various patient populations.

Pros and cons of new oral anticoagulants

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 464-470 ◽  
Author(s):  
Kenneth A. Bauer
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Rapid Onset ◽  
New Oral Anticoagulants ◽  
Therapeutic Class ◽  
Pros And Cons ◽  
Additional Agent

Abstract The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time. Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients.

scholarly journals Hemopericardium with subsequent cardiac tamponade secondary to rivaroxaban treatment: a case report

2020 ◽  
Author(s):  
Pinang Shastri ◽  
Sapan Bhuta ◽  
Carson Oostra ◽  
Todd Monroe
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Cardiac Tamponade ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Thromboembolism Prophylaxis ◽  
Cardiac Device ◽  
Large Pericardial Effusion

Abstract Background The use and utility of novel oral anticoagulants has been increasing in clinical practice due to their relatively lower incidence of side effects such as intracranial haemorrhage, particularly in the elderly, when compared with vitamin K antagonists. Rivaroxaban is a factor Xa and prothrombinase inhibitor indicated for stroke and venous thromboembolism prophylaxis in non-valvular atrial fibrillation as well as treatment of venous thromboembolism. Case summary A patient with history of paroxysmal atrial fibrillation on Rivaroxaban presented with generalized malaise, lightheadedness, and dizziness. The patient was found to be in profound cardiogenic shock despite unremarkable cardiac enzymes. Electrocardiogram revealed rate controlled atrial fibrillation and T-wave inversions in the inferolateral leads without associated electrical alternans. Bedside echocardiogram revealed a large pericardial effusion consistent with cardiac tamponade physiology. Following anticoagulation reversal, the patient underwent urgent pericardiocentesis yielding haemorrhagic fluid, with subsequent improvement in haemodynamic status. Despite the presence of retroperitoneal lymphadenopathy on previous computed tomography of the abdomen and concern for underlying malignant effusion secondary to lymphoma, cytology of the fluid revealed no evidence of malignant cells and follow-up flow cytometry and bone marrow biopsy were unremarkable. Discussion While hemopericardium is not listed as a known side effect of Rivaroxaban, previous cases of hemopericardium secondary to Rivaroxaban have been described in the literature secondary to pre-disposing risk factors including CYP450 drug interactions or cardiac device implantations. In this case, the patient experienced a spontaneous hemopericardium on Rivaroxaban without any previously elucidated risk factors or evidence of malignancy.

scholarly journals Direct oral anticoagulants and venous thromboembolism

2016 ◽  
Vol 25 (141) ◽  
pp. 295-302 ◽  
Author(s):  
Massimo Franchini ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Direct Anticoagulants ◽  
Deep Vein

Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

scholarly journals Clinical characteristics of italian patients with venous thromboembolism enrolled in the RIETE Registry

2012 ◽  
pp. 255-260
Author(s):  
Pierpaolo Di Micco ◽  
Alessandra Bura-Riviere ◽  
Renzo Poggio ◽  
Eros Tiraferri ◽  
Roberto Quintavalla ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Characteristics ◽  
Vitamin K Antagonists ◽  
Treatment Strategies ◽  
Initial Therapy ◽  
Term Therapy ◽  
Vte Prophylaxis ◽  
Fatal Bleeding ◽  
Long Term Therapy

Introduction: The clinical characteristics, treatment strategies and outcome of patients with venous thromboembolism (VTE) may vary from country to country. Materials and methods: The RIETE (Registro Informatizado su la Enfermedad TromboEmbolica) is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. Our aim was to assess the influence of surgery and immobility for non-surgical reasons on 3-month outcomes of all Italian patients registered in the RIETE. Results: Through July 2008, 21,397 patients with acute VTE were registered in the RIETE. Of these, 896 (4.2%) were Italian, and 360 (40%) presented with pulmonary embolism (PE). Overall, 137 (15%) developed VTE after surgery; 156 (17%) developed VTE after >4 days of immobility, and 603 (67%) developed VTE in the absence of surgery or immobility. Most patients (83%) received initial therapy with low-molecular-weight heparin; 15% received unfractionated heparin. For long-term therapy, 63% of patients received vitamin K antagonists. The incidence of fatal PE during the first 3 months of therapy was 1.5% for patients with postoperative VTE, 7.7% for who developed VTE after immobility, and 1.2% for the remaining patients. The incidence of fatal bleeding among these patients was 1.5%, 1.9% and 0.3%, respectively. Of the 137 patients with postoperative VTE, 61% had received VTE prophylaxis. Of the 156 patients with recent immobility, 24% had received VTE prophylaxis. Conclusions: VTE arising after a period of immobility was associated with the highest rates of fatal PE and fatal bleeding during the first 3 months of therapy. The use of thromboprophylaxis in this population should be improved.

Emerging anticoagulants for the treatment of venous thromboembolism

2006 ◽  
Vol 96 (09) ◽  
pp. 274-284 ◽  
Author(s):  
Jeffrey Weitz
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Drugs ◽  
New Anticoagulants ◽  
Postphlebitic Syndrome ◽  
Long Acting ◽  
Two Stages

SummaryAnticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists,such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This paper i) reviews the pharmacology of these agents, ii) outlines their potential strengths and weaknesses, iii) describes the results of clinical trials with these new drugs, and iv) identifies the evolving role of new anticoagulants in the management of VTE.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue

VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 87-95 ◽  
Author(s):  
Giovanna Elmi ◽  
Giuseppe Di Pasquale ◽  
Raffaele Pesavento
Keyword(s):  
Venous Thromboembolism ◽  
Safety Profile ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Recurrence ◽  
Extended Treatment

Abstract. As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

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