Teitel, Jerome M.
Venous thromboembolic diseases are among the most important causes of morbidity and mortality in Canada. Agents which interfere with the coagulation mechanism are highly effective in treating these disorders, but at the potentially high cost of serious hemorrhagic complications. The optimal prevention of both serious outcomes and complications of therapy can be achieved by prophylactic treatment of high risk patients. Heparin and vitamin K antagonists remain the mainstays of antithrombotic therapy. The pharmacology of these agents is reviewed, and a rational approach to their clinical use is presented. PMID:21279098
Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero
Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269
Harter, Katherine; Levine, Michael; Henderson, Sean O.
Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin) for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter. PMID:25671002
Franchini, Massimo; Liumbruno, Giancarlo M.; Bonfanti, Carlo; Lippi, Giuseppe
Arterial and venous thromboembolism are leading causes of morbidity and mortality around the world. For almost 70 years, heparins (unfractionated heparin and low molecular weight heparins) and vitamin K antagonists have been the leading therapeutic medical options for the treatment and prevention of thromboembolic disorders. Nevertheless, the many limitations of these traditional anticoagulants have fuelled the search for novel agents over the past 15 years, and a new class of oral anticoagulants that specifically target activated factor X and thrombin has been developed and is now commercially available. In this narrative review, the evolution of anticoagulant therapy is summarised, with a focus on newer oral anticoagulants. PMID:26710352
Cundiff, David K
Context On the basis of theoretical rationale, heparoids and vitamin K antagonists are prescribed to prevent complications of venous thromboembolism (VTE, including pulmonary emboli [PE] and deep vein thrombosis [DVT]). They have been employed as the standard of care for treatment of VTE for over 40 years. Objective Critique the evidence supporting the efficacy of anticoagulants for the treatment of VTE in reducing morbidity and/or mortality. Data Sources This includes a search of reference lists and Medline. Study Selection This includes studies concerning the diagnosis and incidence of PE and DVT, efficacy of anticoagulants in preventing complications, risks of anticoagulant therapy, and the costs of diagnosis and the treatment of VTE. Data Extraction I analyzed references cited in reviews and meta-analyses of VTE, and from Medline searches concerning diagnosis and treatment. The data quality and validity of studies depended on the consistency of findings and statistical significance of the data. Data Synthesis No placebo-controlled trials of anticoagulants as treatment of PE with objective criteria for diagnosis have been published. Three randomized trials of anticoagulants vs no anticoagulants in DVT showed no benefit with heparin and vitamin K antagonists (combined all-cause mortality: anticoagulants = 6/66, un-anticoagulated controls = 1/60, P = .07). No placebo-controlled trials of low-molecular-weight heparins or thrombolytic drugs have been done; therefore, their efficacy in VTE depends entirely on randomized comparisons with unfractionated heparin. They have not been proven safer or more efficacious than unfractionated heparin. Thrombolysis causes more major and fatal bleeds than heparin and is no more effective in preventing PE. Diagnosing and treating VTE patients in the United States with anticoagulants costs $3.2 to $15.5 billion per year (1992 dollars). Bleeding and complications of angiography cause 1017-3525 deaths annually. Conclusion
Martí-Fàbregas, J; Delgado-Mederos, R; Mateo, J
Vitamin K antagonists have been shown to be effective in the primary and secondary prevention of systemic and cerebral emboli in patients with cardiac causes of embolism, especially atrial fibrillation. The reduced risk of stroke is greater in secondary prevention, although this reduction is accompanied by an inherent risk of hemorrhagic complications, among which cerebral hemorrhage is especially serious. The therapeutic window of these agents is limited and the best benefit/risk profile is obtained with an INR of between 2 and 3. The anticoagulant effect obtained shows marked variability, requiring frequent clinical and laboratory monitoring of the treatment. The introduction of oral anticoagulants that would aid the administration of these agents with equal or greater efficacy and lower risk is required.
Akagi, Satoshi; Kusano, Kengo Fukushima
Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.
Schulman, Sam; Witt, Daniel M.; Vandvik, Per Olav; Fish, Jason; Kovacs, Michael J.; Svensson, Peter J.; Veenstra, David L.; Crowther, Mark; Guyatt, Gordon H.
Background: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. Conclusions: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. PMID:22315259
Herman, W W; Konzelman, J L; Sutley, S H
Despite approximately 40 years of experience with oral anticoagulant drugs, controversy still exists about the safety of dental treatment in a patient receiving this therapy. The authors review the topic in depth and offer detailed recommendations for the dental management of patients receiving coumarin anticoagulant therapy.
Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations. PMID:27617088
Hernández Olmedo, Miguel; Suárez Fernández, Carmen
Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization.
Weibert, R T
The literature on dental surgery in patients receiving oral anticoagulants is reviewed, and methods of managing anticoagulant therapy to minimize the risk of complications are discussed. Although blood loss during and after oral surgery in patients receiving oral anticoagulant drugs can be substantial, research indicates that most bleeding incidents are not serious and can be controlled by local measures. Studies of 241 anticoagulant-treated patients undergoing more than 500 dental extractions during the 1950s and 1960s showed that only 9 had postoperative bleeding. More recent studies indicate that continued anticoagulation can increase the frequency of prolonged bleeding and delay wound healing. An antifibrinolytic mouthwash containing tranexamic acid can effectively suppress postoperative bleeding. Gelatin sponges, oxidized cellulose, and microcrystalline collagen are other useful hemostatic agents. A reduction in the intensity of anticoagulation therapy has been recommended; the prothrombin time should be measured shortly before the procedure in such patients. In many patients the duration of subtherapeutic anticoagulation must be minimized to reduce the possibility of thromboembolism. An option for high-risk patients is to switch them to heparin. Each patient must be evaluated individually, and the level of risk of the dental procedure and the risk of thromboembolism should be taken into account. In patients taking oral anticoagulants who must undergo dental surgery, careful control of the intensity of anticoagulation and improved methods of local hemostasis can minimize the risk of hemorrhagic complications and thromboembolism.
Yoshioka, Daisuke; Toda, Koichi; Hidaka, Takayuki; Yasuda, Soichiro; Saito, Shunsuke; Domae, Keitaro; Sawa, Yoshiki
Anticoagulation therapy with warfarin is essential for postoperative management in patients with left ventricular assist device (LVAD). In this manuscript, we report the case of a patient who developed warfarin resistance after LVAD implantation. Although we administered a novel anticoagulant drug in addition to warfarin and aspirin therapy, the patient developed a major stroke. The patient needed continuous intravenous heparinization until heart transplantation for approximately 2 years. Meticulous management of anticoagulation therapy is essential for a LVAD with warfarin resistance. To our best knowledge, our case is the first case of warfarin resistance in a patient with LVAD.
Dahlberg, Katherine Willett
Abstract: Despite the availability of predictive tools and treatment guidelines, anticoagulant therapies are underprescribed and many patients are undertreated for conditions that predispose to thromboembolic complications, including stroke. This review explores reasons for which physicians fear that the risks of anticoagulation may be greater than the potential benefit. The results of numerous clinical trials confirm that patients benefit from judiciously managed anticoagulation and that physicians can take various approaches to minimize risk. Use of stratification scores for patient selection and accurate estimation of stroke risk may improve outcomes; bleeding risk is less important than stroke risk. Adoption of newer anticoagulants with simpler regimens may help physicians allay their fears of anticoagulant use in patients with atrial fibrillation. These fears, although not groundless, should not overtake caution and hinder the delivery of appropriate evidence-based care. PMID:25285512
Yasaka, Masahiro; Okada, Yasushi
Novel anticoagulants including dabigatran and rivaroxaban have lower incidence of intracranial hemorrhage compared to warfarin. Therefore, in patients with high risks for intracranial hemorrhage, such as past history of brain infarction, brain hemorrhage, microbleeds on MRI, or concomitant use of antiplatelet, novel anticoagulant may be appropriate. Irrespective of any anticoagulants, it is essential to manage controllable risk factors, such as hypertension, diabetes mellitus, smoking habit, and excessive alcohol drinking. Combination therapy of other antithrombotic agents had better be avoided as long as possible. In emergency of hemorrhage complications, discontinuation of anticoagulants, procedure to stop bleeding, and appropriate intravenous infusion is quite important and lowering blood pressure is also important when intracranial hemorrhage happens. There is no antidote to novel anticoagulants. However, oral activated charcoal may be effective if early after taking medicine. The dabigatran can be dialysed. Some experimental evidences support the role of prothrombin complex concentrate to stop bleeding. However, their usefulness in clinical setting has not been established. Collecting and analyzing data regarding immediate reversal of novel anticoagulants is required in near future.
Nowak-Göttl, U; Langer, F; Limperger, V; Mesters, R; Trappe, R U
Oral anticoagulants [Vitamin-K-Antagonists, Dabigatran, Rivaroxaban, Apixaban] or antiplatelet agents [Aspirin, Clopidogrel, Prasugrel, Ticagrelor] are effective in preventing thromboembolic diseases. In case of interventional of surgical procedures patients with indications for chronic anticoagulation [atrial fibrillation, valve prosthesis, venous thromboembolism] or use of antiplatelet agents [cerebrovascular events, cardiovascular events] will require interruption of antithrombotic/antiplatelet therapy with the need of replacement with a short-acting agent. Due to limited data available from randomized studies and meta-analyses the evidence level is low in the majority of recommendations. Therefore for each patient the bleeding and thrombosis risk depending on the individual patient constitution and the planned intervention must be weighted. In patients with an intermediate risk for thrombosis the bleeding risk of the scheduled intervention will influence the bridging recommendation: In patients with a low bleeding risk oral anticoagulation/antiplatelet therapy can be continued or reduced in intensity. In patients with an intermediate or high bleeding risk along with a low thrombosis risk a temporary interruption of the anticoagulation/antiplatelet therapy is feasible. In patients with a high thrombosis and bleeding risk anticoagulation should be bridged with unfractionated heparin [renal insufficiency] or low molecular weight heparin. In the latter risk situation, inhibition of platelet function can be achieved with short-lasting GPIIb-IIIa inhibitors [Eptifibatide, Tirofiban]. Prior to intervention patients treated with the new oral anticoagulants [Dabigatran; Rivaroxaban; Apixaban] are requested to temporary interrupt the anticoagulation depending on the individual drug half-life and their renal function. Bridging therapy with heparin prior to intervention is not necessary with the new oral anticoagulants.
Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281
So, Charlotte H; Eckman, Mark H
The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.
Nerli, R B; Reddy, M N; Devaraju, S; Hiremath, M B
Percutaneous nephrolithotomy (PCNL) is an integral component in the management of large volume renal stone disease either as monotherapy or in combination with shock wave lithotripsy. Stone disease in patients on chronic anticoagulation/antiplatelet therapy, however, poses a difficult scenario. Bleeding is a major concern for any patient undergoing PCNL. We retrospectively analyzed our series of patients with renal calculi who were on chronic anticoagulant therapy and who underwent PCNL. We reviewed the case records of patients undergoing PCNL during the period from January 2005 to December 2011. We analyzed the changes in preoperative and postoperative hemoglobin, serum creatinine, and clotting parameters, as well as intraoperative and postoperative bleeding and thromboembolic complications. During the 5-year study period, a total of 36 patients (30 males and 6 females) with a mean age of 46.33±9.96 years (range, 29-61 years) who were on chronic anticoagulant/antiplatelet therapy underwent PCNL for urolithiasis. The mean size of the stone was 6.40±1.98 cm(2) (range, 2.8-9 cm(2)). The mean operating time was 62.08±10.10 min. The bleeding was successfully managed in all patients and the anticoagulant/antiplatelet agents were restarted after an appropriate duration. The mean rise in serum creatinine at discharge was 0.05±0.03 mg/dl and the mean fall in serum hemoglobin was 1.63±0.77 g/dl. At 3 months after surgery, the stone-free rate was 100%. With careful preoperative care and regulation of anticoagulation/antiplatelet therapy and appropriate intraoperative management, PCNL can be performed safely and successfully in properly selected patients with renal calculi who are on chronic anticoagulant/antiplatelet therapy.
González Bárcenas, Martha L; Pérez Aisa, Ángeles
The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs) impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.
Saour, J N; Ali, H A; Mammo, L A; Sieck, J O
Over a 10-year period a uniform management plan for patients receiving long term oral anticoagulation therapy for prosthetic heart valves and needing dental procedures was instituted. Those undergoing dental extraction or gum hygiene in the presence of gross gum pathology (Group A) had their oral anticoagulation discontinued two days prior to the procedure which was carried out only if the INR was 1.5 or less on the day of the procedure. Patients who needed dental fillings or gum hygiene in the absence of gross gum pathology (Group B) continued their anticoagulation therapy and had these procedures completed provided the INR was 3.0 or less. The main outcome measured were valve thrombosis, thromboembolism and excessive bleeding requiring hospitalization and/or blood transfusion. In Group A, 240 procedures were carried out; 212 dental extractions and 28 dental hygiene in the presence of gross gum pathology. They had a brief period of under-anticoagulation (3-7 days) to an INR of 1.5 or less. In Group B, 156 procedures were performed. No patient developed valve thrombosis or thromboembolism. Two patients, both in Group A needed hospitalization for observation but no blood transfusion. This management plan was easy to implement. Patients needed one extra visit to the anticoagulation clinic within one week of the procedure. It was both safe and effective.
Grzybowski, Andrzej; Kupidura-Majewski, Konrad; Kupidura, Paulina
The number of elderly patients using anticoagulant and antiplatelet treatment in prevention of thromboembolism has significantly increased in recent years. It was believed for many years that those patients may be at higher risk for hemorhages during ocular surgery. Different strategies were proposed to prevent these complications, including discontinuation of anticoagulants, dose reduction, or substitution with low molecular weight heparin. The objective of this work was to evaluate the results of studies presenting the results of vitreoretinal surgeries in patients continuing antiplatelet and/or anticoagulant treatment. We performed a PubMed search of possible intraoperative and postoperative hemorrhages in patients receiving anticoagulant and/or antiplatelet therapy during vitreoretinal surgery in 2007-2014. In most of the studies reviewed there was no substantial increase in intraoperative and postoperative hemorrhages risks during vitreoretinal surgery. However, in some studies, a substantially increased risk has been identified. We conclude that the available data is insufficient to decide whether to continue or discontinue anticoagulant and/or antiplatelet therapy during vitreoretinal surgery and we recommend an individualized approach in consultation with the patient's medical doctors and anesthesiologists.
Beitelshees, Amber L; Voora, Deepak; Lewis, Joshua P
In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin) and anticoagulation (ie, warfarin) medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran) agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and anticoagulation therapy. However, several factors may limit its usefulness and should be considered. PMID:25897256
Spyropoulos, Alex C
The management of patients who need temporary interruption of chronic oral anticoagulant (OAC) therapy for an elective surgical or invasive procedure is problematic and complex. Patient and procedural risk factors for thrombosis and bleeding, anticoagulant-related risks of bleeding, and clinical consequences of a thrombotic or bleeding event need to be assessed and properly risk-stratified in the perioperative period. Certain procedures, such as dental, endoscopic, and cutaneous procedures, can be completed without discontinuing OAC, but most procedures with a high bleeding risk (including major surgeries) will necessitate temporary discontinuation of OAC. Bridging therapy with shorter-acting anticoagulants, such as heparin, for patients at intermediate to high risk of thromboembolism represents one strategy to maintain functional anticoagulation during this period. Large, prospective cohort studies and registries of patients on chronic OAC who underwent bridging therapy mostly with low-molecular-weight heparin have been completed recently. This paper reviews these clinical data on bridging therapy and provides an evidence-based perioperative management strategy for the at-risk patient on chronic OAC.
Gunasekaran, Kulothungan; Rudd, Kelly M.; Murthi, Swetha; Kaatz, Scott; Lone, Nazir
Even though highly vascularized, the thyroid gland rarely has spontaneous bleeding. Bleeding into the thyroid gland can result in potentially lethal acute airway compromise. This case report describes an elderly patient on warfarin for atrial fibrillation, who presented with swelling on the right side of her neck causing acute airway obstruction. An urgent computed tomography of the neck showed an enlarging hemorrhage into the right lobe of the thyroid gland. She was initially intubated for airway protection and her anticoagulation was reversed to stop the bleeding. She was closely monitored in the intensive care unit. After an uncomplicated tracheal extubation and recovery, she was discharged and scheduled for an elective total thyroidectomy. We desire that physicians be aware of this rare, potentially lethal bleeding complication. PMID:28243434
Saheb Sharif-Askari, Fatemeh; Syed Sulaiman, Syed Azhar; Saheb Sharif-Askari, Narjes
Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding. Treatment of patients with CKD should be based on evidence from randomized clinical trials, but usually CKD patients are excluded from these trials. In the past, unfractionated heparins were the anticoagulant of choice for patients with CKD because of its independence of kidney elimination. However, currently low-molecular-weight heparins have largely replaced the use of unfractionated heparins owing to fewer incidences of heparin-induced thrombocytopenia and bleeding. We undertook this review in order to explain the practical considerations for the management of anticoagulation in these high risk population.
Mierzynski, Radzisław; Poniedzialek-Czajkowska, Elzbieta; Kimber-Trojnar, Zaneta; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan
Pregnancy is a specific state of heightened coagulability related to the increase in procoagulant agents and to the reduced fibrinolysis. Pregnancy is associated with a 4-fold increased risk of developing venous thromboembolism (VTE) and this risk still increases to 14-fold during puerperium. A correlation between the metabolic syndrome and development of cardiovascular events and cerebrovascular incidents has been described. Such a relationship is referred to a hypercoagulable state due to increased serum levels of the plasminogen activator inhibitor-1 (PAI-1), fibrinogen, factor (F) VII and VIII, von Willebrand factor and from endothelial activation, caused by increased circulating adhesion molecules. As to the risk of VTE, the probability for its association with cardiovascular incidents is increased by common underlying mechanisms such as the activation of platelets and the blood coagulation. A correlation between idiopathic VTE and the metabolic syndrome has been reported. The anticoagulant therapy may be recommended during the pregnancy for the treatment or the prophylaxis of VTE and, in women with artificial heart valves, for the prevention of the valve thrombosis and systemic embolisation. There are also specific conditions during pregnancy which benefit from anticoagulant use, such as recurrent fetal loss, thrombophilia and assisted reproductive technology. There are no published specific data about using of anticoagulant agents in pregnant patients with the metabolic syndrome except for a few articles addressing reproductive problems. The mechanisms of anticoagulant action were studied with the focus on heparinoids, because of their safety not only for the patient but also for the fetus. The new oral anticoagulants were also shortly described although they have been contraindicated during the pregnancy.
Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.
Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323
Pandya, Ekta Y; Bajorek, Beata
The role of the direct oral anticoagulants (DOACs) in practice has been given extensive consideration recently, albeit largely from the clinician's perspective. However, the effectiveness and safety of using anticoagulants is highly dependent on the patient's ability to manage and take these complex, high-risk medicines. This structured narrative review explores the published literature to identify the factors underpinning patients' non-adherence to anticoagulants in atrial fibrillation (AF), and subsequently contemplates to what extent the DOACs might overcome the known challenges with traditional warfarin therapy. This review comprised a two-tier search of various databases and search platforms (CINAHL, Cochrane, Current Contents Connect, EMBASE, MEDLINE Ovid, EBSCO, PubMed, Google, Google Scholar) to yield 47 articles reporting patients perspectives on, and patients adherence to, anticoagulant therapy. The findings from the literature were synthesised under five interacting dimensions of adherence: therapy-related factors, patient-related factors, condition-related factors, social-economic factors and health system factors. Factors negatively affecting patients' day-to-day lives (especially regular therapeutic drug monitoring, dose adjustments, dietary considerations) predominantly underpin a patient's reluctance to take warfarin therapy, leading to non-adherence. Other patient-related factors underpinning non-adherence include patients' perceptions and knowledge about the purpose of anticoagulation; understanding of the risks and benefits of therapy; socioeconomic status; and expectations of care from health professionals. In considering these findings, it is apparent that the DOACs may overcome some of the barriers to traditional warfarin therapy at least to an extent, particularly the need for regular monitoring, frequent dose adjustment and dietary considerations. However, their high cost, twice-daily dosing and gastrointestinal adverse effects may present
Park, Hyun Oh; Moon, Seong Ho; Kim, Jong Woo; Byun, Joung Hun; Kim, Sung Hwan; Yang, Jun Ho; Lee, Chung-Eun; Kim, Jong-Duk
Hypercoagulable states have been associated with aortic thrombosis. Antiphospholipid syndrome (APS) is one of the commonest types of acquired thrombophilia. We report the case of successful anticoagulation management in an APS patient with mobile thrombi within the aorta. A 58-year-old male patient presented to the emergency department (ED) with right-sided hemiparesis. His first symptoms were noted approximately 12–16 hours before presentation to the ED. Magnetic resonance imaging of the brain showed acute embolic infarction of the left frontal and parietotemporal lobes. Transesophageal echocardiography (TEE) and computed tomography angiography (CTA) demonstrated mobile thrombi attached to the wall of the ascending aorta and aortic arch. The patient was diagnosed with APS based on positivity of anti-beta-2 glycoprotein 1 antibodies, and was initiated on anticoagulation therapy. Repeated TEE and CTA revealed complete resolution of the thrombi after 12 days of treatment; the patient was discharged well. PMID:28042559
Park, Hyun Oh; Moon, Seong Ho; Kim, Jong Woo; Byun, Joung Hun; Kim, Sung Hwan; Yang, Jun Ho; Lee, Chung-Eun; Kim, Jong-Duk
Hypercoagulable states have been associated with aortic thrombosis. Antiphospholipid syndrome (APS) is one of the commonest types of acquired thrombophilia. We report the case of successful anticoagulation management in an APS patient with mobile thrombi within the aorta. A 58-year-old male patient presented to the emergency department (ED) with right-sided hemiparesis. His first symptoms were noted approximately 12-16 hours before presentation to the ED. Magnetic resonance imaging of the brain showed acute embolic infarction of the left frontal and parietotemporal lobes. Transesophageal echocardiography (TEE) and computed tomography angiography (CTA) demonstrated mobile thrombi attached to the wall of the ascending aorta and aortic arch. The patient was diagnosed with APS based on positivity of anti-beta-2 glycoprotein 1 antibodies, and was initiated on anticoagulation therapy. Repeated TEE and CTA revealed complete resolution of the thrombi after 12 days of treatment; the patient was discharged well.
Romero Ruiz, Adolfo; Parrado Borrego, Gema; Rodríguez González, José; Caparrós Miranda, Isabel S; Vargas Lirio, M Isabel; Ortiz Fernández, Primitiva
There is currently around one million people receiving oral anticoagulants in Spain. The drug most used is acenocoumarol, which requires coagulation monitoring to ensure that the patient is within its normal therapeutic range. Patients usually start this treatment in a hospital clinic and, when they are stabilised, they are referred to primary care, where they are followed-up by their community nurses. The usual practice is that nurses are responsible for changes in the dose when the patients are outside the range. This practice is not performed by hospital nurses, despite having sufficient experience and knowledge to adequately manage these types of patients. An Advanced Nursing Practice model has been introduced into the Haematology management unit of the Hospital Universitario Virgen de la Victoria, Málaga. This involves various aspects of attention and care of patients on anticoagulant therapy, and includes adjusting the doses of their treatment following a catalogue of therapeutic and diagnostic ranges.
Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J; Rosano, Giuseppe
The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.
Mischke, Karl; Knackstedt, Christian; Marx, Nikolaus
Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation. PMID:22577538
Cantin, Ariane; Lahaie, Alexandre; Odobasic, Bojan; Tremblay, Marie-Philip; Wazzan, Dana; Caron, Stéphanie; Leblanc, Caroline; Martineau, Josée; Lalonde, Lyne
Background: The ACO Program (Programme ACO), a continuous quality improvement program (CQIP) in anticoagulation therapy, was offered in community pharmacies as a pilot project. Objective: To evaluate the participants’ appreciation for the various activities of the program. Methods: Participants had access to training activities, including an audit with feedback, online training activities (OTA), clinical tools and support from facilitators. Cognitive behavioural learning determinants were evaluated before and 5 months after the beginning of the program. Participants’ satisfaction and perception were documented via online questionnaires and a semistructured interview. Results: Of the 52 pharmacists in the ACO Program, 47 participated in this evaluation. Seventy-seven percent of the participants completed at least 1 OTA and 6% published on the forum. The feeling of personal effectiveness rose from 8.01 (7.67-8.35) to 8.62 (8.24-8.99). The audit and feedback, as well as the high-quality OTA and their lecturers, were the most appreciated elements. Discussion: There was a high OTA participation rate. The facilitators seemed to play a key role in the CQIP. The low level of participation in the forum reflects the known phenomenon of social loafing. Technical difficulties affecting the platform and data collection for the audit with feedback constituted limitations. Conclusion: The CQIP in anticoagulation therapy is appreciated by community pharmacists and is associated with an improved feeling of personal effectiveness. PMID:27829859
Krasny, Marta; Krasny, Kornel; Fiedor, Piotr
Cardiovascular conditions, apart from neoplastic diseases, remain the major cause of death in developed countries; therefore, the number of patients receiving oral anticoagulants is constantly increasing. Anticoagulant therapy considerably reduced mortality in patients with history of myocardial infarction among others. Although many interventions may be performed without withdrawal of the anticoagulant and tooth extraction was qualified as a procedure of low hemorrhage risk, a majority of dentists refer the patient to a cardiologist several days before the elective tooth extraction to withdraw anticoagulants. The aim of the study was to evaluate the efficacy and safety of bone wax used to stop bleeding after dental procedures in a group of patients on chronic anticoagulant therapy and find an answer to a question, whether it is justified to temporarily withdraw anticoagulants for this type of procedures. The study involved 176 patients on chronic anticoagulant therapy undergoing tooth extraction (154 subjects) or surgical extraction of a retained tooth (48 subjects). After the procedure, in each case the alveolus was filled with bone wax to stop bleeding. In all patients involved in the study bleeding from the alveolus was successfully stopped during the procedure. None of the subjects reported increased bleeding from the operational site after coming back home. Bone wax is a good, efficient, and safe material to block bleeding from the alveolus following tooth extractions, also in patients on chronic anticoagulant therapy. The study demonstrated that withdrawal or adjustment of anticoagulant therapy is not necessary before an elective tooth extraction.
Lopes, Antonio Augusto
In pulmonary hypertension (PH), thrombosis and thromboembolism may occur as primary events associated with inherited or acquired thrombophilia. Alternatively, in situ thrombosis may develop as a complication of pre-existing vasculopathy as in the case of idiopathic PH and related disorders (so called pulmonary arterial hypertension). In these disorders, a number of abnormalities has been described involving endothelial cells, platelets and other circulating cellular and soluble elements. These abnormalities are suggestive of a shift of pulmonary vascular microenvironment toward a procoagulant, prothrombotic and antifibrinolytic pattern. The abnormalities described so far include circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P-selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and cytokines. Also, decreased endothelial production of natural anticoagulants (thrombomodulin) and platelet antiaggregating substances (nitric oxide, prostacyclin) have been demonstrated. The present review is focused on the procoagulant, prothrombotic and antifibrinolytic mechanisms so far identified in PH, in both clinical setting and animal models. Understanding of these mechanisms is crucial for a proper selection of anticoagulant and antithrombotic therapies and provides the rationale for development of novel therapeutic options.
Thean, D; Alberghini, M
Several new oral anticoagulants have been studied in the past decade, and have now started to enter the market. These drugs are reported to be as effective as, or more effective than, warfarin. In Australia, the Therapeutic Goods Administration has approved dabigatran, rivaroxaban and apixaban. The use of these newer anticoagulants is likely to increase in time, and it is important for dentists to have a sound understanding of the mechanisms of action, reversal strategies, and management guidelines for patients taking oral anticoagulants. This article discusses the process of coagulation, available anticoagulants and their monitoring and reversal, and provides clinical advice on the management of patients on anticoagulants who require dental treatment.
Zullo, Angelo; Hassan, Cesare; Radaelli, Franco
Periprocedural management of antithrombotics for gastrointestinal endoscopy is a common clinical issue, given the widespread use of these drugs for primary and secondary cardiovascular prevention. For diagnostic procedures, with or without biopsy, no adjustments in antithrombotics are usually needed. For operative procedures, balancing the risk of periprocedural hemorrhage with the continuation of antithrombotics against the chance of recurrent thromboembolic events with their discontinuation may be challenging. Oral anticoagulants need to be temporarily withheld, and consideration must be given to whether a periendoscopic “bridge” therapy, typically a low-molecular-weight heparin, should be used in order to minimize the risk of thromboembolic events. Although some emerging evidence has shown that patients receiving heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to controls, bridging therapy is still recommended for patients on vitamin K antagonists who are at high thrombotic risk. Conversely, bridging therapy is usually not needed for patients taking new oral agents, which are characterized by shorter half-lives, and a rapid offset and onset of action. Management of antiplatelet therapy requires special care in patients on secondary prevention, especially those with coronary stents. This review is intended to summarize the recommendations of updated International Guidelines designed to help the decision-making process in such an intricate field. PMID:28042233
Isola, G; Matarese, G; Cordasco, G; Rotondo, F; Crupi, A; Ramaglia, L
Patients treated with oral anticoagulant therapy (OAT) represent an issue to the dentist, as an increasing number of people are using anticoagulant drugs for cardiovascular disease. The choice of an eventual suspension or continuation of anticoagulant therapy is important when considering an efficient management of the patient. Patients in anticoagulant therapy and requiring dental procedures sometimes represent therapeutic concerns especially concerning the suspension of the anticoagulant treatment. At the moment there is no consensus among international experts of a possible discontinuation of therapy before invasive dental procedures. In this paper, the authors try to focus on this topic through a critical review of the literature. Most of the studies suggest the continuation of the anticoagulant treatment with heparin before invasive oral surgical interventions. Based on the data of the literature, two rules must be adopted in clinical practice: 1) maintenance of anticoagulation related to the international normalized ratio (INR); 2) local application of antifibrinolytic agents to ensure a proper hemostatic process. Given the widespread use of anticoagulant drugs in cardiovascular disease, dentists must often face the problem of the therapy and, since there is no consensus on the management of these patients, the authors propose, after a thorough critical review of the literature, the implementation of a multiphase protocol of surgical approach to be implemented with safety in daily clinical practice.
Lippert, S; Gutschik, E
By administering a questionnaire to 253 patients with cardiac-valve prostheses (89.3% responding), and another to 136 of their attending dentists (79% responding), the level of knowledge among both groups of anticoagulant therapy in connection with dental treatment was investigated. The cardiothoracic department monitored all anticoagulation therapies. Of the anticoagulated patients, 96.6% were able to state their medication (94.1% received phenprocoumon); and of 86 dentists with patients on anticoagulation treatment, 94% were aware of their patients' medication. All 20 dentists stating that their patients did not receive anticoagulants were correct. The great majority (98%) of the dentists employed a special measure to reduce the risk of bleeding associated with invasive dental procedures, most commonly (86%) referring patients to their general practitioner or hospital department for adjustment of the anticoagulant therapy. Around 60% of the dentists considered extractions and operations to require measures to reduce the risk of bleeding complications. We recommend referral of patients to the attending physician for adjustment of anticoagulation to a target International Normalized Ratio (INR) of 4.0 or possibly 3.0 before undergoing dental procedures involving the risk of bleeding. Additional reduction of the bleeding risk can be obtained by local application of an inhibitor of fibrinolysis (tranexamic acid).
Zektser, Miri; Bartal, Carmi; Zeller, Lior; Nevzorov, Roman; Jotkowitz, Alan; Stavi, Vered; Romanyuk, Vitaly; Chudakov, Gregory; Barski, Leonid
Objective The optimal treatment of deep vein thrombosis (DVT) is anticoagulation therapy. Inferior vena cava filter (IVC) placement is another option for the prevention of pulmonary embolism (PE) in patients with deep vein thrombosis. This is used mostly in patients with a contraindication to anticoagulant therapy. The purpose of the present study was to compare the two options. Methods A retrospective cohort study of two groups of patients with DVT: patients who received an IVC filter and did not receive anticoagulation due to contraindications; and patients with DVT and similar burden of comorbidity treated with anticoagulation without IVC insertion. To adjust for a potential misbalance in baseline characteristics between the two groups, we performed matching for age, gender, and Charlson’s index, which is used to compute the burden of comorbid conditions. The primary outcome was an occurrence of a PE. Results We studied 1,742 patients hospitalized with the diagnosis of DVT in our hospital;93 patients from this population received IVC filters. Charlson’s score index was significantly higher in the IVC filter group compared with the anticoagulation group. After matching of the groups of patients according to Charlson’s score index there were no significant differences in primary outcomes. Conclusion Inferior vena cava filter without anticoagulation may be an alternative option for prevention of PE in patients with contraindications to anticoagulant therapy. PMID:27487310
Briongos Figuero, Sem; García Santos-Gallego, Carlos; Badimón, Juan José
For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.
Taherkhani, Maryam; Taherkhani, Adineh; Hashemi, Seyed Reza; Faghihi Langroodi, Taraneh; Sadeghi, Roxana; Beyranvand, Mohammadreza
Abstract Background: The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism (PTE) remains controversial. We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE. Methods: We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but without arterial hypotension or shock. The patients were randomly assigned in a single-blind fashion to receive an anticoagulant [Enoxaparin (1 mg/kg twice a day)] plus a thrombolytic [Alteplase (100 mg) or Streptokinase (1500000 u/2 hours)] or an anticoagulant [Enoxaparin (1 mg/kg twice a day)] alone. The primary endpoint was in-hospital death or clinical deterioration requiring an escalation of treatment. The secondary endpoints of the study were major bleeding, pulmonary hypertension, right ventricular dilatation at the end of the first week, and exertional dyspnea at the end of the first month. Results: Of 50 patients enrolled, 25 patients were randomly assigned to receive an anticoagulant plus a thrombolytic and the other 25 patients were given an anticoagulant alone. The incidence of the primary endpoints was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.022). At the time of discharge, pulmonary artery pressure was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.018); however, reduction in the right ventricular size or normalization of the right ventricle showed non-significant differences between the two groups. There was no significant difference regarding the New York Heat Association (NYHA) functional class between the two groups at the end of the first month (p value = 0.213). No fatal bleeding or cerebral bleeding
Kovac, Mirjana; Mikovic, Zeljko; Mitic, Gorana; Djordjevic, Valentina; Mandic, Vesna; Rakicevic, Ljiljana; Radojkovic, Dragica
The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions.
Lai, Wei; Lu, Shi-Chun; Li, Guan-Yin; Li, Chuan-Yun; Wu, Ju-Shan; Guo, Qing-Liang; Wang, Meng-Long; Li, Ning
AIM: To compare the incidence of early portal or splenic vein thrombosis (PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization. METHODS: We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010. Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation, respectively. Group A (153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin (LMWH) irregularly. Group B (148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery, followed by oral warfarin and aspirin for one month regularly. The target prothrombin time/international normalized ratio (PT/INR) was 1.25-1.50. Platelet and PT/INR were monitored. Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy. RESULTS: The patients’ data were collected and analyzed retrospectively. Among the patients, 94 developed early postoperative mural PSVT, including 63 patients in group A (63/153, 41.17%) and 31 patients in group B (31/148, 20.94%). There were 50 (32.67%) patients in group A and 27 (18.24%) in group B with mural PSVT in the main trunk of portal vein. After the administration of thrombolytic, anticoagulant and anti-aggregation therapy, complete or partial thrombus dissolution achieved in 50 (79.37%) in group A and 26 (83.87%) in group B. CONCLUSION: Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization, and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy. Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT. PMID:22807615
Ullrich, Helen; Gori, Tommaso
Triple anticoagulant therapy is necessary in patients who are at increased risk for both arterial (in stent) and venous thrombosis, or have atrial fibrillation. Triple therapy however also poses a very high risk for bleeding events, particularly because this subset of patients is particularly frail due to the high incidence of comorbidities and advanced age. Very little randomized studies have tested the impact of the many possible combinations of anticoagulant/antiaggregant drugs, and surveys among practicing physicians show that the use of off-label therapies is very common. In a recent survey from our group, we observed that physicians are very divided in terms of what therapy should be recommended to patients with indication to anticoagulation and with a history of stenting. The use of novel anticoagulants was as frequent as that of vitamin K antagonists, and the duration of triple therapy was very variable.While these data probably show that decisions are usually taken on an individual basis, considering the patient's risk of ischemia and hemorrhagic events, much of this variability probably depends on the fact that, failing randomized trials, guidelines in this area are relatively less specific than in other ones.
Doonquah, Ladi; Mitchell, Anika D
Minor oral surgical procedures make up a significant part of the daily practice of dentistry. With the increased sophistication of medical technology and medications there is increased likelihood of performing surgery on patients who are being treated for conditions that require some type of anticoagulant therapy. These patients are at an increased risk for perioperative bleeding or thrombotic complications if anticoagulation is discontinued or the dosage is adjusted. Therefore, a fine balance needs to be obtained and adequate preparation of these patients is the key to establishing this balance. This article reviews suggested approaches to the management of such patients.
Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we review atherothrombotic disease, venous thrombotic disease, and atrial fibrillation in patients with inherited bleeding disorders, and discuss strategies for using anticoagulants in this population using cases to illustrate these considerations. PMID:27106121
Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.
Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an “unacceptable health risk” during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010
Moia, Marco; Mantovani, Lorenzo Giovanni; Carpenedo, Monica; Scalone, Luciana; Monzini, Mara Silvia; Cesana, Giancarlo; Mannucci, Pier Mannuccio
New anticoagulant drugs alternative to vitamin K antagonists are currently under clinical evaluation. Patient's preferences should be considered in the development of new therapeutic strategies. Our study aim was to elicit patient preferences, and estimate their willingness to pay for the different treatment options. A Discrete Choice Experiment was administered to patients consecutively attending an anticoagulation clinic, either on stable oral anticoagulant therapy, or during their first visit at the time of starting therapy. Six treatment characteristics were analysed: route and number of medication administrations, frequency of monitoring, risk of some minor bleeding, the amount of attention required for drug/food interactions, requirement for dose adjustment, and out-of-pocket treatment cost. Relationships between patient's preferences and their characteristics were analysed. 255 patients participated (55 % men, with a mean age 64 years; 35.7 % on stable therapy). A statistically significant importance was attributed to all but two characteristics (the amount of attention required for interaction with other drugs/food and for dose adjustment.) Monthly patient willingness to pay was
Farge, Dominique; Trujillo-Santos, Javier; Debourdeau, Philippe; Bura-Riviere, Alessandra; Rodriguez-Beltrán, Eva Maria; Nieto, Jose Antonio; Peris, Maria Luisa; Zeltser, David; Mazzolai, Lucia; Hij, Adrian; Monreal, Manuel
Abstract In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ± 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8–6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3–7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2–12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy. PMID:26266353
Truong, Teresa; Armor, Becky L
Warfarin is considered a high-risk drug because of its narrow therapeutic window, variability in dose response, and multitude of drug and food interactions. Although travel advice is available for patients who are taking warfarin, it is geared toward patients who are traveling to developed countries and tends to be lacking in detail. We describe a 53-year-old woman with two mechanical heart valves and chronic atrial fibrillation who was taking warfarin for thromboembolism prophylaxis and had plans to travel to Vietnam for 10 weeks. Three days before her departure, she was prescribed amiodarone for long-term use. As a result of the extended duration of her travel and the complexities of warfarin use, the pharmacists who managed the patient's anticoagulation reviewed several aspects of a comprehensive management approach with the patient for a safe international trip. They assessed the patient's thromboembolic and hemorrhagic risks, and determined which other drugs (e.g., enoxaparin, phytonadione), dosages, and adequate supplies would be required along with warfarin, as well as how to safely transport these drugs during travel. In addition, the logistics of effectively monitoring international normalized ratio (INR) levels were evaluated, and methods of managing multiple potential scenarios were carefully planned out. Contact with the patient was made through pharmacist-directed telephone visits throughout the travel period. A total of 12 telephone visits were conducted with the patient during the 10 weeks of travel. Her INR was supratherapeutic on three occasions and was subtherapeutic once; however, neither enoxaparin nor phytonadione were needed during the travel period, and the patient returned safely to the United States. Effective and safe use of high-risk drugs for patients leaving the United States requires extensive pretravel planning, and pharmacists can play a central role in optimizing therapeutic outcomes for these patients during international travel.
Pacemaker lead malpositioning may lead to severe clinical adverse events. Rarely, cases of inadvertent placement of a lead into the left ventricle are reported in the literature. We herein report a case of pacemaker lead malpositioning into the left ventricle via a persistent foramen ovale in a male caucasian patient. After this procedural adverse event, the patient suffered from two ischemic strokes despite antiplatelet and anticoagulation therapy. PMID:24650169
Singh, Prabhat; Kalita, J.; Misra, U.K.
Background & objectives: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. Methods: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. Results: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. Of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. Interpretation & conclusions: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR. PMID:27377498
Collins, R.; MacMahon, S.; Flather, M.; Baigent, C.; Remvig, L.; Mortensen, S.; Appleby, P.; Godwin, J.; Yusuf, S.; Peto, R.
OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer
DU, JUN-DONG; ZHENG, XI; HUANG, ZHI-QIANG; CAI, SHOU-WANG; TAN, JING-WANG; LI, ZHAN-LIANG; YAO, YONG-MING; JIAO, HUA-BO; YIN, HUI-NAN; ZHU, ZI-MAN
The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments. PMID:24944612
Divchev, D; Nienaber, C; Ince, H
There is ongoing development of new therapeutic regimens in the use of antithrombotic agents and anticoagulants focussing on acute coronary syndrome (ACS) with an increasing impact on current guidelines over the last years. This was especially accompanied by an increase in innovative percutaneous coronary interventional (PCI) methods in patients with ACS, non-ST-segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) with a need for therapeutics with more sufficient and effective antiplatelet action. On the other hand, newer direct and indirect thrombin inhibitors with primary use in prevention and therapy of thromboembolic events have been shown to have beneficial and even superior effects in ACS with or without PCI. The current review aims to report on the evidence-based use of approved antithrombotic agents and anticoagulants in ACS with special focus on PCI according to the actualized European guidelines.
Atrial fibrillation (AF) is associated with an increased incidence and severity of strokes. The burden of AF-related stroke is expected to increase in parallel with the aging of the population. Oral anticoagulation with warfarin has been the pharmacologic standard for stroke risk reduction in patients with AF. When used with close attention to dosing and monitoring, warfarin is effective prophylactic therapy against thromboembolic stroke. However, it is underused by physicians, in part because of the known risks of adverse events with warfarin. Consequently, many patients with AF live with an avoidably elevated risk of stroke. New options, ie, oral anticoagulants with novel mechanisms of action, have recently been approved to reduce the risk of stroke in AF, and others are in development. These newer agents may address some of the complexities of warfarin use while providing similar or better efficacy and safety.
Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel
Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483
Armstrong, Melissa J; Schneck, Michael J; Biller, José
Growing evidence suggests that perioperative withdrawal of ASA for secondary stroke prevention increases thromboembolic risk without the associated benefit of decreased bleeding complications. ASA maintenance is acceptable in many procedures, including invasive ones. Many procedures, in particular ophthalmologic, dermatologic, and dental surgeries, also are safe while continuing oral AC. Warfarin has been continued successfully even in some surgeries that have high bleeding risk. When the risk is too high, temporary bridging therapy with LWMH is safe in many populations. Although the exact thromboembolic risks associated with temporary cessation of AP and AC are unknown and likely low, morbidity and mortality associated with thromboembolism are high. Further studies investigating the risks and benefits of maintaining AP and AC during procedures, particularly invasive ones, are needed. Meanwhile, it is critical that physicians understand the risks and benefits of perioperative AP and AC and the variety of procedures in which these agents can be safely continued.
Degirmenci, S-E; Steib, A
Peri-operative management of the risks of hemorrhage and thrombosis related to gastrointestinal surgery tailored to patient characteristics are part of daily multidisciplinary practice tasks. The goal of this update is to discuss current practices concerning antithrombosis prophylaxis and the management of recently developed anticoagulants and antiplatelet agents. The duration of prophylaxis is 1 month for oncological surgery. The recommended doses in bariatric surgery are twice daily injections of low-molecular weight heparin without exceeding a total dose of 10,000 IU/day. Dual antiplatelet therapy is necessary for 6 weeks after placement of bare-metal stents, from 6-12 months for drug-eluting stents, and 12 months after an acute coronary artery syndrome. Abrupt discontinuation of antiplatelet therapy exposes the patient to an increased risk of thrombosis. Data are insufficient to make specific recommendations for antiplatelet therapy in gastrointestinal surgery. For major digestive surgery, prescription of daily aspirin should be discussed case by case. If discontinuation of treatment is absolutely necessary, this should be as short as possible (aspirin: 3 days, ticagrelor and clopidogrel: 5 days, prasugrel: 7 days). The modalities for elective management of new oral anticoagulants are similar to those for classical vitamin K antagonists (VKA) therapy, except that any overlapping with heparin administration must be avoided. In the emergency setting, an algorithm can be proposed depending on the drug, the available coagulation tests and the interval before performing surgery.
Heparin is the most commonly prescribed anticoagulant for continuous renal replacement therapy. There is, however, increasing evidence questioning its safety, particularly in the critically ill. Heparin mainly confers its anticoagulant effect by binding to antithrombin. Heparin binds to numerous other proteins and cells as well, however, compromising its efficacy and safety. Owing to antithrombin consumption and degradation, and to the binding of heparin to acute phase proteins, and to apoptotic and necrotic cells, critical illness confers heparin resistance. The nonspecific binding of heparin further leads to an unpredictable interference with inflammation pathways, microcirculation and phagocytotic clearance of dead cells, with possible deleterious consequences for patients with sepsis and systemic inflammation. Regional anticoagulation with citrate does not increase the patient's risk of bleeding. The benefits of citrate further include a longer or similar circuit life, and possibly better patient and kidney survival. This needs to be confirmed in larger randomized controlled multicenter trials. The use of citrate might be associated with less inflammation and has useful bio-energetic implications. Citrate can, however, with inadequate use cause metabolic derangements. Full advantages of citrate can only be realized if its risks are well controlled. These observations suggest a greater role for citrate. PMID:21345279
Ishikawa, Shinya; Kasai, Yoshitaka; Matsuura, Natsumi; Tarumi, Shintaro; Nakano, Jun; Okuda, Masaya; Goto, Masashi; Ryu, Dagu; Go, Tetsuhiko; Yokomise, Hiroyasu
In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes.
Virdee, Mandeep S; Stewart, Derek
Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA2DS2-VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA2DS2-VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA2DS2-VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA2DS2-VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re
Davis, Estella M; Packard, Kathleen A; Knezevich, Jon T; Campbell, Jennifer A
Abstract Thrombosis is an underlying cause of many cardiovascular disorders, and generation of thrombi in the arterial circulation can lead to unstable angina, myocardial infarction, or ischemic stroke. Antithrombotic therapy is widely used, with proven benefit to prevent ischemic stroke and thromboembolic events in patients with atrial fibrillation (AF) or to prevent further ischemic complications in patients with acute coronary syndrome (ACS). Traditional anticoagulants (including unfractionated heparin, low-molecular-weight heparin, and warfarin) and antiplatelet agents (including aspirin, clopidogrel, and prasugrel) are typically used for these indications. Limitations to their use include variable pharmacokinetic and pharmacodynamic profiles, inability to inhibit fibrin-bound thrombin, risk of heparin-induced thrombocytopenia, delayed onset of action, numerous drug interactions, need for substantial laboratory monitoring and dosage titrations, hyporesponsiveness or resistance, hypersensitivity, adverse events, and bleeding. To overcome some of the limitations of traditional agents, new antithrombotic agents under development are highly selective for specific coagulation factors blocking the synthesis of thrombin. Clinicians must have an understanding of the new anticoagulants to aid in the selection of appropriate therapies for patients. We describe the most relevant phases II and III clinical trials that evaluated several recent emerging anticoagulant drugs for use in patients with AF or ACS. The advantages of many new agents include predictable pharmaco-dynamic response and pharmacokinetic parameters, allowing for fixed oral dosing with no need for laboratory monitoring. For patients with AF, dabigatran is already approved for the prevention of stroke and systemic embolism, rivaroxaban appears to be an effective alternative to warfarin in high-risk patients, and apixaban may also be an effective alternative to aspirin in patients unable to take warfarin
Mutlu, Ilknur; Mutlu, Mehmet Firat; Biri, Aydan; Bulut, Berk; Erdem, Mehmet; Erdem, Ahmet
This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes.
Angiolillo, Dominick J; Ferreiro, José Luis
Coronary atherothrombotic disease, including chronic stable angina and acute coronary syndromes (ACS), is associated with significant global burden. The acute clinical manifestations of atherothrombotic disease are mediated by occlusive arterial thrombi that impair tissue perfusion and are composed of a core of aggregated platelets, generated by platelet activation, and a superimposed fibrin mesh produced by the coagulation cascade. Long-term antithrombotic therapies, namely oral antiplatelet agents and anticoagulants, have demonstrated variable clinical effects. Aspirin and P2Y12 adenosine diphosphate (ADP) receptor antagonists have been shown to reduce the risk for thrombosis and ischaemic events by blocking the thromboxane (Tx) A2 and platelet P2Y12 activation pathways, respectively, whereas the benefits of oral anticoagulants have not been consistently documented. However, even in the presence of aspirin and a P2Y12 receptor antagonist, the risk for ischaemic events remains substantial because platelet activation continues via pathways independent of TxA2 and ADP, most notably the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin. Emerging antithrombotic therapies include those targeting the platelet, such as the new P2Y12 antagonists and a novel class of oral PAR-1 antagonists, and those inhibiting the coagulation cascade, such as the new direct factor Xa antagonists, the direct thrombin inhibitors, and a novel class of factor IX inhibitors. The role of emerging antiplatelet agents and anticoagulants in the long-term management of patients with atherothrombotic disease will be determined by the balance of efficacy and safety in large ongoing clinical trials.
Kobalava, Zh D; Villewalde, S V; Troitskaya, E A
Suboptimal medication adherence to anticoagulation therapy is a widespread problem and is associated with increases in risk of thromboembolic or haemorrhagic events. Standard therapy with warfarin is associated with suboptimal adherence due to narrow therapeutic window, frequent side effects and need for INR control. Much shorter half-life of NOACs raises the question of optimal dosing regimen. Higher efficacy and safety of twice-daily dosing regimen of NOACs is based on the results of pharmacokinetic models, data from phase 2 and phase 3 trials and metanalysis of 4 phase 3 trials. Twice-daily dosing regimen of apixaban reflects the priority of clinical outcomes. AVERROES, ARISTOTLE and AMPLIFY trials provide strong evidence of efficacy and safety of twice-daily dosing regimen of apixaban. First results of AEGEAN-trial have shown high adherence and persistence to apixaban.
Objectives The first non-vitamin K antagonist oral anticoagulant (NOAC) introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH) occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH. Methods We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014. Results ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years). Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset. Conclusion Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg) and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy. PMID:26171862
Cromme, L; Völler, H; Gäbler, F; Salzwedel, A; Taborski, U
Oral anticoagulation using vitamin K antagonists has been established for over 50 years. Although it is highly effective in preventing thromboembolic incidents, its therapeutic control still remains problematic. Therefore, a computer-aided approach is recommended for deriving dosages. Up to now, the dosage is often based on the visual inspection of previous INR measurements, average weekly doses, and the INR target range. Statistical variations of measurement results and time-delayed effects of dosages, however, frequently result in the misinterpretation of data and suggest pseudo-trends. Treating physicians are not only responsible for determining the patient-specific maintenance dose, but must also respond to deviating INR values, overdosage or underdosage, initiate the oral anticoagulation therapy, and control the INR level in case of a new target range (bridging). Instructive examples are provided to illustrate the described difficulties. A computer-aided expert system is currently developed to ensure the therapeutic safety under the specified conditions. We present preliminary results from a study designed to validate mathematical models underlying such expert systems.
Introduction Today, we frequently find patients taking oral anticoagulant therapy (OAT), a prophylaxis against the occurrence of thromboembolic events. An oral surgeon needs to know how to better manage such patients, in order to avoid hemorrhagic and thromboembolic complications. Materials and methods A group of 193 patients (119 men aged between 46 and 82 and 74 women aged between 54 and 76) undergoing OAT for more than 5 years were managed with a standardized management protocol and a 2-months follow-up. The aim of the present study was to apply a protocol, which could provide a safe intra- and postoperative management of patients on OAT. Results Among the 193 patients, only 2 had postoperative complications. Conclusions We think that the protocol used in the present study can be used for complete safety in the treatment of this type of patients. PMID:21771331
Kabłak-Ziembicka, Anna; Bryniarski, Krzysztof; Wrotniak, Leszek; Ostrowska-Kaim, Elżbieta; Żmudka, Krzysztof; Przewłocki, Tadeusz
Introduction Triple anticoagulation therapy (TT), comprising dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC), is essential in atrial fibrillation (AF) patients after percutaneous coronary intervention (PCI), but it increases the bleeding risk. Aim To assess TT models, in- and out-hospital bleeding and thromboembolic complications, and TT alterations. Material and methods During 12 months, consecutive AF post-PCI patients were scheduled for TT. Alterations in TT and thromboembolic events (death, myocardial infarction, ischemic stroke, in-stent thrombosis, peripheral embolization) were recorded. Major, non-major and minor bleeding episodes were assessed. Results One hundred and thirty-six out of 3171 patients, aged 73.0 ±8.4 years (90 male), were included. Intra-hospitally, thrombotic events occurred in 9 (6.6%), while bleeding events occurred in 71 (52.2%) patients. Access-site hematoma and blood transfusions during in-hospital stay predisposed physicians to heparin administration as part of TT on discharge (p = 0.018 and p = 0.033 respectively). Eventually, DAPT plus warfarin or plus novel oral anticoagulant (NOAC) or plus low molecular weight heparin was prescribed in 72 (52.9%), 53 (39%), and 11 (8.1%) patients, respectively. HAS-BLED and CHA2DS2-VASc scores were similar between subgroups (p = 0.63 and p = 0.64 respectively). During 10.2 ±4.2 months of follow-up, 11 (8.1%) deaths, and 9 (6.6%) non-fatal thromboembolic events occurred. Bleeding events occurred in 45 (34.6%) patients, including 14 (10.3%) major. TT was the only factor associated with increased risk of major bleeding (18.6% vs. 4.2%, p = 0.008). Early termination of any TT component, which concerned 59 (45.4%) patients, did not increase the risk of thromboembolic events (p = 0.89). Conclusions Our study indicates that TT is associated with high mortality and bleeding rates in a relatively short period of time. Discontinuation of any TT drug did not increase the thromboembolic event
Cafolla, A; Melizzi, R; Baldacci, E; Pignoloni, P; Dragoni, F; Campanelli, M; Caraccini, R; Foà, R
The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.
Although anticoagulation therapy is the primary treatment for deep vein thrombosis (DVT), it has not been associated with the rapid recanalization of the venous occlusion. Moreover, it is associated with long-term disability due to post-thrombotic syndrome (PTS). In contrast, pharmacomechanical endovascular intervention (PMI) results in more rapid clinical improvement in DVT patients, but there are few reports on its long-term outcomes. This retrospective study evaluated the clinical effectiveness of PMI compared to conventional anticoagulation therapy (ACA) for acute and subacute iliofemoral DVT. We reviewed the medical records of 102 patients with iliofemoral DVT. A total of 46 patients for ACA and 56 patients for PMI were enrolled. We analyzed the clinical differences between the PMI and ACA groups by comparing the clinical signs, residual DVT free-rate, and PTS-free rate. There were no statistically significant differences in the demographic characteristics and risk factors except age between the groups (age: ACA, 52.0 ± 18.0 years; PMI, 59.0 ± 17.0 years; P = 0.035). The 1-, 3-, and 5-year residual DVT-free rate (ACA = 84.7%, 71.6%, and 46.0%; PMI = 82.1%, 76.8%, and 76.8%, respectively; P = 0.235) was not significantly different. However, the 1-, 3-, and 5-year PTS-free rate was significantly different (ACA = 93.5%, 74.0%, and 55.7%; PMI = 92.9%, 90.0%, and 90.0%, respectively; P = 0.019). There was no significant difference in the rate of other complications. PMI showed a lower incidence of PTS during the follow-up period. Therefore, PMI should be considered as an effective therapeutic modality for patients with iliofemoral DVT. PMID:27914131
Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L.
Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receiving AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.
Eckman, Mark H
Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful.
Harris, Leanne F.; Rainey, Paul; Castro-López, Vanessa; O'Donnell, James S.; Killard, Anthony J.
Millions of patients worldwide are receiving anticoagulant therapy to treat hypercoagulable diseases. While standard testing is still performed in the central laboratory, point-of-care (POC) diagnostics are being developed due to the increasing number of patients requiring long-term anticoagulation and with a need for more personalized and targeted therapy. Many POC devices on the market focus on clot measurement, a technique which is limited in terms of variability, highlighting the need for more reliable assays of anticoagulant status. The anti-Xa assay, a factor specific optical assay, was developed to measure the extent to which exogenous factor Xa (FXa) is inhibited by heparinantithrombin complexes. We have developed a novel microfluidic device and assay for monitoring the effect of heparin anticoagulant therapy at the point-of-care. The assay which was also developed in our institute is based on the anti-Xa assay principle but uses fluorescence as the method of detection. Our device is a disposable laminate microfluidic strip, fabricated from the cyclic polyolefin (COP), Zeonor®, which is extremely suitable for application to fluorescent device platforms. We present data on the execution of the anti-Xa assay in this microfluidic format, demonstrating that the assay can be used to measure heparin in human plasma samples from 0 to 0.8 U/ml, with average assay reproducibility of 8% and a rapid result obtained within 60 seconds. Results indicate that with further development, the fluorogenic anti-Xa assay and device could become a successful method for monitoring anticoagulant therapy.
Behranwala, K A; Tisdall, M; Habib, N H; Canelo, R
We report on a case of bilateral subcapsular hematoma of the liver, occurring during treatment with warfarin. A 64-year-old woman was put on long-term warfarin therapy. After a bout of severe right hypochondriac pain, computed tomography (CT) scan showed subcapsular hematoma of the liver. Subsequent CT scan, conservative policy only, showed regression of the hematoma. The patient was discharged from the hospital on the 23rd day. We conclude that a nonruptured spontaneous liver hematoma should not be surgically removed. A conservative management with close observation is the mainstay therapy. A switch from warfarin therapy to another anticoagulation therapy is strongly suggested.
Altman, R; Rouvier, J; Gurfinkel, E; D'Ortencio, O; Manzanel, R; de La Fuente, L; Favaloro, R G
After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications. Final evaluation included 51 and 48 patients, respectively. The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient). The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment. We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves.
Bosch, Luis Ángel Bermúdez
Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often unpredictable inter-individual dosing variations that effectively reach and maintain adequate anticoagulation. Several researchers have developed pharmacogenetic-guided maintenance dose algorithms that incorporate genetics and individual patient characteristics. However, there is limited information available concerning dosing during warfarin initiation. This is considered the most clinically challenging therapeutic phase. In such, the risk of recurrent thromboembolism and hemorrhage are elevated. The objective of this retrospective study is to predict the individual initial doses for Puerto Rican patients (n=175) commencing anticoagulation therapy at Veterans Affairs Caribbean Healthcare System (VACHS) using pharmacogenetic/pharmacokinetic-driven model. A pharmacogenetic driven model (R2=0.4809) was developed in Puerto Rican patients and combined with pharmacokinetic formulas that enabled us to predict the individual initial doses for patients (n=121) commencing anticoagulation therapy. WinNonlin® pharmacokinetic-pharmacodynamic simulations were carried out to determine the predictability of this model. This model demonstrated promising results with few (n=10) simulations outside of their respective therapy range. A customized pharmacogenetic-based warfarin maintenance dose algorithm (R2=0.7659) was developed in a derivation cohort of 131 patients. The predictability of this developed pharmacogenetic algorithm was compared with the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm and it demonstrated superior predictability within our study population. PMID:25285240
Bingham, Angela L; Brown, Rex O; Dickerson, Roland N
We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.
Kawabata, Mihoko; Sasaki, Takeshi; Maeda, Shingo; Shirai, Yasuhiro; Yamauchi, Yasuteru; Nitta, Junichi; Goya, Masahiko; Hirao, Kenzo
Direct oral anticoagulants (DOACs) have been shown to be safe and effective for the prevention of stroke in nonvalvular atrial fibrillation (NVAF) patients, however, experience with peri-AF ablation management of DOACs is scarce. This study aimed to investigate the safety and feasibility of periprocedural anticoagulation therapy with rivaroxaban in Japanese patients undergoing paroxysmal non-valvular AF (NVAF) ablation using radiofrequency energy.This study was a multicenter, prospective pilot study. In paroxysmal NVAF patients, rivaroxaban (15 mg or 10 mg once-daily) was started at least 4 weeks prior to AF ablation, discontinued on the day of the procedure, resumed within 24 hours after ablation, and continued at least 3 months afterwards. During the interruption of rivaroxaban, bridging anticoagulation therapy with unfractionated heparin was given. Follow-up of the patients continued for 3 months.A total of consecutive 74 patients (mean age, 62 ± 9 years, 58 [78.4%] male) were enrolled. The mean follow-up period was 108 ± 79 days. Their mean CHADS2 score and CHA2DS2-VASc score were 1.2 ± 1.0 and 0.6 ± 0.7, respectively. Their mean HAS-BLED score was 1.0 ± 0.8. Neither major bleeding nor thromboembolic events, except in a case with bleeding from gastric cancer (1.4%), were observed in the periprocedural period of the AF ablation.The present multicenter study demonstrated the safety and feasibility of periprocedural anticoagulation therapy with rivaroxaban in Japanese patients undergoing catheter ablation of paroxysmal NVAF.
Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant
Glueck, Charles J.; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping
Background: When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. Case Presentation: A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. Conclusion: When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation. PMID:27536705
Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines.
Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc
The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation);For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation).For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥ 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 - 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation).
Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines
Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc
The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation). For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin The advice for warfarin is fundamentally unchanged from British Society of Gastroenterology (BSG) 2008 guidance. Direct Oral Anticoagulants (DOAC) For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation); For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥48 h before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30–50 mL/min we recommend that the last dose of DOAC be taken 72 h before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID:26873868
Background Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices. Methods Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages. Results The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT. Conclusions Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum
CORRIGENDUM to Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant
Owing to errors made by the authors, Charles J. Glueck, Kevin Lee, Marloe Prince, Vybhav Jetty, Parth Shah, and Ping Wang, the following article contains errors. Glueck CJ, Lee K, Prince M, et al. Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant. J Investig Med High Impact Case Rep. 2016;4(3):1-6. doi: 10.1177/2324709616661833 PMID:28321420
Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Matsusaka, Satoshi; Ozaka, Masato; Ogura, Mariko; Chin, Keisho; Yamaguchi, Toshiharu
Background Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev). We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings. Methods Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E), thrombus >40 mm in diameter (S), thrombus involving the superior vena cava (C), and decreased blood flow (V). Results Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9%) by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%). Of these 56 patients, 11 (19.6%) received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%), as well as V in two (18.2%), S + V + C in one (9.1%), E + S + V in one (9.1%), E + C in one (9.1%), E in one (9.1%), and C in one (9.1%). All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%). Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%), but there were no treatment-related severe adverse events or deaths. Severe thromboembolism was not observed in the other 68 patients. Conclusion Our anticoagulant protocol for asymptomatic thrombosis detected by Doppler ultrasound imaging was effective at preventing severe
Mazzaccara, Cristina; Conti, Valeria; Liguori, Rosario; Simeon, Vittorio; Toriello, Mario; Severini, Angelo; Perricone, Corrado; Meccariello, Alfonso; Meccariello, Pasquale; Vitale, Dino Franco; Filippelli, Amelia; Sacchetti, Lucia
Background and Aim Warfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non genetic factors on warfarin dosage in a South Italian population in the attempt to setup an algorithm easily applicable in the clinical practice. Materials and Methods A total of 266 patients from Southern Italy affected by cardiovascular diseases were enrolled and their clinical and anamnestic data recorded. All patients were genotyped for CYP2C9*2,*3, CYP4F2*3, VKORC1 -1639 G>A by the TaqMan assay and for variants VKORC1 1173 C>T and VKORC1 3730 G>A by denaturing high performance liquid chromatography and direct sequencing. The effect of genetic and not genetic factors on warfarin dose variability was tested by multiple linear regression analysis, and an algorithm based on our data was established and then validated by the Jackknife procedure. Results Warfarin dose variability was influenced, in decreasing order, by VKORC1-1639 G>A (29.7%), CYP2C9*3 (11.8%), age (8.5%), CYP2C9*2 (3.5%), gender (2.0%) and lastly CYP4F2*3 (1.7%); VKORC1 1173 C>T and VKORC1 3730 G>A exerted a slight effect (<1% each). Taken together, these factors accounted for 58.4% of the warfarin dose variability in our population. Data obtained with our algorithm significantly correlated with those predicted by the two online algorithms: Warfarin dosing and Pharmgkb (p<0.001; R2 = 0.805 and p<0.001; R2 = 0.773, respectively). Conclusions Our algorithm, which is based on six polymorphisms, age and gender, is user-friendly and its application in clinical practice could improve the personalized management of patients undergoing warfarin therapy. PMID:23990957
Cho, Yong-Wook; Kim, Euiseong
Nowadays, oral anticoagulants are commonly prescribed to numerous patients for preventing cardiovascular accident such as thromboembolism. An important side effect of anticoagulant is anti-hemostasis. In a major surgery, the oral anticoagulant therapy (OAT) regimen must be changed before the surgery for proper post-operative bleeding control. However, in a minor dental surgery and endodontic surgery, the necessity for changing or discontinuing the OAT is open to debate. In this study, risks of the consequences were weighed and analyzed. In patients who stop the OAT, the occurrence of thromboembolic complication is rare but the result is fatal. In patients who continuing the OAT, post-operative bleeding can be controlled well with the local hemostatic measures. In the endodontic surgery, there are almost no studies about this issue. The intra-operative bleeding control is particularly important in the endodontic surgery because of its delicate and sensitive procedures such as inspection of resected root surface using dental microscope and retrograde filling. Further studies are necessary about this issue in the viewpoint of endodontic surgery.
Nowadays, oral anticoagulants are commonly prescribed to numerous patients for preventing cardiovascular accident such as thromboembolism. An important side effect of anticoagulant is anti-hemostasis. In a major surgery, the oral anticoagulant therapy (OAT) regimen must be changed before the surgery for proper post-operative bleeding control. However, in a minor dental surgery and endodontic surgery, the necessity for changing or discontinuing the OAT is open to debate. In this study, risks of the consequences were weighed and analyzed. In patients who stop the OAT, the occurrence of thromboembolic complication is rare but the result is fatal. In patients who continuing the OAT, post-operative bleeding can be controlled well with the local hemostatic measures. In the endodontic surgery, there are almost no studies about this issue. The intra-operative bleeding control is particularly important in the endodontic surgery because of its delicate and sensitive procedures such as inspection of resected root surface using dental microscope and retrograde filling. Further studies are necessary about this issue in the viewpoint of endodontic surgery. PMID:24010076
Jurcuţ, Ruxandra; Militaru, Sebastian; Geavlete, Oliviana; Drăgotoiu, Nic; Sipoş, Sergiu; Roşulescu, Răzvan; Ginghină, Carmen; Jurcuţ, Ciprian
Background Patient adherence is an essential factor in obtaining efficient oral anticoagulation using vitamin K antagonists (VKAs), a situation with a narrow therapeutic window. Therefore, patient education and awareness are crucial for good management. Auditing the current situation would help to identify the magnitude of the problem and to build tailored education programs for these patients. Methods This study included 68 hospitalized chronically anticoagulated patients (mean age 62.6±13.1 years; males, 46%) who responded to a 26-item questionnaire to assess their knowledge on VKA therapy management. Laboratory and clinical data were used to determine the international normalized ratio (INR) at admission, as well as to calculate CHA2DS2-VASC and HAS-BLED scores for patients with atrial fibrillation. Results The majority of patients (62%) were receiving VKA for atrial fibrillation, the others for a mechanical prosthesis and previous thromboembolic disease or stroke. In the atrial fibrillation group, the mean CHA2DS2-VASC score was 3.1±1.5, while the average HAS-BLED score was 1.8±1.2. More than half of the patients (53%) had an INR outside of the therapeutic range at admission, with the majority (43%) having a low INR. A correct INR value was predicted by education level (higher education) and the diagnostic indication (patients with mechanical prosthesis being best managed). Patients presenting with a therapeutic INR had a trend toward longer treatment duration than those outside the therapeutic range (62±72 months versus 36±35 months, respectively, P=0.06). There was no correlation between INR at admission and the patient’s living conditions, INR monitoring frequency, and bleeding history. Conclusion In a tertiary cardiology center, more than half of patients receiving VKAs are admitted with an INR falling outside the therapeutic range, irrespective of the bleeding or embolic risk. Patients with a mechanical prosthesis and complex antithrombotic regimens
Ghaly, Ramsis F.; Lissounov, Alexei; Candido, Kenneth D.; Knezevic, Nebojsa Nick
Background: Spinal cord stimulators (SCSs) are gaining increasing indications and utility in an expanding variety of clinical conditions. Complications and initial expenses have historically prevented the early use of SCS therapy despite ongoing efforts to educate and promote its utilization. At present, there exists no literature evidence of SCS implantation in a chronically anticoagulated patient, and neuromodulation manufacturers are conspicuously silent in providing warnings or recommendations in the face of anticoagulant use chronically. It would appear as through these issues demand scrutiny and industry as well as neuromodulation society advocacy and support in terms of the provision of coherent guidelines on how to proceed. Case Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Conclusion: Our literature search did not reveal any
Kruse-Loesler, Birgit; Kelker, Matthias; Kleinheinz, Johannes
Background Dental surgery can be carried out on patients under oral anticoagulation therapy by using haemostyptic measures. The aim of the study was a comparative analysis of coagulation by laboratory methods and immediate patient diagnosis on the day of the planned procedure. Methods On the planned day of treatment, diagnoses were carried out on 298 patients for Prothrombin Time (PT), the International Normalised Ratio (INR), and Partial Thromboplastin Time (PTT). The decision to proceed with treatment was made with an INR < 4.0 according to laboratory results. Results Planned treatment did not go ahead in 2.7% of cases. Postoperatively, 14.8% resulted in secondary bleeding, but were able to be treated as out-patients. 1.7% had to be treated as in-patients. The average error between the immediate diagnosis and the laboratory method: 95% confidence interval was -5.8 ± 15.2% for PT, -2.7 ± 17.9 s for PTT and 0.23 ± 0.80 for INR. The limits for concordance were 9.4 and -21.1% for PT, 15.2 and -20.5 s for PTT, and 1.03 and -0.57 for INR. Conclusion This study showed a clinically acceptable concordance between laboratory and immediate diagnosis for INR. Concordance for PT and PTT did not meet clinical requirements. For patients under oral anticoagulation therapy, patient INR diagnosis enabled optimisation of the treatment procedure when planning dental surgery. PMID:16316464
Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.
Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235
Larsen, Torben Bjerregaard; Skjøth, Flemming; Grove, Erik Lerkevang; Nielsen, Peter Brønnum; Christensen, Thomas Decker
Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42-0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44-2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21-0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00-1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency.
Min, Jiangyong; Farooq, Muhammad Umar
Nonvalvular Atrial fibrillation (NVAF) is the most common cardiac arrhythmia associated with an increase in risk of stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home. The present review will focus on the current status of detecting NVAF and stroke prevention when there is AF. The CHA2DS2-VASc risk stratification scheme is discussed for the identification of patients who are at risk for thromboembolic stroke related to NVAF. Patient with a CHA2DS2-VASc score of 2 or greater are candidates for warfarin or a novel oral anticoagulant, irrespective of whether the strategy is for rate or rhythm control. Finally, guidelines and landmark clinical trials in NVAF patients with primary or secondary stroke prevention are discussed.
Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Çağrı; Kalaycıoğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalçık, Macit; Yaman, Mehmet; İnci, Sinan; Altıntaş, Bernas; Kalkan, Sedat; Kırma, Cevat; Biteker, Murat
The definition of non-valvular atrial fibrillation (NVAF) is controversial. We aimed to assess the impact of valvular heart disease on stroke prevention strategies in NVAF patients. The RAMSES study was a multicenter and cross-sectional study conducted on NVAF patients (ClinicalTrials.gov identifier NCT02344901). The study population was divided into patients with significant valvular disease (SVD) and non-significant valvular disease (NSVD), whether they had at least one moderate valvular disease or not. Patients with a mechanical prosthetic valve and mitral stenosis were excluded. Baseline characteristics and oral anticoagulant (OAC) therapies were compared. In 5987 patients with NVAF, there were 3929 (66%) NSVD and 2058 (34%) SVD patients. The predominant valvular disease was mitral regurgitation (58.1%), followed by aortic regurgitation (24.1%) and aortic stenosis (17.8%). Patients with SVD had higher CHA2DS2VASc [3.0 (2.0; 4.0) vs. 4.0 (2.0; 5.0), p < 0.001] and HAS-BLED [2.0 (1.0; 2.0) vs. 2.0 (1.0; 2.0), p = 0.004] scores compared to patients with NSVD. Overall, 2763 (71.2%) of NSVD and 1515 (73.8%) of SVD patients were on OAC therapy (p = 0.035). When the patients with SVD were analyzed separately, the mean CHA2DS2VASc and HAS-BLED scores were higher in patients with mitral regurgitation compared to patients with aortic regurgitation and aortic stenosis [4.0 (3.0; 5.0), 3.0 (2.0; 4.0), 3.0 (2.0; 4.0) p < 0.001 and 2.0 (1.0; 3.0), 1.0 (1.0; 2.0), 1.0 (0.0; 2.0) p < 0.001, respectively]. In patients with SVD, 65.7% of mitral regurgitation, 82.6% of aortic regurgitation and 88.0% of aortic stenosis patients were on OAC therapy. One out of three NVAF patients had at least one moderate valvular heart disease with the predominance of mitral regurgitation. Patients with SVD were at greater risk of stroke and bleeding compared to patients with NSVD. Although patients with mitral regurgitation should be given more aggressive anticoagulant therapy
Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie
Background Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers’ perceptions of what patients should know, rather than on patients’ preferences. Objective To investigate patients’ viewpoints on educational needs and preferred modalities of information delivery. Methods We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Results Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30–2.46). Pharmacists (1.69, 1.58–1.80), nurses (1.05, 0.95–1.16), and patient associations (0.36, 0.29–0.44), along with group sessions (0.85, 0.75–0.95), the internet (0.77, 0.67–0.88), and delivery of material at the patient’s home (1.26, 1.14–1.38), were ranked poorly in terms of delivering educational material. Conclusion This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their
Tompson, Alice; Heneghan, Carl; Fitzmaurice, David; Sutton, Stephen; Harrison, Sian; Ward, Alison
Background Clinical trials suggest that oral anticoagulation therapy (OAT) self-monitoring is safe and effective, however little is known about the patient experience of this process. There is a lack of understanding about how best to train and support patients embarking on OAT self-monitoring. Aim To collect in-depth information about patients’ experiences of OAT self-monitoring outside of clinical trial conditions and to produce a set of recommendations on how best to support such patients. Design and setting Semi-structured qualitative interviews with patients who self-monitor and live in England. Method In total, 26 of the 267 (9.7%) who participated in the Cohort study of Anticoagulation Self-Monitoring (CASM) and were still self-monitoring after 12 months’ follow-up were interviewed. Topics discussed included experiences of OAT self-monitoring, healthcare support, training, and decision making. Framework analysis was used. Results Following initial problems using the monitoring device, interviewees described a mostly positive experience. Although less effort was expended attending monitoring appointments with health professionals, effort was required to conduct self-monitoring tests and to interpret and act on the results. Desire to self-manage was variable, especially when dosing advice systems worked promptly and reliably. Interviewees overcame patchy healthcare system knowledge and support of self-monitoring by educating themselves. Family and friends provided support with learning to use the monitor and managing OAT dosage adjustments. Conclusion Better, more-consistent training and health-service support would have alleviated a number of problems encountered by these patients who were self-monitoring. This training and support will become even more important if self-monitoring becomes more accessible to the general population of people on OAT. PMID:26077266
Funk, Dorothy M Adcock
Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.
Watt, Barbara E; Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister
Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to
Park, Kyung-Hyun; Cheon, Sang-Ho; Lee, Ji-Ho
Purpose This study evaluated the incidence of a venous thromboembolism (VTE) after total knee arthroplasty (TKA) using multidetector row computed tomography-indirect venography (MDCT-indirect venography) and assessed the efficacy of anti-coagulation therapy. Materials and Methods We enrolled 118 patients with 126 cases of TKA. The average age of the patients was 68.4 years. We used 64 channel MDCT-indirect venography for the detection of VTE. We treated selectively proximal deep vein thrombosis (DVT) or pulmonary thromboembolism (PTE) cases according to the results of MDCT-indirect venography. We re-evaluated the change in VTE using follow-up MDCT-indirect venography after 3 months. Results We identified VTE in 35.7%. DVT only was identified in 22.2% including 8 cases of proximal DVT and 20 cases of distal DVT. PTE without DVT was identified in 4.8%, and combined DVT and PTE in 8.7%. All patients with PTE were asymptomatic, but 4 DVT patients had signs of leg swelling. After anti-coagulation therapy, 20 patients showed complete resolution in 16 cases, improvement in 3 cases and one case showed a new distal DVT. Conclusions The incidence of VTE after primary TKA was 35.7% in Korea. Furthermore, anti-coagulation therapy for proximal DVT and PTE patients may be a useful method for preventing the occurrence of a fatal PTE. PMID:22570848
Lagi, Alfonso; Spini, Simona; Meucci, Elisa; Cartei, Alessandro; Cencetti, Simone
Background The aim of this study was to investigate the incidence of digestive hemorrhages in patients with non-valvular atrial fibrillation (NVAF), scheduled for oral anticoagulant therapy. Methods We conducted, over 24 months, a prospective, randomized, population-based observational study on consecutive patients with recurrent paroxysmal, persistent, or permanent NVAF, scheduled for oral anticoagulant therapy. The study initially included 268 patients with NVAF (162 males and 106 females) with a mean age of 74 years (range 42-86 years). Patients were split into two groups: those undergoing preventive Esophago-Gastro-Duodenoscopy (EGD) (Group A) and those who did not (Group B). All patients positive by EGD underwent medical treatment and subsequent 30-day endoscopic controls showed complete healing. The primary outcome of the study was to determine if previous EGD in patients with NVAF resulted in a low risk of bleeding during oral anticoagulant therapy. The two groups were comparable for most variables. Results Significant differences were found between groups for the incidence of antiarrhythmic drugs and for early hemorrhage (P <0.001). The incidences of early hemorrhages were significantly different between the two groups with 12 in group B (12%) and 2 in group A (1.7%). Conclusions Preventive EGD can identify hidden digestive diseases, which may increase the incidence of early hemorrhages.
Casajuana, Josep; Iglesias, Begoña; Fàbregas, Mireia; Fina, Francesc; Vallès, Joan-Antoni; Aragonès, Rosa; Benítez, Mència; Zabaleta, Edurne
Background Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003–2004 season. Interventions: intramuscular administration of influenza vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). Conclusion This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. Registration number NCT00137579 at clinicaltrials.gov PMID:18507871
Beyer-Westendorf, Jan; Förster, Kati; Ebertz, Franziska; Gelbricht, Vera; Schreier, Thomas; Göbelt, Maria; Michalski, Franziska; Endig, Heike; Sahin, Kurtulus; Tittl, Luise; Weiss, Norbert
Aims Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation (SPAF) but little is known about the rates of or reasons for rivaroxaban discontinuations in daily care. Using data from a prospective, non-interventional oral anticoagulation (NOAC) registry, we analysed rivaroxaban treatment persistence. Methods and results Persistence with rivaroxaban in SPAF was assessed in an ongoing, prospective, non-interventional registry of >2600 NOAC patients from daily care using the Kaplan–Meier time-to-first-event analysis. Reasons for and management of rivaroxaban discontinuation were assessed. Potential baseline risk factors for treatment discontinuation were evaluated using Cox regression analysis. Between October 2011 and April 2014, 1204 rivaroxaban SPAF patients were enrolled [39.3% switched from vitamin K antagonists (VKAs) and 60.7% newly treated patients]. Of these, 223 patients (18.5%) stopped rivaroxaban during follow-up (median 544 days), which translates into a discontinuation rate of 13.6 (95% CI 11.8–15.4) per 100 patient-years. Most common reasons for treatment discontinuations were bleeding complications (30% of all discontinuations), followed by other side-effects (24.2%) and diagnosis of stable sinus rhythm (9.9%). A history of chronic heart failure (HR 1.43; 95% CI 1.09–1.87; P = 0.009) or diabetes (HR 1.39; 95% CI 1.06–1.82; P = 0.018) were the only statistically significant baseline risk factors for rivaroxaban discontinuation. After discontinuation of rivaroxaban, patients received antiplatelet therapy (31.8%), VKA (24.2%), another NOAC (18.4%), heparin (9.9%), or nothing (15.7%). Conclusion Our data indicate that overall persistence with rivaroxaban therapy is high, with a discontinuation rate of ∼15% in the first year of treatment and few additional discontinuations thereafter. PMID:25694537
A major concern in the management of patients under anticoagulants is the potential for excessive bleeding after dental procedures. Recommendations for the administration of oral anticoagulants in conjunction with oral surgery range from complete withdrawal of anticoagulants to the maintenance of an unchanged therapy. Rising evidences show that the alteration of anticoagulation is not necessary for patients with INR of 4 or less previous to tooth extractions. Topical antifibrinolytics as tranexamic acid control successfully alveolar bleeding. It is time to stop interrupting anticoagulant therapy for oral surgery. A theoretical risk of hemorrhage after dental surgery in patients at therapeutic levels of anticoagulation exists but it is minimal and is greatly overweighed by the risk of thromboembolism after alteration of the anticoagulant therapy.
Executive Summary Subject of the Evidence-Based Analysis The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT). Clinical Need: Target Population and Condition Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population. Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0. The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis. Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a
Staudacher, Dawid L.; Kaiser, Michael; Hehrlein, Christoph; Bode, Christoph; Ahrens, Ingo
Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple therapy. This combined anticoagulation is applied in patients undergoing coronary artery stent implantation while also having an indication for OAC. Triple therapy increases the risk for bleeding events compared to either DAPT or OAC alone and thereby might be associated with adverse outcomes. Clinical data on the frequency of bleeding events in patients on triple therapy from clinical trials derives from pre-selected patients and may differ from the real world patients. We report data on patient characteristics and bleeding incidence of patients dismissed on triple therapy from a single university hospital. Within the time span from January 2000 to December 2012, we identified a total of 213 patients undergoing PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86% of all patients treated). The usage of triple therapy significantly increased over the observed time period. The average CHA2DS2-VASc Score was 3.1 ± 1.1 with an average HAS-BLED score of 2.5 ± 0.86 representing a high-risk group for thromboembolic events as well as considerable risk for bleeding events. An on-treatment bleeding incidence of 9.4% was detected, with gastrointestinal and airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is consistent with data from clinical trials and confirms the high risk of bleeding in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had an indication for OAC other than non-valvular atrial fibrillation. This substantial patient group is underrepresented by clinical trials and needs further attention. PMID:26439131
Shi, Quan; Xu, Juan; Zhang, Tong; Zhang, Bin; Liu, Hongchen
Background and Objective: Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. Methods: PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. Results: Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722–4.532, P = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825–5.531, P = 0.118) and 2.003 (95% CI: 0.987–4.063, P = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430–5.980, P = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838–5.118, P = 0.000). Conclusion: Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT
Shi, Quan; Xu, Juan; Zhang, Tong; Zhang, Bin; Liu, Hongchen
Background and Objective: Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. Methods: PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. Results: Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722-4.532, P = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825-5.531, P = 0.118) and 2.003 (95% CI: 0.987-4.063, P = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430-5.980, P = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838-5.118, P = 0.000). Conclusion: Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT patients
Macdonald, Denis; Bhalla, Pearl; Cass, William; Gollish, Jeff; Brighton, Roger; Gorenstein, Frayda; Vitunjski, Joseph; Ng, Peggy
Objective Evaluation of the safety and potential cost savings of a computerized, laboratory-based program to manage inpatient warfarin thromboprophylaxis after major joint arthroplasty. Design A consecutive-case study of adults. Setting A tertiary care orthopedic institution. Patients Patients requiring joint arthroplasty who had no recent episodes of thromboembolic disease, no mechanical heart valve, atrial fibrillation, severe liver disease or baseline international normalized ratio [INR] greater than 1.3 admitted over a 54-month period (July 1994–December 1998). All patients received a standard regimen of warfarin beginning on the evening after the operation. Four hundred and thirty randomly selected patients managed by the program were followed up by telephone survey 3 months after discharge. Patients exhibiting erratic responses to warfarin were withdrawn from the program and managed individually thereafter. Intervention Major joint arthroplasty with warfarin therapy administered through the computerized program. Main outcome measures Test results maintained within the desired therapeutic range (INR 2.0–3.0), clinically severe bleeding episodes, readmission rates, clinically symptomatic and venographically proven episodes of venous thrombosis or pulmonary embolism. Results Over the study period 5629 patients underwent joint arthroplasty; 5372 patients were considered for the program; 332 patients were ineligible and were managed individually; 311 entered patients did not complete the program. This left 4729 patients who completed the program. In 2932 (62%) patients test results were maintained in the desired therapeutic range. The major bleeding rate was less than 0.5%, the readmission rate was 3.8%, the deep venous thrombosis rate was 3.7% and the pulmonary embolism rate was 0.2% with no thromboembolic related deaths in the small sample cohort. Conclusions The majority of patients requiring warfarin thromboprophylaxis can be safely and effectively managed
Kumar, Shashi; Danik, Stephan B; Altman, Robert K; Barrett, Conor D; Lip, Gregory Y H; Chatterjee, Saurav; Roubin, Gary S; Natale, Andrea; Danik, Jacqueline S
Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta-analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional
De Vico, Pasquale; Messino, Valentina; Tartaglione, Alessandra; Beccaris, Camilla; Buonomo, Chiara; Talarico, Daniela; Prati, Paolo; Sabato, Alessandro Fabrizio; Colella, Dionisio Fernando
The study's aim was to examine safety and efficiency of citrate anticoagulated continuous renal replacement therapies (CRRT) in cardiac surgery patients with acute kidney injury and associated liver dysfunction. The study was conducted on critical ICU patients, hospitalized after cardiac surgery, who developed renal and liver acute failures due to low-flow syndrome. CRRT in continuous veno-venous hemodiafiltration with regional citrate anticoagulation (RCA) was prescribed to address renal failure and avoid bleeding-risk. Patient Ca(++) was measured to monitor RCA safety, while thromboelastography (TEG) and circuit Ca(++) were used to verify efficacy. CRRT effectiveness was evaluated through creatinine and urea levels, while liver function was monitored through bilirubin, aspartate aminotransferase, glutamic oxaloacetic transaminase (AST GOT) and gamma glutamyl transferase (GT) levels. The study did not require ethical approval. Hepatic and renal failures were confirmed by baseline levels (total bilirubin=3.1 ± 3.37 mg/dL, AST GOT=153 ± 147 U/L and gamma GT=93.3 ± 86 IU/L, creatinine=1.97 ± 0.88 and blood urea nitrogen [BUN] 98.13 ± 71.34) assessed in 15 patients. During treatment, Ca(++) (patient and circuit) remained stable and within range for the whole therapy thanks to low citrate dose (2.8 ± 0.3 mmol/L of blood), while hepatic markers did not show any significant changes the therapy, although treatment with citrate is contraindicated in patients with hepatic failure. RCA quality was confirmed by TEG values, which showed an anticoagulated circuit with no effects on patients. These results involved a high filter lifespan (49.76 ± 22.10 h) and with an effective creatinine and BUN clearance. No episodes of citrate intoxication were reported (total/ionized calcium ratio remained stable and physiologic). RCA during CRRT with dilute solutions proved both effective and safe, even in patients with acute liver failure.
Cakir, Volkan; Gulcu, Aytac; Akay, Emrah; Capar, Ahmet E.; Gencpinar, Tugra; Kucuk, Banu; Karabay, Ozalp; Goktay, A. Yigit
PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical
Benoliel, R; Leviner, E; Katz, J; Tzukert, A
Thirty patients taking anticoagulants received routine dental treatment without altering their prothrombin time values. In a follow-up of 5 years, no serious complications were seen in patients with a prothrombin time value of up to 2.5. A protocol is suggested for dental treatment in these patients.
Liao, Li; Shi, Bingzheng; Chang, Heran; Su, Xiaoxia; Zhang, Lichao; Bi, Chunsheng; Shuai, Yi; Du, Xiaoyan; Deng, Zhihong; Jin, Yan
Systemic infusion of bone marrow-derived mesenchymal stem cells (BMSCs) has become a promising strategy for disease treatment and tissue regeneration. Strategies to enhance the efficiency of BMSC cell therapy are crucial to promote its clinical application. Here, we aimed to improve BMSC cell therapy by inhibiting the BMSC-induced coagulation reaction. Intravenous injection of gradient BMSCs into mice showed that BMSCs were not fully compatible with blood. Large doses of BMSCs induced a series of symptoms of respiratory failure and heart failure. Histological and homeostasis analysis confirmed that large doses of BMSCs induced disseminated intravascular thrombosis, exhaustion of platelets and coagulation factors, and prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Similar to mouse BMSCs, goat and human BMSCs also induced coagulation reactions in vitro and in vivo. The coagulation was induced mostly by tissue factor, the overexpression of which enhanced the procoagulant activity of BMSCs during in vitro culture. Notably, clinical doses of BMSCs in cell therapy also induced mild and reversible coagulation, which increased BMSC lung embolism and clearance. Anticoagulation treatment by heparin (400 U/kg) prevented BMSC-induced coagulation and the acute adverse effects of large-dose BMSCs infusion efficiently. Importantly, heparin treatment led to decreased BMSC lung embolism and enhanced migration and maintenance of BMSCs to target organs in cell therapy. Based on an experimental colitis model, we confirmed that heparin treatment enhanced the effect of BMSC therapy efficiently to reduce mortality, prevent weight loss, suppress inflammation reaction and alleviate tissue injury. In conclusion, BMSCs possess procoagulant activity that could induce disseminated coagulation and thrombosis in recipients. Anticoagulation treatment by heparin is a practical strategy to improve both the safety and therapeutic effect of BMSC therapy. PMID
Eisenstein, Diana Hill
Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers.
Oral anticoagulant therapy for stroke prevention in patients with atrial fibrillation undergoing ablation: results from the First European Snapshot Survey on Procedural Routines for Atrial Fibrillation Ablation (ESS-PRAFA).
Potpara, Tatjana S; Larsen, Torben B; Deharo, Jean Claude; Rossvoll, Ole; Dagres, Nikolaos; Todd, Derick; Pison, Laurent; Proclemer, Alessandro; Purefellner, Helmut; Blomström-Lundqvist, Carina
The European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) is a prospective, multicentre snapshot survey of patients undergoing atrial fibrillation (AF) ablation, conducted to collect patient-based data on current clinical practices in AF ablation in context of the latest AF Guidelines and contemporary oral anticoagulant therapies. The EP Research Network Centres were asked to prospectively enrol consecutive patients during a 6-week period (September/October 2014). Data were collected via the web-based case report form. We present the results pertinent to the use of antithrombotic therapies. Thirteen countries prospectively enrolled 455 eligible consecutive patients [mean age 59 ± 10.8 years, 131 (28.8%) females]. The mean CHA2DS2-VASc score was 1.12 ± 1.06 [137 patients (30.1%) had a score of ≥2]. Before ablation, 443 patients (97.4%) were on anticoagulant therapy [143 (31.4%) on non-vitamin K antagonist oral anticoagulants (NOACs) and 264 (58.0%) on vitamin K antagonists (VKAs)]. Of the latter, 79.7% underwent ablation without VKA interruption, whilst a variety of strategies were used in patients taking NOAC. After ablation, most patients (89.3%) continued the same anticoagulant as before, and 2 (0.4%) were not prescribed any anticoagulation. At discharge, 280 patients (62.2%) were advised oral anticoagulation for a limited period of mean 3.8 ± 2.2 months. On multivariate analysis, CHA2DS2-VASc, AF duration, prior VKA use, and estimated AF ablation success were significantly associated with the decision on short-term anticoagulation. Our results show the increasing use of NOAC in patients undergoing AF ablation and emphasize the need for more information to guide the periprocedural use of both NOACs and VKAs in real-world setting.
Nguyen, Annie Lu; Berg, Jill; Amin, Alpesh; Bachman, Mark; Guo, Yuqing; Evangelista, Lorraine
Background Older adults are at substantial risk for cardiovascular disorders that may require anticoagulation therapy. Those on warfarin therapy report dissatisfaction and reduced quality of life (QOL) resulting from the treatment. Advances in the area of mobile health (mHealth) technology have resulted in the design and development of new patient-centric models for the provision of personalized health care services to improve care delivery. However, there is a paucity of research examining the effectiveness of mHealth tools on knowledge, attitudes, and patient satisfaction with treatment, as well as self-management, adherence to therapy, and QOL in older adults with chronic illness conditions requiring long-term warfarin therapy. Objective The objective of the study was to explore the attitudes and preferences of older adults on warfarin therapy regarding the use of mHealth technology and health games to gain skills for self-management. Methods We conducted group and individual interviews with patients (60 years or older) on warfarin therapy at two anticoagulation clinics affiliated with an academic medical center. We held 4 group and 2 individual interviews, resulting in 11 patient participants and 2 family caregiver participants. We used structured questions on three topic areas including medication self-management strategies, mHealth technology use, and health games for exercise. We demonstrated some commercial health apps related to medication management, vitamin K content of food, and a videogame for balance exercise. Discussions were audiotaped and transcribed verbatim. Common themes were drawn using content analysis. Results The participants reported awareness of the importance of staying on schedule with warfarin therapy. They also acknowledged that negative experiences of friends or family members who were taking warfarin influenced their desire to keep on schedule with warfarin therapy. In addition, the participants expressed that the use of m
Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self-assessment patient survey conducted by the European Heart Rhythm Association.
Hernández Madrid, Antonio; Potpara, Tatjana S; Dagres, Nikolaos; Chen, Jian; Larsen, Torben B; Estner, Heidi; Todd, Derick; Bongiorni, Maria G; Sciaraffia, Elena; Proclemer, Alessandro; Cheggour, Saida; Amara, Walid; Blomstrom-Lundqvist, Carina
The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation.
Ball, J H
An understanding of the primary mechanisms of hemostasis, including the coagulation pathways and the intrinsic, extrinsic, and common systems, is the basis for treating the anticoagulated patient. Two major anticoagulants are used for treating those who may be at risk for thromboembolic crisis. These drugs include Coumadin, which is an oral anticoagulant, and heparin, a parenteral anticoagulant, which is often used for acute thromboembolic episodes or for hospitalization protocols that include significant surgical procedures. The practitioner should be familiar with common dental drugs that can interact with anticoagulants and should consult with the patient's physician before administering any such drugs. By placing the patient into one of three dental treatment categories, appropriate anticoagulation therapy can be rendered to each patient according to his or her needs. Low-risk procedures require no change in anticoagulation medication. For moderate-risk procedures, withdrawal of anticoagulation medication 2 days before the procedure and verified with the PT the day of the procedure is indicated. For high-risk dental procedures, using a heparin protocol should be strongly considered. In all instances of dental treatment, the oral tissues should be treated atraumatically using local hemostatic measures for control of hemorrhage. Treating medically compromised patients who are on a variety of medications is becoming more common in dentistry today. Understanding the underlying disease and the appropriate protocol for treatment of anticoagulated patients reduces the risk of thromboembolism and hemorrhagic complications.
Ageno, Walter; Mantovani, Lorenzo G; Haas, Sylvia; Kreutz, Reinhold; Haupt, Verena; Schneider, Jonas; Turpie, Alexander Gg
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism, poses a substantial clinical risk, and the incidence of these thrombotic-related diseases remains high. Anticoagulation aims to prevent thrombus extension and reduce the risk of recurrent events, particularly fatal pulmonary embolism. In EINSTEIN DVT, rivaroxaban was non-inferior to enoxaparin/vitamin K antagonists for the reduction of recurrent VTE, with a similar safety profile and a net clinical benefit. EINSTEIN EXT investigated patients receiving long-term treatment in whom there was no clear decision about continuing or stopping anticoagulation; rivaroxaban was superior to placebo in the reduction of recurrent VTE, showing an acceptable benefit-risk balance. Rivaroxaban has the potential to replace standard therapy, usually parenteral low molecular weight heparin overlapping with and followed by a vitamin K antagonist, for the treatment of acute symptomatic DVT and the secondary prevention of VTE. As the use of rivaroxaban for DVT treatment increases in clinical practice, a fundamental understanding of its clinical benefits in everyday patient care is essential. XALIA (XArelto for Long-term and Initial Anticoagulation in venous thromboembolism) is a multicentre, prospective, non-interventional, observational study investigating the effectiveness and safety of a single-drug approach with rivaroxaban compared with standard therapy in patients with DVT. The study cohort will include approximately 4800 patients (≥18 years old) with objectively confirmed acute DVT who will be treated for a period of ≥3 months. The primary outcomes will be the incidence of treatment-emergent adverse events (primarily major bleeding), symptomatic recurrent venous thromboembolic events and all-cause mortality. Secondary outcomes include: major cardiovascular events; patient-reported treatment satisfaction and adherence; healthcare resource utilization; reasons for drug switching or
Kumar, K.R. Ashok; Sarvagna, Jagadesh; Gadde, Praveen; Chikkaboriah, Shwetha
Introduction Hemostasis is a fundamental management issue post-operatively in minor oral surgical procedures. To ensure safety and therapeutic efficacy in patients, under oral anti coagulant therapy, is complicated by necessity for frequent determination of prothrombin time or international normalised ratio. Aim The aim of the study was to determine whether early hemostasis achieved by using Hemcon Dental Dressing (HDD) will affect post-operative care and surgical healing outcome in minor oral surgical procedures. Materials and Methods A total of 30 patients, aged 18 years to 90 years, except those allergic to seafood, who consented to participate, were enrolled into this study. Patients were required to have two or more surgical sites so that they would have both surgical and control sites. All patients taking Oral Anticoagulation Therapy (OAT) were included for treatment in the study without altering the anticoagulant regimens. Institutional Review Board approval was obtained for the same. The collected data was subjected to statistical analysis using unpaired t-test. Results All HDD surgically treated sites achieved hemostasis in 1.49 minutes and control wounds in 4.06 minutes (p < 0.001). Post-operative pain at HDD treated sites (1.87,1.27 on 1st and 3rd day respectively) was significantly lower than the control sites (4.0,1.87 on 1st and 3rd day respectively) p-value (0.001, 0.001 respectively). HDD treated oral surgery wounds achieved statistically significant improved healing both at 1st and 3rd post-operative days (p <0.0001). Conclusion The HDD has been proven to be a clinically effective hemostatic dressing material that significantly shortens bleeding time following minor oral surgical procedures under local anaesthesia, including those patients taking OAT. Patients receiving the HDD had improved surgical wound healing as compared to controls. PMID:27790577
António, Natália; Castro, Graça; Ramos, Domingos; Machado, António; Gonçalves, Lino; Macedo, Tice; Providência, Luís A
The management of patients taking long-term oral anticoagulants who require dental surgery is still highly controversial. The risk of bleeding associated with dental treatment under oral anticoagulants must be weighed against the risk of thromboembolism associated with suspension of antithrombotic therapy. Mortality and morbidity associated with thromboembolic events are higher than those associated with hemorrhagic events after minor oral surgery procedures. Evidence-based information does not support oral anticoagulant suspension before minor oral surgery. The authors propose a management protocol for chronically anticoagulated patients who require a dental procedure, to reduce both thromboembolic risk and the risk of bleeding.
Barnes, Geoffrey D; Kline-Rogers, Eva
Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process.
Barnes, Geoffrey D.; Kline-Rogers, Eva
Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process. PMID:25772116
Gómez-Outes, Antonio; Suárez-Gea, Maria Luisa; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Vargas-Castrillón, Emilio
The therapeutic armamentarium of parenteral anticoagulants available to clinicians is mainly composed by unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, recombinant hirudins (i.e. bivalirudin, desirudin, lepirudin) and argatroban. These drugs are effective and safe for prevention and/or treatment of thromboembolic diseases but they have some drawbacks. Among other inconveniences, UFH requires regular anticoagulant monitoring as a result of variability in the anticoagulant response and there is a risk of serious heparin-induced thrombocytopaenia (HIT). LMWH, fondaparinux and recombinant hirudins are mainly cleared through the kidneys and their use in patients with severe renal insufficiency may be problematic. LMWH is only partially neutralized by protamine while fondaparinux and recombinant hirudins have no specific antidote. Novel anticoagulants in development for parenteral administration include new indirect activated factor Xa (FXa) inhibitors (idrabiotaparinux, ultra-low-molecular-weight heparins [semuloparin, RO-14], new LMWH [M118]), direct FXa inhibitors (otamixaban), direct FIIa inhibitors (flovagatran sodium, pegmusirudin, NU172, HD1-22), direct FXIa inhibitors (BMS-262084, antisense oligonucleotides targeting FXIa, clavatadine), direct FIXa inhibitors (RB-006), FVIIIa inhibitors (TB-402), FVIIa/tissue factor inhibitors (tifacogin, NAPc2, PCI-27483, BMS-593214), FVa inhibitors (drotrecogin alpha activated, ART-123) and dual thrombin/FXa inhibitors (EP217609, tanogitran). These new compounds have the potential to complement established parenteral anticoagulants. In the present review, we discuss the pharmacology of new parenteral anticoagulants, the results of clinical studies, the newly planned or ongoing clinical trials with these compounds, and their potential advantages and drawbacks over existing therapies.
Pasin, Laura; Frati, Elena; Cabrini, Luca; Landoni, Giovanni; Nardelli, Pasquale; Bove, Tiziana; Calabrò, Maria Grazia; Scandroglio, Anna Mara; Pappalardo, Federico; Zangrillo, Alberto
Aims: To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies. Settings and Design: Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU). Materials and Methods: Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved. Results: Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred. Conclusions: PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings. PMID:26139737
Heit, J A
Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rheumatic atrial fibrillation, and venous thromboembolism. Perioperative management of the chronically anticoagulated patient is a complex medical problem, and includes the following issues: urgency of surgery, risk of thromboembolism in the absence of anticoagulation, bleeding risk, consequences of bleeding, ability to control bleeding physically, and duration of bleeding risk after the procedure. Most patients can be managed safely by stopping oral anticoagulants 4-5 days before surgery and restarting anticoagulation after the procedure at the patient's usual daily dose. In general, dental procedures and cataract extraction can be performed without interrupting anticoagulation. Most other procedures can be safely performed with an INR < or = 1.4. For patients with double-wing prosthetic valves (e.g., St. Jude, Carbomedics) in the aortic position, uncomplicated atrial fibrillation, or a remote (>3 months) history of venous thromboembolism, oral anticoagulants can be stopped 4-5 days before surgery and restarted at the usual daily dose immediately after surgery. For other patients at higher risk of thrombosis, "bridging therapy" with outpatient low molecular weight heparin is safe and effective. For urgent procedures, a small dose of oral vitamin K usually will reduce the INR within 24-36 hours to a level sufficient for surgery and avoids exposure to transfused blood products.
Koyama, Yasushi; Suzuki, Yasuo
A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy. PMID:27672472
The effect of varying levels of dietary vitamin K intake on therapeutic International Normalized Ratio (INR) values among patients starting warfarin therapy has not been well studied. We performed a prospective cohort study among 282 patients to explore the independent associations between usual in...
Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.
Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.
Purcell, C A
Most anticoagulated patients can be safely managed for routine dental treatment in the outpatient setting by following appropriate guidelines. Management should be based on the present level of anticoagulation as assessed by tests, in particular the international normalised ratio (INR), which should be carried out as close to the intervention as possible. A philosophy of minimal, if any, alteration to the level of anticoagulation should be adopted. This is particularly true for procedures producing minimal bleeding such as scaling and cleaning which, in the past, have resulted in patients having their INR lowered, with its attendant risks. The patient's anticoagulation is potentially life-saving and, where at all possible, should be maintained at therapeutic levels when therapy for non-threatening conditions is planned.
Hammar, Samuel P
We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto(®) (rivaroxaban).
Hammar, Samuel P.
We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban). PMID:26236607
Patel, Anand; Goddeau Jr, Richard P.; Henninger, Nils
Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile. Nevertheless, an increased risk of gastrointestinal bleeding (with the exception of apixaban), increased risk for thrombotic complication with sudden discontinuation, and inability to accurately assess and reverse anticoagulant effect require consideration prior to therapy initiation, and pose a challenge for decision making in acute stroke therapy. PMID:27347226
Khan, Tayyaba Irfan; Kamali, Farhad; Kesteven, Patrick; Avery, Peter; Wynne, Hilary
Of 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0.5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive education about warfarin. Of these, 44 were randomized to self-monitor their INR and 41 returned to clinic. Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [61.1 vs. 70.4; mean difference 8.8; 95% confidence interval (CI): -0.2-17.8; P = 0.054] and following education and self-monitoring (57 vs. 71.1; mean difference 14.1; 95% CI: 6.7-21.5; P < 0.001), compared with those patients following usual clinic care (60.0 vs. 63.2; mean difference 3.2; 95% CI: -7.3-13.7). Using the same comparative periods, the INR SD fell by 0.24 (P < 0.0001) in the group allocated to education and self-monitoring, 0.26 (P < 0.0001) in the group receiving education alone and 0.16 (P = 0.003) in the control group. Inter-group differences were not statistically significant (intervention groups 0.26 +/- 0.30 vs. control 0.16 +/- 0.3, P = 0.10). Quality-of-life measurements and health beliefs about warfarin were unchanged (apart from emotional role limitation) with education or education and self-monitoring. Patient education regarding anticoagulation therapy could be a cost-effective initiative and is worthy of further study.
Llau, Juan V; Ferrandis, Raquel; López Forte, Cristina
Among the drugs most widely consumed by patients are both antiplatelet agents (aspirin, clopidogrel, ticlopidine) and anticoagulants (acenocoumarol, warfarin, low molecular weight heparin, fondaparinux). The use of these drugs in the perioperative period is an essential concern in patient care due to the need to balance the risk of bleeding against thrombotic risk (arterial or venous), which is increased in surgical patients. The present review highlights three main aspects. Firstly, withdrawal of antiplatelet agents is recommended between 1 week and 10 days before surgery to minimize perioperative bleeding. However, this practice has been questioned because patients without the required antiplatelet coverage may be at greater risk of developing cardiac, cerebral or peripheral vascular complications. Therefore, the recommendation of systematic antiplatelet withdrawal for a specific period should be rejected. Currently, risks should be evaluated on an individual basis to minimize the time during which the patient remains without adequate antiplatelet protection. Secondly, thromboprophylaxis is required in most surgical patients due to the high prevalence of venous thromboembolic disease. This implies the use of anticoagulants and the practice of regional anesthesia has been questioned in these patients. However, with the safety recommendations established by the various scientific societies, this practice has been demonstrated to be safe. Finally, "bridge therapy" in patients anticoagulated with acenocoumarol should be performed on an individual basis rather than systematically without taking into account the thrombotic risks of each patient. The perioperative period involves high arterial and venous thrombotic risk and the optimal use of antiplatelet agents and anticoagulants should be a priority to minimize this risk without increasing hemorrhagic risk. Multidisciplinary consensus is essential on this matter.
Chaudhary, Nabin; Bundhun, Pravesh Kumar; Yan, He
Abstract Background: Data regarding the clinical outcomes in patients with atrial fibrillation (AF) receiving dual antiplatelet therapy (DAPT) and an anticoagulant in addition to DAPT (DAPT + vitamin K antagonist [VKA]) after coronary stent implantation are still controversial. Therefore, in order to solve this issue, we aim to compare the adverse clinical outcomes in AF patients receiving DAPT and DAPT + VKA after percutaneous coronary intervention and stenting (PCI-S). Methods: Observational studies comparing the adverse clinical outcomes such as major bleeding, major adverse cardiovascular events, stroke, myocardial infarction, all-cause mortality, and stent thrombosis (ST) in AF patients receiving DAPT + VKA therapy, and DAPT after PCI-S have been searched from Medline, EMBASE, and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to express the pooled effect on discontinuous variables, and the pooled analyses were performed with RevMan 5.3. Results: Eighteen studies consisting of a total of 20,456 patients with AF (7203 patients received DAPT + VKA and 13,253 patients received DAPT after PCI-S) were included in this meta-analysis. At a mean follow-up period of 15 months, the risk of major bleeding was significantly higher in DAPT + VKA group, with OR 0.62 (95% CI 0.50–0.77, P < 0.0001). There was no significant differences in myocardial infarction and major adverse cardiovascular event between DAPT + VKA and DAPT, with OR 1.27 (95% CI 0.92–1.77, P = 0.15) and OR 1.17 (95% CI 0.99–1.39, P = 0.07), respectively. However, the ST, stroke, and all-cause mortality were significantly lower in the DAPT + VKA group, with OR 1.98 (95% CI 1.03–3.81, P = 0.04), 1.59 (95% CI 1.08–2.34, P = 0.02), and 1.41 (95% CI 1.03–1.94, P = 0.03), respectively. Conclusion: At a mean follow-up period of 15 months, DAPT + VKA was associated with significantly lower risk of stroke, ST, and
Mirolovics, Ágnes; Papp, Csaba; Zsuga, Judit; Bereczki, Dániel
The most common cardiogenic cause of ischaemic stroke is atrial fibrillation which increases the probability of stroke five-fold and doubles case fatality. Based on international data the incidence of atrial fibrillation is approx. 2% however this rapidly increases with age. The necessity of using oral anticoagulants in the prevention of non-valvular atrial fibrillation related stroke is decided based on estimated stroke risk. The CHADS2 and the more predictive CHA2DS2-VASc scales are used for this purpose while the bleeding risk of patients treated with anticoagulant may be estimated by the HAS-BLED scoring scale. For decades oral anticoagulation meant using vitamin-K antagonists. Based on international data we can see that rate of anticoagulation is unacceptably low, furthermore most of the anticoagulated patients aren't within the therapeutic range of INR (INR: 2-3). A lot of disadvantages of vitamin-K antagonists are known (e.g. food-drug interaction, need for regular coagulation monitoring, increased risk of bleeding), therefore compounds with new therapeutic target have been developed. The novel oral anticoagulants (NOAC) can be divided in two major subgroups: direct thrombin inhibitors (dabigatran etexilate) and Xa-factor inhibitors (rivaroxaban, apixaban, edoxaban). These products are administered in fix doses, they less frequently interact with other medications or food, and regular coagulation monitoring is not needed when using these drugs. Moreover several studies have shown that they are at least as effective in the prevention of ischaemic stroke than the vitamin-K antagonists, with no more haemorrhagic complications.
Córdoba, Juan Pablo; Larrarte, Carolina; Ruiz, Alvaro
Anticoagulation has been considered essential during plasmapheresis. International publications and guidelines state that anticoagulation should be administered during therapy to avoid circuit clotting and impaired effectiveness. However, anticoagulation has also been associated with bleeding, fluid and electrolyte imbalances and hematological alterations. No published studies have looked at the risk to benefit ratio of the common practice of circuit anticoagulation. We describe the experience with 367 plasmapheresis sessions, in the Hospital Universitario San Ignacio, a tertiary care center in Bogota, Colombia, where no anticoagulation is used in any case. Patient characteristics and therapy complications are described. Coagulation of circuit was never reported.
Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria
Objectives Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. Methods 133 OAT patients were recruited and assessed for warfarin/3’-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups Results In the whole OAT group both warfarin and 3’-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3’-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3’-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001). Interestingly, 3’-hydroxywarfarin reached a strong correlation at c4 respect to warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3’-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and
Chronic antithrombotic therapy involves the use of anticoagulants, antiplatelets given either as monotherapy or in combination for the prevention of thrombotic complications. The most feared and sometimes fatal complication with this therapy is bleeding. It should be considered a “golden rule” that a drug or combination of drugs that maximizes efficiency (decreased thromboembolic risk) will probably be less safe (increased risk of bleeding), and this holds true either for single therapy or during combined therapy. The chances of bleeding indicated by risk tables can be useful but show only a snapshot, and the biological, social, environmental, and drug changes and therapeutic adherence also determine changes in the risk of thrombosis and bleeding. Bleeding is an eventuality that occurs in places of “locus minoris resistentiae,” and the results of careful phase 3 studies thus cannot be completely predictive of outcomes when a medication is introduced on the pharmaceutical market. With the use of warfarin, the International Normalized Ratio (INR) that has been established to indicate adequately balanced therapy is between 2.0 and 3.0. With the new oral anticoagulants, the pharmaceutical companies emphasize that it is not necessary to monitor anticoagulant effects. In studies with different doses of new oral anticoagulants, however, incidence of clinically significant bleeding complications have been directly related to the doses. Therefore, therapeutic excesses can condition bleeding risk and therapeutic limitation can increase thrombotic risk, especially when short-acting drugs such as the new oral anticoagulants are used. Hence, it is imperative to establish an appropriate method for monitoring new oral anticoagulants, setting levels of safety and effectiveness through periodic dosage and monitoring of their anticoagulant effects. Therefore, we still recommend the use of anticoagulation units for monitoring during treatment with the new oral anticoagulants
Dilute Russell's viper venom (DRVV) testing and activated partial thromboplastin time (APTT) have been effectively used in combination for lupus anticoagulant testing. The purpose of our study was to evaluate the role of mixing in activated partial thromboplastin and dilute Russell's viper venom testing for evaluation of lupus anticoagulants. Citrated blood from patients who were not on oral anticoagulant therapy was studied. Mixing study with 1 : 1 normal plasma for elevated APTT and also few samples with elevated screen time was carried out. Elevated APTT was seen in only 48.1% of patients with lupus anticoagulant. Correction of APTT was seen in 27.8% of lupus anticoagulant-positive patients. DRVV test on mixing resulted in 83.8% false-negative values. Integrated DRVV test could be a standalone test for testing lupus anticoagulant. Mixing study may be restricted for patients on oral anticoagulants or patients with strong lupus anticoagulant.
Gómez-Outes, Antonio; Suárez-Gea, Ma Luisa; Calvo-Rojas, Gonzalo; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio
The history of the traditional anticoagulants is marked by both perseverance and serendipity. The anticoagulant effect of heparin was discovered by McLean in 1915, while he was searching for a procoagulant in dog liver. Link identified dicumarol from spoiled sweet clover hay in 1939 as the causal agent of the sweet clover disease, a hemorrhagic disorder in cattle. Hirudin extracts from the medicinal leech were first used for parenteral anticoagulation in the clinic in 1909, but their use was limited due to adverse effects and difficulties in achieving highly purified extracts. Heparins and coumarins (i.e.: warfarin, phenprocoumon, acenocoumarol) have been the mainstay of anticoagulant therapy for more than 60 years. Over the past decades, the drug discovery paradigm has shifted toward rational design following a target-based approach, in which specific proteins, or "targets", are chosen on current understandings of pathophysiology, small molecules that inhibit the target's activity may be identified by high-throughput screening and, in selected cases, these new molecules can be developed further as drugs. Despite the application of rational design, serendipity has still played a significant role in some of the new discoveries. This review will focus on the discovery of the main anticoagulant drugs in current clinical use, like unfractionated heparin, low-molecular-weight heparins, fondaparinux, coumarins (i.e.: warfarin, acenocoumarol, phenprocoumon), parenteral direct thrombin inhibitors (DTIs) (i.e.: argatroban, recombinant hirudins, bivalirudin), oral DTIs (i.e.: dabigatran) and oral direct factor Xa inhibitors (i.e.: rivaroxaban, apixaban).
Dyla, Agnieszka; Mielnicki, Wojciech; Bartczak, Joanna; Zawada, Tomasz; Garba, Piotr
Liver failure is a serious and often deadly disease often requiring MARS (Molecular Adsorbent Recirculating System) therapy. Choosing the safe and effective method of anticoagulation during artificial liver support systems seems to be very difficult and extremely important. The aim of this study was to assess effectiveness and safety of regional anticoagulation with citrate in liver failure patients during MARS. We used a single center observational study. We analyzed 158 MARS sessions performed in 65 patients: 105 (66.5%) sessions in 41 patients with heparin anticoagulation, 40 (25.3%) sessions in 19 patients with citrate, and 13 (8%) sessions in only five patients without anticoagulation, that were excluded from part of the analysis. To determine the effectiveness of regional anticoagulation with citrate, probability of filter survival and changes in laboratory parameters were analyzed according to the applied method of anticoagulation. The safety of citrate was determined by Ca/Ca(2+) ratio, acid-base balance, bleeding complications, and the need for blood product transfusions. The probability of filter survival in the citrate group was 94% and in the heparin group 82% (P = 0.204). There was no relationship between the method of anticoagulation and effectiveness of MARS therapy in lowering the levels of the analyzed parameters. Only one patient had a Ca/Ca(2+) ratio higher than he safety margin. There were no statistically significant changes in pH and lactate level irrespective of anticoagulation; bicarbonate dropped significantly only in the heparin group (P = 0.03). The frequency of bleeding complications and the need for transfusions did not differ significantly between groups. Regional anticoagulation with citrate can be an effective and safe method of anticoagulation during MARS therapy, but requires attentive monitoring and further studies in liver failure patients.
Wheeler, D S; Giugliano, R P; Rangaswami, J
Anticoagulation-related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin-induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short-term and long-term all-cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all-cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment.
Daniels, Paul R
The use of oral anticoagulants is becoming increasingly common. For many years warfarin was the main oral anticoagulant available, but therapeutic options have expanded with the introduction of oral direct thrombin (dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban). Management of patients taking any oral anticoagulant in the peri-procedural period poses a challenge to medical and surgical providers because of the competing risks of thrombosis and hemorrhage. Bridging therapy has been used to minimize time without anticoagulation when warfarin is interrupted for invasive procedures, but validated strategies based on high quality data are lacking. Existing data suggest that the use of bridging therapy may increase the risk of bleeding for some patients without reducing the risk of thrombosis. Clinical trials are currently under way to answer these questions. Because the half lives and time to anticoagulant activity of newer oral anticoagulants are shorter than for warfarin, bridging therapy is not thought to be necessary with these agents. Peri-procedural management of patients taking these agents is complicated by the lack of demonstrated reversal agents in emergency situations, although specific antidotes are being developed and tested. Existing guidelines for peri-procedural management of patients on oral anticoagulants highlight the importance of individualized patient decision making and suggest strategies to minimize complications. From a patient's perspective, given the uncertainties surrounding optimal management, explicit discussions regarding risks and benefits of treatment options and demonstration of effective communication among medical and surgical providers are essential.
Fernandes, Caio Julio Cesar dos Santos; Júnior, José Leonidas Alves; Gavilanes, Francisca; Prada, Luis Felipe; Morinaga, Luciana Kato; Souza, Rogerio
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. PMID:27167437
Tripodi, A; Chantarangkul, V; Clerici, M; Negri, B; Mannucci, P M
A key issue for the reliable use of new devices for the laboratory control of oral anticoagulant therapy with the INR is their conformity to the calibration model. In the past, their adequacy has mostly been assessed empirically without reference to the calibration model and the use of International Reference Preparations (IRP) for thromboplastin. In this study we reviewed the requirements to be fulfilled and applied them to the calibration of a new near-patient testing device (TAS, Cardiovascular Diagnostics) which uses thromboplastin-containing test cards for determination of the INR. On each of 10 working days citrated whole blood and plasma samples were obtained from 2 healthy subjects and 6 patients on oral anticoagulants. PT testing on whole blood and plasma was done with the TAS and parallel testing for plasma by the manual technique with the IRP CRM 149S. Conformity to the calibration model was judged satisfactory if the following requirements were met: (i) there was a linear relationship between paired log-PTs (TAS vs CRM 149S); (ii) the regression line drawn through patients data points, passed through those of normals; (iii) the precision of the calibration expressed as the CV of the slope was <3%. A good linear relationship was observed for calibration plots for plasma and whole blood (r = 0.98). Regression lines drawn through patients data points, passed through those of normals. The CVs of the slope were in both cases 2.2% and the ISIs were 0.965 and 1.000 for whole blood and plasma. In conclusion, our study shows that near-patient testing devices can be considered reliable tools to measure INR in patients on oral anticoagulants and provides guidelines for their evaluation.
Albaladejo, Alberto; Alvarado, Alfonso
Background A new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments. Material and Methods A literature search was conducted through April 2016 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords “dabigatran”, “rivaroxaban”, “apixaban”, “edoxaban”, “new oral anticoagulants”, “novel oral anticoagulants”, “bleeding” and “dental treatment”. Results There is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed. Conclusions The number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures, and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant. Key words:Dabigatran, rivaroxaban, apixaban, edoxaban, novel oral anticoagulants, bleeding. PMID:28210451
Eusébio, Jorge; Reny, Jean-Luc; Fontana, Pierr; Nendaz, Mathieu
If the benefits of antiplatelet and anticoagulant therapies are well established, bleeding complications appear underestimated in trials in comparison to their real-life incidence. Also, a large number of patients receive various associations of antiplatelet or anticoagulant treatments, while the benefit of some associations is not firmly established and data about their safety are missing. Identifying patients at high risk of bleeding is essential to define appropriate strategies. In this article we discuss the risk-benefit of various antiplatelet and anticoagulant molecules taken individually or in combination. An overview of the main clinical scores available to stratify the risk of bleeding is presented.
Pinède, Laurent; Ninet, Jacques
The curative anticoagulant treatment of venous thromboembolism is non fractionated heparin or low molecular weight heparin, secondly substituted by oral anticoagulant therapy. Early mobilisation and elastic contention should be systematically prescribed. Low molecular weight heparin once or twice a day and early substitution by vitamin K antagonist allow an ambulatory treatment for deep vein thrombosis. It is still recommended a hospital management for patients with symptomatic pulmonary embolism. It is necessary to tailor the duration of anticoagulation individually according to the extension of venous thromboembolism and the presence (or absence) of risk or triggering factors. Bleeding is the major risk of anticoagulant therapy, particularly the vitamin K antagonists, justifying patient's education, adapted and regular biological surveillance, co-ordinated care approach with practical recommendations, patient's self-monitoring.
Rojas-Hernandez, Cristhiam M; Garcia, David A
After the introduction of warfarin, long-term oral anticoagulation treatment remained unchanged for more than 50 years. Most recently, with the development and approval of new oral anticoagulants, the treatment of medical conditions that require thrombosis prophylaxis and long-term anticoagulation has become more complex. In the case of venous thromboembolism (VTE) prevention after orthopedic surgery, the new oral agents will be less costly than the parenteral alternative. In other settings (such as atrial fibrillation or treatment of acute VTE), the new agents will offer additional convenience at higher cost, but the degree to which they will reduce clinically important events such as thrombosis or bleeding will be limited, especially for patients on optimally controlled warfarin. As the use of the new oral anticoagulants becomes more widespread, it will be important for all clinicians to have a basic understanding of their pharmacology, advantages, and limitations. Although the need to measure or reverse the effect of these drugs will arise infrequently, clinicians--especially hematologists--will desire evidence-based recommendations about how to manage such scenarios, which will require research studies.
Altenburg, Alexander; Haage, Patrick
In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.
Brejcha, M; Gumulec, J; Penka, M; Klodová, D; Wróbel, M; Bogoczová, E
The management of warfarin therapy in patients undergoing surgery or other invasive procedures involves a balance between the risk of hemorrhage, and the risk of thrombosis. Risk of hemorrhage and the trombosis depends on the type of procedure and on pre-existing conditions. Procedures with low risk of hemorrhage (dental, dermatologic or ophtalmologic procedures, endoscopy) can be provided with continuing anticoagulant therapy. Surgery with high hemorrhagic risk need stop warfarin and start bridging anticoagulant therapy, such as unfractionated heparin or low molecular weight heparin, prior and after surgery. In patients requiring emergency surgery, vitamin K, prothrombin complex concentrate or fresh frozen plasma can be used to improve coagulation.
Barnes, Geoffrey D; Nallamothu, Brahmajee K; Sales, Anne E; Froehlich, James B
Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism, and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban), many have questioned the need for anticoagulation clinic. However, we think that the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline 3 key purposes that a reimagined anticoagulation clinic would serve: (1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), (2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and (3) to encourage ongoing adherence to these life-saving medications. We also describe how repurposing anticoagulation clinics as broader medication safety clinics would promote safe and effective care across a range of cardiovascular conditions for high-risk medications (eg, spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a reimagined anticoagulation or medication safety clinic structure.
Barnes, Geoffrey D.; Nallamothu, Brahmajee K.; Sales, Anne E.; Froehlich, James B.
Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban), many have questioned the need for anticoagulation clinic. However, we believe the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline three key purposes that a “re-imagined” anticoagulation clinic would serve: 1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), 2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and 3) to encourage ongoing adherence to these life-saving medications. We also describe how re-purposing anticoagulation clinics as broader “medication safety clinics” would promoting safe and effective care across a range of cardiovascular conditions for high-risk medications (e.g. spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a re-imagined anticoagulation or medication safety clinic structure. PMID:26933047
Dang, Yi-Ping; Chen, Yun-Fei; Li, Yi-Qing; Zhao, Lei
Deep Vein Thrombosis (DVT) has been known as a common medical problem all over the world. Thrombus traveling in blood vessels may lead to pulmonary embolism (PE), associated with high rates of mortality. Anticoagulant therapy is the mainstay treatment of DVT. Common anticoagulants, Vitamin K antagonists (VKAs), unfractionated heparin (UFH) and Low-molecular-weight heparin (LMWH) have been used in clinical application over decades, but can increase the risk of hemorrhage. Thereby, several new oral anticoagulants (NOACs) have been developed, which includes direct thrombin inhibitors (DTI) and direct factor Xa inhibitors. To be contrast with VKAs and UFH, NOACs have many advantages such as rapid offset action, few drug/food interactions and no need for routine coagulation monitoring, etc. Many NOACs are still being evaluated in Phase III clinical trials such as Betrixaban and Darexaban (YM150). However, NOACs still have problems to be solved such as lack of antidotes and laboratory monitoring, high drug costs, etc. Besides, several agents have already shown the potential to be new anticoagulants. Factor Xa play an important role in thrombin generation and coagulation pathway. Thus, the new compounds directly targeting on factor Xa for prevention DVT are highly anticipated. DPC423, a new series of 6-substituted coumarin derivatives and Phenyltriazolinones as potent factor Xa inhibitors have been recently reported. Recent studies revealed that agents extracted from botanicals not only have anti-coagulant effects but also possess other pharmacological activities such as anti-inflammation to alleviate the post-thrombotic syndromes. All the evidence above suggests that many new compounds might have great potential to be more effective and safe oral anticoagulants.
This study evaluated 44 separate medication withdrawal periods in 17 subjects who were attending a hospital anticoagulation clinic for management of anticoagulation medication. The data suggest that when anticoagulant withdrawal is needed for particular dental procedures, a 2-day hold is an effective period of medication withdrawal. No thromboembolic events were observed after any of the withdrawal periods. Further, no posttreatment hemorrhagic episodes were observed when the anticoagulant medication was reinstituted after dental treatment. Prothrombin time blood levels should be determined in the immediate pretreatment period, however, because the prothrombin time can fluctuate even in the best maintained patients.
Vogel, T; Geny, B; Kaltenbach, G; Lang, P-O
Prescribing anticoagulant therapy when the CHA₂DS₂-VASc score is ≥ 1 prevents strokes secondary to non-valvular atrial fibrillation (AF). However, it is important to remember that whether the aged population has the highest risk of stroke in case of AF, under anticoagulant therapy this population is also at the highest risk of bleeding. Vitamin K antagonists were for decades the molecules of reference with benefits even after 75 years of age. The direct oral anticoagulants have overcome the biological constraints inherent to monitoring vitamin K antagonists and provide a more stable pharmacological action with a limited number of drug-drug interactions. However, the widespread use of these molecules in the older population remains controversial. In this review article, indications and modalities of administration of anticoagulant therapy in the elderly will be detailed and discussed on the basis of the most recent recommendations proposed in particular by the European Society of Cardiology. Particular attention will be paid to new oral anticoagulant therapies compared with vitamin K antagonists and antiplatelet agents.
Steinberg, M J; Moores, J F
Dental professionals frequently treat patients who are receiving anticoagulation therapy. Proper treatment may require adjustment of the anticoagulant dose usually on the basis of the patient's current prothrombin time. This test has been shown to be less accurate than previously thought. The international normalized ratio is another method that attempts to standardize the degree of anticoagulation and to improve reproducibility of results. This system is slowly being implemented in laboratories in the United States. Practitioners who treat patients taking anticoagulants need to be aware of this system in order to make appropriate management decisions.
Carter, Cedric J.
The author briefly reviews the use of anticoagulants, describing the specific tests their use requires. These tests are usually performed in a specialized laboratory. The clinical implication of the laboratory's use of different prothrombin time systems is explained. Implications of the use of oral anticoagulants in family practice are discussed. PMID:21253057
Edmunds, Ian; Avakian, Zorik
The management of anticoagulated patients requiring surgery presents a challenge to hand surgeons. The risk of bleeding related complications needs to be weighed up against the increased risk of thrombotic events if anticoagulants are altered or ceased. There is literature reporting the safety of hand, skin, eye and dental surgery on patients taking anticoagulants, and there is literature highlighting the risks associated with altering regular anticoagulant medication. However, it is common practice to cease or alter patients' anticoagulants peri-operatively for hand surgery. We report a prospective study of 107 patients taking anticoagulants who underwent 121 hand operations from December 2005 to August 2009. There was only one significant complication, that being a haematoma which occurred in a patient taking clopidogrel. We conclude that interruption to therapy with warfarin (provided the INR is not greater than 3.0), clopidogrel or clopidogrel with aspirin is unnecessary for patients undergoing hand surgery.
Radaelli, Franco; Dentali, Francesco; Repici, Alessandro; Amato, Arnaldo; Paggi, Silvia; Rondonotti, Emanuele; Dumonceau, Jean Marc
Acute gastrointestinal bleeding represents the most common adverse event associated with the use of oral anticoagulant therapy. Due to increasing prescription of anticoagulants worldwide, gastroenterologists are more and more called to deal with bleeding patients taking these medications. Their management is challenging because several issues have to be taken into account, such as the severity of bleeding, the intensity of anticoagulation, the patient's thrombotic risk and endoscopy findings. The recent introduction into the marketplace of new direct oral anticoagulants, for whom specific reversal agents are still lacking, further contributes to make the decision-making process even more demanding. Available evidence on this topic is limited and practice guidelines by gastroenterology societies only marginally address key issues for clinicians, including when and how to reverse coagulopathy, the optimal timing of endoscopy and when and how to resume anticoagulation thereafter. The present paper reviews the evidence in the literature and provides practical algorithms to support clinicians in the management of patients on anticoagulants who present with acute gastrointestinal bleeding.
Weitz, Jeffrey I.; Fredenburgh, James C.
Compared with vitamin K antagonists, the direct oral anticoagulants (DOACs) are simpler to administer and are associated with less intracranial bleeding. Nonetheless, even with the DOACs, bleeding still occurs and many patients with atrial fibrillation fail to receive anticoagulant thromboprophylaxis because of the fear of bleeding. Therefore, there is an urgent need for safer anticoagulants. Recent investigations into the biochemistry of hemostasis and thrombosis have identified new targets for development of novel anticoagulants. Using data from complementary sources, including epidemiological studies and investigations in various animal models, the contact pathway has emerged as a potential mediator of thrombosis that plays a minor part in hemostasis. Consequently, factor (F) XII of the contact system and FXI in the intrinsic pathway have been identified as potentially safer targets of anticoagulation than thrombin or FXa. However, further studies are needed to identify which is the better target for the appropriate indication. This review highlights the evidence for focusing on FXI and FXII and examines the novel approaches directed at these new targets. These emerging strategies should address current unmet medical needs and provide new avenues by which to improve anticoagulant therapy by reducing the risk of bleeding. PMID:28286749
Simultaneous administration of the anticoagulants acenocoumarol, phenprocoumon or chlorindion and the antirheumatic substance alclofenac in long term trials has no observable influence on the prothrombin time of stabilized patients. When the anticoagulant (acenocoumarol or phenprocoumon) and the alclofenac therapy are begun simultaneously, a variation of the dose is necessary. Either a one-third lower initial dosage can be given, or, after attaining the maximal anticoagulation effect on the prothrombin time (48 h after beginning acenocoumarol therapy, 72 h with phenprocoumarol), a lower daily dosage must be administered once, in comparison to the other group without alclofenac therapy. The maintenace dosage is not influenced by alclofenac.
Veltkamp, R; Hacke, W
Atrial fibrillation (AF) causes at least 20% of all ischemic strokes. In large randomized trials of primary and secondary stroke prevention, anticoagulation with vitamin K antagonists (VKA) protected much more efficiently than antiplatelet agents against stroke. Because of the problematic pharmacological properties of VKA only part of the AF patients are currently being treated with oral anticoagulants (OAK). The targeted development of specific oral inhibitors of the central coagulation factors thrombin and factor Xa allows reliable anticoagulation without regular coagulation monitoring. In the present review, pharmacological properties of the different agents are compared. Of the four large randomized phase 3 studies in AF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) with the primary efficacy endpoint stroke and systemic embolism, the published data from the RELY trial indicate a superior efficacy of dabigatran etexilate (2 × 150 mg/day) and a lower risk of intracranial hemorrhage compared to warfarin. Favorable preliminary results have been demonstrated for the factor Xa inhibitor rivaroxaban. Apixaban was more efficacious than ASA and had a similar risk of hemorrhage in the AVERROES study. Thus, the available data suggest a favorable benefit-risk ratio for the new substances in addition to improved patient comfort. Currently unresolved issues relate to the verification of patient adherence by suitable coagulation tests and to the emergency coagulation diagnostics and therapy in acute ischemic or hemorrhagic strokes under the new OAC.
Objective: Oral anticoagulants are widely administered to patients with atrial fibrillation in order to prevent the onset of cardiogenic embolisms. However, intracranial bleeding during anticoagulant therapy often leads to fatal outcomes. Accordingly, the use of novel oral anticoagulants (NOACs), which less frequently have intracranial bleeding as a complication, is expanding. A nationwide survey of intracranial bleeding and its prognosis in Japan reported that intracranial bleeding of advanced severity was not common after NOAC administration. In this report, two cases from our institute are presented. Patients: Case 1 was an 85-year-old man with a right frontal lobe hemorrhage while under dabigatran therapy. Case 2 was an 81-year-old man who had cerebellar hemorrhage while under rivaroxaban therapy. Result: In both patients, the clinical course progressed without aggravation of bleeding or neurological abnormalities once anticoagulant therapy was discontinued. Conclusion: These observations suggest that intracranial hemorrhage during NOAC therapy is easily controlled by discontinuation of the drug. NOAC administration may therefore be appropriate despite the risk of such severe complications. Further case studies that include a subgroup analysis with respect to each NOAC or patient background will be required to establish appropriate guidelines for the prevention of cardiogenic embolisms in patients with atrial fibrillation. PMID:27928459
Ciurus, Tomasz; Cichocka-Radwan, Anna
Introduction The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. Material and methods We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. Results The mean age of the patients was 68.8 ± 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 ± 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR ≥ 80% were included in the stable anticoagulation group (TTR ≥ 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). Conclusions The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients. PMID:26855650
Biasiutti, F Demarmels; Strebel, J Kremer Hovinga
For haemostatic and circulatory reasons pregnancy is associated with an about 6-fold relative increase of thrombotic risk which is further raised by additional risk factors, such as history of thrombosis or acquired and hereditary thrombophilia, respectively. Recently, the thrombophilias have been revealed as risk factors for severe preeclampsia, abruptio placentae, fetal growth retardation, abortion and still birth as well. Thus, there are several situations in which the question for the need of antithrombotic medication is raised in a pregnant woman, either for therapy of acute thromboembolism or for prophylaxis of thrombosis and obstetrical complications, respectively. While acute thromboembolism has to be treated in every case, indication for prophylaxis has to be weighed in the light of the individual risk profile of the pregnant woman and the potential side effects and inconvenience of the medication. The first part of this article deals with the pregnancy related problems of coumarins, heparins and aspirin and demonstrates that the low molecular weight heparins are the anticoagulants of choice for most indications in pregnancy. The second part of this overview shows in which specific situations and how the antithrombotic medications mentioned above are used in pregnancy.
Wooten, James M
For years, the pharmaceutical industry has been trying to find a safe and effective drug to replace warfarin. Although warfarin is an effective anticoagulant, its pharmacology, adverse effects, and risk profiles dictate that patients taking this medication must be monitored judiciously. The US Food and Drug Administration has approved two drugs for commercial use, dabigatran and rivaroxaban, that will compete directly with warfarin for use in specific indications. Because of direct marketing to patients, physicians are being asked to comment on these new medications. This brief review illustrates the data available for the two new drugs when compared to warfarin for the specified indications. For some patients, these drugs may be highly beneficial and offer an excellent alternative to warfarin. For others, warfarin may still be the preferred drug.
Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort
Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.
Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063
Babilonia, Katrina; Trujillo, Toby
Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting.
Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting. PMID:24742134
Mommsen, Jens; Rodríguez-Fernández, Javier; Mateos-Micas, Mario; Vázquez-Bouso, Olga; Gumbao-Grau, Victor; Forteza-Gonzalez, Gabriel
Amputation of the auricle is a periodic occurrence leading to disfigurement if not treated properly. Venous stasis is a common complication in reattachments and requires decongestant and anticoagulant treatment. Today, leech therapy is the treatment of choice. Common problems are that it is not available everywhere and that it is usually contraindicated in anticoagulated patients. The peculiarities of leech therapy and the various aspects of surgical management are reviewed. A case of a partial amputation of the auricle in a patient under concomitant anticoagulation therapy with warfarin is presented. The amputated part was reattached in another hospital without microvascular anastomosis. The patient presented to our department with early signs of venous congestion. Leech therapy was started 35 hours after trauma, and the patient continued his anticoagulation therapy. With this treatment, 90% of the amputated part was rescued. The anticoagulation therapy of the patient may have played an important role in the first hours after reattachment, preventing capillary thrombosis and in consequence facilitating the minimal oxygenation necessary. The claim that anticoagulation therapy is a contraindication to leeching should be questioned in cases of reattachments in well-controllable locations without arterial anastomosis.
Mommsen, Jens; Rodríguez-Fernández, Javier; Mateos-Micas, Mario; Vázquez-Bouso, Olga; Gumbao-Grau, Victor; Forteza-Gonzalez, Gabriel
Amputation of the auricle is a periodic occurrence leading to disfigurement if not treated properly. Venous stasis is a common complication in reattachments and requires decongestant and anticoagulant treatment. Today, leech therapy is the treatment of choice. Common problems are that it is not available everywhere and that it is usually contraindicated in anticoagulated patients. The peculiarities of leech therapy and the various aspects of surgical management are reviewed. A case of a partial amputation of the auricle in a patient under concomitant anticoagulation therapy with warfarin is presented. The amputated part was reattached in another hospital without microvascular anastomosis. The patient presented to our department with early signs of venous congestion. Leech therapy was started 35 hours after trauma, and the patient continued his anticoagulation therapy. With this treatment, 90% of the amputated part was rescued. The anticoagulation therapy of the patient may have played an important role in the first hours after reattachment, preventing capillary thrombosis and in consequence facilitating the minimal oxygenation necessary. The claim that anticoagulation therapy is a contraindication to leeching should be questioned in cases of reattachments in well-controllable locations without arterial anastomosis. PMID:22655116
Dannemiller, Robert; Ward, Tucker; Fanikos, John
Thromboembolism afflicts millions of patients annually in the United States and is associated with a significant cost burden. Oral anticoagulants provide clinicians with options for management of these diseases and their use continues to grow. Accordingly, regulatory, legislative, and nonprofit organizations have set performance standards with the goal of improving patient outcomes, ensuring patient safety, and reducing costs. Recent efforts in quality improvement have introduced changes surrounding regulatory requirements, surveillance, litigation, and oversight that clinicians should be familiar with. This article summarizes key updates related to the management of anticoagulant therapy as it relates to thrombosis prevention and treatment.
Tauron, M; Paniagua, P; Muñoz-Guijosa, C; Mirabet, S; Padró, J M
Heparin-induced thrombopenia is a common autoimmune complication. It is a prothrombotic state due to the formation of antibodies against heparin/platelet factor 4 complexes. In this situation drugs other than heparin must be used for anticoagulation during extracorporeal circulation (bypass) surgery. Two cases of heart transplantation are presented in whom bivalirudin was used as an anticoagulant during the cardiopulmonary bypass. Severe bleeding complications were observed in both patients. The diagnosis of heparin-induced thrombopenia needs to be improved, as well as the development of protocols for using new drugs other than heparin. For this reason, we have reviewed current protocols and alternative therapies to heparin.
O'Connell, John Edward; Stassen, Leo F A
Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Over the last 40 years, warfarin has been the oral anticoagulant of choice and has been considered the mainstay of treatment. However, its use is limited by a narrow therapeutic index and complex pharmacodynamics, necessitating regular monitoring and dose adjustments. Recently, two new oral anticoagulants--dabigatran etexilate (a direct thrombin inhibitor) and rivaroxiban (a factor Xa inhibitor)--have been approved for use in North America and Europe. Unlike warfarin, dabigatran and rivaroxiban are relatively small molecules that work as anticoagulants by targeting specific single steps of the coagulation cascade. Their advantages, relative to warfarin, include: predictable pharmacokinetics; limited food and drug interactions; rapid onset of action; and, short half-life. They require no monitoring. However, they lack a specific reversal agent. The number of patients taking dabigatran and rivaroxaban is increasing. Therefore, it is inevitable that dentists will be required to perform invasive procedures on this cohort of patients. This paper outlines the various properties of the new oral anticoagulants and the most recent guidelines regarding the management of these dental patients taking these medications.
Willbanks, O L; Willbanks, S E
Femoral neuropathy occurs when occult retroperitoneal bleeding impinges on the appropriate nerve roots. The syndrome involves the acute onset of groin and thigh pain with characteristic flexion and external rotation of the hip. It may mimic other conditions such as acute arterial occlusion. Thorough knowledge of the anatomy of the femoral nerve explains the clinical features and leads the clinician to suspect the occurrence of this syndrome. Three cases have been reviewed that exhibited this condition as a result of retroperitoneal bleeding, a complication of systemic heparin therapy. The hemophilia that afflicted Alexis, the Crown Prince of Russia and son of Tsar Nicholas and Tsarina Alexandra, resulted in this clinical syndrome. The consequences enabled the sinister starets, Gregory Rasputin, to become intimately involved with the royal family, influencing the response of the Tsar to the political events in Russia, thereby playing an important role in setting the stage for the 1917 Russian communist revolution.
Costopoulos, Charis; Niespialowska-Steuden, Maria; Kukreja, Neville; Gorog, Diana A
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide with a prevalence that has now reached pandemic levels as a consequence of the rapid modernization of the developing world. Its presentation as an acute coronary syndrome (ACS) is a frequent reason for hospital admission and of profound implications for personal, societal and global health. Despite improvements in the management of ACS with anti-platelet and anticoagulant therapy and revascularization techniques, many patients continue to suffer recurrent ischemic events. The need to reduce future cardiovascular events has led to the development of novel therapies to prevent coronary thrombosis, targeting thrombin-mediated pathways. These include direct Xa inhibitors (apixaban, rivaroxaban and darexaban), direct thrombin inhibitors (dabigatran) and PAR 1 antagonists (vorapaxar and atopaxar). This article critically reviews the comparative mechanisms of action, the risks and benefits, together with the clinical evidence base for the use of these novel oral agents in the management of ACS patients.
Ko, Darae; Hylek, Elaine M
The risk for both arterial and venous thrombosis increases with age. Despite the increasing burden of strokes related to atrial fibrillation (AF) and venous thromboembolism (VTE) among older adults, the use of anticoagulant therapy is limited in this population due to the parallel increase in risk of serious hemorrhage. Understanding the risks and their underlying mechanisms would help to mitigate adverse events and improve persistence with these life-saving therapies. The objectives of this review are to: (1) elucidate the age-related physiologic changes that render this high risk subgroup susceptible to hemorrhage, (2) identify mutable risk factors and hazards contributing to an increased bleeding risk in older individuals, and (3) discuss interventions to optimize anticoagulation therapy in this population.
Barnes, Geoffrey D; Kanthi, Yogendra; Froehlich, James B
Initial treatment for venous thromboembolism (VTE) includes the acute and intermediate phases, usually lasting for 3 months. The choice to extend therapy beyond the initial 3-month window involves assessing a combination of risk factors for VTE recurrence and bleeding, along with weighing patient preferences. In some cases, such as VTE provoked by a reversible surgical risk factor, the recurrence risk is sufficiently low that most patients should not receive extended therapy. In other cases, such as VTE associated with malignancy, the recurrence risk is sufficiently high that treatment should be extended beyond the initial 3 months. However, a large number of patients fall into a grey zone where the decision on extended therapy is less clear-cut. In this review, we summarize the evidence for VTE recurrence risk and the role for extended anticoagulation given a variety of patient-specific factors and laboratory results. We also review the role of VTE risk prediction tools and provide a recommended algorithm for approaching the decision of extended anticoagulation therapy. Various agents available for extended VTE therapy, including warfarin, aspirin and the direct oral anticoagulant agents, are discussed. PMID:25832602
Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B
Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH.
Gleason, Lauren Jan; Friedman, Susan M
This article describes current literature and treatment plans for managing anticoagulation and antiplatelet agents in patients presenting with hip fractures. Indications for anticoagulation and antiplatelet agents are discussed, and management techniques for when patients present with hip fractures are reviewed.
... by heart Treatments + Tests What Are Anticoagulants and Antiplatelet Agents? Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. Blood clots can block the ...
Antz, Matthias; Hullmann, Bettina; Neufert, Christian; Vocke, Wolfgang
The correct anticoagulation regimen for prevention of thromboembolic events is essential in patients with atrial fibrillation. However, only a minority of patients receives anticoagulation according to the guidelines. The current guidelines are intended to make the indication for anticoagulation more simple and are summarized in the present article. This includes recommendations for chronic anticoagulation, prevention of thromboembolic events after cardioversion and in ablation of atrial fibrillation.
Katritsis, Demosthenes G; Gersh, Bernard J; Camm, A John
This article presents the current status of the use of anticoagulation for the treatment of AF, particularly with the use of non-vitamin K-dependent anticoagulants. Comparisons between these agents and warfarin are made and methods for assessment of anticoagulant activity and reversal are discussed. PMID:26835109
Sarig, Galit; Garach-Jehoshua, Osnat; Deutch, Varda; Winder, Asher; Hyam, Esti; Katz, Ben Zion; Lahav, Judith; Cassel, Aliza; Zivelin, Ariella; Souroujon, Moshe; Shimron, Orit
Lupus anticoagulants (LAC) are antibodies which are detected by a prolongation of phospholipid-dependent coagulation assays, and are associated with thrombotic events and pregnancy complications in patients with the antiphospholipid syndrome. The antiphospholipid syndrome is defined by arterial or venous thrombosis and/or pregnancy morbidity and by laboratory diagnosis of antiphospholipid antibodies. The laboratory diagnosis is based on LAC and/or anticardiolipin and/or anti-beta2-glycoprotein I antibodies present in plasma, on two or more occasions at least 12 weeks apart. ALthough the presence of LAC correlates best with thrombosis, the Laboratory testing of LAC is not well standardized. In this article, the Laboratory evaluation of LAC will be explained, including the different tests that are recommended by the Israeli Sub-committee of Thrombosis and Hemostasis Laboratories, the possibility to evaluate LAC in patients treated with antithrombotic therapy, and how to report and interpret the results.
Mueller, Edward J.
The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.
anticoagulation are ineligible. Study Design. Patients will undergo surgical removal of metastatic disease under local anesthesia in order to provide...tolerate this treatment . Gene Therapy of Human Breast Cancer - Appendix F 1 1 . Patients who require anticoagulation are not eligible. 12 . There i...pregnancy, or lactation, or any significant uncontrolled medical or pyschiatric illness. Patients wh� require corticosteroids or anticoagulation are
Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip
Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived.
Ten Cate, Hugo
New oral anticoagulants (NOACs) have been introduced to improve anticoagulant therapy worldwide, but safe implementation may require additional measures. First, optimization of dose adjustment based on therapeutic levels of the drug may be more appropriate than fixed dose therapy. The development and implementation in quantitative laboratory assays will enable further dose optimization. Second, non-adherence to medication is a potential threat to the safe use of NOACs. Since cardiovascular medication may not be optimally used in about 50% of patients, procedures to improve adherence are imperative, also for NOAC therapy and in particular in elderly patients.
Carr, M M; Mason, R B
Today's trend toward ambulatory medical care will bring more pharmacological problems into the dental office. While the dental management of patients taking oral anticoagulants is controversial, current research supports the contention that they can be safely treated on an outpatient basis. The use of the International Normalized Ratio (INR) has made better estimates of prothrombin time possible, and patients can be maintained in a narrow therapeutic range. Postoperative hemorrhage can be avoided or controlled with local hemostatic agents.
Point-of-care monitoring of oral anticoagulation therapy in children. Comparison of the CoaguChek XS system with venous INR and venous INR using an International Reference Thromboplastin preparation (rTF/95).
Greenway, Anthea; Ignjatovic, Vera; Summerhayes, Robyn; Newall, Fiona; Burgess, Janet; DeRosa, Lydia; Monagle, Paul
Point-of-care (POC) monitoring of oral anticoagulation has been widely adopted in both paediatric and adult patients. A new POC system, the CoaguChek XS has recently been developed to measure the international normalised ratio (INR) and may offer significant advantages. The CoaguChek XS utilises a new method of electrochemical clot detection based on thrombin generation. This system has not been previously evaluated in children with reference to the laboratory gold standard, the prothrombin time using reference thromboplastin. It was the objective to compare values obtained by the CoaguChek XS system with both the venous INR and the gold standard for anticoagulant monitoring, prothrombin time with reference thromboplastin (rTF/95). To evaluate the impact of testing using the CoaguChek XS on clinical anticoagulant dosing decisions. Fifty paired venous INR and capillary CoaguChek XS results were obtained from 31 children (aged up to 16 years). The laboratory gold standard, a manual prothrombin time with reference thromboplastin (rTF/95) was additionally performed on 26 samples. Correlation between the CoaguChek XS result and the venous INR was r = 0.810. Agreement between the CoaguChek XS result and the reference INR was shown to be higher (r=0.95), in the subset analysed by this method. Correlation between the venous INR and reference INR was r=0.90. Despite changes to the methodology of testing with the CoaguChek XS POC monitoring system, the accuracy of this method when compared with both the venous INR and gold standard reference INR was satisfactory. This resulted in infrequent changes to clinical decision making regarding anticoagulation.
Pototski, Mariele; Amenábar, José M
Antiplatelet and anticoagulant agents have been extensively researched and developed as potential therapies in the prevention and management of arterial and venous thrombosis. On the other hand, antiplatelet and anticoagulant drugs have also been associated with an increase in the bleeding time and risk of postoperative hemorrhage. Because of this, some dentists still recommend the patient to stop the therapy for at least 3 days before any oral surgical procedure. However, stopping the use of these drugs exposes the patient to vascular problems, with the potential for significant morbidity. This article reviews the main antiplatelet and anticoagulant drugs in use today and explains the dental management of patients on these drugs, when subjected to minor oral surgery procedures. It can be concluded that the optimal INR value for dental surgical procedures is 2.5 because it minimizes the risk of either hemorrhage or thromboembolism. Nevertheless, minor oral surgical procedures, such as biopsies, tooth extraction and periodontal surgery, can safely be done with an INR lower than 4.0.
Mohammed, Shaban; Aljundi, Amer H. S.; Kasem, Mohamed; Alhashemi, Mohammed; El-Menyar, Ayman
There is a limited knowledge about the predictors of anticoagulation control in patients with nonvalvular atrial fibrillation (NVAF). Furthermore, few reports addressed the role of time in therapeutic range (TTR) that could reflect the safety and efficacy of anticoagulation therapy. We aimed to assess factors that affect the quality of anticoagulation therapy utilizing TTR in patients with NVAF. A retrospective observational study was conducted for patients with NVAF who were maintained on warfarin >6 months at a tertiary cardiac care hospital. Patients were categorized according to the TTR status (≥65% vs. <65%). A total of 241 eligible patients were identified. A high-quality anticoagulation based on TTR values ≥65% was found in 157 (65.1%) patients; the remaining (34.9%) patients represented the low-quality anticoagulation group (TTR <65%). Demographics and clinical characteristics were comparable in the two TTR groups. Both groups were comparable in terms of warfarin dose and medications use. When compared to patients with high-quality anticoagulation, patients in the low-quality anticoagulation group were more likely to seek outpatient warfarin clinic visits more frequently (22.3 ± 5.5 vs. 18 ± 4.4, P = 0.001) and to have higher rate of polypharmacy (57.1% vs. 42%, P = 0.03). Of note, patients in both groups had similar major bleeding events (P = 0.41). After adjusting for age and sex, polypharmacy use was a predictor of poor coagulation control (odds ratio = 1.89, 95% confidence interval: 1.03–3.33; P = 0.03). In NVAF patients, TTR is generally high in our cohort. Patients with polypharmacy and frequent clinic visits have lower TTR. High-quality oral anticoagulation could be achieved through optimizing TTR without a significant risk of major bleeding. PMID:28217549
Mendenhall, V.M.; Pank, L.F.
Anticoagulants-compounds that prevent clotting of the blood-are extensively used for control of small mammal pests. The potential secondary hazards of 6 anticoagulant rodenticides to birds of prey were examined in this study. Whole rats or mice were killed with each anticoagulant and were fed to 1-3 species of owls. Owls died of hemorrhaging after feeding on rats killed with bromadiolone, brodifacoum, or diphacinone; sublethal hemorrhaging occurred in owls fed rats killed with difenacoum. These results demonstrate potential secondary hazards of 4 anticoagulants to avian predators. No abnormalities were observed in owls fed rats killed with fumarin and chlorophacinone
Shamoun, Fadi; Obeid, Hiba; Ramakrishna, Harish
Atrial fibrillation continues to be a significant source of morbidity and mortality worldwide. Effective anticoagulation remains the cornerstone of outpatient and inpatient treatment. The use of the new generation of anticoagulants (NOACs) continues to grow. Recently published data indicate their cost-effectiveness and overall safety in stroke prevention; compared to vitamin K antagonists, they can be prescribed in fixed doses for long-term therapy without the need for coagulation monitoring. Both United States and European Guidelines recommend NOACs for stroke prevention in patients with atrial fibrillation. This review discusses each of the NOACs, along with their efficacy and safety data. It explores the most recent guidelines regarding their perioperative use in atrial fibrillation patients. It also discusses bleeding complications, perioperative management, and reversal agents. PMID:26221593
Garcia, David A
More than 4 years have passed since the first approval of a target-specific oral anticoagulant (TSOAC) in the United States, and the number of clinicians who have prescribed (or considered prescribing) one or more of these medications is increasing. Although these agents may, in properly selected patients, offer advantages over more traditional therapies, their lack of familiarity can be intimidating. Clinicians who are prescribing the TSOACs face a number of management questions not definitively answered by the registration trials. This chapter reviews some of these situations, including updated information on the periprocedural management of TSOACs and the latest evidence about how to best measure TSOAC effect. The lack of an antidote and other considerations that may be relevant when deciding between newer and more traditional anticoagulant medications are also discussed.
... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question ... care provider before making the change. Anticoagulants and Medicine There are many medicines that can interact with ...
Miranda, M; Martinez, L S; Franco, R; Forte, V; Barlattani, A; Bollero, P
The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant - dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) - have been approved for use in europe. Increasing the number of patients taking these drugs, it is important that the dentist knows these new oral anticoagulants, their indications and methods of action, in particular for the management of patients, who require invasive treatments. With regard to the management of the patient threated with the new oral anticoagulants (NAO), there have been new significant changes in the procedure compared to the one followed by patients treated with warfarin. This led to the development of new guidelines that the dentist has to follow in order to ensure a safe and appropriate dental treatment and reduce any postoperative complications. The aim of this work is to evaluate the effectiveness of the new oral anticoagulants compared to warfarin, especially in terms of risks of bleeding events and intra and postoperative complications, in patients requiring multiple dental extractions.
MIRANDA, M.; MARTINEZ, L.S.; FRANCO, R.; FORTE, V.; BARLATTANI, A.; BOLLERO, P.
SUMMARY The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant – dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) – have been approved for use in europe. Increasing the number of patients taking these drugs, it is important that the dentist knows these new oral anticoagulants, their indications and methods of action, in particular for the management of patients, who require invasive treatments. With regard to the management of the patient threated with the new oral anticoagulants (NAO), there have been new significant changes in the procedure compared to the one followed by patients treated with warfarin. This led to the development of new guidelines that the dentist has to follow in order to ensure a safe and appropriate dental treatment and reduce any postoperative complications. The aim of this work is to evaluate the effectiveness of the new oral anticoagulants compared to warfarin, especially in terms of risks of bleeding events and intra and postoperative complications, in patients requiring multiple dental extractions. PMID:28042443
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da Silva, Rose M.F.L.
Atrial fibrillation is the most frequent arrhythmia in clinical practice, reaching 2% of the people in the world and is associated with systemic embolism. Thus, the use of anticoagulants is indicated if CHA2DS2-VASc score ≥2 or in patients with previous transient ischemic attack or stroke. For decades, warfarin, a vitamin K antagonist, was the only choice for chronic oral anticoagulation. Recently, novel oral anticoagulants (NOACs) have been introduced, offering similar (or better) effectiveness, safety, and convenience to the vitamin K antagonists. Dabigatran was the first NOAC approved and is a direct thrombin inhibitor. Rivaroxaban and apixaban are factor Xa inhibitors. They display rapid onset of action, more predictable of pharmacological profile, less interactions with other drugs, lack of significant effects in the diet, and less risk of intracranial hemorrhage than warfarin. Despite that dose adjustment is necessary for patients with chronic kidney disease or according to body weight, these new drugs do not require regular monitoring. There are recommendations for the start and follow-up therapy with NOACs, planning for cardioversion, ablation and surgical interventions and the management of bleeding. This article is a review of the major studies of the NOACs. The clinical use of these drugs in patients with non-valvular atrial fibrillation is presented. PMID:25470147
Albert, Nancy M
Atrial fibrillation (AF), a common arrhythmia, increases the risk of ischemic stroke. Stroke and bleeding scores for patients with AF can help to stratify risk and determine the need for antithrombotic therapy, for which warfarin has been the gold standard. Although highly effective, warfarin has several limitations that can lead to its underuse. Data from randomized, Phase III clinical trials of the novel oral anticoagulants, dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, indicate these drugs are at least noninferior to warfarin for the prevention of stroke and systemic embolism. They are easier to administer, and have an equivalent or lower risk of bleeding versus warfarin. A better understanding of the risks and benefits of the novel oral anticoagulants, and their use in clinical practice, will prepare clinicians to anticipate and address educational and clinical needs of AF patients and their families, and promote evidence-based prescription of appropriate and safe anticoagulation therapy.
Gu, Kang Mo; Shin, Jong Wook; Park, In Won
Antiphospholipid syndrome (APS) is an acquired systemic autoimmune disorder characterized by a combination of clinical criteria, including vascular thrombosis or pregnancy morbidity and elevated antiphospholipid antibody titers. It is one of the causes of deep vein thrombosis and pulmonary embolism that can be critical due to the mortality risk. Overall recurrence of thromboembolism is very low with adequate anticoagulation prophylaxis. The most effective treatment to prevent recurrent thrombosis is long-term anticoagulation. We report on a 17-year-old male with APS, who manifested blue toe syndrome, deep vein thrombosis, pulmonary thromboembolism, and cerebral infarction despite adequate long-term anticoagulation therapy.
Atrial fibrillation treatment relies on anticoagulation therapy that reduces the risk of stroke. Vitamin K antagonists (VKA) were the only oral anticoagulant drugs for more than 50 years, but they are difficult to manage especially in the elderly. In France, VKA are the main cause of iatrogenic hospitalizations with about 17,000 hospitalizations per year and around 4,000 to 5,000 deaths per year. Pharmacologic properties of VKA, especially the narrow therapeutic margin explain the complexity of their management. Several studies have shown that patients treated with VKA were on average only 50% of the time with an INR in the therapeutic range. In other words, patients are, half of the time, either-under treated or over-treated. Within this framework, development of new oral anticoagulant drugs appeared necessary, in order to obtain drugs with larger therapeutic margin and a better risk/benefit profile than VKA. Three large randomized clinical trials including almost 50,000 patients with 20,000 subjects over 75 years old and 8,000 over 80 years old, show a better risk/benefit profile of the new oral anticoagulants (NOAC) than VKA, characterized by a 50% reduction of cerebral hemorrhages, 22% reduction of stroke and 12% reduction of total mortality. Meanwhile, their renal elimination and the lack of control of the biological efficacy need to be taken into account for their prescription. Renal failure (estimated glomerular filtration rate according to Cockcroft formula < 30 mL/min) contraindicates their use. Their half-life is shorter than that of VKA and the biological monitoring is not available, thus a good adherence to the treatment is important. Studies specifically conducted among geriatric older population with poly-pathologies and frail are therefore needed to evaluate tolerance of NOAC in real life conditions.
Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide–polysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants. PMID:25119520
Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; eg, warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (eg, those with renal impairment) and other specific clinical situations. PMID:26089678
Nutescu, Edith; Chuatrisorn, Ittiporn; Hellenbart, Erika
Clinicians and patients around the world have been intrigued by the concept of developing an oral anticoagulant with a broad therapeutic window and few drug and dietary interactions that can be administered at fixed doses with no or minimal monitoring. The recently approved oral direct thrombin inhibitor dabigatran, along with the emerging oral anti-factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have been developed to address many of the shortcomings of warfarin therapy. As warfarin is associated with extensive food and drug interactions, there is also a need to consider such interactions with the new oral anticoagulants. While to date few drug and dietary interactions have been reported with the new oral anticoagulants, it is still early in their development and clinical use cycle. Pharmacokinetic and pharmacodynamic profiles will have to be closely accounted for when determining the likelihood of a potential drug interaction prior to therapy initiation. As the list of drugs and supplements that interact with warfarin is continuously expanding, and the knowledge on drug interactions with the novel oral anticoagulants is still in its infancy, clinicians need to be vigilant when initiating any of these agents or when any changes in the patient's medication profile occur and perform a close screening for potential drug and dietary interactions. The objective of this paper is to give an update on drug and dietary interactions with warfarin and the novel oral anticoagulants, dabigatran, rivaroxaban, apixaban, and edoxaban.
Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; e.g., warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (e.g., those with renal impairment) and other specific clinical situations.
Smythe, Maureen A; Priziola, Jennifer; Dobesh, Paul P; Wirth, Diane; Cuker, Adam; Wittkowsky, Ann K
Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.
Cundiff, David Keith
Context I coauthored a published review of anticoagulation for venous thromboembolism in the Cochrane Database of Systematic Reviews and published a review on the same topic in MedGenMed (now the Medscape Journal of Medicine). In contrast to the article in Medscape, the discussion and conclusions in the Cochrane review were altered appreciably during the review process. Consequently, I decided to critique all anticoagulation drug-related reviews and protocols in the Cochrane database with feedback letters concerning any issues of potential controversy. Evidence Acquisition Using key words in the search engine of the Cochrane Reviews, I located reviews and protocols involving anticoagulant drugs. I critiqued each anticoagulation review and protocol and sent a total of 57 feedback letters to Cochrane concerning each publication to elicit a response/rebuttal from the authors. Evidence Synthesis Cochrane anticoagulation review editors acknowledged receipt of all letters. As of 12 months after receipt of my last letter, the Cochrane authors have replied to 13 of the 57 and agreed with many of my points. Two protocols were withdrawn after my feedback letters were acknowledged. The 58 Cochrane anticoagulation drug reviews, including mine, contained 9 categories of methodological errors (207 total instances) and 4 types of biases (18 total instances). This review of those Cochrane reviews suggests that the effectiveness of anticoagulants for 30 medical indications is questionable. Conclusions The efficacy of anticoagulants for treatment and prophylaxis for 30 current medical indications should be reconsidered by the scientific community and medical regulatory agencies. At least 50,000 people per year worldwide have fatal bleeding due to anticoagulant treatment or prophylaxis for these indications. PMID:19295926
Douketis, James D.; Spyropoulos, Alex C.; Kaatz, Scott; Becker, Richard C.; Caprini, Joseph A.; Dunn, Andrew S.; Garcia, David A.; Jacobson, Alan; Jaffer, Amir K.; Kong, David F.; Schulman, Sam; Turpie, Alexander G.G.; Hasselblad, Vic; Ortel, Thomas L.
BACKGROUND It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], −0.6 to 0.8; P = 0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P = 0.005 for superiority). CONCLUSIONS In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to
Esophagic Intramural Hematoma is an uncommon clinical condition, with a prognosis which is essentially benign. On most cases, a predisposing or precipitating factor may be seen, with the most common ones being the history of esophagic instrumentation, food impactations and thrombocytopenia. In the following manuscript, the authors present the case of a 54-years-old male with history of valve replacement surgery, who was treated at the Clinica Cardiovascular (Medellin, Colombia), with a clinical case of Intramural Esophagic Hematoma that was later confirmed to be due to a Coumarinic overanticoagulation. On this case, it is evidenced that Intramural Esophagic Hematoma is an unrecognized complication of Courmarinic anticoagulation therapy. PMID:20069068
Zeus, Tobias; Kelm, Malte; Bode, Christoph
Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding.
Rentea, Rebecca M.; Fehring, Charles H.
Causes of colonic and recto-sigmoid hematomas are multifactorial. Patients can present with a combination of dropping hemoglobin, bowel obstruction and perforation. Computed tomography imaging can provide clues to a diagnosis of intramural hematoma. We present a case of rectal hematoma and a review of current management literature. A 72-year-old male on therapeutic anticoagulation for a pulmonary embolism, was administered an enema resulting in severe abdominal pain unresponsive to blood transfusion. A sigmoid colectomy with end colostomy was performed. Although rare, colonic and recto-sigmoid hematomas should be considered as a possible diagnosis for adults with abdominal pain on anticoagulant therapy. PMID:28108634
Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu
Abstract The purpose of this study was to perform a meta-analysis comparing the effectiveness and safety of anticoagulation to antiplatelet therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published through May 31, 2014. Randomized controlled trials comparing anticoagulants (warfarin) and antiplatelet therapy in patients with AF were included. The primary outcomes were the rates of stroke and systemic embolism. Secondary outcomes included the rates of hemorrhage/major bleeding and death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Nine reports of 8 trials that enrolled 4363 patients (2169 patients received anticoagulation and 2194 antiplatelet therapy) were included. All of the studies compared adjusted-dose warfarin or with aspirin, and the majority of the patients were >70 years of age. Anticoagulants were titrated to an international normalized ratio (INR) of 2.0 to 4.5, and aspirin was administered at a dosage of 75 to 325 mg/d. Death occurred in 206 participants treated with an anticoagulant and 229 participants treated with antiplatelet therapy. There was no significant difference in the overall stroke rate between the groups (OR = 0.667, 95% CI 0.426–1.045, P = 0.08); however, patients with nonrheumatic AF (NRAF) treated with an anticoagulant had a lower risk of stroke (OR = 0.557, 95% CI 0.411–0.753, P < 0.001). Anticoagulants were associated with a lower risk of embolism (OR = 0.616, 95% CI = 0.392–0.966, P = 0.04), and this finding persisted in patients with NRAF (OR = 0.581, 95% CI 0.359–0.941, P = 0.03). No significant difference in the rate of hemorrhage/major bleeding was noted (OR = 1.497, 95% CI 0.730–3.070, P = 0.27), and this finding persisted on subgroup analysis. Anticoagulants appear to be more effective than aspirin in preventing
Koenig-Oberhuber, V; Filipovic, M
In our daily anaesthetic practice, we are confronted with an increasing number of patients treated with either antiplatelet or anticoagulant agents. During the last decade, changes have occurred that make the handling of antithrombotic medication a challenging part of anaesthetic perioperative management. In this review, the authors discuss the most important antiplatelet and anticoagulant drugs, the perioperative management, the handling of bleeding complications, and the interpretation of some laboratory analyses related to these agents.
Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo
Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies. PMID:23674896
Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo
Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies.
Mattle, H; Kohler, S; Huber, P; Rohner, M; Steinsiepe, K F
From January 1981 to June 1986 116 patients with anticoagulation-related intracranial haemorrhage were referred to hospital. Seventy six of these haemorrhages were extracerebral, 69 were in the subdural and seven in the subarachnoid space. No epidural haemorrhages were identified. Compared with non-anticoagulation-related haematomas, the risk of haemorrhage was calculated to be increased fourfold in men and thirteenfold in women. An acute subdural haematoma, mostly due to contusion, was more frequently accompanied by an additional intracerebral haematoma than a chronic subdural haematoma. Trauma was a more important factor in acute subdural haematomas than in chronic. Almost half of the patients (48%) had a history of hypertension, more than a third (35%) had heart disease and about one fifth (18%) were diabetic. Headache was the most frequent initial symptom. Later decreased level of consciousness and focal neurological signs exceeded the frequency of headache. Three patients with subarachnoid haemorrhage and nine patients with acute subdural haematomas died, while those with chronic subdural haematomas all survived and had at the most mild, non-disabling sequelae. Myocardial infarction (22%), pulmonary embolism (20%), and arterial disease (20%) were the most frequent reasons for anticoagulant treatment. Critical review based on established criteria for anticoagulation treatment suggests there was no medical reason to treat a third of these patients. The single most useful measure that could be taken to reduce the risk of anticoagulation-induced intracranial haemorrhage would be to identify patients who are being unnecessarily treated and to discontinue anticoagulants. PMID:2769275
Murray, Maureen; Tseng, Florina
Anticoagulant rodenticides inhibit the activation of vitamin K-ependent clotting factors, resulting in fatal hemorrhage. Nontarget species are exposed to these rodenticides primarily by direct consumption of baits or secondarily by consumption of poisoned prey. The diagnosis of anticoagulant rodenticide toxicosis is more challenging in birds than in mammals because of the limited availability of laboratory tests to evaluate avian coagulation. In addition, the presenting signs in birds may differ from those commonly seen in mammals. Treatment for acute blood loss and therapy with vitamin K1 can result in a favorable outcome in birds. This report describes the presenting signs, diagnosis, and successful treatment of a red-tailed hawk (Buteo jamaicensis) with secondary anticoagulant rodenticide toxicosis.
Mező, Erika; Eszenyi, Dániel; Varga, Eszter; Herczeg, Mihály; Borbás, Anikó
Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we elaborated a modular pathway to obtain a series of idraparinux-analogue pentasaccharides bearing one or two primary sulfonic acid moieties. Five protected pentasaccharides with different C-sulfonation patterns were prepared by two subsequent glycosylation reactions, respectively, using two monosaccharide and four disaccharide building blocks. Transformation of the protected derivatives into the fully O-sulfated, O-methylated sulfonic acid end-products was also studied.
Fanikos, John; Fiumara, Karen; Baroletti, Steve; Luppi, Carol; Saniuk, Catherine; Mehta, Amar; Silverman, Jon; Goldhaber, Samuel Z
This study reviewed 863 alerts generated from the infusion of anticoagulants in 355 patients from October 2003 to January 2005. Alerts were generated by smart infusion technology pumps and recorded in the devices' memory. The most common alerts were underdose alerts (59.8%), followed by overdose alerts (31.3%) and duplicate drug therapy alerts (8.9%). In response to the alerts, users' most frequent action was to cancel (46.5%) or reprogram (43.1%) the infusions. The highest percentage of alerts occurred from 2 to 4 p.m. During the study, there were 4 infusion rate errors, compared with 15 in the immediately preceding 16-month period. In conclusion, smart infusion technology intercepted keypad entry errors, thereby reducing the likelihood of intravenous anticoagulant overdose or underdose. Dose or infusion rate programming during intravenous anticoagulation is an important targets for medication safety interventions.
Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms. PMID:27413710
De Vos, J; Hombrouckx, R
Several patients with heparin intolerance were dialysed with tri-sodium citrate as anticoagulant without acute clinical problems (good tolerance). After some weeks however problems arose. In all patients an alkalosis developed: the pre dialysis bicarbonate level rose progressively from 27 mmol/l to 40 mmol/l. This could be tempered by lowering the dialysis fluid bicarbonate concentration from 37 mmol/l to 25 mmol/l. A second problem was a progressive rise in pre dialysis sodium level from a mean of 136 mmol/l to 150 mmol/l. Adapting the dialysis fluid sodium concentration from 140 mmol/l towards 132 mmol/l could solve this. The third problem was a progressive rise in serum aluminium level in patients from 3 microg/l to 38 microg/l. After excluding water, concentrate, dialysis fluid, drug intake, etc... as possible sources, we controlled the aluminium level in the glass bottle containing tri-sodium citrate. We noted the very high value of 35,300 microg/l. After replacing the glass bottles with polyvinylchloride bags with a negligible aluminium content, the serum aluminium levels returned back to normal. It is known that citrate chelates the aluminium present in the glass of bottles or vials.
The dynamic evolution of therapeutic options including the use of vitamin K antagonists (VKA), non-vitamin K oral anticoagulants (NOAC), more potent antiplatelet drugs as well as new generation drug-eluting stents could lead to the view that the current recommendations on the management of patients with percutaneous coronary intervention (PCI) requiring oral anticoagulation do not keep up with the results of several clinical studies published within the last 5 years. In the present overview, we summarize the recent advances in antithrombotic management used in atrial fibrillation patients undergoing PCI for stable coronary artery disease or acute coronary syndrome (ACS). The safety and efficacy of prasugrel and ticagrelor taken with oral anticoagulants also remain to be established in randomized trials; therefore the P2Y12 inhibitor clopidogrel on top of aspirin or without is now recommended to be used together with a VKA or NOAC. It is still unclear which dose of a NOAC in combination with antiplatelet agents and different stents should be used in this clinical setting and whether indeed NOAC are safer compared with VKA in such cardiovascular patients. Moreover, we discuss the use of anticoagulation in addition to antiplatelet therapy for secondary prevention in patients with ACS. To minimize bleeding risk in anticoagulated patients following PCI or ACS, the right agent should be prescribed to the right patient at the right dose and supported by regular clinical evaluation and laboratory testing, especially assessment of renal function when a NOAC is used. PMID:27980542
Norris, John W
There are no reliable data from randomised trials to decide whether anticoagulants or antiplatelet agents are better to prevent further thromboembolic events after cervical arterial dissection. Most neurologists favour anticoagulants based on the underlying pathology and the likely course of acute post-dissection thromboembolism.
Hellfritzsch, Maja; Husted, Steen Elkjaer; Grove, Erik Lerkevang; Rasmussen, Lotte; Poulsen, Birgitte Klindt; Johnsen, Søren Paaske; Hallas, Jesper; Pottegård, Anton
Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non-VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49.9%) and one-third had previously used VKA. Within 1 year, 10.1% switched to VKA, 4.8% switched to another NOAC and 14.4% discontinued treatment. The frequencies of switching to VKA and discontinuation were highest among NOAC users of young age (<55 years) and with low CHA2 DS2 -VASc score (=0). However, the majority of patients (87.3%) stopping NOAC treatment had a CHA2 DS2 -VASc score ≥1. We conclude that switching from VKA to NOAC, and to a lesser extent from NOAC to VKA, is common, as is early treatment discontinuation. The majority of treatment changes are observed in patients at increased risk of stroke. More research is warranted on the risks of bleeding and thromboembolism associated with switching and discontinuation of NOACs as well as the underlying reasons why these treatment changes occur.
Hankey, Graeme J
This review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and stroke prevention in atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In patients prescribed a NOAC, can the anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can "cut-off points" between which anticoagulation is therapeutic (i.e. the "therapeutic range") be defined? 2. In patients who are taking a NOAC and bleeding (e.g. intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can NOAC-associated bleeding and complications be minimised and patient outcome improved? 3. In patients taking a NOAC who experience an acute ischaemic stroke, to what degree of anticoagulation or plasma concentration of NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a NOAC (or warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have atrial fibrillation and are at high risk of stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is there a dose or dosing regimen for each NOAC that is as effective and safe as adjusted-dose warfarin for patients with atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?
Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE). For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. PMID:27217793
Hauguel, M; Boelle, Py; Pichereau, C; Bourcier, S; Bigé, N; Baudel, JL; Maury, E; Guidet, B; Ait-Oufella, H
Abstract Bleeding is the most frequent complication of anticoagulant therapy, responsible for a number of hospitalizations or deaths. However, studies describing the management and prognosis factors of extra-cerebral anticoagulant-related bleedings in intensive care unit (ICU) are lacking. Retrospective observational study in an 18-bed ICU in a tertiary teaching hospital. From January 2000 to December 2013, all consecutive patients, older than 18 years, admitted for severe anticoagulant-related bleeding (SAB) except intracerebral site were included. A total of 100 patients were included, the mean age was 77 ± 11 years and 62% were women. SAB incidence in ICU doubled over 10 years (P = 0.03). In ICU, the average length of stay was 5 ± 6 days and mortality was 30%. Nonsurviving patients had a higher SAPS II (78 ± 24 vs 53 ± 24, P < 0.0001), a higher SOFA (9.0 ± 3.6 vs 4.7 ± 3.4, P < 0.0001) and received more frequently support therapy such as mechanical ventilation (87% vs 16%, P < 0.0001) and vasopressors (90% vs 27%, P < 0.0001). The volume of blood-derived products transfused was more important in nonsurvivors mainly during the first 24 hours of resuscitation. Rapid anticoagulant reversal therapy was associated with better prognosis (ICU survivors 66% vs 39%, Fisher test P = 0.04). Anterior abdominal wall was identified as a frequent site of bleeding (22%) due to epigastric artery injury during subcutaneous injection of heparin and was associated with a large mortality (55%). Extra-cerebral SAB is a life-threatening complication that requires rapid resuscitation and anticoagulant reversal therapy. Injection of heparin should be done carefully in the subcutaneous tissue thereby avoiding artery injury. PMID:26632750
Peterson, Eric D.; Kim, Sunghee; Thomas, Laine; Gersh, Bernard J.; Fonarow, Gregg C.; Kowey, Peter R.; Mahaffey, Kenneth W.; Sherwood, Matthew W.; Chang, Paul; Piccini, Jonathan P.; Ansell, Jack
Background— Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. Methods and Results— The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P=0.0003) and mechanical valve replacements (9.6% versus 2.4%; P<0.0001); however, there was no difference in CHA2DS2-VASc scores (scores ≥2 in 94% versus 95%; P=0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P<0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P=0.0001). Conclusions— Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning
Dézsi, Csaba András; Dézsi, Balázs Bence; Dézsi, Döme András
Coronary artery disease coexists in a clinically relevant number of patients with atrial fibrillation and it often requires percutaneous coronary intervention. These patients represent a particular challenge for clinicians in terms of antithrombotic management. They require combined antiplatelet-anticoagulant therapy to reduce the risk of recurrent ischemic cardiac events and stroke; however, this antithrombotic strategy is associated with an increased risk of bleeding complications. In the absence of randomized, controlled clinical trials, the majority of current recommendations rely on the results of cohort studies, meta-analyses, post-hoc analyses and subgroup analyses of large, phase III studies. Based on the available evidence, the present review discusses the optimal antithrombotic strategy for patients receiving chronic anticoagulant therapy due to atrial fibrillation who require antiplatelet treatment after acute coronary syndrome and/or percutaneous coronary intervention, and discusses the issue of dental procedures. The correct planning of therapy significantly reduces the risk of bleeding complications and thromboembolic events.
Lutz, Jens; Jurk, Kerstin
Progressive impairment of renal function can lead to uremia, which is associated with thus increasing the risk of bleeding as well as thrombosis. Furthermore, many patients with chronic kidney disease (CKD) have an indication for an anticoagulation or antiplatelet therapy due to atrial fibrillation, coronary artery disease, thromboembolic disease, or peripheral artery disease. The treatment usually includes vitamin-K antagonists (VKAs) and/or platelet aggregation inhibitors. The direct oral anticoagulants (DOACs) inhibiting factor Xa or thrombin activity represent an alternative for heparins and VKAs. However, DOACs can further aggravate the bleeding risk in CKD patients. This is related to a combination of an accumulation of the substance due to the reduced renal clearance, an inhibition of thrombin-mediated platelet activation, and uremia associated factors such as impaired coagulation, platelet function, and platelet-vessel wall. Furthermore, platelet aggregation inhibitors can also influence the bleeding risk, particularly if they are administered in combination with anticoagulants in patients with advanced CKD. In this review we discuss the different mechanisms leading to the increased risk of bleeding and thrombosis as well as the different options and problems related to an antiplatelet or anticoagulation therapy in CKD patients.
Mega, Jessica L; Simon, Tabassome
Antithrombotic drugs, which include antiplatelet and anticoagulant therapies, prevent and treat many cardiovascular disorders and, as such, are some of the most commonly prescribed drugs worldwide. The first drugs designed to inhibit platelets or coagulation factors, such as the antiplatelet clopidogrel and the anticoagulant warfarin, significantly reduced the risk of thrombotic events at the cost of increased bleeding in patients. However, both clopidogrel and warfarin have some pharmacological limitations including interpatient variability in antithrombotic effects in part due to the metabolism, interactions (eg, drug, environment, and genetic), or targets of the drugs. Increased knowledge of the pharmacology of antithrombotic drugs and the mechanisms underlying thrombosis has led to the development of newer drugs with faster onset of action, fewer interactions, and less interpatient variability in their antithrombotic effects than previous antithrombotic drugs. Treatment options now include the next-generation antiplatelet drugs prasugrel and ticagrelor, and, in terms of anticoagulants, inhibitors that directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, edoxaban) are available. In this Series paper we review the pharmacological properties of these most commonly used oral antithrombotic drugs, and explore the development of antiplatelet and anticoagulant therapies.
Wittkowsky, Ann K; Nutescu, Edith A; Devine, Emily Beth
Anticoagulation clinics are increasingly used to manage oral anticoagulant therapy in patients with venous thromboembolic disease (VTE). Such clinics may be in a position to assume greater responsibility for other aspects of the long-term management of VTE, including prevention of post-thrombotic syndrome (PTS). Current guidelines suggest use of graduated elastic compression stockings with a pressure of 30-40 mm Hg at the ankle for 2 years following the diagnosis of deep vein thrombosis (DVT) to prevent PTS. A survey of anticoagulation clinic providers was conducted to determine to what extent patients with DVT are prescribed compression stockings and by whom, and the degree of compression and duration of therapy prescribed. Survey results show a very low rate of use of compression stockings in patients with DVT, and limited adherence to current recommendations for strength and duration of use. We believe that healthcare providers practicing in anticoagulation clinics should be encouraged to expand their scope of practice into a more comprehensive model of antithrombosis care, including prevention of PTS. By doing so, the extent of use of compression stockings might be increased, and adherence to current guidelines for strength and duration of compression might be improved.
Pereira, Claudio Maranhão; Gasparetto, Patrícia Freire; Carneiro, Danilo Santos; Corrêa, Maria Elvira P.; Souza, Cármino Antônio
Introduction. Dental treatment performed in patients receiving continuous oral anticoagulant drug therapy is becoming increasingly common in dental offices. For these patients it is imperative to carry out careful anamnesis, as well as a multiprofessional clinical evaluation with regard to the risk and control of hemorrhagic or thromboembolic episodes. Objectives and Material and Methods. The aim is to evaluate postextraction hemorrhagic or thromboembolic episodes in patients who have been on anticoagulant medications for an uninterrupted period of 48 months. Results. Among the 108 patients evaluated, 215 extractions were performed in which there was only one case of postoperative bleeding. Warfarin was used by 98 patients; Warfarin associated with salicylic acetic acid by 9 patients and salicylic acetic acid in only 1 patient. As regards the serologic tests performed, International Normalized Ratio (INR) ranged from 0.8 to 4.9, with a mean of 3.15. Conclusion. Extractions in patients on oral anticoagulants must be performed in the least traumatic manner possible. It is not necessary to stop anticoagulant therapy to perform extractions. Local hemostasis techniques, such as obliterative sutures alone are sufficient to prevent hemorrhagic complications. PMID:21991458
Ezekowitz, Michael D; Spahr, Judy; Ghosh, Pradeepto; Corelli, Kathryn
Anticoagulation for stroke prevention in atrial fibrillation (AF) is effective. Pivotal trials RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE-AF TIMI 48 tested novel agents against warfarin (W). In RE-LY, an open-label trial, dabigatran 150 mg BID (D150) was superior (35%) and 110 mg BID (D110) was noninferior to W. D150 reduced ischemic strokes by 25% and intracerebral bleeds by 74%, but increased major GI bleeds by 0.5 % per year. In ROCKET AF, a double-blind study, rivaroxaban 20 mg daily, downtitrated to 15 mg daily (if CrCl was <49) was noninferior for efficacy and safety, with an increase in GI bleeds. In ARISTOTLE, a double-blind study, apixaban 5 mg BID (downtitrated to 2.5 mg BID if two of the following were present: age, >80; weight, <60 kg; or serum creatinine, >1.5 mg) was superior for safety (31%), efficacy (21%), and all-cause mortality (11%). In ENGAGE-AF TIMI 48, edoxaban 60 mg once daily (30 mg once daily if CrCl 30-50 ml/min, weight <60 kg, or concomitant verapamil or quinidine) was noninferior to W for efficacy, but reduced major bleeding (20%). To translate clinical trials to practice, understanding the disease and each anticoagulant is essential. For all novel agents, rapid anticoagulation, absence of monitoring, and a short half-life differentiate them from W. Bleed rates were either noninferior or lower than for W, without an antidote. Patient compliance is critical. Knowledge of renal function is essential and maintaining patients on therapy is key.
Sawicka-Powierza, Jolanta; Rogowska-Szadkowska, Dorota; Ołtarzewska, Alicja Małgorzata; Chlabicz, Sławomir
Oral anticoagulants (OAC) are commonly used as a life-long therapy in prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease and prosthetic hart valves and in the primary and secondary prevention of venous thromboembolism. They are also used for the prevention of thromboembolic events in patients with acute myocardial infarction and with angina pectoris, in patients with biological hart valves and after some types of orthopaedics surgery. The International Normalized Ratio (INR) is used to evaluate the efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic complications increases when the INR is out of the therapeutic range. The aim of this study was to present information about the factors influencing activity of oral anticoagulants and interactions between oral anticoagulants and drugs or food. The effect of oral anticoagulants is influenced by genetic and environmental factors such as: medicines, food, diseases and pre-existing conditions. A common mutation in the gene coding for the cytochrome P450 (CYP2C9), with one or more combinations of its polymorphisms, is responsible for the reduced warfarin requirements or for the resistance to warfarin. A mutation in the factor IX is responsible for the risk of bleeding during OAC therapy without excessive prolongation of the prothrombin time (PT). Drugs, herbs and multivitamin supplements can alter the absorption, pharmacokinetics or pharmakodynamics of OAC. Nonsteroid anti-inflammatory drugs and paracetamol in combination with OAC seem to be the most dangerous because they are available without prescription and are used without medical consultation. Patients on OAC therapy are sensitive to changing dietary intake of vitamin K, which is supplied from phylloquinones in plants or from vitamin K-containing medicines. The effect of OAC can be influenced by other existing factors like: fever, diarrhoea, alcohol abuse or physical hyperactivity. Some malignancies
Kovacs, Ferenc; Varga, Marina; Pataki, Zsolt; Rigo, Erzsebet
The knowledge of pseudothrombocytopenia (PTCP) is important for the accuracy of a clinical assessment and for avoiding unnecessary treatment. An elderly patient was hospitalized with left lung pneumonia. Severe thrombocytopenia [platelet (PLT) number: 18 × 109/L] without any clinical bleeding was found in ethylenediaminetetraacetic acid blood collection tube. PLT measurement was repeated in various anticoagulant [sodium citrate, lithium heparin, disodium oxalate, hirudin, and magnesium sulfate (Mg-sulfate)] sample collection tubes and all of them showed thrombocytopenia except with Mg-sulfate. To the best of our knowledge, PTCP with five anticoagulant sample collection tubes has not been reported earlier. PMID:28180009
Altman, R; Rouvier, J; Gurfinkel, E
For preventing thromboembolic events, the concurrent use of oral anticoagulant and antiplatelet drugs has been proposed. In prosthetic heart valves the use of moderate intensity anticoagulants [International Normalized Ratio (INR) 2-3] plus aspirin (100 mg/day) decreases the amount and severity of embolic episodes. The possibility that the same regimen could provide benefit in the prevention of thrombotic events in other arterial diseases is also indicated by the ATACS trial in unstable angina. The ongoing studies in ischemic heart diseases will also give the answer to this possibility.
Dashti-Khavidaki, Simin; Ghaffari, Saba; Nassiri-Toossi, Mohsen; Amini, Mohsen; Edalatifard, Maryam
Superwarfarin toxicity may be a serious problem. It needs high clinical suspicious in patients with bleeding diathesis without hematologic or liver diseases even in patients with apparent negative history of warfarin or other anticoagulant accessibility. Here we reported a patient with a negative history of any medical diseases or drug administration who was referred with generalized ecchymosis. Increased international normalized ratio and decreased vitamin K-dependent coagulation factors were detected in this patient. His hematologic and liver evaluations were normal. Clinical pharmacist emphasis in taking history revealed using anticoagulant rodenticide all over the farm the patient lived in that might result in unaware intoxication in this patient who suffered dementia. PMID:25535623
Lowry, Adam W; Moffett, Brady S; Moodie, Douglas; Knudson, Jarrod D
Management of warfarin in pediatric patients remains a clinical challenge. Warfarin may be administered after congenital heart surgery, and the risks of morbidity can be high. Currently, no data exist to describe the initiation of warfarin and the risk factors for morbidity in post-congenital heart surgery patients. This study aimed to characterize the time required to reach anticoagulation for patients administered warfarin therapy after cardiac surgery and to identify and characterize the risk factors for supratherapeutic anticoagulation and adverse events after warfarin initiation. This retrospective study reviewed all patients between 2006 and 2011 who received warfarin anticoagulation after cardiac surgery at our institution. Factors associated with a prolonged time required to reach an international normalized ratio (INR) of 2 and factors related to supratherapeutic anticoagulation (INR ≥ 4) were identified. The inclusion criteria were met by 59 patients. The median time required to reach an INR of at least 2 after initiation of warfarin was 2 days (interquartile range (IQR), 2-4). The only groups that required a significantly longer time to reach an INR of 2 were those with a postoperative delay in initiation of warfarin and those receiving heparin anticoagulation before and during warfarin initiation. Nine patients experienced an INR of 4 or more. However, no thrombotic events occurred, and significant bleeding was uncommon. In the largest reported group of patients undergoing anticoagulation after cardiac surgery, warfarin was well tolerated across all age groups. The median time required to reach an INR of 2 after loading with warfarin was 2 days, and adverse events were uncommon.
Gulba, D C; Broscaru, L
Since first used in 2009, non-vitamin K oral anticoagulants (NOAC) have gained world-wide acceptance. Two groups of NOAC are currently used: the direct thrombin antagonist dabigatran and three direct factor Xa antagonists apixaban, edoxaban, and ricaroxaban. With their increasing use for prevention of thromboembolism, the probability increases that NOAC-pretreated patients are admitted to emergency departments or intensive care units.The clinical challenge in NOAC preanticoagulated patients is to adequately cope with the given anticoagulated status of such patients. Because of their short half-life, many patients will be adequately treated with a "wait and see" approach, and surgeries and interventions are postponed until anticoagulant activities have totally subsided. In the few cases where immediate action is mandated, based on appropriate risk assessments it can be decided either to take the increased hemorrhagic risk of early intervention or to transfuse factor concentrates like PPSB or FEIBA which can safely reverse the anticoagulant activities of the three factor Xa antagonists (and potentially also of dabigatran). Recently a humanized Fab antibody fragment for dabigatran, idarucizumab, has been introduced onto the market, that can immediately reverse the anticoagulant effects of dabigatran. For the reversal of dabigatran, idarucizumab is therefore the drug of choice.In addition, in some specific indications of emergency and intensive care medicine, the primary use of a NOAC can be considered advantageous. Such indications are early cardioversion in patients admitted for new episodes of atrial fibrillation and patients with acute pulmonary embolism. For the widespread use of low-molecular-weight heparins in such indications, however, the decision to use a NOAC for anticoagulant therapy is frequently postponed to the treatment phase when the stabilized patient is already treated on the general ward.
Noble, Simon; Matzdorff, Axel; Maraveyas, Anthony; Holm, Majbrit V; Pisa, Giovanni
Low molecular weight heparins have demonstrated superiority over coumarins in the extended treatment of cancer-associated thrombosis and are recommended as first-line therapy in clinical guidelines. Non-vitamin K oral antagonists are yet to be evaluated against low molecular weight heparin for this indication. Nevertheless, a perception that patients favor oral anticoagulants over injections may lead to an increased prescribing of warfarin or non-vitamin K oral antagonists despite the evidence gap. There has been no evaluation of cancer patient preferences for anticoagulants and whether such an evidence gap is an acceptable trade-off for patients prescribed orals. We conducted a study to assess what features are most important to CAT patients regarding their choice of anticoagulant. Two modules were applied: Initial in-depth interviews with 9 patients diagnosed with cancer-associated thrombosis, and thereafter quantitative research, where a further 100 patients completed a choice-based-conjoint exercise, where 15 different scenarios were presented to identify the most important attributes of an anticoagulant. Seventy percent of the patients were treated with injected medication (low molecular weight heparin) and 30% with oral medications. Patients most valued an anticoagulant with minimal interference with their cancer treatment (39%), low thrombosis recurrence rate (24%), and low risk of major bleed (19%). Preference for oral administration over injection had moderate importance (13%). The results show that patients prefer an anticoagulant that does not interfere with their cancer treatment, suggesting the primacy of the cancer disease over venous thromboembolism in these patients. Patients also favor efficacy and safety over convenience of route of administration.
Nuttall, Marc T; Rodgers, George M
Many patients with underlying cardiovascular disease require long-term anticoagulation. The perioperative or periprocedural management of patients who require temporary interruption of anticoagulant or antiplatelet medications is a common and often challenging clinical problem. It requires a fine balance between the risk of thromboembolic events during anticoagulant interruption and the risk of bleeding in the setting of antithrombotic therapy administered around the time of surgery. Interruption of anticoagulation is associated with an increased risk of thromboembolic events. Stratifying patients into thromboembolic risk groups may be helpful in directing anticoagulation management in the perioperative setting. Bridging anticoagulation, generally with low-molecular-weight heparin (LMWH), is often an integral part of perioperative thrombosis risk reduction. Perioperative anticoagulation management varies depending on the indication for anticoagulation and the anticoagulant or antiplatelet agent being used by the patient. In this article, we review some of the general principles involved with perioperative anticoagulation and discuss the perioperative management of patients taking vitamin K antagonists (VKAs), bridging regimens for anticoagulants and antiplatelet agents, and strategies for managing patients on the newer oral anticoagulants.
Huber, Kurt; Bates, Eric R; Valgimigli, Marco; Wallentin, Lars; Kristensen, Steen Dalby; Anderson, Jeffrey L; Lopez Sendon, Jose Luis; Tubaro, Marco; Granger, Christopher B; Bode, Christoph; Ohman, Erik Magnus; Steg, Philippe Gabriel
Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.
Woods, Erin A; Ackman, Margaret L; Graham, Michelle M; Koshman, Sheri L; Boswell, Rosaleen M; Barry, Arden R
Background: Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. Objective: To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. Methods: A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. Results: Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA
Prisco, Domenico; Cenci, Caterina; Silvestri, Elena; Ciucciarelli, Lucia; Di Minno, Giovanni
Atrial fibrillation is the most common rhythm disorder and represents a major public health problem because it carries an increased risk of arterial thromboembolism and ischemic stroke. Current european society of cardiology guidelines recommend to stratify atrial fibrillation patients according to the CHA2DS2-VASc score and to administer anticoagulation, preferably with novel oral anticoagulants, that is, dabigatran, rivaroxaban, or apixaban, if the CHA2DS2-VASc score is at least 1. All novel anticoagulants have shown the same, if not greater, efficacy and safety as warfarin, with some advantages. The choice among the novel oral anticoagulants depends on their different pharmacokinetic profile, patients' stroke and bleeding risk, comorbidities, drug tolerability and costs and, finally, patients' preferences.
Rodger, Marc A
Thrombophilias are not yet established as a cause of the placenta-mediated pregnancy complications (pregnancy loss, pre-eclampsia, small for gestational age and placental abruption). A thrombophilia may be only one of many factors that lead to development of these complications. Our recent large systematic review of prospective cohort studies highlight that the association between thrombophilia and placenta mediated pregnancy complications is far from proven. The small step of previously describing an association in case control studies has led a large number of clinicians and opinion leaders to take the large leap of accepting this relationship as being causal and potentially treatable with anticoagulant interventions. Furthermore, while data in women with prior severe pre-eclpamsia, abruption and small for gestational age births without thrombophilia suggests some promise for anticoagulant prophylaxis to prevent complications in subsequent pregnancies in these women, in the absence of large well done and generalisable "no intervention" controlled studies adopting anticoagulant prophylaxis to prevent these complications is premature. The absence of strong evidence, coupled with the small potential for harm from anticoagulant prophylaxis suggests that these drugs should be considered experimental in thrombophilic and non-thrombophilic women with prior placenta mediated pregnancy complications.
Ku, Sae-Kwang; Kim, Tae Hoon; Bae, Jong-Sup
Persicarin and isorhamnetin were isolated from Oenanthe javanica and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). In addition, the effects of persicarin and isorhamnetin on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). The data obtained showed that persicarin and isorhamnetin both prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. In addition, they both inhibited the generations of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, persicarin and isorhamnetin prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by persicarin. Interestingly, the anticoagulant and profibrinolytic effects of persicarin were greater than those of isorhamnetin, which suggest that the sulfonate group of persicarin positively regulates its anticoagulatory function. Accordingly, our results suggest that persicarin and isorhamnetin possess antithrombotic activities and that they could provide bases for the development of new anticoagulant agents.
Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla
The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo.
Rojas-Hernandez, Cristhiam M; Oo, Thein Hlaing; García-Perdomo, Herney Andrés
Intracranial hemorrhage (ICH) in cancer patients can result from tumor bleeding and from antitumor and anticoagulation therapy. The effect of anticoagulation on the incidence of ICH in cancer patients has not been quantified. Our objective was to determine the risk of intracranial hemorrhage associated with anticoagulation therapy for cancer-associated venous thromboembolism (VTE). Systematic review and meta-analysis of studies assessing the safety of anticoagulation therapy in patients with cancer-associated VTE. The primary endpoint of interest was the incidence of ICH and secondary outcomes included all major bleeding, and the time to ICH and major bleeding. After identifying 595 studies, five studies and 2089 patients were included in the analyses. We found that the relative risk (RR) for ICH was 0.494, 95 % CI (0.105-2.331) when low molecular weight heparin (LMWH) with vitamin K antagonist (VKA) anticoagulants were compared. No statistically significant differences in risk were measured. The risk of major bleeding using any type of anticoagulation therapy in patients with cancer-associated VTE was RR 0.853, 95 % CI (0.549, 1.327). After meta-analytic review of data published through August 2015, we conclude that therapeutic anticoagulation with LMWH given ≤6 months does not increase the risk of ICH in cancer patients compared to VKA. The risk of ICH in cancer patients is also similar to that of non-cancer patients. Available data were insufficient to determine if the ICH risk increase changes when the duration of anticoagulation is >6 months.
Bacci, Christian; Maglione, Michele; Favero, Lorenzo; Perini, Alessandro; Di Lenarda, Roberto; Berengo, Mario; Zanon, Ezio
Following favourable results from a previous study, a large, multicentre, prospective, case-control study was performed to further assess the incidence of bleeding complications after dental extraction in patients taking oral anticoagulant therapy (OAT). Four hundred fifty-one patients being treated with warfarin who required dental extraction were compared with a control group of 449 non-anticoagulated subjects undergoing the same procedure. In the warfarin-treated group, the oral anticoagulant regimen was maintained unchanged, such that the patients had an International Normalised Ratio ranging between 1.8 and 4, and local haemostatic measures (i.e. fibrin sponges, silk sutures and gauzes saturated with tranexamic acid) were adopted. All the procedures were performed in an outpatient setting. Seven bleeding complications occurred in the OAT group and four in the control group; the difference in the number of bleeding events between the two groups was not statistically significant (OR=1.754; 95% CI 0.510 - 6.034; p=0.3727). No post-operative late bleeds requiring hospitalisation and/or blood transfusions were recorded, and the adjunctive local haemostatic measures were adequate to stop the bleeding. The results of our protocol applied in this large, multicenter study show that dental extractions can be performed easily and safely in anticoagulated outpatients without any modification of the ongoing anticoagulant therapy, thus minimising costs and reducing discomfort for patients.
Washam, Jeffrey B; Piccini, Jonathan P
Over the past several years, non-vitamin K oral anticoagulants (NOACs) have been introduced into clinical practice for the treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Clinical trials have shown these agents to have similar or less risk of major bleeding as compared to warfarin therapy. Moreover, when patients do experience a major bleeding event administration of advanced factor products is rare, and post-bleed outcomes are similar in those receiving a NOAC compared to those receiving warfarin. However, there are situations where urgent reversal of NOAC anticoagulation would be desirable. The following review focuses on the outcomes and management strategies for patients experiencing a major bleed with warfarin or NOAC agents and describes the rationale for the development of therapies capable of targeted NOAC-reversal.
Mejak, Brian; Giacomuzzi, Carmen; Shen, Irving; Boshkov, Lynn; Ungerleider, Ross
Abstract: A patient was born with transposition of the great arteries, double-outlet right ventricle, interrupted aortic arch, and a ventricular septal defect and underwent a Damus–Kaye–Stansel procedure with a modified Blalock–Taussig shunt at 14 days old. Three months later, this patient presented with hypoxia and bradycardia was found to have a thrombus present in the main pulmonary artery extending to right pulmonary artery. After initiation of thrombolytic therapy, the patient became severely hypoxic and required the institution of extracorporeal membrane oxygenation. As the result of unknown heparin resistance independent of adequate antithrombin III levels, argatroban therapy was used to achieve desired anticoagulation. The patient was taken to the operating room and converted to conventional cardiopulmonary bypass once adequate activated clotting times were achieved using argatroban. This case report summarizes the use of argatroban as an anticoagulant for a 6.0-kg pediatric patient undergoing cardiopulmonary bypass. PMID:16350385
Newman, Peter Alexander; Deo, Sunny
We describe an unusual case of non-traumatic compartment syndrome in three compartments of the left lower limb in a 57-year-old male inpatient. He had recently been started on anticoagulation therapy for multiple pulmonary emboli and deep vein thrombosis of the left posterior tibial and peroneal veins. Three of the four osteofascial compartments had pressures above 70 mm Hg, hence four compartment fasciotomies were performed. Postoperatively, intravenous heparin therapy was started resulting in a significant blood loss, but he had no neurovascular deficit. At reoperation, for primary wound closure, his tissues looked healthy. Non-traumatic causes of acute compartment syndrome, including deep venous thrombosis and anticoagulation, are considered. PMID:24443334
Violi, Francesco; Lip, Gregory YH; Pignatelli, Pasquale; Pastori, Daniele
Abstract Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables. The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs. Data sources are MEDLINE via PubMed and Cochrane database. All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone. We performed a systematic review of the literature up to October 2015, searching for a combination of “food,” “diet,” “vitamin K,” “phylloquinone,” “warfarin,” “INR,” “coagulation,” and “anticoagulant.” Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day). Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable. The available evidence does not support current advice to modify
Alexander, Ricardo; Ferretti, Alan C; Sorensen, Jason R
Many dental patients have medical problems that require the administration of oral anticoagulants to prevent catastrophic or life-threatening thromboembolic events. Examples include patients with medical conditions such as atrial fibrillation, mechanical heart valves, recent pulmonary embolism, stroke, deep vein thrombosis, anticardiolipin syndrome and coronary artery disease. The oral anticoagulant used most commonly in these instances is Coumadin. Stopping the administration of Coumadin to perform routine dental procedures can be life threatening. Many physicians and dentists believe these patients may not have routine dental procedures, including cleanings and uncomplicated extractions, while on Coumadin for fear of serious postoperative bleeding. No scientific evidence exists to support removing these patients from Coumadin to perform routine dental procedures and uncomplicated extractions, provided the patient's level of anticoagulation is within therapeutic range. Science clearly indicates that in the case of routine dental work, including uncomplicated extractions, the risk of a patient on Coumadin having a life-threatening thromboembolic event if the anticoagulant therapy is stopped is three- to five-times greater than the risk of the patient having postoperative bleeding that cannot be controlled with local measures.
Habert, Jeffrey Steven
Many primary care physicians are wary about using direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AF). Factors such as comorbidities, concomitant medications, and alcohol misuse increase concerns over bleeding risk, especially in elderly and frail patients with AF. This article discusses strategies to minimize the risk of major bleeding events in patients with AF who may benefit from oral anticoagulant therapy for stroke prevention. The potential benefits of the DOACs compared with vitamin K antagonists, in terms of a lower risk of intracranial hemorrhage, are discussed, together with the identification of reversible risk factors for bleeding and correct dose selection of the DOACs based on a patient’s characteristics and concomitant medications. Current bleeding management strategies, including the new reversal agents for the DOACs and the prevention of bleeding during preoperative anticoagulation treatment, in addition to health care resource use associated with anticoagulation treatment and bleeding, are also discussed. Implementing a structured approach at an individual patient level will minimize the overall risk of bleeding and should increase physician confidence in using the DOACs for stroke prevention in their patients with nonvalvular AF. PMID:27785089
Cayla, Guillaume; Leclercq, Florence; Schmutz, Laurent; Cornillet, Luc; Ledermann, Bertrand; Messner, Patrick; Lattuca, Benoit
Venous thromboembolism and atrial fibrillation are two important indications of direct oral anticoagulants. Acute coronary syndrome is another potential indication of prolonged antithrombotic therapy in addition to antiplatelet therapy. Phase 2 and 3 studies were conducted with different molecules at different doses in acute coronary syndrome in addition to dual antiplatelet therapy. Studies have not shown a reduction of ischemic events for dabigatran and apixaban, but an excess of bleeding complications was observed. A reduction of ischemic events and stent thrombosis was observed with low dose of rivaroxaban taken twice a day but with an increased risk of major bleeding complications. This data was used to obtain a European marketing authorization but the positioning of the molecule remains difficult. A new study is currently being conducted to test rivaroxaban in association with a P2Y12 inhibitor without aspirin. Direct oral anticoagulants can also be used after percutaneous coronary intervention in patients requiring long-term oral anticoagulants. Dedicated studies are currently being conducted to confirm the optimal doses and the ideal association of antithrombotic drugs.
You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.
Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized
Basile, Antonio; Medina, Jose Garcia; Mundo, Elena; Medina, Vicente Garcia; Leal, Rafael
We report a case of concurrent rectus sheath and psoas hematomas in a patient undergoing anticoagulant therapy, treated by transcatheter arterial embolization (TAE) of inferior epigastric and lumbar arteries. Computed tomography (CT) demonstrated signs of active bleeding in two hematomas of the anterior and posterior abdominal walls. Transfemoral arteriogram confirmed the extravasation of contrast from the right inferior epigastric artery (RIEA). Indirect signs of bleeding were also found in a right lumbar artery (RLA). We successfully performed TAE of the feeding arteries. There have been few reports in the literature of such spontaneous hemorrhages in patients undergoing anticoagulation, successfully treated by TAE.
Alegret, Josep M.; Viñolas, Xavier; Arias, Miguel A.; Martínez-Rubio, Antoni; Rebollo, Pablo; Ràfols, Carles; Martínez-Sande, José L.
New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL. PMID:24843316
Jin, Ng Zhang; Gopinath, Subash C B
Hemostasis initiates a wound healing process and stops bleeding of blood within a damaged tissue, an important process in human and animal systems. However, this process needs to revert temporarily during surgery and analyze the clotting mechanism. In the past decade, heparin has been used widely as an anticoagulant in surgery to prevent unwanted blood clotting as it is not expensive, not difficult to control, lack of suitable replacement as well as less harmful to the human. However, heparin has several disadvantages, which include thrombocytopenia and non-specific plasma binding. Moreover, using heparin it may lead dysfunction and platelet aggregation. In this overview, potential clotting factors and anticoagulants are reviewed and special focus was given to get more insights.
Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L
In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics.
Bialkowski, Walter; Bruhn, Roberta; Edgren, Gustaf; Papanek, Paula
An estimated 2.4 million volunteer apheresis blood donation procedures were performed in the United States in 2010, and increases in the proportion of transfused blood products derived from apheresis blood collections have been consistently reported. Anticoagulation is required during apheresis and is achieved with citrate. Donor exposure to citrate causes an acute physiological response to maintain serum mineral homeostasis. Some data are available on the sequelae of this acute response in the days and weeks following exposure, raising questions about bone mineral density in regular apheresis donors. New research is emerging that addresses the potential long-term health outcomes of repeated citrate exposure. This article reviews the acute physiological response to citrate anticoagulation in volunteer blood donors, presents contrasting perspectives on the potential effects of citrate exposure on bone density, and identifies key knowledge gaps in our understanding of long-term health outcomes in apheresis donors. J. Clin. Apheresis 31:459-463, 2016. © 2015 Wiley Periodicals, Inc.
Das, Moloy; Panter, Lee; Wynn, Gareth J; Taylor, Rob M; Connor, Neil; Mills, Joseph D; Kirchhof, Paulus; Gupta, Dhiraj
Objective Stroke-risk in atrial fibrillation (AF) can be significantly reduced by appropriate thromboembolic prophylaxis. However, National Institute for Health and Care Excellence estimates suggest that up to half of eligible patients with AF are not anticoagulated, with severe consequences for stroke prevention. We aimed to determine the outcome of an innovative Primary Care AF (PCAF) service on anticoagulation uptake in a cohort of high-risk patients with AF in the UK. Methods The PCAF service is a novel cooperative pathway providing specialist resources within general practitioner (GP) practices. It utilises a four-phase protocol to identify high-risk patients with AF (CHA2DS2-VASc ≥1) who are suboptimally anticoagulated, and delivers Consultant-led anticoagulation assessment within the local GP practice. We assessed rates of anticoagulation in high-risk patients before and after PCAF service intervention, and determined compliance with newly-initiated anticoagulation at follow-up. Results The PCAF service was delivered in 56 GP practices (population 386 624; AF prevalence 2.1%) between June 2012 and June 2014. 1579 high-risk patients with AF with suboptimal anticoagulation (either not taking any anticoagulation or taking warfarin but with a low time-in-therapeutic-range) were invited for review, with 86% attending. Of 1063 eligible patients on no anticoagulation, 1020 (96%) agreed to start warfarin (459 (43%)) or a non-vitamin K antagonist oral anticoagulant (NOAC, 561 (53%)). The overall proportion of eligible patients receiving anticoagulation improved from 77% to 95% (p<0.0001). Additionally, 111/121 (92%) patients suboptimally treated with warfarin agreed to switch to a NOAC. Audit of eight practices after 195 (185–606) days showed that 90% of patients started on a new anticoagulant therapy had continued treatment. Based on data extrapolated from previous studies, around 30–35 strokes per year may have been prevented in these previously under
Chih-Wen Cheng; Hang Wu; Thompson, Pamela J; Taylor, Julie R; Zehnbauer, Barbara A; Wilson, Karlyn K; Wang, May D
Patients with certain clotting disorders or conditions have a greater risk of developing arterial or venous clots and downstream embolisms, strokes, and arterial insufficiency. These patients need prescription anticoagulant drugs to reduce the possibility of clot formation. However, historically, the clinical decision making workflow in determining the correct type and dosage of anticoagulant(s) is part science and part art. To address this problem, we developed Anticoagulation Manager, an intelligent clinical decision workflow management system on iOS-based mobile devices to help clinicians effectively choose the most appropriate and helpful follow-up clotting tests for patients with a common clotting profile. The app can provide physicians guidance to prescribe the most appropriate medication for patients in need of anticoagulant drugs. This intelligent app was jointly designed and developed by medical professionals in CDC and engineers at Georgia Tech, and will be evaluated by physicians for ease-of-use, robustness, flexibility, and scalability. Eventually, it will be deployed and shared in both physician community and developer community.
Stassens, P; Bergum, P W; Gansemans, Y; Jespers, L; Laroche, Y; Huang, S; Maki, S; Messens, J; Lauwereys, M; Cappello, M; Hotez, P J; Lasters, I; Vlasuk, G P
Hookworms are hematophagous nematodes that infect a wide range of mammalian hosts, including humans. There has been speculation for nearly a century as to the identity of the anticoagulant substances) used by these organisms to subvert host hemostasis. Using molecular cloning, we describe a family of potent small protein (75-84 amino acids) anticoagulants from the hookworm Ancylostoma caninum termed AcAP (A. caninum anticoagulant protein). Two recombinant AcAP members (AcAP5 and AcAP6) directly inhibited the catalytic activity of blood coagulation factor Xa (fXa), while a third form (AcAPc2) predominantly inhibited the catalytic activity of a complex composed of blood coagulation factor VIIa and tissue factor (fVIIa/TF). The inhibition of fVIIa/TF was by a unique mechanism that required the initial formation of a binary complex of the inhibitor with fXa at a site on the enzyme that is distinct from the catalytic center (exo-site). The sequence of AcAPc2 as well as the utilization of an exo-site on fXa distinguishes this inhibitor from the mammalian anticoagulant TFPI (tissue factor pathway inhibitor), which is functionally equivalent with respect to fXa-dependent inhibition of fIIa/TF. The relative sequence positions of the reactive site residues determined for AcAP5 with the homologous regions in AcAP6 and AcAPc2 as well as the pattern of 10 cysteine residues present in each of the inhibitors suggest that the AcAPs are distantly related to the family of small protein serine protease inhibitors found in the nonhematophagous nematode Ascaris lumbricoides var. suum.
Wiggins, Barbara S; Northup, Amanda; Johnson, Dominic; Senfield, Jeffrey
Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant
Munson, C F; Reid, A J
Novel oral anticoagulants (NOACs) have emerged as a good alternative to warfarin in the prevention of stroke for patients with atrial fibrillation. NOAC use is increasing rapidly; therefore, greater understanding of their use in the perioperative period is important for optimal care. Studies and reviews that reported on the use of NOACs were identified, with particular focus on the perioperative period. PubMed was searched for relevant articles published between January 2000 and August 2015. The inevitable rise in the use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™), edoxaban (Lixiana™) and dabigatran (Pradaxa™) may present a simplified approach to perioperative anticoagulant management due to fewer drug interactions, rapidity of onset of action and relatively short half-lives. Coagulation status, however, cannot reliably be monitored and no antidotes are currently available. When planning for discontinuation of NOACs, special consideration of renal function is required. Advice regarding the management of bleeding complications is provided for consideration in emergency surgery. In extreme circumstances, haemodialysis may be considered for bleeding with the use of dabigatran. NOACs will increasingly affect operative planning in plastic surgery. In order to reduce the incidence of complications associated with anticoagulation, the management of NOACs in the perioperative period requires knowledge of the time of last dose, renal function and the bleeding risk of the planned procedure. Consideration of these factors will allow appropriate interpretation of the current guidelines.
Kalabalik, Julie; Rattinger, Gail B; Sullivan, Jesse; Slugocki, Malgorzata; Carbone, Antonia; Rivkin, Anastasia
Atrial fibrillation is a commonly encountered arrhythmia associated with increased risk for thromboembolic events. Anticoagulation is necessary to decrease the risk of ischemic stroke. Traditionally, warfarin has been the only oral pharmacotherapeutic option for long-term anticoagulation in patients with nonvalvular atrial fibrillation (NVAF). Recently, non-vitamin K antagonist oral anticoagulants (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban, have become available as alternatives for warfarin in the prevention of stroke in patients with NVAF. Recently published atrial fibrillation guidelines contain new recommendations for risk stratification tools in determining the need for anticoagulant therapy and incorporate NOAC pharmacotherapy options for stroke prevention in patients with NVAF. NOACs offer several advantages over warfarin, including the elimination of routine laboratory monitoring, fewer drug and food interactions, and rapid therapeutic onset and offset. However, the lack of antidote in the case of serious bleeding and lack of data for long-term use in patient populations at risk for bleeding is problematic. Older adults are at high risk for thromboembolic and bleeding events as a result of anticoagulation and require special consideration when selecting anticoagulant therapy. The risk of drug accumulation and bleeding is concerning in the presence of renal impairment. The objective of this review is to provide the clinician with an update on the use of NOACs for NVAF, focusing on older adults and patients with renal impairment in light of recently published atrial fibrillation guidelines. Available data on using NOACs in coronary artery stenting, cardioversion, and ablation are also reviewed.
Patients undergoing surgery for total hip arthroplasty (THA) or total knee arthroplasty (TKA) are at particularly high risk for developing venous thromboembolism (VTE). Despite the existence of effective therapies for VTE prevention, THA/TKA patients remain at risk for developing thrombi. Furthermore, the incidence of VTE is predicted to increase as an aging and increasingly obese population experiences joint damage necessitating THA and TKA. Current guidelines recommend the use of a wide range of antithrombotic agents in patients undergoing THA and TKA. These agents include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, and the new oral anticoagulants. However, adherence to guidelines in clinical practice is disappointingly low. The limitations of traditional anticoagulants present management challenges following orthopedic surgery. Vitamin K antagonists present a number of drawbacks, including a narrow therapeutic window and unpredictable pharmacokinetics and pharmacodynamics. The subcutaneous route of administration of fondaparinux and low-molecular-weight heparins may make them unacceptable to patients in the outpatient setting. The introduction of a new generation of anticoagulants promises to address many of the drawbacks associated with the traditional agents. Clinical studies have shown the new oral anticoagulants to be as effective as traditional thromboprophylaxis, with good tolerability profiles. Clinical knowledge of these new agents will be essential to ensure that patients receive appropriate care following orthopedic surgery. This article will discuss the prevention of VTE after THA and TKA based on current evidence-based practice guidelines, the limitations of conventional anticoagulants, and the promise of new therapeutics.
Shaikh, Safiya Imtiaz; Kumari, R. Vasantha; Hegade, Ganapati; Marutheesh, M.
Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin (LMWH), fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring interventions. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease to use and more favorable pharmacodynamic profiles. Increasingly, anesthesiologists are being requested to anesthetize patients who are on some form of anticoagulants and hence it is important to have sound understanding of pharmacology, dosing, monitoring, and toxicity of anticoagulants. We searched the online databases including PubMed Central, Cochrane, and Google Scholar using anticoagulants, perioperative management, anesthetic considerations, and LMWH as keywords for the articles published between 1994 and 2015 while writing this review. In this article, we will review the different classes of anticoagulants and how to manage them in the perioperative settings. PMID:28298749
Capranzano, Piera; Miccichè, Eligio; D'Urso, Lucia; Privitera, Fiorella; Tamburino, Corrado
For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection.
Krueger, Kirsten; Schmutz, Axel; Zieger, Barbara; Kalbhenn, Johannes
Extracorporeal lung support and therapeutic anticoagulation are dogmatically linked for most clinicians in fear of clotting of the extracorporeal circuit. In the last decade, however, we have learned that bleeding complications in the course of extracorporeal membrane oxygenation (ECMO) therapy are common and not occasionally limiting or fatal. Even though international guidelines lowered the PTT-target values, ECMO therapy without anticoagulation has only been reported sporadically in case reports heretofore. This monocentric, observational study was designed to evaluate a protocol for venovenous ECMO therapy without additional anticoagulation. Patients without former thrombotic events solely received thrombosis prophylaxis with 40 mg subcutaneous enoxaparin per day like every critical care patient. After approval by the local ethics committee (Albert-Ludwigs-University Freiburg ethics committee, EK 513/14) all consecutive patients treated with venovenous ECMO therapy since introduction of the protocol have been identified. Digital charts of the patients have been evaluated with special regard to bleeding and thrombotic or embolic events or breakdown of the extracorporeal circuit. Sixty-one patients received venovenous ECMO therapy with prophylactic subcutaneous enoxaparin only. Median duration of ECMO therapy was 7 days (2-32). Overall 560 ECMO days have been observed. No system exchange because of thrombotic occlusion was necessary within the permitted 5 days run time of the centrifugal pump. Overall we identified thrombotic complications in four patients. In three of them centrifugal pump after a runtime of more than 5 days unexpectedly stopped completely because of thrombotic occlusion. In all cases pump exchange was performed promptly and patients did not incur hypoxic deficit. One other patient received substitution of blood products and coagulation factor concentrates because of severe bleeding and sustained myocardial infarction the day after. Only 18% of
Yu, Amy Y.X.; Malo, Shaun; Wilton, Stephen; Parkash, Ratika; Svenson, Lawrence W.; Hill, Michael D.
Background: Atrial fibrillation increases the risk of stroke and death. Anticoagulation therapy is an effective treatment for stroke prevention, but remains underused in the community. We sought to determine the effectiveness and safety of anticoagulation therapy in an inception cohort with new-onset atrial fibrillation in the province of Alberta, Canada. Methods: We conducted a population-based cohort study of atrial fibrillation using an administrative database from Alberta's publicly funded and universally available health care system. All new-onset atrial fibrillation patients from Jan. 1, 2009, to Dec. 31, 2010, were included in the cohort and followed through Dec. 31, 2013. We assessed anticoagulation status as a predictor of stroke and death using time-to-event analysis and adjusted for sex and CHADS2 (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke or transient ischemic attack) score using Cox proportional hazards modelling. Results: We identified 10 745 patients, 7358 (68.5%) of whom received anticoagulation therapy, principally with warfarin (n = 6997, 95.1%). Anticoagulation therapy was associated with significantly decreased risk of ischemic stroke (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), all stroke (HR 0.77, 95% CI 0.65-0.91), all stroke and death (HR 0.70, 95% CI 0.62-0.72) and all-cause mortality (HR 0.67, 95% CI 0.62-0.72), despite an association with increased risk of hemorrhagic stroke (HR 1.92, 95% CI 1.17-3.16). There was a neutral association with subdural (HR 1.01, 95% CI 0.53-1.93) and gastrointestinal (HR 0.96, 95% CI 0.70-1.31) hemorrhage. Interpretation: Anticoagulation therapy is effective and safe for stroke prevention and decreases mortality in patients with incident atrial fibrillation. These population data support an aggressive approach to screening for atrial fibrillation and treatment with anticoagulant medicines to prevent stroke and death. PMID:27280108
Diagnostic of global coagulation parameters is part of the daily clinical routine practice in conservative as well in operative disciplines. The correct interpretation of in vitro test results in context to the ex vivo influence of anticoagulant drugs and the in vivo hemostatic system of the individual patient is dependent on the doctors clinical and laboratory experience. This article shortly reviews the laboratory interference of oral anticoagulants including the target-specific inhibitors dabigatran, rivaroxaban and apixaban on coagulation parameters and discusses the potential of several methods for measuring the anticoagulant effect of the direct oral anticoagulants.
Galvão Braga, Carlos; Ribeiro, Sílvia; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Primo, João; Magalhães, Sónia; Correia, Adelino
Pheochromocytoma is a rare catecholamine-producing tumor, discovered incidentally in 50% of cases. We present the case of a 44-year-old male with a history of paroxysmal palpitations. Baseline ECG, transthoracic echocardiogram and ECG stress test showed no relevant alterations. Paroxysmal atrial fibrillation was detected on 24-hour Holter ECG. After antiarrhythmic therapy, the patient remained symptomatic, and was accordingly referred for electrophysiological study and atrial fibrillation ablation. Anticoagulation was initiated before the procedure. After ablation and still anticoagulated, he complained of hematospermia. The abdominal and pelvic imaging study showed a 10-cm left adrenal mass, predominantly cystic, compatible with pheochromocytoma, which was confirmed after biochemical tests (increased urine metanephrines and plasma catecholamines). Metaiodobenzylguanidine scintigraphy scanning confirmed localized disease in the adrenal gland, excluding other uptake foci. Following appropriate preoperative management, surgical resection of the giant mass was performed successfully and without complications.
Gray, Richard J.; Stupka, Jonathan C.; Emken, Michael R.; Scotten, Lawrence N.; Siegel, Rolland
Valvular heart disease remains a large public health problem for all societies; it attracts the attention of public health organizations, researchers and governments. Valve substitution is an integral part of the treatment for this condition. At present, the choice of valve prosthesis is either tissue or mechanical. Tissue valves have become increasingly popular in spite of unresolved problems with durability, hemodynamics, cost and need for anticoagulation therapy. As a consequence, mechanical valve innovation has virtually ceased; the last successful mechanical design is 25 years old. We postulate that with improved technology, knowledge and experience gained over the last quarter century, the best possible solution to the problem of valve substitution can be achieved with a mechanical valve that is anticoagulant independent, durable, hemodynamically and cost efficient. At present, it is possible to design, test and produce a valve that can accomplish these goals. PMID:28149886
Chaux, Aurelio; Gray, Richard J; Stupka, Jonathan C; Emken, Michael R; Scotten, Lawrence N; Siegel, Rolland
Valvular heart disease remains a large public health problem for all societies; it attracts the attention of public health organizations, researchers and governments. Valve substitution is an integral part of the treatment for this condition. At present, the choice of valve prosthesis is either tissue or mechanical. Tissue valves have become increasingly popular in spite of unresolved problems with durability, hemodynamics, cost and need for anticoagulation therapy. As a consequence, mechanical valve innovation has virtually ceased; the last successful mechanical design is 25 years old. We postulate that with improved technology, knowledge and experience gained over the last quarter century, the best possible solution to the problem of valve substitution can be achieved with a mechanical valve that is anticoagulant independent, durable, hemodynamically and cost efficient. At present, it is possible to design, test and produce a valve that can accomplish these goals.
Ene, Gabriela; Garcia Raso, Aránzazu; Gonzalez-Dominguez Weber, Almudena; Hidalgo-Vega, Álvaro; Llamas, Pilar
Background: The initiation of oral anticoagulation therapy after valve replacement surgery requires strict monitoring because these patients are at high risk for the development of thrombotic complications and present an increased risk of bleeding. Objectives: The aim of this study was to examine the total healthcare costs of oral anticoagulant treatment with vitamin K antagonists in patients with metallic prosthetic valves in the mitral position. Methods: Data from clinical records were used in the study including international normalized ratio results, number of medical visits, type of anticoagulant, use of rescue medication and hospital admissions from related complications. The drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included in the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the diagnosis-related group price for each case. Results: We collected data from 151 patients receiving oral anticoagulation therapy with vitamin K antagonist who were diagnosed with mitral prosthesis (n = 90), mitro-aortic prosthesis (n = 57), and mitral and tricuspid prosthesis (n = 4). The total direct healthcare cost was €15302.59, with a mean total cost per patient per year of €1558.15 (±2774.58) consisting of 44.38 (±42.30) for drug cost, €71.41 (±21.43) for international normalized ratio monitoring, €429.52 (±126.87) for medical visits, €26.31 (±28.38) for rescue medication and €986.53 (±2735.68) for related complications. Conclusion: Most direct healthcare costs associated with the sampled patients arose from the specialist-care monitoring required for treatment. Good monitoring is inversely related to direct healthcare costs. PMID:27579168
Pieri, Marina; Agracheva, Natalia; Di Prima, Ambra Licia; Nisi, Teodora; De Bonis, Michele; Isella, Francesca; Zangrillo, Alberto; Pappalardo, Federico
Bivalirudin is a direct thrombin inhibitor that is increasingly used in patients undergoing mechanical circulatory support as it presents many advantages compared with unfractionated heparin. The aim of this study was to describe our experience with bivalirudin as primary anticoagulant in patients undergoing ventricular assist device (VAD) implantation. An observational study was performed on 12 consecutive patients undergoing VAD implantation at our institution. Patients received a continuous infusion of bivalirudin, with a starting dose of 0.025 mg/kg/h; the target activated partial thromboplastin time (aPTT) was between 45 and 60 s. Patients never received heparin during hospitalization nor had a prior diagnosis of heparin-induced thrombocytopenia (HIT). All patients received a continuous flow pump except one. Preoperative platelets count was 134 000 ± 64 000 platelets/mm(3) . Mean bivalirudin dose was 0.040 ± 0.026 mg/kg/h over the course of therapy (5-12 days). Lowest platelets count during treatment was 73 000 ± 23 000 platelets/mm(3) . No thromboembolic complications occurred. Two episodes of minor bleeding from chest tubes that subsided after reduction or temporary suspension of bivalirudin infusion were observed. Intensive care unit stay was 8 (7-17) days, and hospital stay was 25 (21-33) days. Bivalirudin is a valuable option for anticoagulation in patients with a VAD and can be easily monitored with aPTT. The use of a bivalirudin-based anticoagulation strategy in the early postoperative period may overcome many limitations of heparin and, above all, the risk of HIT, which is higher in patients undergoing VAD implantation. Bivalirudin should no longer be regarded as a second-line therapy for anticoagulation in patients with VAD. [Correction added on 6 December 2013, after first online publication: The dose of bivalirudin in the Abstract to 0.025 mg/kg/h].
Faxon, David P
Thrombosis superimposed on arteriosclerosis is the principal cause of mortality and morbidity in patients with arteriosclerosis. The use of antiplatelet agents and anticoagulants in the treatment of arteriosclerosis is well established, based on many large randomized trials. Aspirin is indicated for primary prevention in patients at increased risk of developing symptomatic atherosclerotic vascular disease. For patients with known vascular disease, antiplatelet therapy with aspirin is a well-established treatment. For high-risk patients such as those with acute coronary syndromes (ACS; unstable angina, myocardial infarction), dual antiplatelet therapy with aspirin and clopidogrel is indicated, based on results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. Platelet glycoprotein IIb/IIIa agents are powerful inhibitors of platelet function and are also effective in ACS, but the benefit is confined to high-risk patients. Anticoagulation with heparin or low-molecular-weight heparin (eg, enoxaparin) is also effective, with an approximately 50% reduction in cardiovascular events. These agents are also indicated for patients undergoing percutaneous coronary intervention. Prolonged dual antiplatelet therapy (at least 6 months) is recommended for patients receiving drug-eluting stents. The efficacy of antiplatelet therapy is thus well established in treating atherothrombosis, but aggressive therapy is associated with an increased bleeding risk. Newer agents may provide improved efficacy with a lower risk of bleeding.
Sharma, Munish; Khalighi, Koroush
Ischemic stroke is the most common complication of atrial fibrillation (AF). Anticoagulation therapy reduces the risk of systemic embolization in almost all patients with AF irrespective of the type of AF (paroxysmal, persistent or permanent). But, all patients are not suitable candidates for systemic anticoagulation mainly due to the risk of bleeding. Left atrial appendage closure (LAAC) devices have been found to be very effective non-pharmacologic alternative therapy for such patients. There are various types of LAAC devices but United States Food and Drug Administration (US-FDA) have approved only Watchman device. Initially, bigger medical centers in the US had started the insertion of Watchman device but with improving procedural techniques and exciting outcomes, even the community-based hospitals have started to embrace this therapy. We have presented the first three cases of Watchman device placement performed in our hospital and discussed about the indications for placement of LAAC devices. We have also reviewed their efficacy individually. PMID:28243428
The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.
Ten Cate, V; Ten Cate, H; Verheugt, F W A
There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.
Borst, G H A; Counotte, G H M
Second-generation anticoagulant rodenticides can give rise to unexpected casualties in nontarget species in zoos. The first two offspring of a pair of turkey vultures (Cathartes aura) died of brodifacoum toxicosis. The adult birds fed rodenticide-killed mice to their offspring. There are previous case reports of small carnivorous birds (Dacelo novae-guinae and Tockus deckeni) killed eating poisoned (difenacoum and brodifacoum) mice. Even a granivorous species (Rollulus roulroul) died, probably by contamination of its food by cockroaches that transported the rodenticide.
Annoni, Giorgio; Mazzola, Paolo
Background In elderly patients, especially those older than 80 years, atrial fibrillation (AF) is associated with an almost 25% increased risk of stroke. Stroke prophylaxis with anticoagulants is therefore highly recommended. The prevalence of factors that have been associated with a lower rate of prescription and adherence to anticoagulant therapy in these patients is little known. The objective of this study was to explore the clinical characteristics of elderly subjects, with and without AF, consecutively admitted to an acute geriatric unit, discussing factors that may decrease the persistence on stroke prophylaxis therapy. We also highlight possible strategies to overcome the barriers conditioning the current underuse of oral anticoagulants in this segment of the population. Methods A retrospective observational study was performed on a cohort of elderly patients with and without AF admitted to the Acute Geriatric Unit of San Gerardo Hospital (Monza, Italy). Results Compared to patients without AF (n = 1216), those with AF (n = 403) had a higher Charlson Comorbidity Index (3 vs. 2, P < 0.001), number of administered drugs (4 vs. 3, P < 0.001), rate of heart failure (36.5% vs. 12%, P < 0.001) and chronic kidney disease (20.6 vs. 13.2, P < 0.001). Many patients with AF were frail (54%) or pre-frail (29%). Conclusions Elderly patients with AF have higher rates of conditions that affect adherence to traditional anticoagulant therapy (vitamin K antagonists, VKA). New direct oral anticoagulants (DOAs) can help overcome this problem. In order to prescribe the most appropriate VKA or DOAs, with the best efficacy/safety profile and the highest compliance, a comprehensive geriatric assessment should always accompany the scores for thrombotic and hemorrhagic risk stratification. PMID:27103917
Wilson, S. Jo-Anne; Wells, Philip S.; Kovacs, Michael J.; Lewis, Geoffrey M.; Martin, Janet; Burton, Erica; Anderson, David R.
Background There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care. Methods We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range ± 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups. Results Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by
Hess, Paul L; Mirro, Michael J; Diener, Hans-Christoph; Eikelboom, John W; Al-Khatib, Sana M; Hylek, Elaine M; Bosworth, Hayden B; Gersh, Bernard J; Singer, Daniel E; Flaker, Greg; Mega, Jessica L; Peterson, Eric D; Rumsfeld, John S; Steinberg, Benjamin A; Kakkar, Ajay K; Califf, Robert M; Granger, Christopher B
Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.
Misasi, Silvia; Martini, Giuliana; Paoletti, Oriana; Calza, Stefano; Scovoli, Giovanni; Marengoni, Alessandra; Testa, Sophie; Caimi, Luigi; Marchina, Eleonora
Abstract Vitamin K antagonists (VKAs) are highly effective but have a narrow therapeutic index and require routine monitoring of the INR. The primary aim of pharmacogenetics (PGx) is to optimize patient care, achieving drug treatments that are personalized according to the genetic profile of each patient. The best-characterized genes involved in VKA PGx involve pharmacokinetics (VKORC1) and pharmacodynamics (CYP2C9) of VKA metabolism. The role of these genes in clinical outcomes (bleeding and thrombosis) during oral anticoagulant (OAC) therapy is controversial. The aim of the present study was to evaluate any potential association between genotype VKORC1 and CYP2C9 and adverse events (hemorrhagic and/or thrombotic), during initiation and long-term VKA treatment, in Caucasian patients. Furthermore, we aimed to determine if the concomitant prescription of other selected drugs affected the association between genotype and adverse events. We performed a retrospective, matched case-control study to determine associations between multiple gene variants, drug intake, and any major adverse effects in anticoagulated patients, monitored in 2 Italian anticoagulation clinics. Our results show that anticoagulated patients have a high risk of adverse events if they are carriers of 1 or more genetic polymorphisms in the VKORC1 (rs9923231) and CYP2C9 (rs1799853 and rs1057910) genes. Information on CYP2C9 and VKORC1 variants may be useful to identify individualized oral anticoagulant treatment for each patient, improve management and quality of VKA anticoagulation control, and monitor drug surveillance in pharmacovigilance programs. PMID:28033245
Alaali, Yathreb; Barnes, Geoffrey D; Froehlich, James B; Kaatz, Scott
Approximately 4.2 million patients in the United States are taking warfarin, making it the 11th most prescribed drug. Warfarin is primarily used for treatment of venous thromboembolic disease and stroke prevention in patients with atrial fibrillation and mechanical heart valves. Dentists frequently encounter anticoagulated patients and are faced with management decisions in these patients who require dental procedures. Observational studies suggest the risk of thrombosis if anticoagulation is suspended during dental procedures is higher than the risk of bleeding if anticoagulation is not suspended. Several groups now offer guidelines that recommend most minor dental procedures should be performed while on therapeutic warfarin. The recent approval of several new oral anticoagulants has introduced greater complexity to the management of the anticoagulated patient, and this narrative review will discuss current guidelines, the scientific underpinnings of the guidelines, and offer some practical suggestions for patients that are receiving the new agents.
Hankey, Graeme J; Norrving, Bo; Hacke, Werner; Steiner, Thorsten
Each year, 1·0–2·0% of individuals with atrial fibrillation and 0·1–0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2–0·5% of individuals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offers practical approaches to the management of patients receiving novel oral anticoagulants who present with an ischemic or hemorrhagic stroke. Specifically, we discuss the role of thrombolysis in anticoagulated patients with acute ischemic stroke and factors to consider concerning restarting anticoagulation after acute ischemic and hemorrhagic stroke. PMID:24891030
Muscarella, Marilena; Armentano, Antonio; Iammarino, Marco; Palermo, Carmen; Amorena, Michele
This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high‑performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice.
Fitzmaurice, D A; Murray, E T; McCahon, D; Holder, R; Raftery, J P; Hussain, S; Sandhar, H; Hobbs, F D R
Objective To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. Design Multicentre open randomised controlled trial. Setting Midlands region of the UK. Participants 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. Intervention Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. Main outcome measure Percentage of time spent within the therapeutic range of international normalised ratio. Results No significant differences were found in percentage of time in the therapeutic range between self managment and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (χ2(df = 1) = 0.02, P = 0.89). Conclusion With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375. PMID:16216821
Kataranovski, Milena; Mirkov, Ivana; Vrankovic, Jelena; Kataranovski, Dragan; Subota, Vesna
Percutaneous toxicity of anticoagulant rodenticides is usually manifested by coagulopathy and/or fatal outcome. There are, however, virtually no data on other biological effects of this class of pesticides that gain access into the organism via skin. In this study, percutaneous toxicity of epicutaneously applied warfarin was evaluated by measuring changes in peripheral blood granulocytes in rats. Application of 10 mug (0.05 mg/kg) or 100 mug (0.5 mg/kg) of warfarin (WF) for 3 consecutive days resulted in an increase in prothrombin time, documenting the access of warfarin to systemic circulation. Application of warfarin led to an increase in relative numbers of granulocytes at higher dose, whereas both doses resulted in increased metabolical viability, evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Higher warfarin dose resulted in both granulocyte activation and priming (evaluated by cytochemical nitroblue tetrazolium, NBT, reduction assay of respiratory burst), whereas only a tendency toward activation was noted at lower WF dose. Soluble mediators from the circulation seem responsible for the observed effects, as exogenous plasma from WF-treated animals stimulated NBT reduction by isologous or naïve granulocytes. Data presented in this study are relevant for the recognition of biological effects, other than those affecting hemostasis, of anticoagulant rodenticides that gain access to systemic circulation through the skin.
Potpara, Tatjana S; Polovina, Marija M; Licina, Marina M; Stojanovic, Radan M; Prostran, Milica S; Lip, Gregory Y H
Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality
Zheng, Huan Jie; Ouyang, Shu Kun; Zhao, Yue; Lu, Kai; Luo, Su Xin; Xiao, Hua
Background Oral anticoagulants (OACs) are effective for the prophylaxis of stroke in patients with atrial fibrillation (AF). This cross-sectional study aimed to investigate the status of anticoagulation treatment for hospitalized AF patients in Southwest China. Methods A total of 4760 hospitalized patients with AF were enrolled from 21 hospitals in Chongqing city from January 1 to December 31, 2013. Results Among the enrolled patients, 3785 were diagnosed with nonvalvular AF. These patients had a mean age of 74.4±10.1 years. The mean CHADS2 score of all subjects was 2.60±1.34, and 80.7% of the patients had CHADS2 ≥2. The use rate of OACs was only 11.5% for patients with a high risk for stroke (CHADS2 ≥2) and was much lower in patients from the second-level hospitals than in patients from the third-level hospitals (5.8% vs. 16.9%, P<0.001). The leading reason for the underuse of OACs in high-risk patients was physician’s nonfeasance. Conclusion This study demonstrated that the underuse of anticoagulation therapy in hospitalized patients with nonvalvular AF was particularly serious in Southwest China, especially in the second-level hospitals. Urgent and effective measures are desperately needed to improve this alarming situation in China. PMID:28293117
Spolarich, A E; Andrews, L
Dental professionals routinely treat patients taking prescription, nonprescription, and herbal medications that are known or have the potential to alter bleeding. Prescription anticoagulant and antiplatelet medications, as well as over-the-counter drugs such as aspirin, are typically taken to reduce the risk of thromboembolic events, including stroke. Herbal supplements are widely used for a variety of indications, and both patients and health care practitioners are often unaware of the anticoagulant and antiplatelet effects that occur as either predictable pharmacologic effects or adverse side effects of herbal medicines. In addition, patient use of these herbal supplements is usually undisclosed to health care providers. The purpose of this literature review is to examine the mechanisms of action of drugs and herbs that alter bleeding, and to educate dental professionals as to the proper care and management of patients using these medications. Decision-making strategies, including interpretation of laboratory tests, and when to discontinue the use of these medications are discussed. Patients undergoing routine dental and dental hygiene procedures do not need to discontinue the use of anticoagulant and antiplatelet medications. However, alterations in drug use may be required for those patients undergoing invasive surgical procedures. It is recommended that herbal supplements must be discontinued 2 weeks prior to receiving invasive surgical procedures. Dental practitioners must learn to weigh the risks of discontinuing drug therapy against the potential risks to patients, and implement risk reduction strategies to minimize adverse bleeding complications associated with dental treatment.
Lecumberri, Ramón; Páramo, José A; Rocha, Eduardo
The association between cancer and an increased incidence of venous thromboembolism (Trousseau syndrome) is well characterized and recent studies have shown that the hemostatic system plays a key role at different stages in the process of tumorigenesis. Anticoagulant drugs therefore appear to be an attractive strategy in cancer therapy, with an effect that would surpass the benefit of preventing thrombosis. This hypothesis was initially supported by the post-hoc analysis of clinical trials not primarily designed to evaluate the effect of anticoagulants, mainly low molecular weight heparins (LMWH), on cancer survival. Other studies regarding the addition of unfractionated heparin or oral anticoagulants to standard cancer treatment offered controversial results. However, recent investigations among cancer patients without deep venous thrombosis, with cancer-related mortality as the primary end point, suggest that at least in some patients LMWH may exert an antineoplastic effect in vivo and alter the natural history of malignant disease by increasing the response rates and, therefore, improving survival. Additional research on this field is needed to clarify the biological mechanisms involved and to answer yet unsolved questions such as the types of tumor and stages of disease most suitable for this treatment as well as how to optimize treatment regimens.
Raimondi, Peter; Hylek, Elaine M; Aronis, Konstantinos N
There is an increasing prevalence of cardiovascular diseases that warrant antithrombotic therapy. Antithrombotic therapy includes antiplatelet agents and anticoagulation therapy with vitamin K antagonists (VKAs) or non-Vitamin K oral anticoagulants (NOACs). Antithrombotic therapy is associated with increased rates of bleeding. In this review we summarize the evidence and provide strategies for the management of severe bleeding in the setting of antithrombotic therapy. There is limited data on the management of bleeding in the setting of antiplatelet therapy. We recommend discontinuation of the antiplatelet, as well as administration of platelet transfusions and desmopressin only in the setting of life-threatening bleeding. For patients presenting with severe bleeding in the setting of VKAs, we recommend discontinuation of VKA and prompt administration of 10 mg intravenous vitamin K plus 50 units/kg 4-factor prothrombin complex concentrate (PCC). If 4-factor PCC is not available 3-factor PCC or fresh frozen plasma (FFP) can be used, but these are inferior to 4-factor PCC. For patients presenting with severe bleeding while on dabigatran, we recommend discontinuation of dabigatran and intravenous administration of 5g idarucizumab. There is currently no available reversal agent for factor Xa inhibitors. Andexanet alpha is a factor Xa-specific inhibitor that is currently undergoing FDA review. Until andexanet alpha becomes available we recommend discontinuation of the factor Xa inhibitor and administration of 50 units/kg 4-factor PCC. The decision to discontinue and/or reverse antithrombotic therapy should be made on a case-by-case basis and the competing risk from discontinuation and/or reversal of antithrombotic therapy should be taken in consideration.
Lopes, Renato D; Guimarães, Patricia O; Kolls, Bradley J; Wojdyla, Daniel M; Bushnell, Cheryl D; Hanna, Michael; Easton, J Donald; Thomas, Laine; Wallentin, Lars; Al-Khatib, Sana M; Held, Claes; de Barros E Silva, Pedro Gabriel Melo; Alexander, John H; Granger, Christopher B; Diener, Hans-Christoph
We investigated the frequency and characteristics of intracranial hemorrhage (ICH), factors associated with risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients in ARISTOTLE with ICH who received ≥1 dose of study drug (n=18,140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.2%) versus traumatic (28.8%). Apixaban resulted in significantly less ICH (0.33%/year), regardless of type and location, than warfarin (0.80%/year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th) time from most recent international normalized ratio (INR) to ICH was 13 (6, 21) days. Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale at discharge was ≥4 in 55.7%, and mortality at 30 days was 43.3%. No difference was observed in the rates of all-cause death post-ICH, regardless of treatment. ICH occurred at a rate of 0.80%/year with warfarin regardless of INR control and 0.33%/year with apixaban, and was associated with high short-term morbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients with older age.
Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel
Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904
Poposka, Lidija; Boskov, Vladimir; Risteski, Dejan; Taleski, Jane; Georgievska-Ismail, Ljubica
INTRODUCTION: In patients with an implanted pacemaker, asymptomatic atrial fibrillation (AF) is associated with an increased risk of thrombo-embolic complications. There is still no consensus which duration of episodes of atrial fibrillation should be taken as an indicator for inclusion of oral anticoagulation therapy (OAC). MATERIAL AND METHODS: A total of 104 patients who had no AF episodes in the past and have an indication for permanent pacing were included in the study. RESULTS: During an average follow-up of 18 months, 33 of the patients developed episodes of AF. Inclusion of OAC was performed in 17 patients, in whom AF was recorded, although in all patients CHA2DS2-VASc score was ≥ 1. The inclusion of OAC showed a statistically significant correlation with increasing duration of episodes of AF (r = 0.502, p = 0.003). During the follow-up period none of the patients developed thrombo-embolic complication. CONCLUSION: Considering that our group of patients had no thrombo-embolic events, we could conclude that dividing the AF episodes in less than 1% in 24 hours and longer than 1% within 24 hours could be an indicator for decision-making to include OAK if the CHA2DS2-VASc score is ≥ 1. PMID:27335594
Tugcu, Aylin; Yildirimturk, Ozlem; Demiroglu, I C Cemsid; Aytekin, Saide
We report the case of a patient with completely painless chronic aortic dissection, who presented to another hospital with a left hemiparesia 3 months ago and received anticoagulation therapy with a diagnosis of ischemic stroke. Most of her symptoms had resolved when she presented to our outpatient clinic except for numbness of her left hand and dysphasia. Physical examination found a diastolic murmur at the left sternal border and a bruit over the right carotid artery. Transthoracic echocardiography and carotid sonography demonstrated aortic dissection with extension into the internal right carotid artery and severe aortic regurgitation. Surgery was performed successfully and the patient was discharged. This case emphasizes that the diagnosis of a completely painless aortic dissection with only neurologic symptoms at presentation can be extremely difficult and should always be considered as a cause of ischemic stroke to avoid catastrophic antithrombolytic or anticoagulation therapy.
Damin-Pernik, Marlène; Espana, Bernadette; Lefebvre, Sebastien; Fourel, Isabelle; Caruel, Hervé; Benoit, Etienne; Lattard, Virginie
Second-generation anticoagulant rodenticides (SGARs) have been used since the 1980s for pest management. They are highly efficient even in warfarin-resistant rodents. Nevertheless, because of their tissue persistence, nontarget poisoning by SGARs is commonly described in wildlife. Due to this major problem, a new generation of anticoagulants must be developed to limit this risk. This study proposes a method of developing a new generation of anticoagulant rodenticides by revisiting the old SGARs based on the concept of stereochemistry. Each current SGAR is a mixture of diastereomers. Diastereomers of each compound were purified, and their biologic properties were compared by determining their ability to inhibit vitamin K epoxide reductase (VKOR) activity involved in the activation of vitamin K-dependent clotting factors and their toxicokinetic properties. Systematically, for each SGAR, both diastereomers are as effective in inhibiting VKOR activity. However, their toxicokinetic properties are very different, with one of the two diastereomers always more rapidly cleared than the other one. For all SGARs except flocoumafen, the less persistent diastereomer is always the less predominant isomer present in the current mixture. Therefore, the development of baits containing only the less persistent diastereomer would avoid the ecotoxicological risk associated with their use without decreasing their efficacy.
Pino, Christopher J; Farokhrani, Amin; Lou, Liandi; Smith, Peter L; Johnston, Kimberly; Buffington, Deborah A; Humes, H David
Selective cytopheretic inhibitory device (SCD) therapy is an immunomodulatory treatment provided by a synthetic biomimetic membrane in an extracorporeal circuit, which has shown promise in preclinical large animal models of severe sepsis as well as in clinical trials treating patients with acute kidney injury and multiple organ failure. During SCD therapy, citrate is administered to lower ionized calcium levels in blood for anticoagulation and inhibition of leukocyte activation. Historically, citrate has been known to interfere with sorbent dialysis, therefore, posing a potential issue for the use of SCD therapy with a portable dialysis system. This sorbent dialysis SCD (sorbent SCD) would be well suited for battlefield and natural disaster applications where the water supply for standard dialysis is limited, and the types of injuries in those settings would benefit from SCD therapy. In order to explore the compatibility of sorbent and SCD technologies, a uremic porcine model was tested with the Allient sorbent dialysis system (Renal Solutions Incorporated, Fresenius Medical Care, Warrendale, PA, USA) and concurrent SCD therapy with regional citrate anticoagulation. The hypothesis to be assessed was whether the citrate load required by the SCD could be metabolized prior to recirculation from systemic blood back into the therapeutic circuit. Despite the fact that the sorbent SCD maintained urea clearance without any adverse hematologic events, citrate load for SCD therapy caused an interaction with the sorbent column resulting in elevated, potentially toxic aluminum levels in dialysate and in systemic blood. Alternative strategies to implement sorbent-SCD therapy will be required, including development of alternate urease-sorbent column binding chemistry or further changes to the sorbent-SCD therapeutic circuit along with determining the minimum citrate concentration required for efficacious SCD treatment.
Khorev, N G; Momot, A P; Kon'kova, V O
During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation). The review contains the data on the existing therapeutic regimens of treating haemorrhage on the background of taking these coagulants. This is followed by analysing the present-day results of clinical trials aimed at working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors. Administration of these agents makes it possible to reverse coagulation and minimize the aftermaths of haemorrhage in patients taking these drugs, in emergency situations.
This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict. PMID:27625521
Scott, Alun; Gibson, John; Crighton, Alexander
Recently, new oral anticoagulants have been introduced as alternatives to warfarin. While national guidelines for treatment of dental patients taking warfarin as an anticoagulant are well-established, no such information is available for these novel therapeutic agents. At present, the local guidance available is contradictory between different health boards/health planning units, and liaison with the medical practitioner managing the individual patient's anticoagulation is imperative if any invasive procedure is proposed. This paper examines the available evidence regarding these drugs and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care.
Agarwal, Manoj; Mittal, Sankalp; Vijay, Sharmistha; Yadav, Pooja; Panwar, Vasim Raja; Gupta, Neha
Patients taking anticoagulant medication pose a challenge for the clinician. Dentists are often required to manage bleeding as part of routine oral surgery or dental procedures, and altered hemostasis can lead to complications. Nevertheless, use of these medications is generally important for the patient's health and any alteration in the anticoagulant regimen may have untoward sequelae. In addition, several medications can affect the clotting mechanism, potentially compromising hemostasis. This article will review a variety of anticoagulant medications and the medical conditions that necessitate their use.
Sáez-Peñataro, J; Avendaño-Solá, C; González-Juanatey, J R
The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen.
Amer, Mohamed Zaghlool; Mourad, Samah I.; Salem, Ahmed S.; Abdelfadil, Ehab
Objectives: The management of patients receiving oral anticoagulant therapy (OAT) undergoing minor oral surgeries is controversial. This study was designed to evaluate the correlation between International Normalized Ratio (INR) values and the sufficiency of two different local hemostatic measures in controlling postextraction bleeding in anticoagulated patients. Materials and Methods: One hundred and sixty patients receiving Warfarin OAT were included in this study. Patients were selected so that 80 patients have INR values of ≤2, whereas the remaining patients have the INR values ranging from 2 to 3. Forty patients were then randomly selected from each category to form two equal groups. Forty-five patients who had never been on OAT were selected as a negative control group (group 1). Failure to achieve hemostasis using a pressure pack was managed using either tranexamic acid (group 2) or Ankaferd Blood Stopper (ABS) (group 3). Results: The INR values of patients included in group 2 and 3 ranged from 1.5 to 3, with a mean of 2.2. No significant difference was recorded between the use of either tranexamic acid or ABS in achieving hemostasis in anticoagulated patients with INR values ranging between 2 and 3 (P = 0.93). Conclusion: Based on our findings, ABS is a hemostatic agent of good efficacy. The effect of ABS in controlling post-extraction bleeding in anticoagulated patients with INR values ≤3 is comparable to tranexamic acid with no evidence to support the superiority of tranexamic acid over ABS. PMID:25512727
Whalley, D; Skappak, C; Lang, E S
The new factor Xa inhibitors and direct thrombin inhibitors have offered alternatives to traditional anticoagulants, with benefits of no routine monitoring, less drug interactions, and oral administration. Current approved uses of these agents include prophylaxis of stroke in non-valvular atrial fibrillation and prevention of venous thromboembolism (VTE) following hip and knee arthroplasty. However, concern over bleeding risk in the context of having no specific antidotes available is a topic of focus for many physicians in an acute care setting. This manuscript examines the recent literature in the management of acute bleeding and the various methods of reversing anticoagulation in this setting. Literature published over the last 18 months (2011/07/01-present) was gathered from PubMed, Ovid, and Medline under a combined search strategy covering bleeding, reversal, and new oral anticoagulants, both factor Xa and direct thrombin inhibitors. The use of prothrombin complex concentrate, fresh frozen plasma, activated recombinant factor VII, activated prothrombin complex concentrate, as well as adjuncts of charcoal, hemodialysis, and antifibrinolytics are discussed. Recommendations are based on the determination of the severity of the bleed and physiological markers of anticoagulation, and involve the use of prothrombin complex concentrate, activated recombinant factor VII, and adjunctive therapy as appropriate.
Whitworth, Maegan M; Haase, Krystal K; Fike, David S; Bharadwaj, Ravindra M; Young, Rodney B; MacLaughlin, Eric J
Background Scant literature exists evaluating utilization patterns for direct oral anticoagulants (DOACs). Objectives The primary objective was to assess DOAC prescribing in patients with venous thromboembolism (VTE) and nonvalvular atrial fibrillation (NVAF) in outpatient clinics. Secondary objectives were to compare utilization between family medicine (FM) and internal medicine (IM) clinics, characterize potentially inappropriate use, and identify factors associated with adverse events (AEs). Methods This was a retrospective cohort study of adults with NVAF or VTE who received a DOAC at FM or IM clinics between 10/19/2010 and 10/23/2014. Descriptive statistics were utilized for the primary aim. Fisher’s exact test was used to evaluate differences in prescribing using an adapted medication appropriateness index. Logistic regression evaluated factors associated with inappropriate use and AEs. Results One-hundred twenty patients were evaluated. At least 1 inappropriate criterion was met in 72 patients (60.0%). The most frequent inappropriate criteria were dosage (33.0%), duration of therapy (18.4%), and correct administration (18.0%). Apixaban was dosed inappropriately most frequently. There was no difference in dosing appropriateness between FM and IM clinics. The odds of inappropriate choice were lower with apixaban compared to other DOACs (odds ratio [OR]=0.088; 95% confidence interval [CI] 0.008–0.964; p=0.047). Twenty-seven patients (22.5%) experienced an AE while on a DOAC, and the odds of bleeding doubled with each inappropriate criterion met (OR=1.949; 95% CI 1.190–3.190; p=0.008). Conclusion Potentially inappropriate prescribing of DOACs is frequent with the most common errors being dosing, administration, and duration of therapy. These results underscore the importance of prescriber education regarding the appropriate use and management of DOACs. PMID:28331354
Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet-vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk.
Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L
Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care.
Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi
AIM To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB (P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB (P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants. PMID:28018108
Borgman, Mark P; Pendleton, Robert C; McMillin, Gwendolyn A; Reynolds, Kristen K; Vazquez, Sara; Freeman, Andrew; Wilson, Andrew; Valdes, Roland; Linder, Mark W
We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient's genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management.
Brasselet, C; Duval, S
New oral anticoagulants constitute an important breakthrough for cardiologists and their patients. After reviewing their mechanism of action, their role in the context of interventional cardiology, particularly for patients with acute coronary syndromes, is discussed.
del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve
New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed.
Sivolella, Stefano; De Biagi, Marleen; Brunello, Giulia; Berengo, Mario; Pengo, Vittorio
The development of new orally administered anticoagulants, such as dabigatran, rivaroxaban, and apixaban, in the past few years has focused on avoiding some of the drawbacks associated with warfarin. This work aims to illustrate the main features of the most commonly used new oral anticoagulants, reviewing the current literature on the management of patients taking these drugs and needing oral and implant surgery, and discussing the currently proposed related guidelines.
Belmar Vega, Lara; de Francisco, A L M; Bada da Silva, Jairo; Galván Espinoza, Luis; Fernández Fresnedo, Gema
Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.
Obamiro, Kehinde O.; Chalmers, Leanne; Bereznicki, Luke R. E.
Background Assessing and improving patients’ anticoagulation knowledge can lead to better treatment outcomes. While validated knowledge instruments exist for use in people taking warfarin, these tools are not necessarily applicable to patients taking direct-acting oral anticoagulants. Objective To develop and validate an oral anticoagulation knowledge instrument that is applicable to all oral anticoagulant medications. Methods Ten anticoagulation experts participated in the development of the Anticoagulation Knowledge Tool to ensure content validity. The knowledge instrument was administered to three groups of participants comprising of 44 pharmacists, 50 patients and 50 members of the general public. A subgroup of participants in the patient and pharmacist group were retested approximately 2–3 months after the initial testing. Statistical tests were conducted to determine the validity and reliability of the scale, and item analysis was used to determine the performance of individual questions. Results The 28-item instrument developed had a scale content validity index of 0.92, supporting content validity. The pharmacist group’s mean score was significantly higher than that of the patient group, and the patient group scored significantly higher than the general public group (94% vs 62% vs 20%, respectively; p<0.001), supporting construct validity. Internal consistency reliability was acceptable with a Cronbach’s α value of > 0.7 across the three groups, and the test–retest reliability was confirmed with a Pearson’s correlation coefficient of 0.72 and 0.78 for the pharmacist and patient groups, respectively. Conclusion The Anticoagulation Knowledge Tool is a valid and reliable instrument that can be used in routine clinical practice to assess patients’ anticoagulation knowledge. PMID:27351746
Wilke, Andreas; Wende, Christian M.; Horst, Michael; Steverding, Dietmar
Patients with prosthetic heart valves require lifelong oral anticoagulant therapy based on vitamin K antagonists. These patients may need interruption of their anticoagulant therapy if they have to undergo surgery. The clinical challenge is to identify patients who can safely undergo surgery while continuing their vitamin K antagonist treatment and those who have to take short-acting heparin as part of a bridging therapy. Here we present a case of a patient with a prosthetic mitral valve whose oral anticoagulant therapy was unnecessarily discontinued by the GP prior to an upcoming cataract surgery. As a result, the patient developed thrombosis of the prosthetic mitral valve which needed to be surgically replaced.
Feagins, Linda Anne
Colonoscopy frequently is performed for patients who are taking aspirin, NSAIDs, antiplatelet agents and other anticoagulants. These colonoscopies often involve polypectomy, which can be complicated by bleeding. The risks of precipitating thromboembolic complications if anticoagulants are stopped must be weighed against the risk of postpolypectomy bleeding if these agents are continued. This article systematically reviews the management of anticoagulation during elective and emergency colonoscopy. For patients undergoing colonoscopic polypectomy, the overall of risk of postpolypectomy bleeding is less than 0.5%. Risk factors for postpolypectomy bleeding include large polyp size and anticoagulant use, especially warfarin and thienopyridines. For patients who do not stop aspirin or other NSAIDs prior to colonoscopy, the rate of postpolypectomy bleeding is not significantly different than that for patients who do not take those medications. For patients who continue thienopyridines and undergo polypectomy, the risk of delayed postpolypectomy bleeding is approximately 2.4%. Even for patients who interrupt warfarin, the risk of postpolypectomy bleeding is increased. The direct oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) have a rapid onset and offset of action, and periprocedural bridging generally is not necessary. For the thienopyridines, warfarin and the direct oral anticoagulants, the decision to interrupt or continue these agents for endoscopy will involve considerable exercise of clinical judgment.
Wahl, Michael J; Pinto, Andres; Kilham, Jessica; Lalla, Rajesh V
In a literature review, the incidence and morbidity of bleeding complications after dental surgery in anticoagulated patients was compared with embolic complications when anticoagulation was interrupted. Over 99% of anticoagulated patients had no postoperative bleeding that required more than local hemostatic measures. Of more than 5431 patients undergoing more than 11,381 surgical procedures, with many patients at higher than present therapeutic intenational normalized ratio (INR) levels, only 31 (∼0.6% of patients) required more than local hemostasis to control the hemorrhage; none died due to hemorrhage. Among at least 2673 patients whose warfarin dose was reduced or withdrawn for at least 2775 visits for dental procedures, there were 22 embolic complications (0.8% of cessations), including 6 fatal events (0.2% of cessations). The embolic morbidity risk in patients whose anticoagulation is interrupted for dental surgery exceeds that of significant bleeding complications in patients whose anticoagulation is continued, even when surgery is extensive. Warfarin anticoagulation, therefore, should not be interrupted for most dental surgery.
Tompson, Alice; Heneghan, Carl; Sutton, Stephen; Fitzmaurice, David; Ward, Alison
Objective To explore the impact self-funding has on patient experience of oral anticoagulation therapy self-monitoring. Design Semistructured, qualitative interviews were conducted. Transcripts were analysed thematically using constant comparison. Setting England. Participants Interviewees were participants of the Cohort Study of Anticoagulation Self-Monitoring (CASM). Cohort members were recruited as they bought a monitor from the major manufacturer in the UK. A purposive sample was invited to be interviewed on completion of the 12-month cohort follow-up. Data Patient narratives on their experiences of self-monitoring their oral anticoagulation therapy in non-trial conditions. Results 26 interviews were completed. Interviewees viewed purchasing the monitoring device as a long-term commitment balancing the limitations of clinic-based monitoring against the cost. They were unable to try out the monitor prior to purchase and therefore had to be confident in their own ability to use it. The variable provision of self-monitoring equipment caused resentment, and interviewees were uncomfortable negotiating with healthcare professionals. High test strip usage while learning how to use the monitor caused anxiety that was exacerbated by worries about their cost. However, self-funding did mean that interviewees felt a sense of ownership and were determined to persevere to overcome problems. Conclusions Self-funding has negative implications in terms of equity of access; however, the money invested acts as a barrier to discontinuation. If oral anticoagulation therapy self-monitoring devices and consumables were provided free of charge in routine care, the training and support available in England may need to be reviewed to prevent discontinuation rates rising to those observed in clinical trials. PMID:28011812
Wawrzyńska, L; Przedlacki, J; Hajduk, B; Tomkowski, W; Fijałkowska, A; Ostrowski, K; Torbicki, A
A broad spectrum of indications for low molecular weight heparin (LMWH) requires an assessment of side effects especially during prolonged administration. There are common risk factors for venous thromboembolism (VTE) and osteoporosis; heparin is "the drug of choice" for VTE treatment. The aim of our study was to assess the effect of treatment and prophylaxis with LMWH (enoxaparine sodium) and oral anticoagulant (acenocoumarol) for bone structure. Material consists of in- and outpatients. 49 densitometries were performed in 31 patients (in 15 cases double examination). We observed a decrease of bone mineral density in comparison to the initial examination in most cases: mean change of bone mass for examined areas was 3.05%.
Streiff, Michael B
Cancer is associated with a four to sevenfold increased risk of venous thromboembolism (VTE). This risk is influenced by the site and extent of cancer and its treatment. Despite its availability, effective VTE prophylaxis is used in less than 50% of oncology patients. Pharmacologic VTE prophylaxis should be administered to all hospitalized medical and surgical oncology patients for the duration of their hospitalization or up to 10-14 days, whichever is longer. Extended duration (up to 4 weeks post-operation) VTE prophylaxis is recommended for high-risk surgical oncology patients. Routine use of prophylaxis in ambulatory medical oncology patients awaits prospective testing of VTE risk assessment models. Routine prophylactic dose anticoagulation to prevent central venous catheter (CVC) thrombosis is ineffective and not indicated. Low molecular weight heparin is the first line choice for acute and chronic therapy of VTE in cancer patients. Therapy should continue for at least 3 months or the duration of the malignancy, whichever is longer. Anticoagulation is indicated for at least 3 months or the duration of the catheter for CVC thrombosis. Preliminary data indicate that some cancer patients with pulmonary embolism may be managed as outpatients. Prospective validation of these studies and testing of current risk assessment strategies in oncology patients is warranted. Management of recurrent VTE and unsuspected VTE in the cancer patient are also reviewed.
Pinto, Ian; Giri, Anshu; Arshad, Umbreen; Gajra, Ajeet
The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's have comparable efficacy to traditional vitamin K antagonists with similar rates of major bleeding. However there is no standardized method for reversal of these agents and no specific antidote. This is of concern not only in acute bleeding episodes but also in clinical scenarios where emergency surgery is required. Recent studies have investigated reversal of dabigatran, rivaroxaban, and apixaban using prothrombin complex concentrates (PCC), recombinant factor VIIa, and in the case of dabigatran, a monoclonal antibody. These studies have been encouraging in showing improvement of bleeding times and blood loss in most models, especially with the use of PCCs and the dabigatran antibody. Of note the majority of common currently used coagulation assays may not correlate with clinical reversal. The management of overt bleeding with NOACs is difficult due to the lack of clinical trials. Current animal trials, case reports and hemostatic testing on human blood have shown some promise; provide guidance but warrant further investigation.
Leonardi, Filippo; Maria, Nicola De; Villa, Erica
The liver plays a crucial role in coagulation cascade. Global hemostatic process is profoundly influenced by the presence of liver disease and its complications. Patients with cirrhosis have impaired synthesis of most of the factors involved in coagulation and fibrinolysis process due to a reduced liver function and altered platelet count secondary to portal hypertension. Altered routine tests and thrombocytopenia were considered in the past as associated with increased risk of bleeding. These concepts explain both the routine use of plasma and/or platelets transfusion in patients with liver cirrhosis, especially before invasive procedures, and why these patients were considered “auto-anticoagulated”. New recent evidences show that patients with liver cirrhosis have a more complex hemostatic alteration. Despite the presence of altered levels of factors involved in primary hemostasis, coagulation and fibrinolysis, patients with stable cirrhosis have a rebalanced hemostatic, which however can easily be altered by decompensation or infection, both in hemorrhagic or thrombotic direction. Patients with cirrhosis have an increased risk of venous thrombotic events (namely portal vein thrombosis) while bleeding seems to be related to the grade of portal hypertension rather than to a hemostatic imbalance. The use of anticoagulants both as treatment or prophylaxis is safe, reduces the rate of portal vein thrombosis and decompensation, and improves survival. Standard laboratory coagulation tests are unable to predict bleeding and are inadequate for the assessment of hemostatic status in these patients, hence more comprehensive tests are required to guide the management of thrombotic and bleeding complications. PMID:28288507
Nickel, Katrin F; Labberton, Linda; Long, Andrew T; Langer, Florian; Fuchs, Tobias A; Stavrou, Evi X; Butler, Lynn M; Renné, Thomas
Cancer is an established risk factor for venous thromboembolism (VTE) and VTE is the second leading cause of death in patients with cancer. The incidence of cancer-related thrombosis is rising and is associated with worse outcomes. Despite our growing understanding on tumor-driven procoagulant mechanisms including cancer-released procoagulant proteases, expression of tissue factor on cancer cells and derived microvesicles, as well as alterations in the extracellular matrix of the cancer cell milieu, anticoagulation therapy in cancer patients has remained challenging. This review comments on a newly discovered cancer-associated procoagulant pathway. Experimental VTE models in mice and studies on patient cancer material revealed that prostate cancer cells and associated exosomes display the inorganic polymer polyphosphate on their plasma membrane. Polyphosphate activates blood coagulation factor XII and initiates thrombus formation via the intrinsic pathway of coagulation. Pharmacologic inhibition of factor XII activity protects mice from VTE and reduces thrombin coagulant activity in plasma of prostate cancer patients. Factor XII inhibitors provide thrombo-protection without impairing hemostatic mechanisms and thus, unlike currently used anticoagulants, do not increase bleeding risk. Interference with the polyphosphate/factor XII pathway may provide the novel opportunity for safe anticoagulation therapy in patients with malignancies.
Introduction: For over 50 years, vitamin K antagonists such as warfarin (Aldocumar®) and acenocoumarol (Sintrom®) have been the gold standard for reducing the risk of cerebrovascular events. In the last 5 years alternative anticoagulants have been evaluated that act directly upon a concrete target within the coagulation cascade, thereby affording a more predictable anticoagulant effect. The present study offers an update on the new oral anticoagulants and reviews the implications referred to the dental care of patients administered these substances. Material and methods: An exhaustive PubMed-Medline and Cochrane Library search was made of the main alternatives to conventional oral anticoagulation, covering those studies published in English and Spanish over the last 10 years. Specialized textbooks and pharmaceutical catalogs were also consulted. A total of 184 articles were identified, of which 76 met the inclusion criteria. Results: The new oral anticoagulants dabigatran, rivaroxaban and apixaban are safe and effective, and offer a series of advantages, including rapid action, no need for constant monitoring, few drug and food interactions, and a broad therapeutic margin. These drugs are expensive, however, and some lack a specific antidote, while others must be administered twice a day. Regarding the dental treatment of patients receiving these drugs, suspension or modification of the background medication is not required when performing invasive dental procedures, except where indicated by the prescribing physician. Conclusions: The new oral anticoagulants do not pose significantly greater risks than conventional oral anticoagulants when providing invasive dental treatment, and their suspension is not strictly required in such situations. Key words:Dabigatran, rivaroxaban, apixaban, dental, hemostasis. PMID:24455094
Apsner, R; Buchmayer, H; Lang, T; Unver, B; Speiser, W; Sunder-Plassmann, G; Hörl, W H
In a randomized crossover trial, we compared a simple citrate anticoagulation protocol for high-flux hemodialysis with standard anticoagulation by low-molecular-weight heparin (dalteparin). Primary end points were urea reduction rate (URR), Kt/V, and control of electrolyte and acid-base homeostasis. Secondary end points were bleeding time at vascular puncture sites and markers of activation of platelets, coagulation, and fibrinolysis. Solute removal during citrate dialysis was excellent (URR, 0.71 +/- 0.06; Kt/V, 1.55 +/- 0.3) and similar to results of conventional bicarbonate hemodialysis anticoagulation with dalteparin (URR, 0.72 +/- 0.04; Kt/V, 1.56 +/- 0.2). Electrolyte control was effective with both anticoagulation regimens, and total and ionized calcium, sodium, potassium, and phosphate concentrations at the end of dialysis did not differ. Alkalemia was less frequent after citrate than conventional dialysis (pH 7.5 in 25% versus 62% of patients; mean pH at end of dialysis, 7.46 +/- 0.06 versus 7.51 +/- 0.07; P < 0.01). Bleeding time at puncture sites was shorter by 30% after citrate compared with dalteparin anticoagulation (5.43 +/- 2.80 versus 7.86 +/- 2.93 minutes; P < 0.001). Activation of platelets, coagulation, and fibrinolysis was modest for both treatments and occurred mainly within the dialyzer during dalteparin treatment and in the vascular-access region during citrate anticoagulation. Citrate-related adverse events were not observed. We conclude that citrate anticoagulation for high-flux hemodialysis is feasible and safe using a simple infusion protocol.
Hohwy, Thomas; Jensen, Martin Glümer; Tøttrup, Anders; Steiniche, Torben; Fogh, Karsten
Malignant atrophic papulosis (Degos' disease) is a very rare condition characterized by atrophic papular skin lesions and variable association of systemic involvement. We describe a 33-year-old man who presented with a widespread skin eruption consistent with malignant atrophic papulosis. During the course of the disease he even developed penile ulcerations, a symptom that has been reported only a few times previously. He subsequently died of multiple perforations of the small bowel 2.5 years after onset of the disease. Laboratory investigations revealed a mutation of factor V Leiden and the presence of lupus anticoagulant, but no anti-cardiolipin antibodies. The patient was treated with narrow-band ultraviolet (UV)B, prednisolone and, later, aspirin, pentoxifyllin and warfarin. Despite this very intensive anticoagulant and anti-platelet therapy, the treatment had no effect on the skin lesions and could not prevent systemic involvement.
Fernandes, Carina; Pereira, Pedro; Rodrigues, Miguel
Spontaneous iliopsoas muscle haematoma is an infrequent complication of anticoagulation, potentially causing neurological dysfunction through compression of the femoral nerve or lumbar plexus. The authors report the case of a puerperal woman admitted for an extensive cerebral venous thrombosis. Anticoagulation was started, with clinical improvement. The patient later reported low back pain irradiating to the right thigh and developed neurological impairment consistent with lumbar plexus dysfunction. A pelvic CT scan revealed a right iliopsoas muscle haematoma. Considering the risk of anticoagulation suspension, a conservative approach was chosen, with maintenance of anticoagulation. Clinical and functional improvement occurred, with mild right hip and knee flexion paresis as sequelae. Anticoagulation complications are challenging, especially when interruption of anticoagulation may threaten vital and functional outcomes. Therefore, a careful evaluation is essential, since no clinical guidelines are available. In this case, continuing anticoagulation provided a good functional outcome. PMID:25750219
Fernandes, Carina; Pereira, Pedro; Rodrigues, Miguel
Spontaneous iliopsoas muscle haematoma is an infrequent complication of anticoagulation, potentially causing neurological dysfunction through compression of the femoral nerve or lumbar plexus. The authors report the case of a puerperal woman admitted for an extensive cerebral venous thrombosis. Anticoagulation was started, with clinical improvement. The patient later reported low back pain irradiating to the right thigh and developed neurological impairment consistent with lumbar plexus dysfunction. A pelvic CT scan revealed a right iliopsoas muscle haematoma. Considering the risk of anticoagulation suspension, a conservative approach was chosen, with maintenance of anticoagulation. Clinical and functional improvement occurred, with mild right hip and knee flexion paresis as sequelae. Anticoagulation complications are challenging, especially when interruption of anticoagulation may threaten vital and functional outcomes. Therefore, a careful evaluation is essential, since no clinical guidelines are available. In this case, continuing anticoagulation provided a good functional outcome.
Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.
Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193
Ashizuka, Shinya; Nishiura, Ryosuke; Ishikawa, Naoto; Yamaga, Junichi; Inatsu, Haruhiko; Fujimoto, Shouichi; Eto, Tanenao
Leukocytapheresis (LCAP) is a therapeutic strategy for extra corporeal immunomodulation that has been used to treat several immunological disorders, including ulcerative colitis (UC), with encouraging results, inducing remission in steroid-resistant patients. However, we have experienced some complications during or after LCAP therapy. Common adverse effects include fever, chills, nausea, vomiting, and hypotension. One of the reasons for these adverse effects might be the use of nafamostat mesilate (NM) as an anticoagulant. In the present study, 75 patients with UC were divided into two groups, an NM group and a dalteparin sodium (DS) group. The clinical efficacy of these treatments, improvement after treatment, changes in leukocyte differential count, and adverse effects after LCAP therapy were then compared. The clinical efficacy, improvement after treatment, and changes in leukocyte classification were not significantly different between the two groups, while some adverse effects were observed in the NM group but not in the DS group. In conclusion, LCAP therapy is a useful therapy for patients with moderate to severe UC who fail to respond to glucocorticoid therapy, however, a safe anticoagulant should be used to avoid its related adverse effects.
Bennett, Mosi K.
Heart failure continues to be a worldwide epidemic, effecting over 23 million persons. Despite advances in medical therapy, the disease is progressive and a significant proportion of patients will need advanced heart replacement therapy. Continuous flow assist devices have become a standard approach for many patients both as a bridge to cardiac transplantation and as destination therapy (DT). However, device related complications such as bleeding and thrombosis continue to hinder further advancements of this technology. The field is rapidly advancing and efforts to reduce pump complications are directed towards improving hemocompatibility and maximizing blood flow without clinically significant hemolysis, areas of stasis or turbulent flow. PMID:26793333
Broekema, Ferdinand I; van Minnen, Baucke; Jansma, Johan; Bos, Rudolf R M
To avoid increasing the risk of thromboembolic events, it is recommended that treatment with anticoagulants should be continued during dentoalveolar operations. We have evaluated the incidence of bleeding after dentoalveolar operations in a prospective study of 206 patients, 103 who were, and 103 who were not, taking anticoagulants. Seventy-one were taking thrombocyte aggregation inhibitors and 32 vitamin K antagonists. Patients were treated according to guidelines developed at the Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands. The operations studied included surgical extraction (when the surgeon had to incise the gingiva before extraction), non-surgical extraction, apicectomy, and placement of implants. Patients were given standard postoperative care and those taking vitamin K antagonists used tranexamic acid mouthwash postoperatively. No patient developed a severe bleed that required intervention. Seven patients (7%) taking anticoagulants developed mild postoperative bleeds. Patients taking vitamin K antagonists reported 3 episodes (9%) compared with 4 (6%) in the group taking thrombocyte aggregation inhibitors. Among patients not taking anticoagulants, two (2%) developed mild bleeding. The differences between the groups were not significant. All bleeding was controlled by the patients themselves with compression with gauze. We conclude that dentoalveolar surgery is safe in patients being treated with anticoagulants provided that the conditions described in the ACTA guidelines are met.
Sunkara, Tagore; Ofori, Emmanuel; Zarubin, Vadim; Caughey, Megan E.; Gaduputi, Vinaya; Reddy, Madhavi
Direct oral anticoagulants (DOACs) are in wide use among patients requiring both short- and long-term anticoagulation, mainly due to their ease of use and the lack of monitoring requirements. With growing use of DOACs, it is imperative that physicians be able to manage patients on these medications, especially in the perioperative period. We aim to provide guidance on the management of DOACs in the perioperative period. In this review, we performed an extensive literature search summarizing the management of patients on direct-acting anticoagulants in the perioperative period. A total of four direct-acting oral anticoagulants were considered appropriate for inclusion in this review. The drugs were dabigatran etexilate mesylate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). Management of patients on DOACs in the perioperative period involves an assessment of thromboembolic event risk while off anticoagulation compared to the relative risk of bleeding if such drug is continued. DOACs may not need to be discontinued in minor surgeries or procedures, and in major surgeries, they may be discontinued hours prior depending on drug pharmacokinetics and renal function of the patients. PMID:28008269
Diener, H C; Easton, J D; Hankey, G J; Hart, R G
In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K antagonists (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26 percent. Vitamin-K antagonists have a number of well documented shortcomings. Recently the results of randomised trials for three new oral anticoagulants that do not exhibit the limitations of vitamin-K antagonists have been published. These include direct factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide promising results for the new agents, including higher efficacy and a significantly lower incidence of intracranial bleeds compared with warfarin or aspirin. The new drugs show similar results in secondary as well as in primary stroke prevention in patients with AF. Apixaban was demonstrated to be clearly superior to aspirin and had the same rate of major bleeding complications. Meta-analyses show that the novel anticoagulants are superior to warfarin for the reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants add to the therapeutic options for patients with AF, and offer a number of advantages over warfarin, for both the clinician and patient, including a favorable bleeding profile and convenience of use. Aspirin is no longer an option in secondary stroke prevention in patients with atrial fibrillation. Consideration of these new anticoagulants will improve clinical decision making.
Glauser, Bianca F; Mourão, Paulo A S; Pomin, Vitor H
Marine organisms are a rich source of sulfated polysaccharides with unique structures. Fucosylated chondroitin sulfate (FucCS) from the sea cucumber Ludwigothurea grisea and sulfated galactan from the red alga Botryocladia occidentalis are one of these unusual molecules. Besides their uncommon structures, they also exhibit high anticoagulant and antithrombotic effects. Earlier, it was considered that the anticoagulant activities of these two marine glycans were driven mainly by a catalytic serpin-dependent mechanism likewise the mammalian heparins. Its serpin-dependent anticoagulant action relies on promoting thrombin and/or factor Xa inhibition by their specific natural inhibitors (the serpins antithrombin and heparin cofactor II). However, as opposed to heparins, these two previously mentioned marine glycans were proved still capable in promoting coagulation inhibition using serpin-free plasmas. This puzzle observation was further investigated and clearly demonstrated that the cucumber FucCS and the red algal sulfated galactan have an unusual serpin-independent anticoagulant effect by inhibiting the formation of factor Xa and/or thrombin through the procoagulants tenase and prothrombinase complexes, respectively. These marine polysaccharides with unusual anticoagulant effects open clearly new perspectives for the development of new antithrombotic drugs as well as push the glycomics project.
Purrucker, Jan C.; Haas, Kirsten; Wolf, Marcel; Rizos, Timolaos; Khan, Shujah; Kraft, Peter; Poli, Sven; Dziewas, Rainer; Meyne, Johannes; Palm, Frederick; Jander, Sebastian; Möhlenbruch, Markus; Heuschmann, Peter U.; Veltkamp, Roland
Background and Purpose To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months. Results 231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5–26] vs. 1 d [0–4], P<0.001). Conclusions The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation. PMID:28178406
Tran, Arlene; Cheng-Lai, Angela
For more than 5 decades, warfarin has been the mainstay of therapy when oral anticoagulation is required. It has been shown to be effective in the prevention as well as treatment of various thromboembolic disorders. However, drawbacks of warfarin, such as time-consuming requirements for frequent international normalized ratio monitoring, as well as drug and food interactions, have encouraged the development of alternative oral agents. One such agent, dabigatran, has risen up to the challenge. Due to its predictable anticoagulation response, dabigatran does not require routine anticoagulation monitoring. Another advantage dabigatran has over warfarin is its more favorable drug and food interaction profiles. Dabigatran was shown to be noninferior to warfarin in studies evaluating the prevention of stroke and systemic embolism in patients with atrial fibrillation, thus leading to the US Food and Drug Administration approval for this indication. Dabigatran has also demonstrated efficacy in the prevention of venous thromboembolism in patients undergoing total hip or knee replacement surgery as well as the prevention of recurrent venous thromboembolism, although these are not current Food and Drug Administration-approved indications. The safety profile appears to be similar to warfarin with regards to overall bleeding risk, though the risk for gastrointestinal bleeds was higher in patients on dabigatran 150 mg twice daily. Disadvantages of dabigatran may include a higher frequency of dyspepsia compared with warfarin, lack of dosing information in severe renal impairment, possible missed opportunities for periodic health examinations and interventions due to elimination of regular physician's visit for international normalized ratio monitoring, and drug costs. This article provides an overview of the clinical studies, pharmacokinetic profile, adverse effects, drug interactions as well as advantages and disadvantages associated with dabigatran.
Sun, Yihong; Wang, Yitong; Jiang, Juan; Wang, Lina; Hu, Dayi
We investigated the risk of stroke associated with renal dysfunction and the impact of warfarin therapies in Chinese patients with nonvalvular atrial fibrillation (NVAF). Information was collected on age, sex, height, weight, type of atrial fibrillation, and serum creatinine within the previous 6 months, together with the variables needed to calculate the CHADS2 score. For patients not taking warfarin, reasons why not were recorded. Three thousand seventeen eligible patients with NVAF, mean (1 standard deviation [SD]) age of 67.7 (13.0) years, from 50 Chinese hospitals were included from May 2012 to October 2012, with a mean (1SD) CHADS2 score of 2.0 (1.5). Of these, 58.3% were male and 86.2% were at high risk of stroke with a CHADS2 score ≥1. Only 42.6% were on warfarin, and 22.5% of the patients had moderate or severe renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m(2)). After adjustment for the CHADS2 score, renal dysfunction remained moderately but significantly associated with the risk of stroke/TIA (odds ratio = 1.005, 95% confidence interval: 1.002-1.009, P = .002). There was, however, no significant difference in anticoagulant usage between patients with or without impaired renal dysfunction. The most common anticoagulant concerns were the low proportion of patients with regular international normalized ratio monitoring (43.0%) and the risk of bleeding (33.3%). Renal impairment was common and independently associated with the risk of cerebrovascular embolism in Chinese patients with NVAF but not independently related to underuse of anticoagulant treatment.
Walenga, Jeanine M; Thethi, Indermohan; Lewis, Bruce E
The topic of adverse effects of drugs is now receiving due attention in both the lay and medical communities. For drugs of the coagulation disorder class, such as anticoagulants and antiplatelet agents, the obvious adverse effects are bleeding from a dose too high and thrombosis from a dose too low. However, these drugs have other potential adverse effects that are not directly related to blood coagulation, yet cannot be dismissed due to their medical importance. There has been a recent advancement of several new drugs in this category and this number will soon grow as more drugs are reaching the end of their clinical trials. This article will discuss the nonhemostatic adverse effects of anticoagulants and antiplatelet drugs. As the adverse effects of bleeding and thrombosis will be excluded, this article will be in contrast to the typical discussions on the anticoagulant and antiplatelet drug classes.
Bernstein, M L; Salusinsky-Sternbach, M; Bellefleur, M; Esseltine, D W
Endogenous circulating anticoagulants are unusual in children without a congenital factor deficiency. In particular, the lupus anticoagulant has only rarely been reported in children. Despite its functioning in vitro to prolong the partial thromboplastin time, patients more frequently have problems with thrombosis than bleeding, unless there is a coexistent prothrombin deficiency or thrombocytopenia. We report the cases of three children with the lupus anticoagulant. Two children had associated thromboses. One had a thrombosis of the iliofemoral system and the other had a partial Budd-Chiari syndrome, a thrombosis of the deep calf veins and ureteric obstruction. The third child had a concomitant prothrombin deficiency and bleeding after tooth extraction. Associated findings in these patients included a positive antinuclear antibody test in two, a positive anti-DNA antibody test in two, a false-positive VDRL test in two, and an antiphospholipid antibody test in two.
Rusconi, Christopher P; Roberts, Joseph D; Pitoc, George A; Nimjee, Shahid M; White, Rebekah R; Quick, George; Scardino, Elizabeth; Fay, William P; Sullenger, Bruce A
Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.
Mikhail, M W; Kamilia; Allam, A M; Soliman, M I
Susceptibiliy level to bromadilone, difencoum and coumtertraly anticoagulants were studied in different species of Norway rat Rattus norvegicus and roof rat Rattus rattus trapped from El-Qualyobia Governorate in which the anticoagulant rodenticides were used to control rodents for long periods in some rural regions at Qualyobia. Complete mortality was showed for both species and sex within a standard feeding period (6 days) indicated to be susceptible to the three anticoagulant rodenticides. The bait eaten and corresponding active ingredient showed a noticeable more intake for R. rattus than R. norvegicus for the three compounds. The time to death showed highest mean values for R. rattus comparison to R. norvegicus. Difencoum recorded highest values of time to death compare with bromadilone and coumatetralyl.
King, Nathan; Tran, Minh-Ha
Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment
Akin, Ibrahim; Nienaber, Christoph A
Non-valvular atrial fibrillation is associated with a significantly increased risk of embolic stroke due to blood clot forming predominantly in the left atrial appendage (LAA). Preventive measures to avoid embolic events are permanent administration of anticoagulants or surgical closure of the LAA. Various clinical trials provide evidence about safety, effectiveness and therapeutic success of LAA occlusion using various cardiac occluder devices. The use of such implants for interventional closure of the LAA is likely to become a valuable alternative for stroke prevention, especially in patients with contraindication for oral anticoagulation as safety, clinical benefit and cost-effectiveness of LAA occlusion has recently been demonstrated. PMID:28289527
Tsoumani, Maria E; Tselepis, Alexandros D
Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration. In this review, we critically discuss their main pharmacodynamic and pharmacokinetic characteristics as well as recent advances in daily clinical practice.
Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Liumbruno, Giancarlo M.; Franchini, Massimo
Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect. PMID:27136433
Kang, Eungu; Kim, Yoon-Myung; Kim, Dae-Hee; Yoo, Han-Wook; Lee, Beom Hee
Abstract Rationale: Angiokeratomas are the earliest manifestation of Fabry disease (FD), and the extent of their appearance is related to disease severity. Angiokeratomas are mostly found on cutaneous regions. Patient concerns, diagnoses, interventions, and outcomes: Here we report an FD patient with widespread gastrointestinal angiokeratomas who developed life-threatening bleeding following anticoagulation for atrial fibrillation. Lessons: Careful observation for gastrointestinal bleeding is warranted for patients on anticoagulation with extensive cutaneous angiokeratomas. Furthermore, our experience suggests that surveillance is needed to assess the prevalence and extent of gastrointestinal angiokeratomas in patients with FD. PMID:28178158
Romero Ruiz, Adolfo; Romero-Arana, Adolfo; Gómez-Salgado, Juan
In recent years, a new line of treatment for the prevention of stroke in non-valvular atrial fibrillation, the so-called direct anticoagulants or new anticoagulants has appeared. The proper management and follow-up of these patients is essential to minimize their side effects and ensure patient safety. In this article, a description of these drugs is given, analyzing their characteristics, functioning and interactions together with the most habitual nursing interventions, as well as a reflection on the implications for the practice.
Laroche, J-P; Schved, J-F
Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) are now in competition. The companies are trying to replace VKA by DOACs, totally or at least greatly VKA should VKA disappear in favor of DOACs? There are still many questions about DOACs. The purpose of this article is to make a well-considered decision in this area. The aim is not to denigrate one or the other but to share things between these two families of anticoagulants. Physicians using these drugs must have a full knowledge about compared efficacy and safety. We feel necessary to increase distance between effective results of the clinical trials and industrial communication around DOACs.
Parekh, Parth J; Merrell, Jonathan; Clary, Meredith; Brush, John E; Johnson, David A
The discovery of the first oral anticoagulant, warfarin, was a milestone in anticoagulation. Warfarin's well-known limitations, however, have led to the recent development of more effective anticoagulants. The rapidly growing list of these drugs, however, presents a challenge to endoscopists who must treat patients on these sundry medications. This review is intended to summarize the pharmacological highlights of new anticoagulants, with particular attention to suggested "best-practice" recommendations for the withholding of these drugs before endoscopic procedures.
Study objective The acute management of patients on warfarin with spontaneous or traumatic intracranial hemorrhage continues to be debated in the medical literature. The objective of this paper was to conduct a structured review of the medical literature and summarize the advantages and risks of the available treatment options for reversing warfarin anticoagulation in patients who present to the emergency department with acute intracranial hemorrhage. Methods A structured literature search and review of articles relevant to intracranial hemorrhage and warfarin and treatment in the emergency department was performed. Databases for PubMed, CINAHL, and Cochrane EBM Reviews were electronically searched using keywords covering the concepts of anticoagulation drugs, intracranial hemorrhage (ICH), and treatment. The results generated by the search were limited to English- language articles and reviewed for relevance to our topic. The multiple database searches revealed 586 papers for review for possible inclusion. The final consensus of our comprehensive search strategy was a total of 23 original studies for inclusion in our review. Results Warfarin not only increases the risk of but also the severity of ICH by causing hematoma expansion. Prothrombin complex concentrate is statistically significantly faster at correcting the INR compared to fresh frozen plasma transfusions. Recombinant factor VIIa appears to rapidly reverse warfarin's effect on INR; however, this treatment is not FDA-approved and is associated with a 5% thromboembolic event rate. Slow intravenous dosing of vitamin K is recommended in patients with ICH. The 30-day risk for ischemic stroke after discontinuation of warfarin therapy was 3-5%. The risks of not reversing the anticoagulation in ICH generally outweigh the risk of thrombosis in the acute setting. Conclusions Increasing numbers of patients are on anticoagulation including warfarin. There is no uniform standard for reversing warfarin in intracranial
Valentinis, Alissia; Ivers, Noah; Bhatia, Sacha; Meshkat, Nazanin; Leblanc, Kori; Ha, Andrew; Morra, Dante
anticoagulation and an additional 8.7% (6 of 69) had documented reasons why they were not taking anticoagulants. Conclusion When assessed using the 2012 Canadian Cardiovascular Society AF guidelines, the proportion of patients receiving appropriate SPAF therapy in this primary care setting decreased substantially. All patients with CHADS2 scores of 0 or 1 should be reassessed to ensure that they are receiving optimal stroke prevention treatment. PMID:24627401
New oral anticoagulants offer several potential advantages including oral administration, fixed doses, no regular coagulation monitoring and dose adjustment and wide therapeutic index. The results from clinical studies for prevention and treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation show that these agents are at least as effective as or superior to currently available therapies depending on the molecules and dose regimen. Physicians will have to make choices among available new agents taking into account their pharmacokinetic properties, half-life, route of elimination and patient comorbidities. But the use of these new agents in daily practice raises some issues such as temporary discontinuation in patients undergoing invasive procedures and management of patients with bleeding in the absence of specific antidote. New oral anticoagulants should be used with caution in daily practice in special populations such as elderly patients, patients with renal impairment and patients with cancer. Primary care physicians will have to play a role in monitoring and evaluating the long-term efficacy and safety of these agents in daily practice.
Hanna, Michael S; Mohan, Puneet; Knabb, Robert; Gupta, Elora; Frost, Charles; Lawrence, John H
The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk. Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels. Our discussion here focuses on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation (NVAF). Supporting this indication, a pair of registrational trials was conducted that enrolled the full spectrum of patients who, by guidelines, were eligible for anticoagulation. In the AVERROES study of patients who were unsuitable for warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke or systemic embolism (SSE), without a significant increase in major bleeding (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the rates of SSE, MB, and all-cause mortality. Overall, these studies have demonstrated a substantially favorable benefit-risk profile for apixaban over warfarin and aspirin in NVAF.
Peacock, W Frank; Rafique, Zubaid; Singer, Adam J
Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)-dabigatran, rivaroxaban, apixaban, and edoxaban-have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.
Boos, Christopher J; More, Ranjit S
Objectives Ximelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF). Materials and methods We provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF. Results Adjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 × normal) in 6% of patients. Conclusions Current data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed. PMID:15104801
Peacock, W. Frank; Rafique, Zubaid; Singer, Adam J.
Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895
Karimi, Ebrahim; Ardestani, Seyyed Hadi Samimi; Jafari, Mehrdad; Hagh, Ali Bagheri
Objectives Free flaps are widely used to reconstruct head and neck defects. Despite the improvement in the surgical techniques and the surgeons’ experiences, flap failures still occur due to thrombotic occlusion after small vessels anastomosis. To reduce the possibility of flap loss as a result of thrombotic occlusion, various anticoagulants have been used. In this study we decided to evaluate a new protocol for anticoagulation therapy and its effect on flap survival and complications. Methods In this interventional study, 30 patients with head and neck cancer underwent surgical defects were reconstructed by microvascular free flap between 2013 and 2014. In the postoperative period patients have taken aspirin (100 mg/day) for 5 days and enoxaparin (40 mg/day subcutaneously) for 3 days. The flap survival was followed for three weeks. Results Given that there was no complete necrosis or loss of flap, the free flap success rate was as much as 100%. The need for re-exploration occurred in 3 patients (10%). Only in one patient the need for re-exploration was due to problem in venous blood flow. Conclusion The aspirin-enoxaparin short-term protocol may be a good choice after free flap transfer in reconstruction of head and neck surgical defects. PMID:27337950
Gurbel, Paul A; Tantry, Udaya S
There has been a 3-fold increase in hospital discharges for heart failure (HF) and also significantly increased mortality rate in HF patients in recent years. A major focus of HF research has been in the area of neurohormonal control and resynchronization therapy. There is a great urgency in better understanding the pathophysiology underlying the exceedingly high mortality and a need for exploration of therapeutic strategies beyond those that influence neurohormonal pathways. The decision to treat patients with HF with antiplatelet therapy remains largely influenced by the presence or absence of concomitant arterial disease. Antithrombotic therapy has been shown to be effective in many forms of cardiac disease, including patients with HF and atrial fibrillation. Although it is clear that platelet activation and hypercoagulability are present in HF, and there is evidence that stroke is reduced by warfarin therapy in the HF patient, the available data suggest that the risk of major bleeding overshadows the antithromboembolic benefit in HF patients in sinus rhythm. The utility of oral anticoagulant and/or antiplatelet therapy has never been evaluated in an adequately powered dedicated clinical trial of HF patients in sinus rhythm. In this state-of-the art paper we explore the evidence for targeting the inhibition of platelet function and coagulation to improve outcomes in the HF patient.
Grigorjeva, M E; Lyapina, L A
The effects of semax on anticoagulant, fibrinolytic, and platelet components of the anticoagulation system were studied on albino rats under conditions of acute and chronic immobilization stress. Semax exhibited a protective antistress effect after repeated intranasal administration under conditions of hypercoagulation developing in response to immobilization stress of different degree. The effect manifested in stimulation of the anticoagulation system.
Prins, Martin H; Marrel, Alexia; Carita, Paulo; Anderson, David; Bousser, Marie-Germaine; Crijns, Harry; Consoli, Silla; Arnould, Benoit
Background The side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment. Methods A conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31) and clinician (n = 17) interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF), deep venous thrombosis (DVT), or pulmonary embolism (PE). Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions. Results Initial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items), "Convenience" (11 items), "Burden of Disease and Treatment" (2 items) and "Anticoagulant Treatment Satisfaction" (7 items). No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated. Conclusion The PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients. Its validation and
Hartmann, S; Biliouris, K; Lesko, LJ; Nowak‐Göttl, U
Warfarin is the anticoagulant of choice for venous thromboembolism (VTE) treatment, although its suppression of the endogenous clot‐dissolution complex APC:PS may ultimately lead to longer time‐to‐clot dissolution profiles, resulting in increased risk of re‐thrombosis. This detrimental effect might not occur during VTE treatment using other anticoagulants, such as rivaroxaban or enoxaparin, given their different mechanisms of action within the coagulation network. A quantitative systems pharmacology model was developed describing the coagulation network to monitor clotting factor levels under warfarin, enoxaparin, and rivaroxaban treatment. The model allowed for estimation of all factor rate constants and production rates. Predictions of individual coagulation factor time courses under steady‐state warfarin, enoxaparin, and rivaroxaban treatment reflected the suppression of protein C and protein S under warfarin compared to rivaroxaban and enoxaparin. The model may be used as a tool during clinical practice to predict effects of anticoagulants on individual clotting factor time courses and optimize antithrombotic therapy. PMID:27647667
Long, Jianhai; Peng, Xiaobo; Luo, Yuan; Sun, Yawei; Lin, Guodong; Wang, Yongan; Qiu, Zewu
Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models.Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients' sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period.Only VKSTT (partial regression coefficient -1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period.After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10-120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration.
Long, Jianhai; Peng, Xiaobo; Luo, Yuan; Sun, Yawei; Lin, Guodong; Wang, Yongan; Qiu, Zewu
Abstract Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models. Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients’ sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period. Only VKSTT (partial regression coefficient −1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period. After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10–120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration. PMID:28002326
Recommended Therapeutic INR Range for Patients with Antiphospholipid Syndrome on Warfarin Anticoagulation: Is Moderate-Intensity (INR 2.0 - 3.0) or High-Intensity (INR 3.1 - 4.0) Better for Reducing Risk of Recurrent Thromboembolic Events?
Do, Tiffanie; Peacock, Katie; Takundwa, Prisca T
Patients with antiphospholipid syndrome (APS) are at increased risk of recurrent thromboembolic events due to the pathology of the disease. While prolonged anticoagulation is the treatment of choice for patients with thrombosis, much debate remains about the optimum intensity of anticoagulation. Anticoagulation with warfarin has been shown to decrease rates of thrombosis recurrence, but definitive evidence regarding targeted therapy to an INR of moderate (2.0 - 3.0) or high (3.1 - 4.0) intensity is lacking. PMID:27725921
The principal complication of the atrial arrythmias is the thrombo-embolic accident, notably the cerebro-vascular accident. The efficacity of the oral anticoagulants in reducing cerebro-vascular accidents has been demonstrated in numerous studies. This is significantly superior to that obtained with the anti-platelet drugs. However, the anti-vitamin K drugs (warfarin) carry a risk of serious haemorrhage of around 5% per year. This restricts the proposal of this treatment to patients with an elevated risk of vascular accidents: age, diabetes, previous cerebro-vascular accidents, and cardiac failure are the risk factors. Nevertheless, the risk of haemorrhage is responsible for an under prescription of the anticoagulants in the elderly. This explains the interest aroused by alternative therapeutics: the results of trials on ximelagatran, a direct anti-thrombin, are promising. In patients with an arrythmia, cardioversion carries a thrombo-embolic risk of around 1%. This risk is reduced by prior anticoagulant treatment. The procedure for this treatment is orientated by a trans-oesophageal echocardiogram. The incertitude of the duration of anticoagulant therapy without cardioversion calls for respect of the arrythmia. The treatment of this is limited to control of the cardiac rhythm and anticoagulant treatment.
Murakami, Takashi; Hina, Kazuyoshi; Higashiya, Shunichi; Kawamura, Hiroshi; Murakami, Masaaki; Kamikawa, Shigeshi; Komatsubara, Issei; Kusachi, Shozo
Background: Some patients with atrial fibrillation (AF) received underdoses of non-vitamin K antagonist oral anticoagulants (NOACs) in the real world. Underdosing is defined as administration of a dose lower than the manufacturer recommended dose. Objectives: To identify the efficacy and safety of underdosing NOACs as perioperative anticoagulation for atrial fibrillation ablation. Methods: We retrospectively analyzed patients who received rivaroxaban or dabigatran etexilate according to dosage: adjusted low dosage (reduced by disturbed renal function; n = 30), underdosage (n = 307), or standard dosage (n = 683). Non-vitamin K antagonist oral anticoagulants and dosing decisions were at the discretion of treating cardiologists. Results: Patients who received underdosed NOACs were older, more often female, and had lower body weight and lower renal function than those who received standard dosages. Activated clotting time at baseline in patients who received adjusted low dosage or underdosages was slightly longer than that in patients receiving standard dosages (156 ± 23, 151 ± 224, and 147 ± 24 seconds, respectively). Meaningful differences were not observed in other coagulation parameters. Adjusted low-, under-, and standard-dosing regimens did not differ in perioperative thromboembolic complications (0/30, 0.0%; 1/307, 0.3%; and 0/683, 0%, respectively) or major (0/30, 0.0%; 2/307, 0.6%; 3/683, 0.4%) and minor (1/30, 3.3%; 13/307, 4.2%; 25/683, 3.6%) bleeding episodes. When comparisons were performed for each NOAC, similar results were observed. Conclusions: With consideration of patient condition, age, sex, body weight, body mass index, and renal function, underdosing NOACs was effective and safe as a perioperative anticoagulation therapy for atrial fibrillation ablation. The therapeutic range of NOACs is potentially wider than manufacturer recommendations. PMID:28170360
Garg, Vaani Panse; Halperin, Jonathan L
This article reviews the pivotal studies of several novel antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran, rivaroxaban, and apixaban) agents. The clinical use of these drugs in cardiac intensive care is discussed, focusing on the management of acute coronary syndromes, ischemic stroke, atrial fibrillation, and venous thromboembolism.
Duric, Kemal; Kovac-Besovic, Elvira E.; Niksic, Haris; Muratovic, Samija; Sofic, Emin
Platelet hyperactivity and platelet interaction with endothelial cells contribute to the development and progression of many cardiovascular diseases such as atherosclerosis and thrombosis. The impact of platelet activity with different pharmacological agents, such as acetylsalicylic acid and coumarin derivatives, has been shown to be effective in the prevention of cardiovascular disease. Artemisia dracunculus, L. Asteraceae (Tarragon) is used for centuries in the daily diet in many Middle Eastern countries, and it is well known for its anticoagulant activity. The present study investigates the presence of coumarins in tarragon leaves and subsequently determines the extract with a major amount of coumarin derivatives. The solvents of different polarities and different pH values were used for the purpose of purifying the primary extract in order to obtain fractions with the highest coumarin content. Those extracts and fractions were investigated for their anticoagulant activity by determining prothrombin time (PT) and the international normalized ratio (INR), expressed in relation to the coagulation time of the healthy person. Purified extracts and fractions obtained from plant residue after essential oil distillation, concentrated in coumarin derivatives, showed the best anticoagulant activity, using samples of human blood. INR maximum value (2.34) and consequently the best anticoagulant activity showed the methanol extract at concentration of 5%. The INR value of normal plasma in testing this extract was 1.05. PMID:26042507
Diener, H C; Hajjar, K; Frank, B; Perrey, M
Oral anticoagulation with vitamin K antagonists (warfarin, phenprocoumon) is successful in both primary and secondary stroke prevention for patients with atrial fibrillation (AF), yielding a 60-70% relative reduction in stroke risk compared with placebo and a mortality reduction of 26%. However, these agents have a number of well documented shortcomings. This review describes the current landscape and developments in stroke prevention in patients with AF with special reference to secondary prevention. A number of new drugs for oral anticoagulation that do not exhibit the limitations of vitamin K antagonists are under investigation. These include direct factor Xa inhibitors and direct thrombin inhibitors. Recent studies (RE-LY, ROCKET-AF, AVERROES, ARISTOTLE) provide promising results for these new agents including higher efficacy and significantly lower incidences of intracranial bleeding compared with warfarin. The new substances show similar results in secondary as well as in primary stroke prevention in patients with AF. The new anticoagulants add to the therapeutic options for patients with AF and offer a number of advantages over warfarin for both clinician and patient, including a favorable bleeding profile and convenience of use. Consideration of these new anticoagulants will improve clinical decision-making.
Arvidsson, S; Askendal, A; Lindahl, T L; Tengvall, P
Surface mediated immune complement activation can be detected by a variety of antibody utilizing methods such as ELISA, fluorescence- or radiolabelling techniques, QCM, and ellipsometry. In the present work we investigated how the common anticoagulants heparin, dalteparin, fondaparinux and sodium citrate affected the binding of anti-complement factor 3c (anti-C3c) on a model complement activator surface, immobilised IgG, after incubation in human blood serum. The results show, as expected, that different anticoagulants affect the antibody binding differently. Increasing amounts of heparin, dalteparin and sodium citrate in normal serum resulted in a decreasing anti-C3c binding. The antibody deposition was not sensitive for the fondaparinux concentration. Surprisingly high concentrations of anti-coagulantia were needed to completely eradicate the antibody binding. Experiments in EGTA-serum showed that anticoagulants interfered directly with both the classical and alternative pathways. Control C3a-des arg ELISA measurements show that the lowered antibody surface binding was not a result of complement depletion in serum. Kallikrein generation by hydrophilic glass surfaces was not affected by high anticoagulant concentrations.
Middleberg, Robert A; Homan, Joseph
Rodenticide anticoagulants are used in the control of rodent populations. In addition to accidental ingestions in humans, such agents have also been used for homicidal and suicidal purposes. There are two major groups of rodenticide anticoagulants - hydroxycoumarins and indanediones. Before the advent of LC-MS/MS, analysis for such agents was relegated to such techniques as TLC and HPLC with nonspecific modes of detection. LC-MS/MS has been used to determine any given number of rodenticide anticoagulants in animal tissues, foods, plasma, etc. Use of this technique allows for the simultaneous identification of individual compounds within both classes of rodenticide anticoagulants. The LC-MS/MS method presented allows for simultaneous qualitative identification of brodifacoum, bromadiolone, chlorphacinone, dicumarol, difenacoum, diphacinone, and warfarin in blood, serum, and plasma using ESI in the negative mode. Two transitions are monitored for each analyte after a simple sample preparation. Chromatographic separation is accomplished using a gradient of ammonium hydroxide in water and ammonium hydroxide in methanol. Chloro-warfarin is used as internal standard.
Adiguzel, Cafer; Iqbal, Omer; Hoppensteadt, Debra; Jeske, Walter; Cunanan, Josephine; Litinas, Evangelos; He Zhu; Walenga, Jeanine M; Fareed, Jawed
Sulodexide represents a novel antithrombotic agent with multiple sites of action on blood coagulation and vascular processes. The purpose of this study was to compare sulodexide and enoxaparin on anticoagulant effects, tissue factor (TF)-induced activation of platelets, inhibition of microparticle generation and to investigate their effect on heparin-induced platelet aggregation (HIPA). Sulodexide was compared with enoxaparin at equigravimetric concentrations. When compared to enoxaparin, sulodexide produced a stronger anticoagulant effect in the prothrombin time (PT), activated partial thromboplastin time (APTT), Heptest, and thrombin time (TT) assays. In addition, sulodexide had a stronger inhibitory effect on TF-mediated microparticle generation (IC(50) = 2.8 microg/ mL), P-selectin expression (IC(50) = 4.8 microg/ml), and platelet aggregate formation (IC(50) = 8.5 microg/mL) compared to higher IC(50) values with enoxaparin. Sulodexide and enoxaparin exhibited a similar effect on heparin-induced thrombocytopenia (HIT) antibody-mediated platelet activation HIPA assays. These results suggest that sulodexide is a relatively stronger anticoagulant agent than enoxaparin. Sulodexide is subcutaneously absorbed. Its ability to inhibit TF-mediated platelet activation may contribute to the observed therapeutic effects of sulodexide in microvascular vasculopathy such as diabetic nephropathy. These results also suggest that inhibition of TF activation of platelets by sulodexide may be independent of its anticoagulant effects. These results warrant further investigation of sulodexide in additional preclinical and clinical studies.
Bliden, Kevin P; Chaudhary, Rahul; Mohammed, Nafees; Muresan, Adina A; Lopez-Espina, Carlos G; Cohen, Eli; Raviv, Gabriel; Doubleday, Marc; Zaman, Fowzia; Mathew, Blessy; Tantry, Udaya S; Gurbel, Paul A
Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs. Blood from healthy volunteers (n = 26) was used to obtain a baseline reference range. Data derived from patients on factor Xa inhibitors (FXi) (rivaroxaban and apixaban) (n = 39), and direct thrombin inhibitors (DTIs) (dabigatran) (n = 25) were compared against the reference range for detection of drug effect and drug classification. TEG®6s R-time highly correlated to each NOAC. Presence of NOACs caused elongation of R-time on the AFXa assay compared to the reference range (4.3 ± 1.7 vs. 1.3 ± 0.3 min. for FXi, p < 0.001 and 3.5 ± 1.2 vs. 1.3 ± 0.3 min. for DTI, p < 0.001). R-time on the DTI assay was elongated only in presence of a DTI (3.4 ± 1.0 vs. 1.5 ± 0.2 min, p < 0.001). The cutoff for detection of a DTI effect was an R time of 1.9 min and for anti-Xa effect was 1.95 min. For detection of NOAC therapy, there was ≥92% sensitivity and ≥95% specificity. The automated TEG®6s NOAC assay may be an effective tool to identify an anticoagulant effect from NOAC therapy and facilitate care of patients with bleeding or at risk of bleeding in the event of needing emergency surgery.
Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar
Purpose The risk of venous thromboembolism (VTE) recurrence is high following an initial VTE event, and it persists over time. This recurrence risk decreases rapidly after starting with anticoagulation treatment and reduces by ~80%–90% with prolonged anticoagulation. Nonpersistence with anticoagulants could lead to increased risk of VTE recurrence. This systematic review aimed to estimate persistence at 3, 6, and 12 months with anticoagulants in patients with VTE, and to evaluate the risk of VTE recurrence in nonpersistent patients. Methods PubMed and Embase® were searched up to May 3, 2014 and the search results updated to May 31, 2015. Studies involving patients with VTE aged ≥18 years, treatment with anticoagulants intended for at least 3 months or more, and reporting data for persistence were included. Proportions were transformed using Freeman–Tukey double arcsine transformation and pooled using the DerSimonian–Laird random-effects approach. Results In total, 12 observational studies (7/12 conference abstracts) were included in the review. All 12 studies either reported or provided data for persistence. The total number of patients meta-analyzed to estimate persistence at 3, 6, and 12 months was 71,969 patients, 58,940 patients, and 68,235 patients, respectively. The estimated persistence for 3, 6, and 12 months of therapy was 83% (95% confidence interval [CI], 78–87; I2=99.3%), 62% (95% CI, 58–66; I2=98.1%), and 31% (95% CI, 22–40; I2=99.8%), respectively. Only two studies reported the risk of VTE recurrence based on nonpersistence – one at 3 months and the other at 12 months. Conclusion Limited evidence showed that persistence was suboptimal with an estimated 17% patients being nonpersistent with anticoagulants in the crucial first 3 months. Persistence declined over 6 and 12 months. Observational data on persistence with anticoagulation treatment, especially direct oral anticoagulants, in patients with VTE and its effect on risk of VTE
Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana
Introduction Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30–40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. Trial registration number ACTRN12614000418673, Pre-results. PMID:27932335
Pršić, Adnan; Kiwanuka, Elizabeth; Caterson, Stephanie A.
Microvascular free flaps are key components of reconstructive surgery, but despite their common use and usual reliability, flap failures still occur. Many pharmacological agents have been utilized to minimize risk of flap failure caused by thrombosis. However, the challenge of most antithrombotic therapy lies in providing patients with optimal antithrombotic prophylaxis without adverse bleeding effects. There is a limited but growing body of evidence suggesting that the vasoprotective and anti-inflammatory actions of statins can be beneficial for free flap survival. By inhibiting mevalonic acid, the downstream effects of statins include reduction of inflammation, reduced thrombogenicity, and improved vasodilation. This review provides a summary of the pathophysiology of thrombus formation and the current evidence of anticoagulation practices with aspirin, heparin, and dextran. In addition, the potential benefits of statins in the perioperative management of free flaps are highlighted. PMID:26617953
Leitgeb, Anna M.; Blomqvist, Karin; Cho-Ngwa, Fidelis; Samje, Moses; Nde, Peter; Titanji, Vincent; Wahlgren, Mats
The binding of Plasmodium falciparum parasitized erythrocytes to uninfected erythrocytes (rosetting) is associated with severe malaria. The glycosaminoglycan heparan sulfate is an important receptor for rosetting. The related glycosaminoglycan heparin was previously used in treatment of severe malaria, although abandoned because of the occurrence of severe bleedings. Instead, low anticoagulant heparin (LAH) has been suggested for treatment. LAH has successfully been evaluated in safety studies and found to disrupt rosettes and cytoadherence in vitro and in vivo in animal models, but the effect of LAH on fresh parasite isolates has not been studied. Herein, we report that two different LAHs (DFX232 and Sevuparin) disrupt rosettes in the majority of fresh isolates from Cameroonian children with malaria. The rosette disruption effect was more pronounced in isolates from complicated cases than from mild cases. The data support LAH as adjunct therapy in severe malaria. PMID:21363975
Ruan, Yuheng; Bridges, Jonathan S; Kumar, Kapil; Raphael, Jonelle A; Acharjee, Subroto; Welty, Francine K
Antiphospholipid syndrome (APS) is a disorder characterized by recurrent venous or arterial thrombosis and/or fetal loss; involvement of cardiac valves is also seen. A seronegative variant has been described previously. We report a case of a woman with recurrent pregnancy loss, prior strokes, and a negative workup for known antiphospholipid antibodies. During her current pregnancy, she presented with acute stroke and mitral valve vegetation. Her workup for antiphospholipid syndrome and other thrombophilias remained negative even after the stroke. Her mitral valve vegetation resolved completely with aspirin, heparin, and warfarin. We believe this to be the first report of complete resolution of valvular vegetation with antiplatelet and anticoagulant therapy alone in a patient with seronegative antiphospholipid syndrome. Moreover, this appears to be the first report of stroke associated with this condition.
Ouwendijk, R J; Koster, J C; Wilson, J H; Stibbe, J; Lameris, J S; Visser, W; Benhamou, J P
The case of a 20 year old woman is reported with Budd-Chiari syndrome in whom lupus anticoagulant and anticardiolipin antibodies were shown; treatment with oral anticoagulants induced a considerable improvement. This treatment was interrupted after one year; interruption was followed by redevelopment of ascites. Further treatment with anticoagulants was continued for five years with noticeable improvement. When treatment with oral anticoagulants was stopped because of pregnancy, the patient redeveloped ascites and had a spontaneous miscarriage. Subsequently, treatment with oral anticoagulants was reintroduced and again resulted in noticeable improvement. In conclusion patients with Budd-Chiari syndrome should be tested for lupus anticoagulants and anticardiolipin antibodies, Budd-Chiari syndrome resulting from this cause may have a good response to treatment with oral anticoagulants; this treatment should be maintained permanently, and pregnancy in such patients may initiate serious difficulties. Images p1004-a PMID:8063206
Oprita, R; Oprita, B; Diaconescu, B; Bratu, MR; Berceanu, D
Anticoagulants are frequently used medications in diverse cardiovascular diseases. Their uses highly increase the risk of bleeding from upper and lower gastrointestinal sources, whether there is a classic vitamin K antagonist or a novel oral anticoagulant. Their interruption can promote procoagulation status with different thromboembolic accidents. Discontinuation of oral anticoagulants before the elective procedures is standardized but there are no guidelines for managing bleeding lesions of upper gastrointestinal tract concomitant with anticoagulation. Also, because some of the anticoagulants are new comers, there is no specific antidote, and so their anticoagulation effect cannot be antagonized fast in order to reduce the bleeding. Therefore, the endoscopic hemostasis must be definitive and efficient. This is a short review of the current management for the bleeding lesions of the upper gastrointestinal tract in patients taking oral anticoagulants. PMID:28255372
Date, Kazuma; Kishimoto, Satoru; Fujii, Yutaka; Togo, Konomi; Kakuta, Yukihide; Mizuno, Toshihide; Tsukiya, Tomonori; Takewa, Yoshiaki; Nishimura, Takashi; Ono, Minoru; Tatsumi, Eisuke
For the continued development of improved mechanical circulatory systems, longer term evaluation of new devices in animal model experiments may be critical. The effects of anticoagulants in adult goats have not been well studied. We assessed the effects of oral warfarin in three adult goats during fasting or after feeding. The goats [weighing 57.8 ± 8.1 kg (53.0-67.2 kg)] were administered warfarin orally beginning at a dose of 5 mg/day and then increasing to 10, 20, 40, and 60 mg every 2 weeks. One goat (receiving 10 mg/day warfarin) was killed on day 27 because of the inability to stand. After administration of 60 mg warfarin, the remaining goat received no warfarin for 4 days to return to coagulated state. The goats were then fasted and treated with 40 mg warfarin. During warfarin administration, both goats required a dose of 60 mg/day to achieve International Normalized Ratios (INRs) of approximately 2.5; however, when, the animals were in the fasted condition, precipitous extension of INR was observed in 5 days. After resuming feeding, the INR was reduced to the proper range. We showed the tendency that warfarin therapy in goats required higher doses than the doses administered to human patients and that the effects of therapy were related to the feeding state. The results of this study provide important information for development of anticoagulation protocols to assess mechanical circulatory support devices for long-term use in preclinical examination.
Saray, Aida; Mesihović, Rusmir; Vukobrat-Bijedić, Zora; Gornjaković, Srđan; Vanis, Nenad; Mehmedović, Amila; Papović, Vedad; Glavaš, Sanjin
Previous studies have reported reduced synthesis of various hemostatic factors in patients with chronic liver disease. Whether changes in plasma levels of these proteins reflect recovered liver synthetic function following virological eradication therapy has not been approved yet. The aim of the study was to determine the impact of sustained viral suppression achieved with pegylated interferon alpha and ribavirin on hemostatic parameters including natural anticoagulants in patients with chronic hepatitis C. The following coagulation screening tests were obtained in thirty patients with chronic viral hepatitis C before and after completion of antiviral treatment: activated partial thromboplastin time, prothrombin time, plasma fibrinogen and natural anticoagulant proteins antithrombin III, protein C (PC) and total protein S (PS) activity. Only patients who achieved durable virus suppression were included. The mean PC and PS levels were significantly lower in patients with chronic viral hepatitis C before antiviral therapy than in healthy controls (79.04 ± 16.19 % vs. 109.92 ± 21.33% and 54.04 ± 16.11% vs. 87.60 ± 8.15%, respectively; (p<0.001). Mean levels of PC exhibited a significant increase by 14.69 % after the completion of antiviral treatment (93.73 ± 14.18%, p<0.001) as well as PS levels, which significantly increased by 21.46% (75.50 ± 15.43, p<0.001) when compared with pre-treatment values. No remarkable fluctuations in other hemostatic parameters were noted. Protein C and protein S are sensitive markers of hepatocyte synthetic impairment and are valuable markers in monitoring the efficacy of antiviral treatment in chronic hepatitis C patients. Larger studies are needed to confirm our results.
Mosler, P; Mergener, K; Denzer, U; Kiesslich, R; Galle, P R; Kanzler, S
Anticoagulants and antiplatelet agents are widely used in the prophylaxis and management of thromboembolic and cardiovascular diseases. Gastrointestinal bleeding is a well-known complication of these agents. Modification of anticoagulant and antiplatelet therapy is often required in patients undergoing surgical procedures and specific recommendations for the perioperative period have been issued. Fewer data exist with regard to the use of these agents around the time of endoscopic procedures. A survey of the American Society for Gastrointestinal Endoscopy (ASGE), performed several years ago, showed a wide variation between endoscopists in the management of anticoagulants and antiplatelet agents in the periendoscopic period. Subsequently, guidelines have been proposed by the ASGE as well as the German Society for Gastroenterology (DGVS). The aim of this study was to investigate the current practices among German endoscopists regarding the use of these medications in patients undergoing endoscopic procedures and to assess their adherence to published guidelines. Our data demonstrate that, in spite of the dissemination of guidelines, there is still a wide variation in the periendoscopic management of patients who are at increased risk for bleeding due to anticoagulants, especially in patients taking antiplatelet agents.
Witt, Daniel M; Clark, Nathan P; Kaatz, Scott; Schnurr, Terri; Ansell, Jack E
Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This article, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. Well-managed warfarin therapy remains an important anticoagulant option and it is hoped that anticoagulation providers will find the guidance contained in this article increases their ability to achieve optimal outcomes for their patients with VTE Pivotal practical questions pertaining to this topic were developed by consensus of the authors and were derived from evidence-based consensus statements whenever possible. The medical literature was reviewed and summarized using guidance statements that reflect the consensus opinion(s) of all authors and the endorsement of the Anticoagulation Forum's Board of Directors. In an effort to provide practical and implementable information about VTE and its treatment, guidance statements pertaining to choosing good candidates for warfarin therapy, warfarin initiation, optimizing warfarin control, invasive procedure management, excessive anticoagulation, subtherapeutic anticoagulation, drug interactions, switching between anticoagulants, and care transitions are provided.
Conway, Susan E; Marcy, Todd R
Clinical practice guidelines currently suggest extended anticoagulation therapy for primary and secondary prevention of venous thromboembolism (VTE). The optimal duration of anticoagulation has been an active area of clinical investigation for patients undergoing orthopedic surgeries and those diagnosed with a first episode of unprovoked VTE. Practice guidelines, VTE incidence, clinical predictors/mediators, and clinical trial evidence is reviewed to help pharmacists and other health care providers make an informed, patient-specific decision on the optimal duration of anticoagulation therapy. Extended anticoagulation up to 5 weeks following orthopedic surgery for primary VTE prevention and indefinitely following a first episode of unprovoked VTE for secondary VTE prevention should be considered only if the risk of bleeding is not high and the cost and burden of anticoagulation is acceptable to the patient. The optimal duration of anticoagulation therapy for primary or secondary prevention of VTE should include the health care provider and patient making a decision based on evaluation of individual benefits, risks, and preferences.
Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain.
Narouze, Samer; Benzon, Honorio T; Provenzano, David A; Buvanendran, Asokumar; De Andres, José; Deer, Timothy R; Rauck, Richard; Huntoon, Marc A
Interventional spine and pain procedures cover a far broader spectrum than those for regional anesthesia, reflecting diverse targets and goals. When surveyed, interventional pain and spine physicians attending the American Society of Regional Anesthesia and Pain Medicine (ASRA) 11th Annual Pain Medicine Meeting exhorted that existing ASRA guidelines for regional anesthesia in patients on antiplatelet and anticoagulant medications were insufficient for their needs. Those surveyed agreed that procedure-specific and patient-specific factors necessitated separate guidelines for pain and spine procedures. In response, ASRA formed a guidelines committee. After preliminary review of published complication reports and studies, committee members stratified interventional spine and pain procedures according to potential bleeding risk as low-, intermediate-, and high-risk procedures. The ASRA guidelines were deemed largely appropriate for the low- and intermediate-risk categories, but it was agreed that the high-risk targets required an intensive look at issues specific to patient safety and optimal outcomes in pain medicine. The latest evidence was sought through extensive database search strategies and the recommendations were evidence-based when available and pharmacology-driven otherwise. We could not provide strength and grading of these recommendations as there are not enough well-designed large studies concerning interventional pain procedures to support such grading. Although the guidelines could not always be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide sound recommendations and the evidentiary basis for such recommendations.
Background There is evidence suggesting that most thromboembolic complications could be prevented with adequate pharmacological anticoagulation. We estimated the direct health care costs of anticoagulant treatment with oral vitamin K antagonists in patients diagnosed with non-valvular atrial fibrillation. Methods This observational study examined the clinical records of patients diagnosed with non-valvular atrial fibrillation who received anticoagulant treatment with oral vitamin K antagonists. Data from clinical records were used in the study: international normalized ratio, number of monitoring visits, type of anticoagulant, hospital admissions from complications, and concomitant medication. Drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the Diagnosis Related Group price for each case. Hospital visits costs were calculated by one of four different scenarios, using either the invoice rates for the regional health care authority or cost per visit as established by analytical accounting methods. Results We collected data from 1,257 patients diagnosed with non-valvular atrial fibrillation who were receiving oral anticoagulant therapy. Depending on the scheme used, the direct health care costs for these patients ranged from €423,695 - €1,436,038 per annum. The average cost per patient varied between €392 - €1,341, depending on the approach used. Patients with international normalized ratio values within the therapeutic range on 25% of their visits represented an average cost between €441.70 - €1,592. Those within the therapeutic range on 25%–50% of visits had associated costs of €512.37 - €1,703.91. When international normalized ratio values were within the therapeutic range on 50% - 75% of the visits, the costs ranged between €400.80- €1,375.74. The
Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong
Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.
Baron, Todd H; Kamath, Patrick S; McBane, Robert D
A large number of patients worldwide receive anticoagulant and antiplatelet agents, collectively known as antithrombotic agents. Several new anticoagulants and antiplatelet agents recently were approved for use. Gastroenterologists may be unfamiliar with the mechanism of action, indications for use, and pharmacokinetics of these newer drugs. In patients undergoing elective and urgent endoscopic procedures, clinicians must be familiar with these medications to optimize outcomes. When the decision is made to continue the newer antithrombotic agents for elective procedures, the clinician must understand the risk that these agents may impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the presence of acute gastrointestinal bleeding. In this article the use of newer antithrombotic agents is reviewed.
Cohen, Harold V; Quek, Samuel Y P; Subramanian, Gayathri; Abbas, Ali
A recent occurrence in dental practice is the noting of new "blood thinners" when the clinician is reviewing a patient's medical history and medications. "Doc, I take Pradaxa or Effient or Xarelto" etc. After many years of the widespread use of aspirin and Coumadin there has appeared a new generation of medications focused on reducing thromboembolic events in patients at risk. This trend has been driven by a need for drugs providing better drug efficacy based on patient biologic processing of the medications and the frequency and cost factors associated with the monitoring the degree of anticoagulation. Guidelines for assessing bleeding risk and managing patients on these new medications in dental practice are not yet defined and are empirically based on medical practitioner experience. This paper will review these new medications and will discuss current considerations for dental patient care. (Note that not all new antiplatelet and anticoagulant medications will be reviewed in this paper.)
Crowther, Mark; Crowther, Mark A
The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.
Imran, Muhammad; Shafi, Humera; Wattoo, Sardar Ali; Chaudhary, Muhammad Taimoor; Usman, Hafiz Faisal
Anticoagulant rodenticides belong to a heterogeneous group of compounds which are used to kill rodents. They bind to enzyme complexes responsible for recycling of vitamin K, thus producing impairment in coagulation process. Rodenticides are among the most common house hold toxicants and exhibit wide variety of toxicities in non-target species especially in human, dogs and cats. This article reviews published analytical methods reported in literature for qualitative and quantitative determination of anticoagulant rodenticides in biological specimens. These techniques include high performance liquid chromatography coupled with ultraviolet and florescence detectors, liquid chromatography electrospray ionization tandem mass spectrometry, liquid chromatography with high resolution tandem mass spectrometry, ultra performance liquid chromatography mass spectrometry, gas chromatography mass spectrometry, ion chromatography with fluorescence detection, ion chromatography electrospray ionization ion trap mass spectrometry and ion chromatography electrospray ionization tandem mass spectrometry.
Liu, Xiaoqi; Cao, Ye; Zhao, Mengli; Deng, Jianhua; Li, Xifei; Li, Dejun
Graphene may have attractive properties for some biomedical applications, but its potential adverse biological effects, in particular, possible modulation when it comes in contact with blood, require further investigation. Little is known about the influence of exposure to COOH+-implanted graphene (COOH+/graphene) interacting with red blood cells and platelets. In this paper, COOH+/graphene was prepared by modified Hummers' method and implanted by COOH+ ions. The structure and surface chemical and physical properties of COOH+/graphene were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. Systematic evaluation of anticoagulation, including in vitro platelet adhesion assays and hemolytic assays, proved that COOH+/graphene has significant anticoagulation. In addition, at the dose of 5 × 1017 ions/cm2, COOH+/graphene responded best on platelet adhesion, aggregation, and platelet activation.
Madan, Shivanshu; Shah, Shenil; Dale, Patrick; Partovi, Sasan
New oral anticoagulants (NOAC) serve as alternatives for patients currently using warfarin for the prevention and treatment of venous thromboembolic (VTE) disease. This article provides a brief summary of the clinical use of these drugs as well as a review of the landmark clinical trials which evaluated described their safety and efficacy. As more data becomes available, a fundamental understanding of these medications will be vital to cardiovascular practitioners managing patients with VTE. PMID:28123977
Samama, Mm; Depasse, F
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.
Degoutin, S; Jimenez, M; Casetta, M; Bellayer, S; Chai, F; Blanchemain, N; Neut, C; Kacem, I; Traisnel, M; Martel, B
The aim of this work is to prepare non-woven polypropylene (PP) textile functionalized with bioactive molecules in order to improve its anticoagulation and antibacterial properties. This paper describes the optimization of the grafting process of acrylic acid (AA) on low-pressure cold-plasma pre-activated PP, the characterization of the modified substrates and the effect of these modifications on the in vitro biological response towards cells. Then, the immobilization of gentamicin (aminoglycoside antibiotic) and heparin (anticoagulation agent) has been carried out on the grafted samples by either ionic interactions or covalent linkages. Their bioactivity has been investigated and related to the nature of their interactions with the substrate. For gentamicin-immobilized AA-grafted samples, an inhibition radius and a reduction of 99% of the adhesion of Escherichia coli have been observed when gentamicin was linked by ionic interactions, allowing the release of the antibiotic. By contrast, for heparin-immobilized AA-grafted PP samples, a strong increase of the anticoagulant effect up to 35 min has been highlighted when heparin was covalently bonded on the substrate, by contact with the blood drop.
Martin, Jennifer A; Parekh, Parag; Kim, Youngmi; Morey, Timothy E; Sefah, Kwame; Gravenstein, Nikolaus; Dennis, Donn M; Tan, Weihong
Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT). Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug), and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction) and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.
Isokangas, Juha-Matti Peraelae, Jukka M.
The purpose of this study was to report a single hospital's experience of endovascular treatment of patients with retroperitoneal hemorrhage (RPH) secondary to anticoagulant treatment. Ten consecutive patients treated in an intensive care unit and needing blood transfusions due to RPH secondary to anticoagulation were referred for digital subtraction angiography (DSA) to detect the bleeding site(s) and to evaluate the possibilities of treating them by transcatheter embolization. DSA revealed bleeding site(s) in all 10 patients: 1 lumbar artery in 4 patients, 1 branch of internal iliac artery in 3 patients and multiple bleeding sites in 3 patients. Embolization could be performed in 9 of them. Coils, gelatin and/or polyvinyl alcohol were used as embolic agents. Bleeding stopped or markedly decreased after embolization in 8 of the 9 (89%) patients. Four patients were operated on prior to embolization, but surgery failed to control the bleeding in any of these cases. Abdominal compartment syndrome requiring surgical or radiological intervention after embolization developed in 5 patients. One patient died, and 2 had sequelae due to RPH. All 7 patients whose bleeding stopped after embolization had a good clinical outcome. Embolization seems to be an effective and safe method to control the bleeding in patients with RPH secondary to anticoagulant treatment when conservative treatment is insufficient.
Yoo, Hayoung; Ku, Sae-Kwang; Lee, Wonhwa; Kwak, Soyoung; Baek, Young-Doo; Min, Byung-Woon; Jeong, Gil-Saeng; Bae, Jong-Sup
Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudrania tricuspidata Bureau, is known to possess hepatoprotective, antiproliferative and anti-inflammatory activities. However, antiplatelet, anticoagulant, and profibrinolytic properties have not been studied. The anticoagulant activities of CTXA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). The effects of CTXA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells. Our data showed that CTXA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. CTXA prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by CTXA. Collectively, these results indicate that CTXA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents.
Bijak, Michal; Saluk, Joanna; Szelenberger, Rafal; Nowak, Pawel
Blood coagulation is a physiological process whose main task is prevention of blood loss from injured vessels. This process consists of a series of zymogens proteolytic activation leading to the generation of the main coagulation enzyme - thrombin. Besides its important role in blood coagulation process, thrombin is involved in many cardiovascular diseases, which are responsible for almost half of fatalities in economically developed countries. The evidence for the increased generation and in vivo activity of thrombin was observed in the plasma of individuals at high risk for clinically significant venous and arterial thromboembolic complications. Antioxidants activity of plants extracts has been well known for many years and was confirmed by many publications. However, during the last decade many research centers presented results suggesting anticoagulant potential of various plant extracts. Many researchers have also provided evidence that polyphenol compounds are able to inhibit the activity of many enzymes, including serine proteases. All research described in this review clearly indicate that polyphenols and polyphenol-rich extracts possess not only antioxidative but also anticoagulant properties and may be useful in creation of new therapeutic agents or dietary supplements. Based on described properties polyphenols would be very helpful with both prevention and treatment of thromboembolic complications associated with multiple failures of haemostasis, because the available therapeutic agents do not offer such double-effects (antioxidant and anticoagulant).
Karamichalakis, Nikolaos; Georgopoulos, Stamatis; Vlachos, Konstantinos; Liatakis, Ioannis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P
Atrial fibrillation and venous thromboembolism (VTE) are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of anticoagulants quite challenging. Novel oral anticoagulants (NOACs) have recently emerged as alternatives to Vitamin K Antagonists (VKAs) and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been well-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population. PMID:27781063
Hong, Sung Kuk; Hwang, Sang Mee; Kim, Ji-Eun; Kim, Hyun Kyung
The mixing test is used to determine the presence of inhibitors in laboratory diagnoses of lupus anticoagulant. Updated international guidelines state that an integrated lupus anticoagulant test system does not require the mixing test; an appraisal of the mixing tests in integrated lupus anticoagulant test systems is, therefore, required. We investigated the clinical relevance of mixing tests by using the best cutoff value of the mixing test through thrombotic risk analysis. A retrospective analysis was performed on 525 specimens with positive screening tests by using two integrated lupus anticoagulant tests: diluted Russell's Viper venom (dRVVT) and silica clotting time. The diagnostic performance of two interpretation formulas (percentage correction, Rosner index) was assessed, and the thrombotic risk of a subgroup based on the mixing results was investigated. Finally, the thrombotic risk of lupus anticoagulant positivity based on the integrated lupus anticoagulant test system procedures was assessed for the appraisal of mixing test exclusion in integrated lupus anticoagulant test systems. The best cutoff values of mixing test interpretation methods based on dRVVT were as follows: 60.1% for percentage correction and 15.7 for Rosner index. There was no substantial difference in the thrombotic risk between percentage correction and the Rosner index. The mixing-positive group showed a higher lupus anticoagulant titer and higher thrombotic risk than the mixing-negative group. However, even the mixing-negative group carried a significant risk of thrombosis. Finally, lupus anticoagulant positivity determined by the updated two-step procedure (screening and confirmation tests) showed higher thrombotic risk than that determined by the traditional three-step procedure (screening, mixing, and confirmation tests). Although a positive mixing result can predict a high risk of thrombosis, negative mixing results are also associated with a substantial thrombotic risk. The
Dolmella, A.; Gatto, S.; Girardi, E.; Bandoli, G.
Coumatetralyl and chlorophacinone, two substances related to 4-hydroxycoumarin (HC) and to 1,3-indandione (ID), respectively, show activity as anticoagulant rodenticides. In the present study we have investigated the solid-state structures of coumatetralyl and chlorophacinone by means of X-ray single-crystal and powder diffraction, along with thermal analysis. The crystal structures of the two compounds have been used as input geometries for a series of computational chemistry efforts, involving other anticoagulant derivatives as well. Thus, ab initio, semiempirical molecular orbital, molecular mechanics and molecular dynamics/simulated annealing calculations have been performed on thirteen anticoagulant rodenticides. In particular, the annealing calculations have been made to assess the conformational freedom of the compounds under scrutiny. All the generated conformers have been classified into families. The classification has first been made empirically, and then validated by means of a cluster analysis. A number of structural and physico-chemical parameters derived from the calculations has been used in turn for structure-activity relationships (SARs) investigations. In the latter, we have assessed how the selected parameters affect toxicity. The results seem to be consistent with a three-dimensional biophore model, in which higher toxicity is predicted for the more voluminous rodenticides. We suggest that these compounds better fit the active site of the target enzyme vitamin K 2,3-epoxide reductase (KO-reductase).
Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D; Granger, Christopher B; Halperin, Jonathan L; Hohnloser, Stefan H; Hylek, Elaine M; Kirchhof, Paulus; Lane, Deirdre A; Verheugt, Freek W A; Veltkamp, Roland; Lip, Gregory Y H
Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation.
Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E
Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.
Guimarães, Patrícia O; Kaatz, Scott; Lopes, Renato D
Atrial fibrillation (AF) is an important risk factor for thromboembolic events, and anticoagulation therapy can reduce this risk. Vitamin K antagonists (VKAs), such as warfarin, have been used for decades in patients with AF for stroke prevention. Currently, non-VKA oral anticoagulants (NOACs) are approved and available for non-valvular AF patients who are at increased risk of stroke. These agents are safe and effective and have important advantages over VKAs, such as significant reduction in intracranial hemorrhage and no need for routine laboratory monitoring. Thus, should all VKA-treated patients be switched to a NOAC? The aims of this article are: 1) to review the advantages of NOACs over VKAs; 2) to identify the group of patients who most benefit from receiving a NOAC and, therefore, are higher priority to be switched from VKAs; and 3) to provide clinical and practical guidance on how to switch patients safely from VKAs to NOACs. PMID:26379443
Coagulability increases during pregnancy, and thromboembolism can easily occur. Venous thromboembolism is a cause of death in pregnant women, but arterial thrombosis such as ischemic stroke in pregnancy is also not uncommon. In pharmacotherapy for thromboembolism in pregnant women, fetal toxicity and teratogenicity must be carefully considered. As anticoagulants in pregnant women, unfractionated heparin and low-molecular-weight heparin are recommended, but warfarin is not recommended since it has a low molecular weight and crosses the placenta. Various types of new oral anticoagulant drugs have been available in Japan since 2011. However, the Japanese package inserts for these anticoagulants advise quite cautious administration in pregnant women. The guidelines on pregnant women include less information about antiplatelet drugs than anticoagulant drugs. Aspirin may cause teratogenicity and fetal toxicity, and perinatal mortality is increased. However, when low doses of aspirin are administered as antiplatelet therapy, the US Food and Drug Administration has assigned pregnancy category C, and treatment is relatively safe. Neurosurgeons and neurologists commonly encounter pregnant women with thromboembolism, such as ischemic stroke. Up-to-date information and correct selection of drugs are necessary in consultation with specialists in perinatal care.
de Andrade Moura, Laura; Ortiz-Ramirez, Fredy; Cavalcanti, Diana Negrao; Ribeiro, Suzi Meneses; Muricy, Guilherme; Teixeira, Valeria Laneuville; Fuly, Andre Lopes
The ischemic disorders, in which platelet aggregation and blood coagulation are involved, represent a major cause of disability and death worldwide. The antithrombotic therapy has unsatisfactory performance and may produce side effects. So, there is a need to seek molecules with antithrombotic properties. Marine organisms produce substances with different well defined ecological functions. Moreover, some of these molecules also exhibit pharmacological properties such as antiviral, anticancer, antiophidic and anticoagulant properties. The aim of this study was to evaluate, through in vitro tests, the effect of two extracts of brown algae and ten marine sponges from Brazil on platelet aggregation and blood coagulation. Our results revealed that most of the extracts were capable of inhibiting platelet aggregation and clotting measured by plasma recalcification tests, prothrombin time, activated partial thromboplastin time, and fibrinogenolytic activity. On the other hand, five of ten species of sponges induced platelet aggregation. Thus, the marine organisms studied here may have molecules with antithrombotic properties, presenting biotechnological potential to antithrombotic therapy. Further chemical investigation should be conducted on the active species to discover useful molecules for the development of new drugs to treat clotting disorders. PMID:21892349
Lucke-Wold, Brandon P.; Turner, Ryan C.; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay
Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion
Lucke-Wold, Brandon P; Turner, Ryan C; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay
Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion
da Costa, Mário Augusto Cray; Krum, Lucas Kraeski; Geraldino, Juliana da Silva; Schafranski, Marcelo Derbli; Gomes, Ricardo Zanetti; Reis, Elise Souza dos Santos
INTRODUCTION: In patients with mechanical prosthetic heart valves or atrial fibrillation requiring anticoagulation to prevent thromboembolic events, several factors influence adherence and anticoagulation complications. OBJECTIVE: To evaluate the factors that interfere with the quality and complications of anticoagulation with vitamin K antagonists. METHODS: A retrospective cohort study of 100 patients, in the period from 2011 to 2014, was performed. Anticoagulation conditions in the last year, regarding the presence of complications (embolisms/bleeding) and inadequate treatment were assessed: achievement of less than 8 annual prothrombin times and International Normalized Ratio outside therapeutic target in more than 40% of prothrombin times. RESULTS: There were 31 complications (22 minor bleeding without hospitalization and 9 major complications: 7 bleeding with hospitalization and two emboli); 70 were with International Normalized Ratio outside the target in more than 40% of the tests and 36 with insufficient number of prothrombin times. Socioeconomic factors, anticoagulant type and anticoagulation reason had no relationship with complications or with inadequate treatment. There were more complications in patients with longer duration of anticoagulation (P=0.001). Women had more International Normalized Ratio outside the target range (OR 2.61, CI:1.0-6.5; P=0.04). Patients with lower number of annual prothrombin times had longer times of anticoagulation (P=0.03), less annual consultations (P=0.02) and less dose adjustments (P=0.003). Patients with longer duration of anticoagulation have more complications (P=0.001). CONCLUSION: There was a high rate of major complications and International Normalized Ratio was outside the goal. Less annual prothrombin times was related to longer duration of anticoagulation, less annual consultations and less dose adjustments. More major complications occurred in patients with longer duration of anticoagulation. PMID:27737407
Baik, Seo Hyon; Hernandez, Inmaculada; Zhang, Yuting
BACKGROUND As alternatives to warfarin, 2 novel oral anticoagulants (NOACs), dabigatran and rivaroxaban, were approved in 2010 and 2011 to prevent stroke and other thromboembolic events in patients with atrial fibrillation. It is unclear how patient characteristics are associated with the initiation of anticoagulants. OBJECTIVE To evaluate how patient demographics, clinical characteristics, types of insurance, and patient out-of-pocket spending affect the initiation of warfarin and 2 NOACs—dabigatran and rivaroxaban. METHODS We used pharmacy claims data from a 5% random sample of Medicare beneficiaries to identify patients who were newly diagnosed with atrial fibrillation between October 1, 2010, and October 31, 2012, and who were prescribed an oral anticoagulant within 60 days of diagnosis. We identified key predictors of initiation of NOACs using a multinomial logistic regression model with generalized logit link. RESULTS Patients who were black and who had a history of acute myocardial infarction, stroke or transient ischemic attack, chronic kidney disease, or congestive heart failure were significantly associated with lower odds of receiving NOACs compared with warfarin. Age greater than 65 years, a history of hypertension, and use of nonsteroidal anti-inflammatory drugs were positively associated with the initiation of NOACs. Rivaroxaban was most likely to be initiated among women, followed by warfarin and dabigatran. Individuals receiving a low-income subsidy were more likely to initiate warfarin than NOACs, even though they paid little copayment. Individuals with supplemental Part D drug coverage, such as national Programs for All-Inclusive Care for the Elderly or employer-sponsored plans, were more likely to initiate NOACs compared with warfarin. CONCLUSIONS We found that race, sex, type of Part D plans, and some clinical conditions were associated with the initiation of NOACs relative to warfarin. But patient demographic and clinical characteristics did
Frontera, Antonio; Wilson, D G; Sekhon, H; Duncan, E R; Thomas, G
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac conditions. Atrial fibrillation (AF) has been demonstrated to be the most frequent arrhythmia encountered in HCM patients. Research focusing on AF and embolic stroke in HCM patients has been sparse and the sample size of most studies is small. The prognostic significance of AF in HCM patients is still not well known. The aim of this article is to provide further understanding of the anti-coagulation requirement of HCM patients with AF.
Riaz, Azra; Khan, Rafeeq Alam; Ahmed, Shahida Parveen
Effect of evening primrose oil (EPO) was assessed on coagulation parameters following 30 and 60 days administration of 90, 180 and 360 microl/kg oil to healthy rabbits of either sex. There was significant increase in all assays except Fibrinogen time. These effects might be due to inactivation or inhibition of factors affecting coagulation. The intake of evening primrose oil also significantly decreased platelet count. Results of this study suggest that evening primrose oil shows considerable anti-anticoagulant and anti-platelet activity in animals and has potential to reduce cardiovascular morbidity and mortality.
Expósito, Víctor; Seras, Miguel; Fernández-Fresnedo, Gema
Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain.
Zhou, Hai Yan; Hong, Jun Li; Shu, Pan; Ni, Yue Juan; Qin, Min Jian
A new dicoumarin, named as dimeresculetin (1), together with another dicoumarin, euphorbetin (2) and esculetin (3) were isolated from the ethyl acetate extract of the dried whole plants of Viola yedoensis Makino. The structure of 1 was elucidated as 7-hydroxy-6-[(6,7-dihydroxy-2-oxo-2H-1-benzopyran-5-yl)oxy]-2H-1-benzopyran-2-one on the basis of extensive NMR, as well as the other spectral analysis. Compounds 1-3 exhibited anticoagulant activities with respect to activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT).
Sarich, Troy C; Seltzer, Jonathan H; Berkowitz, Scott D; Costin', James; Curnutte, John T; Gibson, C Michael; Hoffman, Maureane; Kaminskas, Edvardas; Krucoff, Mitchell W; Levy, Jerrold H; Mintz, Paul D; Reilly, Paul A; Sager, Philip T; Singer, Daniel E; Stockbridge, Norman; Weitz, Jeffrey I; Kowey, Peter R
This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at the FDA's White Oak Headquarters on April 22, 2014. Attention focused on a development pathway for reversal agents for the novel oral anticoagulants (NOACs). This is important because anticoagulation is still widely underused for stroke prevention in patients with atrial fibrillation. Undertreatment persists, although NOACs, in general, overcome some of the difficulties associated with anticoagulation provided by vitamin K antagonists. One reason for the lack of a wider uptake is the absence of NOAC reversal agents. As there are neither widely accepted academic and industry standards nor a definitive regulatory policy on the development of such reversal agents, this meeting provided a forum for leaders in the fields of cardiovascular clinical trials and cardiovascular safety to discuss the issues and develop recommendations. Attendees included representatives from pharmaceutical companies; regulatory agencies; end point adjudication specialist groups; contract research organizations; and active, academically based physicians. There was wide and solid consensus that NOACs overall offer improvements in convenience, efficacy, and safety compared with warfarin, even without reversal agents. Still, it was broadly accepted that it would be helpful to have reversal agents available for clinicians to use. Because it is not feasible to do definitive outcomes studies demonstrating a reversal agent's clinical benefits, it was felt that these agents could be approved for use in life-threatening bleeding situations if the molecules were well characterized preclinically, their pharmacodynamic and pharmacokinetic profiles were well understood, and showed no harmful adverse events in early human testing. There was also consensus
Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. The aim of this study was to determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular dis...
Numerous factors have been identified as risk factors for instability of oral anticoagulation, including variability in vitamin K intake. However few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a rando...
Cheung, K; Halliwell, R; Cope, L; Khong, D
Management guidelines for patients on antithrombotic agents presenting for surgery have long been disseminated. Clinical practice, however, does not always follow published guidelines in a timely manner, despite their dissemination. This project is an audit of the management of patients on anticoagulants or antiplatelet agents presenting for elective surgery in a large metropolitan teaching hospital. An audit was conducted of the management of patients on anticoagulants or antiplatelet agents presenting for elective surgery at Westmead Hospital to determine the percentage of patients whose management complied with guidelines, and to identify the prevailing reasons for guideline deviation. This was an observational study with qualitative and quantitative aspects. Data was collected for the 102 patients who fulfilled the inclusion criteria: 55.4% of decisions by surgeons and 51.4% of decisions by anaesthetists made in this study matched guidelines; 31.4% of decisions made by anaesthetists were fully compliant with guidelines; 20% of anaesthetic decisions were unintentionally compliant and 48.6% of anaesthetic decisions were noncompliant. A variety of reasons were cited for decisions made without the use of guidelines such as other clinical imperatives, lack of guideline awareness and a belief that it is not the role of the anaesthetist to manage perioperative antithrombotic therapy, amongst others. It is evident from this audit that compliance with guidelines remains an area where there is an opportunity for further practice improvement.
Camm, A John; Pinto, Fausto J; Hankey, Graeme J; Andreotti, Felicita; Hobbs, F D Richard
Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers.
Chantarangkul, Veena; Biguzzi, Eugenia; Asti, Daniela; Palmucci, Claudia; Tripodi, Armando
This study shows the diagnostic outcome of an APTT-based and two dRVVT-based commercial confirmatory integrated tests with the application of the recommendations by the Scientific and Standardization Committee (SSC) on Lupus anticoagulant (LA)/antiphospholipid syndrome (APS) of the International Society on Thrombosis and Haemostasis (ISTH) issued in 2009 concerning the cut-off values for the screening, mixing and confirmatory tests for the detection of LA and the mandatory need to perform mixing tests of patient plasma with pooled normal plasma. The study population included 565 patients collected from a large central coagulation laboratory, for which the attending physicians requested LA detection. One-hundred-six healthy subjects (HS) and 131 selected patients on oral anticoagulant therapy (OAT) were included as negative controls. The results suggest that the performance of mixing tests is indicated for those methods with relatively poor specificity, but is less needed for those methods with high specificity. Furthermore, the SSC recommendation to use normal mid-value (i.e. the 50th percentile of distribution of results from healthy subjects) as the cut-off to interpret results of confirmatory tests, showed a modest increase in LA detection rate (sensitivity) but at the expense of specificity, particularly in methods with low specificity.
Camm, A. John; Pinto, Fausto J.; Hankey, Graeme J.; Andreotti, Felicita; Hobbs, F.D. Richard
Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. PMID:26116685
Sherwood, Matthew W.; Becker, Richard C.
Atrial fibrillation is a common arrhythmia. One of the important aspects of the management of atrial fibrillation is stroke prevention. Warfarin has been the longstanding anticoagulant used for stroke prevention in patients with atrial fibrillation. There are now three novel oral anticoagulants, which have been studied in randomized controlled trials and subsequently approved by the Federal Drug Administration for stroke prevention in patients with atrial fibrillation. Special patient populations, including renal insufficiency, elderly, prior stroke, and extreme body weights, were represented to varying degrees in the clinical trials of the novel oral anticoagulants. Furthermore, there is variation in the pharmacokinetics and pharmacodynamics of each anticoagulant, which affect the patient populations differently. Patients and clinicians are faced with the task of selecting among the available anticoagulants, and this review is designed to be a tool for clinical decision-making. PMID:23846737
Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke
Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and (1)H nuclear magnetic resonance ((1)H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R1 and R2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.
Ellis, Gidon; John Camm, Alan; Datta, Soumendra N
Novel oral anti-coagulants (NOACs) are increasingly being used in clinical practice and are set to almost entirely replace the vitamin K antagonists, such as warfarin, in the near future. Similarly, new antiplatelet agents are now regularly used in place of older agents, such as aspirin and clopidogrel. In an ageing population, with an increasing burden of complex comorbidities, urologists will frequently encounter patients who will be using such agents. Some background knowledge, and an understanding, of these drugs and the issues that surround their usage, is essential. The present article will provide readers with an understanding of these new drugs, including their mechanisms of action, the up-to-date evidence justifying their recent introduction into clinical practice and the appropriate interval for stopping them before surgery. It will also consider the risks of perioperative bleeding for patients taking these drugs and the risks of venous thromboembolism in those in whom they are stopped. Strategies to manage anticoagulant-associated bleeding are discussed.
Elad, S; Marshall, J; Meyerowitz, C; Connolly, G
Currently, 4 novel Direct Oral Anticoagulants (DOACs) were approved by the FDA. This review focuses on these agents and proposes a matrix for the general dentists to assess bleeding risk in dental management of patient on DOACs. The outline covers the pharmacology of DOACs (rivaroxaban, apixaban, edoxaban and dabigatran), bleeding complications, risk associated with discontinuation, monitoring/reversal, and implications for the dental practitioners. A total of 18 randomized controlled trials were identified with mixed results in regards to the risk for bleeding. Considering the pharmacology of DOACs and challenges in monitoring and reversing their effect, the dentist should consider carefully the management of patients on DOACs as it may differ from patients on conventional anticoagulants. Based on the type of dental procedure and the medical risk assessment, several general treatment approaches can be considered: continue DOACs, time dental treatment as late as possible after the last DOACs dose, discontinue DOACs for 24hrs, or discontinue DOACs for 48hrs. Based on the current reported dental literature, limited dental surgery may benefit from the first 2 conservative options. However, this needs to be proven in comparative clinical trials.
Kim, Ji Soo; Kim, Min Jae; Bae, E Young
Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), a very rare disease that is caused by the presence of antifactor II antibodies, is usually counterbalanced by the prothrombotic effect of lupus anticoagulant (LAC). Patients with LAHPS are treated using fresh frozen plasma, steroids, immunosuppressive agents, and immunoglobulins for managing the disease and controlling hemorrhages. Notably, steroids are the important treatment for treating hypoprothrombinemia and controlling the bleeding. However, some patients suffer from severe, life-threatening hemorrhages, when factor II levels remain very low in spite of treatment with steroids. Here, we report a case of LAHPS in a 15-year-old girl who experienced pulmonary hemorrhage with rapid progression. She was referred to our hospital owing to easy bruising and prolonged bleeding. She was diagnosed with LAHPS that presented with pancytopenia, positive antinuclear antibody, proloned prothrombin time, activated partial thromboplastin time, positive LAC antibody, and factor II deficiency. Her treatment included massive blood transfusion, high-dose methylprednisolone, vitamin K, and immunoglobulin. However, she died due to uncontrolled pulmonary hemorrhage. PMID:24868219
Zhang, Qinglei; Lu, Xiaolong; Yang, Shichun; Zhang, Qingzhao; Zhao, Lihua
In this study, polyvinylidene fluoride (PVDF) hollow fiber membranes (HFMs) were modified by coating with polyvinyl alcohol (PVA) and chitosan. The influences of PVA and chitosan amount on PVDF membrane mechanical and separation performance were investigated. The results showed that the modified PVDF membranes had better mechanical and separation performance when the amount of PVA and chitosan was 20 mg/m2. At the same time, the biocompatibility of PVDF membranes was also investigated. Compared with virgin PVDF membranes, the modified PVDF membranes showed better anticoagulation, hydrophilicity, less bovine serum albumin (BSA) adsorption, and lower hemolytic ratio. The anticoagulation behavior of modified PVDF membranes coating with PVA had been obviously improved. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of the modified PVDF membrane are 44.8 s and 72.5 s while the PT and APTT of virgin PVDF membrane are 15.6 s and 37.3 s. The advancing water contact angle (WCA) and BSA adsorption of the modified PVDF membrane coating with PVA are 24° and 23 mg/m2 while virgin PVDF membrane is 52° and 49 mg/m2. However, further biocompatibility evaluation is needed to obtain a more comprehensive conclusion.
Kearon, Clive; Comerota, Anthony J.; Prandoni, Paolo; Bounameaux, Henri; Goldhaber, Samuel Z.; Nelson, Michael E.; Wells, Philip S.; Gould, Michael K.; Dentali, Francesco; Crowther, Mark; Kahn, Susan R.
Background: This article addresses the treatment of VTE disease. Methods: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. Results: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). Conclusion: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences. PMID:22315268
Russo, Vincenzo; Rago, Anna; Proietti, Riccardo; Di Meo, Federica; Antonio Papa, Andrea; Calabrò, Paolo; D’Onofrio, Antonio; Nigro, Gerardo; AlTurki, Ahmed
The aim of our article is to provide a concise review for clinicians entailing the main studies that evaluated the efficacy and safety of target-specific oral anticoagulants (TSOAs) for thromboembolic stroke prevention in the real-world setting. Atrial fibrillation (AF) is one of the most common supraventricular arrhythmias that requires anticoagulation therapy to prevent stroke and systemic embolism. TSOAs, dabigatran, apixaban and rivaroxaban have become available as an alternative to warfarin anticoagulation in nonvalvular atrial fibrillation (NVAF). Randomized clinical trials showed non-inferior or superior results in efficacy and safety of the TSOAs compared with warfarin for stroke prevention in NVAF patients. For this reason, the 2012 update to the European Society of Cardiology guidelines for the management of AF recommends TSOAs as broadly preferable to vitamin K antagonists (VKAs) in the vast majority of patients with NVAF [Camm et al. 2012]. Although the clinical trial results and the guideline’s indications, there is a need for safety and efficacy data from unselected patients in everyday clinical practice. Recently, a large number of studies testing the efficacy and the safety of TSOAs in clinical practice have been published. The aim of our article is to provide a concise review for clinicians, outlining the main studies that evaluated the efficacy and safety of TSOAs for thromboembolic stroke prevention in the real-world setting. PMID:28255434
Powless, R Andrew; Omar, Hesham R; Mangar, Devanand; Camporesi, Enrico M
The management of antiplatelet and anticoagulant therapy before full-mouth extraction is a major concern for dentists. Approach should vary depending on the risk of bleeding and adverse cardiac events. We have adapted a more conservative approach with continuation of antiplatelet therapy in the majority of patients while implementing local hemostatic measures with good outcomes. Specific recommendations are provided for antiplatelet therapy before mouth extraction.
Worm, Marie; Köhler, Elodie C.; Panda, Rachita; Long, Andy; Butler, Lynn M.; Stavrou, Evi X.; Nickel, Katrin F.; Fuchs, Tobias A.
The plasma protein factor XII (FXII) is the initiating protease of the procoagulant and proinflammatory contact system. FXII activates both the bradykinin (BK) producing kallikrein-kinin system and the intrinsic pathway of coagulation. Contact with negatively charged surfaces induces auto-activation of zymogen FXII that results in activated FXII (FXIIa). Various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, nucleic acids and polyphosphate. Murine models have established a central role of FXII in arterial and venous thromboembolic diseases. Despite the central function of FXII in pathologic thrombosis, its deficiency does not impair hemostasis in animals or humans. The selective role of FXIIa in thrombosis, but not hemostasis, offers an exciting novel strategy for safe anticoagulation based on interference with FXIIa. We have generated the recombinant fully human FXIIa-blocking antibody 3F7, which abolished FXIIa enzymatic activity and prevented thrombosis in a cardiopulmonary bypass system in large animals, in the absence of increased therapy-associated bleeding. Furthermore, 3F7 also interfered with BK-driven edema in the severe swelling disorder hereditary angioedema (HAE) type III. Taken together, targeting FXIIa with 3F7 appears to be a promising approach to treat edema disorders and thrombosis. PMID:26605293
Robati, R; Farokhi, MM
Background Some of the dental procedures can cause bleeding. Bleeding control can be difficult in some patients because of systemic disease or chronic anticoagulant therapy, so they may be at increased risk for bleeding occurrences or even death following invasive dental procedures. This study was schemed to measure the knowledge of general dentists in Shiraz city regarding coagulation tests performed in bleeding disorders during 2011 to 2012. Materials and Methods In this descriptive-analytical study, a questionnaire (consist 23 questions) was designed with the help of specialists in the field of oral medicine and hematology. This questionnaire was distributed among 146 general practitioners. Collected information was analyzed with SPSS version 16. Results The mean mark for dentist’s knowledge was 9.40 ± 1.30 (categorized moderate level). There was no significant difference in the mean knowledge scores among male and female dentists. Tukey’s test displayed a significant difference in the mean knowledge level among 21 to 30 years old and over forty years' old dentists (p< 0.03). Conclusions This study showed that knowledge of the dentists regarding bleeding disorders is not at optimal level which needs planning for continuing education courses. PMID:24575290
The nonvitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban are associated with an equal or lower incidence of stroke and systemic embolism and a much lower incidence of intracranial hemorrhage and hemorrhagic stroke than warfarin is, without the need for routine laboratory monitoring. However, reversal strategies are not currently established in the case of NOAC-related hemorrhagic stroke. In emergency situations, well-defined management for NOAC-related hemorrhagic stroke may improve clinical outcomes. Thus, in this chapter, general measures initially required to prevent the expansion of intracerebral hematomas, charcoal administration to reduce NOAC absorption from the gastrointestinal tract, application of hemodialysis to remove dabigatran, and coagulation factor therapy including 4-factor prothrombin complex concentrate and recombinant activated factor VII are reviewed. The specific reversal agents idarucizumab, which is a monoclonal antibody against dabigatran; andexanet alfa, a recombinant human factor Xa decoy for Xa inhibitors; and PER977, a small synthetic molecule for reversal of both Xa and thrombin inhibitors, are currently under development. These agents will facilitate the clinical management of NOAC-associated hemorrhagic stroke and other severe bleeding.
LaBonte, Michelle L
Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework.
Salmane, Chadi; Pandya, Bhavi; Lafferty, Kristen; Patel, Nileshkumar J; McCord, Donald
Sixty percent of the patients going for valve replacement opt for mechanical valves and the remaining 40% choose bioprosthetics. Mechanical valves are known to have a higher risk of thrombosis; this risk further varies depending on the type of valve, its position, and certain individual factors. According to current guidelines, long-term anticoagulation is indicated in patients with metallic prosthetic valve disease. We report two unique cases of patients who survived 27 and 37 years event free, respectively, after mechanical aortic valve replacement (AVR) without being on any form of anticoagulation. The latter case described the longest survival in a human with a prosthetic aortic valve without anticoagulation. A review of literature demonstrated few cases of prosthetic valves with no anticoagulation in the long term without significant embolic events reported as case reports. These cases have been summarized in this article. Some cases of long-term survival (in the absence of anticoagulation) were attributed to good luck, and others as the result of genetic variations. New mechanical prosthetic valves can be promising, such as microporus-surfaced valves that may be used without full anticoagulation. The use of dual antiplatelet agents alone can be currently recommended only when a patient cannot take oral anticoagulation after AVR, and it should be followed with measuring and monitoring of platelet reactivity. PMID:27053922
Elmeros, Morten; Christensen, Thomas Kjær; Lassen, Pia
Anticoagulant rodenticides are widely used to control rodent populations but they also pose a risk of secondary poisoning in non-target predators. Studies on anticoagulant rodenticide exposure of non-target species have mainly reported on frequency of occurrence. They have rarely analyzed variations in residue concentrations. We examine the occurrence and concentrations of five anticoagulant rodenticides in liver tissue from 61 stoats (Mustela erminea) and 69 weasels (Mustela nivalis) from Denmark. Anticoagulant rodenticides were detected in 97% of stoats and 95% of weasels. 79% of the animals had detectable levels of more than one substance. Difenacoum had the highest prevalence (82% in stoats and 88% in weasels) but bromadiolone was detected in the highest concentrations in both stoat (1.290 μg/g ww) and weasel (1.610 μg/g ww). Anticoagulant rodenticide concentrations were highest during autumn and winter and varied with sampling method. Anticoagulant rodenticide concentrations were higher in stoats and weasels with unknown cause of death than in specimens killed by physical trauma. There was a negative correlation between anticoagulant rodenticide concentrations and body condition. Our results suggest that chemical rodent control in Denmark results in an extensive exposure of non-target species and may adversely affect the fitness of some stoats and weasels.
Greco, Michele; Benedetto, Filippo; Spinelli, Francesco; Traxer, Olivier; Tefik, Tzevat; Pappalardo, Rosa
Spontaneous subcapsular renal hematoma is a rare condition in clinical practice. It is caused by renal cysts, benign and malignant renal tumors, vascular lesions, and antiplatelet or anticoagulant therapy. In this paper we report an unusual case of rupture of a renal cyst of a 66-year-old male patient during an aortic and iliac endovascular procedure for a massive calcified atheroma above the iliac bifurcation. We suspected that the bolus of high weight molecular heparin given during the procedure caused the rupture of the cyst. According to the literature, this is the first case of renal cyst rupture during an endovascular aortic procedure after administering a high weight molecular heparin bolus. PMID:27579210
Domingues, Renan; Bruniera, Gustavo; Brunale, Fernando; Mangueira, Cristóvão; Senne, Carlos
The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations