scholarly journals Updates on Anticoagulation and Laboratory Tools for Therapy Monitoring of Heparin, Vitamin K Antagonists and Direct Oral Anticoagulants

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 264
Author(s):  
Osamu Kumano ◽  
Kohei Akatsuchi ◽  
Jean Amiral
Keyword(s):  
Dose Adjustment ◽  
Therapy Monitoring ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Monitoring Methods ◽  
Anticoagulant Drugs

Anticoagulant drugs have been used to prevent and treat thrombosis. However, they are associated with risk of hemorrhage. Therefore, prior to their clinical use, it is important to assess the risk of bleeding and thrombosis. In case of older anticoagulant drugs like heparin and warfarin, dose adjustment is required owing to narrow therapeutic ranges. The established monitoring methods for heparin and warfarin are activated partial thromboplastin time (APTT)/anti-Xa assay and prothrombin time – international normalized ratio (PT-INR), respectively. Since 2008, new generation anticoagulant drugs, called direct oral anticoagulants (DOACs), have been widely prescribed to prevent and treat several thromboembolic diseases. Although the use of DOACs without routine monitoring and frequent dose adjustment has been shown to be safe and effective, there may be clinical circumstances in specific patients when measurement of the anticoagulant effects of DOACs is required. Recently, anticoagulation therapy has received attention when treating patients with coronavirus disease 2019 (COVID-19). In this review, we discuss the mechanisms of anticoagulant drugs—heparin, warfarin, and DOACs and describe the methods used for the measurement of their effects. In addition, we discuss the latest findings on thrombosis mechanism in patients with COVID-19 with respect to biological chemistry.

Safety and Feasibility of Treatment with Rivaroxaban in Children for Non-Routine Indications: A Case Series Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5014-5014 ◽  
Author(s):  
Kathryn E. Dickerson ◽  
Ravi Sarode ◽  
Ayesha Zia
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Case Series ◽  
Bleeding Complications ◽  
Fixed Dose ◽  
The Mean ◽  
Recurrent Vte

Background. Anticoagulation therapy is the cornerstone of acute treatment of venous thromboembolism (VTE) and for prevention of recurrent VTE. The need for anticoagulation is increasing in children, largely in part due to increasing VTE rates. Conventional anticoagulants, including heparin, low-molecular weight heparins (LMWH), Fondaparinux, and vitamin K antagonists (VKA) are widely used in children but have limitations. Standard of care management with these agents is plagued with the trade-off between daily or twice daily injections or frequent monitoring of therapeutic effect. The advent of direct oral anticoagulants (DOACs) have catalyzed significant changes in the therapeutic landscape of VTE management. DOACs have been evaluated for safety and efficacy in large, randomized controlled trials in the treatment and prevention of VTE in adults, with results that are comparable to conventional therapy. None of the current DOACs have FDA-approved indications and dosing in children yet. Off-label use of these agents is largely based on adult data and doses, and is increasing at many Children's Hospitals across US. Rivaroxaban, a DOAC, is a factor Xa inhibitor with predictable pharmacokinetic and pharmacodynamics properties. Methods. We describe a case series of 8 unique pediatric cases, treated with Rivaroxaban, for a variety of non-routine indications, due either to adverse effects, intolerability of LMWH or VKA or the need for ongoing, long term anticoagulation. Rivaroxaban was started after informed consent and assent from parents or patients respectively, and was initiated at a fixed dose but titrated to a final dose after monitoring of trough and peak Rivaroxaban levels (Aniara, West Chester,OH, USA). Results. The mean age of patients in this case series is 14 years (median: 16, range 3-17) (see Table). The most common indication to use Rivaroxaban was the need for long term anticoagulation after having completed therapeutic anticoagulation, except in two patients, one of whom developed warfarin skin necrosis due to protein C deficiency and another with heparin induced thrombocytopenia. Only two patients needed dose adjustments to achieve target trough and peak drug levels. The mean duration of follow-up is 9 months (median= 5.5; range 3-24) (see Table) at this time. None of the patients developed recurrent VTE while on Rivaroxaban. A soft tissue traumatic bleed occurred in one patient which was treated with holding off the drug for 48 hours. No other bleeding complications were observed. Conclusions. Clinical application of DOACs in a real world clinical setting, including strong thrombophilia and malignancy, results in treatment profile of high efficacy and safety in children; however, larger studies are needed to validate these findings. Disclosures Sarode: CSL Behring: Consultancy, Honoraria.

scholarly journals Practical Considerations for the Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation

2016 ◽  
Vol 23 (1) ◽  
pp. 5-19 ◽  
Author(s):  
Zachary Stacy ◽  
Sara Richter
Keyword(s):  
Atrial Fibrillation ◽  
Treatment Guidelines ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Significant Risk ◽  
The United States ◽  
Assessment Tools ◽  
Long Term Outcome

Atrial fibrillation (AF) is a significant risk factor for stroke and peripheral thromboembolic events (TEs). Preventing blood clots in the heart to reduce stroke and TE risk is a key goal of AF therapy. Traditional stroke risk assessment tools for patients with nonvalvular AF include the CHADS2 and CHA(2)DS(2)-VASc scores, while long-term outcome data with the newer direct oral anticoagulants (DOACs) are emerging. The goals of this review were to assess traditional therapies and existing treatment guidelines and to discuss key pharmacologic properties of the DOACS, noting how these may benefit at-risk patients with AF. This narrative review was developed on the basis of the authors’ clinical knowledge, extensive reading of the literature, and broad pharmacy experience in the management of patients with AF. Limitations of oral vitamin K antagonists (VKAs) include slow onset of action, the need for regular monitoring of their anticoagulation effect, significant food and drug interactions, and unpredictable dose–response properties. Key clinical trial data led to the approvals of apixaban, dabigatran etexilate, edoxaban, and rivaroxaban in the United States to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF. With predictable pharmacologic properties and limited drug and/or dietary interactions, the DOACs offer several benefits over traditional oral anticoagulation therapy with VKA. However, they have limitations, including the absence of immediate reversal agents and limited options for monitoring their anticoagulation effects in clinical practice. As experience with the use of DOACs grows, optimized treatment regimens and improved patient care are expected.

scholarly journals Optimization of Pharmacotherapy with Direct Oral Anticoagulants: the Need to Choose the Right Dosage Regimen

2019 ◽  
Vol 15 (4) ◽  
pp. 593-603
Author(s):  
A. I. Kochetkov ◽  
O. D. Ostroumova
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Coronary Intervention ◽  
International Normalized Ratio ◽  
Efficacy And Safety ◽  
High Efficacy ◽  
Drug Label ◽  
Coronary Syndrome ◽  
Number Of Patients

In recent years, there has been a persistent trend towards the more frequent prescription of direct oral anticoagulants (DOACs) compared with vitamin K antagonists due to the extensive body of evidence showing their high safety and efficacy, which in some cases exceed those of warfarin, and also by reason of there is no necessity for regular monitoring of international normalized ratio. However, the question of the reasonable and rational prescription of DOACs becomes relevant, including issues of their dosing, especially as a result of increasing in the number of patients with a complex cardiovascular risk profile and multimorbidity. In these terms, apixaban stands high among the DOAC class, and its high efficacy and safety both in full dose and reasonably reduced dosage has been proved, including older patients, patients with chronic kidney disease, coronary artery disease, with history of acute coronary syndrome and individuals undergoing percutaneous coronary intervention. This DOAC has strict indications to reduce the dose, they are specified in the drug label, and in such cases a reduced dose should be prescribed, in these clinical conditions the effectiveness and safety of apixaban is also proven. The favorable apixaban pharmacokinetic properties, consisting in low renal clearance, lack of clinically relevant interaction with food and the linear smooth effect on the blood coagulation components without episodes of hypo- and hypercoagulation, are the most important components of high efficacy and safety of this DOAC. The optimal efficacy and safety coupling of apixaban is reflected in the exclusively high patients’ adherence to the treatment confirmed by evidence-based medicine data, and therefore there is no necessity for additional procedures to maintain adherence. All the aforementioned facts allow us to recommend apixaban for widespread use in patients requiring anticoagulant therapy for optimal prevention of systemic thromboembolism and minimizing the associated risk of bleeding.

scholarly journals Direct oral anticoagulants (DOAC) for prevention of recurrent arterial or venous thromboembolic events (ATE/VTE) in myeloproliferative neoplasms

2020 ◽  
Author(s):  
Karlo Huenerbein ◽  
Parvis Sadjadian ◽  
Tatjana Becker ◽  
Vera Kolatzki ◽  
Eva Deventer ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Thromboembolic Events ◽  
Number Of Patients ◽  
Increased Risk ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic

AbstractIn patients with BCR-ABL-negative myeloproliferative neoplasms (MPN), arterial or venous thromboembolic events (ATE/VTE) are a major burden. In order to control these complications, vitamin K antagonists (VKA) are widely used. There is no robust evidence supporting the use of direct oral anticoagulants (DOAC) in MPN patients. We therefore compared the efficacy and safety of both anticoagulants in 71 cases from a cohort of 782 MPN patients. Seventy-one of 782 MPN patients (9.1%) had ATE/VTE with nine ATE (12.7%) and 62 VTE (87.3%). Forty-five of 71 ATE/VTE (63.4%) were treated with VKA and 26 (36.6%) with DOAC. The duration of anticoagulation therapy (p = 0.984), the number of patients receiving additional aspirin (p = 1.0), and the proportion of patients receiving cytoreductive therapy (p = 0.807) did not differ significantly between the VKA and DOAC groups. During anticoagulation therapy, significantly more relapses occurred under VKA (n = 16) compared to DOAC treatment (n = 0, p = 0.0003). However, during the entire observation period of median 3.2 years (0.1–20.4), ATE/VTE relapse-free survival (p = 0.2) did not differ significantly between the two anticoagulants. For all bleeding events (p = 0.516) or major bleeding (p = 1.0), no significant differences were observed between VKA and DOAC. In our experience, the use of DOAC was as effective and safe as VKA, possibly even potentially beneficial with a lower number of recurrences and no increased risk for bleedings. However, further and larger studies are required before DOAC can be routinely used in MPN patients.

scholarly journals Broadening the Categories of Patients Eligible for Extended Venous Thromboembolism Treatment

2019 ◽  
Vol 120 (01) ◽  
pp. 014-026 ◽  
Author(s):  
Marc Schindewolf ◽  
Jeffrey Ian Weitz
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Profile Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Specific Risk ◽  
Increased Risk

AbstractTraditionally, venous thromboembolism (VTE) resulting from major transient risk factors (e.g., surgery or trauma) or a major persistent risk factor such as cancer, has been defined as being provoked, whereas unprovoked VTE encompasses events without an identifiable cause. These categorizations influence anticoagulant treatment duration; unlike VTE provoked by major transient risk factors, extended anticoagulation beyond 3 months is advised for patients with cancer or unprovoked VTE due to risk persistence after treatment cessation. However, some patients with VTE provoked by minor transient or minor persistent risk factors may also be candidates for extended anticoagulation therapy due to the continuing risk of recurrence. In patients who require extended therapy, vitamin K antagonists (VKAs) are effective but are associated with an increased risk of bleeding and various treatment burdens (e.g., anticoagulation monitoring and dose adjustment). Evaluations of extended VTE treatment with the less-burdensome direct oral anticoagulants such as apixaban, dabigatran, edoxaban, and rivaroxaban show that they are at least as safe and effective as VKAs in a broad range of patients. In addition, apixaban and rivaroxaban offer more than one dosing option, allowing tailoring of treatment to the patient's specific risk factor profile. Analysis of more granular definitions for risk factor groupings has also yielded vital information on the most appropriate strategies for the treatment of patients with specific risk factors, highlighting that extended anticoagulation treatment may benefit those with minor transient and persistent environmental and nonenvironmental risk factors who commonly receive shorter-duration therapy.

scholarly journals Cerebral Ischemia in Patients on Direct Oral Anticoagulants

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 873-879 ◽  
Author(s):  
Kosmas Macha ◽  
Armin Marsch ◽  
Gabriela Siedler ◽  
Lorenz Breuer ◽  
Erwin F. Strasser ◽  
...  
Keyword(s):  
Vitamin K ◽  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Large Vessel ◽  
Stroke Severity ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion

Background and Purpose— In patients with ischemic stroke on therapy with vitamin K antagonists, stroke severity and clinical course are affected by the quality of anticoagulation at the time of stroke onset, but clinical data for patients using direct oral anticoagulants (DOACs) are limited. Methods— Data from our registry including all patients admitted with acute cerebral ischemia while taking oral anticoagulants for atrial fibrillation between November 2014 and October 2017 were investigated. The activity of vitamin K antagonists was assessed using the international normalized ratio on admission and categorized according to a threshold of 1.7. DOAC plasma levels were measured using the calibrated Xa-activity (apixaban, rivaroxaban, and edoxaban) or the Hemoclot-assay (dabigatran) and categorized into low (<50 ng/mL), intermediate (50–100 ng/mL), or high (>100 ng/mL). Primary objective was the association between anticoagulant activity and clinical and imaging characteristics. Results— Four hundred sixty patients were included (49% on vitamin K antagonists and 51% on DOAC). Patients on vitamin K antagonists with low international normalized ratio values had higher scores on the National Institutes of Health Stroke Scale and a higher risk of large vessel occlusion on admission. For patients on DOAC, plasma levels were available in 75.6% and found to be low in 49 (27.7%), intermediate in 41 (23.2%), and high in 87 patients (49.2%). Low plasma levels were associated with higher National Institutes of Health Stroke Scale scores on admission (low: 8 [interquartile range, 3–15] versus intermediate: 4 [1–11] versus high: 3 [0–8]; P <0.001) and higher risk of persisting neurological deficits or cerebral infarction on imaging (85.7% versus 75.6% versus 54.0%; P <0.001). Low DOAC plasma levels were an independent predictor of large vessel occlusion (odds ratio, 3.84 [95% CI, 1.80–8.20]; P =0.001). Conclusions— The activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity and presence of large vessel occlusion.

scholarly journals Guidelines for mono, double and triple antithrombotic therapy

2021 ◽  
pp. postgradmedj-2020-138938
Author(s):  
Renate C A E van Uden ◽  
Ilse Houtenbos ◽  
Anita Griffioen-Keijzer ◽  
Diego A M Odekerken ◽  
Patricia M L A van den Bemt ◽  
...  
Keyword(s):  
Vitamin K ◽  
Antithrombotic Therapy ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Duration Of Therapy ◽  
European Guidelines ◽  
Therapeutic Anticoagulation ◽  
Triple Antithrombotic Therapy

Guidelines for antithrombotic therapy are complex, especially if a patient has several indications that require antithrombotic therapy. In general, no patient should receive lifelong double or triple antithrombotic therapy. In this overview, we outline the most common indications for mono, double and triple antithrombotic therapy; the preferred antithrombotic therapy and the recommended duration of therapy. Both antiplatelet therapy and therapeutic anticoagulation therapy with vitamin K antagonists or direct oral anticoagulants were included. European guidelines were used or, if no European guidelines were available, the Dutch guidelines were used.

Anticoagulation Therapy in Children

2017 ◽  
Vol 43 (08) ◽  
pp. 877-885 ◽  
Author(s):  
Vlad Radulescu
Keyword(s):  
Phase I ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Thrombin Inhibitors ◽  
Anticoagulant Drugs ◽  
Pediatric Use ◽  
Ongoing Phase ◽  
Future Management

AbstractVenous thromboembolism (VTE) is very uncommon in children and adolescents compared with older adults, though its incidence has significantly increased over the past two decades. Given the rarity of the condition, the data on pediatric VTE lag behind the adult experience and consequently the management of VTE in children is, in large part, modeled on the adult strategies. This approach has certain limitations, given that young children have developmental particularities of the hemostatic system and differences in the pharmacokinetics and pharmacodynamics of various anticoagulant agents. The most commonly used anticoagulants in children continue to be the heparins and the vitamin K antagonists. Direct intravenous thrombin inhibitors, argatroban, bivalirudin, have very limited pediatric use. The non–vitamin K antagonist oral anticoagulant drugs (novel oral anticoagulants) present potential advantages in terms of efficacy, safety, and convenience, though pediatric data are limited to preclinical and small phase I trials. There are several ongoing phase I, II, and III trials for dabigatran rivaroxaban, apixaban, and edoxaban, the results of which are likely to change the future management of pediatric thromboses.

Validation of Bleeding Risk Prediction Scores for Patients With Major Bleeding on Direct Oral Anticoagulants

2020 ◽  
Vol 54 (12) ◽  
pp. 1175-1184 ◽  
Author(s):  
Stephanie Tchen ◽  
Nicole Ryba ◽  
Vishal Patel ◽  
Joseph Cavanaugh ◽  
Jesse B. Sullivan
Keyword(s):  
Diagnostic Accuracy ◽  
Risk Prediction ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Primary Objective

Background: Direct oral anticoagulants (DOACs) offer many benefits over vitamin K antagonists (VKAs) but still carry a significant risk of major bleeding. Bleeding risk prediction scores such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, and Drugs/Alcohol (HAS-BLED), Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk, and Stroke (HEMORR2HAGES), Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA), Registro Informatizado Enfermedad TromboEmbólica (RIETE), and CHEST scores were validated or evaluated for use with VKAs and parenteral anticoagulants, but evidence for use with DOACs is lacking. Objective: This study aims to evaluate bleeding risk prediction scores for DOAC patients presenting with major bleeding. Methods: A retrospective analysis of patients presenting from 2015 to 2018 was performed. Patients were separated into bleed and nonbleed groups. The primary objective was to assess the diagnostic accuracy of the bleeding risk prediction scores utilizing the receiver operating characteristic (ROC) curve. Results: A total of 126 patients were included in the analyses. The areas under the curve (AUC) for the ROC curves of the HAS-BLED, HEMORR2HAGES, ATRIA, RIETE, and CHEST scores were 0.645, 0.675, 0.580, 0.638, and 0.667, respectively. Conclusion and Relevance: The HAS-BLED, HEMORR2HAGES, RIETE, and CHEST scores were found to have sufficient diagnostic accuracy for predicting risk of major bleeding in our study population; however, no score was identified as having an AUC greater than 0.7. Caution may be considered when utilizing these scores for patients on DOACs.

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