Pharmacology of anticoagulants used in the treatment of venous thromboembolism

Nutescu, Edith A.; Burnett, Allison; Fanikos, John; Spinler, Sarah A.; Wittkowsky, Ann K.

doi:10.1007/s11239-015-1314-3

Cited by 121 publications

(124 citation statements)

References 74 publications

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“…Therefore, the aPTT may underestimate high concentrations, posing a significant problem in overdose assessment . When a more sensitive assay (e.g., ECT, dTT) is unavailable, the aPTT may provide qualitative assessment of dabigatran . Because sensitivity of different assays vary, checking the sensitivity of aPTT to dabigatran at each institution is recommended .…”

Section: Laboratory Coagulation Monitoringmentioning

confidence: 99%

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Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know

et al. 2017

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The direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, have favorable pharmacokinetic and pharmacodynamic properties and equal or superior efficacy and an improved safety profile compared with warfarin. Noted shortcomings with DOACs are shorter half-lives requiring stricter adherence, lack of standardized laboratory monitoring, lack of anticoagulation reversal agents, and loss of routine coagulation monitoring leading to fewer patient-clinician interactions. This review addresses many of these limitations including monitoring of DOACs for efficacy and toxicity, an assessment of selected qualitative and quantitative tests, and development of monitoring strategies for special populations. Coagulation monitoring is generally recommended only in overdose situations, but once standardized assays are readily available, they could be helpful to ensure efficacy, assess bleeding, and aid in drug selection in a number of other patient scenarios. Coagulation tests that may provide qualitative assessment include activated partial thromboplastin time, prothrombin time, and thrombin time. Methods with potential utility for quantitative assessment of DOACs include plasma drug concentrations, ecarin clotting time, dilute thrombin time, and antifactor Xa concentrations. Noncoagulation laboratory monitoring should include serum creatinine, liver function tests, and complete blood counts. Clinical monitoring of the DOAC-treated patient should include routine assessment of adherence, bleeding risks, and drug interactions. Frequency of monitoring should be 1-3 months after initiation and then at least every 6 months, with more frequent follow-up (i.e., 3 months) based on patient specific characteristics such as age, renal impairment, hepatic impairment, and concomitant drug therapy. The authors provide a practical tool to assist in DOAC monitoring and recommend that pharmacists collaborate with physicians in selecting appropriate patients and tailoring patient-specific monitoring plans.

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Section: Laboratory Coagulation Monitoringmentioning

confidence: 99%

“…Because sensitivity of different assays vary, checking the sensitivity of aPTT to dabigatran at each institution is recommended . A normal aPTT does not exclude clinically relevant dabigatran activity …”

Section: Laboratory Coagulation Monitoringmentioning

confidence: 99%

Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know

et al. 2017

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“…We note that Rudd et al have reported independently on possible rivaroxaban failure in patients treated during the postpartum period, possibly due to pharmacokinetic alterations seen in the postpartum period that can contribute to decreased drug exposure and reduced anticoagulant efficacy [16]. In fact, rivaroxaban is well known to be metabolized by the cytochrome P450 isoenzyme CYP 3A4 and binds to P-glycoprotein; hence, leading to risks of pharmacokinetic interactions that may alter its anticoagulant properties [17]. In practice, it may be best at this time to choose between these several available anticoagulant drugs on a case-by-case basis, taking into account patient preferences, monitoring constraints, difficulty controlling the INR, the risk of bleeding and interactions, and the cost of treatment [18].…”

Section: Discussionmentioning

confidence: 99%

Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

et al. 2016

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BackgroundThe relative effectiveness of vitamin K antagonists compared with novel oral anticoagulants in treating pulmonary embolism remains unclear. Recent trials comparing the efficacy of vitamin K antagonists with factor Xa inhibitors for the treatment of pulmonary emboli have been non-inferiority studies based primarily on risk reduction (such as bleeding events), rather than resolution of specific diseases such as pulmonary embolism. Consequently, there is a lack of evidence indicating which of these agents are more effective. Here, we present a case where pulmonary emboli were treated with novel oral anticoagulants followed by warfarin to discuss the potential limitations in the use of novel oral anticoagulants as prevention or treatment of thromboembolism and the continued role for warfarin in this setting.Case presentationA 34-year-old African American woman presented to our clinic with shortness of breath and pleuritic chest pain several months post-surgery. She was identified as having multiple bilateral pulmonary embolisms and was treated with several novel oral anticoagulants, which failed to resolve the clots. Complete resolution was achieved upon switching to warfarin.ConclusionsThe patient described in this report failed to respond to novel oral anticoagulant therapy, but her emboli resolved when she was treated with warfarin. This study challenges the notion that factor Xa inhibitors are better alternatives to vitamin K anticoagulants in the treatment of pulmonary emboli based on their safety profile and ease of use alone. As a result, further post-marketing investigations into the efficacy of these agents in the management of pulmonary emboli may be warranted.

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“…Studies in healthy volunteers suggest that obesity has only modest effects on the pharmacokinetic profile of dabigatran, rivaroxaban, or apixaban and that dose adjustments for obesity may not be necessary. 29 For thromboprophylaxis after orthopedic surgery, a meta-analysis found similar efficacy and safety of DOACs in elderly obese and non-obese patients. 30 A meta-analysis of the major DOAC trials for treatment of VTE found no difference in efficacy or major bleeding between subgroups of patients with body weight ,100 kg vs .100 kg.…”

Section: Doacsmentioning

confidence: 99%

Thrombosis in the setting of obesity or inflammatory bowel disease

Lentz

2016

Blood

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Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to wax and wane with disease severity. Because of the lack of high-quality evidence to guide management decisions, approaches to the prevention and treatment of thrombosis in patients with obesity or IBD are based on extrapolation from general guidelines for antithrombotic therapy. Obesity alters the pharmacokinetics of some anticoagulant drugs, and IBD patients present the added management challenge of having a high risk of gastrointestinal bleeding while taking anticoagulants. An extended duration of anticoagulant therapy is often recommended for obese or IBD patients with unprovoked venous thromboembolism unless there is a high risk of bleeding, although more data and better biomarkers are needed to determine whether anticoagulation can be safely stopped in a subset of IBD patients during remission of active disease. Most patients with obesity or IBD require thromboprophylaxis in conjunction with hospitalization or surgery, with adjustment of anticoagulant dosing in patients with severe obesity.

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Pharmacology of anticoagulants used in the treatment of venous thromboembolism

Cited by 121 publications

References 74 publications

Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know

Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know

Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

Thrombosis in the setting of obesity or inflammatory bowel disease

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