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Due to their widespread use, testing for direct oral anticoagulants (DOACs) has become urgent in certain clinical situations. Screening based on widely available, rapid, and simple hemostasis assays such as prothrombin time, activated partial thromboplastin time, or even diluted Russel Viper venom time may provide sufficient evidence of "over-coagulation" and could be used "in small/peripheral/spoke laboratories" as an emergency strategy, but is not thought to be reliable for driving clinical decision making. Given their good correlation with plasma concentration, urine dipsticks may be considered a valuable alternative for emergency screening, although their performance is dependent on renal function, may vary depending on the time since the last urination, and there may be problems of interfacing with the laboratory/hospital information system. Separation methods based on liquid chromatography and mass spectrometry may be clinically questionable, since they measure the concentration rather than the actual inhibitory effect of DOACs, are relatively expensive, cumbersome and time consuming, and therefore seem unsuitable for most conditions requiring urgent clinical decision making. A proposed approach therefore involves establishing a network of routine clinical laboratories, designating a reference center where DOAC tests could be available 24/7, establishing a clear diagnostic care pathway for ordering the tests from the laboratory and standard operating procedures for performing them, the use of the diluted thrombin time for dabigatran and anti-FXa assays (drug-calibrated) for rivaroxaban, apixaban, and edoxaban, as well as providing expert advice throughout the testing process, from ordering to interpretation of results. [ABSTRACT FROM AUTHOR]

The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection. [ABSTRACT FROM AUTHOR]

Patients with thrombotic antiphospholipid syndrome (APS) require long-term anticoagulation due to the high-thrombotic recurrence risk. Vitamin K antagonists (VKA) have been traditionally considered the standard of care in thrombotic APS. Nevertheless, the risk of recurrence persists with VKA. There are publications considering different intensities of anticoagulation with VKA; however, the standard-intensity anticoagulation (international normalized ratio between 2.0 and 3.0) is the most recommended. Furthermore, there is no consensus on the role of antiplatelet treatment in thrombotic APS. Nonvitamin K antagonist oral anticoagulants (NOACs) have emerged as an alternative to VKA for many indications. There are, however, discrepancies regarding the management with NOACs in thrombotic APS. In this review, we update the different clinical trials with NOACs in venous, arterial, and microvascular thrombosis and suggest how these patients should be managed in agreement with the expert panels. Although scarce data are published regarding the current role of NOACs in thrombotic APS, the clinical trials failed to demonstrate noninferiority of NOACs compared with VKA, especially in patients with triple antiphospholipid antibodies positivity and/or arterial thrombosis. Single or double antiphospholipid positivity should be analyzed on a case-by-case basis. In addition, we focus on different areas of uncertainty that still remain in thrombotic APS and NOACs. To summarize, emerging clinical trials are needed to provide robust data on the management of thrombotic APS. [ABSTRACT FROM AUTHOR]

Anticoagulant therapy is the cornerstone of treatment and prevention of arterial and venous thromboembolism. Taking a historical perspective, starting in the 1960s, and progressing through to 2022, we discuss key clinical trials of anticoagulants that have changed clinical practice, and examine obstacles encountered in bringing these anticoagulants to the clinic. The design of some of the early studies that shaped clinical practice was poor by current standards, but their results were influential because nothing better was available. Both heparin and vitamin K antagonists had been in clinical use for several decades before well-designed trials in the 1980s optimized their dosing and enhanced their safety and efficacy. Low-molecular-weight heparin then replaced unfractionated heparin because it had a more predictable dose–response and a longer half-life, thereby allowing it to be used conveniently in out-of-hospital settings. More recently, direct oral anticoagulants became the oral anticoagulants of choice for most indications because they were shown to be at least as safe and effective as vitamin K antagonists when used in fixed doses without the need for laboratory monitoring. The design of the trials that led to the approval of the direct oral anticoagulants was excellent, but further studies are required to optimize their dosing in selected patients who were underrepresented in these trials. [ABSTRACT FROM AUTHOR]

The association between heritability of venous thromboembolism (VTE) and thrombophilia was first reported clinically in 1956, later followed by the first description of a congenital cause of hypercoagulability—antithrombin deficiency—in 1965. Since then, our knowledge of hereditary causes of hypercoagulability, which may predispose carriers to VTE has improved greatly. Novel genetic defects responsible for severe thrombophilia have been recently identified and we have learned that a wide range of interactions between thrombophilia and other genetic and acquired risk factors are important determinants of the overall individual risk of developing VTE. Furthermore, therapeutic strategies in thrombophilic patients have benefited significantly from the introduction of direct oral anticoagulants. The present review is an overview of the current knowledge on the mechanisms underlying inherited thrombophilia, with a particular focus on the latest achievements in anticoagulation protocols and prevention strategies for thrombosis in carriers of this prothrombotic condition. [ABSTRACT FROM AUTHOR]

There are situations where monitoring direct oral anticoagulants (DOACs) would be useful, including bleedings and trauma. The thromboelastographic technique has proven useful in bleeding situations in trauma and heart surgery. The aim of this study was to examine the effect of DOACs on all currently commercially available conventional TEG®5000 assays as well as novel modified assay using Ecarin and human factor Xa (HFXa). Healthy male volunteers were given single dose of oral dabigatran 150 mg, rivaroxaban 20 mg, or apixaban 5 mg. Kaolin, RapidTEG, functional fibrinogen, PlateletMapping assay, and novel modified assays using Ecarin and HFXa were prepared. All TEG parameters were recorded. DOAC concentrations were correlated to the parameters with highest response to the DOAC effect. Sensitivity and negative predictive value of the parameter with highest response to DOAC concentration of 50 ng/mL was calculated. None of the conventional TEG assays demonstrated significant response to the effect on apixaban. Using Ecarin, reaction time R was strongly correlated with dabigatran concentrations. Using HFXa assay, R was strongly correlated with rivaroxaban and apixaban concentrations: r  = 0.96, 0.84, and 0.86, respectively; p  < 0.0001 for all. The R times obtained with the modified assays demonstrated strong sensitivity and negative predictive values for DOAC levels of ≥50 ng/mL. We have demonstrated that TEG®5000 can monitor the DOAC effect on hemostasis when the appropriate activator is used with significant correlation with DOAC concentrations. Larger clinical studies are warranted for correlation of TEG profile and clinical outcomes. [ABSTRACT FROM AUTHOR]

Ambulatory cancer patients undergoing chemotherapy are at a substantial risk for venous thromboembolism (VTE) over the course of therapy and beyond it. Factors accounting for this risk include the activation of extrinsic and intrinsic coagulation pathways, platelet activation, impaired fibrinolysis, use of catheters, infusion of blood products, and thrombogenic potential of several chemotherapeutic drugs. A few stratification models can help identify patients at a higher risk of chemotherapy-associated VTE, who may benefit from preventive strategies. Although low-molecular-weight heparins (LMWHs) effectively reduce the risk of VTE, current guidelines recommend against their routine use. Based on the results of recent randomized controlled clinical trials, the administration of prophylactic doses of the novel direct oral anticoagulants (DOACs) to ambulatory cancer patients undergoing chemotherapy has the potential to offer an effective and safe protection against VTE, obviating the inconveniences of heparins. Except for patients in whom the novel drugs are unsuitable or are contraindicated, in all other patients LMWHs should be replaced by low-dose DOACs. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are increasingly used worldwide for the prevention of stroke in patients with atrial fibrillation and to prevent or treat venous thromboembolism. In situations such as serious bleeding, the need for urgent surgery/intervention or the management of a thromboembolic event, the laboratory measurement of DOACs levels or anticoagulant activity may be required. Rotational thromboelastometry (ROTEM) is a viscoelastic hemostatic assay (VHA) which has been used in emergencies (trauma and obstetrics), and surgical procedures (cardiac surgery and liver transplants), but experience with this assay in DOACs-treated patients is still limited. This article reviews the use of ROTEM in the setting of DOACs therapy, focusing on DOACs-associated bleeding and the use of this VHA for the management of reversal strategies for DOACs-associated anticoagulation. [ABSTRACT FROM AUTHOR]

Measurement of direct oral anticoagulants (DOACs) activity is not routinely necessary. Indeed, evaluation of DOACs plasmatic concentration is discouraged for the majority of patients, due to the lack of outcome data supporting this approach. Nevertheless, DOAC measurements may be useful in emergency situations such as serious bleeding events, need for urgent invasive procedures, and acute ischemic stroke or in managing anticoagulation in "special populations" not adequately studied in clinical trials, for example the very elderly or those at the extremes of body weight. The aim of this review is to describe and summarize the methods for DOACs activity evaluation and the settings in which their plasma level measurement may be indicated, analyzing indications from scientific societies and evidence from clinical trials, as well as real world data on the usefulness of DOACs plasma levels "monitoring." [ABSTRACT FROM AUTHOR]

Disseminated intravascular coagulation (DIC) is a relatively rare but life-threatening condition, the outcome of which depends largely on timely and accurate therapeutic management. Inhibiting the activation of blood coagulation is an effective option for limiting the burden of diffuse intravascular thrombosis for attenuating consumption of clotting factors and platelets and ultimately preventing massive bleeding. Direct oral anticoagulants (DOACs) are a relatively new generation of drugs that specifically inhibit activated factors II (thrombin) and X, thus providing effective anticoagulation while concomitantly limiting the hemorrhagic risk compared with other conventional anticoagulant agents. The peculiar mechanism of action would hence at least theoretically support their usage in patients with DIC, especially in those with a more pronounced thrombotic phenotype. A comprehensive literature search on the use of DOACs in patients with intravascular coagulopathies currently yielded only 15 documents, all case reports, totaling 21 patients (dabigatran, n  = 5; rivaroxaban, n  = 13; apixaban, n  = 3; edoxaban, n  = 0). Taken together, the current literature data suggest that these drugs may have low prophylaxis efficacy and thereby their indication for preventing DIC in high-risk patients may be limited. Nevertheless, DOACs seem at least therapeutically equivalent to heparin in some forms of DIC, especially in those with prevalent thrombotic phenotype, while having more favorable oral administration. The inherent risk of hemorrhages from heparin injection is also shared by DOACs; therefore, their use in DIC patients with a prevalent bleeding phenotype will probably remain unwarranted. Major caution should also be used in patients with impaired drug metabolism, especially those progressing toward liver or renal failure or receiving aggressive antimicrobial treatment. Where potentially indicated, further clinical trials should be planned to test the therapeutic efficacy of these drugs in patients with different types or forms of DIC. [ABSTRACT FROM AUTHOR]

Interruption of chronic anticoagulation due to the bleeding risk associated with an elective procedure may also lead to an elevated risk of thromboembolism. Periprocedural bridging with either unfractionated heparin or low-molecular weight heparin had been the mainstay of therapy for many patients receiving chronic warfarin treatment based on an estimation of a patient's thromboembolic risk. However, recent results from cohort studies and placebo-controlled randomized trials in the periprocedural use of heparin bridging for warfarin-treated patients reveal a consistent two- to three-fold increase in the risk of major bleeding and no benefit in terms of a reduction in the risk of stroke and systemic embolism. The most recent antithrombotic guidance statements suggest that the majority of patients on chronic warfarin, except those at high risk of thromboembolism, may safely interrupt and resume warfarin without heparin bridging in elective periprocedural settings. In addition, data from the use of heparin bridging in patients on direct oral anticoagulants during temporary interruption for an elective procedure also reveal harm and no benefits of this approach. A strategy that considers the pharmacokinetic properties of the direct oral anticoagulants, the bleeding risk of each procedure, and patient renal function would safely obviate the need for heparin bridging. In this review, the authors summarize the major studies of heparin bridging for patients on chronic oral anticoagulants that may lead to a change in practice in periprocedural antithrombotic management and define an evidence-based heparin bridging protocol for those patient groups who may be the candidates for this approach. [ABSTRACT FROM AUTHOR]

Cancer-associated thrombosis (CAT) is a common occurrence in the journey of a cancer patient and its management poses significant challenges. Low molecular weight heparin (LMWH) is the standard of care but the high cost and the inconvenience of daily injections have led to low persistence with therapy. Direct oral anticoagulants (DOACs) are effective and safe for the treatment of venous thromboembolism (VTE) compared with vitamin K antagonist (VKA) therapy in noncancer patients, and emerging data comparing their use with LMWH in CAT are rapidly changing clinical practice. Recent randomized controlled trials also reported that specific DOACs are effective for primary prevention of CAT in patients undergoing systemic cancer therapy, but this benefit might be offset by an increased risk of bleeding. Undoubtedly, the option of an effective and safe oral anticoagulant is appealing to physicians and patients but critical limitations of DOACs, particularly bleeding and drug-drug interaction, need careful consideration. Understanding the scientific data, as well as each patient's preferences and values, are paramount in individualizing therapy in this special population of patients. This review summarizes the current evidence for DOACs for the treatment and prevention of CAT, discusses the importance of careful patient selection, and highlights upcoming new studies that will inform guideline recommendations. [ABSTRACT FROM AUTHOR]

Anticoagulant drugs comprise a specific subcategory of antithrombotic agents that act to inhibit blood coagulation at various stages, reducing clot development and ultimately lowering the risk of developing new-onset or recurrent thrombosis. Although the long history of anticoagulant drugs has been characteristically shaped by coumarin and heparin derivatives, a new generation of direct oral anticoagulants (DOACs), which specifically inhibit thrombin or activated factor X, combine many advantages of their progenitor drugs, and hence are prepotently revolutionizing the landscape of antithrombotic therapy. Several drugs (apixaban [BMS-562247], dabigatran [BIBR953], edoxaban [DU-1766], rivaroxaban [BAY 59–7939]) have already received widespread approval by national or supranational medicinal agencies. This narrative article provides a state-of-the-art for these and for several other DOACs at different stages of clinical evaluation (betrixaban, darexaban, eribaxaban, letaxaban, nokxaban), and certain others whose development has been discontinued (AZD-0837, fidexaban, LY517717, odiparcil, otamixaban, TTP889, and ximelagatran). What clearly emerges from our analysis is that DOACs sharing very similar mechanisms of action are still characterized by different efficacy and safety profiles. This not only depends on biochemical, biological, and pharmacokinetic characteristics, but also on lack of standardization between different clinical trials in terms of targeted disease, patient recruitment, sample size, duration and endpoints, as well as lack of harmonization around procedures used for drug licensing. These factors contribute to challenging the minds of physicians, who may find difficulty navigating their way through multiple indications, different pharmacological profiles, various side effects, and specific drug-to-drug interactions. Such considerations also burden laboratory professionals, who may face organizational and economic challenges in developing and/or implementing multiple assays to assess the pharmacodynamics (effect on coagulation) or pharmacokinetics (drug levels) of DOACs. [ABSTRACT FROM AUTHOR]

The direct oral anticoagulants (DOACs) currently require no monitoring for routine therapy of atrial fibrillation or venous thromboembolism. Measurement of activity, however, may be important in patients with major and life-threatening bleeding, patients needing emergent surgery, in reversal situations, or in patients at high risk of bleeding or thrombosis due to underlying conditions. For these patients, a widely available and rapid turnaround assay would be optimal. To date, there is no such assay available, especially for the direct factor Xa inhibitors. This report describes the performance of a new, rapid turnaround, point-of-care (PoC) assay for measuring the activity of a range of anticoagulants, including DOACs and heparins, in emergency situations and for routine measurement in high-risk patients. Perosphere Technologies' PoC coagulometer is a handheld instrument that performs individual coagulation tests on samples of fresh whole blood (∼10 µL) with clotting activated by glass contact and endpoint determination performed by infrared spectroscopy. In preclinical studies using rats anticoagulated with therapeutic doses of edoxaban or enoxaparin, the PoC coagulometer showed a strong linear correlation between pharmacokinetic parameters and clotting time with edoxaban ( r 2  = 0.994) and with enoxaparin ( r 2  = 0.967). These preclinical results suggest that this PoC coagulometer would be ideal to assess the pharmacodynamic effects of anticoagulants and their reversal agents. The PoC bedside instrument delivers results within minutes and requires no more than a drop of whole blood. Studies are underway to confirm these results in humans and to further characterize the performance of the instrument. [ABSTRACT FROM AUTHOR]

The assessment of the anticoagulant effect of direct oral anticoagulants (DOACs) can be important for rapid medical decision-making, especially in patients needing immediate management. An assay that screens for the absence or presence of a DOAC would help accelerate treatment in these situations. Chromogenic and coagulation methods have several limitations, including limited accuracy, long turnaround time, and their need of specialized laboratories. Oral factor Xa and thrombin inhibitors are also eliminated by the kidneys and can be detected in patient urine samples using a single, rapid, sensitive, and patient-specific qualitative assay. In these tests, the presence or absence of a DOAC in urine can be identified by visually observing specific colors after a few minutes. Several studies have demonstrated the robustness and repeatability of these assays. The specific colors of the test strip also detect creatinine in the urine, which shows whether DOAC excretion is reduced, thus suggesting renal impairment. Persons with amblyopia may use a specific reader. Current indications for using the DOAC Dipstick test include emergency medical situations with severe bleeding and thrombotic events or before urgent major surgical interventions to accelerate medical decision-making. [ABSTRACT FROM AUTHOR]

Patients with acute spinal cord injury (SCI) have the highest risk of venous thromboembolism (VTE) among hospitalized patients. The incidence of total deep vein thrombosis ranges from 50 to 100% in untreated patients and pulmonary embolism is the third most common cause of mortality in these patients. The pathophysiology of the increased risk of VTE is explained by venous stasis after injury, endothelial vessel wall injury from surgery, and a hypercoagulable state associated with trauma. The current thromboprophylaxis options are limited, with low-molecular-weight heparin (LMWH) being the current standard of care. LMWH is commonly administered for 3 months, during which period the risk of VTE is especially high. Some uncertainty exists regarding the optimal timing to initiate pharmacological thromboprophylaxis and the best regimen of LMWH prophylaxis. High-quality data are currently lacking in thromboprophylaxis in patients with SCI. Many questions in this area remain to be answered, which are described in this narrative review. [ABSTRACT FROM AUTHOR]

For procedures associated with minimal bleeding risk, there are data and experience to support the practice of continuing vitamin K antagonists rather than interrupting therapy, to prevent exposing patients to the undue risk of developing thromboembolism during anticoagulation cessation. Despite the increasing use of non–vitamin K oral anticoagulants (NOACs), there is little evidence to guide the management of these drugs around minimal bleeding risk procedures. This review examines and discusses the major society guidelines and recommendations addressing the management of NOACs around minimal bleeding risk procedures. Additionally, it summarizes the existing evidence, and highlights the gaps in knowledge where evidence is not yet available. Finally, recommendations are made to assist the proceduralist deal with this area of limited evidence. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a leading cause of morbidity with potentially detrimental career consequences in elite athletes. Their unique predisposing factors entail a higher-than-expected VTE incidence. Anticoagulation treatment is challenging, especially among those athletes wishing to resume their competitive activities. The authors review the current VTE treatment guidelines from the perspective of treating elite athletes. They then provide an expert opinion individualized treatment approach based on the pharmacokinetic properties of direct oral anticoagulants that permits tailoring the drug's timing to the athlete's competitive endeavors. They also present low-molecular-weight heparin as an alternative. The proposed risk management approach allows mitigation against VTE recurrence, reducing the chance of major bleeding, and honoring the athlete's self-determination to resume their career while accepting the risks involved. A shared decision making with the athlete and his/her team along with the presence of adequate resources are key components. Ultimately, the authors hope this work will serve as a stepping stone to validated VTE treatment regimens that consider the particularities of elite athletes. [ABSTRACT FROM AUTHOR]

The current mainstay of the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS) is anticoagulation with warfarin or other vitamin K antagonists (VKAs). In addition to their well-known limitations, VKAs are often problematic in APS patients because of the variable sensitivity of thromboplastins to lupus anticoagulant. As a result, the international normalized ratio may not accurately reflect the intensity of anticoagulation. Direct oral anticoagulants (DOACs) are established as therapeutic alternatives to VKAs for a wide range of indications, including the treatment and secondary prevention of venous thromboembolism. Definition of the role of DOACs in the treatment of thrombotic APS is emerging with the results of recent and ongoing clinical studies. This review focuses on the current situation with regard to DOACs for secondary thromboprophylaxis in APS and issues pertinent to DOAC use in APS patients, as well as potential future directions. [ABSTRACT FROM AUTHOR]

The advent of direct oral anticoagulants (DOACs) has revolutionized anticoagulation management in both stroke prevention and venous thromboembolism (VTE) treatment/prevention. Clinical trials and secondary real-world data have shown that DOACs have similar efficacy and, in some cases, improved bleeding safety profiles compared with vitamin K antagonists. Together with benefits of patient convenience, this has shifted the risk-benefit ratio toward long-term anticoagulation. However, current VTE risk assessment models are based on vitamin K antagonists and do not take into account the new paradigm of DOACs. Therefore, challenges to the thrombosis community remain to determine patients who would benefit from long-term anticoagulation in the DOAC era. Here, the authors review the current literature on risks and benefits of DOACs and their potential role in long-termVTE thromboprophylaxis as well as in current risk assessment models. The increasing use of DOACs, led by their convenience of use and generally lower bleeding rates, calls for a reevaluation of the current models as the benefits of long-term anticoagulation may begin to outweigh risks and inconvenience associated with their predecessors. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) provide an effective, safe, and convenient therapeutic alternative to warfarin and other vitamin K antagonists (VKAs), and are now established for a wide range of indications. The use of DOACs in women merits special consideration due to two main situations: first, in relation to fertility, pregnancy, and lactation in women of reproductive age; second, because of their bleeding risk, leading to abnormal uterine and/or other genital tract bleeding. This review focuses on these two clinical situations, including approaches to management in the context of available information. [ABSTRACT FROM AUTHOR]

Introduction Limited information exists on gender-related differences in the safety and efficacy of non-vitamin K antagonist oral anticoagulants (NOACs). Aim of the Study To assess the safety and efficacy of direct oral anticoagulants (DOACs)/ NOACs in men and women pooling data from randomized controlled trials on the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) and on the acute and extended treatment of venous thromboembolism (VTE). Methods MEDLINE and EMBASE databases were searched up to June 2014. The efficacy outcome was defined as the prevention of stroke and systemic embolism (AF studies), or as the prevention of recurrent VTE or VTE-related death (VTE studies). The safety outcome was defined as the occurrence of major and/or clinically relevant nonmajor bleeding. Differences in the efficacy and safety outcomes were expressed as risk ratio (RR) with pertinent 95% confidence intervals (95% CI). Results A total of 13 studies (> 100,000 patients) were included. DOACs appeared to have a similar efficacy and safety compared with vitamin K antagonists in female and male patients treated for nonvalvular AF and acute VTE. In the extended treatment of VTE NOACs had a RR of bleeding of 4.97 (95% CI 1.06, 23.41) in males and 1.33 (95% CI 0.63, 2.83) in females compared with placebo (subgroup difference chi-square test: 2.25, p = 0.13). Conclusions No gender-related difference in the efficacy and safety of NOACs in patients with AF or acute VTE was found. A trend toward an increased risk of bleeding in male patients as compared with female patients was detected in the extended treatment of VTE. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) have changed the paradigm of anticoagulation management, improving patient convenience as well as possibly reducing the incidence of spontaneous intracranial hemorrhage. However, concerns remain with these agents because of the lack of monitoring capacity and availability of readily accessible specific antidotes. This is particularly pertinent in the older population, specifically the frail older adults who have multiple comorbidities, higher risk of falls, and increased bleeding risk. This group has not been specifically studied in the DOAC randomized controlled trials and, hence, extrapolation of these data into this population should be done cautiously. We provide a review of the use of DOACs in the older frail population from both hematological and geriatric perspectives, as well as propose an algorithm for how these agents may be used in this frail population. [ABSTRACT FROM AUTHOR]

The direct oral anticoagulants (DOACs) are increasingly used in patients with atrial fibrillation and venous thromboembolism. The decision making of clinicians and especially emergency physicians for the appropriate management of patients taking DOACs entails a thorough understanding of pharmacologic profile, practical guidance on their usage, and management of bleeding and/or thrombotic events. The available evidence suggests that the bleeding complications observed in patients taking DOACs are less frequent and potentially less severe than those in patients taking vitamin K antagonists or heparins. This should be regarded as an advantage for emergency physicians, since it would decrease the admission rate of anticoagulated patients and probably require a less aggressive treatment in the emergency department (ED). The greatest challenge of DOACs is so far represented by the lack of clinically usable antidotes, since these (i.e., idarucizumab, andexanet alfa, and aripazine) are in different phases of development. A second major concern is the current lack of consensus about laboratory monitoring for these drugs. Although there is widespread perception that patients on DOACs do not require dose adjustment based on laboratory testing, in some selected clinical situations, laboratory testing may be taken into consideration in the ED. The type of laboratory diagnostics needed for emergency management should hence include tests that are promptly available, affordable to all stat laboratories, and cost effective. The aim of this article is to provide a personal overview on quality and safety issues of DOACs with an ED perspective. [ABSTRACT FROM AUTHOR]

Dabigatran, rivaroxaban, and apixaban are direct oral anticoagulants (DOAC) inhibiting thrombin or factor Xa and effectively preventing thromboembolic complications using fixed doses without need for laboratory-guided dose adjustment. Plasma samples are needed to determine the actual concentration or activity of DOACs, which may be required for special patient populations such as those with acute deterioration of renal function due to any disease, before surgical interventions, during bleeding or thrombotic episodes while on therapy with DOACs, the elderly and youngest populations, unexpected pregnancy, suspicion of overdose and toxication, and to control adherence to therapy. Serum samples have several advantages over plasma samples such as no need of sampling with a specific coagulation tube, reduced pre-analytical errors, and longer storage stability. Determination of rivaroxaban and apixaban from serum samples of patients on treatment performed well and better than samples of patients treated with dabigatran compared with plasma samples. Specific adaption to automated coagulation platforms may improve the performance of the assays from serum samples. [ABSTRACT FROM AUTHOR]

Because their anticoagulant effect is dose predictable, steady, and little influenced by diet and drugs, laboratory monitoring was deemed unnecessary in trials on venous and arterial thromboprophylaxis with the direct oral anticoagulant drugs (DOACs) rivaroxaban, apixaban, edoxaban, or dabigatran. However, there are special clinical settings in which measurement of their anticoagulant effect may be clinically desired. Because of lack of standardization between reagents employed and their global nature, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) are not generally suitable for accurately assessing the anticoagulant effect of DOACs. The modified (diluted) PT reliably quantifies the anticoagulant effect of rivaroxaban or of apixaban. However, a higher intra-individual variability from one PT reagent to another is found when the data are compared with those obtained with standard PT. The HEMOCLOT (HYPHEN BioMed, France) assay is a modified (diluted) thrombin time (TT) provided with dabigatran calibrators. However, it is performed only in few specialized centers. Anti-factor Xa (anti-FXa) chromogenic assays employ routine automated coagulometers or manual spectrometers, and kits for anti-FIIa assays that measure dabigatran levels and kits for anti-Xa with rivaroxaban calibrators are commercially available. However, no correlation has been identified between any of these tests and clinical outcomes in patients taking any of the DOACs. Thus, currently, there are evidence gaps regarding the role of laboratory testing for surveillance and management of adverse events associated with DOACs. In view of this, in addition to standardization, validation of such assays is mandatory before they can be used to make clinical decisions. [ABSTRACT FROM AUTHOR]