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1.
Am J Ther ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31833874

RESUMO

BACKGROUND: The optimal monitoring strategy for anticoagulation management in extracorporeal membrane oxygenation (ECMO) remains a clinical controversy. The Extracorporeal Life Support Organization Anticoagulation Guidelines suggest that multiple anticoagulation assays may be needed but do not specify a preferred management strategy. STUDY QUESTION: In adult ECMO patients, which anticoagulation assays demonstrate the highest correlation with unfractionated heparin (UFH) dose requirements? STUDY DESIGN: We performed a retrospective chart review of adult patients cannulated to ECMO between February 2013 and July 2015. MEASURES AND OUTCOMES: The primary outcome was the correlation between activated clotting time (ACT), activated partial thromboplastin time (aPTT), and anti-Xa and UFH dose. Secondary outcomes included correlations between anticoagulation assays. Correlations were calculated for the entire cohort, with subgroup analysis of venoarterial and venovenous ECMO patients. RESULTS: Forty-eight patients were included in the analysis, 26 initially cannulated to venoarterial ECMO and 22 to veno-venous ECMO. The median duration of ECMO therapy was 7 days. Mean UFH requirements were 1149 units/h or 15.3 units/kg/h. Total UFH dose was most correlated with anti-Xa levels (r = 0.467), whereas weight-based heparin dose was most correlated with aPTT (0.405). For correlations between anticoagulation assays, anti-Xa and aPTT were more highly correlated with each other (r = 0.633) compared with ACT. CONCLUSIONS: In adult patients requiring ECMO, anti-Xa and aPTT monitoring were correlated more closely with UFH dosing than ACT.

2.
Blood ; 134(23): 2002-2003, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805193
3.
Hematology Am Soc Hematol Educ Program ; 2019(1): 71-79, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808892

RESUMO

The association between malignancy and thrombosis has been recognized for over a century and a half. Patients with cancer have an elevated risk of both initial and recurrent venous thromboembolism (VTE) compared with patients without cancer owing to cancer- and patient-specific factors. Recurrent VTE is common despite anticoagulation, presenting additional management challenges. Patients with cancer also have an increased risk of bleeding when on anticoagulants compared with patients without cancer. This bleeding risk is heightened by the thrombocytopenia common in patients with hematologic malignancies and those treated with intensive myelosuppressive chemotherapy regimens. Despite the advancements in cancer-directed therapy made over the past 15 years, numerous large studies have confirmed that bleeding and VTE recurrence rates remain high in cancer patients. Balancing the increased and competing risks of clotting and bleeding in these patients can be difficult, because management of cancer-associated thrombosis requires anticoagulation despite known increased risks for bleeding. In the context of challenging illustrative cases, this review will describe management approaches to clinical scenarios in which data are sparse: cancer patients with recurrent VTE despite anticoagulation and cancer patients with a new VTE in the setting of severe thrombocytopenia.

4.
Gastroenterology ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31843588

RESUMO

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC. METHODS: We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow up. The secondary end points were progression-free survival (PFS) and overall survival (OS) times. RESULTS: During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% CI, 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head, hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P=.027) and stage (locally advanced vs resectable or borderline HR, 1.66; 95% CI 1.10-2.51, P=.016 and metastatic vs resectable or borderline HR, 2.50; 95% CI, 1.64-3.79; P<.001) were independent risk factors for onset of VTE. Patients who developed VTE during follow up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P=.004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P<.001). CONCLUSION: In an analysis of data from the BACAP study, we found that frequent and early onset of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE.

7.
Blood Adv ; 3(22): 3770-3779, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31770442

RESUMO

The association between malignancy and thrombosis has been recognized for over a century and a half. Patients with cancer have an elevated risk of both initial and recurrent venous thromboembolism (VTE) compared with patients without cancer owing to cancer- and patient-specific factors. Recurrent VTE is common despite anticoagulation, presenting additional management challenges. Patients with cancer also have an increased risk of bleeding when on anticoagulants compared with patients without cancer. This bleeding risk is heightened by the thrombocytopenia common in patients with hematologic malignancies and those treated with intensive myelosuppressive chemotherapy regimens. Despite the advancements in cancer-directed therapy made over the past 15 years, numerous large studies have confirmed that bleeding and VTE recurrence rates remain high in cancer patients. Balancing the increased and competing risks of clotting and bleeding in these patients can be difficult, because management of cancer-associated thrombosis requires anticoagulation despite known increased risks for bleeding. In the context of challenging illustrative cases, this review will describe management approaches to clinical scenarios in which data are sparse: cancer patients with recurrent VTE despite anticoagulation and cancer patients with a new VTE in the setting of severe thrombocytopenia.

8.
Clin Appl Thromb Hemost ; 25: 1076029619876030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31530176

RESUMO

Clinical uncertainty exists regarding which assay should be designated as the standard monitoring coagulation test for intravenous unfractionated heparin (UFH). Several studies have compared the use of activated partial thromboplastin time (aPTT) and antifactor-Xa (anti-Xa) and have come out with varying results. The correlation between these 2 tests varied, markedly from strong to weak. Some have demonstrated that monitoring with anti-Xa heparin assay leads to fewer dose adjustments, resulting in fewer laboratory tests, while others have not. In the current study, we evaluated the correlation between aPTT and anti-Xa values to guide clinical management of UFH, with the intention to develop a new correlation nomogram.

9.
Lancet Oncol ; 20(10): e566-e581, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492632

RESUMO

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

11.
Semin Thromb Hemost ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537028

RESUMO

Surgical patients, following procedural interventions or traumatic injury, often bleed due to ongoing blood loss or coagulopathy. Volume resuscitation and transfusion management are critical for the massively bleeding patient. While transfusions may correct coagulopathy, they carry multiple risks including circulatory overload and transfusion-related acute lung injury. Factor concentrates, specifically prothrombin complex concentrates (PCCs), are often used as part of multimodal therapy for bleeding along with laboratory testing to rapidly assess underlying coagulopathy. Although they are commonly used as part of management algorithms, studies evaluating their efficacy against fresh frozen plasma (FFP) or other potential therapies are needed. Further, PCCs are indicated to treat the coagulopathy associated with non-vitamin K oral anticoagulants in the perioperative setting. The focus of this commentary will be the perioperative use of PCCs, plasma, and FFP.

12.
Curr Opin Cardiol ; 34(6): 603-609, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31389825

RESUMO

PURPOSE OF REVIEW: Patients with pulmonary embolism commonly undergo thrombophilia evaluation for a variety of reasons including risk stratification for recurrent venous thromboembolism (VTE) and treatment planning. However, the utility of thrombophilia testing in many clinical scenarios remains unclear. This review evaluates current recommendations for thrombophilia testing described in consensus VTE guidelines, recent literature on the clinical application of these recommendations, novel genetic assessments for hereditary thrombophilias, and studies evaluating use of direct oral anticoagulants (DOACs) in VTE patients with thrombophilias. RECENT FINDINGS: Current VTE guidelines advise limited use of thrombophilia testing, recognizing that testing may be misinterpreted and frequently does not lead to a change in management. Testing and test results are not necessarily benign, are frequently misinterpreted, and can lead to increased anxiety in both patients and clinicians. Recent studies have offered innovative techniques to better align clinical practice with these recommendations as well as expanded genomic assessments to improve the scope and predictive value of thrombophilia testing. There is also emerging literature on the appropriateness of direct oral anticoagulant therapy for VTE patients with hereditary thrombophilias or antiphospholipid syndrome. SUMMARY: Thrombophilia testing in its current form does not significantly impact clinical management or improve outcomes for most VTE patients. Therefore, it should be employed judiciously and only in patients for whom it is likely to alter clinical management. Novel expanded genomic thrombophilia testing approaches and additional studies evaluating optimal anticoagulant treatment in various thrombophilia subpopulations will make thrombophilia testing more useful for patients moving forward.

13.
J Thromb Haemost ; 17(11): 1790-1797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465627

RESUMO

The medical care of transgender patients relies on the use of sex hormones to develop and maintain the physical characteristics consistent with gender identity as the first step in transitioning. Hormonal therapy is usually continued indefinitely, even following gender-affirming surgeries. The use of hormonal treatments is associated with a multitude of positive effects as well as complications and side effects. The risk of venous thromboembolism (VTE) is a major concern. Transgender patients are often referred to coagulation specialists for advice regarding an individual patient's risk for VTE, especially if there is a personal or family history of VTE. Coagulation specialists need to be familiar with endocrine therapy including the goals of treatment and the VTE risks associated with currently used hormone regimens. We will review common referral questions and the available data and their limitations for the use of hormonal therapy in transgender patients focusing on the risk of VTE.

14.
Vasc Health Risk Manag ; 15: 175-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417269

RESUMO

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer. Compared with the general population, cancer patients with VTE have higher rates of both VTE recurrence and bleeding. While low molecular weight heparin (LMWH) has been the mainstay of treatment for cancer-associated VTE for over a decade, direct oral anticoagulants (DOACs) have recently emerged as a new therapeutic option due to their ease of administration and because they do not require laboratory monitoring. Several large randomized clinical trials have been performed or are ongoing at the time of writing, comparing DOACs with LMWH in this population. Three of these trials have thus far been published and suggest that DOACs are a reasonable alternative to LMWH for management of cancer-associated VTE. Despite the advantages offered by DOACs, these agents may not be appropriate for certain patient groups owing to increased risk of bleeding, organ compromise, extremes of weight, and other issues. Finally, data are emerging suggesting that DOACs may be useful for primary thromboprophylaxis in cancer patients in conjunction with validated risk assessment scores. In this evidence-based review, data for the use of DOACs to treat cancer-associated VTE will be examined, focusing on efficacy, safety, and timing of treatment. Guidance on choosing the optimal anticoagulant for a given patient is also offered.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/mortalidade , Recidiva , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidade
17.
A A Pract ; 13(7): 271-273, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265446

RESUMO

Andexanet alfa is a recombinant factor Xa decoy molecule capable of reversing direct and indirect factor Xa-inhibiting anticoagulants. We present an adult patient on apixaban for nonvalvular atrial fibrillation who required urgent reoperative aortic surgery for an aortic root pseudoaneurysm. Apixaban was reversed with andexanet alfa. A second dose of andexanet alfa was required before surgical incision for persistently elevated antifactor Xa levels. Intraoperative management required use of cardiopulmonary bypass (CPB). No major adverse cardiovascular, cerebrovascular, hemorrhagic, or thromboembolic events were observed.

18.
BMJ Qual Saf ; 28(10): 835-842, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31243156

RESUMO

BACKGROUND: Clinical guidelines recommend anticoagulation for patients with atrial fibrillation (AF) at high risk of stroke; however, studies report 40% of this population is not anticoagulated. OBJECTIVE: To evaluate a population health intervention to increase anticoagulation use in high-risk patients with AF. METHODS: We used machine learning algorithms to identify patients with AF from electronic health records at high risk of stroke (CHA2DS2-VASc risk score ≥2), and no anticoagulant prescriptions within 12 months. A clinical pharmacist in the anticoagulation service reviewed charts for algorithm-identified patients to assess appropriateness of initiating an anticoagulant. The pharmacist then contacted primary care providers of potentially undertreated patients and offered assistance with anticoagulation management. We used a stepped-wedge design, evaluating the proportion of potentially undertreated patients with AF started on anticoagulant therapy within 28 days for clinics randomised to intervention versus usual care. RESULTS: Of 1727 algorithm-identified high-risk patients with AF in clinics at the time of randomisation to intervention, 432 (25%) lacked evidence of anticoagulant prescriptions in the prior year. After pharmacist review, only 17% (75 of 432) of algorithm-identified patients were considered potentially undertreated at the time their clinic was randomised to intervention. Over a third (155 of 432) were excluded because they had a single prior AF episode (transient or provoked by serious illness); 36 (8%) had documented refusal of anticoagulation, the remainder had other reasons for exclusion. The intervention did not increase new anticoagulant prescriptions (intervention: 4.1% vs usual care: 4.0%, p=0.86). CONCLUSIONS: Algorithms to identify underuse of anticoagulation among patients with AF in healthcare databases may not capture clinical subtleties or patient preferences and may overestimate the extent of undertreatment. Changing clinician behaviour remains challenging.

19.
J Thromb Thrombolysis ; 48(3): 382-386, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228036

RESUMO

Malignancy is a well-established risk factor for venous thromboembolism and while low-molecular-weight heparin therapy has been standard of care for cancer-associated thrombosis for many years, many patients find injection therapy burdensome. The direct oral anticoagulant edoxaban has been shown to be noninferior to dalteparin for the treatment of cancer-associated thrombosis. In a Markov simulation model, edoxaban with 6-month time horizon and a United States societal perspective with 2017 US dollars, edoxaban was the preferred strategy in the general cancer population (6-month cost $6061 with 0.34 quality adjusted life years) and in a subgroup of patients with gastrointestinal malignancy (6-month cost $7227 with 0.34 quality adjusted life years). The incremental cost effectiveness ratio of dalteparin compared to edoxaban was $1,873,535 in the general oncology population and $694,058 in the gastrointestinal malignancy population.

20.
ASAIO J ; 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31192853

RESUMO

Durable left ventricular assist device (LVAD) recipients require long-term anticoagulation to prevent thromboembolic complications. Their management is complicated by the risk of bleeding, which may require rapid anticoagulation reversal. We conducted a narrative review of data published from January 2007 to September 2018, analyzing anticoagulation reversal strategies in patients with durable, continuous-flow LVADs. The aim of this review is to provide guidance for reversal strategies in patients with LVADs experiencing bleeding complications or needing urgent surgical procedures, incorporating four-factor prothrombin complex concentrate (4F-PCC). Most data were from small, retrospective studies. Data for 4F-PCC use were more robust for heart transplant than for other surgical procedures or bleeding management. In patients undergoing heart transplant, 4F-PCC reversed warfarin more rapidly and reduced total blood product use versus other reversal strategies. Most surgical procedures were conducted without excess bleeding when utilizing 4F-PCCs. Time to warfarin reversal was shorter when managing intracranial hemorrhage with 4F-PCC. No differences in thromboembolic rates between 4F-PCC and control groups were observed. Overall, the use of 4F-PCC resulted in more rapid and predictable warfarin reversal in LVAD patients with no apparent risk of thromboembolism. Well-designed, larger prospective trials are required to better define 4F-PCC use in patients with LVADs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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