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Background/Objectives: Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. Methods: We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Results: Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; p < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients (p = 0.049, p < 0.001, p < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients (p = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. Conclusions: This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.
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OBJECTIVES: Antiphospholipid syndrome (APS)-associated heart valve disease (HVD) is well described. Nonetheless, limited data exist on clinical parameters associated with the course of primary APS (pAPS) patients with HVD. The goal of this study was to assess clinical features and related outcomes in patients with APS associated HVD. METHODS: In this multicentre retrospective study, we identified 33 pAPS patients with HVD (pAPS-HVD group) and compared their clinical course with 128 pAPS patients with normal heart valves on echocardiography (pAPS-control group). RESULTS: pAPS-HVD patients had more cerebrovascular events 56.3% vs 25% (p= 0.005) and livedo reticularis 24.2% vs 7.8% (p= 0.013) than pAPS-controls. Furthermore, catastrophic-APS (CAPS) (12.1% vs 2.4%, p= 0.034), recurrent thrombosis (33.3% vs 4.7%, p< 0.001), and need for advanced therapy (i.e. IVIG, plasmapheresis or rituximab) were more frequent in pAPS-HVD patients. Anti-B2GPI-IgG. [84.8% vs 63.2% (p= 0.034)], anti-cardiolipin IgG [90.9% vs. 64.8% (p= 0.005)] and triple positive aPL [75.8% vs 56.5% (p= 0.047)] were commoner in pAPS-HVD patients vs pAPS-controls. Ten of the 33 patients with pAPS-HVD underwent valve surgery which was associated with male gender, smoking, arterial limb ischaemia and livedo reticularis. CONCLUSION: pAPS-HVD patients had a more severe APS clinical course including CAPS and thrombotic events as well as with specific serology namely IgG isotype aPL antibodies and triple positivity. Our data suggest that pAPS-HVD represents a high-risk subgroup of APS patients.
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Multiple myeloma (MM) is associated with an increased risk of venous and arterial thrombosis. Pathophysiologic mechanisms include patient, disease and treatment related factors. Risk assessment models have been developed to determine whichpatients are at highest thrombotic risk and pursuant to this, risk adapted thrombosis prophylaxis has been suggested. Areas in which further basic and clinical research is imperative include the molecular and cellular mechanisms of thrombosis in myeloma, the inclusion of relevant biomarkers in risk assessment scores and controlled clinical trials of VTE prophylaxis and treatment using direct oral anticoagulants.
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Mieloma Múltiplo , Trombose , Tromboembolia Venosa , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/terapia , Anticoagulantes/efeitos adversos , Medição de Risco , Trombose/prevenção & controle , Trombose/complicações , Fatores de RiscoRESUMO
BACKGROUND: Venous thromboembolism (VTE) in the Intensive Care Unit (ICU) is associated with significant morbidity and mortality therefore prevention is imperative to reduce its burden. VTE prophylaxis in ICU patients is primarily pharmacological using low molecular weight heparin (LMWH). Plasma anti-factor Xa (anti-FXa) levels may be used to measure LMWH activity. This study aims to determine the proportion of acutely ill patients in a general ICU receiving standard VTE prophylaxis that achieve adequate peak or trough anti-FXa prophylactic levels and to determine the effect of LMWH dose adjustment in patients not achieving adequate anti-FXa prophylactic levels. METHODS: Peak and trough anti-FXa levels were measured at four and 23 hours respectively after receiving the second consecutive daily enoxaparin 40 mg sc injection. Patients in whom peak anti-FXa levels were found to be sub-prophylactic (<0.2 IU/mL), were dose escalated to enoxaparin 60 mg once daily. Peak and trough levels were repeated as above. RESULTS: Sixty-one percent of study patients (N.=46) were found to have sub-prophylactic peak anti-FXa levels. Twenty-seven patients received an increased enoxaparin dose of 60 mg/d. Of these, nine patients (33.3%) still failed to achieve the target prophylactic peak anti-FXa level (0.2-0.4 IU/mL). Male gender and high body mass index (BMI) were significantly and strongly correlated with sub-prophylactic anti-FXa levels. CONCLUSIONS: Most ICU patients in this study did not achieve recommended prophylactic anti-FXa levels while receiving a standard dose of enoxaparin and these levels failed to increase after enoxaparin dose escalation in a significant proportion of patients. High BMI and male gender are associated with sub-prophylactic levels of anti-FXa in critically ill patients.
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Enoxaparina , Tromboembolia Venosa , Humanos , Masculino , Enoxaparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Unidades de Terapia IntensivaRESUMO
The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion. This ensures no one misses out. The 2022 scientific program highlights new developments in hemophilia and its treatment, acquired and other inherited bleeding disorders, thromboinflammation, platelets and coagulation, clot structure and composition, fibrinolysis, vascular biology, venous thromboembolism, women's health, arterial thrombosis, pediatrics, COVID-related thrombosis, vaccine-induced thrombocytopenia with thrombosis, and omics and diagnostics. These areas are elegantly reviewed in this Illustrated Review article. The Illustrated Review is a highlight of the ISTH Congress. The format lends itself very well to explaining the science, and the collection of beautiful graphical summaries of recent developments in the field are stunning and self-explanatory. This clever and effective way to communicate research is revolutionary and different from traditional formats. We hope you enjoy this article and will be inspired by its content to generate new research ideas.
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Introduction: Primary obstetric antiphospholipid syndrome (OAPS) is defined by specific morbidities and/or losses of pregnancy in the presence of persistent antiphospholipid antibodies (aPL). This variant of APS is usually treated during pregnancy and the post-partum period. Data on occurrence of thrombotic event during long term follow-up of OAPS patients is limited. Methods: A multi-centre retrospectively cohort of female patients with primary APS (pAPS) was assembled during 2004-2019. Patients were grouped according to disease presentation as pure OAPS or thrombotic APS (tAPS) for those presenting with thrombosis. Clinical and serological data were compared between groups. Results: Of 219 pAPS female patients 67 (30.6%) were diagnosed with OAPS and 152 (69.4%) with tAPS. During >10 years of follow-up 24/67 (35.8%) OAPS and 71/152 (50%) tAPS suffered a new thrombotic event (p = 0.06), while obstetric morbidity was more likely in the OAPS group (31.3 vs. 10.5%, p < 0.001) respectively. Among patients with OAPS at presentation heart valve disease and the presence of ANA were related to thrombosis following diagnosis (25 vs. 4.7%, p = 0.02; and 45.8 vs. 20.8%, p = 0.04 respectively). Conclusion: Thrombotic event following diagnosis were common among female patients with pAPS regardless of disease presentation. Heart valve disease and ANA positivity may be risk factors for thrombosis during follow-up of patients presenting with pure OAPS.
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Background: Antiphospholipid syndrome (APS) is an acquired hypercoagulable condition associated with antiphospholipid antibody (aPL) presence. Data on re-thrombosis following APS-diagnosis are limited. Methods: This is a retrospective analysis of new thrombotic events among primary APS (pAPS) patients followed for up to 15 years in three medical centers in Israel. Results: Among 312 primary-APS patients, 143 (46%) had new thrombotic event classified to three patterns: (1) Arterial-associated with heart valve disease (OR 7.24, 95% C.I. 2.26-24.6), hypertension (OR 3, 95% C.I. 1.44-6.25), elevated anti-B2-GPI IgM (OR 1.04, 95% C.I. 0.996-1.08), arterial thrombosis at presentation (OR 1.74 95% C.I. 0.992-3.26), and older age (41 vs. 34 years, p < 0.001). (2) Venous-linked with venous thrombosis at presentation (OR 12.9, 95% C.I. 5.27-31.6, p < 0.001), heart valve disease (OR 9.81 95% C.I. 1.82-52.9, p = 0.018), aGAPSS (OR 1.15 95% C.I. 1.02-1.29), and younger age (31 vs. 36.5 years, p = 0.001); and (3) Combined pattern-associated with heart valve disease (OR 40.5 95% C.I. 7.7-212) and pulmonary embolism (OR 7.47 95% C.I. 1.96-28.5). A 4th variant "the Breakthrough pattern" defined by re-thrombosis despite prophylactic therapy was observed in 100/143 (70%) patients and linked with heart valve disease (OR 8. 95% C.I. 2.43-26.3), venous thrombosis at presentation (OR 2.61 95% C.I. 1.47-4.66), leg ulcers (OR 12.2, 95% C.I. 1.4-107), hypertension (OR 1.99, 95% C.I. 0.92-4.34), and higher aGAPSS (OR 1.08, 95% C.I. 0.99-1.18). Conclusion: In this real-life observation, re-thrombosis was common among pAPS patients including in those recommended to receive prophylactic therapy. Different patterns of recurrence were identified and linked with presenting symptoms, specific serological markers, APS manifestations, and comorbidities. Studies that will address interventions to prevent recurrences of APS-related events are needed.
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Síndrome Antifosfolipídica , Doenças das Valvas Cardíacas , Hipertensão , Trombose , Trombose Venosa , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Seguimentos , Humanos , Hipertensão/complicações , Estudos Retrospectivos , Trombose/complicações , Trombose/etiologiaRESUMO
Polycythemia vera (PV) has long been recognized as a disease characterized by excess blood cell production leading to thromboembolic phenomena. While the focus of treatment is on prevention of thromboembolic complications, achieved by hematocrit control and administration of low dose aspirin, attention has begun to shift to other elements of this chronic neoplasm, namely symptom control and arrest of disease progression. Clearly, phlebotomy is not able to accomplish these goals, and the ability of cytoreductive agents such as hydroxyurea (HU), to influence these elements of the disease is limited. Novel and repurposed drugs have recently entered this space, based on promising initial studies demonstrating their effects on biologic outcomes such as JAK2 V617F variant allele frequency (VAF). In this review, we present updated results of randomized clinical trials of pegylated interferon (IFN) and ruxolitinib and summarize emerging data from early phase trials of novel agents in PV.
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Policitemia Vera , Humanos , Hidroxiureia/uso terapêutico , Janus Quinase 2/genética , Policitemia Vera/diagnóstico , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genéticaRESUMO
OBJECTIVE: Antiphospholipid syndrome (APS) is an acquired coagulopathy associated with the presence of antiphospholipid antibodies. Whether ethnicity modulates APS clinical course is not known. The aim of our study was to assess the interplay of ethnicity and APS in Israel. METHODS: We retrospectively evaluated the ethnic distribution of APS patients from 3 medical centers in Israel compared to the general population. Ethnic groups were defined according to the Israeli Bureau of Statistics as Ashkenazi (European), former Union of Soviet Socialist Republics (USSR), North African, Asian (West Asia, Greece, and Turkey), Israeli Arab individuals, and others. RESULTS: Our cohort included 382 patients. The prevalence of Ashkenazi and Asian ethnicities was more pronounced (33% versus 12.8% and 15.4% versus 7.7%, respectively; P < 0.001), while Israeli Arabs were less represented (5.2% versus 31.1%; P < 0.001) relative to their part in the general population. Arab patients were younger at presentation (mean ± SD 28 ± 10 years versus 34 ± 13 years; P < 0.001) and were more likely to present with venous thrombosis (50% versus 35%; P = 0.037) and to suffer from venous thrombotic recurrence (45% versus 16%; P < 0.001) compared to other ethnicities. Mortality was higher among patients of Asian ethnic origin (8.8% versus 1.1%; P = 0.005); intriguingly, this group experienced cardiovascular risk factors more often (i.e., dyslipidemia and hypertension). CONCLUSION: Ethnicity may affect the prevalence and/or natural course of APS, which is less prevalent and differs clinically in Israeli Arab patients, while mortality was linked with Asian ethnicity.
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Síndrome Antifosfolipídica , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Etnicidade , Israel/epidemiologia , Estudos Retrospectivos , Anticorpos AntifosfolipídeosRESUMO
BACKGROUND: Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS: The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS: In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.
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Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Preservação de Sangue/tendências , Transfusão de Eritrócitos/tendências , Eritrócitos/fisiologia , Idoso , Idoso de 80 Anos ou mais , Preservação de Sangue/efeitos adversos , Transfusão de Eritrócitos/efeitos adversos , Feminino , Humanos , Unidades de Terapia Intensiva/tendências , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The thyroid hormones, T3 and T4, bind the αvß3 integrin and activate phosphorylates ERK (pERK). These tumor-promoting actions were reported in a number of malignancies, but not in CLL. METHODS: Primary cells from 22 CLL patients were verified for disease markers (CD5/CD19/CD23) and analyzed for αvß3 by flow cytometry (FC), ImageStream, Western blots (WB), and immunohistochemistry (IHC) in archival bone marrow (BM, n = 6) and lymph node (LN, n = 5) tissues. Selected samples (n = 8) were incubated with T3 (1-100 nM) or T4 (0.1-10 µM) for 30 min, and the expression levels of αvß3, pERK and PCNA (cell proliferation marker) were determined (WB). RESULTS: αvß3 was detected on the membrane of circulating CLL cells and in the BM but not in the LN. T3 and T4 enhanced αvß3 protein levels in primary CLL cells. Similarly, pERK and PCNA were rapidly induced in response to T3 and T4 exposure. CONCLUSIONS: αvß3 integrin is expressed on primary CLL cells and is induced by thyroid hormones. We further suggest that the hormones are mitogenic in these cells, presumably via αvß3-mediated signaling.
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Cardiovascular complications are increasingly reported with the use of certain tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML). We studied neutrophil extracellular trap (NET) formation in CML and evaluated the effect of TKIs on NET formation. Neutrophils isolated from treatment-naïve patients with CML showed a significant increase in NET formation compared to matched controls at baseline and after stimulation with ionomycin (IO) and phorbol 12-myristate 13-acetate (PMA). Expression of citrullinated histone H3 (H3cit), peptidyl arginine deiminase 4 (PAD4) and reactive oxygen species (ROS) was significantly higher in CML samples compared to controls. Pre-treatment of neutrophils with TKIs was associated with a differential effect on NET formation, and ponatinib significantly augmented NET-associated elastase and ROS levels as compared to controls and other TKIs. BCR-ABL1 retroviral transduced HoxB8-immortalized mouse hematopoietic progenitors, which differentiate into neutrophils in-vitro, demonstrated increased H3cit & myeloperoxidase (MPO) expression consistent with excess NET formation. This was inhibited by Cl-amidine, a PAD4 inhibitor, but not by the NADPH inhibitor diphenyleneiodonium (DPI). Ponatinib pre-exposure significantly increased H3cit expression in HoxB8-BCR-ABL1 cells after stimulation with IO. In summary, CML is associated with increased NET formation, which is augmented by ponatinib, suggesting a possible role for NETs in promoting vascular toxicity in CML.
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Venous thromboembolism comprising deep venous thrombosis and pulmonary embolus is common. Patients with venous thromboembolism may present to a variety of health care providers, and while a significant proportion of patients begin treatment in the hospital, ambulatory management of both deep venous thrombosis and pulmonary embolus is feasible and becoming more common. Initial anticoagulant management, investigation of venous thromboembolism etiology, and decisions about extended anticoagulation require coordinated care by physicians from multiple specialties. Comprehensive management of venous thromboembolism requires coordinated care from the time of presentation in order to expedite diagnosis, initiate timely anticoagulant treatment, determine the need for extended anticoagulation based on risk of bleeding and recurrent thrombosis, and advise on thromboprophylaxis during future high-risk periods for venous thromboembolism. In this review we use case scenarios to provide an operational framework, based on current evidence-based recommendations, for informed decision-making about a number of clinical practice issues that are frequently encountered in the management of venous thromboembolism patients.
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Anticoagulantes/uso terapêutico , Tomada de Decisão Clínica , Tromboembolia Venosa/tratamento farmacológico , Adulto , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The reported prevalence of hypercalcemia at diagnosis in non-Hodgkin-lymphoma ranges between 1.3% and 7.4%. These studies included all patients, regardless of lymphoma subtype. We performed a retrospective case-control study to determine the prevalence of hypercalcemia at time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL). Among 250 newly diagnosed patients, 46 (18%) had hypercalcemia. When compared with age-sex matched patients and normal calcium levels, those with hypercalcemia had higher levels of LDH, lower levels of albumin and more advanced stage. These differences were translated to shorter progression-free-survival and overall survival, but only in patients with hypercalcemia and low levels of parathyroid hormone (PTH). These findings suggest that in newly diagnosed patients with DLBCL, hypercalcemia is more frequent than previously appreciated. Furthermore, lymphoma-related but not primary hyperparathyroidism-related hypercalcemia is associated with adverse prognostic factors and adverse clinical outcomes in DLBCL. Hence, PTH should be obtained in patients with DLBCL and hypercalcemia at diagnosis.
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Hipercalcemia/epidemiologia , Hipercalcemia/etiologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Vitamina D/administração & dosagemAssuntos
Policitemia , Substituição de Aminoácidos , Eritropoetina/sangue , Feminino , Ferritinas/sangue , Humanos , Janus Quinase 2/genética , Testes de Função Renal , Testes de Função Hepática , Masculino , Mutação de Sentido Incorreto , Médicos , Policitemia/sangue , Policitemia/diagnóstico , Policitemia/genéticaRESUMO
OBJECTIVE: Although direct oral anticoagulants (DOAC) are the recommended antithrombotic therapy for patients with non-valvular atrial fibrillation (NVAF), anticoagulation in patients with NVAF is still inadequate. The effect of withholding DOAC therapy on patient survival is unknown. Therefore, our objective was to compare all-cause mortality rates between DOAC-treated patients with NVAF and similar patients receiving no anticoagulation. METHODS: We performed a retrospective cohort study analysing Clalit Health Services' extensive electronic database, regarding all newly diagnosed, anticoagulant-naïve patients with NVAF who were eligible for DOAC therapy from 1 January 2011 to 31 December 2016. Patients who received DOAC therapy were matched by propensity scoring to patients receiving no anticoagulation. The primary outcome was all-cause mortality. Final patient follow-up date was 15 May 2017. RESULTS: 18 901 eligible patients were identified. 8298 received treatment with a DOAC and 10 603 received no anticoagulation therapy. Of those, 5657 patients who received DOAC therapy were matched with 5657 patients who did not receive any anticoagulant. Death occurred in 715 patients in the DOAC-treated group (7.6% per year) and in 2075 patients in the non-anticoagulated patient group (11.1% per year). DOAC therapy was associated with significantly lower risk for all-cause mortality (HR=0.69, 95% CI 0.63 to 0.75, p<0.001). The benefit of DOAC therapy was demonstrated across all subgroups analysed. CONCLUSIONS: In this cohort of newly diagnosed patients with NVAF, DOAC therapy was associated with a significantly lower risk of death compared with no oral anticoagulation. Our findings provide further evidence for the importance of providing DOAC anticoagulation in patients with NVAF.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Administração Oral , Idoso , Transtornos Cerebrovasculares/epidemiologia , Estudos de Coortes , Feminino , Hemorragia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Análise por Pareamento , Estudos RetrospectivosRESUMO
INTRODUCTION: The direct oral anticoagulants (DOACs) are a class of drugs used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for prevention and treatment of venous thrombo-embolism. They are as effective and are safer than the vitamin K antagonists that were the oral drugs previously used for this purpose. The DOACs are convenient to use because of their fixed dose-response relationship which makes routine monitoring of drug levels unnecessary. Further, they have no food interactions and relatively few drug interactions. A number of practical considerations related to the routine clinical use of the DOACs have become apparent. These include choosing the appropriate drug and importantly dose-based on patient characteristics, managing the use of DOACs peri-operatively and the appropriate management of the acutely bleeding DOAC-treated patient. Recent controlled and observational studies provide guidance for dealing with these clinical situations thus enhancing the efficacy and safety of DOAC treatment in routine clinical practice.