Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients

Abstract Purpose The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19. Methods This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants. Results Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients Conclusion Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.

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The prevalence of long-term oral anticoagulation therapy in a cardiology center in Bucharest, Romania

Medicine and Pharmacy Reports ◽

10.15386/cjmed-837 ◽

2018 ◽

Vol 91 (1) ◽

pp. 37-41

Author(s):

Adelina-Mihaela Sorescu ◽

Tudor Enache ◽

Suzana Guberna

Keyword(s):

Oral Anticoagulation ◽

Economic Status ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Cross Sectional Study ◽

Similar Data ◽

Cross Sectional ◽

Oral Anticoagulation Therapy ◽

Vein Thrombosis

Background and aims. Few studies discuss the prevalence of oral anticoagulation therapy (OAT) in clinical practice, despite their increasing use worldwide. In America, studies established that 20% to 80% of the patients with indication benefit from OAT. In Romania, there is no data regarding the utilization of oral anticoagulants. Thus, this study aims to determine the trends of OAT.Methods. We designed a cross-sectional study of the patients admitted to the Cardiology Department of the “Bagdasar-Arseni” Clinical Emergency Hospital, Bucharest, from the 1st of November 2016 until the 31st of January 2017. We considered OAT indications to be: atrial fibrillation/flutter (AF), pulmonary embolisms (PE), deep vein thrombosis (DVT), intramural or intracavitary thrombi and left ventricle aneurysms. Statistical analysis was performed with EpiInfo.Results. There were 783 patients admitted, 253 of these having an OAT indication (mean age 73.25 years, 53.75% female). Only 162 patients (64.03%) received it, either Vitamin K Antagonists (VKA) (78 patients, 48.14%), or Novel Oral Anticoagulants (NOAC) (84 patients, 51.85%). Reasons for not indicating such therapy included the hemorrhage risk (43.27%), the lack of adherence to the treatment (18.56%), the impossibility of INR monitoring (21.84%), the economic status (10.21%) and others (6.12%). 221 patients had AF (87.35%), 141 (63.8%) receiving OAT, VKA (67 patients, 47.51%), or NOAC (74 patients, 52.48%). 17 patients (6.71%) had a PE and/or DVT. 15 (88.23%) received OAT, AVK (11 patients, 73.33%), or NOAC (4 patients, 26.67%). 15 patients (5.92%) had other OAT indications (excepting AF or PE/DVT), 11 receiving OAT (73.33%), AVK (8 patients, 72.72%), or NOAC (3 patients, 27.27%).Conclusions. Our study determined that 64.03% of those with indication received OAT. Similar data is reported in the USA, suggesting an underuse of anticoagulants. The risk of hemorrhage, lack of adherence, the impossibility of INR monitoring or the economic status were some of the reasons for not recommending OAT.

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New developments in anticoagulants: Past, present and future

Thrombosis and Haemostasis ◽

10.1160/th16-10-0807 ◽

2017 ◽

Vol 117 (07) ◽

pp. 1283-1288 ◽

Cited By ~ 36

Author(s):

Jeffrey I. Weitz ◽

Job Harenberg

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Factor Xii ◽

Heparin Induced Thrombocytopenia ◽

New Developments ◽

Oral Anticoagulation Therapy ◽

Reversal Agents ◽

The Past

SummaryThrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90% subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

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Quality and predictors of oral anticoagulation therapy with vitamin K antagonists in adult congenital heart disease: TTR and INR variability

Thrombosis Research ◽

10.1016/j.thromres.2021.08.025 ◽

2021 ◽

Author(s):

Daniel Samarai ◽

Nazim Isma ◽

Sandra Lindstedt ◽

Joanna Hlebowicz

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Vitamin K ◽

Oral Anticoagulation ◽

Congenital Heart ◽

Adult Congenital Heart Disease ◽

Vitamin K Antagonists ◽

Anticoagulation Therapy ◽

Oral Anticoagulation Therapy ◽

Adult Congenital

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Impact of oral anticoagulation therapy on postoperative atrial fibrillation outcomes: a systematic review and meta-analysis

Thrombosis Journal ◽

10.1186/s12959-021-00342-2 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Mariana Fragão-Marques ◽

Francisco Teixeira ◽

Jennifer Mancio ◽

Nair Seixas ◽

João Rocha-Neves ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiac Surgery ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Random Effect ◽

Anticoagulation Therapy ◽

Thromboembolic Events ◽

Oral Anticoagulation Therapy ◽

All Cause Mortality

Abstract Background Post-operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Recent studies had shown this phenomenon is no longer considered transitory and is associated with higher risk of thromboembolic events or death. The aim of this study was to systematically review and analyze previous studies comparing oral anticoagulation therapy with no anticoagulation, regarding these long-term outcomes. Methods PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Database were systematically searched to identify the studies comparing the risk of stroke, or thromboembolic events or mortality of POAF patients who received anticoagulation compared with those who were not anticoagulated. Incidence of stroke, thromboembolic events and all-cause mortality were evaluated up to 10 years after surgery. Time-to-event outcomes were collected through hazard ratio (HR) along with their variance and the early endpoints using frequencies or odds ratio (OR). Random effect models were used to compute statistical combined measures and 95% confidence intervals (CI). Heterogeneity was evaluated through Q statistic-related measures of variance (Tau2, I2, Chi-squared test). Results Eight observational cohort studies were selected, including 15,335 patients (3492 on Oral Anticoagulants (OAC) vs 11,429 without OAC) that met the inclusion criteria for qualitative synthesis. Patients had a wide gender distribution (38.6–82.3%), each study with a mean age above 65 years (67.5–85). Vitamin K antagonists were commonly prescribed anticoagulants (74.3–100%). OAC was associated with a protective impact on all-cause mortality at a mean of 5.0 years of follow-up (HR is 0.85 [0.72–1.01]; p = 0.07; I2 = 48%). Thromboembolic events did not differ between the two treatment arms (HR 0.68 [0.40–1.15], p = 0.15). Conclusion Current literature suggests a possibly protective impact of OAC therapy for all-cause mortality in patients with new-onset atrial fibrillation after cardiac surgery. However, it does not appear to impact thromboembolism rate.

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Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657025 ◽

1979 ◽

Vol 42 (04) ◽

pp. 1296-1305 ◽

Cited By ~ 29

Author(s):

R M Bertina ◽

W van der Marel-van Nieuwkoop ◽

E A Loeliger

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Factor V ◽

Anticoagulant Treatment ◽

Factor Ii ◽

K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

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Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account

Journal of Clinical Medicine ◽

10.3390/jcm10153212 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3212

Author(s):

Fabiana Lucà ◽

Simona Giubilato ◽

Stefania Angela Di Fusco ◽

Laura Piccioni ◽

Carmelo Massimiliano Rao ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Thrombus Formation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Significant Advance ◽

Thromboembolic Events ◽

Thromboembolic Risk ◽

Pharmacological Cardioversion

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

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Management of Oral Anticoagulation Therapy After Gastrointestinal Bleeding: Whether to, When to, and How to Restart an Anticoagulation Therapy

Annals of Pharmacotherapy ◽

10.1177/1060028017717019 ◽

2017 ◽

Vol 51 (11) ◽

pp. 1000-1007 ◽

Cited By ~ 9

Author(s):

Kazuhiko Kido ◽

Michael J. Scalese

Keyword(s):

Gastrointestinal Bleeding ◽

Cohort Studies ◽

Oral Anticoagulation ◽

Retrospective Cohort ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Cochrane Library ◽

Oral Anticoagulation Therapy ◽

Retrospective Cohort Studies

Objective: To evaluate current clinical evidence for management of oral anticoagulation therapy after gastrointestinal bleeding (GIB) with an emphasis on whether to, when to, and how to resume an anticoagulation therapy. Data Sources: Relevant articles from MEDLINE, Cochrane Library, and EMBASE databases were identified from 1946 through May 20, 2017, using the keywords: gastrointestinal hemorrhage or gastrointestinal bleeding and antithrombotic therapy or anticoagulation therapy or warfarin or dabigatran or rivaroxaban or apixaban or edoxaban.Study Selection and Data Extraction: All English-language studies assessing management of oral anticoagulation therapy after GIB were evaluated. Data Synthesis: A total of 9 studies were identified. Four retrospective cohort studies showed that resuming anticoagulation therapy was associated with significantly lower rate of thromboembolism (TE) in the general population. Meta-analyses and prospective cohort studies also supported this finding. Two retrospective cohort studies indicated an increase in GIB when anticoagulation reinitiation occurred in less than 7 days without a decrease in TE. Resuming therapy between 7 and 15 days did not demonstrate a significant increase in GIB or TE. A large retrospective study showed that apixaban was associated with the significantly lowest risk of GIB compared with both rivaroxaban and dabigatran. Conclusion: Anticoagulation therapy resumption is recommended, with resumption being considered between 7 and 14 days following GIB regardless of the therapy chosen. Data for warfarin management after GIB should be applied with caution to direct oral anticoagulants (DOACs) because of the quicker onset and experimental nature of reversal agents. Apixaban may be a preferred option when restarting a DOAC therapy.

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Inferior Vena Cava Agenesis and Deep Vein Thrombosis: A Pharmacological Alternative to Vitamin K Antagonists

European Journal of Case Reports in Internal Medicine ◽

10.12890/2019_001310 ◽

2019 ◽

Author(s):

Inês Esteves Cruz ◽

Pedro Ferreira ◽

Raquel Silva ◽

Francisco Silva ◽

Isabel Madruga

Keyword(s):

Deep Vein Thrombosis ◽

Inferior Vena Cava ◽

Vitamin K ◽

Oral Anticoagulation ◽

Inferior Vena ◽

Vitamin K Antagonists ◽

Anticoagulation Therapy ◽

Vena Cava ◽

Vein Thrombosis ◽

Deep Vein

Inferior vena cava (IVC) agenesis is a rare congenital abnormality affecting the infrarenal segment, the suprarenal or the whole of the IVC. It has an estimated prevalence of up to 1% in the general population that can rise to 8.7% when abnormalities of the left renal vein are considered. Most IVC malformations are asymptomatic but may be associated with nonspecific symptoms or present as deep vein thrombosis (DVT). Up to 5% of young individuals under 30 years of age with unprovoked DVT are found to have this condition. Regarding the treatment of IVC agenesis-associated DVT, there are no standard guidelines. Treatment is directed towards preventing thrombosis or its recurrence. Low molecular weight heparin and oral anticoagulation medication, in particular vitamin K antagonists (VKAs) are the mainstay of therapy. Given the high risk of DVT recurrence in these patients, oral anticoagulation therapy is suggested to be pursued indefinitely. As far as we know, this is the first case reporting the use of a direct factor Xa inhibitor in IVC agenesis-associated DVT. Given VKA monitoring limitations, the use of a direct Xa inhibitor could be an alternative in young individuals with anatomical defects without thrombophilia, but further studies will be needed to confirm its efficacy and safety.

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